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Spontaneous galactosylation of agalactoglycoproteins in colostrum.

We have found that spontaneous galactosylation of GlcNAc residues occurs in bovine colostrum, but not in dialyzed colostrum, without adding UDP-Gal as a donor substrate. UDP-Gal was shown to be present in bovine colostrum at a level ranging from 200 to 600 microM. When a tracer UDP-[(14)C]Gal was added to the dialyzed colostrum together with a Gal beta1,4-specific beta-galactosidase, remarkable incorporation of radioactivity into 24-28 kDa and 33 kDa RCA1-positive glycoproteins was demonstrated by SDS-PAGE/autoradiography. Some 100-140 kDa agalactoglycoproteins of a CHO mutant cell line were also galactosylated on a blotted membrane by the incubation in the colostrum.

Animals↗

Transforming growth factor-beta1 in mothers' colostrum and immune responses to cows' milk proteins in infants with cows' milk allergy.

BACKGROUND: Breast milk contains immune factors that compensate for the underdeveloped defenses of the gut of the newborn infant. OBJECTIVE: We sought to study the importance of these factors in the immune responses of infants with cows' milk allergy (CMA) to the proteins in cows' milk (CM). METHODS: We prospectively followed the development of CMA in 6209 healthy infants and collected samples of colostrum from mothers. Samples from mothers of infants with CMA and from control subjects were analyzed for immunoglobulins, CM-specific antibodies, and cytokines. In infants with CMA, correlations between the concentration of transforming growth factor (TGF)-beta1 in colostrum and the extent of the immune response to CM proteins were studied. RESULTS: The concentration of TGF-beta1 in colostrum samples from mothers of infants with IgE-mediated CMA (n = 65) was lower (mean, 589 pg/mL; 95% confidence interval [CI], 413-840) than from mothers of infants with non-IgE-mediated CMA (n = 37; mean, 1162 pg/mL; 95% CI, 881-1531; t = 2.57, P =.012). In 126 control subjects the mean concentration was 807 pg/mL (95% CI, 677-963). In the infants with CMA (n = 96-100), the concentration of TGF-beta1 in colostrum was positively correlated with IgA antibodies to beta-lactoglobulin and IgG antibodies to alpha-casein and whole formula and negatively with the diameter of a skin prick test response to CM and lymphocyte stimulation indices to alpha-casein and beta-lactoglobulin. CONCLUSIONS: In an infant prone to having CMA, the TGF-beta1 content of mother's colostrum may promote IgG-IgA antibody production and inhibit IgE- and cell-mediated reactions to CM.

Animals↗

Detection of cytokines in bovine colostrum.

Colostrum contains factors that are protective for the neonate and may be a source of immunomodulary molecules that positively influence the immune status of the neonate. To confirm that colostrum contains a variety of cytokines with immunomodulatory properties, we established a bovine cytokine specific ELISA and five cytokines (IL-1 beta, IL-6, TNF-alpha, INF-gamma or IL-1 receptor antagonist, IL-1ra) in the whey samples from cows at different stages of lactation were monitored. The expression of cytokine mRNAs (IL-1 beta, IL-6, TNF-alpha and INF-gamma) in the colostral cells was detected by RT-PCR. The concentrations of cytokines in colostrum were significantly higher concentrations than those in the mature milk. A positive correlation was observed between the concentrations of IL-1ra and IL-1 beta in the colostrum samples. In conclusion, colostrum contains high levels of cytokines that could be produced and secreted in the mammary gland and that may have an immunomodulatory activity and influence neonatal immunity.

Animals↗

The effect of nonspecific immunostimulation of pregnant mares with 1,3/1,6 glucan and levamisole on the immunoglobulins levels in colostrum, selected indices of nonspecific cellular and humoral immunity in foals in neonatal and postnatal period.

