BIOLOGICAL PROPERTIES OF WHEY COMPONENTS

UPDATE OF LITERATURE JUNE 2001- OCTOBER 2003

W. James Harper

Department of Food Science and Nutrition

The Ohio State University

Columbus, Ohio

The role of whey components in promoting health beyond the well known nutritional benefits continues to accumulate. Studies reported since mid-2001 are presented in this report. A few key papers, published prior to 2001 and not included in previous versions of this report are included. There are an increasing number, although limited, or reports of human clinical trials in support of previous in-vitro and animal studies.

Of special interest is the new information that shows that whey proteins enhance and increases anti-oxidative protection through increasing glutathione in cells and plasma. This effect of whole whey protein products has been reported for cancer, HIV infections and possibly, also, as a protections against stroke and Alzheimer’s disease.

Protection by whey proteins and peptides of the cardiovascular system also continues to gain support, with some clinical trials showing benefits – especially as anti-inflammatory agents.

Lactoferrin continues to receive a lot of attention. The real significance of possible synergistic effects of the different whey components remains to be fully elucidated. There is a good probability the effectiveness of whey protein concentrates (WPC) and whey protein isolates (WPI) may be related to the additive or synergistic affects of the various components.

FURTHER KNOWLEDGE ABOUT KNOWN BENEFITS OF WHEY, WHEY PRODUCTS AND WHEY COMPONENTS:

Most of the potential health benefits of whey products and their components were mentioned to some degree previously in this series (Harper, 2000, 2001) and by: Walzem et al. (2002). Those that are new or continue to gain support are:

ENHANCEMENT OF PROTECTION AGAINST OXIDATIVE STRESS

Whey proteins have been shown to be a good source of sulfur amino acids (cysteine), which enhances glutathione in the body and protects against oxidative stress.

PROTECTION FROM SOME CANCERS HAS BEEN SUGGESTED FOR:

Some of the suggested whey products and components that may have anti-carcinogenic activities are summarized below. It must be emphasized that this information in based on only on cellular and animal studies, and not based on human clinical studies.

Cancer	WPC	LF/LP	CLA	BSA	PEPTIDES
Colon	+	+	+	+	+
Breast	+		+	+	+
Skin		+
Prostate	(+)		+		+
Gastric			+

WPC= whey protein concentrate; LF/LP= lactoferrrin/lactoperoxidase; CLA=conjugated linoleic acid; BSA = bovine serum albumin

ENHANCING CARDIOVASCULAR HEALTH INCLUDING ANTI-INFLAMMATORY EFFECT

Activity	WPC	WPI	Peptides	LF	Vit B	Other
Hypertension	+	+	+		+	Calcium
Anti-inflammatory	+		+
Ant-thrombic	+		+	+
Reduce cholesterol	+	+	+			Stearic acid

IMMUNE MODULATION:

Evidence continues to grow that a number of whey products and components participate in the modulation of the immune system. These include: WPC, WPI, immunoglobulins, lactoferrin, lactoperoxidase and the glycomacropeptide. Immune modulation functions include enhancement of:

• Antibody response
• Lymphocytes
• Macrophages
• Humeral immune response
• Production of lymphokines

ANTIMICROBIAL/VIRAL AFFECTS:

In the past three years new information has been presented in respect to the anti-viral activity of whey products and their components.

New Information On Anti-Viral Activities:

Considerable attention has been given to the components in milk and whey that have antiviral activity include lactoferrin, lactoperoxidase, immunoglobulins and fatty acids.

During the past several years there have been several reports, including clinical trials that have shown that whey proteins can be beneficial to patients with HIV infections.

Supplementation with whey proteins provided an increase in the plasma glutathione in with 30 patients with advance HIV infections, and the treatment was well tolerated. During a two-week trial, the commercial source of protein did influence the extent of increase in plasma glutathione levels. (Micke, et al., 2001, 2002). Whey protein also has been shown to improve muscle strength in women with HIV (Agin, et al., 2001)

Lactoferrin, but not casein or casein peptides, has been shown to be inhibitory to HIV virus (Berkhout, et al., 2003).

Component	Anti-viral	HIV	Herpes	Hepatitis C
WPC	+	+
lactoferrin	+	+	+	+
lactoferricin	+	+/-
Alpha-lactalbumin	+	+
Glycol-macro-peptide	+
Immuno-globulins	+

NEW ROLES REPORTED FOR CALCIUM:

Whey is a good source of calcium and a number of calcium products derived from whey are being marketed. In the past few years, information has shown that calcium has a much larger role in health that just contributing to bone health. Newer roles for calcium include:

· Anticancer activity

· Control of weight gain

· Regulation of insulin turn-over

· Immune modulation

WHEY PROTEIN CONCENTRATES, WHEY PROTEIN ISOLATES AND THE WHEY PORTION OF MILK

General:

Aimutis, W. R. (2002) Safety aspects related to milk-derived bioactives. Bulletin of the International Dairy Federation 375: 116-126.

Bajaj, Rajesh Kumar; Sangwan, R. B. (2002). Health enhancing potential of whey proteins - a review. Indian Journal of Dairy Science 55(5): 253-260.

Clare, D. A.; Catignani, G. L.; Swaisgood, H. E. (2003) Biodefense properties of milk: The role of antimicrobial proteins and peptides. Current Pharmaceutical Design 9(16): 1239-1255.

Dangin, Martial; Guillet, Christelle; Garcia-Rodenas, Clara; Gachon, Pierre; Bouteloup-Demange, Corinne; Reiffers-Magnani, Kristel; Fauquant, Jacques; Ballevre, Olivier; Beaufrere, Bernard (2003) The rate of protein digestion affects protein gain differently during aging in humans. Journal of Physiology 549(2): 635-644.

Dewille, Normanella T.; Mazer, Terrence B.; Liebrecht, Jeffery W. (2003) Gelled nutritional composition and process suitable for dysphagia patients and children. U.S. Pat. Appl. Publ. US 2003091613 A1 20030515.

German, J. B.; Roberts, M. A.; Fay, L.; Watkins, S. M. (2002) Metabolomics and individual metabolic assessment: the next great challenge for nutrition. Journal of Nutrition 132(9):2486-2487.

Georgiev, George; Iliev, Stefko; Toncheva, Ventsislava (2001) Iron fortificated whey protein concentrate. Godishnik na Sofiiskiya Universitet "Sv. Kliment Okhridski", Khimicheski Fakultet 92-94:137-147.

Ha, Ewan; Zemel, Michael B. (2003) Functional properties of whey, whey components, and essential amino acids: mechanisms underlying health benefits for active people (review). Journal of Nutritional Biochemistry 14(5): 251-258.

Haggarty, N. W. (2001) Bovine milk proteins: a cornucopia or Pandoras box of health opportunities. Proceedings of the Nutrition Society of New Zealand 26:21-29.

Hall, W.L.; Millward, D.J.; Long, S.J.; Morgan, L.M. (2003)Casein and whey exert different effects on plasma amino acid profiles, gastrointestinal hormone secretion and appetite. British Journal of Nutrition. 89(2): 239-248.

Harper, W.J. (2000, 2001) Biological Properties of Whey Components. A Review. The American Dairy Products Institute. Chicago, IL

Jost, Rolf (2003) Shelf-stable nutritional formulation containing non-hydrolyzed whey protein. Eur. Pat. Appl EP 1314361 A1 .

Kelly, Owen; Cusack, Siobhan; Cashman, Kevin D. (2003) The effect of bovine whey protein on ectopic bone formation in young growing rats. British Journal of Nutrition 90(3):557-564.

Osada, Kyoichi. (2003) Studies on nutritional bioactivities of cholesterol oxidation products. Nippon Eiyo, Shokuryo Gakkaishi 56(2):109-116.

Prates, J. A. Mestre; Mateus, Cristina M. R. P. (2002) Functional foods from animal sources and their physiologically active components. Revue de Medecine Veterinaire 153(3):155-160.

Rosaneli, C. F.; Bighetti, A. E.; Antonio, M. A.; Carvalho, J. E.; Sgarbieri, V. C. (2002) Efficacy of a Whey Protein Concentrate on the Inhibition of Stomach Ulcerative Lesions Caused by Ethanol Ingestion. Journal of Medicinal Food 5(4):221-228.

Vosen, Dennis (2003) Whey protein isolates: Characterization and applications in health. Abstracts of Papers, 225th ACS National Meeting, New Orleans, LA, United States, March 23-27, 2003

Walzem, R. L.; Dillard, C. J.; German, J. B.(2002) Whey components: Millennia of evolution create functionalities for mammalian nutrition: What we know and what we may be overlooking. Critical Reviews in Food Science and Nutrition 42(4):353-375.

Weaver, C.M., Liebman, M. (2002) Biomarkers of bone health appropriate for evaluating functional foods designed to reduce risk of osteoporosis. British Journal of Nutrition Volume: 88(6): 225-232

Weel, Koen G. C.; Boelrijk, Alexandra E. M.; Burger, Jack J.; Claassen, Nicole E.; Gruppen, Harry; Voragen, Alphons G. J.; Smit, Gerrit. (2003) Effect of Whey Protein on the In Vivo Release of Aldehydes. Journal of Agricultural and Food Chemistry 51(16):4746-4752.

Anti-cancer

Belobrajdic, D.P.; McIntosh, G.H.; Owens, J.A. (2003) Whey proteins protect more than red meat against azoxymethane induced ACF in Wistar rats. Cancer Letters Volume: 198 (1): 43-51.

Mc Intosh GH, Le Leu R K (2001) The influence of dietary proteins on colon cancer risk. Nutrition Research 21(7):1053-1066.

Parodi, P. W. (2002) Milk components with anticancer potential. Bulletin of the International Dairy Federation 375:97-102

Simpson, Kaylene J.; Nicholas, Kevin R. (2002) The Comparative Biology of Whey Proteins Journal of Mammary Gland Biology and Neoplasia 7(3):313-326.

Antiviral/HIV:

Agin, D, Gallagher, D., Wang, J, Heymsfield, S.B., Pierson, R. N. & Kottler, D.P. (2001) Effect of whey protein and resistant exercise of body cell mass, muscle strength and quality of life in women with HIV. Aids 15(18) 2431-2440.

Micke, P., Beeh, K.M., Schlaak, J.F & Buhl, R. (2001) Oral supplementation with whey proteins increases plasma glutathione levels of HIV infected patients. European Journal of Journal Clinical Investigation. 31(2):171-178.

Micke, P, Beeh, K.M. & Buhl, R. (2002) Effect of long term supplementation with whey proteins on plasma glutathione levels of HIV infected patients. European Journal of Nutrition 41:12-18.

Meisel, H.; Bernard, H.; Fairweather-Tait, S.; FitzGerald, R. J.; Hartmann, R.; Lane, C. N.; McDonagh, D.; Teucher, B.; Wal, J. M. (2001) Nutraceutical and functional food ingredients for food and pharmaceutical applications. British Journal of Nutrition 85(5): 635.

Oevermann, Anna; Engels, Monika; Thomas, Ursula; Pellegrini, Antonio (2003) The antiviral activity of naturally occurring proteins and their peptide fragments after chemical modification. Antiviral Research 59(1):23-33.

