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Eric M. Weaver - One of the best experts on this subject based on the ideXlab platform.
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Serum Bovine Immunoglobulins Improve Inflammation and Gut Barrier Function in Persons with HIV and Enteropathy on Suppressive ART.
Pathogens and Immunity, 2019Co-Authors: Netanya S. Utay, Bryon W Petschow, Christopher J. Detzel, Eric M. Weaver, Audrey L. Shaw, John Hinkle, Ma Somsouk, Anoma Somasunderam, Carl J. Fichtenbaum, David M. AsmuthAbstract:Background: Systemic inflammation persists in chronic HIV infection and is associated with increased rates of non-AIDS events such as cardiovascular and liver disease. Increased gut permeability and systemic exposure to microbial products are key drivers of this inflammation. Serum-derived Bovine Immunoglobulin/protein isolate (SBI) supports gut healing in other conditions such as inflammatory bowel disease. Methods: In this randomized, double-blind study, participants receiving suppressive antiretroviral therapy (ART) with chronic diarrhea received placebo or SBI at 2.5 g BID or 5 g BID for 4 weeks, followed by a 20-week placebo-free extension phase with SBI at either 2.5 or 5 g BID. Intestinal fatty acid binding protein (I-FABP), zonulin, flagellin, lipopolysaccharide (LPS) and LPS-binding protein, and inflammatory markers were measured by ELISA or multiplex assays. Non-parametric tests were used for analysis. Results: One hundred three participants completed the study. By week 24 SBI significantly decreased circulating levels of I-FABP (-0.35 ng/mL, P = 0.002) and zonulin (-4.90 ng/mL, P = 0.003), suggesting improvement in gut damage, and interleukin-6 (IL-6) (-0.40 pg/mL, P = 0.002), reflecting improvement in systemic inflammation. In participants with the lowest quartile of CD4+ T-cell counts at baseline (189-418 cells/mL), CD4+ T-cell counts increased significantly (26 cells/mL; P = 0.002). Conclusions: Oral SBI may decrease inflammation and warrants further exploration as a potential strategy to improve gut integrity and decrease systemic inflammation among persons receiving prolonged suppressive ART. Keywords: HIV infection; CD4 T cell; Serum Bovine Immunoglobulin protein; Interleukin; Inflammation; Intestine; I-FABP
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Absorption and safety of serum-derived Bovine Immunoglobulin/protein isolate in healthy adults
Clinical and experimental gastroenterology, 2016Co-Authors: Audrey L. Shaw, Bryon W Petschow, Christopher J. Detzel, Eric M. Weaver, Gerald L. Klein, David W Mathews, John Hinkle, Timothy P BradshawAbstract:PURPOSE Previous studies have shown that oral administration of Bovine Immunoglobulin protein preparations is safe and provides nutritional and intestinal health benefits. The purpose of this study was to evaluate the plasma amino acid response following a single dose of serum-derived Bovine Immunoglobulin/protein isolate (SBI) and whether Bovine Immunoglobulin G (IgG) is present in stool or in blood following multiple doses of SBI in healthy volunteers. METHODS A total of 42 healthy adults were administered a single dose of placebo or SBI at one of three doses (5 g, 10 g, or 20 g) in blinded fashion and then continued on SBI (2.5 g, 5 g, or 10 g) twice daily (BID) for an additional 2 weeks. Serial blood samples were collected for amino acid analysis following a single dose of placebo or SBI. Stool and blood samples were collected to assess Bovine IgG levels. RESULTS The area under the curve from time 0 minute to 180 minutes for essential and total amino acids as well as tryptophan increased following ingestion of 5 g, 10 g, or 20 g of SBI, with a significant difference between placebo and all doses of SBI (p
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serum derived Bovine Immunoglobulin protein isolate in the alleviation of chemotherapy induced mucositis
Supportive Care in Cancer, 2016Co-Authors: Emma Bateman, Eric M. Weaver, Gerald L. Klein, Anthony Wignall, Belinda Wozniak, Erin Plews, Dorothy M. K. Keefe, Bronwen Mayo, Imogen WhiteAbstract:Background Gastrointestinal (GI) mucositis caused by chemotherapy is associated with diarrhoea and intestinal barrier disruption caused by apoptosis, immune dysfunction and microbiome alterations. Serum-derived Bovine Immunoglobulin/protein isolate (SBI) has been shown to manage HIV-associated enteropathy and irritable bowel syndrome with diarrhoea (IBS-D). We investigated in a rat model whether SBI was effective in alleviating symptoms of irinotecan-induced GI mucositis.
