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ever-diminishing

    SUMMARY OF MEDICAL PUBLICATIONS ON

    IMMUNOCAL/HMS 90

    MEDICAL HYPOTHESES (1999) 53(4): 347-349 - 1999 HARCOURT PUBLISHERS LTD. - ARTICLE NO. MEHY. 1998.0780

    1- COMPETITION FOR GLUTATHIONE PRECURSORS BETWEEN THE IMMUNE

    SYSTEM AND THE SKELETAL MUSCLE: PATHOGENESIS OF CHRONIC

    FATIGUE SYNDROME

     12G. Bounous, J Molson 1Former Professor, Department of Surgery, McGill University, and career Investigation of the Medical Research Council of Canada 21994 Quebec Cycling Champion. Road and Time Trial

    SUMMARY - The chronic fatigue syndrome (CFS) is Because GSH is also essential to aerobic muscular typically associated or follows a recognized or contraction, an undesirable competition for GSH presumed infection. Abnormalities of both precursors between the immune and muscular humoral and cellular immunity have been systems may develop. It is conceivable that the demonstrated in a substantial proportion of patients priority of the immune system for the survival of with CFS. The most consistent findings are of the host has drawn to this vital area the ever-impaired lymphocyte responses to mitogen. As an diminishing GSH precursors, thus depriving the antioxidant, glutathione (GSH) is essential for skeletal muscle of adequate GSH precursors to allowing the lymphocyte to express its full potential sustain a normal aerobic metabolism resulting in without being hampered by oxiradical fatigue and eventually myalgia. ? 1999 Harcourt accumulation. Hence, protracted challenge of the Publishers Ltd.

    immunocytes may lead to cellular GSH depletion.

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Anticancer RESEARCH 15: 2643-2650, 1995

    2- THE USE OF A WHEY PROTEIN CONCENTRATE IN THE TREATMENT OF

    PATIENTS WITH METASTATIC CARCINOMA: A PHASE I-II CLINICAL STUDY

     1123RENEE S. KENNEDY, GEORGE P. KONOK, GUSTAVO BOUNOUS, SYLVAIN BARUCHEL 4and TIMOTHY D.G. LEE

     1Department of Surgery, Dalhousie University, Halifax, Nova Scotia: 2Department of Surgery, McGill University, Montreal Quebec 3Department of Pediatrics and Oncology, McGill University, Montreal, Quebec: 4Department of Immunology and Microbiology, Dalhousie University, Halifax, Nova Scotia, Canada

    ABSTRACT. Glutathione (GSH) concentration is months. In six patients the blood lymphocyte GSH high in most tumor cells and this may be an levels were substantially above normal at the outset, important factor in resistance to chemotherapy. reflecting high tumor GSH levels. Two patients Previous in-vitro and animal experiments have (#1, #3) exhibited signs of tumor regression, shown a differential response of tumor versus normalization of haemoglobin and peripheral normal cells to various cysteine delivery systems. lymphocyte counts and a sustained drop of More specifically, an in-vitro assay showed that at lymphocyte GSH levels towards normal. Two concentrations that induce GSH synthesis in normal patients (#2, #7) showed stabilization of the tumor, human cells, a specially prepared whey protein increased haemoglobin levels. In three patients (#4, concentrate, Immunocal?, caused GSH depletion #5, #6) the disease progressed with a trend toward and inhibition of proliferation in human breast higher lymphocyte GSH levels. These results cancer cells. On the basis of this information five indicate that whey protein concentrate might patients with metastatic carcinoma of the breast, deplete tumor cells of GSH and render than more one of the pancreas and one of the liver were fed 30 vulnerable to chemotherapy.

    grams of this whey protein concentrate daily for six

Clin Invest Med, 16: 204-209, 1993

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    3- WHEY PROTEINS AS A FOOD SUPPLEMENT IN HIV-SEROPOSITIVE

    INDIVIDUALS

    G. Bounous, S. Baruchel, J. Falutz, P. Gold

Departments of Surgery and Medicine, The Montreal General Hospital and McGill University, Montreal, Quebec