The objectives of the studies were to evaluate the effect of levamisole and 1,3/1,6 glucan applied in pregnant mares on parameters of non-specific cellular and humoral immunity of foals. Eighteen mares in three experimental groups (six animals in each) and their progeny were examined. Multiparous mares, crossbreed of Polish, full-blood and Hannover lines (400-500 kg), 4-9 years old, originated from four different farms. They were kept under identical zoohygienic and nutritional conditions. The animals were randomly chosen in experimental groups. None of mares had been previously vaccinated. In group I, levamisole was injected three times at 7-day intervals at a dose of 2.5 mg/kg of body weight. Group II was injected at the same periods of time and manner with 1,3/1,6 glucan at a dose of 0.19 mg/kg of body weight, whereas mares in group III served as controls. Injection of the immunostimulators started in mares 4-6 weeks before expected parturition. Blood was taken from foals before the first dose of colostrum, then 18 and 36 h after the first dose of colostrum and on Days 7, 14, 21, 28, 35, 42, 49 and 56 of life. The parameters determined in blood were reduction of NBT by PMNs, phagocytic activity, phagocytic index, test of intracellular killing and in blood sera were total protein, gamma-globulin fraction, lysozyme activity, level of IgG, IgG(T), IgM and IgA. In the first dose of colostrum taken just after parturition, specific gravity, total protein, gamma-globulin complex, lysozyme activity, level of IgG, IgG(T), IgM, IgA were determined. Colostrum of mares immunostimulated with levamisole or 1,3/1,6 glucan were characterized by a high content of IgG and IgG(T) compared to the colostrum of nonstimulated mares. The level of immunity was higher in foals from dams immunostimulated with levamisole or 1,3/1,6 glucan. Clinical examinations in neonatal and postnatal period did not show any abnormalities in these foals.

Adjuvants, Immunologic↗

The pharmacokinetics of the prostaglandin E1 analogue misoprostol in plasma and colostrum after postpartum oral administration.

OBJECTIVE: To study pharmacokinetics of prostaglandin E1 analogue, misoprostol in plasma and colostrum after postpartum oral administration. STUDY DESIGN: Twenty women received 600 microg doses of misoprostol orally after delivery. Plasma levels of the principal metabolite, misoprostol acid, were measured at 2, 10, 20, 30, 40, 50, 60, 90, 120, 180, 240 and 300 min (48 samples). Colostrum was expressed from the breasts to measure misoprostol acid at 60, 120, 180, 240, and 300 min (24 samples). Assay was done using isotope dilution gas chromatography (GC)/negative ion chemical ionisation mass spectrometry (MS). RESULTS: The plasma concentration of misoprostol acid rose quickly. Two minutes after oral administration its mean level was 91.5 pg/ml, peaked at 20 min (344 pg/ml), then fell steeply by 120 min (27.8 pg/ml) and remained low for the duration of the study. Misoprostol acid in colostrum reached maximum concentration of 20.9 pg/m within 1h after oral administration. It then declined gradually to 17.8 pg/ml at 2h, 2.8 pg/ml at 4h and to <1 pg/ml at 5h. Areas under misoprostol concentration versus time curves up to 5h were 290.1 pgh/ml in the plasma and 51.4 pgh/ml in colostrum, respectively. CONCLUSION: Misoprostol acid is secreted in colostrum within 1h of oral administration of 600 microg of misoprostol; the pharmacokinetics of misoprostol after oral administration during postpartum is similar to that of other pregnancy periods.

Adolescent↗

Passive protection of neonatal calves against bovine coronavirus-induced diarrhea by administration of egg yolk or colostrum antibody powder.

The protective effect of egg yolk and colostrum powders prepared from hens and cows vaccinated with inactivated bovine coronavirus (BCV) antigen was evaluated in a challenge model with a virulent BCV strain. Twenty three calves from BCV-free herds were randomly divided into control and several treatment groups. All calves were orally challenged with 1 x 10(9) TCID50 of the virulent Kakegawa strain of BCV at 24 to 36 h after birth. Calves in treatment groups received either egg yolk powder or cow colostrum containing BCV specific antibodies. Daily treatment with these antibody preparations started 6 h until 7 days post-challenge. Control calves which received no antibody had severe diarrhea and all died within 6 days after infection. In contrast, calves fed milk containing egg yolk or colostrum with neutralization titers of 1:2560 or 1:10,240 respectively all survived and had positive weight gain unlike the other treatment groups. These results indicate that the orally administered egg yolk and colostrum powders protected against BCV-induced diarrhea in neonatal calves and that the egg yolk used provided a higher degree of protection compared to colostrum powder on a titer basis. Treatment with whole egg yolk from immunized hens therefore provides a more efficacious alternative to the existing methods of specific passive protection against BCV.