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Attenuation of Colitis by Serum-Derived Bovine Immunoglobulin/Protein Isolate in a Defined Microbiota Mouse Model
Digestive Diseases and Sciences, 2015Co-Authors: Abigail L Henderson, Meghan Wymore Brand, Ross J. Darling, Kenneth J. Maas, Christopher J. Detzel, Jesse Hostetter, Michael J Wannemuehler, Eric M. WeaverAbstract:Background The pathogenesis of inflammatory bowel disease (IBD) is complex and multifaceted including genetic predisposition, environmental components, microbial dysbiosis, and inappropriate immune activation to microbial components. Pathogenic bacterial provocateurs like adherent and invasive E. coli have been reported to increase susceptibility to Crohn’s disease. Serum-derived Bovine Immunoglobulin/protein isolate (SBI) is comprised primarily of Immunoglobulins (Igs) that bind to conserved microbial components and neutralize exotoxins. Aim To demonstrate that oral administration of SBI may modulate mucosal inflammation following colonization with E. coli , LF82, and exposure to dextran sodium sulfate (DSS). Methods Defined microbiota mice harboring the altered Schaedler flora (ASF) were administered SBI or hydrolyzed collagen twice daily starting 7 days prior to challenge with E. coli LF82 and continuing for the remainder of the experiment. Mice were treated with DSS for 7 days and then evaluated for evidence of local and peripheral inflammation. Results Igs within SBI bound multiple antigens from all eight members of the ASF and E. coli LF82 by western blot analysis. Multiple parameters of LF82/DSS-induced colitis were reduced following administration of SBI, including histological lesion scores, secretion of cytokines and chemokines from cecal biopsies, intestinal fatty acid binding protein (I-FABP) and serum amyloid A from plasma. Conclusions Oral administration of SBI attenuated clinical signs of LF82/DSS-induced colitis in mice. The data are consistent with the hypothesis that SBI Immunoglobulin binding of bacterial antigens in the intestinal lumen may inhibit the inflammatory cascades that contribute to IBD, thus attenuating DSS-induced colitis.
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Serum-derived Bovine Immunoglobulin/protein isolate in the alleviation of chemotherapy-induced mucositis
Supportive Care in Cancer, 2015Co-Authors: Emma Bateman, Eric M. Weaver, Gerald L. Klein, Anthony Wignall, Belinda Wozniak, Erin Plews, Bronwen J. Mayo, Imogen A. White, Dorothy M. K. KeefeAbstract:Background Gastrointestinal (GI) mucositis caused by chemotherapy is associated with diarrhoea and intestinal barrier disruption caused by apoptosis, immune dysfunction and microbiome alterations. Serum-derived Bovine Immunoglobulin/protein isolate (SBI) has been shown to manage HIV-associated enteropathy and irritable bowel syndrome with diarrhoea (IBS-D). We investigated in a rat model whether SBI was effective in alleviating symptoms of irinotecan-induced GI mucositis.
Christopher J. Detzel - One of the best experts on this subject based on the ideXlab platform.
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Serum Bovine Immunoglobulins Improve Inflammation and Gut Barrier Function in Persons with HIV and Enteropathy on Suppressive ART.
Pathogens and Immunity, 2019Co-Authors: Netanya S. Utay, Bryon W Petschow, Christopher J. Detzel, Eric M. Weaver, Audrey L. Shaw, John Hinkle, Ma Somsouk, Anoma Somasunderam, Carl J. Fichtenbaum, David M. AsmuthAbstract:Background: Systemic inflammation persists in chronic HIV infection and is associated with increased rates of non-AIDS events such as cardiovascular and liver disease. Increased gut permeability and systemic exposure to microbial products are key drivers of this inflammation. Serum-derived Bovine Immunoglobulin/protein isolate (SBI) supports gut healing in other conditions such as inflammatory bowel disease. Methods: In this randomized, double-blind study, participants receiving suppressive antiretroviral therapy (ART) with chronic diarrhea received placebo or SBI at 2.5 g BID or 5 g BID for 4 weeks, followed by a 20-week placebo-free extension phase with SBI at either 2.5 or 5 g BID. Intestinal fatty acid binding protein (I-FABP), zonulin, flagellin, lipopolysaccharide (LPS) and LPS-binding protein, and inflammatory markers were measured by ELISA or multiplex assays. Non-parametric tests were used for analysis. Results: One hundred three participants completed the study. By week 24 SBI significantly decreased circulating levels of I-FABP (-0.35 ng/mL, P = 0.002) and zonulin (-4.90 ng/mL, P = 0.003), suggesting improvement in gut damage, and interleukin-6 (IL-6) (-0.40 pg/mL, P = 0.002), reflecting improvement in systemic inflammation. In participants with the lowest quartile of CD4+ T-cell counts at baseline (189-418 cells/mL), CD4+ T-cell counts increased significantly (26 cells/mL; P = 0.002). Conclusions: Oral SBI may decrease inflammation and warrants further exploration as a potential strategy to improve gut integrity and decrease systemic inflammation among persons receiving prolonged suppressive ART. Keywords: HIV infection; CD4 T cell; Serum Bovine Immunoglobulin protein; Interleukin; Inflammation; Intestine; I-FABP
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Absorption and safety of serum-derived Bovine Immunoglobulin/protein isolate in healthy adults