    ABSTRACT On the basis of numerous animal replenishment per se was not likely the cause of experiments, a pilot study was undertaken to increased body weight. The glutathione content of evaluate the effect of undenatured, biologically the blood mononuclear cells was, as expected, active, dietary whey protein in 3 HIV-seropositive below normal values in all patients at the beginning individuals over a period of 3 months. Whey of the study. Over the 3-month period, GSH levels protein concentrate was prepared so that the most increased and in one case rose by 70% to reach thermosensitive proteins, such as serum albumin normal value. The increase in body weight which contains 6 glutamylcysteine groups, would observed in these patients did not correlate with be in undenatured form. Whey protein powder increase in energy or protein intake. dissolved in a drink of the patient’s choice was

    drunk cold in quantities that were increased In conclusion, these preliminary data indicate that, progressively from 8.4 to 39.2 g per day. Patients in patients who maintain an adequate total caloric took whey proteins without adverse side effects. In intake, the addition of “bioactive” whey protein the 3 patients whose body weight had been stable in concentrate as a significant portion of total protein the preceding 2 months, weight gain increased intake increases body weight and shows elevation progressively between 2 and 7 kg, with 2 of the of glutathione (GSH) content of mononuclear cells patients reaching ideal body weight. Serum toward normal levels. This pilot study will serve as proteins, including albumin, remained unchanged a basis for a much larger clinical trial. and within normal range, indicating that protein

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CLIN INVEST MED, 14: 296-309, 1991

4- THE BIOLOGICAL ACTIVITY OF UNDENATURED DIETARY WHEY PROTEINS:

    ROLE OF GLUTATHIONE.

    G. Bounous, P. Gold

    Department of Surgery, Montreal General Hospital, Research Institute, Quebec

    ABSTRACT This study compared the effects of greater relative concentration of the thermolabile different sources of whey protein concentrate (20 cystine rich proteins. In addition, the mice fed this g/100 g diet) and of casein on the spleen, liver, and type of whey protein concentrate exhibit higher heart glutathione content of C3H/HeJ mice, and on levels of tissue glutathione. The presence in the the immune response of their spleen cells to sheep serum albumin fraction of glutamylcysteine groups red blood cells. Body weight curves were similar (rare in food protein) and the specific in all dietary groups. Our data indicate that the intramolecular bond as related to the undenatured humoral immune response is highest in mice fed a conformation of the molecule are considered to be dietary whey protein concentrate exhibiting the key factors in the glutathione-promoting activity of highest solubility (undenatured conformation) and a the protein mixture.

CANCER LETTERS, 57: 91-94, 1991

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    5- WHEY PROTEINS IN CANCER PREVENTION

    G. Bounous*, G. Batist** and P. Gold***

*Professor of Surgery, McGill University, and Career Investigator of the Medical Research Council of Canada,

    **Director, Experimental Therapeutics, Department of Oncology, McGill University, ***Chairman, Department of

    Medicine, McGill University, and Physician-in-Chief, The Montreal General Hospital.

    ABSTRACT Epidemiological and experimental diets result in increased glutathione (GSH) studies suggest that dietary milk products may exert concentration in a number of tissues, and that some an inhibitory effect on the development of several of the beneficial effects of whey protein intake are types of tumors. Some recent experiments in abrogated by inhibition of GSH synthesis. Whey rodents indicate that the antitumor activity of the protein is particularly rich in substrates for GSH dairy products is in the protein fraction and more synthesis. We suggest that whey protein may be specifically in the whey protein component of milk. exerting its effect on carcinogenesis by enhancing We and others have demonstrated that whey protein GSH concentration.

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TUMOR BIOL 11: 129-136, 1990

    6- DIETARY MILK PROTEINS INHIBIT THE DEVELOPMENT OF

    DIMETHYLHYDRAZINE-INDUCED MALIGNANCY

     aaabR. Papenburg, G. Bounous, D. Fleiszer, P. Gold

     abDepartments of Surgery and Medicine, The Montreal General Hospital and McGill University,

    Montreal, Quebec, Canada

    ABSTRACT This study investigated the continuously fed the whey protein diet were found influence of two formula diets containing 20 g/100 to be alive, whereas 33% of those on the casein or g diet of either whey protein concentrate or casein, Purina diet had died. Animals fed Purina diet for or Purina mouse chow on 1,2dimethylhydrazine 20 weeks and then switched to either milk protein (DMH)-induced colon carcinoma in A/J mice. diet for a further 8 weeks exhibited a decrease in thFour weeks after the 24 DMH treatment the tumour burden as compared to those animals fed incidence of tumour and tumour area in the whey the Purina diet continuously. Body weights were protein-fed mice was substantially less in similar in all dietary groups. In conclusion, a whey comparison to either the casein or Purina groups. protein diet appears to significantly influence the The Purina group exhibited the greatest tumour development of chemically induced colon tumours burden. At the end of the experiment all animals and the short-term survival of mice.