Cardiovascular

Davis, Martin E.; Nelson, Laurie A.; Keenan, Joeseph M.; Pins, Joel J. (2003) Reducing cholesterol with hydrolyzed whey protein. Pat.. Appl. WO 0363778 A2 20030807

van der Ven, Cornelly; Gruppen, Harry; de Bont, Dries B.A.; Voragen, Alphons G.J. (2002) Optimisation of the angiotensin converting enzyme inhibition by whey protein hydrolysates using response surface methodology. International Dairy Journal Volume: 12 (10):813-820.

Vermeirssen Vanessa; Van Camp John; Augustijns Patrick; Verstraete Willy (2002) Angiotensin-I Converting Enzyme (ACE) inhibitory peptides derived from pea and whey protein. Meded Rijksuniv Gent Fak Landbouwkd Toegep Biol Wet (2002), 67(4):27-30.

Vermeirssen, V.; Van Camp, J.; Decroos, K.; Van Wijmelbeke, L.; Verstraete, W. (2003) The impact of fermentation and in vitro digestion on the formation of angiotensin-I-converting enzyme inhibitory activity from pea and whey protein. Journal of Dairy Science 86(2):429-438.

Vermeirssen, Vanessa; Van Camp, John; Devos, Liesbet; Verstraete, Willy (2003) Release of Angiotensin I Converting Enzyme (ACE) Inhibitory Activity during in Vitro Gastrointestinal Digestion: from Batch Experiment to Semicontinuous Model. Journal of Agricultural and Food Chemistry 51(19):5680-5687

Immuno-modulation:

Hayasawa, Hirotoshi; Tamura, Yoshitaka; Miyakawa, Hiroshi; Yamada, Akio; Kuhara, Tetsuya; Ochi, Hiroshi. (2003) Interleukin-18-inducing agents containing whey protein hydrolyzates, and manufacture thereof. Pat. Appl. WO 0337364 A1.

Low, P. P. L.; Rutherfurd, K. J.; Cross, M. L.; Gill, H. S. (2001) Enhancement of mucosal antibody responses by dietary whey protein concentrate. Food and Agricultural Immunology 13(4):255-264.

Low, P. P. L.; Rutherfurd, K. J.; Gill, H. S.; Cross, M. L. (2003) Effect of dietary whey protein concentrate on primary and secondary antibody responses in immunized BALB/c mice. International Immunopharmacology 3(3):393-401.

Middleton, N.; Reid, J.R.; Coolbear, T.; Jelen, P. (2003) Proliferation and intracellular glutathione in Jurkat T cells with concentrated whey protein products. International Dairy Journal 13 (7): 565-573.

Roth, J. A.; Frank, D. E.; Weighner, P.; Weighner, M. (2001) Enhancement of neutrophil function by ultrafiltered bovine whey. Journal of Dairy Science 84(4): 824-829.

Wroblewska, Barbara; Jedrychowski, Lucjan. Influence of technological and biotechnological processes on the immunoreactivity of cow milk whey proteins. Polish Journal of Food and Nutrition Sciences (2002), 11(SI 2), 156-159.

Protection against oxidative stress:

Bounous, Gustavo; Molson, John H. (2003) The antioxidant system. Anticancer Research 23(2B):1411-1416.

Kent, K.D.; Harper, W.J.; Bomser, J.A. (2003) Effect of whey protein isolate on intracellular glutathione and oxidant-induced cell death in human prostate epithelial cells Toxicology in Vitro 17 (1):27-33.

Middleton, N.; Reid, J. R.; Coolbear, T.; Jelen, P.(2003) Proliferation and intracellular glutathione in Jurkat T cells with concentrated whey protein products. International Dairy Journal 13(7):565-573.

Nicodemo, Antonio; Ismail, Ashraf A.; Lands, Larry C.; Kubow, Stan. (2000) The effects of whey proteins on lipoprotein metabolism and oxidative stress: A review of human and animal studies. Recent Research Developments in Lipids 4(Pt. 2):245-302.

Weight Reduction:

Aoyama, Toshiaki; Fukui, Kensuke; Nakamori, Toshihiro; Hashimoto, Yukio; Yamamoto, Takashi; Takamatsu, Kiyoharu; Sugano, Michihiro (2000) Effect of soy and milk whey protein isolates and their hydrolysates on weight reduction in genetically obese mice. Bioscience, Biotechnology, and Biochemistry 64(12):2594-2600.

Ha, Ewan; Zemel, Michael B. (2003) Functional properties of whey, whey components, and essential amino acids: mechanisms underlying health benefits for active people (review). Journal of Nutritional Biochemistry 14(5):251-258.

WHEY COMPONENTS AND THEIR ASSOCIATED HEALTH BENEFITS

BETA-LACTOGLOBULIN:

General:

Lynen, Frederic; Van Thuyne, Wim; Borremans, Frans; Vanhoenacker, Gerd; Sandra, Pat (2003) Measurement of the binding of retinoic acid to b-lactoglobulin B by affinity capillary electrophoresis. Journal of Separation Science 26(1/2): 53-60.

Kushibiki, Shiro; Hodate, Koichi; Kurisaki, Junichi; Shingu, Hiroyuki; Ueda, Yasuko; Watanabe, Akira; Shinoda, Mitsuru. (2001) Effect of b-lactoglobulin on plasma retinol and triglyceride concentrations, and fatty acid composition in calves. Journal of Dairy Research 68(4):579-586

Zsila, Ferenc; Bikadi, Zsolt; Simonyi, Miklos. (2002) Retinoic acid binding properties of the lipocalin member b-lactoglobulin studied by circular dichroism, electronic absorption spectroscopy and molecular modeling methods. Biochemical Pharmacology 64(11):1651-1660.

Antiviral:

Oevermann, Anna; Engels, Monika; Thomas, Ursula; Pellegrini, Antonio. (2003) The antiviral activity of naturally occurring proteins and their peptide fragments after chemical modification. Antiviral Research 59(1):23-33.

Ng, T.B.; Lam, T.L.; Au, T.K.; Ye, X.Y.; Wan, C.C. (2001)Inhibition of human immunodeficiency virus type 1 reverse transcriptase, protease and integrase by bovine milk proteins Life Sciences 69(19):2217-2223.

Anti-microbial:

Pellegrini, A.; Dettling, C.; Thomas, U.; Hunziker, P. (2001) Isolation and characterization of four bactericidal domains in the bovine beta-lactoglobulin. Biochimica et Biophysica Acta 1526(2):131-140.

Pellegrini, A.; Schumacher, S.; Stephan, R. (2003) In-vitro activity of various antimicrobial peptides developed from the bactericidal domains of lysozyme and beta-lactoglobulin with respect to Listeria monocytogenes, Escherichia coli O157, Salmonella spp. and Staphylococcus aureus. Archiv fuer Lebensmittelhygiene 54(2):34-36.

Cardiovascular:

Hernández-Ledesma, Blanca; Recio, Isidra; Ramos, Mercedes; Amigo, Lourdes (2002) Preparation of ovine and caprine β-lactoglobulin hydrolysates with ACE-inhibitory activity. Identification of active peptides from caprine β-lactoglobulin hydrolysed with thermolysin. International Dairy Journal Volume: 12(10):805-812.

Immunomodulation:

Ametani, Akio; Sakurai, Toshio; Katakura, Yoshinori; Kuhara, Satoru; Hirakawa, Hideki; Hosoi, Tomohiro; Dosako, Shun-ichi; Kaminogawa, Shuichi. (2003) Amino acid residue substitution at T-cell determinant-flanking sites in b-lactoglobulin modulates antigen presentation to T cells through subtle conformational change. Bioscience, Biotechnology, and Biochemistry 67(7):1507-1514.

Bonomi, Francesco; Fiocchi, Alessandro; Frokiaer, Hanne; Gaiaschi, Antonella; Iametti, Stefania; Poiesi, Claudio; Rasmussen, Patrizia; Restani, Patrizia; Rovere, Pierpaolo (2003) Reduction of immunoreactivity of bovine b-lactoglobulin upon combined physical and proteolytic treatment. Journal of Dairy Research 70(1):51-59.

Kobayashi, Kazuo; Yoshida, Tadashi; Takahashi, Koji; Hattori, Makoto (2003). Modulation of the T Cell Response to b-Lactoglobulin by Conjugation with Carboxymethyl Dextran. Bioconjugate Chemistry 14(1): 168-176.

Sutton, Leonard Franklin, Jr. (2002) Influence of beta-lactoglobulin on the uptake and passage of Igg in the intestinal cell in vivo and in vitro. 116 pp.

Yamauchi, Rena; Sonoda, Soushi; Jinsmaa, Yunden; Yoshikawa, Masaaki (2002) Antinociception induced by b-lactotensin, a neurotensin agonist peptide derived from b-lactoglobulin, is mediated by NT2 and D1 receptors. Life Sciences 73(15):1917-1923.

ALPHA-LACTALBUMIN

General:

Hayasawa, Hirotoshi; Toida, Tomohiro (2001) Gastroprotective effect of a-lactalbumin. Gekkan Fudo Kemikaru 17(7): 19-22.

Hayasawa, Hirotoshi; Toida, Tomohiro; Shimokawa, Yukiko; Matsumoto, Hiroshi. (2001) Lactoalbumins as anti-ulcer agents. Pat. Appl. WO 2001007077 A1.

James, Kerry A C; Butts, Christine A; Koolaard, John P; Donaldson, Helen E; Scott, Margaret F (2002) The effect of feeding regimen on apparent and true ileal nitrogen digestibility for rats fed diets containing different sources of protein Journal of the Science of Food and Agriculture Volume: 82(9):1050-1060.

Kelleher, Shannon L.; Chatterton, Dereck; Nielsen, Karin; Loennerdal, Bo. (2003) Glycomacropeptide and a-lactalbumin supplementation of infant formula affects growth and nutritional status in infant rhesus monkeys. American Journal of Clinical Nutrition 77(5):1261-1268.

Kuhlman, Charles F.; Lien, Eric; Weaber, John; O'Callaghan, Daniel. (2003) Infant formula compositions with increased amounts of a-lactalbumin. U.S. Pat. Appl. Publ. US 2003124237 A1.

Lien, Eric L. (2003) Infant formulas with increased concentrations of a-lactalbumin. American Journal of Clinical Nutrition 77(6):1555S-1558S.

Matin, M. A.; Mizumoto, G.; Otani, H.. (2001) Cytotoxic properties of alpha-lactalbumins toward mammalian cells. Milchwissenschaft 56(8):430-433.

Matsumoto, H; Shimokawa, Y; Ushida, Y; Toida, T; Hayasawa-H (2001) New biological function of bovine alpha-lactalbumin: protective effect against ethanol- and stress-induced gastric mucosal injury in rats. Bioscience,-Biotechnology,-and-Biochemistry; 65(5):1104-1111.

Pantako, Odile T.; Amiot, Jean. (2001) The effects of a-lactalbumin and whey protein concentrate on a-amino acids, calcium and phosphorus levels in blood and gastrointestinal tract of rats. Reproduction, Nutrition, Development 41(3):227-238.

