Milk proteins are composed of casein, further classified into αS1-casein, αS2-casein, β-casein, and κ-casein, and whey protein, which is separated into α-lacatalbumin, β-lactoglobulin, serum albumin, and some minor proteins, such as lactoferrin and immunoglobulin. To reduce the allergenicity of protein, heat treatment and enzymatic protein hydrolysis by endopeptidase are necessarily required. Additionally, membrane technology should be applied to produce a protein hydrolyzate, which has consistent molecular weight of peptide and low in free amino acid without allergenic peptide or protein. Extensive casein hydrolyzate and whey protein hydrolyzate are used for protein source of mainly extensively hydrolyzed protein formula (eHF) intended for the treatment of cow's milk allergy. Also, partially hydrolyzed formula (pHF) is developed, which is using a single protein source e.g., whey protein hydrolyzate. The allergenicity of infant formula can be determined according to molecular weight profile and antigenicity reduction compared to intact protein. More than 90% peptides are present in eHF have a molecular weight of <3,000 Da. Peptide molecular weight profiles of pHF range mainly between 3,000 and 10,000 Da, but have a small percentage of >10,000 Da. Generally, antigenicity reduction in eHF and pHF is 10-6 and 10-3, respectively. Even if protein hydrolyzate is manufactured under strict quality control, there is still a risk of cross contamination of allergenic milk components through environmental conditions and the shared manufacturing process. Thus, quality assessment of protein hydrolyzate formula must be performed routinely.
Caseins ; Hot Temperature ; Humans ; Hydrolysis ; Immunoglobulins ; Infant Formula* ; Infant* ; Lactoferrin ; Membranes ; Milk ; Milk Hypersensitivity ; Milk Proteins ; Molecular Weight ; Peptides ; Quality Control ; Serum Albumin ; Whey Proteins

OBJECTIVEIn the present study, we investigated the antioxidant and anti-aging effects of Silybum marianum protein hydrolysate (SMPH) in D-galactose-treated mice.

METHODSD-galactose (500 mg/kg body weight) was intraperitoneally injected daily for 7 weeks to accelerate aging, and SMPH (400, 800, 1,200 mg/kg body weight, respectively) was simultaneously administered orally. The antioxidant and anti-aging effects of SMPH in the liver and brain were measured by biochemical assays. Transmission electron microscopy (TEM) was performed to study the ultrastructure of liver mitochondri.

RESULTSSMPH decreased triglyceride and cholesterol levels in the D-galactose-treated mice. It significantly elevated the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC), which were suppressed by D-galactose. Monoamine oxidase (MAO) and malondialdehyde (MDA) levels as well as the concentrations of caspase-3 and 8-OHdG in the liver and brain were significantly reduced by SMPH. Moreover, it increased Bcl-2 levels in the liver and brain. Furthermore, SMPH significantly attenuated D-galactose-induced liver mitochondrial dysfunction by improving the activities of Na+-K+-ATPase and Ca2+-Mg2+-ATPase as well as mitochondrial membrane potential (ΔΨm) and fluidity. TEM showed that the degree of liver mitochondrial damage was significantly decreased by SMPH.

CONCLUSIONThe results indicated that SMPH protects against D-galactose-induced accelerated aging in mice through its antioxidant and anti-aging activities.

Aging ; drug effects ; Animals ; Antioxidants ; pharmacology ; Brain ; drug effects ; Caspase 3 ; metabolism ; Galactose ; toxicity ; Gene Expression Regulation, Enzymologic ; drug effects ; Glutathione Peroxidase ; metabolism ; Male ; Malondialdehyde ; metabolism ; Maze Learning ; drug effects ; Mice ; Milk Thistle ; chemistry ; Mitochondria, Liver ; drug effects ; Oxidative Stress ; drug effects ; Plant Proteins ; chemistry ; pharmacology ; Protective Agents ; pharmacology ; Protein Hydrolysates ; chemistry ; pharmacology ; Superoxide Dismutase ; metabolism

