Pubmed - Colostral proline-rich polypeptides--immunoregulatory properties and prospects of therapeutic use in Alzheimer's disease

Department of Immunochemistry, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 R. Weigla, 53-114 Wrocław, Poland. janusz@iitd.pan.wroc.pl

Abstract

A proline-rich polypeptide complex (PRP), subsequently called Colostrinin(CLN), was first isolated from ovine colostrum, was shown to possess immunoregulatory properties, including effects on the maturation and differentiation of murine thymocytes and humoral and cellular immune responses, both in vivo and in vitro. 

PRP seems to restore balance in cellular immune functions and is not species specific. PRP is a complex of peptides of molecular masses ranging from 500 to 3000 Da. The polypeptide contains 25% proline and 40% hydrophobic amino acids. PRP shows a regulatory activity in cytokine (IFN, TNF-alpha, IL-6, IL-10) induction and possesses the ability to inhibit the overproduction of oxygen reactive species and nitric oxide. Besides its immunoregulatory activity, PRP also showed psychotropic properties, improving cognitive activity and behavior of old rats, humans, and chickens. 

The properties of PRP prompted the authors to propose the complex for the treatment neurodegenerative disorders. Beneficial effects of PRP/Colostrinin were shown for the first time in double-blind placebo-controlled trials and long-term open-label studies. The results were confirmed in multicenter clinical trials. 

A very important property of PRP/Colostrinin is the prevention of Abeta aggregation and the disruption of already existing aggregates. The same properties were expressed by one of PRP's components, a nonapeptide (NP). Moreover, PRP modulates neurite outgrowth, suppresses uncontrolled activation of cells, reduces 4-HNE-mediated cellular damage, and modulates expression in cellular redox regulation, cell proliferation, and differentiation. 

Its biological response modifying activity can play an important role in its use in the treatment of Alzheimer's disease.

http://www.ncbi.nlm.nih.gov/pubmed/19939229

Pubmed - Antioxidative properties of lactoferrin from bovine colostrum before and after its lyophilization

Institute for Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine, Kharkov, Ukraine. cryo@online.kharkov.ua

Abstract

The effect of lactoferrin (LF) derived from native, frozen and lyophilized bovine colostrum on the intensity of free-radical processes in model systems has been investigated. It was shown that LF, not depending on the source of its obtaining, is an efficient iron chelator and decreases intensity of peroxidative processes. It was established, that antioxidative properties of LF from lyophilized colostrum have remained unchanged within 12 months of dry colostrum storage under proper conditions.

http://www.ncbi.nlm.nih.gov/pubmed/14566387

Pubmed - Bovine immune colostrum against 17 strains of diarrhea bacteria and in vitro and in vivo effects of its specific IgG

Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 122 Nanjing Ninghai Road, Nanjing 210097, PR China.

Abstract

Bovine colostral antibodies of cows immunized with a multivalent vaccine consisting of whole cells of 17 strains of pathogenic diarrhea bacteria were generated, and the specific IgG with high activities and titres directed against these pathogens was purified using an ammonium sulfate precipitation and verified by SDS-PAGE. We demonstrate that specific IgG has a strong activity of inhibiting in vitro growth and colonization in pathogens by agglutinating with bacteria and destroying cell walls. Normal IgG purified from non-immunized bovine colostrum is incapable of eliciting the same consequences as specific IgG. Specific IgG prevents enteroinvasive Escherichia coli/Salmonella typhi-induced diarrhea and may exert an effective protection by enhancing splenic NK cell activity, elevating IL-2 level and inhibiting excessive release of TNF-alpha in mice. Thus, the specific IgG from colostral antibodies of immunized bovine can provide effective protection or therapy for multibacteria-induced diarrhea.

http://www.ncbi.nlm.nih.gov/pubmed/16314006

Pubmed - Factors in ruminant colostrum that influence cell growth and murine IgE antibody responses

Department of Food Science, Aarhus University, Blichers Allé 20, DK-8830 Tjele, Denmark.

Abstract

Characterization and identification of peptides with bioactivity from food have received considerable interest recently since such bioactive components must be adequately documented if they are part of functional food claims. We have characterized peptides from colostrum or those generated by a simulated gastrointestinal digest (GI) and tested them for bioactivity using murine intestinal (mIC(c12)) cells and compared with bioactivity of intact colostrum. 