Sabharwal, Hemant K. (2003) Compositions containing bacteria and a-lactalbumin for pharmaceuticals and nutriceuticals. U.S. Pat. Appl. Publ. US 2003077255 A1

Teschemacher, H. (2003) Opioid receptor ligands derived from food proteins. Current Pharmaceutical Design 9(16):1331-1344.

Ushida, Yoshihiko; Shimokawa, Yukiko; Matsumoto, Hiroshi; Toida, Tomohiro; Hayasawa, Hirotoshi. (2003) Effects of bovine a-lactalbumin on gastric defense mechanisms in naive rats. Bioscience, Biotechnology, and Biochemistry 67(3):577-

583.

Anti-cancer

Chandrasekaran, E.V.; Chawda, Ram; Piskorz, Conrad; Locke, Robert D.; Ta, Alyssa; Sharad, Ghamande (2001) Human ovarian cancer, lymphoma spleen, and bovine milk GlcNAc:b1,4Gal/GalNAc transferases: two molecular species in ovarian tumor and induction of GalNAcb1,4Glc synthesis by a-lactalbumin. Carbohydrate Research Volume: 334(2): 105 - 118.

Sternhagen, Lisa G.; Allen, Jonathan C. (2001) Growth rates of a human colon adenocarcinoma cell line are regulated by the milk protein alpha-lactalbumin. Advances in Experimental Medicine and Biology 501: 115-120.

Anti-microbial:

Brück, W.M.; Graverholt, G.; Gibson, G.R. (2003) A two-stage continuous culture system to study the effect of supplemental α-lactalbumin and glycomacropeptide on mixed cultures of human gut bacteria challenged with enteropathogenic Escherichia coli and Salmonella serotype Typhimurium Journal of Applied Microbiology 95(1): 44-53.

Anti-viral

Berkhout, Ben; van Wamel, Jeroen L. B.; Beljaars, Leonie; Meijer, Dirk K. F.; Visser, Servaas; Floris, Rene (2003) Characterization of the anti-HIV effects of native lactoferrin and other milk proteins and protein-derived peptides. Antiviral Research 55(2): 341-355.

Oevermann, Anna; Engels, Monika; Thomas, Ursula; Pellegrini, Antonio. The antiviral activity of naturally occurring proteins and their peptide fragments after chemical modification. Antiviral Research (2003), 59(1), 23-33.

Stress Reduction:

Bell, Stacey J.; Shabert, Judy (2002). Nutritional supplement to alleviate stress symptoms associated with reduced levels of serotonin. U.S. Pat. Appl. Publ Cont.-in-part of U.S. Ser. No. 783,709. US 2002147153 A1

Markus, C. Rob; Olivier, Berend; De Haan, Edward H. F. (2002) Whey protein rich in a-lactalbumin increases the ratio of plasma tryptophan to the sum of the other large neutral amino acids and improves cognitive performance in stress-vulnerable subjects. American Journal of Clinical Nutrition 75(6): 1051-1056.

Matsumoto, Hiroshi; Shimokawa, Yukiko; Ushida, Yoshihiko; Toida, Tomohiro; Hayasawa, Hirotoshi. (2001) New biological function of bovine alpha-lactalbumin: protective effect against ethanol- and stress-induced gastric mucosal injury in rats. Bioscience, Biotechnology, and Biochemistry 65(5):1104-1111.

IMMUNOLOBULINS

General:

Bell, Stacey J. (2000) Whey protein concentrates with and without immunoglobulins: a review. Journal of Medicinal Food 3(1):1-13.

Elfstrand, Lidia; Lindmark-Mansson, Helena; Paulsson, Marie; Nyberg, Lena; Akesson, Bjorn. (2002) Immunoglobulins, growth factors and growth hormone in bovine colostrum and the effects of processing. International Dairy Journal 12(11):879-887.

Hayasawa, Hirotoshi; Toida, Tomohiro; Shimokawa, Yukiko; Matsumoto, Hiroshi. (2001) Lactoalbumins as anti-ulcer agents. PCT Int. Appl.

Hayasawa, Hirotoshi; Toida, Tomohiro. Gastroprotective effect of a-lactalbumin. Gekkan Fudo Kemikaru (2001), 17(7), 19-22.

Anti-cancer:

Chandrasekaran, E.V.; Chawda, Ram; Piskorz, Conrad; Locke, Robert D.; Ta, Alyssa; Sharad, Ghamande (2001) Human ovarian cancer, lymphoma spleen, and bovine milk GlcNAc:b1,4Gal/GalNAc transferases: two molecular species in ovarian tumor and induction of GalNAcb1,4Glc synthesis by a-lactalbumin. Carbohydrate Research Volume: 334(2): 105-118.

Sternhagen, Lisa G.; Allen, Jonathan C. (2001) Growth rates of a human colon adenocarcinoma cell line are regulated by the milk protein alpha-lactalbumin. Advances in Experimental Medicine and Biology 501: 115-120.

Anti-microbial:

Yoder, Ralph D.; Strohbehn, Ronald E. (2002) Antimicrobial protein derived from bovine IgG. Pat. Appl WO 2002061136 A2

Immune modulations:

Crum, Albert. (2003) Selenium-colostrum-whey immunostimulant nutritional or therapeutic supplement and method. Pat. Appl. Cont.-in-part of U.S. Ser. No. 85,994. US 2003124198 A1.

Rokka, Susanna; Korhonen, Hannu; Nousiainen, Juha; Marnila, Pertti. (2001) Colostral whey concentrate supplement increases complement activity in the sera of neonatal calves. Journal of Dairy Research 68(3):357-367.

Thorig, L.; de Groot, N.; Hensgens, C. M. H. (2001) Bovine hyperimmune whey protein concentrate with specific biological activity as a replacement ingredient. Innovations in Food Technology 13: 57-60.

Stress reduction:

Zommara, Mohsen A.; Toubo, Hirokazu; Imaizumi, Katsumi. (2002) Supplementing bovine milk immunoglobulin G prevents rats fed on a vitamin E-deficient diet from developing peroxidation stress. Annals of Nutrition & Metabolism 46(3-4):97-102.

BOVINE SERUM ALBUMIN

General:

Hu, Tao; Su, Zhiguo(2002) Bovine serum albumin-bovine hemoglobin conjugate as a candidate blood substitute Biotechnology Letters 24(4): 275-278.

Saha, Pratik; Kou, Jim H. (2002)Effect of bovine serum albumin on drug permeability estimation across Caco-2 monolayersEuropean Journal of Pharmaceutics and Biopharmaceutics. 54(3): 319-324.

Tsukada, Miki; Schröder, Mandy; Seltmann, Holger; Orfanos, Constantin E.; Zouboulis, Christos C. (2002) High Albumin Levels Restrict the Kinetics of 13-cis Retinoic Acid Uptake and Intracellular Isomerization to All-trans Retinoic Acid and Inhibit its Anti-Proliferative Effect on SZ95 Sebocytes. Journal of Investigative Dermatology 119(1): 182-185.

Anti-toxin:

Burkin, A. A.; Kononenko, G. P.; Soboleva, N. A.(2003)Products of Spontaneous Conjugation of Aflatoxins with Bovine Serum Albumin: Immunochemical Properties Applied Biochemistry and Microbiology 39(2):202-209.

Immune Modulation:

Conlan, J. Wayne; Shen, Hua; Webb, Ann; Perry, Malcolm B.(2002) Mice vaccinated with the O-antigen of Francisella tularensis LVS lipopolysaccharide conjugated to bovine serum albumin develop varying degrees of protective immunity against systemic or aerosol challenge with virulent type A and type B strains of the pathogen. Vaccine 20(29-30):3465-3471.

LACTOFERRIN

General:

Clarke, Julie; Butler, Ross; Howarth, Gordon; Read, Leanna; Regester, Geoff 2002)Exposure of oral mucosa to bioactive milk factors reduces severity of chemotherapy-induced mucositis in the hamster. Oral Oncology 38(5):478-485.

Edde, Lynn; Hipolito, Ronaldo B.; Hwang, Freda F. Y.; Headon, Denis R.; Shalwitz, Robert A.; Sherman, Michael P. (2001) Lactoferrin protects neonatal rats from gut-related systemic infection. American Journal of Physiology 281(5, Pt. 1):G1140-G1150.

McAnalley, Bill H. (2001) Dietary supplement compositions containing colostrum, lactoferrin, pectin and beta-glucan. PCT Int. Appl. WO 0247612.

Takakura, Natsuko; Wakabayashi, Hiroyuki; Ishibashi, Hiroko; Teraguchi, Susumu; Tamura, Yoshitaka; Yamaguchi, Hideyo; Abe, Shigeru. (2003) Oral lactoferrin treatment of experimental oral candidiasis in mice. Antimicrobial Agents and Chemotherapy (47(8):2619-2623.

Weinberg, Eugene D. 2001) Human lactoferrin: a novel therapeutic with broad spectrum potential. Journal of Pharmacy and Pharmacology 53(10): 1303-1310.

Cardiovascular:

Griffiths CEM, Cmberbatch M, Tucker SC, Dearman RJ, Andrew S, Headon DR & Kimber I (2001) Exoxenous topical lactoferrin inhibits alleergen-induce Langerhams cell migration and cutaneous inflammnatin in hummans. British Journal of Dermatology 144 (4):715-725.

Anti-microbial:

Caccavo, Domenico; Pellegrino, Nelly M.; Altamura, Maria; Rigon, Amelia; Amati, Luigi; Amoroso, Antonio; Jirillo, Emilio (2002). Antimicrobial and immunoregulatory functions of lactoferrin and its potential therapeutic application. Journal of Endotoxin Research 8(6): 403-417.

Diarra M S; Petitclerc D; Lacasse P (2002) Effect of lactoferrin in combination with penicillin on the morphology and the physiology of Staphylococcus aureus isolated from bovine mastitis. Journal of Dairy Science 85(5):1141-9.

Schaible, Ulrich E.; Collins, Helen L.; Priem, Friedrich; Kaufmann, (2002) Stefan H. E. Correction of the iron overload defect in beta-2-microglobulin knockout mice by lactoferrin abolishes their increased susceptibility to tuberculosis. Journal of Experimental Medicine 196(11):1507-1513.

Anti-viral:

Marchetti, M.; Superti, F. (2001) Antiviral activity of lactoferrin. (2001)

Recent-Developments-in-Antiviral-Research. 2001(1):193-203

Ng, T.B.; Lam, T.L.; Au, T.K.; Ye, X.Y.; Wan, C.C. (2001) Inhibition of human immunodeficiency virus type 1 reverse transcriptase, protease and integrase by bovine milk proteins. Life-Sciences. 69(19):2217-2223

Meijer, D.K.F.; Heeswijk, R.P.G.-van; Swart, P.J.; Beljaars, L.; Huisman, J.G.; Koenderman, A.;

The, T.H.; Harmsen, M.C.; Floris, R.; Berg, J.J.M.-van-den; Smit,C.:BakkerH. Strate-BWA-van-der; Kuipers,E. Jansen-RW; Molema-G; Berkhout-B; der-Strate-BWA-van; van-Heeswijk-RPG;

van-den-Berg-JJM; van-der-Strate-BWA (2001) Charge-modified plasma and milk proteins that

interfere with HIV and CMV/target cell binding and fusion.

