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1.
Heiner Syndrome and Milk Hypersensitivity: An Updated Overview on the Current Evidence.
Arasi, S, Mastrorilli, C, Pecoraro, L, Giovannini, M, Mori, F, Barni, S, Caminiti, L, Castagnoli, R, Liotti, L, Saretta, F, et al
Nutrients. 2021;(5)
Abstract
Infants affected by Heiner syndrome (HS) display chronic upper or lower respiratory tract infections, including otitis media or pneumonia. Clinically, gastrointestinal signs and symptoms, anemia, recurrent fever and failure to thrive can be also present. Chest X-rays can show patchy infiltrates miming pneumonia. Clinical manifestations usually disappear after a milk-free diet. The pathogenetic mechanism underlying HS remains unexplained, but the formation of immune complexes and the cell-mediated reaction have been proposed. Patients usually outgrow this hypersensitivity within a few years. The aim of this review is to provide an updated overview on the current evidence on HS in children, with a critical approach on the still undefined points of this interesting disease. Finally, we propose the first structured diagnostic approach for HS.
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2.
Precision medicine in cow's milk allergy.
D'Auria, E, Venter, C
Current opinion in allergy and clinical immunology. 2020;(3):233-241
Abstract
PURPOSE OF REVIEW The aim of this review is to describe the role of precision medicine in the diagnosis, treatment, and monitoring of cow's milk allergy. RECENT FINDINGS The development of 'omics' sciences in the field of food allergy has led to a better understanding of the allergenicity of cow's milk proteins and significant advances in the knowledge of the pathogenesis and mechanisms of cow's milk allergy. Omics-based technologies allow the practitioner to better differentiate cow's milk allergy subtypes and to predict cow's milk allergy (CMA) persistence over time. Precision medicine extends the role of the oral food challenge, to determine the individual's threshold doses, and to establish tolerance to baked milk products. Other than symptom relief, dietary strategies are currently being investigated for the potential to induce tolerance. Oral immunotherapy offers a treatment option for patients with severe and persistent IgE-mediated CMA. Individual baseline-immune profiles may be predictive of cow's milk oral immunotherapy safety and efficacy.Patient data derived from current technology, in combination with the patient's history, can be translated into treatments targeted at patient-tailored interventions. SUMMARY The identification of novel biomarkers may improve diagnostic accuracy and also predict patient responsiveness to treatments. Integration of patient data will become increasingly important as omics technologies become more widely used in the clinical setting.
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3.
Transforming growth factor beta in human milk and allergic outcomes in children: A systematic review.
Khaleva, E, Gridneva, Z, Geddes, DT, Oddy, WH, Colicino, S, Blyuss, O, Boyle, RJ, Warner, JO, Munblit, D
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2019;(9):1201-1213
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Abstract
BACKGROUND Human milk (HM) transforming growth factor beta (TGF-β) is critical for inflammation regulation and oral tolerance promotion. Previous reports suggested that variations in HM TGF-β levels are associated with allergic outcomes. OBJECTIVE We undertook a systematic review (PROSPERO 2017 CRD42017069920) to reassess the evidence on the relationships between HM TGF-β and allergic outcomes in children. METHODS Electronic bibliographic databases (MEDLINE, EMBASE and Cochrane Library) were systematically searched. Two independent reviewers screened reference lists, extracted the data and assessed risk of bias using the National Institute for Clinical Excellence methodological checklist. RESULTS A total of 21 studies were identified. Sixteen studies assessed relationships between HM TGF-β and risk of eczema; 14, allergic sensitization; nine, wheezing/asthma; six, food allergy; three, allergic rhinitis/conjunctivitis. Five cohorts (5/18, 28%) reported a protective effect of TGF-β1, while 3 (3/10, 30%) suggested increased risk of allergic outcomes development and 1 (1/10, 10%), a protective effect of TGF-β2 on eczema. Meta-analysis was not possible due to significant heterogeneity in methodology, age of outcome assessment and differing statistical approaches. 71% (15/21) of studies carried a high risk of bias. CONCLUSION AND CLINICAL RELEVANCE In contrast with previous findings, we did not find strong evidence of associations between HM TGF-β and allergic outcomes. Differences in studies' methodology and outcomes do not allow unconditional rejection or acceptance of the hypothesis that HM TGF-β influences the risk of allergy development. Future studies on diverse populations employing standardized methods, accurate phenotyping of outcomes and evaluation of the effect of TGF-β in combination with other HM immune markers, microbiome and oligosaccharides are required.
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[Advances in the knowledge about human milk proteins].