The peptides were recovered in the permeate after dialysis. The presence of peptides in the permeate was confirmed by C(18) RP-HPLC, determination of free amino termini and MALDI MS. The bioactivity of the intact colostrum and colostral peptides in the permeate was tested using mIC(c12) cells stimulated in the absence or presence of different bacterial ligands that mediate cellular activation through stimulation of Toll-like receptors (TLR). 

Whereas intact colostrum generally reduced TLR-mediated signaling, the isolated peptides seemed to either stimulate or reduce the immune response depending on the bacterial ligand used for stimulation. Interestingly, the most potent bioactive peptides originated from nondigested colostrum, which had only been subject to endogenous protease activity. Identified peptides in the nondigested colostrum originated exclusively from the casein fraction of colostrum as shown by MALDI MS/MS identification. 

Thus, multiple components with different bioactivities towards the innate immune response appear in bovine colostrum.

http://www.ncbi.nlm.nih.gov/pubmed/19904766

Pubmed - Bovine colostrum as a biologic in clinical medicine: a review--Part II: clinical studies

Center for Transfusion Medicine Muenster, German Red Cross Blood Transfusion Service West gGmbH, Muenster, Germany.

Abstract

The value of bovine colostrum as a biologic in medicine is documented in clinical trials and supported by relatively large databases containing case reports and anecdotal findings. The main actions include an antibacterial effect and modulation of the immune response. The ability of bovine colostrum concentrates (BCC are polyvalent bovine colostrum concentrates produced from the colostrums of several 100 cows) to neutralize lipopolysaccharides, i.e. endotoxins arising from Gram-negative bacterial pathogens and to inhibit enterogenic endotoxemia in animal models as shown in the last review to have its counterpart in patient therapy. 

Clinical trials with BCC provide evidence that oral application reduces the influx of LPS from the gut and this appears to be a major mechanism underlying its therapeutic effect in patients at risk for Gram-negative septic shock; data from two well-controlled clinical studies with a total of 100 surgical patients have shown that the inhibition of intestinal LPS absorption measured after the application of BCC not only reduced the LPS levels in the peripheral blood but also inflammatory parameters like IL-6 and CRP were found to be diminished. 

The usual daily dose of the commercially available BCC preparation, LactobinA (LC1) is 10 â 20 g daily, but higher doses can be used in the majority of patients because of the low incidence of intolerance problems. In chronic diarrhea involving severe forms of secondary immunodeficiencies, patients receiving LC1 were disease-free for about 4 weeks but the response may be lower in patients with AIDS. 

BCC is effective in infants with hemorrhagic diarrhea caused by infections with enterohemorrhagic E. coli and reduces the likelihood of the disease progressing to a hemolytic uremic syndrome. The safety of newer BCC products obtained from BSE-free regions seems now beyond contention. In the case of LC1, which was used as a commercial dietary foodstuff in Germany until 1992 and tested in three Phase 1 and 5 clinical studies (two trials in patients with secondary immunodeficiencies, one in surgical patients with gastrointestinal disorders, one in patients undergoing open heart surgery and one in pediatric patients with EHEC infections), there were no cases of BSE-associated disease such as the new variant of Creutzfeldt-Jakob disease. 

Side effects of clinical relevance are limited to possible intolerance to lactose and sensitivity to milk proteins as these are also present in many commonly used foodstuffs. Important synergistic actions with conventional drug therapies have been observed with BCC including a reduction in LPS plasma levels in patients with Gram-negative bacterial infections treated with bactericidal antibiotics. 

In healthy persons there are only small concentrations of LPS detectable in peripheral blood (normal values: 3 â 10 pg/ ml plasma, i.e. approximately 0.1 EU/ml). In contrast, elevated systemic levels with concentrations > 300 pg/ml are common in patients with severe Gram-negative sepsis and septic shock. Raised LPS levels occur mainly in patients with Gram-negative bacterial infections who have been treated with bacteriocidal antibiotics. The LPS-lowering effects of BCC are probably due to the numerous active components present in BCC which have their origin in the innate humoral and adaptive immune system of their biologic source, the cow.

http://www.ncbi.nlm.nih.gov/pubmed/18538107

Pubmed - Bovine colostrum promotes growth and migration of the human keratinocyte HaCaT cell line

San Gallicano Dermatological Institute, IRCCS, Rome, Italy.