Recent-Developments-in-Antiviral-Research. 2001(1):81-115.

*Shii, K.; Takamura, N.; Shinohara, M.; Shin, H.; Kawafune, T.; Sumino, Y.; Yamauchi, K.;

Teraguchi, S.; Hayasawa, H. (2001) Short-term effects of orally administered lactoferrin on patients with chronic hepatitis C. Biochemistry and Cell Biology 80(1): 151.

Superto, F.;Siciliano, R.:Rega, B.: Giansanti, F.: Valente, P.; Antonini, G. (2001) Involvement of bovinelactoferrin metal saturation, sialic acid and protein fragments in the inhibition of Rotavirus infection. Biochimica-et-Biophysica-Acta,-General-Subjects. 2001, 1528(2-3):107-115.

Strate, .B.W.A.vander: Beljaars, L.; Molema, G.; Harmsen, M.C.; Meijer, D.K.F.

(2001) Antiviral activities of lactoferrin. Antiviral-Research. 52(3):225-239

Strate, B.W.A. van der; Harmsen, M.C.; Schafer, P.; Swart, P.J.; The,T.H.; Jahn, G.; Speer, C.P.; Meijer, D.K.F.; Hamprecht, K. (2001) Viral load in breast milk correlates with transmission of human cytomegalovirus to preterm neonates, but lactoferrin concentrations do not Clinical-and-Diagnostic-Laboratory-Immunology. 8(4):818-821.

Anti-Cancer

De Waard, R.; Van Belzen, N. (2003) The anti-carcinogenic potential of lactoferrin. Agro Food Industry Hi-Tech 14(2): 35-39.

Fujita, Ken-Ichi; Ohnishi, Takamasa; Sekine, Kazunori; Iigo, Masaaki; Tsuda, Hiroyuki (2002)

Down-regulation of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)-induced CYP1A2

expression is associated with bovine lactoferrin inhibition of MeIQx-induced liver and colon

carcinogenesis in rats. Japanese Journal of Cancer Research 93(6):616-625

Frydecka, I.; Zimecki, M.; Bocko, D.; Kosmaczewska, A.; Teodorowska, R.; Ciszak, L.; Kruzel, M.; Wlodarska-Polinska, J.; Kuliczkowski, K.; Kornafel, J. (2992( Lactoferrin-induced up-regulation of zeta chain expression in peripheral blood T lymphocytes from cervical cancer patients. Anticancer Research 22(3):1897-1901.

Hara, Kazushi; Kuwahara, Yuji; Tamai, Yoichi; Watabe, Yasuo; Kumar, Roy Moray; Azuma,

Takuya. (2003) Preparation of peptides as inhibitors of proliferation of human leukemia cell.

Pat Appl JP 2003171399 A2.

Onishi, Katsushige. (2001) Transgenic Bacteroides uniformis expressing human lactoferrin and

its uses for repression of carcinogenesis and E. coli growth. Pat. Appl JP 2001346577 A2.

Tsuda, H.; Sekine, K.; Fujita, K.; Iigo, M.; Vogel, H.J. (2002) Cancer prevention by bovine lactoferrin and underlying mechanisms -- a review of experimental and clinical studies. 5th International conference on lactoferrin: structure, function and applications, Banff Centre, Banff, Alberta, Canada, 4-9. Biochemistry-and-Cell-Biology. 80(1):131-136

Tsuda, Hiroyuki; Sekine, Kazunori; Iigo, Masaaki. (2002) Inhibition of carcinogenesis by bovine lactoferrin and analysis of mechanisms. Foods & Food Ingredients Journal of Japan 200:27-35.

van Belzen, Nico. (2002) The role of lactoferrin in cancer prevention. Sciences des Aliments

22(4): 461-468.

Yang, Nannan; Lejon, Tore; Rekdal, Oystein. (2003) Antitumour activity and specificity

as a function of substitutions in the lipophilic sector of helical lactoferrin-derived peptide.

Journal of Peptide Science 9(5): 300-311.

Anti-stress:

Hayasawa, Hironori; Teraguchi, Susumu; Yamauchi, Koji; Kuwata, Hidefumi. (2001) Lactoferrins for stress relief. Pat Appl. JP 2001354583 A2.

Immune-modulation:

Artym, Jolanta; Zimecki, Michal; Kruzel, Marian L. (2003) Reconstitution of the cellular immune response by lactoferrin in cyclophosphamide-treated mice is correlated with renewal of T cell compartment. Immunobiology 207(3):197-205.

Kuhara, T.; Hayasawa, H (2002) Enhanced production of IL-18 in intestinal epithelium and antiallergic effect of orally administered bovine lactoferrin. Biochemistry and Cell Biology 80(1):146.

Middleton, N.; Reid, J. R.; Coolbear, T.; Jelen, P. (2003) Proliferation and intracellular glutathione in Jurkat T cells with concentrated whey protein products. International Dairy Journal 13(7):565-573.

Morita, H.; Yoo, Y.-C.; Kim, W.-S.; Tanaka, T.; Kumura, H.; Shimazaki, K. (2002) The detection of lactoferrin receptor on jurkat human lymphoblastic T-cell line. Biochemistry and Cell Biology 80(1):143

Tanaka, Katsuaki; Hayasawa, Hirotoshi; Teraguchi, Susumu; Yamauchi, Koji. (2002) Interferon therapeutic effect-potentiating agents Pat.. Appl WO 0243752 A1.

Thomas-LL; Xu-W; Ardon-TT (2002) Immobilized lactoferrin is a stimulus for eosinophil activation. Journal-of-Immunology. 169(2):993-999;

Wakabayashi-H; Takakura-N; Teraguchi-S; Tamura-Y (2003) Lactoferrin feeding augments peritoneal macrophage activities in mice intraperitoneally injected with inactivated Candida albicans. Microbiology-and-Immunology. 47(1):37-43.

Yoo, Y C.; Morita, H.; Yu, D.-Y.; Tanaka, T.; Shimazaki, K. (2002) Bovine lactoferrin suppresses CD3-mediated T-cell activation in mice. Biochemistry and Cell Biology 80(1): 162.

LACTOFERRICIN:

General:

Tomita M; Wakabayashi H; Yamauchi K; Teraguchi S; Hayasawa H (2002) Bovine lactoferrin and lactoferricin derived from milk: production and applications. Biochemistry and Cell Biology 80(1): 109-12.

Vogel Hans J; Schibli David J; Jing Weiguo; Lohmeier-Vogel Elke M; Epand Raquel F; Epand Richard M. (2002) Towards a structure-function analysis of bovine lactoferricin and related tryptophan- and arginine-containing peptides. Biochemistry and Cell Biology 80(1): 49-63.

Wakabayashi, H.; Takase, M.; Tomita, M. (2003) Lactoferricin derived from milk protein lactoferrin. Current Pharmaceutical Design 9(16):1277-1287.

Anti-cancer:

Eliassen, Liv Tone; Berge, Gerd; Sveinbjornsson, Baldur; Svendsen, John S.; Vorland, Lars H.; Rekdal, Oystein. (2003) Evidence for a direct antitumor mechanism of action of bovine lactoferricin. Anticancer Research 22(5):2703-2710

Anti-microbial:

Britigan B E; Lewis T S; Waldschmidt M; McCormick M L; Krieg A M (2001) Lactoferrin binds CpG-containing oligonucleotides and inhibits their immunostimulatory effects on human B cells. Journal of Immunology 167(5):2921-8.

Di Biase, Assunta Maria; Pietrantoni, Agostina; Tinari, Antonella; Siciliano, Rosa; Valenti, Piera; Antonini, Giovanni; Seganti, Lucilla; Superti, Fabiana. Heparin-interacting sites of bovine lactoferrin Schibli David J; Epand Raquel F; Vogel Hans J; Epand Richard M (2002) Tryptophan-rich antimicrobial peptides: comparative properties and membrane interactions. Biochemistry And Cell Biology 80(5):667-77.

Diarra, Moussa Sory; Lacasse, Pierre; Deschenes, Elaine; Grondin, Gilles; Paradis-Bleau, Catherine; Petitclerc, Denis (2003). Ultrastructural and cytochemical study of cell wall modification by lactoferrin, lactoferricin and penicillin G against Staphylococcus aureus. Journal of Electron Microscopy 52(2):207-215.

Haug B E; Svendsen J S (2001) The role of tryptophan in the antibacterial activity of a 15-residue bovine lactoferricin peptide. Journal of Peptide Science 7(4): 190-6.

Haug Bengt Erik; Andersen Jill; Rekdal Oystein; Svendsen John S (2002) Synthesis of a 2-arylsulphonylated tryptophan: the antibacterial activity of bovine lactoferricin peptides containing Trp(2-Pmc). Journal of Peptide Science 8(7):307-13.

Haukland H H; Vorland L H (2001) Post-antibiotic effect of the antimicrobial peptide lactoferricin on Escherichia coli and Staphylococcus aureus. Journal Of Antimicrobial Chemotherapy 48(4): 569-71.

Haukland H H; Ulvatne H; Sandvik K; Vorland L H. (2001) The antimicrobial peptides lactoferricin B and magainin 2 cross over the bacterial cytoplasmic membrane and reside in the cytoplasm. Febs Letters 508(3): 389-93

Kim, Ha-Kun; Kang, Dae-Kyung; Lee, Ju-Hoon. (2003) Bovine mutant lactoferricin and magainin fusion gene and E. coli transformant for antibacterial agent preparation. Pat.. Appl. WO 2003046002 A1

Kuwata H; Yamauchi K; Teraguchi S; Ushida Y; Shimokawa Y; Toida T; Hayasawa H (2001)Functional fragments of ingested lactoferrin are resistant to proteolytic degradation in the gastrointestinal tract of adult rats. Journal of Nutrition 131(8): 2121-7.

Masschalck B; Van Houdt R; Michiels C W (2001)High pressure increases bactericidal activity and spectrum of lactoferrin, lactoferricin and nisin. International Journal of Food Microbiology 64(3):325-32.

Omata Y; Satake M; Maeda R; Saito A; Shimazaki K; Yamauchi K; Uzuka Y; Tanabe S; Sarashina T; Mikami T (2001) Reduction of the infectivity of Toxoplasma gondii and Eimeria stiedai sporozoites by treatment with bovine lactoferricin. Journal of Veterinary Medical Science 63(2):187-90.

Strom, Morten B.; Rekdal, Oystein; Svendsen, John S. (2001) Structure-antibacterial activity relationships of 15-residue murine lactoferricin derivatives. Peptides Proceedings of the European Peptide Symposium, 26th, Montpellier, France, Sept. 10-15, 2000.

Strom, M. B.; Rekdal, O.; Stensen, W.; Svendsen, J. S. (2001) Increased antibacterial activity of 15-residue murine lactoferricin derivatives. Journal of Peptide Research 57(2):127-139.

