Protease Inhibitors in Human Milk

Lindberg, Tor

doi:10.1203/00006450-197909000-00003

Cited by 64 publications

(33 citation statements)

References 17 publications

(24 reference statements)

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“…The protective effect of proteins could explain some of the contradictory reported data since fasted or fed subjects were used without discrimination. The presence of protease inhibitors in human milk and bovine milk [33,114,120,121,233] could also explain this protective effect.…”

Section: Epidermal Growth Factormentioning

confidence: 99%

Growth factors from bovine milk and colostrum: composition, extraction and biological activities

Gauthier

Pouliot

Maubois

2006

Lait

125

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-EGF, BTC, IGF-I, IGF-II, TGF-β1, TGF-β2, FGF1 and 2, and PDGF are the main growth factors present in bovine milk and colostrum. All of these growth factors are also found in human milk but at a lower concentration. The various compositional data reported in the literature vary greatly but it is evidenced that the day of lactation has the most important effect. Milk growth factors are characterized by a neutral to alkaline isoelectric point (pI) and a molecular mass between 6400 g·mol -1 and 30000 g·mol -1 . However, many of the growth factors are in a latent form, bound to high-molecular-mass proteins. Milk growth factors are resistant generally to pasteurization but disulfide reducing agents have been found to inactivate some species such as TGF-β's. The published data on bioavailability of milk growth factors are somewhat contradictory but it is generally accepted that they are resistant to gastric digestion and they can exert local and systemic effects on the gastrointestinal tract. Cation-exchange chromatography has been widely used for the extraction of milk growth factors because of the basic nature of these molecules. Membrane separations such as microfiltration (MF) have also been used successfully for the extraction of immunoglobulins and of some growth factors from colostrum, while ultrafiltration (UF) was successful only at separating IGF-I and IGF-II in whey. Milk growth factor extracts have been developed for various applications such as treatment of gastrointestinal disorders and skin diseases, wound healing, and induction of oral tolerance.

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Section: Epidermal Growth Factormentioning

confidence: 99%

Growth factors from bovine milk and colostrum: composition, extraction and biological activities

Gauthier

Pouliot

Maubois

2006

Lait

125

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“…The amount of A1PI in human milk decreases with postnatal age. While colostrum can contain up to 520 mg/l, the concentration decreases to 0.4-13.4 mg/l in mature milk [31,32]. Likewise, packed red blood cells contain 60 mg/l of A1PI [20].…”

Section: Discussionmentioning

confidence: 99%

Functional and Antigenic Concentrations of Alpha-1-Proteinase Inhibitor after Administration for the Prevention of Chronic Lung Disease of Prematurity

et al. 1999

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Objective and Methods: Alpha-1-proteinase inhibitor (A1PI) supplementation has been used in adults with inherited alpha-1-antitrypsin (A1AT) deficiency to impede the development of emphysema. A1PI supplementation may also be useful for protecting premature neonates who receive mechanical ventilation from the development of chronic lung disease (CLD). However, the pharmacokinetics of exogenous A1PI in this population are unknown. We attempted to determine the disposition of A1PI in premature infants with birth weight 600–1,250 g who received 60 mg/kg on days 0, 4, 7 and 14 in a randomized, placebo-controlled, double-blind trial. Functional and antigenic plasma concentrations of A1PI were measured at specified time points. Results: On both functional and antigenic assays, concentrations began in the normal adult range and rose from day 0 to 10 then fell slightly, but remained above initial values. The concentrations were not significantly different between the treatment and placebo groups. Conclusions: The results of this study indicate that neonatal pharmacokinetics of A1PI differ markedly from those of the adult. Total plasma clearance of exogenous A1PI seems high in the ventilated premature neonate. Higher or more frequent doses may be necessary to maintain A1PI plasma concentrations above baseline.

