Pubmed - New insights into clinical trial for Colostrinin in Alzheimer's disease

Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, Texas 77555, USA.

Abstract

BACKGROUND:

The pathomechanism of Alzheimer's disease (AD) is multifactorial although the most popular hypotheses are centered on the effects of the misfolded, aggregated protein, amyloid beta (Abeta) and on Tau hyperphosphorylation.

OBJECTIVES:

Double blinded clinical trials were planned to demonstrate the effect of Colostrinin (CLN) on instrumental daily activities of AD patients. The potential molecular mechanisms by which CLN mediates its effects were investigated by gene expression profiling.

METHODS:

RNAs isolated from CLN-treated cells were analyzed by high-density oligonucleotide arrays. Network and pathway analyses were performed using the Ingenuity Pathway Analysis software.

RESULTS:

The Full Sample Analysis at week 15 showed a stabilizing effect of CLN on cognitive function in ADAS-cog (p = 0.02) and on daily function in IADL (p = 0.02). The overall patient response was also in favor of CLN (p = 0.03). Patients graded as mild on entry also showed a superior response of ADAS-cog compared to more advanced cases (p = 0.01). Data derived from microarray network analysis show that CLN elicits highly complex and multiphasic changes in the cells' transcriptome. Importantly, transcriptomal analysis showed that CLN alters gene expression of molecular networks implicated in Abeta precursor protein synthesis, Tau phosphorylation and increased levels of enzymes that proteolitically eliminate Abeta. In addition, CLN enhanced the defense against oxidative stress and decreased expression of inflammatory chemokines and cytokines, thereby attenuating inflammatory processes that precede Alzheimer's and other neurological diseases.

CONCLUSION:

Together these data suggest that CLN has promising potential for clinical use in prevention and therapy ofAlzheimer's and other age-associated central nervous system diseases.

http://www.ncbi.nlm.nih.gov/pubmed/19262960

Pubmed - Determination of soluble immunoglobulin G in bovine colostrum products by Protein G affinity chromatography-turbidity correction and method validation

Cawthron Institute, Nelson, New Zealand. patrick.holland@cawthron.org.nz

Abstract

Immunoglobulin-containing food products and nutraceuticals such as bovine colostrum are of interest to consumers as they may provide health benefits. Commercial scale colostrum products are valued for their immunoglobulin G (IgG) content and therefore require accurate analysis. One of the most commonly used methods for determining total soluble IgG in colostrumproducts is based on affinity chromatography using a Protein G column and UV detection. 

This paper documents improvements to the accuracy of the Protein G analysis of IgG in colostrum products, especially those containing aggregated forms of IgG. Capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) analysis confirmed that aggregated IgG measured by Protein G does not contain significant amounts of casein or other milk proteins. 

Size exclusion chromatography identified the content of soluble IgG as mainly monomeric IgG and aggregated material MW > 450 kDa with small amounts of dimer and trimer. The turbidity of the eluting IgG, mainly associated with aggregated IgG, had a significant effect on the quantitative results. Practical techniques were developed to correct affinity LC data for turbidity on an accurate, consistent, and efficient basis. The method was validated in two laboratories using a variety of colostrum powders. Precision for IgG was 2-3% (RSD(r)) and 3-12% (RSD(R)). Recovery was 100.2 ± 2.4% (mean ± RSD, n = 10). Greater amounts of aggregated IgG were solubilized by a higher solution:sample ratio and extended times of mixing or sonication, especially for freeze-dried material. 

It is concluded that the method without acid precipitation and with turbidity correction provides accurate, precise, and robust data for total soluble IgG and is suitable for product specification and quality control of colostrum products.

http://www.ncbi.nlm.nih.gov/pubmed/21524111

Pubmed - Bovine milk antibodies for health

Agricultural Research Centre of Finland, Food Research, FIN-31600 Jokioinen, Finland. hannu.j.korhonen@mtt.fi

Abstract

The immunoglobulins of bovine colostrum provide the major antimicrobial protection against microbial infections and confer a passive immunity to the newborn calf until its own immune system matures. The concentration in colostrum of specific antibodies against pathogens can be raised by immunising cows with these pathogens or their antigens. Immune milk products are preparations made of such hyperimmune colostrum or antibodies enriched from it. 

These preparations can be used to give effective specific protection against different enteric diseases in calves and suckling pigs. Colostral immunoglobulin supplements designed for farm animals are commercially available in many countries. Also, some immune milk products containing specific antibodies against certain pathogens have been launched on the market. A number of clinical studies are currently in progress to evaluate the efficacy of immune milks in the prevention and treatment of various human infections, including those caused by antibiotic resistant bacteria. 

Bovine colostrum-based immune milk products have proven effective in prophylaxis against various infectious diseases in humans. Good results have been obtained with products targeted against rotavirus, Shigella flexneri, Escherichia coli, Clostridium difficile, Streptococcus mutans, Cryptosporidium parvum and Helicobacter pylori. Some successful attempts have been made to use immune milk in balancing gastrointestinal microbial flora. 