Strom, Morten B.; Haug, Bengt Erik; Rekdal, Oystein; Skar, Merete L.; Stensen, Wenche; Svendsen, John S. (2002) Important structural features of 15-residue lactoferricin derivatives and methods for improvement of antimicrobial activity. Biochemistry and Cell Biology 80(1):65-74.

Strom, Morten B.; Rekdal, Oystein; Svendsen, John S. (2002) The effects of charge and lipophilicity on the antibacterial activity of undecapeptides derived from bovine lactoferricin. Journal of Peptide Science 8(1):36-43.

Ulvatne H; Vorland L H (2001) Bactericidal kinetics of 3 lactoferricins against Staphylococcus aureus and Escherichia coli. Scandinavian Journal of Infectious Diseases 33(7):507-11.

Vogel Hans J; Schibli David J; Jing Weiguo; Lohmeier-Vogel Elke M; Epand Raquel F; Epand Richard M (2002) Towards a structure-function analysis of bovine lactoferricin and related tryptophan- and arginine-containing peptides. Biochemistry and Cell Biology 80(1):49-63.

Wakabayashi Hiroyuki; Teraguchi Susumu; Tamura Yoshitaka (2002) Increased Staphylococcus-killing activity of an antimicrobial peptide, lactoferricin B, with minocycline and monoacylglycerol. Bioscience, Biotechnology, and Biochemistry 66(10):2161-7.

Anti-viral:

Andersen J H; Osbakk S A; Vorland L H; Traavik T; Gutteberg T J (2003) Lactoferrin and cyclic lactoferricin inhibit the entry of human cytomegalovirus into human fibroblasts. Antiviral Research 51(2): 141-9

Berkhout, Ben, van Wamel, Jeroen L.B.^, Beljaars, Leonie^, Meijer, Dirk K.F., Visser, Servaas^, & Floris, René (2003) Characterization of the anti-HIV effects of native lactoferrin and other milk proteins and protein-derived peptides. Antiviral Research 55:341-355.

Immunomodulatoin:

Britigan B E; Lewis T S; Waldschmidt M; McCormick M L; Krieg A M (2001) Lactoferrin binds CpG-containing oligonucleotides and inhibits their immunostimulatory effects on human B cells. Journal of Immunology 167(5):2921-8.

LACTOPEROXIDASE

General:

Ando, Kunio; Shimizu, Hirohiko; Moteki, Hideko. (2003) Oral hygiene compositions containing lactoferrin, lactoperoxidase, conalbumin, and/or lysozyme. Patent Appl. JP 2003137809 A2

Ballard, Francis John; Francis, Geoffrey Leonard; Regester, Geoffrey Owen; Read, Leanna Christine; Belford, David Andrew. (2002) Growth-promoting agent for treatment of surface wounds and gastrointestinal injuries and diseases and ulcers. U.S. Pat. Appl. Publ. Cont.-in-part of U.S. Ser. No. 912,040; US 2003059477 A1

Bruck, Thomas B.; Harvey, Patricia J. (2003) Oxidation of mitoxantrone by lactoperoxidase. Biochimica et Biophysica Acta 1649(2):154-163.

Blel, Mustapha; Guingamp, Marie-France; Gaillard, Jean-Luc; Humbert, Gerard. (2001)Improvement of a method for the measurement of lactoperoxidase activity in milk. International Dairy Journal 11(10):795-799.

Clare, D. A.; Catignani, G. L.; Swaisgood, H. E. (2003) Biodefense properties of milk: The role of antimicrobial proteins and peptides. Current Pharmaceutical Design 9(16): 1239-1255.

Pruitt, K (2003). Lactoperoxidase. Advanced Dairy Chemistry (3rd Edition) (Part A): 563-570.

Dana, Frederic. (2003) Dentifrice compositions containing antimicrobial enzymes. U.S. Pat. Appl. Publ., Cont.-in-part of U.S. Ser. No. 872,829, abandoned: US 2003003059 A1

Fonteh, Florence A.; Grandison, Alistair S.; Lewis, Michael J. (2002) Variations of lactoperoxidase activity and thiocyanate content in cows' and goats' milk throughout lactation. Journal of Dairy Research 69(3):401-409.

Furtmueller, Paul Georg; Jantschko, Walter; Regelsberger, Guenther; Jakopitsch, Christa; Arnhold, Juergen; Obinger, Christian. (2002) Reaction of lactoperoxidase compound I with halides and thiocyanate. Biochemistry 41(39), 11895-11900.

Garcia-Graells, Cristina; Van Opstal, Isabelle; Vanmuysen, Suzy C. M.; Michiels, Chris W. (2002) The lactoperoxidase system increases efficacy of high-pressure inactivation of foodborne bacteria. International Journal of Food Microbiology 81(3):211-221.

Nakano, Hiroshi; Morita, Hiroshi; Shimatani, Masaji. (2001) Nutrient compositions containing lactoperoxidase and lactoferrins for digestive function control. Pat. Appl. JP 2001029011 A2.

Nawar, M. A. (2001) Purification and molecular characterization of lactoperoxidase and lactoferrin from buffaloes milk. Egyptian Journal of Dairy Science 29(1):1-8.

Tanaka, Miyako; Morita, Yukikazu; Kawakami, Hiroshi. (2001) Lactoperoxidase and/or lactoferrins as liver function improving agents and health foods. Pat Appl. JP 2001226289 A2.

Wijkstrom-Frei, Corinne; El-Chemaly, Souheil; Ali-Rachedi, Radia; Gerson, Cynthia; Cobas, Miguel A.; Forteza, Rosanna; Salathe, Matthias; Conner, Gregory E. (2003) Lactoperoxidase and human airway host defense. American Journal of Respiratory Cell and Molecular Biology 29(2):206-212.

Savci, Z.; Sezgin, E.; Yildirim, Z. (2002) Enhancing keeping quality of raw cow's, sheep's and goat's milks by activation of the lactoperoxidase system. Milchwissenschaft 57(1):13-15

Tamura, Yoshitaka; Teraguchi, Susumu; Yamauchi, Koji; Atarshi, Koichiro. (2003) Health food for improving intestinal flora. Jpn. Kokai Tokkyo Koho (2003) Patent Appl. JP 2003246753 A2

Antimicrobial:

Cailliez-Grimal, Catherine; Revol-Junelles, A.-M.; Linder, M.; Milliere, J.-B. (2002) Antimicrobial activity spectra of the glucose/glucose-oxidase and the lactoperoxidase systems (SCN-) modified by I- or IO-3 anion. Milchwissenschaft 57(11/12):656-660.

Fadel, Mohamed; Courtois, Philippe. (2001) Inhibitory effect of lactoperoxidase-generated hypothiocyanite upon black pigmented anaerobe growth. International Journal of Molecular Medicine 8(1)59-62.

Ihalin, Riikka; Nuutila, Jari; Loimaranta, Vuokko; Lenander, Marianne; Tenovuo, Jorma; Lilius, Esa-Matti. (2003) Susceptibility of Fusobacterium nucleatum to killing by peroxidase-iodide-hydrogen peroxide combination in buffer solution and in human whole saliva. Anaerobe 9(1): 23-30.

Ihalin, Riikka; Pienihakkinen, Kaisu; Lenander, Marianne; Tenovuo, Jorma; Jousimies-Somer, Hannele. (2003) Susceptibilities of different Actinobacillus actinomycetemcomitans strains to lactoperoxidase-iodide-hydrogen peroxide combination and different antibiotics. International Journal of Antimicrobial Agents 21(5):434-440.

liris, Rene; Recio, Isidra; Berkhout, Ben; Visser, Servaas. (2003) Antibacterial and antiviral effects of milk proteins and derivatives thereof. Current Pharmaceutical Design 9(16):1257-1275.

Joseph, P. V.; Mathew, Jyothis; Jacob, Claramma; Haridas, M. (2003) Antibacterial activity of lactoperoxidase from sheep colostrum. Asian Journal of Chemistry 15(2):1149-1151.

Ludikhuyze, Linda R.; Claeys, Wendie L.; Hendrickx, Marc E.(2001) Effect of temperature and/or pressure on lactoperoxidase activity in bovine milk and acid whey. Journal of Dairy Research 68(4):625-637.

McLay, J. C.; Kennedy, M. J.; O'Rourke, A.-L.; Elliot, R. M.; Simmonds, R. S. (2002) Inhibition of bacterial foodborne pathogens by the lactoperoxidase system in combination with monolaurin. International Journal of Food Microbiology 73(1):1-9.

Marks, N. E.; Grandison, A. S.; Lewis, M. J. (2001) Challenge testing of the lactoperoxidase system in pasteurized milk. Journal of Applied Microbiology 91(4):735-741

Michiels, Christiaan; Garcia Graelis, Cristina; Van Opstal, Isabelle; Wuytack, Elke. (2002) Killing microorganisms with peroxidase under superatmospheric pressure. UK Pat. Appl. GB 2367997 A1

Revol-Junelles, A.-M.; Boussouel, N.; Ramet, J.-P.; Milliere, J.-B. (2001) Antibacterial activities of lactoperoxidase systems (LPS) modified by I- and IO3- anions. Milchwissenschaft 56(6):329-332

Shin, K.; Hayasawa, H.; Lonnerdal, B. (2001) Inhibition of Escherichia coli respiratory enzymes by the lactoperoxidase-hydrogen peroxide-thiocyanate antimicrobial system. Journal of Applied Microbiology 90(4):489-493.

Shin, K.; Yamauchi, K.; Teraguchi, S.; Hayasawa, H.; Imoto, I. (2002) Susceptibility of Helicobacter pylori and its urease activity to the peroxidase-hydrogen peroxide-thiocyanate antimicrobial system. Journal of Medical Microbiology 51(3):231-237.

IMMUNOGLOBULINS

General:

Masuno, Takashi (2002) Immunoglobulin-containing agents for decrease of fecal malodor, and foods containing them. Patent Appl. JP 2002121140 A2.

Thorig, L.; de Groot, N.; Hensgens, C. M. H. (2001) Bovine hyperimmune whey protein concentrate with specific biological activity as a replacement ingredient. Innovations in Food Technology 13:57-60.

Takemura, K.; Hogan, J. S.; Smith, K. L. (2003) Effect of immunoglobulin G from cows immunized with ferric citrate receptor (FecA) on iron uptake by escherichia coli. Journal of Dairy Science 86(1):133-137.

Trexler, Maria; Banyai, Laszlo; Patthy, Laszlo(2001) A human protein containing multiple types of protease-inhibitory modules. Proceedings of the National Academy of Sciences of the United States of America 98(7):3705-3709.

Williams, Charles Edward; Hobman, Peter Graeme; Yarrow, Simon Stephen. 2002) Colostrum-based pharmaceutical compositions. Pat Appl. WO 0240051.

A1.

Antimicrobial:

Yoder, Ralph D.; Strohbehn, Ronald E. (2002) Antimicrobial protein derived from bovine IgG. PCT Int. Appl. WO 0261136 A2.