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“…The resistance of SOX to pepsin, trypsin, and chymotrypsin in our in vitro studies suggests that a significant quantity of the enzyme could remain intact in the intestine. Furthermore, all milks studied contain protease inhibitors, e.g., anti-trypsin and anti-chymotrypsin (26), which may decrease the rate of proteolytic digestion in the intestine of the suckling neonate.…”

Section: Discussionmentioning

confidence: 99%

Sulfhydryl Oxidase in Human Milk: Stability of Milk Enzymes in the Gastrointestinal Tract

et al. 1984

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SummarySulfhydryl oxidase (SOX) is present in human milk and in milk from all species that have been studied. The pH optimum of human milk SOX is in the neutral range between 7.0 and 7.5. Human milk SOX is stable in an acid environment: 50% of its activity remains after 1 h at pH 2.5. Acid stability is also characteristic of 7-glutamyltranspeptidase, another membranebound enzyme in skim milk. SOX is resistant to pepsin (4000 U/ ml), trypsin (50 pg/ml), chymotrypsin (200 pg/ml), and to trypsin plus chymotrypsin (25 pg eachlml). Milk SOX activity has been detected in the stomach and proximal small intestine contents of suckling rats. Human and bovine SOX are relatively heat stable: 75% of the latter remains after treatment at 62.S°C for 30 min and 65% of the former remains after treatment at 60°C for 10 min. Neither remains after 62.5"C for 30 min. AbbreviationsDTT, dithiothreitol GGT, 7-glutamyltranspeptidase GI, gastrointestinal GSH, reduced glutathione GSSG, oxidized glutathione SIgA, secretory IgA SOX, sulfhydryl oxidase Some 60-70 enzymes have been reported to be present in milk (4, 35) but little is known about their function. Milk enzymes may act in the milk itself, in the intestine, or may be absorbed by intestinal epithelial cells and transported to target tissues. At least two human milk enzymes, bile salt-stimulated lipase and mammary amylase, have been shown to play a physiologic role in the digestion of milk nutrients (15,18,19,22,23,28). It is unlikely, considering the strict control of secretory processes (29), that a significant number of enzymes occur in milk simply because of "spillage" from the blood or acinar cells.Sulfhydryl oxidases are a class of enzymes that catalyze the net synthesis of disulfide bonds (21). These enzymes use molecular oxygen and both low molecular weight sulfhydryl compounds and protein sulfhydryls as substrates in vitro (3, 3 1, 34); they produce H202 plus a disulfide. Sulfhydryl oxidases were originally described in bovine milk (24) but have subsequently been found in skin (38), seminal vesicle (31), epididymis (6), and in mouse plasmacytomas producing IgM (34). The in vivo substrates for SOX in mouse plasmacytomas were shown to be IgM monomers and the associated J chain (34). But in vivo substrates for the sulfhydryl oxidases found in mammalian secretions and tissues have not been established. Milk SOX might play a role in altering the structure of milk or intestinal proteins that are dependent upon the redox state of their sulfhydryls for function.The present experiments were designed to determine whether or not SOX and other milk enzymes had stability characteristics similar to those of milk proteins, such as secretory immunoglobulins (13, 25), which have been shown to be active in the gastrointestinal tract of the suckling neonate. Studies, both in vitro and in vivo, were done in order to measure the stability of SOX to acid and to gut protease. MATERIALS AND METHODSHuman milk samples were obtained through the La Leche League of Staten Island. The milk was frozen im...

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Protease Inhibitors in Human Milk

Cited by 64 publications

References 17 publications

Growth factors from bovine milk and colostrum: composition, extraction and biological activities

Growth factors from bovine milk and colostrum: composition, extraction and biological activities

Functional and Antigenic Concentrations of Alpha-1-Proteinase Inhibitor after Administration for the Prevention of Chronic Lung Disease of Prematurity

Sulfhydryl Oxidase in Human Milk: Stability of Milk Enzymes in the Gastrointestinal Tract

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