Clinical and experimental gastroenterology, 2016Co-Authors: Audrey L. Shaw, Bryon W Petschow, Christopher J. Detzel, Eric M. Weaver, Gerald L. Klein, David W Mathews, John Hinkle, Timothy P BradshawAbstract:PURPOSE Previous studies have shown that oral administration of Bovine Immunoglobulin protein preparations is safe and provides nutritional and intestinal health benefits. The purpose of this study was to evaluate the plasma amino acid response following a single dose of serum-derived Bovine Immunoglobulin/protein isolate (SBI) and whether Bovine Immunoglobulin G (IgG) is present in stool or in blood following multiple doses of SBI in healthy volunteers. METHODS A total of 42 healthy adults were administered a single dose of placebo or SBI at one of three doses (5 g, 10 g, or 20 g) in blinded fashion and then continued on SBI (2.5 g, 5 g, or 10 g) twice daily (BID) for an additional 2 weeks. Serial blood samples were collected for amino acid analysis following a single dose of placebo or SBI. Stool and blood samples were collected to assess Bovine IgG levels. RESULTS The area under the curve from time 0 minute to 180 minutes for essential and total amino acids as well as tryptophan increased following ingestion of 5 g, 10 g, or 20 g of SBI, with a significant difference between placebo and all doses of SBI (p
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Attenuation of Colitis by Serum-Derived Bovine Immunoglobulin/Protein Isolate in a Defined Microbiota Mouse Model
Digestive Diseases and Sciences, 2015Co-Authors: Abigail L Henderson, Meghan Wymore Brand, Ross J. Darling, Kenneth J. Maas, Christopher J. Detzel, Jesse Hostetter, Michael J Wannemuehler, Eric M. WeaverAbstract:Background The pathogenesis of inflammatory bowel disease (IBD) is complex and multifaceted including genetic predisposition, environmental components, microbial dysbiosis, and inappropriate immune activation to microbial components. Pathogenic bacterial provocateurs like adherent and invasive E. coli have been reported to increase susceptibility to Crohn’s disease. Serum-derived Bovine Immunoglobulin/protein isolate (SBI) is comprised primarily of Immunoglobulins (Igs) that bind to conserved microbial components and neutralize exotoxins. Aim To demonstrate that oral administration of SBI may modulate mucosal inflammation following colonization with E. coli , LF82, and exposure to dextran sodium sulfate (DSS). Methods Defined microbiota mice harboring the altered Schaedler flora (ASF) were administered SBI or hydrolyzed collagen twice daily starting 7 days prior to challenge with E. coli LF82 and continuing for the remainder of the experiment. Mice were treated with DSS for 7 days and then evaluated for evidence of local and peripheral inflammation. Results Igs within SBI bound multiple antigens from all eight members of the ASF and E. coli LF82 by western blot analysis. Multiple parameters of LF82/DSS-induced colitis were reduced following administration of SBI, including histological lesion scores, secretion of cytokines and chemokines from cecal biopsies, intestinal fatty acid binding protein (I-FABP) and serum amyloid A from plasma. Conclusions Oral administration of SBI attenuated clinical signs of LF82/DSS-induced colitis in mice. The data are consistent with the hypothesis that SBI Immunoglobulin binding of bacterial antigens in the intestinal lumen may inhibit the inflammatory cascades that contribute to IBD, thus attenuating DSS-induced colitis.
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Attenuation of Colitis by Serum-Derived Bovine Immunoglobulin/Protein Isolate in a Defined Microbiota Mouse Model
Digestive Diseases and Sciences, 2015Co-Authors: Abigail Henderson, Meghan Wymore Brand, Ross J. Darling, Kenneth J. Maas, Christopher J. Detzel, Jesse Hostetter, Michael J Wannemuehler, Eric M. WeaverAbstract:Background The pathogenesis of inflammatory bowel disease (IBD) is complex and multifaceted including genetic predisposition, environmental components, microbial dysbiosis, and inappropriate immune activation to microbial components. Pathogenic bacterial provocateurs like adherent and invasive E. coli have been reported to increase susceptibility to Crohn’s disease. Serum-derived Bovine Immunoglobulin/protein isolate (SBI) is comprised primarily of Immunoglobulins (Igs) that bind to conserved microbial components and neutralize exotoxins.
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attenuation of colitis by serum derived Bovine Immunoglobulin protein isolate in a defined microbiota mouse model
Digestive Diseases and Sciences, 2015Co-Authors: Abigail Henderson, Meghan Wymore Brand, Ross J. Darling, Kenneth J. Maas, Christopher J. Detzel, Jesse Hostetter, Michael J Wannemuehler, Eric M. WeaverAbstract:Background The pathogenesis of inflammatory bowel disease (IBD) is complex and multifaceted including genetic predisposition, environmental components, microbial dysbiosis, and inappropriate immune activation to microbial components. Pathogenic bacterial provocateurs like adherent and invasive E. coli have been reported to increase susceptibility to Crohn’s disease. Serum-derived Bovine Immunoglobulin/protein isolate (SBI) is comprised primarily of Immunoglobulins (Igs) that bind to conserved microbial components and neutralize exotoxins.
Bryon W Petschow - One of the best experts on this subject based on the ideXlab platform.
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Serum Bovine Immunoglobulins Improve Inflammation and Gut Barrier Function in Persons with HIV and Enteropathy on Suppressive ART.