Immune relatinsips:

Germano, Carl. Nutrient therapy for immunocompromised patients. (2003) US Pat Appl. 6503506 B1.

Stress:

Levieux, Didier; Morgan, Francois; Geneix, Nathalie; Masle, Isabelle; Bouvier, Frederic.

Zommara, Mohsen A.; Toubo, Hirokazu; Imaizumi, Katsumi. (2002) Supplementing bovine milk immunoglobulin G prevents rats fed on a vitamin E-deficient diet from developing peroxidation stress. Annals of Nutrition & Metabolism 46(3-4):97-102.

MINOR PROTEINS

Charlwood Joanne; Hanrahan Sarah; Tyldesley Richard; Langridge James; Dwek Miriam; Camilleri Patrick (2002) Use of proteomic methodology for the characterization of human milk fat globular membrane proteins. Analytical Biochemistry 301(2):314-324.

Fox, P. F.; Kelly, A. L. (2003) Developments in the chemistry and technology of milk proteins. 2. Minor milk proteins. Food Australia 55(6):231-234.

Mao, Yumin; Xie, Yi. (2002) Human butyrophilin 52.91 and its cDNA and therapeutic use thereof. Faming Zhuanli Shenqing Gongkai Shuomingshu Pat. Appl. CN 1333226 A1.

Murakami, Kouki; Lagarde, Margaret; Yuki, Yoshikazu. (1998) Identification of minor proteins of human colostrum and mature milk by two-dimensional electrophoresis. Electrophoresis 19(14):2521-2527.

Newburg D S; Peterson J A; Ruiz-Palacios G M; Matson D O; Morrow A L; Shults J; Guerrero M L; Chaturvedi P; Newburg S O; Scallan C D; Taylor M R; Ceriani R L (1998) Pickering L K Role of human-milk lactadherin in protection against symptomatic rotavirus infection. Lancet 351(9110):1160-4.

Peterson, Jerry A.; Scallan, Ciaran D.; Ceriani, Roberto L.; Hamosh, Margit. (2001) Structural and functional aspects of three major glycoproteins of the human milk fat globule membrane. Advances in Experimental Medicine and Biology 501:179-187

Shi, Jialan; Gilbert, Gary E. (2003) Lactadherin inhibits enzyme complexes of blood coagulation by competing for phospholipid-binding sites. Blood 101(7):2628-2636.

Stefferl, Andreas; Schubart, Anna; Storch, Maria; Amini, Aminullah; Mather, Ian; Lassmann, Hans; Linington, Christopher (2000) Butyrophilin, a milk protein, modulates the encephalitogenic T cell response to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis. Journal of Immunology 165(5):2859-2865.

Su, Sharyn X.; Ming, Fang; Yang, Mengyan; Ichinomiya, Akimoto; Davis, Martin E. (2002) MUC1 isolation from bovine milk and whey. Pat Appl. WO 2002062374 A2 20020815.

Ye, Aiqian; Singh, Harjinder; Taylor, Michael W.; Anema, Skelte. (2002) Characterization of protein components of natural and heat-treated milk fat globule membranes. International Dairy Journal 12(4):393-402.

Wang, X.; Hirmo, S.; Willen, R.; Wadstrom, T (2001) Inhibition of Helicobacter pylori infection by bovine milk glycoconjugates in a BALB/cA mouse model. Journal of Medical Microbiology 50(5):430-435.

Wilcox, C. P.; Janolino, V. G.; Swaisgood, H. E. (2002) Isolation and partial characterization of CD36 from skim milk. Journal of Dairy Science 85(8):1903-1908.

Yamada, Masamichi; Murakami, Kouki; Wallingford, John C.; Yuki, Yoshikazu (2002) Identification of low-abundance proteins of bovine colostral and mature milk using two-dimensional electrophoresis followed by microsequencing and mass spectrometry. Electrophoresis 23(7-8):1153-1160.

Yoshida, Shigeru. (1988) Isolation of some minor milk proteins, distributed in acid whey from approximately 100,000 to 250,000 daltons of particle size. Journal of Dairy Science 71(1):1-9.

MILK FAT GLOBULE MEMBRANE:

Cavaletto, Maria; Giuffrida, Maria Gabriella; Fortunato, Donatella; Gardano, Laura; Dellavalle, Giuseppina; Napolitano, Lorenzo; Giunta, Carlo; Bertino, Enrico; Fabris, Claudio; Conti, Amedeo. (2002) A proteomic approach to evaluate the butyrophilin gene family expression in human milk fat globule membrane. Proteomics 2(7):850-856.

Danthine, Sabine; Blecker, Christophe; Paquot, Michel; Innocente, Nadia; Deroanne, Claude (2000) Progress in milk fat globule membrane research: a review. Lait 80(2):209-222.

Peterson, Jerry A.; Scallan, Ciaran D.; Ceriani, Roberto L.; Hamosh, Margit. (2001) Structural and functional aspects of three major glycoproteins of the human milk fat globule membrane. Advances in Experimental Medicine and Biology 501:179-187.

Schroten, H.; Bosch, M.; Nobis-Bosch, R.; Koehler, H.; Hanisch, F.-G.; Plogmann, R. (2001) Anti-infectious properties of the human milk fat globule membrane. Advances in Experimental Medicine and Biology 501:189-192.

Scolozzi, C.; Martini, M.; Cianci, D. (2002) The milk fat globule membrane. Progress in Nutrition 4(3):190-194.

Wang, X.; Hirmo, S.; Willen, R.; Wadstrom, T (2001) Inhibition of Helicobacter pylori infection by bovine milk glycoconjugates in a BALB/cA mouse model. Journal of Medical Microbiology 50(5):430-435.

Ye, Aiqian; Singh, Harjinder; Taylor, Michael W.; Anema, Skelte. (2002) Characterization of protein components of natural and heat-treated milk fat globule membranes. International Dairy Journal 12(4):393-402.

CASEIN GLYCO MACROPEPTIDE:

Alonso, J. Fontecha; Martin, A. B. (2002) Casein macropeptide: A bioactive peptide and potential food additive. Alimentacion, Equipos y Tecnologia 173:81-86.

Brody, Ernest P (2003). Method of processing a proteinaceous material to recover k-casein macropeptide and polymers of a-lactalbumin and b-lactoglobulin. Pat. Appl. US 2003166866 A1.

Doultani, S.; Turhan, K. N.; Etzel, M. R. (2003) Whey protein isolate and glyco-macropeptide recovery from whey using ion exchange chromatography. Journal of Food Science 68(4): 1389-1395.

Etzel, Mark R. (2001) Production of substantially pure kappa casein macropeptide. Cont.-in-part of U.S. 5,968,586. Pat. Appl. US 6168823 B1.

Korhonen, H.; Pihlanto, A. (2003) Food-derived bioactive peptides - opportunities for designing future foods. Current Pharmaceutical Design 9(16):1297-1308.

Kratky, Zdenek; Maire, Jean-Claude; Ballevre, Olivier; Haschke, Ferdinand; Jost, Rolf; Kuslys, Martinas; Meister, Niklaus; Secretin, Marie-Christine. (2001) Composition for an infant formula having a low threonine content. Pat. Appl. WO 0111990 A1.

McCarthy, Anthony; McDonough, Elizabeth Cecilia; O'Connor, John Anthony. (2002) Dairy products containing casein macropeptides. Pat.. Appl. WO 0230210 A1.

Manso, M. A.; Escudero, C.; Alijo, M.; Lopez-Fandino, R. (2003) Platelet aggregation inhibitory activity of bovine, ovine, and caprine kappa-casein macropeptides and their tryptic hydrolysates. Journal of Food Protection 65(12):1992-1996.

Martin-Diana, Ana Belen; Fraga, Maria Jesus; Fontecha, Javier. (2002) Isolation and characterization of casein macropeptide from bovine, ovine, and caprine cheese whey. European Food Research and Technology 214(4):282-286.

Moreno, F. Javier; Recio, Isidra; Olano, Agustin; Lopez-Fandino, Rosina. (2001) Heterogeneity of caprine k-casein macropeptide. Journal of Dairy Research 68(2):197-208.

Moreno, F. J.; Olano, A.; Villamiel, Mar. (2001) N-acetyl- and N-glycolyl-neuraminic acid content in kappa-casein macropeptides. Milchwissenschaft 56(12): 669-671.

Oh, Sejong; Worobo, Randy W.; Kim, Byoung-Chul; Rheem, Sungsue; Kim, Saehun. (2000) Detection of the cholera toxin-binding activity of k-casein macropeptide and optimization of its production by the response surface methodology. Bioscience, Biotechnology, and Biochemistry 64(3):516-522.

Portman, Robert. (2002) Nutritional intervention composition for enhancing and extending satiety. . Pat. Appl. Cont.-in-part of U.S. 6,207,638. A1.

PEPTIDES

General:

Fosset, S.; Fromentin, G.; Gietzen, D. W.; Dubarry, M.; Huneau, J. F.; Antoine, J. M.; Lang, V.; Mathieu-Casseron, F.; Tome, D. (2002) Peptide fragments released from Phe-caseinomacropeptide in vivo in the rat. Peptides 23(10):1773-1781.

Hayasawa, Hirotoshi; Tamura, Yoshitaka; Miyakawa, Hiroshi; Yamada, Akio; Kuhara, Tetsuya; Ochi, Hiroshi. (2003) Interleukin-18-inducing agents containing whey protein hydrolyzates, and manufacture thereof. PCT Int. Appl. 2003037364 A1.

Korhonen, H.; Pihlanto-Leppala, A. (2001) Milk protein-derived bioactive peptides. Novel opportunities for health promotion. Bulletin of the International Dairy Federation 363:17-26.

Korhonen, Hannu; Pihlanto-Leppala, Anne. (2002) Formation of bioactive peptides from milk proteins through fermentation by dairy starters. ACS Symposium Series 816:173-186.

Korhonen, H.; Pihlanto, A. (2003) Food-derived bioactive peptides - opportunities for designing future foods. Current Pharmaceutical Design 9(16):1297-1308.

Mallee, Leon Franciscus; Nimmagudda, Ram; Boumans, Johannes Wilhelmus Leonardus. (2002) Cysteine/glycine rich peptides for treatment of oxidative damage and increasing cellular glutathione. Eur. Pat. Appl. EP 1201137 A1.

Meisel, H.; FitzGerald, R. J. (2003) Biofunctional peptides from milk proteins: Mineral binding and cytomodulatory effects. Current Pharmaceutical Design 9(16):1289-1295.

Meisel, H.; Bernard, H.; Fairweather-Tait, S.; FitzGerald, R. J.; Hartmann, R.; Lane, C. N.; McDonagh, D.; Teucher, B.; Wal, J. M. (2003) Detection of caseinophosphopeptides in the distal ileostomy fluid of human subjects. British Journal of Nutrition 89(3):351-358.

Oevermann, Anna; Engels, Monika; Thomas, Ursula; Pellegrini, Antonio. (2993( The antiviral activity of naturally occurring proteins and their peptide fragments after chemical modification. Antiviral Research 59(1): 23-33.

