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PubMed2003

Modulation of 4HNE-mediated signaling by proline-rich peptides from ovine colostrum.

In previous studies we showed that colostrinin (CLN), a complex of proline-rich polypeptides derived from ovine colostrum, induces mitogenic stimulation, as well as a variety of cytokines in human peripheral blood leukocytes, and possesses antioxidant activity in pheochromocytoma (PC12) cells. In this study we investigated the effects of CLN on 4-hydroxynonenal (4HNE)-mediated adduct formation, generation of reactive oxygen species (ROS), glutathione (GSH) metabolism, and the modification of signal transduction cascade that leads to activation of c-Jun N-terminal kinase (JNK) in PC12 cells. Here we demonstrate that CLN (1) reduced the abundance of 4HNE-protein adducts, as shown by fluorescent microscopy and Western blot analysis; (2) reduced intracellular levels of ROS, as shown by a decrease in 2',7'-dichlorodihydro-fluorescein-mediated fluorescence; (3) inhibited 4HNE-mediated GSH depletion, as determined fluorimetrically; and (4) inhibited 4HNE-induced activation of JNKs. Together, these findings suggest that CLN appears to down-regulate 4HNE-mediated lipid peroxidation and its product-induced signaling that otherwise may lead to pathological changes at the cellular and organ level. These findings also suggest further that CLN could be useful in the treatment of diseases such as Alzheimer's, as well as those in which ROS are implicated in pathogenesis.

Aldehydes↗
PubMed1979

Effect of modification of reactive lysine on antitryptic and antichymotryptic activity of proteinase inhibitor from cow colostrum.

40% of the primary structure of the cow colostrum proteinase inhibitor (CTI) is homologous with the structure of the trypsin kallikrein inhibitor (TKI) from bovine organs; the positions of the reactive lysine residues are also the same in both inhibitors. Both CTI and TKI were modified by carbamoylation and the fully labeled derivatives were isolated by ion-exchange chromatography. The effect of the modification on the antitryptic and antichymotryptic activity of both inhibitors was investigated. The antichymotryptic activity of both inhibitors is not decreased after the modification. The antitryptic activity of modified TKI is retained, yet the dissociation constant of the complex of the modified inhibitor with trypsin is considerably increased; nevertheless, modified TKI is a good trypsin inhibitor. The antitryptic activity of modified CTI is hardly detectable. We explain this difference in the behaviour of both inhibitors by a replacement of basic residues Arg-17 and Arg-39 in TKI by neutral amino acids Ala-20 and Gln-42 in CTI.

Amino Acids↗
PubMed1981

Localisation of the prosthetic sugar groups of bovine colostrum kappa-casein.

The study of glycopeptides obtained after enzymic digestions of bovine colostrum kappa-caseinoglycopeptide obtained 15 minutes after calving, demonstrated the presence of two prosthetic sugar groups linked to threonine residues, instead of only one and up to 10 in the case of bovine (normal) and human caseinoglycopeptides, respectively. The secondary structure of bovine kappa-caseinoglycopeptide was reinvestigated.

Acetylgalactosamine↗
PubMed1987

Separation of biologically active chromium complex from cow colostrum.

By a procedure based on ion-exchange chromatography, five chromium-containing fractions were separated from the ethanol extract (50-90%) of cows' colostrum which should provide infant with all or most of the chromium needed in available form. Three of the fractions are anionic (A-1, A-2 and A-3) and two are cationic (C-1 and C-2). Two major fractions, A-1 and A-3, comprise together about 77% of the total chromium recovered in the effluent after ion-exchange chromatography and C-1 and C-2 comprise together only about 21%. Approximate molecular weight was determined by the Sephadex gel chromatography to be 1,500 for A-1 and C-2 and 2,000 for C-1. A-3 was eluted from the Sephadex gel column at the elution position corresponding to that of inorganic trivalent chromium. Among five fractions, A-1 shows glucose tolerance factor (GTF) activity as measured by the stimulation of [U-14C] glucose oxidation to 14CO2 in rat epididymal adipocytes. A-1 stimulates glucose oxidation at chromium concentration as low as 100 pg/ml only when it is incubated with insulin. These findings suggest that A-1 fraction separated from cow milk contains a low-molecular-weight, chromium complex which plays a role in glucose metabolism in close relation with the action of insulin.