Pathogens and Immunity, 2019Co-Authors: Netanya S. Utay, Bryon W Petschow, Christopher J. Detzel, Eric M. Weaver, Audrey L. Shaw, John Hinkle, Ma Somsouk, Anoma Somasunderam, Carl J. Fichtenbaum, David M. AsmuthAbstract:Background: Systemic inflammation persists in chronic HIV infection and is associated with increased rates of non-AIDS events such as cardiovascular and liver disease. Increased gut permeability and systemic exposure to microbial products are key drivers of this inflammation. Serum-derived Bovine Immunoglobulin/protein isolate (SBI) supports gut healing in other conditions such as inflammatory bowel disease. Methods: In this randomized, double-blind study, participants receiving suppressive antiretroviral therapy (ART) with chronic diarrhea received placebo or SBI at 2.5 g BID or 5 g BID for 4 weeks, followed by a 20-week placebo-free extension phase with SBI at either 2.5 or 5 g BID. Intestinal fatty acid binding protein (I-FABP), zonulin, flagellin, lipopolysaccharide (LPS) and LPS-binding protein, and inflammatory markers were measured by ELISA or multiplex assays. Non-parametric tests were used for analysis. Results: One hundred three participants completed the study. By week 24 SBI significantly decreased circulating levels of I-FABP (-0.35 ng/mL, P = 0.002) and zonulin (-4.90 ng/mL, P = 0.003), suggesting improvement in gut damage, and interleukin-6 (IL-6) (-0.40 pg/mL, P = 0.002), reflecting improvement in systemic inflammation. In participants with the lowest quartile of CD4+ T-cell counts at baseline (189-418 cells/mL), CD4+ T-cell counts increased significantly (26 cells/mL; P = 0.002). Conclusions: Oral SBI may decrease inflammation and warrants further exploration as a potential strategy to improve gut integrity and decrease systemic inflammation among persons receiving prolonged suppressive ART. Keywords: HIV infection; CD4 T cell; Serum Bovine Immunoglobulin protein; Interleukin; Inflammation; Intestine; I-FABP
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Impact of serum-derived Bovine Immunoglobulin/protein isolate therapy on irritable bowel syndrome and inflammatory bowel disease: a survey of patient perspective
Patient preference and adherence, 2017Co-Authors: Audrey L. Shaw, Bryon W Petschow, Timothy P Bradshaw, Adam Tomanelli, Bruce BurnettAbstract:BACKGROUND Patients with irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD) commonly experience diarrhea, abdominal pain, bloating, and urgency. These symptoms significantly compromise the patient's quality of life (QoL) by limiting participation in normal daily activities and adversely affect work productivity and performance. PURPOSE The aim of this study was to understand from the patient's perspective how oral serum-derived Bovine Immunoglobulin/protein isolate (SBI) impacts bowel habits, management of condition, and basic QoL. METHODS A 1-page questionnaire was distributed randomly to >14,000 patients who were prescribed SBI (EnteraGam®) for relevant intended uses. The survey was designed to collect data related to the influence of IBS or IBD on daily life activities and the impact of SBI usage on daily stool frequency, management of their condition, and QoL. Patient-reported responses were analyzed using a paired t-test to compare mean change in daily stool output and descriptive statistics for continuous variables. RESULTS A total of 1,377 patients returned the surveys. Results from 595 surveys were analyzed with a focus on patients with IBS or IBD who had provided numeric responses regarding daily stool frequency. Respondents with IBS who reported having a normal stool frequency (≤4 stools per day) increased from 35% prior to using SBI to 91% while using SBI. A similar change toward normal stool frequency was reported by IBD respondents. Mean daily stool numbers decreased for respondents in the combined IBS and IBD groups (P=0.0001) from 6.5±4.3 before SBI to 2.6±1.9 following SBI use. The majority of respondents agreed strongly or very strongly that SBI helped them manage their condition (66.9%) and helped them return to the activities they enjoyed (59.1%). CONCLUSION Results from this patient survey suggest that SBI use can lead to clinically relevant decreases in daily stool frequency in patients with IBS or IBD along with improvements in the overall management of their condition and aspects of QoL.
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impact of serum derived Bovine Immunoglobulin protein isolate therapy on irritable bowel syndrome and inflammatory bowel disease a survey of patient perspective
Patient Preference and Adherence, 2017Co-Authors: Audrey L. Shaw, Bryon W Petschow, Timothy P Bradshaw, Adam Tomanelli, Bruce BurnettAbstract:BACKGROUND Patients with irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD) commonly experience diarrhea, abdominal pain, bloating, and urgency. These symptoms significantly compromise the patient's quality of life (QoL) by limiting participation in normal daily activities and adversely affect work productivity and performance. PURPOSE The aim of this study was to understand from the patient's perspective how oral serum-derived Bovine Immunoglobulin/protein isolate (SBI) impacts bowel habits, management of condition, and basic QoL. METHODS A 1-page questionnaire was distributed randomly to >14,000 patients who were prescribed SBI (EnteraGam®) for relevant intended uses. The survey was designed to collect data related to the influence of IBS or IBD on daily life activities and the impact of SBI usage on daily stool frequency, management of their condition, and QoL. Patient-reported responses were analyzed using a paired t-test to compare mean change in daily stool output and descriptive statistics for continuous variables. RESULTS A total of 1,377 patients returned the surveys. Results from 595 surveys were analyzed with a focus on patients with IBS or IBD who had provided numeric responses regarding daily stool frequency. Respondents with IBS who reported having a normal stool frequency (≤4 stools per day) increased from 35% prior to using SBI to 91% while using SBI. A similar change toward normal stool frequency was reported by IBD respondents. Mean daily stool numbers decreased for respondents in the combined IBS and IBD groups (P=0.0001) from 6.5±4.3 before SBI to 2.6±1.9 following SBI use. The majority of respondents agreed strongly or very strongly that SBI helped them manage their condition (66.9%) and helped them return to the activities they enjoyed (59.1%). CONCLUSION Results from this patient survey suggest that SBI use can lead to clinically relevant decreases in daily stool frequency in patients with IBS or IBD along with improvements in the overall management of their condition and aspects of QoL.