Brunser, O
Revista chilena de pediatria. 2018;(2):261-269
Abstract
The mammary gland and maternal milk are the product of millions of years of evolution that resul ted in an optimal composition that sustains the growth and development of newborns and infants. Maternal milk supports the growth, adaptation and survival of this immature organism. Recent studies have detected 1606 different proteins in human milk, most of them synthesized in the acini of the glandular tissue while others originate from distant organs such as the lymphoid tissue and the digestive tract. Maternal milk enzymes modify its proteins and liberate peptides with antimicrobial, antihypertensive or stimulatory activities. This proteolytic activity occurs at specific sites in peptide chains. To prevent the extemporaneous activation of these proteolytic enzymes, that would result in inflammatory processes, maternal milk also contains inhibitory peptides that together with the stimulatory peptides conform a complex regulatory system. Some enzymes in maternal milk main tain their activity in the gastrointestinal tract of infants and compensate for the decreased activity of digestive tract enzymes in newborns. Thus, the milk enterokynase stimulates the release of pancreatic proteases as it induces the liberation of cholecystokynin/pancreozymin. The bile salt-activated lipase of human milk is activated in the duodenum by the infants' bile salts and partially compensates for the low levels of pancreatic lipase in newborns. These milk enzymes probably contribute to the nutrition of premature infants as they increase the availability of amino acids and peptides in their upper gastrointestinal tract; furthermore, as their intestinal epithelium is more permeable to peptides and partially digested protein this may help induce immune tolerance. The most relevant issues in the physiology and composition of the maternal milk are presented in this review.
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Effects of nutritional supplementation for HIV patients starting antiretroviral treatment: randomised controlled trial in Ethiopia.
Olsen, MF, Abdissa, A, Kæstel, P, Tesfaye, M, Yilma, D, Girma, T, Wells, JC, Ritz, C, Mølgaard, C, Michaelsen, KF, et al
BMJ (Clinical research ed.). 2014;:g3187
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Abstract
OBJECTIVES To determine the effects of lipid based nutritional supplements with either whey or soy protein in patients with HIV during the first three months of antiretroviral treatment (ART) and to explore effects of timing by comparing supplementation at the start of ART and after three months delay. DESIGN Randomised controlled trial. SETTING Three public ART facilities in Jimma, Oromia region, Ethiopia. PARTICIPANTS Adults with HIV eligible for ART with body mass index (BMI) >16. INTERVENTION Daily supplementation with 200 g (4600 kJ) of supplement containing whey or soy during either the first three or the subsequent three months of ART. OUTCOME MEASURES Primary: lean body mass assessed with deuterium dilution, grip strength measured with dynamometers, and physical activity measured with accelerometer and heart rate monitors. Secondary: viral load and CD4 counts. Auxiliary: weight and CD3 and CD8 counts. RESULTS Of 318 patients enrolled, 210 (66%) were women, mean age was 33 (SD 9), and mean BMI was 19.5 (SD 2.4). At three months, participants receiving the supplements containing whey or soy had increased their lean body mass by 0.85 kg (95% confidence interval 0.16 kg to 1.53 kg) and 0.97 kg (0.29 kg to 1.64 kg), respectively, more than controls. This was accompanied by an increased gain of grip strength of 0.68 kg (-0.11 kg to 1.46 kg) for the whey supplement group and 0.93 kg (0.16 kg to 1.70 kg) for the soy supplement group. There were no effects on physical activity. Total weight gain increased by 2.05 kg (1.12 kg to 2.99 kg) and 2.06 kg (1.14 kg to 2.97 kg) for the whey and soy groups, respectively. In addition, in the whey supplement group overall CD3 counts improved by 150 cells/µL (24 to 275 cells/µL), of which 112 cells/µL (15 to 209 cells/µL) were CD8 and 25 cells/µL (-2 to 53 cells/µL) were CD4. Effects of the soy containing supplement on immune recovery were not significant. The effects of the two supplements, however, were not significantly different in direct comparison. Exploratory analysis showed that relatively more lean body mass was gained by patients with undetectable viral load at three months. Patients receiving delayed supplementation had higher weight gain but lower gains in functional outcomes. CONCLUSIONS Lipid based nutritional supplements improved gain of weight, lean body mass, and grip strength in patients with HIV starting ART. Supplements containing whey were associated with improved immune recovery. Trial registration Controlled-trials.com ISRCTN32453477.
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[Immune stimulative potency of milk proteins].
Ambroziak, A, Cichosz, G
Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego. 2014;(212):133-6
Abstract
Milk proteins are characterized by the highest immune stimulative potency from among all the proteins present in human diet. Whey proteins and numerous growth factors that regulate insulin secretion, differentiation of intestine epithelium cells, and also tissue restoration, are priceless in stimulation the immune system. Lactoferrin shows the most comprehensive pro-health properties: antioxidative, anticancer, immune stimulative and even chemopreventive. Also peptides and amino acids formed from casein and whey proteins possess immune stimulative activity. The most valuable proteins, i.e. lactoferrin, immune globulins, lactoperoxidase and lisozyme, together with bioactive peptides, are resistant to pepsin and trypsin activity. This is why they maintain their exceptional biological activity within human organism. Properly high consumption of milk proteins conditions correct function of immune system, especially at children and elderly persons.