Pihlanto-Leppala, A. (2000) Bioactive peptides derived from bovine whey proteins. Opioid and ACE-inhibitory peptides. Trends in Food Science & Technology 2000, 11(9-10):347-356.

Schaefer, Christian; Waesche, Andreas. (2003) Whey protein hydrolysates and peptide fractions derived from whey protein with a bioactive action, obtained by hydrolysis with proteases. Pat. Appl. WO 2003059083 A1.

Manso, M. A.; Escudero, C.; Alijo, M.; Lopez-Fandino, R. Platelet aggregation inhibitory activity of bovine, ovine, and caprine kappa-casein macropeptides and their tryptic hydrolysates. Journal of Food Protection 65(12):1992-1996.

Anti-cancer

Roy, M. K.; Kuwabara, Y.; Hara, K.; Watanabe, Y.; Tamai, Y. (2002) Peptides from the N-terminal end of bovine lactoferrin induce apoptosis in human leukemic (HL-60) cells. Journal of Dairy Science 85(9):2065-2074.

Yang, N.; Stensen, W.; Svendsen, J. S.; Rekdal, O. (2002) Enhanced antitumor activity and selectivity of lactoferrin-derived peptides. Journal of Peptide Research 60(4):187-197.

Antimicrobial:

Pellegrini, Antonio. 2003) Antimicrobial peptides from food proteins. Current Pharmaceutical Design 9(16):1225-1238.

Cardiovascular:

Davis, Martin E.; Rao, Anand; Gauthier, Sylvie; Pouliot, Yves; Gourley, Line; Allain, Ann Francoise. (2001) Enzymatic treatment of whey proteins for the production of antihypertensive peptides, the resulting products and treatment of hypertension in mammals. Pat. Appl. WO 0185984 A1.

Pihlanto-Leppala, A. (2001) Bioactive peptides derived from bovine whey proteins. Opioid and ACE-inhibitory peptides. Trends in Food Science & Technology (2001), 11(9-10):347-356.

Wanasundara, P.K.J.P.D.; Ross, A.R.S.; Amarowicz, R.; Ambrose, S.J.; Pegg, R.B.; Shand, P.J. (2002) Peptides with angiotensin I-converting enzyme (ACE) inhibitory activity from defibrinated, hydrolyzed bovine plasma. Journal-of-Agricultural-and-Food-Chemistry; 50 (24) 6981-6988.

Wang, Haiyan; Zhang, Jiacheng. (2001) Study on antihypertensive peptide derived from dairy products. Shipin Yu Fajiao Gongye 27(11):70-73.

van der Ven, Cornelly; Gruppen, Harry; de Bont, Dries B.A.; Voragen, Alphons G.J. (2002) Optimisation of the angiotensin converting enzyme inhibition by whey protein hydrolysates using response surface methodology International Dairy Journal 12(12) 813-820.

van der Ven, Cornelly; Gruppen, Harry; de Bont, Dries B. A.; Voragen, Alphons G. J. (2002) Optimisation of the angiotensin converting enzyme inhibition by whey protein hydrolysates using response surface methodology. International Dairy Journal 12(10):813-820.

Yamauchi, Rena; Jinsmaa, Yunden; Takenaka, Yasuyuki; Yoshikawa, Masaaki. (2001) Hypocholesterolemic activity of b-lactotensin as a neurotensin receptor agonist. Peptide Science 37:225-228.

Hypocholesterolemic:

Nagaoka, Satoshi; Futamura, Yu; Miwa, Keiji; Awano, Takako; Yamauchi, Kouhei; Kanamaru, Yoshihiro; Tadashi, Kojima; Kuwata, Tamotsu. (2001) Identification of Novel Hypocholesterolemic Peptides Derived from Bovine Milk beta-Lactoglobulin. Biochemical and Biophysical Research Communications 281(1):11-17.

Nagaoka, S. (2002) New hypocholesterolemic peptides. Hissu Aminosan Kenkyu 164: 99-105.

Immune response:

Xiao, Chaowu; Jin, L. Z.; Zhao, Xin. (2001) Bovine casein peptides co-stimulate naive macrophages with lipopolysaccharide for proinflammatory cytokine production and nitric oxide release. Journal of the Science of Food and Agriculture 81(3):300-304.

Zhang, F. M.; Otani, H.. (2003) Immunogenicity and antigenicity of casein phosphopeptides. Milchwissenschaft 58(1/2):9-13.

LIPIDS

CLA:

General:

Bassaganya-Riera, J.; Hontecillas, R.; Wannemuehler, M. J. Special symposium (2002) 2001 congress symposium on nutraceuticals/edible vaccines nutritional impact of conjugated linoleic acid: A model functional food ingredient. In Vitro Cellular & Developmental Biology: Plant 38(3):241-246.

Belury, Martha A. (2002) Dietary conjugated linoleic acid in health: physiological effects and mechanisms of action. Annual Review of Nutrition 22:505-531.

Anti-Cancer:

Belury, Martha A. (2002) Inhibition of carcinogenesis by conjugated linoleic acid: potential mechanisms of action. Journal of Nutrition 132(10):2995-2998.

Seol, So Mi; Bang, Myung Hee; Choi, Ok Suk; Park, Jung Han Yoon; Kim, Woo Kyoung. (2003) Effects of conjugated linoleic acid (CLA) on matrix metalloproteinase (MMP) activity and cell motility in human colon cancer cell lines. Hanguk Yongyang Hakhoechi 36(3):280-286.

Anti-viral

Bassaganya-Riera J.; Hontecillas R.; Zimmerman D. R.; Wannemuehler M .J. (2002) Long-term influence of lipid nutrition on the induction of CD8(+) responses to viral or bacterial antigens. Vaccine 20(9-10):1435-44.

Diabetes:

Belury, Martha A.(2003) Conjugated linoleic acids in type 2 diabetes mellitus: implications and potential mechanisms. Advances in Conjugated Linoleic Acid Research 2:302-315.

Pariza, Michael W. (2002) Conjugated linoleic acid may be useful in treating diabetes by controlling body fat and weight gain. Diabetes Technology & Therapeutics 4(3):335-338.

*Remmereit, Jan; Wadstein, Jan; Klaveness, Jo. (2002) Conjugated linoleic acid in treatment and prophylaxis of diabetes. Pat. Appl. U.S.

Immune modulation:

Kelley, D. S.; Warren, J. M.; Simon, V. A.; Bartolini, G.; Mackey, B. E.; Erickson, K. L. (2002) Similar effects of c9,t11-CLA and t10,c12-CLA on immune cell functions in mice. Lipids 37(7):725-728.

Kelley, D. S.; Erickson, K. L. (2003) Modulation of body composition and immune cell functions by conjugated linoleic acid in humans and animal models: Benefits vs. risks. Lipids 38(4): 377-386

Ntambi, James M.; Choi, Youngjin; Park, Yeonhwa; Peters, Jeffrey M.; Pariza, Michael W. (2002) Effects of conjugated linoleic acid (CLA) on immune responses, body composition and stearoyl-CoA desaturase. Canadian Journal of Applied Physiology 27(6):617-627.

Weight Loss:

Hayman, Ann; MacGibbon, Alastair; Pack, Rodger J.; Rutherfurd, Kay; Green, J. Hilary. (2002) High intake, but not low intake, of CLA impairs weight gain in growing mice. Lipids 37(7): 689-692.

Yang Mingder; Cook Mark E (2003) Dietary CLA decreased weight loss and extended survival following the onset of kidney failure in NZB/W F1 mice. Lipids 38(1), 21-4.

SPHINGOLIPIDS:

General:

Kester, Mark; Kolesnick, Richard. (2003) Sphingolipids as therapeutics. Pharmacological Research 47(5):365-371.

Korhonen, H.; Pihlanto, A. (2003) Food-derived bioactive peptides - opportunities for designing future foods. Current Pharmaceutical Design 9(16):1297-1308.

Kume, Hisae; Sasaki, Hajime; Mizumoto, Kenji; Yamaguchi, Makoto. (2002) Whey protein and phospholipid for improvement of lipid metabolism. Pat. Appl. JP 2002226394.

Tanaka, Miyako; Kawakami, Hiroshi. (2003) Sphingomyelins for the prevention and treatment of memory loss. Pat Appl. JP 2003146883 A2.

Anti-cancer:

Engedal, Nikolai; Saatcioglu, Fahri. (2001) Ceramide-induced cell death in the prostate cancer cell line LNCaP has both necrotic and apoptotic features. Prostate 46(4):289-297.

Fillet, Marianne; Bentires-Alj, Mohamed; Deregowski, Valerie; Greimers, Roland; Gielen, Jacques; Piette, Jacques; Bours, Vincent; Merville, Marie-Paule. (2003) Mechanisms involved in exogenous C2- and C6-ceramide-induced cancer cell toxicity. Biochemical Pharmacology 65(10):1633-1642.

Schmelz EM, Sullards MC, Dillehay DL, Merrill AH Jr. Colonic cellproliferation (2000)
and aberrant crypt foci formation are inhibited by dairyglycosphingolipids in 1,2-dimethylhydrazine-treated CF1 mice. Journal Nutrition130(3):522-7.

Shabbits, Jennifer A.; Mayer, Lawrence D. (2003) P-glycoprotein modulates ceramide-mediated sensitivity of human breast cancer cells to tubulin-binding anticancer drugs. Molecular Cancer Therapeutics 1(3):205-213.

Tan, Xiaohua; Zhang, Yali; Jiang, Bo; Zhou, Dianyuan. (2002) Changes in ceramide levels upon catechins-induced apoptosis in LoVo cells. Life Sciences 70(17):2023-2029.

Tilly, Jonathan L.; Kolesnick, Richard N. (2002) Sphingolipids, apoptosis, cancer treatments and the ovary: investigating a crime against female fertility. Biochimica et Biophysica Acta 1585(2-3):135-138.

PREBIOTICS

Ajisaka, Katsumi; Kaneko, Tetsuo; Otomo, Hideo; Yamamoto, Yuichi. (2003) Infant formula containing milk-derived neutral oligosaccharides having antiinfective effect. Jpn. Kokai Tokkyo Koho Pat. Appl JP 2003047402 A2.

Fujimoto, Yoshinori; Ono, Terumi; Unno, Takehiro; Sumiyoshi, Hideyuki; Yamamoto, Mikio. (2002) Agents and method for taste improvement of milk-containing foods using glucooligosaccharides. Jpn. Kokai Tokkyo Koho Pat. Appl. JP 2002335903 A2.

Holma, R.; Juvonen, P.; Asmawi, M. Z.; Vapaatalo, H.; Korpela, R. (2002) Galacto-oligosaccharides stimulate the growth of bifidobacteria but fail to attenuate inflammation in experimental colitis in rats. Scandinavian Journal of Gastroenterology 37(9):1042-1047.

Quigley, J. D., III; Kost, C. J.; Wolfe, T. A. (2002) Effects of spray-dried animal plasma in milk replacers or additives containing serum and oligosaccharides on growth and health of calves. Journal of Dairy Science 85(2):413-421.

