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Cytokine-inducing activity of a proline-rich polypeptide complex (PRP) from ovine colostrum and its active nonapeptide fragment analogs.

A complex of proline-rich polypeptides (PRP) was isolated from ovine colostrum in our laboratory and was shown to possess immunomodulatory properties and psychotropic activity, including beneficial effects in the treatment of Alzheimer's disease. A nonapeptide fragment (NP): Val-Glu-Ser-Tyr-Val-Pro-Leu-Phe-Pro, isolated from the chymotryptic digestion products of PRP, and its C-terminal fragment, a hexapeptide (HP): Tyr-Val-Pro-Leu-Phe-Pro also exhibited immunoregulatory activity. Although NP and HP expressed activity similar to that of PRP in studies on humoral and cellular immune responses, in other immune processes, e.g. induction of cytokines, they showed markedly lower activity than PRP. In the search for more active peptides, in the present study, we compared the cytokine-inducing ability of PRP, NP, HP, and linear oligomers of NP or HP. For this purpose, the induction of IFN, TNF-alpha, IL-6, and IL-10 in human whole blood cell cultures was measured. NP, HP, and their oligomers showed differential effects in the induction of cytokines, generally lower than that of PRP. Only the PRP complex showed a bell-shaped dose-response dependence suggesting regulatory properties. There were no distinct differences between monomeric forms of NP (NP1) or HP (HP1) and their oligomers in the induction of IFN and TNF-alpha (Th1 cytokines) but such differences were found in the induction of IL-6 and IL-10 (Th2 cytokines). Dimer (NP2) was less active than the monomeric NP1 nonapeptide in the induction of IL-6 and IL-10. On the other hand, oligomers: HP3 and HP4, showed a significantly higher ability to induce Th2 cytokines compared to HP1, HP2 or NP peptides. This was especially evident in the case of IL-10 induction, where the activity of HP4 surpassed the activity of PRP and approached the activity of LPS-PHA. The results obtained showed that some of the peptides studied, when used at higher concentrations (100 microg/ml) may replace the PRP complex as cytokine inducers. Our data also suggest the possibility of using certain oligomers for selective induction of particular cytokines.

Adjuvants, Immunologic↗

Colostrinin proline-rich polypeptide complex from ovine colostrum--a long-term study of its efficacy in Alzheimer's disease.

BACKGROUND: Colostrinin, a proline-rich polypeptide complex (PRP) isolated from ovine colostrum, with immunoregulatory and procognitive properties, has shown positive effects in the treatment of Alzheimer's disease (AD). The aim of the present study was to evaluate the effects of long-term Colostrinin treatment of AD patients. MATERIAL/METHODS: The patients were taking Colostrinin tablets (containing 100 mg of PRP complex) every other day for three weeks, followed by a 2-week hiatus to avoid the development of hyporeactivity. This mode of application, '3+2 weeks,' was used consistently throughout the trial. The efficacy of treatment was assessed by the MMSE scale, and each patient was evaluated at 4-month intervals. 33 patients were treated for 16 months. However, 13 patients from this group had already been treated with Colostrinin for 12 months during placebo-controlled studies, and thus participated in the trial for a total of 28 months. RESULTS: The results we obtained showed that Colostrinin induced slight but statistically significant improvement or stabilization of the health status of the patients in the trial. The adverse reactions observed, if any, were remarkably mild, including anxiety, logorrhea, and insomnia, and subsided spontaneously within a short period of time (3-4 days). CONCLUSIONS: Colostrinin is a very promising preparation which can be used to retard the development of AD.

Aged↗

[Necessary care of newborn lambs using ovine colostrum. 2. Duration of administration].

Sheep colostrum, pooled from 0-12 h milkings, was fed to 38 newborn lambs for either 6, 12, 18 or 24 hrs after birth. The influence of the duration of feeding periods on the transintestinal passage of immunoglobulins, the growth performance, the loss rate and the onset of immunoglobulin synthesis were investigated by monitoring the serum concentrations of IgG1, IgG2, IgM and IgA during months 1 through 9 of life. Feeding of 3 portions of 100 ml at 2 h intervals resulted in lower serum levels of Ig's than the extension of the feeding to 12 x 100 ml every second hour. There was, however, no difference in the onset of endogenous Ig production between both groups. Growth performance and the loss rate were also identical.

Animals↗

[Necessary provision of newborn lambs with sheep colostrum].

Twenty new-born lambs of each of the breeds Schwarzkopf, Texel and Finnish were fed with 600 ml of pooled colostrum (0-12 h) on the first day of life. The total allocation was fed in portions ranging from 25 to 150 ml at intervals of 1, 2, 3, or 6 hours. The effect of the different intervals and portion volumes on the transintestinal passage of immunoglobulins, the onset of endogenous synthesis, the growth performance of the lambs and the mortality rate was investigated. The concentrations of IgG1, IgG2, IgM and IgA in the sera were analyzed over the course of a nine-week period. 1. The extent of passive immunization by transintestinal passage remained essentially unaffected by different feeding schedules. 2. There was also no effect on the onset of endogenous Ig synthesis. 3. Growth performance and mortality rate likewise showed no discernible differences.