Adipose Tissue↗
PubMed2000

Successful hyperimmune bovine colostrum treatment of Savanna monitors (Varanus exanthematicus) infected with Cryptosporidium sp.

Therapy based on the protective passive immunity of hyperimmune bovine colostrum (HBC) (raised against Cryptosporidium parvum in cows) was applied to 4 Savanna monitors (Varanus exanthematicus) with gastric Cryptosporidium sp. infections. All lizards were moderately emaciated, and their fecal and gastric lavage samples contained moderate numbers of Cryptosporidium sp. oocysts. The first 3 of 7 gastric HBC treatments at 1-wk interval each decreased the numbers of oocysts in the fecal and gastric samples to undetectable levels. Neither feces nor lavages of the HBC-treated lizards contained Cryptosporidium sp. oocysts after the HBC therapy, whereas such samples of a single control lizard remained positive for oocysts. Two of the HBC-treated lizards died spontaneously due to metastasized carcinoma and septicemia of unknown etiology, respectively, and 2 lizards treated and killed during the experiment were histologically negative for developmental stages of Cryptosporidium sp. The control lizard died spontaneously of septicemia of unknown etiology and contained developmental stages of Cryptosporidium sp. in the gastric region. The HBC therapy was efficacious in V. exanthematicus and is recommended for lizards with gastric cryptosporidiosis.

Animals↗
PubMed1993

Effects of elevated blood insulin-like growth factor-I (IGF-I) concentration upon IGF-I in bovine mammary secretions during the colostrum phase.

The objectives of these studies were to determine if the concentration of insulin-like growth factor-I (IGF-I) in mammary colostrum secretions could be altered through manipulation of IGF-I concentrations in blood and to compare the temporal changes of IGF-I in mammary secretions to those occurring for IgG1. Milking of 15 pregnant Holstein cows was stopped at 8 weeks prepartum and they were randomly assigned to one of three treatments. A control (C) treatment consisted of feeding the animals 100% of NRC requirements for protein and energy. A second group of cows was fed as the control group and injected with 1.8 mumol bovine GH/day. The third group was fed at 70% of NRC requirements for protein and energy to cause a moderate nutrient restriction (NR). Body weight was measured weekly. Blood was collected by tail venepuncture at 4 h intervals for 24 h. Mammary secretions were collected and pooled among contralateral front and rear quarters (diagonal) for measurement of volume, IGF-I and IgG1 concentrations. Samples were collected at -7, -5, -2, 0 and 1 week postpartum. Cows on the NR treatment failed to gain weight during the dry period compared with C cows (P < 0.05). Blood GH and IGF-I concentrations (P > 0.1) were unaffected by NR treatment. Cows treated with GH had higher (P < 0.01) serum GH and IGF-I levels throughout the entire treatment period, and higher serum IgG1 at 5 and 2 weeks prepartum (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Nutritional Physiological Phenomena↗
PubMed1996

Viable AC-2, a new adult bovine serum- and colostrum-based supplement for the culture of mammalian cells.

In this study we have shown that Viable AC-2, a medium based on the ultrafiltrate fraction of bovine colostrum and adult bovine serum, can be used successfully as a fetal bovine serum (FBS) substitute in the culture of several anchorage-dependent and independent cell lines. Of the 15 cell lines cultured in 8% Viable AC-2 in microplates, 10 reached the maximum cell density of 65%-123% of that in 10% FBS, 4 cell lines reached maximum cell density of 35%-65% of that in 10% FBS and only one cell line, a human osteosarcoma G-292, grew slowly in Viable AC-2. In a small-scale suspension culture, 8%-15% Viable AC-2 supports the growth of Chinese hamster ovary cells (CHO-K1) on microcarriers in spinner flasks significantly better than 10% FBS. Shionogi mouse mammary tumour cell line (S115) transfected with human alpha 2-adrenergic receptor subtype C2 was used as a model to study recombinant protein production in Viable AC-2-supplemented medium. The results showed that in cell culture flasks and in an ACUSYST-R bioreactor, the alpha 2-C2 receptor expression level per mg of total protein was similar in both Viable AC-2 and FBS.