Gastrointestinal hemorrhage in neonates is commonly associated with necrotizing enterocolitis, cow's milk protein allergy, and gastrointestinal malformation. Gastrointestinal bleeding on the first day of life, presenting as the first manifestation of a disorder, has rarely been reported associations with gastric ulceration, Salmonella infection, and allergic colitis. Hemophilia B is also a rare cause of gastrointestinal bleeding during the neonatal period. In the present case, a male infant developed repetitive hematemesis on the first day of life. His initial level of coagulation factor IX was 1.9%, and he was diagnosed with moderate hemophilia B. No further hematemesis or melena was observed during recombinant factor IX therapy. The infant did not have a family history of hemophilia. In conclusion, although gastrointestinal hemorrhage on the first day of life as the first manifestation of a disease is rare, infants who present with spontaneous gastrointestinal hemorrhage after birth and with unexplained prolonged activated partial thromboplastin time should be evaluated for coagulation factor deficiency regardless of whether they have any family history of hemophilia.
Blood Coagulation Factors ; Colitis ; Enterocolitis, Necrotizing ; Factor IX ; Gastrointestinal Hemorrhage* ; Hematemesis ; Hemophilia A* ; Hemophilia B* ; Hemorrhage ; Humans ; Hypersensitivity ; Infant ; Infant, Newborn ; Male ; Melena ; Milk Proteins ; Partial Thromboplastin Time ; Parturition ; Salmonella Infections ; Stomach Ulcer

This paper covers algorithms for the management of regurgitation, constipation and infantile colic in infants. Anti-regurgitation formula may be considered in infants with troublesome regurgitation, while diagnostic investigations or drug therapy are not indicated in the absence of warning signs. Although probiotics have shown some positive evidence for the management of functional gastrointestinal disorders (FGIDs), the evidence is not strong enough to make a recommendation. A partially hydrolyzed infant formula with prebiotics and β-palmitate may be considered as a dietary intervention for functional constipation in formula fed infants. Lactulose has been shown to be effective and safe in infants younger than 6 months that are constipated. Macrogol (polyethylene glycol, PEG) is not approved for use in infants less than 6 months of age. However, PEG is preferred over lactulose in infants >6 months of age. Limited data suggests that infant formula with a partial hydrolysate, galacto-oligosaccharides/fructo-oligosaccharides, added β-palmitate may be of benefit in reducing infantile colic in formula fed infants in cases where cow's milk protein allergy (CMPA) is not suspected. Evidence suggests that the use of extensively hydrolyzed infant formula for a formula-fed baby and a cow's milk free diet for a breastfeeding mother may be beneficial to decrease infantile colic if CMPA is suspected. None of the FGIDs is a reason to stop breastfeeding.
Breast Feeding ; Colic ; Consensus* ; Constipation ; Diagnosis* ; Diarrhea ; Diet ; Drug Therapy ; Gastrointestinal Diseases* ; Humans ; Hypersensitivity ; Infant Formula ; Infant* ; Lactulose ; Middle East* ; Milk ; Milk Proteins ; Mothers ; Polyethylene Glycols ; Prebiotics ; Probiotics