Animals↗

Superoxide dismutase activity in colostrum, transitional and mature human milk.

Colostrum and mature human milk are rich sources of nutrients and contain biologically active molecules that are essential for specific antioxidant functions. The aim of the present study was to determine the activity of copper, zinc superoxide dismutase (CuZnSOD) and manganese superoxide dismutase (MnSOD) activity in different phases of lactation. Specific enzyme activity was determined in colostral milk (3rd-5th days after delivery), and in mature milk in the third week (15-20 days), and the fourth and seventh months of lactation. In the third week of lactation, the activity of CuZnSOD and MnSOD was significantly higher in comparison to the colostral phase. In the fourth month of lactation, the activity of both enzymes was suppressed, while in the seventh month of lactation the MnSOD activity was increased, and the CuZnSOD activity was not significantly changed. These findings show that the activities of superoxide dismutases significantly change during different phases of lactation.

Adult↗

[Heterogeneous forms of prolactin in the blood and colostrum of ruminants].

The monomer form of prolactin prevailed in the blood of cows and she-goats in the physiological conditions associated with an intensive prolactin secretion. The dimer's content increased at the final stage of lactation and in pregnancy. High level of prolactin was found in the colostrum, a form of the prolactin with the milk mass over 100000 having been identified in the soluble fraction of milk. This particular form seems to appear directly in the mammal gland by means of binding of the monomer with an unknown protein.

Animals↗

[Presence of leptin in mammalian colostrum and milk and in artificial milk formulas].

Leptin is a 167-amino acid protein, involved in the regulation of adipose tissue, food intake and body weight in humans and animals. Recently, leptin synthesis has been found in the placenta and mammary glands in human and numerous animal species suggesting a role in controlling growth of the foetus and neonate. Colostrum and milk contain high amounts of leptin, in particular during the first few days of lactation. Milk leptin is associated with milk fats what may affect the results of analysis. In humans, a correlation was found between the milk leptin and plasma leptin, body weight and body mass index. In sows, no correlation have been found between the concentration of leptin in blood plasma and milk during the first week of lactation. Milk replacer formulas contain less leptin and leptin supplementation reverses the negative influence of formula feeding on the functional development of the gastro-intestinal tract in neonatal piglets. Data obtained so far suggest that breast milk leptin may control the gut development in newborns.

Animals↗

Determination of minor proteins of bovine milk and colostrum by optical biosensor analysis.

Automated, rapid, sensitive, and label-free biosensor-based immunoassays for immunoglobulin G (IgG), folate binding protein, lactoferrin, and lactoperoxidase in bovine milk using surface plasmon resonance optical detection with direct binding assay format are described. Samples are prepared for analysis by direct dilution into buffer. Analysis conditions, including ligand immobilization, flow rate, contact time, and regeneration are defined and nonspecific binding considerations evaluated. The technique has been applied to the measurement of these proteins in consumer milks, colostrum, milk products, and infant formulas, and their temporal change during early bovine lactation followed.

Animals↗

[Human colostrum and milk cells].

This review dwells on the major cell defense factors of human colostrum and milk: phagocytes, lymphocytes, epithelial cells, and natural-killer cells (NK). Other elements are also presented, of humoral origin, which take part in such fluid. The cells are morphofunctionally characterized and reasons are given that make it more difficult for a detailed study (great variability, atypical morphology, presence of fatty globules). Finally, the function of maternal milk is stressed as a transmitter of systemic immunity and of nutritional elements to the neonate, therefore the importance of breastfeeding.

Colostrum↗

Insulin-like growth factor I (IGF-I) from cow colostrum: purification and characterization.

Insulin-like growth factor I (IGF-I) has been purified from defatted cow colostrum. The purification procedure involved cation exchange chromatography on CM Affigel blue, acid gel-filtration and two HPLCs. This purification process constitutes a significant improvement, in terms of yield and rapidity, over the previously reported procedures. Purified IGF-I was found to be 95% pure by N-terminal amino acid sequence analysis. After isolation of peptides from a digest of IGF-I obtained using staphylococcus aureus protease, the complete sequence was established and found to be identical to that of bovine or human plasma IGF-I.

Animals↗

[Inhibition of adhesion of the classical enteropathogenic Escherichia coli 0111 ab: H2 to HeLa cells using colostrum and human milk in different experimental conditions].

Adherence of enteropathogenic Escherichia coli (EPEC) to enterocytes with subsequent destruction of microvilli is supposed to be their mechanism of virulence. Adhesion may be studied in vitro systems using HeLa or HEp-2 cells, to which EPEC adhere in a localized pattern. We show here that colostrum and human milk inhibit E. coli 0111ab:H2 adherence to HeLa cells in different experimental conditions. Lactose does not seem to be involved in the in vitro inhibition since no effect was observed when a concentration of 7.5% was used during the test. A bacterial growth curve performed in same conditions of adherence test showed no bacteriostatic effect of human milk. S-IgA and receptor analogues could be responsible for the adherence inhibition observed.