Animals↗

Feeding different amounts of colostrum or only milk replacer modify receptors of intestinal insulin-like growth factors and insulin in neonatal calves.

Colostrum intake influences growth and development of the gastrointestinal tract (GIT) in several species and colostral insulin-like growth factors I and II (IGF-I and IGF-II), and insulin are involved in neonatal intestinal tissue growth. We have studied IGF type 1, IGF type 2, and insulin receptors in the intestine of 8-day-old calves fed different amounts of colostrum or only milk replacer. Calves were fed colostrum of the first six milkings on the first 3 days and then milk replacer (GrC(6)) or colostrum only once and then milk replacer (GrC(1)) or they were fed only milk replacer from the beginning, i.e., no colostrum (GrM). Competitive binding studies and ligand blots confirmed the presence of IGF type 1, IGF type 2, and insulin receptors in mucosal cell membranes of duodenum, jejunum, ileum, and colon. The IGF type 1 receptor number in ileum and total intestine in GrC(6) was greater (P<0.05) than in GrC(1) and in GrM, and IGF type 2 receptor number in total intestine was greater (P<0.05) in GrC(6) than in GrM. Insulin binding was best fitted by a model with two binding sites. High affinity insulin receptor numbers in duodenum, ileum, and total intestine were greater (P<0.05) in GrC(6) than in GrM. The data demonstrate that IGF type 1, IGF type 2, and insulin receptors in intestinal mucosa of neonatal calves are influenced by feeding.

Animals↗

Effect of colostrum intake on diarrhoea incidence in new-born calves.

In a survey which lasted one year and included data of 73 dairy cows with their calves, colostrum immunoglobulin G (IgG) of 22 primiparous cows and serum IgG of their calves were lower than the corresponding IgG levels of 51 multiparous cows and their calves. Serum IgG concentration was not correlated with diarrhoea incidence. Although there were no seasonal differences in the IgG concentration of colostrum and calf serum, neonatal diarrhoea incidence was higher in calves which were born in winter than in calves which were born in summer (P < 0.01). Thus the high diarrhoea incidence in winter was not a consequence of an insufficient IgG transfer to the calves. The 60 calves of the second study were fed colostrum on the first day of life. From the second to the tenth day 28 experimental calves received milk and 0.5 l of surplus colostrum of the first and second milking twice a day, whereas 32 control calves received milk only twice a day. Two of the 28 experimental and 11 of the 32 control calves suffered from diarrhoea during the first ten days of life (P < 0.05). These results show that the ingestion of surplus colostrum in addition to milk after the first day of life protects the new-born calf against infectious diarrhoea.

Animals↗

Triacylglycerol composition in colostrum, transitional and mature human milk.

OBJECTIVE: Milk triglycerides from colostrum, transitional and mature human milk, were analyzed and compared in order to determine the differences in triacylglycerol composition throughout lactation. SETTING: Department of Food and Nutrition, University of Barcelona, Spain, and Neonatology Department of the University Hospital of Granada, Spain. SUBJECTS: Twenty-two healthy lactating women aged 21-35. DESIGN AND INTERVENTIONS: The triacylglycerol profiles of 47 breast milk samples including colostrum (1-3 days), transitional milk (7-10 days) and mature milk (25-60 days) were analyzed by high-performance liquid chromatography (HPLC), with light-scattering detection (LSD). RESULTS: Significant differences regarding several triglycerides were found between three milk classes when the Kruskal-Wallis nonparametric test was applied to 47 human milk samples that had been compared using the complete chromatographic triacylglycerol profile. The ANOVAS for each equivalent carbon number (ECN) group of triglycerides revealed significant differences between colostrum, transitional milk and mature milk. By the discriminant analysis of triacylglycerol percentages, in 19 colostrum samples, 14 transitional milk samples and 14 mature milk samples, three milk types were distinguished, and three triglycerides (peak no. 4, LnOO and SOO) were found to be the most predictive variables over all the triacylglycerol profile or ECN groups. CONCLUSIONS: Each state of lactation shows a specific profile of triacylglycerol composition in human milk. However the two most abundant triacylglycerides in colostrum, POO and POL, which account for more than 49% of the total, are also dominant in transitional (34%) and mature milk (42%).

