Evaluation of Children with Cow's Milk Allergy Who Received Measles or Measles, Mumps, and Rubella Vaccines Containing Alpha-Lactalbumin.

Objective: Cases of cow's milk allergy (CMA) who reacted to measles or measles, mumps, and rubella (MMR) vaccines containing alpha-lactalbumin have been reported. The purpose of this study was to assess patients with CMA who received measles or MMR vaccines containing alpha-lactalbumin, as well as the characteristics of those who developed reactions to these vaccines. Study Design: Patients followed up in the allergy clinic for CMA and who received measles or MMR vaccines containing alpha-lactalbumin at 9 or 12 months of age were included in the study, and their characteristics were analyzed retrospectively from the hospital registry system. Results: Forty-nine patients were included in the study. Six patients received the measles vaccine, whereas 43 patients received the MMR vaccine containing alpha-lactalbumin. Vaccine skin tests were performed on these 6 patients. One patient had a positive intradermal test, so an alternative vaccine not containing alpha-lactalbumin was administered. The other 5 patients were vaccinated, and no reaction was observed. Anaphylaxis was observed in 3 of 43 patients who received the MMR vaccine containing alpha-lactalbumin. In all of these patients, the first reaction to dairy products was anaphylaxis. In 2 of those patients, cow's milk-specific IgE (spIgE) levels were >100 kU/L, and alpha-lactalbumin-spIgE levels were also high at 97 and 90 kU/L. The third patient's cow's milk-spIgE level was 15.9 kU/L, whereas the alpha-lactalbumin-spIgE level was 0.04 kU/L. Conclusion: Especially in patients with an initial reaction of anaphylaxis to dairy products and high cow's milk-spIgE levels, the risk of reaction is high with the MMR vaccine.

Dietary α-lactalbumin alters energy balance, gut microbiota composition and intestinal nutrient transporter expression in high-fat diet-fed mice.

Recently there has been a considerable rise in the frequency of metabolic diseases, such as obesity, due to changes in lifestyle and resultant imbalances between energy intake and expenditure. Whey proteins are considered as potentially important components of a dietary solution to the obesity problem. However, the roles of individual whey proteins in energy balance remain poorly understood. This study investigated the effects of a high-fat diet (HFD) containing α-lactalbumin (LAB), a specific whey protein, or the non-whey protein casein (CAS), on energy balance, nutrient transporters expression and enteric microbial populations. C57BL/6J mice (n 8) were given an HFD containing either 20 % CAS or LAB as protein sources or a low-fat diet containing CAS for 10 weeks. HFD-LAB-fed mice showed a significant increase in cumulative energy intake (P=0·043), without differences in body weight, energy expenditure, locomotor activity, RER or subcutaneous and epididymal white adipose tissue weight. HFD-LAB intake led to a decrease in the expression of glut2 in the ileum (P=0·05) and in the fatty acid transporter cd36 (P<0·001) in both ileum and jejunum. This suggests a reduction in absorption efficiency within the small intestine in the HFD-LAB group. DNA from faecal samples was used for 16S rRNA-based assessment of intestinal microbiota populations; the genera Lactobacillus, Parabacteroides and Bifidobacterium were present in significantly higher proportions in the HFD-LAB group. These data indicate a possible functional relationship between gut microbiota, intestinal nutrient transporters and energy balance, with no impact on weight gain.

Dietary α-lactalbumin induced fatty liver by enhancing nuclear liver X receptor αß/sterol regulatory element-binding protein-1c/PPARγ expression and minimising PPARα/carnitine palmitoyltransferase-1 expression and AMP-activated protein kinase α phosphorylation associated with atherogenic dyslipidaemia, insulin resistance and oxidative stress in Balb/c mice.