CLIN INVEST MED, 12: 343-349, 1989

    7- THE INFLUENCE OF DIETARY WHEY PROTEIN ON TISSUE

    GLUTATHIONE AND THE DISEASES OF AGING

     1,21,31,331,3 Gustavo Bounous, Francine Gervais, Victor Amer, Gerald Batist, and Phil Gold

     123 The Montreal General Hospital Research Institute and McGill University, Departments of Surgery, and Medicine

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    ABSTRACT This study compared the effects of a chow over the 6.3 month observation period whey-rich diet (20 g / 100 g diet), with that of extending from the age of 21 months Purina mouse chow or casein-rich diet (20 g / 100 g (corresponding to a human age of 55 years) to 26-diet), on the liver and heart glutathione content and 27 months of age (corresponding to a human age of on the survival of old male C57BL / 6 NIA mice. 80 years), during which time 55% mortality was The study was performed during a limited observed. The corresponding mean survival time observation period of 6.3 months. In mice fed the of mice fed the defined casein diet is almost whey protein-rich diet between 17 months and 20 identical to that of Purina-fed controls. Body months of age, the heart tissue and liver tissue weight curves were similar in all three dietary glutathione content were enhanced above the groups. Hence, a whey protein diet appears to corresponding values of the casein diet-fed and enhance the liver and heart glutathione Purina-fed mice. Mice fed the whey protein diet at concentration in aging mice and to increase the onset of senescence, exhibited increased longevity over a 6.3 month observation period. longevity as compared to mice fed Purina mouse

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CLIN INVEST MED, 12: 154-61, 1989

8- IMMUNOENHANCING PROPERTY OF DIETARY WHEY PROTEIN IN MICE:

    ROLE OF GLUTATHIONE

    G. Bounous, G. Batist, P. Gold

    Montreal General Hospital, Quebec

    ABSTRACT The spleen cells immune response more sustained production of splenic glutathione to sheep red blood cells of C3H/HeJ mice fed a 20 during the antigen driven clonal expansion of the g whey protein/100 g diet is substantially higher lymphocyte in whey protein fed mice in than that of mice fed an equivalent casein diet of comparison to mice fed the equivalent casein or the similar nutritional efficiency. The present study cysteine-enriched casein diet. Hence the efficiency indicates that the observed immunoenhancing of dietary cysteine in inducing supernormal effect of the whey protein mixture is dependent on glutathione levels is greater when it is delivered in the overall amino acid pattern resulting from the the whey protein than as free cysteine. contribution of all its protein components. Whey Administration of S-(n-butyl) homocysteine protein contains substantially more cysteine than sulfoximine, which reduces splenic glutathione casein. Dietary cysteine is considered to be a rate level by half, produces a 4-5 fold drop in the limiting substrate for the synthesis of glutathione humoral immune response of whey protein diet-fed which is necessary for lymphocyte proliferation. mice. This is further evidence of the important role Our studies show that enhancement of host humoral of glutathione in the immunoenhancing effect of immune response is associated with greater and dietary whey protein.

CLINICAL AND INVESTIGATIVE MEDICINE, VOL. 11,.NO. 4,.PP 271-278,. 1988.

    9- THE IMMUNOENHANCING PROPERTY OF DIETARY WHEY

    PROTEIN CONCENTRATE

     1,21,3 1,4 Gustavo Bounous, Patricia A.L. Kongshavnand Phil Gold123The Montreal General Hospital Research Institute, [)epartments of Surgery, Physiology, and 4Medicine, McGill University, Montreal, Quebec (ORIGINAL MANUSCRIPT SUBMITTED OCTOBER 22, 1987: ACCEPTED IN REVISED FORM JANUARY 25, 1988)

    ABSTRACT - The plaque-forming cell response to formula diets of similar nutritional efficiency sheep red blood cells was found to be enhanced in containing 20 g / 100 g diet of either casein, soy, mice fed a formula diet containing 20 g lactalbumin wheat or corn protein, egg albumin, beef or fish /100 g diet in comparison to mice fed equivalent protein, Spirulina maxima, or Scenedesmus protein,

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or Purina mouse chow. This effect was manifest response in comparison to that of mice fed diets after 2 weeks and persisted for at least 8 weeks of containing 20% soy protein or casein. dietary treatment. Mixing lactalbumin with either

    casein or soy protein in a 20 g protein / 100 g diet key words: dietary whey protein, humoral immune formula significantly enhanced the immune response.