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Absorption and safety of serum-derived Bovine Immunoglobulin/protein isolate in healthy adults
Clinical and experimental gastroenterology, 2016Co-Authors: Audrey L. Shaw, Bryon W Petschow, Christopher J. Detzel, Eric M. Weaver, Gerald L. Klein, David W Mathews, John Hinkle, Timothy P BradshawAbstract:PURPOSE Previous studies have shown that oral administration of Bovine Immunoglobulin protein preparations is safe and provides nutritional and intestinal health benefits. The purpose of this study was to evaluate the plasma amino acid response following a single dose of serum-derived Bovine Immunoglobulin/protein isolate (SBI) and whether Bovine Immunoglobulin G (IgG) is present in stool or in blood following multiple doses of SBI in healthy volunteers. METHODS A total of 42 healthy adults were administered a single dose of placebo or SBI at one of three doses (5 g, 10 g, or 20 g) in blinded fashion and then continued on SBI (2.5 g, 5 g, or 10 g) twice daily (BID) for an additional 2 weeks. Serial blood samples were collected for amino acid analysis following a single dose of placebo or SBI. Stool and blood samples were collected to assess Bovine IgG levels. RESULTS The area under the curve from time 0 minute to 180 minutes for essential and total amino acids as well as tryptophan increased following ingestion of 5 g, 10 g, or 20 g of SBI, with a significant difference between placebo and all doses of SBI (p
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Bovine Immunoglobulin protein isolate binds pro inflammatory bacterial compounds and prevents immune activation in an intestinal co culture model
PLOS ONE, 2015Co-Authors: Christopher J. Detzel, Alan Horgan, Bryon W Petschow, Christopher D Warner, Abigail Henderson, Kenneth J. Maas, Eric M. WeaverAbstract:Intestinal barrier dysfunction is associated with chronic gastrointestinal tract inflammation and diseases such as IBD and IBS. Serum-derived Bovine Immunoglobulin/protein isolate (SBI) is a specially formulated protein preparation (>90%) for oral administration. The composition of SBI is greater than 60% Immunoglobulin including contributions from IgG, IgA, and IgM. Immunoglobulin within the lumen of the gut has been recognized to have anti-inflammatory properties and is involved in maintaining gut homeostasis. The binding of common intestinal antigens (LPS and Lipid A) and the ligand Pam3CSK4, by IgG, IgA, and IgM in SBI was shown using a modified ELISA technique. Each of these antigens stimulated IL-8 and TNF-α cytokine production by THP-1 monocytes. Immune exclusion occurred as SBI (≤50 mg/mL) bound free antigen in a dose dependent manner that inhibited cytokine production by THP-1 monocytes in response to 10 ng/mL LPS or 200 ng/mL Lipid A. Conversely, Pam3CSK4 stimulation of THP-1 monocytes was unaffected by SBI/antigen binding. A co-culture model of the intestinal epithelium consisted of a C2BBe1 monolayer separating an apical compartment from a basal compartment containing THP-1 monocytes. The C2BBe1 monolayer was permeabilized with dimethyl palmitoyl ammonio propanesulfonate (PPS) to simulate a damaged epithelial barrier. Results indicate that Pam3CSK4 was able to translocate across the PPS-damaged C2BBe1 monolayer. However, binding of Pam3CSK4 by Immunoglobulins in SBI prevented Pam3CSK4 translocation across the damaged C2BBe1 barrier. These results demonstrated steric exclusion of antigen by SBI which prevented apical to basal translocation of antigen due to changes in the physical properties of Pam3CSK4, most likely as a result of Immunoglobulin binding. This study demonstrates that Immunoglobulins in SBI can reduce antigen-associated inflammation through immune and steric exclusion mechanisms and furthers the mechanistic understanding of how SBI might improve immune status and reduce inflammation in various intestinal disease states.
Gerald L. Klein - One of the best experts on this subject based on the ideXlab platform.