The effect and the role played by dietary α-lactalbumin (α-LAC) on hepatic fat metabolism are yet to be fully elucidated. We reported previously that α-LAC intake induced atherogenic dyslipidaemia in Balb/c mice. The aim of the present study was to investigate if this atherogenic effect could be due to a possible α-LAC-induced hepatic steatosis. We examine the ability of dietary α-LAC to induce liver steatosis, identifying the molecular mechanisms underlying hepatic lipid metabolism in association with the lipid profile, peripheral insulin resistance (IR) and changes in the hepatic oxidative environment. Male Balb/c mice (n 6) were fed with diets containing either chow or 14 % α-LAC for 4 weeks. The α-LAC-fed mice developed abdominal adiposity and IR. Moderate liver steatosis with increased TAG and NEFA contents was correlated with atherogenic dyslipidaemia. There was increased nuclear expression of liver X receptor αß (LXRαß), sterol regulatory element-binding protein-1c (SREBP-1c) and PPARγ transcription factors and of the cytosolic enzymes acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase involved in the hepatic de novo lipogenesis. The opposite was found for the nuclear receptor PPARα and the mitochondrial enzyme carnitine palmitoyltransferase-1 (CPT-1), leading to reduced fatty acid ß-oxidation (FAO). These changes were associated with a significant decrease in both p-Thr172-AMP-activated protein kinase α (AMPKα) (inactivation) and p-Ser79-ACC1 (activation) and with a more oxidative liver environment increasing lipid peroxidation and protein oxidation and reducing GSH:GSSG ratio in the α-LAC-fed mice. In conclusion, 4 weeks of 14 % α-LAC feeding induced liver steatosis associated with atherogenic dyslipidaemia, IR and oxidative stress by enhancing nuclear LXRαß/SREBP-1c/PPARγ expression and diminishing PPARα/CPT-1 expression and AMPKα phosphorylation shifting the hepatic FAO toward fatty acid synthesis in Balb/c mice.

Gastric digestion of α-lactalbumin in adult human subjects using capsule endoscopy and nasogastric tube sampling.

In the present study, structural changes in the milk protein α-lactalbumin (α-LA) and its proteolysis were investigated for the potential formation of protein-fatty acid complexes during in vivo gastric digestion. Capsule endoscopy allowed visualisation of the digestion of the test drinks, with nasogastric tubes allowing sampling of the gastric contents. A total of ten healthy volunteers had nasogastric tubes inserted into the stomach and ingested test drinks containing 50 g/l of sucrose and 25 g/l of α-LA with and without 4 g/l of oleic acid (OA). The samples of gastric contents were collected for analysis at 3 min intervals. The results revealed a rapid decrease in the pH of the stomach of the subjects. The fasting pH of 2·31 (SD 1·19) increased to a pH maxima of pH 6·54 (SD 0·29) after ingestion, with a subsequent decrease to pH 2·22 (SD 1·91) after 21 min (n 8). Fluorescence spectroscopy and Fourier transform IR spectroscopy revealed partial protein unfolding, coinciding with the decrease in pH below the isoelectric point of α-LA. The activity of pepsin in the fasting state was found to be 39 (SD 12) units/ml of gastric juice. Rapid digestion of the protein occurred: after 15 min, no native protein was detected using SDS-PAGE; HPLC revealed the presence of small amounts of native protein after 24 min of gastric digestion. Mirocam® capsule endoscopy imaging and video clips (see the online supplementary material) revealed that gastric peristalsis resulted in a heterogeneous mixture during gastric digestion. Unfolding of α-LA was observed during gastric transit; however, there was no evidence of a cytotoxic complex being formed between α-LA and OA.

An α-lactalbumin-enriched and symbiotic-supplemented v. a standard infant formula: a multicentre, double-blind, randomised trial.

The aim of the present study was to evaluate the safety, tolerance and preventive effect on atopic dermatitis of an experimental α-lactalbumin-enriched and symbiotic-supplemented infant formula. A total of ninety-seven non-breastfed term neonates were enrolled into a double-blind, multicentre, randomised controlled trial in which they received experimental (n 48) or standard formula (n 49) for 6 months. The primary outcome was weight at 6 months of age. Secondary outcomes were gastrointestinal tolerance and manifestation of atopic dermatitis. Faecal secretory IgA (SIgA) concentration and microbiota composition of forty-three infants were analysed at 1 and 6 months. Growth was similar in both groups. At 1 month, compared to those in the control group, infants in the experimental group exhibited less crying or agitation, and more quiet behaviour (P=0·03). At 6 months, atopic dermatitis was less frequently observed in the experimental group (P<0·05). Decrease of faecal SIgA concentration between 1 and 6 months was mainly observed in the control group. This decrease was significantly associated with atopic dermatitis (P<0·014) and negatively correlated to the level of colonisation by bifidobacteria (P<0·005). In conclusion, compared to the control formula, the experimental formula guaranteed a similar growth, was better tolerated at 1 month and had a protective effect against the development of atopic dermatitis.