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Identification of MFG-E8 as a novel therapeutic target for diseases.
Li, BZ, Zhang, HY, Pan, HF, Ye, DQ
Expert opinion on therapeutic targets. 2013;(11):1275-85
Abstract
INTRODUCTION Milk fat globule-epidermal growth factor-factor 8 (MFG-E8), a peripheral membrane glycoprotein has been widely studied in recent years due to its omnipresent locations, express and multiple functions. Traditionally, MFG-E8 was identified as an outstanding factor for phagocytosis of apoptotic cells and a significant factor in immune systems. Recent studies with some new findings have shed an interesting light on the old peripheral membrane glycoprotein in various diseases. AREAS COVERED In inflammatory and the systemic lupus erythematosus-type autoimmune disease, age-related diseases and tumors, MFG-E8 plays a multifunctional role in attenuating inflammation and improving prognosis, healing wound and remodeling arterial and enhancing tumorigenicity and cancer metastasis. This review provides a comprehensive view on the latest advances in the field. The summarized knowledge will help to explore the potential therapeutic roles of MFG-E8 and to design MFG-E8-based strategies for the treatment of these diseases. EXPERT OPINION Though the exact roles of MFG-E8 have not been fully elucidated in diseases. MFG-E8 may serve as a promising therapeutic strategy.
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War and peace between WAP and HIV: role of SLPI, trappin-2, elafin and ps20 in susceptibility to HIV infection.
Drannik, AG, Henrick, BM, Rosenthal, KL
Biochemical Society transactions. 2011;(5):1427-32
Abstract
Despite tremendous advances in our understanding of HIV/AIDS since the first cases were reported 30 years ago, we are still a long way from understanding critical steps of HIV acquisition, pathogenesis and correlates of protection. Our new understanding of the importance of the mucosa as a target for HIV infection, as well as our recent observations showing that altered expression and responses of innate pattern recognition receptors are significantly associated with pathogenesis and resistance to HIV infection, indicate that correlates of immunity to HIV are more likely to be associated with mucosal and innate responses. Most of the heterosexual encounters do not result in productive HIV infection, suggesting that the female genital tract is protected against HIV by innate defence molecules, such as antiproteases, secreted mucosally. The present review highlights the role and significance of the serine protease inhibitors SLPI (secretory leucocyte protease inhibitor), trappin-2, elafin and ps20 (prostate stromal protein 20 kDa) in HIV susceptibility and infection. Interestingly, in contrast with SLPI, trappin-2 and elafin, ps20 has been shown to enhance HIV infectivity. Thus understanding the balance and interaction of these factors in mucosal fluids may significantly influence HIV infection.
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Invited review: physiological properties of bioactive peptides obtained from whey proteins.
Madureira, AR, Tavares, T, Gomes, AM, Pintado, ME, Malcata, FX
Journal of dairy science. 2010;(2):437-55
Abstract
Processing of whey proteins yields several bioactive peptides that can trigger physiological effects in the human body: on the nervous system via their opiate and ileum-contracting activities; on the cardiovascular system via their antithrombotic and antihypertensive activities; on the immune system via their antimicrobial and antiviral activities; and on the nutrition system via their digestibility and hypocholesterolemic effects. The specific physiological effects, as well the mechanisms by which they are achieved and the stabilities of the peptides obtained from various whey fractions during their gastrointestinal route, are specifically discussed in this review.
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Proteins in human milk.
López Alvarez, MJ
Breastfeeding review : professional publication of the Nursing Mothers' Association of Australia. 2007;(1):5-16
Abstract
The human baby is born extremely immature, with its major organs and immune system not fully developed. for its survival, the infant depends on an extraordinarily well-adapted evolutionary strategy shared by all mammals: breastfeeding. But what does milk contain that makes it so essential for the newborn and how does it provide immunity, nutrition, and a source for optimal growth? Human milk is a very complex living fluid which comprises proteins, carbohydrates, lipids, cells and other biologically important components. These milk components interact synergistically with each other and their environment (the infant's gut) at a biomolecular level with the final result being that breastmilk feeds and protects the newborn. This article summarises the key characteristics of breastmilk proteins and describes their functions as critical molecules conferring human milk with its diverse bioactive properties. Also presented are some of the factors which hav an influence on the quantity and quality of breastmilk proteins.