One of the severe complications of osteoporosis is hip fracture, which can occur even with minimal trauma. This burdensome complication is closely associated with an increased risk of mortality, impairment, and decreased quality of life, resulting in enormous health care costs. Hip fracture is significantly related to a previous history of fracture, and its risk can be determined by bone strength and type of trauma-with falls posing an especially high risk. The first step to prevent osteoporotic fracture is the detection of osteoporosis, relying on the quantification of bone density via imaging techniques such as dual-energy X-ray absorptiometry and quantitative computed tomography. In addition, various preventive strategies have been introduced. Above all, proper supplementation of vitamin D, protein, milk, calcium, folic acid, vitamin B12, and vitamin K is beneficial for prevention of osteoporotic fracture for elderly patients who are susceptible to nutrition imbalance. For elderly patients, rehabilitation is considered to be crucial for increasing function and improving patients' activities of daily living as well. A fall-preventive intervention program has been known to be the effective and useful way for elderly patients to reduce fall risk, which can be assessed with the 'timed up and go' test. A home hazard modification program such as wearing anti-slip shoe devices has been proven to decrease fall risk in community-living elderly. Therefore, diagnosis of osteoporosis, proper supplementation of nutrients, rehabilitation, and a fall-preventive intervention program are essential components in the prevention of hip fracture.
Absorptiometry, Photon ; Accidental Falls ; Activities of Daily Living ; Aged* ; Bone Density ; Calcium ; Diagnosis ; Folic Acid ; Health Care Costs ; Hip Fractures ; Hip* ; Humans ; Milk Proteins ; Mortality ; Osteoporosis ; Osteoporotic Fractures ; Quality of Life ; Rehabilitation ; Shoes ; Vitamin B 12 ; Vitamin D ; Vitamin K

Female ; Humans ; Immunoglobulin E ; blood ; Infant ; Male ; Milk Hypersensitivity ; diagnosis ; Milk Proteins ; immunology

PURPOSE: Soy-based formulas are widely used as dairy substitutes to treat milk allergy patients. However, reactions to soy have been reported in a small proportion of patients with IgE-mediated milk allergies. The aim of this work was to explore whether P34, a mayor soybean allergen, is involved in this cross-reactivity. METHODS: In vitro recognition of P34 was evaluated by immunoblotting, competitive ELISA and basophil activation tests (BAT) using sera from allergic patients. In vivo cross-reactivity was examined using an IgE-mediated milk allergy mouse model. RESULTS: P34 was recognized by IgE antibodies from the sera of milk allergic patients, casein-specific monoclonal antibodies, and sera from milk-allergic mice. Spleen cells from sensitized mice incubated with milk, soy or P34 secreted IL-5 and IL-13, while IFN-gamma remained unchanged. In addition, the cutaneous test was positive with cow's milk proteins (CMP) and P34 in the milk allergy mouse model. Moreover, milk-sensitized mice developed immediate symptoms following sublingual exposure to P34. CONCLUSIONS: Our results demonstrate that P34 shares epitopes with bovine casein, which is responsible for inducing hypersensitivity symptoms in milk allergic mice. This is the first report of the in vivo cross-allergenicity of P34.
Animals ; Antibodies ; Antibodies, Monoclonal ; Basophils ; Caseins* ; Enzyme-Linked Immunosorbent Assay ; Epitopes ; Food Hypersensitivity ; Humans ; Hypersensitivity ; Immunoblotting ; Immunoglobulin E ; Interleukin-13 ; Interleukin-5 ; Mice ; Milk ; Milk Hypersensitivity ; Milk Proteins ; Soy Milk ; Soybeans* ; Spleen

The milk fat globule-EGF-factor 8 protein (MFG-E8) has been identified in various tissues, where it has an important role in intercellular interactions, cellular migration, and neovascularization. Previous studies showed that MFG-E8 is expressed in different cell types under normal and pathophysiological conditions, but its expression in hematopoietic stem cells (HSCs) during hematopoiesis has not been reported. In the present study, we investigated MFG-E8 expression in multiple hematopoietic tissues at different stages of mouse embryogenesis. Using immunohistochemistry, we showed that MFG-E8 was specifically expressed in CD34+ HSCs at all hematopoietic sites, including the yolk sac, aorta-gonad-mesonephros region, placenta and fetal liver, during embryogenesis. Fluorescence-activated cell sorting and polymerase chain reaction analyses demonstrated that CD34+ cells, purified from the fetal liver, expressed additional HSC markers, c-Kit and Sca-1, and that these CD34+ cells, but not CD34- cells, highly expressed MFG-E8. We also found that MFG-E8 was not expressed in HSCs in adult mouse bone marrow, and that its expression was confined to F4/80+ macrophages. Together, this study demonstrates, for the first time, that MFG-8 is expressed in fetal HSC populations, and that MFG-E8 may have a role in embryonic hematopoiesis.
Animals ; Antigens, CD34/analysis ; Antigens, Surface/*analysis ; Bone Marrow/ultrastructure ; Female ; Hematopoietic Stem Cells/*cytology ; Liver/embryology ; Mice/*embryology ; Milk Proteins/*analysis ; Placentation ; Pregnancy