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Absorption and safety of serum-derived Bovine Immunoglobulin/protein isolate in healthy adults
Clinical and experimental gastroenterology, 2016Co-Authors: Audrey L. Shaw, Bryon W Petschow, Christopher J. Detzel, Eric M. Weaver, Gerald L. Klein, David W Mathews, John Hinkle, Timothy P BradshawAbstract:PURPOSE Previous studies have shown that oral administration of Bovine Immunoglobulin protein preparations is safe and provides nutritional and intestinal health benefits. The purpose of this study was to evaluate the plasma amino acid response following a single dose of serum-derived Bovine Immunoglobulin/protein isolate (SBI) and whether Bovine Immunoglobulin G (IgG) is present in stool or in blood following multiple doses of SBI in healthy volunteers. METHODS A total of 42 healthy adults were administered a single dose of placebo or SBI at one of three doses (5 g, 10 g, or 20 g) in blinded fashion and then continued on SBI (2.5 g, 5 g, or 10 g) twice daily (BID) for an additional 2 weeks. Serial blood samples were collected for amino acid analysis following a single dose of placebo or SBI. Stool and blood samples were collected to assess Bovine IgG levels. RESULTS The area under the curve from time 0 minute to 180 minutes for essential and total amino acids as well as tryptophan increased following ingestion of 5 g, 10 g, or 20 g of SBI, with a significant difference between placebo and all doses of SBI (p
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serum derived Bovine Immunoglobulin protein isolate in the alleviation of chemotherapy induced mucositis
Supportive Care in Cancer, 2016Co-Authors: Emma Bateman, Eric M. Weaver, Gerald L. Klein, Anthony Wignall, Belinda Wozniak, Erin Plews, Dorothy M. K. Keefe, Bronwen Mayo, Imogen WhiteAbstract:Background Gastrointestinal (GI) mucositis caused by chemotherapy is associated with diarrhoea and intestinal barrier disruption caused by apoptosis, immune dysfunction and microbiome alterations. Serum-derived Bovine Immunoglobulin/protein isolate (SBI) has been shown to manage HIV-associated enteropathy and irritable bowel syndrome with diarrhoea (IBS-D). We investigated in a rat model whether SBI was effective in alleviating symptoms of irinotecan-induced GI mucositis.
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Management of inflammatory bowel disease with oral serum-derived Bovine Immunoglobulin.
Therapeutic Advances in Gastroenterology, 2015Co-Authors: I Shafran, Patricia Burgunder, David Wei, Hayley E. Young, Gerald L. Klein, Bruce BurnettAbstract:Introduction:The clinical effect of oral serum-derived Bovine Immunoglobulin/protein isolate (SBI) on symptom and disease management in patients with inflammatory bowel disease (IBD) is reported in...
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Serum-derived Bovine Immunoglobulin isolate increases peripheral and mucosal CD4 T cell count in patients with HIV enteropathy
Journal of the International AIDS Society, 2015Co-Authors: David M. Asmuth, Audrey L. Shaw, John Hinkle, Eric A. Weaver, Ma Somsouk, Peter W. Hunt, Christopher J. Miller, Gerald L. KleinAbstract:Oral serum-derived Bovine Immunoglobulin improves duodenal immune reconstitution and absorption function in patients with HIV enteropathy David M. Asmuth a,b , Zhong-Min Ma c,d , Anthony Albanese b , Netanya G. Sandler e , Sridevi Devaraj f , Thomas H. Knight a , Neil M. Flynn a , Tammy Yotter a , Juan-Carlos Garcia a , Emily Tsuchida g , Tsung-Teh Wu h , Daniel C. Douek e and Christopher J. Miller b,c Objectives: To examine the impact of serum-derived Bovine Immunoglobulin, an oral medical food known to neutralize bacterial antigen and reduce intestinal inflammation, on restoration of mucosal immunity and gastrointestinal function in individuals with HIV enteropathy. Design: Open-label trial with intensive 8-week phase of Bovine serum immuno- globulin (SBI) 2.5 g twice daily with a 4-week washout period and an optional 9-month extension study. Methods: HIV enteropathy was defined as chronic gastrointestinal symptoms including frequent loose or watery stools despite no identifiable, reversible cause. Upper endoscopy for tissue immunofluorescent antibody assay and disaccharide gut permeability/absorption studies were performed before and after 8 weeks of SBI to test mucosal immunity and gastrointestinal function. Blood was collected for markers of microbial translocation, inflammation, and collagen kinetics. A validated gastro- intestinal questionnaire assessed changes in symptoms. Results: All eight participants experienced profound improvement in symptoms with reduced bowel movements/day (P ¼ 0.008) and improvements in stool consistency (P ¼ 0.008). Gut permeability was normal before and after the intervention, but D -xylose absorption increased in seven of eight participants. Mucosal CD4 þ lymphocyte densities increased by a median of 139.5 cells/mm 2 from 213 to 322 cells/mm 2 (P ¼ 0.016). Intestinal-fatty acid binding protein (I-FABP), a marker of enterocyte damage, initially rose in seven of eight participants after 8 weeks (P ¼ 0.039), and then fell below baseline in four of five who continued receiving SBI (P ¼ 0.12). Baseline serum I-FABP levels were negatively correlated with subsequent rise in mucosal CD4 þ lymphocyte densities (r ¼ 0.74, P ¼ 0.046). Conclusion: SBI significantly increases intestinal mucosal CD4 þ lymphocyte counts, improves duodenal function, and showed evidence of promoting intestinal repair in the s 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins setting of HIV enteropathy. AIDS 2013, 27:2207–2217 a University of California Davis Medical School, b Veterans Administration Northern California Healthcare System, Sacramento, University of California - Davis, d Center for Comparative Medicine, Davis, California, e Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, f Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas, g CARES Clinic, Sacramento, California, and h Mayo Clinic, Rochester, Minnesota, USA. Correspondence to David M. Asmuth, MD, Professor of Medicine, Division of Infectious & Immunologic Diseases, UC Davis Medical Center, 4150 V Street, PSSB G500, Sacramento, CA 95817, USA. Tel: +1 916 734 8695; fax: +1 916 734 7766; e-mail: david.asmuth@ucdmc.ucdavis.edu Received: 4 April 2013; revised: 2 May 2013; accepted: 3 May 2013. c DOI:10.1097/QAD.0b013e328362e54c ISSN 0269-9370 Q 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivitives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