Modulation of mammary gland development in pre-pubertal mice as affected by soya and milk protein supplements.

The objective of the present study was to determine the effects of soya and whey milk protein, α-lactalbumin (α-LA), on mammary gland morphology and the structural support of the gland, in pre-pubertal mice after 7 d of treatment. In Expt 1, weaned (day 21) CD1 mice were given one of the four treatments, three included dietary supplements: (1) control diet, casein, (2) soya, (3) α-LA and (4) subcutaneous injection of 2·5 µg oestradiol benzoate in 20 µl maize oil and fed the control diet. All diets were isoenergetic with equal protein concentrations. All groups that were not treated with oestradiol received the vehicle. Whole-mount analyses were performed to determine longitudinal ductal growth and terminal end bud development. DNA was extracted from the gland and assessed by spectrophotometry (260/280 nm). Tissue extracts for extracellular matrix (ECM) proteins, matrix metalloproteinase-2 (MMP(2)), tissue inhibitor of MMP(2) (TIMP(2)), and serum oestradiol and mammary tissue epidermal growth factors (EGF) were measured by immunoassays. Expt 2 utilised the Her2/neu transgenic strain, with the same protocols. Statistical significance was determined by one-way ANOVA. From Expt 1 and 2, soya and α-LA significantly increased ductal elongation when compared with the oestrogen and control groups. These results were corroborated by data on total DNA and the ratio of MMP(2):TIMP(2). The ratio of MMP(2):TIMP(2) was affected by α-LA. Serum oestradiol was decreased only in the oestradiol-treated groups in both experiments. Soya is known to be oestrogenic and can act on epithelia directly. The mechanism by which α-LA affects glandular development is by modulating the ECM or by promoting the synthesis/activity of EGF.

Gastrointestinal sensitivity to soy and milk proteins in patients with IgA nephropathy.

BACKGROUND: sensitivity to food antigens has been postulated as a contributing factor to the pathogenesis of IgA nephropathy (IgAN). METHODS: in this study we used a recently developed mucosal patch technique to evaluate rectal mucosal sensitivity to soy and cow's milk (CM) proteins in IgAN patients (n = 28) compared to healthy subjects (n = 18). The rectal mucosal production of nitric oxide (NO) and release of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were measured. Serum samples were analyzed for IgA and IgG antibodies to alpha-lactalbumin, beta-lactoglobulin, casein and soy. RESULTS: 14 of 28 (14/28) patients experienced a rectal mucosal reaction, measured by increased NO and/or MPO levels, upon rectal challenge with soy and/or cow's milk proteins. The levels of IgG antibodies to alpha-lactalbumin, beta-lactoglobulin and casein were significantly higher in CM sensitive as compared with non-sensitive IgAN patients, whereas the mean serum levels of IgA antibodies were similar. No differences were seen in serum levels of IgA or IgG antibodies to soy. CONCLUSION: it is concluded that approximately half of our IgAN patients have a rectal mucosal sensitivity to soy or CM, and that an immune reactivity against antigens may be involved in the pathogenesis of IgAN in this subgroup of patients.

Alpha-lactalbumin-enriched and probiotic-supplemented infant formula in infants with colic: growth and gastrointestinal tolerance.

Studies undertaken with alpha-lactalbumin-enriched formulae never addressed infants with colic. This study evaluated the nutritional adequacy, the gastrointestinal tolerance and the effect on colic of an alpha-lactalbumin-enriched and probiotic-supplemented formula. A double-blind, placebo-controlled study enrolled 66 healthy infants with colic, aged 3 weeks to 3 months, fed during 1 month with the either experimental formula (EF, Modilac Digest 1) or control formula (CF) and evaluated for efficacy and safety parameters at days 15 and 30. Weight and height gains were identical in the two groups and complied with standards (1023.4+/-360.4 g (EF) and 1047.4+/-372.1 g (CF), NS; 4.2+/-1.4 cm (EF) and 4.3+/-1.9 cm (CF), NS). No differences were found between groups for crying duration. 'Feeding-related' gastrointestinal side effects were significantly lower with EF than with CF (P=0.011). An alpha-lactalbumin-enriched and probiotic-supplemented formula guaranteed good weight and length gains to infants with colic and seemed to provide good gastrointestinal tolerance.

Cow's milk allergy in adults is rare but severe: both casein and whey proteins are involved.