Immune milk products are promising examples of health-promoting functional foods, or nutraceuticals. This review summarises the recent progress in the development of these products and evaluates their potential as dietary supplements and in clinical nutrition.

http://www.ncbi.nlm.nih.gov/pubmed/11242458

Pubmed - Remission of diarrhoea due to cryptosporidiosis in an immunodeficient child treated with hyperimmune bovine colostrum

Abstract
A boy aged 6 months who presented with poor weight gain, diarrhoea, and infection with Pneumocystis carinii was found to have congenital hypogammaglobulinaemia, which did not improve despite monthly treatment with intravenous gammaglobulin. At the age of 3 years and 2 months he developed severe vomiting and diarrhoea due to cryptosporidiosis, which failed to respond to conventional treatment. Infusion of hyperimmune bovine colostrum produced against parasite antigen, given by nasogastric tube, was started after symptoms had persisted for three weeks. His vomiting and diarrhoea resolved within five days of treatment, and oocysts were no longer seen in the stools after eight days. Later, however, he developed a rare complication, and oocysts were found in the common bile duct. Hyperimmune bovine colostrum may be useful in the treatment of many patients with immunodeficiency disorders.

PMID: 3096462 http://www.ncbi.nlm.nih.gov/pubmed/3096462

Pubmed - Passive immunization of hamsters against disease caused by Clostridium difficile by use of bovine immunoglobulin G concentrate

Department of Anaerobic Microbiology, Virginia Polytechnic Institute and State University, Blacksburg 24061.

Abstract
Gestating Holstein cows were vaccinated with Clostridium difficile toxoid prepared from the culture filtrate of a strain that produces high levels of toxins A and B and other antigens. A bovine immunoglobulin G (IgG) concentrate was prepared from colostrum collected at parturition. The results of our studies showed that hamsters treated prophylactically with the hyperimmune bovine IgG concentrate were protected against C. difficile disease. These results suggest that orally administered hyperimmune bovine IgG specific for C. difficile culture filtrate may be useful in prophylaxis against C. difficile disease.

PMID: 2037383 http://www.ncbi.nlm.nih.gov/pubmed/2037383

Pubmed - Human colostrum: a natural source of probiotics

Instituto Fernandes - IFF / Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.

Abstract
OBJECTIVE:
The aim of the present study was to obtain data on the microbiota of human colostrum, and to correlate it with a possible source of probiotics transferred from mother to infant during breastfeeding.

METHODS:
70 samples of milked human colostrum were analyzed as to the presence of mesophylic, thermoduric, psychrotrophic, proteolytic, proteolytic-psychrotrophic, lipolytic microorganisms, molds and yeasts, Staphylococcus aureus, total coliforms, fecal coliforms, Group D Streptococcus species and lactic acid bacteria.

RESULTS:
the microbiological analyses revealed several classical groups of microorganisms: mesophylic (68.6%); thermoduric (38.6%); psychrotrophic (8.6%); proteolytic (15.7%); proteolytic-psychrotrophic (1,4%); lipolytic (4.3%); molds and yeasts (11.4%); Staphylococcus aureus (44.3%); total coliforms (7.2%); and lactic acid bacteria (37.2%), thus characterizing a diversified microbiota. Thermoduric-psychrotrophic microorganisms, fecal coliforms and Group D Streptococcus species were not identified in any of the samples.

CONCLUSIONS:
The results show a microbiota rich in lactic acid bacteria, which may work as probiotics if delivered to infants within the first days of life.

PMID: 14647857 http://www.ncbi.nlm.nih.gov/pubmed/14647857

Microbial adhesion of Cryptosporidium parvum: identification of a colostrum-derived inhibitory lipid

Department of Pathobiology, College of Veterinary Medicine, University of Illinois; Urbana, IL 61802, USA.

Abstract
We previously described an unidentified lipid purified from calf small intestine that inhibits the in vitro adhesion of Cryptosporidium parvum sporozoites to host cells [Johnson JK, Schmidt J, Gelberg HB, Kuhlenschmidt MS. Microbial adhesion of Cryptosporidium parvum sporozoites: purification of an inhibitory lipid from bovine mucosa. J Parasitol 2004;90:980-90]. Intestinal mucosa from some calves, however, failed to yield this bioactive lipid. Accordingly, we examined other potential sources, especially dietary sources, of the inhibitory lipid and discovered it was principally derived from bovine colostrum. Interestingly, fresh colostrum yielded little or no inhibitory lipid, however, the lipid was found in relatively large quantities following incubation of colostrum with the aqueous fraction of calf intestinal contents. Using FAB-MS and NMR analysis, the sporozoite inhibitory lipid (SIL) was identified as oleic acid, a monounsaturated fatty acid likely released from colostrum triglycerides and phospholipids by digestion in the lumen of the calf small intestine. Oleic acid dose-dependently inhibited in vitro sporozoite-host cell adhesion with an inhibitory constant (IC(50)) of approximately 5 microM. Comparison of oleic acid with other C-18 fatty acids revealed linolenic, but not stearic acid, also displayed potent inhibitory activity. Neither linolenic nor oleic acid, however, affect either sporozoite or host cell viability at concentrations that inhibit sporozoite adhesion. These results suggest certain colostrum-derived long-chain fatty acids may serve as natural inhibitors of the early steps in C. parvum sporozoite-host cell interactions.

PMID: 18675305

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