Abstract

Bovine colostrum represents a rich source of growth factors, which are known to play a central role in wound healing. The aim of our study was to investigate the possible mitogenic and motogenic effects induced by colostrum on human keratinocytes. 

Cell proliferation evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide test and 5-Bromo-2'-deoxyuridine incorporation revealed that colostrum exerts a growth promoting activity. Scratch assay and immunofluorescence of actin cytoskeleton showed its effectiveness also in inducing cell migration. 

Furthermore, colostrumtreatment increases the levels of tyrosine phosphorylated proteins and the activated forms of the extracellular signal-regulated kinases 1 and 2 and such effects appear to be repressed by the tyrosine kinase inhibitor genistein. Our results indicate that the biological activities of colostrum are specifically mediated by the growth factor-induced activation of tyrosine kinase receptors and underline the relevance of the synergistic action exerted by the growth factors in stimulating keratinocyte proliferation and migration essential for tissue repair.

http://www.ncbi.nlm.nih.gov/pubmed/19919532

Pubmed - Improvement of growth performance and sanitary status of weaned piglets fed a bovine colostrum-supplemented diet.

INRA, UMR 1079 SENAH, F-35590 Saint-Gilles, France.

Abstract

The present study investigated the effect of 3 different durations of feeding a diet supplemented with defatted bovinecolostrum (Col) on growth performance and sanitary status of the weaned piglet. At 28 d of age, piglets were weaned and fed 1 of the 2 following diets: a control (Ctrl) starter diet or a starter diet supplemented with Col. 

Two experiments were conducted. In Exp. 1, 310 piglets (12 pens consisting 10 piglets/pen and 10 pens consisting 19 piglets/pen) were allocated to 1 of the 2 dietary treatments for 12 d. In Exp. 2, 522 piglets (18 pens consisting 10 piglets/pen and 18 pens consisting 19 piglets/pen) were allocated to 1 of the following 3 dietary treatments: fed the Ctrl diet from d 1 to 12 (Ctrl), Col diet from d 1 to 4 and then the Ctrl diet up to d 12 (Col-4d), or the Col diet from d 1 to 6 and then the Ctrl diet up to d 12 (Col-6d). 

For both experiments, a commercial second phase diet was fed to piglets from d 12 to 46. Feed intake, growth performance, and cleanliness of floor and hindquarters of animals were investigated during the first 7 post-weaning wk. In Exp. 1, from d 0 to 12, ADFI, ADG, and G:F were 16 (P = 0.004), 23 (P < 0.001), and 5% (P = 0.069) greater, respectively, in Col piglets compared to Ctrl piglets. Thereafter, ADFI and ADG were 7 (P < 0.001) and 9% (P < 0.001) greater, respectively, in Col piglets than Ctrl piglets (d 12 to 46). On d 12 after weaning, piglets fed the Col diet had more normal feces (+13%) and less soft or liquid feces (-9 and -4%, respectively) than piglets fed the Ctrl diet (P = 0.06). 

Compared to Ctrl piglets, feeding the Col diet led to more days with normal feces for the floor cleanliness (+22%; P < 0.001) from d 7 to 11. In Exp. 2, compared with Ctrl piglets, ADFI, ADG, and G:F were 8, 23, and 13% greater (P < 0.05) in Col-6d piglets from d 0 to 9, whereas values for Col-4d piglets were intermediate and did not differ from the values of the other dietary treatments. On d 9 after weaning, piglets fed the Col-4d or the Col-6d diet had more normal feces (+6 and +4%, respectively) and less liquid feces (-4 and -3%, respectively) than piglets fed the Ctrl diet (P = 0.08). 

No long lasting effects were observed thereafter. In conclusion, there was a reduction of weaning-induced growth check and diarrheal episodes in weaned piglets fed the Col diet. The beneficial effects of the bovine colostrum were observed beyond the period of treatment when the supplementation covered the first 6 d post-weaning, which corresponded to the acute phase of postweaning digestive disturbances.

http://www.ncbi.nlm.nih.gov/pubmed/22079995