Animals↗
PubMed2000

Growth performance, metabolic and endocrine traits, and absorptive capacity in neonatal calves fed either colostrum or milk replacer at two levels.

Colostrum (CO) contains high amounts, whereas whole milk and milk replacer (MR) contain small amounts, of bioactive and growth-promoting substances, such as IGF-I. An experiment was designed to study the effects of feeding CO or MR on the first 3 d to neonatal calves, followed by whole milk up to d 7, at low and high density. Intestinal absorptive capacity, plasma metabolite and hormone concentrations, and growth performance were measured during the 1st wk of life. Body weight increased (P < .05) similarly in calves fed low or high amounts of CO but did not rise in MR-fed calves. Loose feces were more frequent (P < .05) and absorption of xylose on d 5 was lower (P < .01) in MR- than in CO-fed calves, but there were no effects of feeding density within CO-fed or within MR-fed groups. However, high feeding density within CO-fed groups enhanced (P < .05) total protein, globulin, triglyceride, cholesterol, and insulin concentrations, whereas in the initially high and low MR-fed groups only plasma glucose and insulin after the first meal and plasma NEFA on d 2 were modified (P < .05) by different feeding density. Thus, feeding different amounts of CO partly influenced protein and fat metabolism in calves during the 1st wk of life, but it did not measurably affect intestinal function. However, feeding different amounts of MR, in the absence of CO, barely affected metabolic and endocrine traits and absorptive capacity. Thus, high density CO feeding, and therefore a high supply of nutrients, together with greater amounts of bioactive and growth-promoting substances influenced neonatal metabolism and growth more than a high density of MR feeding containing only small amounts of bioactive and growth-promoting substances. Factors in addition to nutrient density seem to be important for the development of neonatal calves.

Absorption↗
PubMed1984

Isolation of lactoferrin and its concentration in sows' colostrum and milk during a 21-day lactation.

Levels of lactoferrin, an Fe-binding protein with bacteriostatic properties, were determined in the colostrum and milk of Yorkshire sows during a 21-d lactation. Lactoferrin levels averaged 1,100 to 1,300 micrograms/ml near the time of farrowing, then declined sharply during the first week of lactation. Concentration of lactoferrin showed considerable variation among sows, but not among teat positions (anterior to posterior). A method for isolating high purity swine lactoferrin is described.

Animals↗
PubMed1975

Purification and properties of galactosyltransferase from human colostrum.

The galactosyltransferase (Uridine diphosphate-D-galactose: D-glucose 1-galactosyltransferase EC 2.4.1.22) was purified from human colostrum by chromatography on DEAE-cellulose, cellulose phosphate, sephadex G-100, and hydroxylapatite after removal of caseins by centrifugation. The final preparation showed two forms of protein on polyacrylamide disc gel electrophoresis, and both of them exhibited galactosyltransferase activity. The molecular weights of the two forms of the protein were estimated as 44,000 to 45,000 and 55,000 to 57,000 by polyacrylamide disc gel electrophoresis containing sodium dodecyl sulfate. General properties of galactosyltransferase were investigated.

Chromatography↗
PubMed1982

Incorporation of [hydrogen-3] alkylglycerolether and [carbon-14] hexadecanol into bovine colostrum and milk lipids.

[Hydrogen-3] glycerol ether and [carbon-14] hexadecanol were infused into the mammary gland or jugular vein of cows in colostral or full phases of lactation to determine their relative rates of synthesis and degradation. Neutral alkylglycerols were both synthesized and cleaved in the bovine gland. Oxidation of fatty alcohols and cleaving of neutral alkylglycerol ethers was faster during the milk than the colostral phase of lactation. In the colostral phase, both increased rate of synthesis and decreased cleavage contributed to increased neutral alkylglycerol concentration; however, synthesis changes were greater. Disappearance of [carbon-14] fatty alcohol and [hydrogen-3] alkylglycerol ether from the blood was the magnitude of fatty acid disappearance in previous studies, but uptake by the mammary gland was slower. Alkylglycerols were taken up from the blood and secreted intact into both colostrum and milk.