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Serum-derived Bovine Immunoglobulin/protein isolate in the alleviation of chemotherapy-induced mucositis
Supportive Care in Cancer, 2015Co-Authors: Emma Bateman, Eric M. Weaver, Gerald L. Klein, Anthony Wignall, Belinda Wozniak, Erin Plews, Bronwen J. Mayo, Imogen A. White, Dorothy M. K. KeefeAbstract:Background Gastrointestinal (GI) mucositis caused by chemotherapy is associated with diarrhoea and intestinal barrier disruption caused by apoptosis, immune dysfunction and microbiome alterations. Serum-derived Bovine Immunoglobulin/protein isolate (SBI) has been shown to manage HIV-associated enteropathy and irritable bowel syndrome with diarrhoea (IBS-D). We investigated in a rat model whether SBI was effective in alleviating symptoms of irinotecan-induced GI mucositis.
Kenneth J. Maas - One of the best experts on this subject based on the ideXlab platform.
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Attenuation of Colitis by Serum-Derived Bovine Immunoglobulin/Protein Isolate in a Defined Microbiota Mouse Model
Digestive Diseases and Sciences, 2015Co-Authors: Abigail L Henderson, Meghan Wymore Brand, Ross J. Darling, Kenneth J. Maas, Christopher J. Detzel, Jesse Hostetter, Michael J Wannemuehler, Eric M. WeaverAbstract:Background The pathogenesis of inflammatory bowel disease (IBD) is complex and multifaceted including genetic predisposition, environmental components, microbial dysbiosis, and inappropriate immune activation to microbial components. Pathogenic bacterial provocateurs like adherent and invasive E. coli have been reported to increase susceptibility to Crohn’s disease. Serum-derived Bovine Immunoglobulin/protein isolate (SBI) is comprised primarily of Immunoglobulins (Igs) that bind to conserved microbial components and neutralize exotoxins. Aim To demonstrate that oral administration of SBI may modulate mucosal inflammation following colonization with E. coli , LF82, and exposure to dextran sodium sulfate (DSS). Methods Defined microbiota mice harboring the altered Schaedler flora (ASF) were administered SBI or hydrolyzed collagen twice daily starting 7 days prior to challenge with E. coli LF82 and continuing for the remainder of the experiment. Mice were treated with DSS for 7 days and then evaluated for evidence of local and peripheral inflammation. Results Igs within SBI bound multiple antigens from all eight members of the ASF and E. coli LF82 by western blot analysis. Multiple parameters of LF82/DSS-induced colitis were reduced following administration of SBI, including histological lesion scores, secretion of cytokines and chemokines from cecal biopsies, intestinal fatty acid binding protein (I-FABP) and serum amyloid A from plasma. Conclusions Oral administration of SBI attenuated clinical signs of LF82/DSS-induced colitis in mice. The data are consistent with the hypothesis that SBI Immunoglobulin binding of bacterial antigens in the intestinal lumen may inhibit the inflammatory cascades that contribute to IBD, thus attenuating DSS-induced colitis.
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Attenuation of Colitis by Serum-Derived Bovine Immunoglobulin/Protein Isolate in a Defined Microbiota Mouse Model
Digestive Diseases and Sciences, 2015Co-Authors: Abigail Henderson, Meghan Wymore Brand, Ross J. Darling, Kenneth J. Maas, Christopher J. Detzel, Jesse Hostetter, Michael J Wannemuehler, Eric M. WeaverAbstract:Background The pathogenesis of inflammatory bowel disease (IBD) is complex and multifaceted including genetic predisposition, environmental components, microbial dysbiosis, and inappropriate immune activation to microbial components. Pathogenic bacterial provocateurs like adherent and invasive E. coli have been reported to increase susceptibility to Crohn’s disease. Serum-derived Bovine Immunoglobulin/protein isolate (SBI) is comprised primarily of Immunoglobulins (Igs) that bind to conserved microbial components and neutralize exotoxins.
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attenuation of colitis by serum derived Bovine Immunoglobulin protein isolate in a defined microbiota mouse model
Digestive Diseases and Sciences, 2015Co-Authors: Abigail Henderson, Meghan Wymore Brand, Ross J. Darling, Kenneth J. Maas, Christopher J. Detzel, Jesse Hostetter, Michael J Wannemuehler, Eric M. WeaverAbstract:Background The pathogenesis of inflammatory bowel disease (IBD) is complex and multifaceted including genetic predisposition, environmental components, microbial dysbiosis, and inappropriate immune activation to microbial components. Pathogenic bacterial provocateurs like adherent and invasive E. coli have been reported to increase susceptibility to Crohn’s disease. Serum-derived Bovine Immunoglobulin/protein isolate (SBI) is comprised primarily of Immunoglobulins (Igs) that bind to conserved microbial components and neutralize exotoxins.