BACKGROUND: Studies on cow's milk allergy (CMA) in adults are scarce. Little is known about the clinical symptoms, eliciting doses (ED), and allergens involved. OBJECTIVE: The aim of this study was to analyse the clinical symptoms, ED and allergen recognition in adult CMA patients, compared with cow's milk (CM)-sensitized, but tolerant controls. METHODS: Adult CMA patients were evaluated by standardized questionnaires (n=30), skin prick tests (SPTs) and specific IgE for CM allergens (n=18), and a double-blind placebo-controlled food challenge (DBPCFC, n=10). A control group (n=25) of CM-sensitized, but tolerant adults was included. RESULTS: The majority of CMA patients (20/30, 67%) reported severe symptoms. In all patients participating in DBPCFC, CMA was confirmed. ED for subjective symptoms (0.3-300 mg CM protein) were significantly lower than that for objective symptoms (300-9000 mg CM protein). The severity of CMA by history and ED was not correlated with SPT or IgE. Patients had higher SPT reactivity than controls for CM, alpha-lactalbumin and beta-lactoglobulin (P=0.002, P=0.014 and P=0.004) but not for casein. Specific IgE to CM tended to be higher (P=0.068) and IgE to casein was higher in patients than that in controls (P=0.016). No difference was observed for IgE to alpha-lactalbumin and beta-lactoglobulin. CONCLUSION: Adult CMA is severe in nature. ED are low, starting from 0.3 mg CM protein. Patients with CMA recognize the same major allergens (casein and whey proteins) as controls, but display a stronger SPT and IgE reactivity.

Use of prick-tests in the screening of immediate allergy to protein: 16 cases.

BACKGROUND: Allergy to protein hydrolysates seem to be on the rise but screening is difficult because of the wide range of symptoms. The goal of our study was to improve the screening process by skin prick testing infants with an anaphylactic form of allergy to cow's milk. METHODS: We studied 92 infants who were allergic to cow's milk. The diagnosis was based on the results of skin prick tests, specific IgE assays, and oral food challenges. The skin prick tests were performed using a number of protein hydrolysate formulae and a synthetic amino acid-based formula available in France. RESULTS: We detected sensitisation to the hydrolysates in 16 infants (17.3%), 15 by positive skin prick tests and one due to persistent symptoms on protein hydrolysate formulae (gastrointestinal manifestations, atopic dermatitis, and multiple food allergies), which completely receded when the synthetic amino acid formula was used as a substitute. Two infants had a positive hydrolysate oral food challenge test. There were no statistically significant differences in terms of age, sex, breastfeeding, clinical manifestations, family history, skin reaction size, or associated allergies. The infants who were sensitised to the hydrolysates had significantly higher specific IgE levels (whole milk,(_)-lactalbumin, and casein; median = 25.6 kU/L for cow's milk, p = 0.03) than those who were allergic to cow's milk but not sensitised to the hydrolysates. CONCLUSIONS: Skin prick tests can be used to screen for sensitisation to hydrolysates in infants with IgE-mediated cow's milk allergy. They can also be used to determine the most suitable hydrolysate formula for individual infants.

Identification of a masked allergen, alpha-lactalbumin, in baby-food cereal flour guaranteed free of cow's milk protein.

We report on a baby food, cereal flour P (CFP), which, although guaranteed free of cow's milk protein, caused failure to thrive and diarrhea, vomiting, and coughing fits in a 22-month-old child. The purpose of this study was to identify the allergen involved. The investigation used prick tests, RAST, and the RAST inhibition method. Specific IgE was elevated to 100 kU/l for cow's milk and to 15.3 kU/l for alpha-lactalbumin (2.5 kU/l for casein, 0.7 kU/l for beta-lactoglobulin). Antibovine IgG IgEs were associated. RAST inhibition experiments demonstrated the presence of alpha-lactalbumin in "food-quality" lactose used in this flour, at a dose of 1-5 micrograms/g of CFP. The daily intake of alpha-lactalbumin was found to be less than 70 micrograms. This exquisite clinical sensitization was attributed to the intestinal hyperpermeability (IH) which favors the access of milk allergen to the blood, leading to an ever-growing state of hypersensitivity. It could have been due to egg- and mustard-associated allergies as well as to giardiasis and intestinal candidosis. This work underlines the risk of masked food allergens and the need of thoroughly informative labeling.