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CLIN INV MED, 11: 213-217, 1988

    10- DIETARY WHEY PROTEIN INHIBITS THE DEVELOPMENT OF

    DIMETHYLHYDRAZINE-INDUCED MALIGNANCY

    G. Bounous*, R. Papenburg*, P.A.L Kongshavn**, P. Gold†, and D. Fleiszer*

    Departments of Surgery*, Physiology**, and Medicine†, Montreal General Hospital and McGill University

    ABSTRACT This study investigates the influence treatment the incidence of tumors in the whey of two formula diets containing 20 g/100 g diet of protein-fed mice was substantially lower than that either whey protein concentrate or casein or Purina in mice fed either the casein or Purina diet. mouse chow, on the humoral immune Similarly, the tumor area was less in the whey responsiveness and dimethylhydrazine induced protein group in comparison to either the casein or colon carcinogenesis in A/J mice. After 20 weeks Purina groups, with some difference between of dimethylhydrazine treatment, the number of casein and Purina groups. Body weight curves plaque forming cells per spleen, following were similar in all dietary groups. 6intravenous inoculation with 5 x 10 sheep red

    blood cells, was nearly three times greater in the In conclusion, a whey protein diet appears to whey protein-fed group than in the casein-fed mice significantly inhibit the incidence and growth of although both values were substantially below chemically induced colon tumors in mice. normal. After 24 weeks of dimethylhydrazine

J. NUTR. 115: 1409-1417, 1985

11- MECHANISM OF ALTERED B-CELL RESPONSE INDUCED BY CHANGES

    IN DIETARY PROTEIN TYPE IN MICE

    G. Bounous, N. Shenouda,* P.A.L. Kongshavn† and D.G. Osmond*

Department of Surgery, Centre Hospitalier Universitaire, Sherbrooke, Quebec, Canada, J1H 5N4; *Department of

    Anatomy, McGill University, Montreal, Quebec, Canada, H3A 2B2; and †Department of Physiology, McGill

    University, Montreal, Quebec, Canada, H3A 2B2

    ABSTRACT The effect of 20 g/100 g dietary or non purified diet. A similar pattern of dietary lactalbumin (L) or casein (C) diets or a nonpurified protein effect in (CBA/N x DBA/2J) F mice 1carrying the xid defect was observed following (NP) diet on the immune responsiveness of

    C57B1/6J, C3H/HeJ and BALB/cJ mice has been challenge with sheep red blood cells (SRBC). An investigated by measuring the response to the T even greater enhancing effect of dietary L was cell-independent antigen, TNP-Ficoll. To noted in normal (DBA/2J x CBA/N) F mice after 1investigate the possible influence of dietary protein immunization with SRBC, but in contrast, the type on the supply of B lymphocytes, bone marrow normal large-scale production of B lymphocytes in lymphocyte production has been examined by a mouse bone marrow was independent of the type of radioautographic assay of small lymphocyte dietary protein. Dietary protein type did not affect renewal and an immuno-fluorescent stathmokinetic blood level of minerals and trace metals. The free assay of pre-B cells and their proliferation. The plasma amino acid profile essentially conformed to humoral response of all mice fed the L diet was the amino acid composition of the ingested protein, found to be higher than that of mice fed the C diet suggesting that the changes in plasma amino acid C:\CONVERT\TEMP\68291549.DOC 5

    profile might be a crucial factor in diet-dependent functional responsiveness of the B lymphocytes enhancement or depression of the B-cell response. themselves or in the processes leading to their The findings indicate that the observed effects of activation and differentiation in the peripheral altered dietary protein type on humoral immune lymphoid tissues.

    responsiveness are not exerted centrally on the rate

    of primary B-lymphocyte production in the bone INDEXING KEY WORDS: DIET PROTEIN IMMUNITY

    marrow, but may reflect changes either in the B-CELL RESPONSE - MICE

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J. NUTR. 115: 1403-1408, 1985.