Animals↗
PubMed1994

Regulation of colostrum formation in beef and dairy cows.

Fifteen beef cows and 13 dairy cows were used to investigate the physiological basis of breed differences in IgG1 concentration in colostrum. Concentrations of progesterone and alpha-LA in sera and IgG1 in sera and secretion were quantified in samples collected prepartum. Serum progesterone concentration decreased significantly between 30 and 10 d prepartum, but breeds did not differ. Serum alpha-LA concentration was initially low but increased to 150 ng/ml in beef cows and 720 ng/ml in dairy cows at parturition. Serum IgG1 concentrations averaged 8.4 in beef cows and 5.7 mg/ml in dairy cows between 28 d and 24 d prepartum and subsequently declined to 6.7 in beef and 1.4 mg/ml in dairy cows between 4 d prepartum and calving. Overall, IgG1 concentration was greater in secretion from beef cows (113.4 mg/ml) than from dairy cows (42.7 mg/ml). The greater disappearance of IgG1 from serum suggested that more IgG1 was transferred into secretion of dairy cows, but concentration in secretion was lower. The reduced IgG1 concentration in secretion was associated with greater lactogenic activity in dairy cows, evidenced by fivefold higher alpha-LA concentration in sera. Dilution of IgG1 in secretion may be responsible for breed differences in colostral IgG1 concentration.

Animals↗
PubMed1997

Identification and partial purification of a basic fibroblast growth factor-like growth factor derived from bovine colostrum.

Bovine colostrum that had been collected up to 6 h postpartum was fractionated by ammonium sulfate precipitation, and various fractions were examined for basic fibroblast growth factor activity. Activity that stimulated cell growth was detected in the cream fraction, which was purified by isoelectric focusing and heparin affinity chromatography. Three peaks were eluted from the heparin affinity column at approximately 0.5, 1, and 1.75 M NaCl. Although activity that stimulated cell growth was detected in the second and third peaks, a reaction with antibasic fibroblast growth factor antibody was observed only in the third peak. Fractions in the second and third peaks were examined by SDS-PAGE and Western blot analysis. Activity that stimulated cell growth was detected in the second and third peaks; however, after Western blot analysis using antibasic fibroblast growth factor, only the third peak yielded positive bands at 15 and 28 kDa. These fractions were further subjected to a neutralization test using antibasic fibroblast growth factor antibody. The activity that stimulated cell growth in the second peak was virtually unchanged; however, the activity in the third peak was diminished, showing a relative activity of less than 10% at 1.25 micrograms/ml. Therefore, neutralization of the activity that stimulates cell growth by antibasic fibroblast growth factor antibody suggests that the third peak, which was eluted at approximately 1.5 to 2 M NaCl in heparin affinity chromatography, might be a basic fibroblast growth factor-like growth factor.

Animals↗
PubMed1975

Rat immunoglobulins in serum and secretions: comparison of IgM, IgA and IgG in serum, colostrum, milk and saliva of protein malnourished and normal rats.

Immunoglobulin levels in colostrum and milk of normal and protein malnourished rat dams and in serum and saliva of their offspring were quantitated by radial immunodiffusion employing purified anti-rat alpha, gamma and mu. In general, no significant difference was observed in the level of colostral IgA in malnourished as compared to normal rat dams or in the level of serum IgA and IgM and salivary IgA and IgG2a of their offspring. On the other hand, malnourished mothers demonstrated approximately twofold lower levels of colostral IgG2a than normal mothers throughout the entire period of lactation. In addition, at every interval tested, the level of IgG was approximately 1.5- to 2-fold less in malnourished as compared to normal offspring.

Animals↗
PubMedDate not supplied

Hyperimmune bovine colostrum treatment of moribund Leopard geckos (Eublepharis macularius) infected with Cryptosporidium sp.