Bacterial Adhesion↗

Immunogold labeling of stages of Cryptosporidium parvum recognized by immunoglobulins in hyperimmune bovine colostrum.

Ultrathin sections of mouse ileum infected with Cryptosporidium parvum were stained by immunogold techniques. Sections first were stained with polyvalent antibodies in whey from hyperimmune bovine colostrum (HBC), then stained by secondary antibodies in rabbit antibovine IgA, IgM, IgG1, and IgG2, and lastly labeled by goat anti-rabbit gold conjugate. Examination of the immunostained specimens by electron microscopy revealed that each bovine immunoglobulin isotype in the whey recognized antigens in meronts, merozoites, microgametocytes, microgametes, and macrogamonts. Based on these findings it is hypothesized that antigens in all stages of C. parvum provide targets of opportunity for the antiparasitic activity of HBC whey antibodies thereby accounting for its efficacy as an immunotherapeutic agent.

Animals↗

The effect of vaccination on titres of antibody to rotavirus in colostrum and milk.

The continued presence of antibody to rotavirus in the gut of the neonatal ruminant has been shown to be important in protecting against clinical disease associated with rotavirus infections. This effect is dependant upon the amount of antibody included in the diet. Titres of antibody to rotavirus may be relatively high in ruminant mammary secretions immediately after parturition but decline rapidly over the course of the first day. The influence of vaccination on the titres of antibody, the concentrations of immunoglobulin and their respective of decline in the mammary secretion following parturition has been studied. Ewes vaccinated two to three weeks prior to mating with an inactivated preparation of lamb rotavirus produced colostrum and milk after the subsequent pregnancy which contained significantly higher titres of antibody to the virus than did the mammary secretions from non-vaccinates. The antibody activity appears to be associated with IgG and it is suggested that vaccination may be of value in the alleviation of neonatal diarrhoea associated with rotavirus infection in cattle and sheep.

Animals↗

The experimental production of diarrhoea in colostrum deprived axenic and gnotoxenic calves with enteropathogenic Escherichia coli, rotavirus, coronavirus and in a combined infection of rotavirus and E. coli.

We attempted to produce diarrhoea experimentally in the newborn calf by orally injecting 17 colostrum-deprived calves with two serotypes of Escherichia coli Ent+ K99+, a rotavirus and a coronavirus. With E. coli alone, a dose of 2 x 10(8) bacteria administered 24 hours after birth causes a mild attack of diarrhoea, whereas 1 x 10(10) bacteria leads to dehydration and death. An inoculation of rotavirus is followed by diarrhoea which always contains large quantities of rotavirus. These animals were anorectic for a time, but none was dehydrated or died. With coronavirus, there were large quantities of watery diarrhoea, which led to dehydration and death. The inoculation of rotavirus, not lethal in itself, followed by a similarly non lethal inoculation of E. coli in doses of 3 x 10(8) to 2 x 10(9) led to dehydration and death. The authors conclude that dehydration and death of the animal can caused by large doses of E. coli or coronavirus or by two non-lethal doses of rotavirus and E. coli administered one after the other.

Animals↗

Antibodies from colostrum in oral immunotherapy.

An immunoglobulin preparation for oral use was prepared from pooled bovine colostrum from more than 100 animals. The preparation has high antibacterial antibody titres, and a high capacity for the neutralization of bacterial toxins. It is well tolerated and highly effective in the treatment of severe diarrhoea, e.g. in AIDS patients. The preparation is spray-dried and stable at 2-8 degrees C.

Acquired Immunodeficiency Syndrome↗

[Udder immunization for the protection of calves from salmonella infections. 2. Estimation of serological findings of colostrum with regard to its protective activity].

Colostrum from cows which had been mammary gland vaccinated against salmonellosis were tested for antibodies by four different serological tests. Results from these tests were related to the protective activity for artificially infected calves. In opposition to agglutinating antibodies and antibodies detected by ELISA, complement fixing antibodies of the IgG1 class were shown to transfer early protection in artificially infected calves.

Animals↗

Time-course levels of alpha 2-macroglobulin and albumin in cow colostrum and milk and alpha 2-macroglobulin levels in mastitic cow milk.

Time-course levels of alpha 2-macroglobulin and albumin in cow's colostrum and milk during lactation were investigated in order to obtain data that could help to elucidate the biological role of alpha 2-macroglobulin in mammary secretions. Levels of these proteins were also studied in mastitic cow milk and were related to the degree of mastitis, which could allow its use as a mastitis marker. The highest concentration of alpha 2-macroglobulin was found in the first milking (386.7 micrograms/ml). This value decreased very rapidly during the colostral period, attaining its definitive value during the 2nd wk postpartum (4.5 micrograms/ml). The albumin/alpha 2-macroglobulin ratio increased by 6.8 in the first milking to 44.4 at 2 wk postpartum, indicating that the increase of alpha 2-macroglobulin was greater than that of albumin. In mastitic cow's milk, the concentration of alpha 2-macroglobulin (48.1, 71.4, and 89.0 microgram/ml) was also higher than that in normal milk. This increase was found to be related to the degree of mastitis as determined by the California Test.

Animals↗