12- DIFFERENTIAL EFFECT OF DIETARY PROTEIN TYPE ON THE B-CELL AND

    T-CELL IMMUNE RESPONSES IN MICE

    Gustavo Bounous and Patricia A.L. Kongshavn*

Centre Hospitalier Universitaire, Sherbrooke, Québec, Canada, J1H 5N4 and *Montreal General Hospital Research

    Institute and Department of Physiology, McGill University, Montreal, Quebec, Canada, H3G 1Y6

    ABSTRACT The effect of 20 g/100 g diet of differ among mice fed the various diets. Similarly, lactalbumin (L), casein (C), soy (S) and wheat (W) the type of diet did not appear to influence host protein on the immune responsiveness of C3H/HeN resistance to Salmonella typhymurium. It is

    mice has been investigated by measuring the postulated that the type of protein in the diet humoral immune response to the T cell-influences directly the intrinsic capacity of the B independent antigen, TNP-Ficoll. The humoral lymphocytes to respond to an immunogenic immune response of mice fed the L diet was found stimulus.

    to be higher than that of mice fed the C, S and W

    diets. On the other hand, delayed-type Indexing Key Words: diet * protein * immunity * hypersensitivity, and splenic cell mitogen responses mice

    to phytohemagglutinin and concanavalin A did not

    J. NUTR. 113: 1415-1421, 1983

13- INFLUENCE OF DIETARY PROTEIN TYPE ON THE IMMUNE SYSTEM OF MICE

    G. Bounous, L. Létourneau and P.A.L. Kongshavn†

Centre hospitalier universitaire, Sherbrooke, Quebec, Canada; J1H 5N4 and †Montreal General Hospital Research

    Institute and Department of Physiology, McGill University, Montreal, Quebec, Canada, H3G 1Y6

    ABSTRACT The effect of graded amounts of substantially lower than that of mice fed stock diet, dietary lactalbumin (L), casein (C), soy (S), wheat whereas that of mice fed L diet was higher. The (W) protein and Purina rodent chow (stock diet) on above-described immune effect of all tested the immune responsiveness of C3H/HeN mice has proteins was obtained at 20 g/100 g concentration been investigated by measuring the specific with no further increments with 30- and 40 g/100 g humoral immune response to sheep red blood cells protein in the diet. Mitogen responsiveness to PHA (SRBC), and horse red blood cells (HRBC) as well and Con A in L diet-fed mice was only slightly as the nonspecific splenic cell responsiveness to higher than that of C diet-fed mice. Little phyto-hemagglutinin (PHA) and concanavalin A difference in immune responses was noted among (Con A) after stimulation with Myco-bacterium mice fed C, S or W protein diets. The principal bovis, strain BCG. The nutritional efficiency of factor responsible for the observed immune effect these diets was normal and similar. The immune does not appear to be the availability or response of mice fed the L diets, was found to be concentration of single essential amino acids but almost five times higher than that of mice fed the rather the composite effect of the specific amino corresponding C diets. The humoral immune acid distribution in the protein.

    response of mice fed C, S, and W diets was

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MINERVA DIETOL GASTROENTEROL 35(4): 241-5, 1989

14- CHANGES IN BILIARY SECRETORY IMMUNOGLOBULINS A IN MICE FED

    WHEY PROTEINS

    Costantino AM, Balzola F, Bounous G.

    A whey protein diet has been shown to enhance recorded and the gall-bladder was removed and its splenic immune response to sheep red blood cells whole content analyzed by ELISA to determine S-(SBRC) in mice. This study was designed to IgA secretion. Body weight curves were similar in investigate the influence of the type of dietary all dietary groups; higher biliary levels of S-IgA protein on the biliary secretory IgA. A/J mice were appeared in the whey protein fed mice than in the fed defined formula diets containing either 20% casein (p less than 0.025) or purine (p less than whey protein, or 20% casein. Another group was 0.025) fed mice. Dietary protein type may have a fed Purina mouse chow. After 3 weeks of dietary direct influence on the immune response in the treatment the body weight of each mouse was gastrointestinal tract, without affecting body weight.

OXIDATIVE STRESS, CELL ACTIVATION AND VIRAL INFECTION C. PASQUIER ET AL. (EDS) 1994 BIRKHÄUSER VERLAG

    BASEL/SWITZERLAND

15- PLACE FOR AN ANTIOXIDANT THERAPY IN HUMAN IMMUNODEFICIENCY

    VIRUS (HIV) INFECTION

     1,2 22S. BaruchelG. Bounous, P. Gold 1McGill University, Dept. of Pediatrics; McGill AIDS Centre. Montreal. Qc. H3H 1P3, Canada 2 McGill University, Dept of Medicine; McGill AIDS Centre. Montreal. Qc. H3G 1A4, Canada

    SUMMARY - Oxidative stress, a known activator agents promoting GSH synthesis, are discussed. of HIV replication in vitro, has a potential role as a The review also includes the early results of cofactor of HIV disease progression. Arguments nutritional interventions based on a diet enriched supporting the role of oxidative stress as a cofactor with IMMUNOCAL, a whey protein concentrate in HIV activation are summarized in this review. prepared in a proprietary manner.