Therapy based on the protective passive immunity of hyperimmune bovine colostrum (HBC) was applied to 12 moribund Leopard geckos (Eublepharis macularius) infected with Cryptosporidium sp. The geckos were lethargic and moderately to severely emaciated, weighing on average 36% of the baseline body weight value. Seven gastric HBC treatments at 1-week intervals each decreased the relative output of Cryptosporidium sp. oocysts and the prevalence of oocyst-positive fecal specimens. Histologically, after 8 weeks of therapy, seven out of 12 geckos had only single developmental stages of Cryptosporidium sp. in the intestinal epithelium, and three, one and one geckos had low, moderate and high numbers, respectively, of the pathogen developmental stages. The HBC therapy was efficacious in decreasing the parasite load in moribund geckos. Morphometric and immunologic analysis of Cryptosporidium sp. oocyst isolates originating from Leopard geckos (E. macularius) demonstrated differences between gecko-derived oocyst isolates and isolates of C. serpentis recovered from snakes.

Animals↗
PubMed1999

Colostrinin: a proline-rich polypeptide (PRP) complex isolated from ovine colostrum for treatment of Alzheimer's disease. A double-blind, placebo-controlled study.

A proline-rich polypeptide (PRP) complex, subsequently called Colostrinin, was isolated from ovine colostrum. The complex showed immunomodulatory properties in mice, rats, and chickens, inducing maturation and differentiation of thymocytes. It was recently found that Colostrinin is a cytokine-like factor that acts as an inducer of interferon gamma (IFN-gamma) and other cytokines in human peripheral blood and cord blood leukocyte cultures and has psycho-immuno-enhancing activity in volunteers. These observations prompted us to study the effect of Colostrinin on patients with Alzheimer's disease (AD). Forty six AD patients were divided into 3 groups and randomly assigned to receive orally either Colostrinin (100 microg per tablet, every second day), commercially available bioorganic selenium (100 microg selenium per tablet, every second day) or placebo tablets. One cycle of the treatment lasted 3 weeks and was separated from the next cycle by a 2 week hiatus. Each patient received 10 cycles of treatment during the year of the clinical trial. Outcomes were assessed by psychiatrists blinded to the treatment assignment. Eight of the 15 AD patients treated with Colostrinin improved and in the 7 others the disease had stabilized. In contrast, none of the 31 patients from the selenium or placebo groups with similar mild or moderate AD improved. The administration of selenium promoted stabilization in 13 of the 15 patients, whereas in the placebo group only 8 of the 16 patients were stabilized at the 12 month trials end-evaluation. Colostrinin was found to be a remarkably safe drug. Mild and transient effects were anxiety, stimulation, insomnia, and tiredness. The results obtained showed that oral administration of Colostrinin improves the outcome of AD patients with mild to moderate dementia. The results are very encouraging and deserve further research.

Adjuvants, Immunologic↗
PubMed2000

Vaccination of neonatal colostrum-deprived calves against Pasteurella haemolytica A1.

Colostrum-deprived Holstein calves were vaccinated at 2 and 4 wk of age with a Pasteurella haemolytica A1 culture supernatant vaccine to determine whether active immune responses and protection could be induced in this age group in the absence of maternal antibodies. All calves responded to vaccination with high titers of IgM antibodies to capsular polysaccharide within 1 wk of primary vaccination. Mean titers of IgG1 and IgG2 antibodies to this antigen increased significantly by 2 wk after secondary vaccination, but peak antibody titers were low. All of the vaccinated calves seroconverted with production of leukotoxin-neutralizing antibodies, but peak antibody titers were low. Vaccinated calves experienced considerable lung damage after experimental challenge, but survival rate, clinical scores, and percent lung involvement were significantly better than those of control (placebo-injected) calves.

Animals↗
PubMedDate not supplied

[Interaction of trypsin with a trypsin inhibitor from bovine colostrum].

Kinetics of trypsin association with trypsin inhibitor from colostrum (IC) was studied. The association rate constant is 3-10-5 M- minus 1 sec- minus 1 at pH 7,8, 25 degrees C. The rate constant for the complex dissociation was determined from the kinetics of the IC displacement from the complex with trypsin by a specific substrate and was found to be 5-10- minus 6 sec- minus 1 (pH 7,8; 25 degrees C). The equilibrium constant (Ki) was measured in a special experiment and was equal to 4-10- minus 12 M (p H 7,8; 25 degrees C). The similarity of this reaction and the association of trypsin with other protein inhibitors was discussed.

Animals↗