Adult↗

Modulation of the immune system and the response against pathogens with bovine colostrum concentrates.

The growth, development and health conditions for children living under deprived conditions in developing countries are so adverse that immediate public health measures to reduce morbidity and improve nutrition are urgently needed. Preventing and shortening the course of diarrhoeal episodes, eliminating protozoal colonization, and balancing intestinal microflora would all contribute to these goals. The consumption by humans of part of the colostrum produced when a dairy animal gives birth is an established tradition in many traditional societies. Recent advances in food technology in industrial dairying allow for continuous availability of stabilized bovine colostrum concentrate, both natural and hyperimmunized against specific human pathogens. This is safe for the calves of the producers themselves, for laboratory animals, and generally for humans, with the caveat of the milk-allergic. Moreover, substantial amounts of orally ingested bovine colostrum concentrate survive their passage through the stomach to remain intact and active in the lower reaches of the bowel. Studies in animals, human volunteers and naturally infected humans have demonstrated a therapeutic efficacy of oral bovine colostrum with certain infections. Similarly, attempts to prevent gastrointestinal infections in animals, exposed volunteers and at-risk populations have met with limited success with specific pathogens. It is time to begin to assess the feasibility and potential effectiveness and efficiency of employing seasonal or chronic bovine colostrum feeding in populations of deprived infantile populations to reduce the rates of recurrent gastroenteritis and decrease immunostimulation to improve vitality and nutritional status in early life.

Animals↗

Lactase phlorhizin hydrolase turnover in vivo in water-fed and colostrum-fed newborn pigs.

We have estimated the synthesis rates in vivo of precursor and brush-border (BB) polypeptides of lactase phlorhizin hydrolase (LPH) in newborn pigs fed with water or colostrum for 24h post partum. At the end of the feeding period, piglets were anaesthetized and infused intravenously for 3h with L-[4-3H]- phenylalanine. Blood and jejunal samples were collected at timed intervals. The precursor and BB forms of LPH were isolated from jejunal mucosa by immunoprecipitation followed by SDS/PAGE, and their specific radioactivity in Phe determined. The kinetics of precursor and BB LPH labelling were analysed by using a linear compartmental model. Immunoisolated LPH protein consisted of five polypeptides [high-mannose LPH precursor (proLPHh), complex glycosylated LPH precursor (proLPHe), intermediate complex glycosylated LPH precursor (proLPH1i) and two forms of BB LPH]. The fractional synthesis rate (Ks) of proLPHh and proLPHc (approx. 5%/min) were the same in the two groups but the absolute synthesis rate (in arbitrary units, min-1) of proLPHh in the colostrum-fed animals was twice that of the water-fed animals. The Ks values of proLPHi polypeptides were significantly different (water-fed, 3.89%/min; colostrum-fed, 1.6%/min), but the absolute synthesis rates did not differ. The Ks of BB LPH was not different between experimental treatment groups (on average 0.037%/min). However, the proportion of newly synthesized proLPHh processed to BB LPH was 48% lower in colostrum-fed than in water-fed animals. We conclude that in neonatal pigs, the ingestion of colostrum stimulates the synthesis of proLPHh but, at least temporarily, disrupts the processing of proLPH polypeptides to the BB enzyme.

Amino Acid Sequence↗

Natural polyreactive IgA and IgM autoantibodies in human colostrum.