Ziggers, Dick. (2001) TOS, a new prebiotic derived from whey. Feed Mix 9(6): 7-9.

Nidetzky, Bernd; Petzelbauer, Inge; Terler, Katherine; Haltrich, Dietmar. (2003) Making more from lactose II: Production of galactooligosaccharides using a thermostable glycosidase in kinetically controlled reaction conditions. Abstracts of Papers, 225th ACS National Meeting, New Orleans, LA, United States, March 23-27, 2003.

Haltrich, Dietmar; Nidetzky, Bernd; Volc, Jindrich; Kulbe, Klaus D. (2003) Making more from lactose I: Production of prebiotic ketose sugars by enzymatic processes. Abstracts of Papers, 225th ACS National Meeting, New Orleans, LA, United States, March 23-27, 2003.

McComas, K. A., Jr.; Gilliland, S. E. (2003) Growth of probiotic and traditional yogurt cultures in milk supplemented with whey protein hydrolysate. Journal of Food Science 68(6):2090-2095.

Holma, R.; Juvonen, P.; Asmawi, M. Z.; Vapaatalo, H.; Korpela, R. (2002) Galacto-oligosaccharides stimulate the growth of bifidobacteria but fail to attenuate inflammation in experimental colitis in rats. Scandinavian Journal of Gastroenterology 37(9):1042-1047.

Maase, Kamiel; Steijns, Johannes Maria Jozef Margaretha. (2002) Use of alpha-lactalbumin as prebiotic agent. Eur. Pat. Appl EP 1228707 A1 20020807.

MINERALS

CALCIUM

Anti-Cancer:

*Kim, Edward J.; Helfman, David M. (2003) Characterization of the Metastasis-associated Protein, S100A4. Roles of calcium binding and dimerization in cellular localization and interaction with myosin. Journal of Biological Chemistry 278(32)

Tang, K. Y.; Yu, C. C.; Huang, J. K. (2001) Fendiline, an anti-anginal drug, increases intracellular Ca2+ in PC3 human prostate cancer cells. Cancer Chemotherapy and Pharmacology 48(1):37-41.

Cardiovascular:

*Hasebe, Naoyuki; Kikuchi, Kenjiro. (2002) Hypertension. Calcium in Internal Medicine 417-432.

Isshiki, Masashi. (2002) Intercellular ionized calcium: dysfunctional regulation in hypertension Igaku no Ayumi 202(9):599-604.

Ketteler, Markus; Wanner, Christoph; Metzger, Thomas; Bongartz, Philipp; Westenfeld, Ralf; Gladziwa, Ulrich; Schurgers, Leon J.; Vermeer, Cees; Jahnen-Dechent, Willi; Floege, Jurgen. (2003) Deficiencies of calcium-regulatory proteins in dialysis patients: A novel concept of cardiovascular calcification in uremia. Kidney International, Supplement 84:S84-S87.

Nakagawa, Keigo; Matsuura, Hideo. (2000) Calcium metabolism and hypertension. Clinical Calcium 10(8):902-906.

Zemel, Michael B. (2001) Calcium modulation of hypertension and obesity: Mechanisms and implications. Journal of the American College of Nutrition 20(5, Suppl.): 428S-435S.

Weight Control:

Carruth, B. R.; Skinner, J. D. (2001) The role of dietary calcium and other nutrients in moderating body fat in preschool children. International Journal of Obesity 25(4):559-566.

Fung, Teresa T.; Rimm, Eric B.; Spiegelman, Donna; Rifai, Nader; Tofler, Geoffrey H.; Willett, Walter C.; Hu, Frank B. (2001) Association between dietary patterns and plasma biomarkers of obesity and cardiovascular disease risk. American Journal of Clinical Nutrition 73(1):61-67.

Melanson, E. L.; Sharp, T. A.; Schneider, J.; Donahoo, W. T.; Grunwald, G. K.; Hill, J. O. (2003) Relation between calcium intake and fat oxidation in adult humans. International Journal of Obesity 27(2):196-203.

Miller,G.D.;Jarvis, J.K., & McBean, L.D. (2000) Handbook of Dairy Foods and Nutrition. 2^nd Ed. CRC Press, Inc. Boco Raton, Fl.

Papakonstantinou, Emilia; Flatt, William P.; Huth, Peter J.; Harris, Ruth B. S. (2003) High dietary calcium reduces body fat content, digestibility of fat, and serum vitamin D in rats. Obesity Research 11(3):387-394.

Parikh, Shamik J.; Yanovski, Jack A. (2003) Calcium intake and adiposity. American Journal of Clinical Nutrition 77(2):281-287.

Shi, Hang; Dirienzo, Douglas; Zemel, Michael B. (2001) Effects of dietary calcium on adipocyte lipid metabolism and body weight regulation in energy-restricted aP2-agouti transgenic mice. FASEB Journal 15(2):291-293.

Teegarden, Dorothy; Zemel, Michael B. (2003) Dairy product components and weight regulation: symposium overview. Journal of Nutrition 133(1):243S, 244S.

Zemel, Michael B.; Shi, Hang; Zemel, Paula C. (2001) Materials and methods using calcium for the treatment or prevention of obesity. U.S. Pat. Appl. Publ. Cont.-in-part of U.S. 6,384,087. US 2002192264 A1 .

Zemel, Michael B.. Calcium, dairy products and weight control. Sciences des Aliments (2002), 22(4), 451-458.

Zemel, Michael B.(2003) Role of dietary calcium and dairy products in modulating adiposity. Lipids 38(2):139-146.

Xue, Bingzhong; Greenberg, Andrew G.; Kraemer, Frederic B.; Zemel, Michael B (2001) Mechanism of intracellular calcium ([Ca2+]i) inhibition of lipolysis in human adipocytes. FASEB Journal 15(13):2527-2529.

METHODS OR RECOVERY OF WHEY COMPONENTS

Individual Proteins:

Alpha-lactalbumin:

Muller, Arabelle; Chaufer, Bernard; Merin, Uzi; Daufin, Georges (2003) Prepurification of a-lactalbumin with ultrafiltration ceramic membranes from acid casein whey: study of operating conditions. Lait 83(2): 111-129.

Beta-lactogobulin:

Konrad, Gerd; Lieske, Barbel; Faber, Wolfgang (2001) A large-scale isolation of native beta-lactoglobulin: Characterization of physicochemical properties and comparison with other methods. International Dairy Journal 10(10):713-721.

Konrad, Gerd; Gorzki, Dieter; Lieske, Baerbel. (2001) Process for the production of beta-lactoglobulin. Pat. Appl. DE 19953979 A1 20010531.

Lactoferrin:

Ulber, R.; Plate, K.; Weiss, T.; Demmer, W.; Buchholz, H.; Scheper, T (2001) Downstream processing of bovine lactoferrin from sweet whey. Acta Biotechnologica 21(1):27-34.

Immunoglobulins:

Su, Chia-Kai; Chiang, Been Huang (2003) Extraction of immunoglobulin-G from colostral whey by reverse micelles. Journal of Dairy Science 86(5):1639-1645.

Protein Fractionation:

Brody, Ernest P. Method of processing a proteinaceous material to recover k-casein macropeptide and polymers of a-lactalbumin and b-lactoglobulin. U.S. Pat. Appl. US 2003166866 A1.

Cheang, Beelin; Zydney, Andrew L. (2003) Separation of alpha-lactalbumin and Beta-lactoglobulin using membrane ultrafiltration. Biotechnology and Bioengineering 83(2): 201-209.

Choi, Du Young; Row, Kyung Ho. (2002) Separation of proteins in whey by strong anion-exchange membrane of Q sepharose. Hwahak Konghak 40(4):461-466.

Doultani, S.; Turhan, K. N.; Etzel, M. R. (2003) Whey protein isolate and glyco-macropeptide recovery from whey using ion exchange chromatography. Journal of Food Science 68(4):1389-1395.

Gurgel, Patrick V.; Carbonell, Ruben G.; Swaisgood, Harold E. (2001) Fractionation of whey proteins with a hexapeptide ligand affinity resin. Bioseparation 9(6):385-392.

Hobman, Peter Graeme; Boswell, Robert Philip; Hutchinson, Joanne Campbell; Klarwill, Georgina Aureen. (2001) Method of obtaining protein isolates and concentrates from colostrum. Pat. Appl. WO 0103515 A1.

Kersten, Martin (2001) Protein fractionation using the membrane filtration method. Verfahrenstechnik (2001):709.

Kim, Jung Il; Choi, Du Young; Row, Kyung Ho (2003) Separation of whey proteins by anion-exchange membranes. Korean Journal of Chemical Engineering 20(3):538-541.

Kulozik, Ulrich; Kersten, Martin. (2001) Fractionation of proteins by microfiltration. Chemie Ingenieur Technik 73(12):1622-1625.

Lan, Qingdao; Bassi, Amarjeet; Zhu, Jing-Xu; Margaritis, Argyrios. (2002) Continuous protein recovery from whey using liquid-solid circulating fluidized bed ion-exchange extraction. Biotechnology and Bioengineering 78(2):157-163.

Lihme, Allan Otto Fog; Hansen, Marie Bendix; Andersen, Inga Vaarst; Olander, Morten Aae (2002) Fractionation of protein containing mixtures. Par. Appl. WO 0296215 A1.

Riccio, Paolo; Balestrazzi, Emilio Paolo; Mastronardi, Enzo; Rossano, Rocco; Vigna, Luciano; Cipriani, Francesco (2001) Single-stage separation of lactose from proteins and recovery of purified proteins from a charge from processing of milk or cheese whey. Pat. Appl. IT 99BA0028 A1.

Peptides:

Glyco macropeptide:

Etzel, Mark R. (2001) Production of substantially pure kappa casein macropeptide. Pat. Appl. Cont.-in-part of U.S. 5,968,586. US 6168823 B1 20010102.

Nakano, T.; Ozimek, L (2002) Isolation of glycomacropeptide from sweet whey by gel chromatography on Sephacryl S-200 at pH 7.0 and 3.5. Milchwissenschaft (2002), 57(3):128-130.

Silva-Hernandez, Eryck R.; Nakano, Takuo; Ozimek, Lech. (2002) Isolation and Analysis of k-Casein Glycomacropeptide from Goat Sweet Whey. Journal of Agricultural and Food Chemistry 50(7):2034-2038.

Nakano, Takuo; Silva-Hernandez, Eryck R.; Ikawa, Noriaki; Ozimek, Lech. (2002) Purification of k-Casein Glycomacropeptide from Sweet Whey with Undetectable Level of Phenylalanine. Biotechnology Progress 18(2):409-412.

Others:

Groleau, Paule Emilie; Jimenez-Flores, Rafael; Gauthier, Sylvie F.; Pouliot, Yves (2002) Fractionation of b-lactoglobulin tryptic peptides by ampholyte-free isoelectric focusing. Journal of Agricultural and Food Chemistry 50(3):578-583.

Schaefer, Christian; Waesche, Andreas (2003) Bioactive whey protein hydrolyzates and peptide fractions obtained by hydrolysis with proteases. Pat. Appl WO 0359083 A1.