PURPOSE: The aim of study was to assess the value of recombinants in predicting the degree of symptoms in children with and without anaphylaxis to cow's milk. METHODS: The study included 79 children (70+/-40 months) referred to the Allergological Unit of the Pediatric Department between the years 2008-2012. Group A was composed of 17 children (78+/-49.6 months) with anaphylaxis after ingestion of milk. Group B was composed of 62 children (73.1+/-38.6 months) without a history of anaphylaxis, but with less severe symptoms (gastrointestinal and/or skin symptoms). All patients from Group B had a positive open challenge with cow's milk. All patients underwent an allergic evaluation and blood samples were collected to test for IgE to recombinans of milk (nBos d 4, 5, 8). RESULTS: A significant difference in nBos d 8 emerged with higher levels in Group A (median [IQR]=2.80 [0.91-16.1]) than B (0.65 [0.24-1.67]; P=0.006), whereas there were no statistically significant differences for nBos d 4 and 5. The recombinants' sum was higher in Group A than B: 8.39 [2.72-41.39] vs 3.04 [1.85-7.31] kUA/L; P=0.044. The recombinant nBos d 8 was superior to the other recombinants in identifying children at risk for anaphylaxis, with an area under the curve of 0.718 (95% CI, 0.57-0.86, P=0.006). Considering a cutoff of 1.8 kUA/L, nBos d 8 had the most favorable sensitivity and specificity ratio (sensitivity=0.65, specificity=0.77) with an odd ratio of 6.02 (95% C.I: 1.89-19.23). CONCLUSIONS: This study suggested 2 phenotypes of allergic children, "high-anaphylaxis-risk" and "milder-risk". These types can be differentiated through measuring the level of IgE to nBos d 8.
Anaphylaxis ; Antibodies* ; Child* ; Eating ; Humans ; Hypersensitivity ; Immunoglobulin E* ; Methods ; Milk* ; Phenotype ; Recombinant Proteins ; Skin

Necrotizing enterocolitis (NEC) is a major gastrointestinal disorder in premature infants associated with high morbidity and mortality rates. When NEC is clinically suspected, radiological and laboratory studies should be performed to confirm the diagnosis and to aid in the management of patients. As the clinical manifestations of NEC are usually nonspecific, diagnoses are often made using abdominal radiographic findings, such as pneumatosis intestinalis. Clinicians typically consider the presence of pneumatosis intestinalis on radiographs as the definite evidence of stage II NEC. Here, we report 3 cases of preterm infants who had radiographic findings of pneumatosis intestinalis but did not have any other associated laboratory and clinical evidence of NEC, except bloody stools. The infants' systemic manifestations were mild or absent, and all of them completely recovered within 2-3 days, as demonstrated by the resolution of pneumatosis intestinalis on abdominal radiographs. The combination of hematochezia and intestinal pneumatosis in preterm infants strongly suggests the diagnosis of NEC. In our cases, there was no laboratory evidence of inflammation or platelet consumption, and the clinical course was benign without any sings of surgical abdomen. Additionally, our patients had barium-induced colitis or milk protein allergy, which are other possible causes of pneumatosis intestinalis. Because pneumatosis intestinalis can result from causes other than NEC, it is important to consider clinical, laboratory, and radiological findings to confirm the diagnosis of NEC.
Abdomen ; Blood Platelets ; Colitis ; Diagnosis ; Enterocolitis, Necrotizing* ; Gastrointestinal Hemorrhage ; Humans ; Hypersensitivity ; Infant, Newborn ; Infant, Premature* ; Inflammation ; Milk Proteins ; Mortality