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Bovine Immunoglobulin protein isolate binds pro inflammatory bacterial compounds and prevents immune activation in an intestinal co culture model
PLOS ONE, 2015Co-Authors: Christopher J. Detzel, Alan Horgan, Bryon W Petschow, Christopher D Warner, Abigail Henderson, Kenneth J. Maas, Eric M. WeaverAbstract:Intestinal barrier dysfunction is associated with chronic gastrointestinal tract inflammation and diseases such as IBD and IBS. Serum-derived Bovine Immunoglobulin/protein isolate (SBI) is a specially formulated protein preparation (>90%) for oral administration. The composition of SBI is greater than 60% Immunoglobulin including contributions from IgG, IgA, and IgM. Immunoglobulin within the lumen of the gut has been recognized to have anti-inflammatory properties and is involved in maintaining gut homeostasis. The binding of common intestinal antigens (LPS and Lipid A) and the ligand Pam3CSK4, by IgG, IgA, and IgM in SBI was shown using a modified ELISA technique. Each of these antigens stimulated IL-8 and TNF-α cytokine production by THP-1 monocytes. Immune exclusion occurred as SBI (≤50 mg/mL) bound free antigen in a dose dependent manner that inhibited cytokine production by THP-1 monocytes in response to 10 ng/mL LPS or 200 ng/mL Lipid A. Conversely, Pam3CSK4 stimulation of THP-1 monocytes was unaffected by SBI/antigen binding. A co-culture model of the intestinal epithelium consisted of a C2BBe1 monolayer separating an apical compartment from a basal compartment containing THP-1 monocytes. The C2BBe1 monolayer was permeabilized with dimethyl palmitoyl ammonio propanesulfonate (PPS) to simulate a damaged epithelial barrier. Results indicate that Pam3CSK4 was able to translocate across the PPS-damaged C2BBe1 monolayer. However, binding of Pam3CSK4 by Immunoglobulins in SBI prevented Pam3CSK4 translocation across the damaged C2BBe1 barrier. These results demonstrated steric exclusion of antigen by SBI which prevented apical to basal translocation of antigen due to changes in the physical properties of Pam3CSK4, most likely as a result of Immunoglobulin binding. This study demonstrates that Immunoglobulins in SBI can reduce antigen-associated inflammation through immune and steric exclusion mechanisms and furthers the mechanistic understanding of how SBI might improve immune status and reduce inflammation in various intestinal disease states.
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Bovine Immunoglobulin/Protein Isolate Binds Pro-Inflammatory Bacterial Compounds and Prevents Immune Activation in an Intestinal Co-Culture Model
PLOS ONE, 2015Co-Authors: Christopher J. Detzel, Alan Horgan, Bryon W Petschow, Christopher D Warner, Abigail Henderson, Kenneth J. Maas, Eric M. WeaverAbstract:Intestinal barrier dysfunction is associated with chronic gastrointestinal tract inflammation and diseases such as IBD and IBS. Serum-derived Bovine Immunoglobulin/protein isolate (SBI) is a specially formulated protein preparation (>90%) for oral administration. The composition of SBI is greater than 60% Immunoglobulin including contributions from IgG, IgA, and IgM. Immunoglobulin within the lumen of the gut has been recognized to have anti-inflammatory properties and is involved in maintaining gut homeostasis. The binding of common intestinal antigens (LPS and Lipid A) and the ligand Pam3CSK4, by IgG, IgA, and IgM in SBI was shown using a modified ELISA technique. Each of these antigens stimulated IL-8 and TNF-α cytokine production by THP-1 monocytes. Immune exclusion occurred as SBI (≤50 mg/mL) bound free antigen in a dose dependent manner that inhibited cytokine production by THP-1 monocytes in response to 10 ng/mL LPS or 200 ng/mL Lipid A. Conversely, Pam3CSK4 stimulation of THP-1 monocytes was unaffected by SBI/antigen binding. A co-culture model of the intestinal epithelium consisted of a C2BBe1 monolayer separating an apical compartment from a basal compartment containing THP-1 monocytes. The C2BBe1 monolayer was permeabilized with dimethyl palmitoyl ammonio propanesulfonate (PPS) to simulate a damaged epithelial barrier. Results indicate that Pam3CSK4 was able to translocate across the PPS-damaged C2BBe1 monolayer. However, binding of Pam3CSK4 by Immunoglobulins in SBI prevented Pam3CSK4 translocation across the damaged C2BBe1 barrier. These results demonstrated steric exclusion of antigen by SBI which prevented apical to basal translocation of antigen due to changes in the physical properties of Pam3CSK4, most likely as a result of Immunoglobulin binding. This study demonstrates that Immunoglobulins in SBI can reduce antigen-associated inflammation through immune and steric exclusion mechanisms and furthers the mechanistic understanding of how SBI might improve immune status and reduce inflammation in various intestinal disease states.