Occupational asthma and rhinoconjunctivitis from inhalation of dried cow's milk caused by sensitization to alpha-lactalbumin.

A chocolate candy worker was diagnosed as having occupational asthma and rhinoconjunctivitis on the basis of clinical record and methacholine challenge. Positive conjunctival and bronchial challenge tests with lactalbumin showed that this protein was the pathogenetic agent. Type I hypersensitivity mechanism is demonstrated by means of skin prick test and RAST.

[Histologic manifestations in the skin in alpha-lactoalbumin intradermal tests in patients with chronic urticaria]. / Histoloske pojave u kozi u toku intradermnog testa alfa-laktoalbuminom kod bolesnika s hronicnom urtikarijom.

Intradermal injection with alpha-lactoalbumine, 2000 PNU/ml was carried out in seven patients (1 male, 6 females, mean age 32.4 years) suffering from milk intolerance. None of the patients had a positive allergen-specific IgE antibodies in the sera (RAST). Skin test was performed on the volar part of the forearms at the same time. The area of skin reaction was estimated and measured within 36 hours on the right arm. Skin biopsy was done with a 4 mm punch after 8 hours from site of antigen injection on the left arm. Various cells infiltrating the site of antigen instillation were present. Leukocytoclastic vasculitis was only found in patients with dual intradermal reaction (immediate and late onset of response; 8 12 hours). These results indicate that local skin reaction to alpha-lactoal-bumine is mediated by diverse immune mechanisms, and that it may be of clinical significance for the diagnosis of cow milk allergy in adults.

Cow's milk protein allergy--results of skin-prick test with purified milk proteins.

The diagnosis of milk-protein allergies is difficult. Therefore, the main cow's milk proteins (alpha-lactalbumin, beta-lactoglobulin A + B, alpha s-casein, beta-casein, kappa-casein), purified to the highest available standards, were used for differential diagnosis of allergic individuals by applying skin-prick test. In the case of adults with uncertain medical history, milk proteins rarely caused skin reactions, while distinct skin reactions were observed in 11 of 13 children with strongly suspected milk-protein allergy. In the presented study alpha-lactalbumin and beta-lactoglobulin B were the main allergens, because skin reactions to these proteins were provoked with highest prevalence and intensity. Intensity and prevalence of reactions to alpha- and kappa-casein were significantly less. In two cases skin reactions to alpha-lactalbumin were observed exclusively.

Hypersensitivity reaction in an infant fed hydrolyzed lactalbumin contained in a semielemental formula.

Following introduction of milk protein formula feedings, a 6-month-old male developed profuse, watery diarrhea progressing to shock, requiring cardiopulmonary resuscitation. Reinstitution of enteral feedings with a formula containing hydrolyzed lactalbumin (Travasorb STD) resulted in recurrence of diarrhea with fever. Intestinal and rectal biopsies showed only nonspecific inflammatory changes. He was discharged on an elemental formula (Vivonex). Twenty-three months later, while admitted for evaluation of hypophosphatemic rickets, immunologic testing using the lymphocyte migration inhibition factor (LIF) test demonstrated positive reactions, especially to alpha-lactalbumin (56% inhibition) and whole cow's milk (22%, normal of less than 20% inhibition). Skin tests revealed sensitivity to cow's milk and eggs. Soy formula also produced diarrhea and bloody stools. Protein hydrolysate formulas, touted as hypoallergenic diets, are useful in infants with intolerance to milk protein. This is the first documented case of an immunological reaction to the hydrolyzed whey protein, lactalbumin. Although protein hydrolysate formulas are effective treatment in most infants with milk protein intolerance, allergic reactions are possible. Caution and close observation should be exercised in immunologically sensitized infants rechallenged with any formula.

Effects of dietary protein and butylated hydroxytoluene on the kidneys of rats.

Semipurified diet using Na-caseinate or lactalbumin as the only protein source was given to female rats to study the influence of nephrocalcinosis on butylated hydroxytoluene (BHT) induced kidney damage. The study showed, that BHT induces nephropathy in female rats irrespective of the diet used. Pronounced nephrocalcinosis was only found in rats fed the Na-caseinate diet. Thus, this study does not indicate a connection between the development of the BHT-nephropathy and nephrocalcinosis. The results from this study once more stress the influence of the diet on reaction of the animal to experimental procedures.