Secretory antibodies against bacteria and viruses in human colostrum and milk are known to be important protective factors for the breast-fed infant. The authors have shown by enzyme immunoassay that colostrum contains IgA and IgM antibodies to a number of autoantigens: native DNA, actin, myosin, myoglobin, laminin, transferrin and thyroglobulin. These antibodies were polyspecific-those with anti-DNA reactivity immunopurified on a DNA-cellulose affinity column bound to a panel of self- and environmental antigens. The levels of natural autoantibodies in the immunoglobulin fraction of human colostrum were 3-10 times lower (when presented as antibody activity per microgram of immunoglobulin) than in the immunoglobulin fraction of serum. The biological significance of the presence of B cells with autoantibody specificity in the mammary gland and of natural autoantibodies in colostrum and milk is not clear. It has been suggested that self-reacting autoantibodies in serum play a major role in the selection of the pre-immune B-cell repertoire and in the maintenance of the immune homeostasis. The authors hypothesize that the natural autoantibodies in colostrum and milk may contribute to the selection process of physiological repertoire during the early postnatal period in breast-fed infants. This could explain the lower frequency of allergic, inflammatory and autoimmune diseases and lymphomas which is seen in their later life when compared with that observed in children who have been formula-fed after birth.

Antibody Specificity↗

Oral administration of pectin-rich plant extract enhances C3 and C4 complement concentration in woman colostrum.

C3 and C4 components of the complement are normally present in human colostrum. These compounds are natural antibacterial agents. Pectin-rich plant extracts have been shown to induce prolactin release and milk synthesis when administered by the oral route in rat. In the present work, extract from a plant rich in pectin, Gossypium herbaceum was given orally to women 2 days after parturition. The extract enhanced concentration of C3 and C4 in colostrum but did not modify the total hemolytic complement activity (TCH50). No change in the concentration of the three compounds was observed in serum of the treated women. Control experiments showed that a treatment by placebo had no effect on colostrum composition. These data suggest that pectin-rich plant extracts favour transfer of C3 and C4 from blood to colostrum by an unknown mechanism. This observation suggests that some plant extracts might be used to reinforce the antibacterial activity of human colostrum.

Adult↗

Effects of a bovine colostrum-supplemented diet on some gut parameters in weaned piglets.

The present study investigated the effects of a bovine colostrum-supplemented diet on gut post-weaning adaptation and health in piglets. Thirty-six 21-d-old piglets were allocated to one of the three following dietary treatments: sow-reared (SR), weaned on a control starter diet (WCtrl) or on a starter diet supplemented with bovine colostrum (WCol) until slaughter at 28 d or 35 d of age. Gastric pH and intestinal bacteriological, structural and functional parameters were determined. Compared to WCtrl, the gastric pH was lower (P < 0.05) and the duodenal lactobacilli:coliform ratio was higher (P = 0.05) in WCol piglets. The relative small intestine weight was 18% (P < 0.05) higher in WCol piglets than in SR piglets. Duodenal villous height was lower (P < 0.01) in WCtrl than in SR piglets, whereas the value for WCol piglets was intermediate. The weaning-increased crypt cell proliferation was not affected by bovine colostrum supplementation. The mucosal ribosomal capacity was higher (P < 0.05) in W than in SR piglets. In conclusion, a diet supplemented with colostrum induced, although not always significantly, variations of gut parameters, suggesting that globally, colostrum may limit weaning-induced gut structural and microbial alterations. The observed effects occurred early and were maintained throughout the post-weaning adaptive phase.

Adaptation, Physiological↗

Nucleotide and polyamine levels in colostrum and mature milk in relation to maternal atopy and atopic development in the children.

The prophylactic benefit of breastfeeding against atopic disease is still controversial. It seems to be limited to infants with genetic propensities to allergy in combination with late solid food introduction. Lower levels of n-3 polyunsaturated fatty acids in human milk have been related to atopy in children, stressing a non-specific role of nutritional components in the development of atopy. Nucleotides and polyamines have been related to intestinal integrity and immune function in infancy. The main sources of these nutrients are human milk nucleotides and polyamines early in life. Our aim was to study the composition of nucleotides and polyamines in colostrum and mature milk from atopic and non-atopic mothers and the relationship to sensitization against egg, milk or cat in their children during the first year of life. The nucleotide/nucleoside and polyamine levels were measured by HPLC in colostrum and in milk at 3 mo of lactation from mothers of 21 atopic and 14 non-atopic children. Among the mothers, 10 were atopic and 25 non-atopic. The nucleotides cytidine monophosphate (CMP), uridine monophosphate (UMP), adenosine monophosphate (AMP) and guanosine monophosphate (GMP) and the nucleosides cytidine and uridine were detected in human milk. In colostrum, CMP dominated, and the levels increased in mature milk, while the levels of the other compounds remained constant. The nucleotide/nucleoside composition was similar in colostrum from all mothers independent of the development of sensitization in their babies, except for the higher cytidine levels in mature milk from atopic mothers of atopic babies, as compared to healthy mothers of atopic babies. The polyamine levels were similar in colostrum from atopic and non-atopic mothers. However, putrescine and spermine levels were lower in mature milk from atopic mothers than non-atopic mothers. No relationship was found between milk putrescine and spermine levels and development of atopy in the children. In conclusion, low levels of human milk putrescine and spermine seem to be related to maternal atopy.