    The role of intracellular antioxidants such as

    glutathione (GSH), and drugs and nutriceutical

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J. Nutr. 112:1747-1755, 1982. - Reprinted from THE JOURNAL OF NUTRITION

    Vol. 112, no. 9, September 1982 ? The American Institute of Nutrition 1982

    16- INFLUENCE OF DIETARY PROTEINS ON

    1 THE IMMUNE SYSTEM OF MICE

     2oG. Bounous and PAL Kongshavn†

     oCentre Hospitalier Universitaire, Sherbrooke, Quebec, Canada, J1H 5N4 and †Montreal General Hospital Research

    Institute and Department of Physiology, McGill University, Montreal, Quebec, Canada, H3G 1Y6

    ABSTRACT The effect of graded amounts of response to sheep red blood cells (SRBC) and the dietary laetalbumin (L) and casein (C) hydrolyzates nonspecific splenic cell responsiveness to on the immune responsiveness of C3H/HeN and phytohemagglutinin, concanavalin A and DBA/2 strain mice has been investigated by Escherichia coli lipopolysaccharide after

    measuring both the specific humoral immune stimulation with Mycobacteriurn bovis, strain BCG.

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    The nutritional efficiency of these diets was similar humoral immune response. The enhancement of at both 12 and 28% amino acid levels. The immune immune responsiveness observed in mice fed the responses of mice fed the L diets were found to be 28% L diet was moderately reduced by the addition significantly greater than those of mice fed the of phenylalanine to the diet, indicating that the corresponding C diets, especially at the 28% level. lower level of this amino acid in the L protein may Furthermore in the mice fed L diet, increasing the be of some significance. These dietary effects on concentration of amino acid in the diet from 12 to immune responsiveness were remarkably similar in 28% greatly enhanced immune responsiveness by both mouse strains tested.

     both parameters measured. In the C-fed mice, a INDEXING KEY WORDS: diet - protein comparable enhancement of mitogen immunity - mice responsiveness with increasing amino acid level of

    diet was seen, but there was no change in the

THE JOURNAL OF INFECTIOUS DISEASES, 144: 281, 1981

17- INFLUENCE OF DIETARY LACTALBUMIN HYDROLYSATE ON THE IMMUNE

    SYSTEM OF MICE AND RESISTANCE TO SALMONELLOSIS

    G. Bounous, M.M. Stevenson*, P.A.L. Kongshavn†

Centre hospitalier universitaire, Sherbrooke, Quebec, Canada; *Montreal General Hospital Research Institute and

    †McGill University, Montreal, Quebec, Canada

    ABSTRACT In the present study we investigated in the diet above the minimum requirement (12% the effect of four weeks of treatment with a diet LAH) and thus produce augmented humoral containing lactalbumin hydrolysate (LAH: Nestlé, immune responsiveness and resistance to Vevey, Switzerland) on the immune response of salmonellosis.

    C3H/HeN mice. Our data indicate that it was

    possible to increase the level of this type of protein Lactalbumin = Whey Protein Concentrate

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JOURNAL OF APPLIED PHYSIOLOGY, 87: 1381-1385, 1999

    18- THE EFFECT OF SUPPLEMENTATION WITH A CYSTEINE DONOR ON

    MUSCULAR PERFORMANCE

    LC Lands, MD, PhD*†, VL Grey, PhD†‡, AA Smountas, BSc*

*Division of Respiratory Medicine, † Department of Pediatrics, ‡Department of Biochemistry, McGill University