Chromatography, High Pressure Liquid↗

Bovine IL-18 ELISA: detection of IL-18 in sera of pregnant cow and newborn calf, and in colostrum.

In this study, we examined the concentration of bovine IL-18 in the sera of pregnant cows, their fetuses and newborn calves, and in colostrum in order to examine the role of IL-18 in bovine pregnancy and the neonatal period. A sandwich-ELISA to quantify bovine IL-18 was established using anti-porcine IL-18 monoclonal antibodies, which cross-reacted with bovine IL-18, and used it to measure the concentration of bovine IL-18 in the sera of pregnant cows, their fetuses and newborn calves, and in colostrum. Significant levels of IL-18 were detected in the sera of pregnant cows, but not in the sera obtained from the corresponding fetuses, umbilical arteries and veins. After birth, IL-18 levels in the sera of 1-day and 1-week old calves were low, and significantly increased in the sera of 1-month and 4-month old calves. IL-18 was also detected in colostrum, with the concentration of IL-18 in the first colostrum produced after delivery being the highest, and then decreasing depending on the number of milkings. Furthermore, the serum IL-18 concentration of newborn calves was increased after the oral administration of colostrum. These results suggest that IL-18 during bovine pregnancy and in the newborn period may play important roles in the maintenance of pregnancy and in the maturation of neonatal immunity.

Animals↗

Escherichia coli associated with colostrum-free neonatal pigs raised in isolation.

Escherichia coli 08 was the most frequent coliform isolated from the blood and liver of morbid and dead neonatal, colostrum-free piglets raised under extremely sanitary conditions. This strain accounted for 67 per cent of the typable E. coli. The next most numerous strain occurred at a frequency of 6 per cent. Hence, E. coli 08 was considered the main coli enteropathogen in our experimental, isolated environment. In random samples of the feces of healthy and diarrhetic neonatal piglets, 24 per cent of the typable E. coli was type 08. When a directed effort was made to isolate E. coli 08 from the feces of neonatal piglets in a healthy, colostrum-free litter, this strain was isolated from 17 per cent of the total E. coli colonies examined. Thus, the enteropathogen E. coli 08 was ubiquitous in the feces of piglets in our environment, making up approximately 20 per cent of the fecal E. coli. 85 per cent of the bacteremia and death in which E. coli was isolated from blood or liver occurred in piglets fed diets void in bovine and porcine gamma globulin. Tube agglutination tests demonstrated that agglutinins to E. coli 08, and other serotypes as well, were present in bovine colostrum and to a lesser extent in porcine colostrum. These agglutinins were practically lacking in solutions of porcine and bovine gamma globulin. Feeding 10(9)E. coli 08 bacteria to 2-week-old, colostrum-free, gamma globulin-free, 08 agglutinin-free piglets did not produce visible disease.

Animals↗

Colostrum and milk-derived peptide growth factors for the treatment of gastrointestinal disorders.

Colostrum is the specific first diet of mammalian neonates and is rich in immunoglobulins, antimicrobial peptides, and growth factors. In this article we review some of these constituents of human and bovine colostrum in comparison with those of mature milk. Recent studies suggest that colostral fractions, or individual peptides present in colostrum, might be useful for the treatment of a wide variety of gastrointestinal conditions, including inflammatory bowel disease, nonsteroidal antiinflammatory drug-induced gut injury, and chemotherapy-induced mucositis. We therefore discuss the therapeutic possibilities of using whole colostrum, or individual peptides present in colostrum, for the treatment of various gastrointestinal diseases and the relative merits of the 2 approaches.

Animals↗