    Health Centre-Montreal Children’s Hospital, Montreal, Quebec, Canada

    ABSTRACT: Oxidative stress contributes to measuring Peak Power and 30-sec Work Capacity. muscular fatigue. Glutathione (GSH) is the major Lymphocyte GSH was used as a marker of tissue intracellular antioxidant, whose biosynthesis is GSH. There were no baseline differences (age, ht, dependent upon cysteine availability. We wt, % ideal wt, Peak Power, 30-sec Work Capacity). hypothesized that supplementation with a whey-Follow-up data on 18 subjects (9 Immunocal, 9 based cysteine donor (Immunocal (HMS90)) placebo) were analyzed. Both Peak Power designed to augment intracellular GSH, would (meanse: 133.5%, p;0.02) and 30-sec Work

    enhance performance. Twenty healthy young Capacity (133.7%, p;0.03) increased significantly adults (10 m) were studied pre- and 3 months post-in the Immunocal group, with no change (29.0 and supplementation with either Immunocal (20 gm/day) 19.3%) in the placebo group. Lymphocyte GSH or casein placebo. Muscular performance was also increased significantly in the Immunocal group assessed by whole leg isokinetic cycle testing,

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    defenses resulted in improved volitional (35.511.04%, p;0.02) with no change in the

    performance. placebo group (-0.99.6%). This is the first study to demonstrate that prolonged supplementation Key words: oxidative stress, exercise with a product designed to augment antioxidant

ACCEPTED FOR PUBLICATION IN “CHEST

    19- TREATMENT OF OBSTRUCTIVE AIRWAY DISEASE WITH A CYSTEINE

    DONOR PROTEIN SUPPLEMENT: A CASE REPORT

    Bryce Lothian, MD*, Vijaylaxmi Grey, PhD*†, R. John Kimoff, MD‡, Larry Lands, MD, PhD*?

*Department of Pediatrics, †Department of Biochemistry, ?Division of Respiratory Medicine, McGill University

    Health Centre-Montreal Children’s Hospital, Montreal, Quebec, Canada

    ‡Division of Respiratory Medicine, McGill University Health Centre-Royal Victoria Hospita, Montreal, Quebec,

    Canada

    ABSTRACT:Oxidant/antioxidant imbalance can glutathione levels. Following one month of occur in obstructive airways disease, as a result of supplementation with a whey-based oral ongoing inflammation. Glutathione plays a major supplement, designed to provide glutathione role in pulmonary antioxidant protection. As an precursors, whole blood glutathione levels and alternative or complement to anti-inflammatory pulmonary function significantly and dramatically therapy, augmenting antioxidant protection could increased. The potential for such supplementation diminish the effects of inflammation. We describe in pulmonary inflammatory conditions deserves a case of a patient with obstructive lung disease, further study.

    responsive to corticosteroids, with low whole blood

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PR514

    20- TREATMENT OF CHRONIC HEPATITIS USING

    WHEY PROTEIN (NON-HEATED)

    A. Watanabe, K. Higuchi, K. Okada, Y. Shimizu, Y. Kondo* and H. Kohri* 4

    Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan, and * Otsuka

    Pharmaceutical Factory, Inc., Nutrition Research Institute, Tokushima. Japan.

    In an open study, the clinical efficacy of whey week intervals for 18 weeks to evaluate the efficacy protein (Immunocal: cysteine content; 7.6-fold that of Immunocal. As a result, serum ALT activity of casein) isolated from fresh milk and purified decreased in 6 of 8 patients with chronic hepatitis B without being heated was evaluated based on liver 12 weeks after the start of supplement with function test, immunological parameters, plasma or Immunocal food. Plasma GSH concentrations were lymphocyte GSH concentrations and hepatitis virus increased in 5 of the 8 patients. Serum . markers in 25 patients with chronic hepatitis B or C. concentrations of lipid peroxides significantly Immunocal (12 g as protein) food (mousse) was decreased 8 weeks after Immunocal food. Serum given twice a day, in the morning and evening, for IL-2 levels began to increase 8 weeks and remained 12 weeks (test period). Casein (12 g as protein) high even after supplement with Immunocal -food food (mousse) was given for 2 weeks prior to the had ended. Furthermore, NK activity was start of -supplement with Immunocal food significantly increased. However, an item (induction period) and for 4 weeks after the end correlating with reduced serum ALT activity could (follow-up period). The effects of Immunocal food not be clarified. In 17 patients with chronic on various clinical parameters were examined at 4-hepatitis C, there wore no significant Immunocal-C:\CONVERT\TEMP\68291549.DOC 9

    related changes in liver function test or B, and a further clinical study that long-term immunological parameters. These findings suggest combination therapy with Immunocal and other that long-term supplement with Immunocal alone agents including interferon may be effective for may be effective for patients with chronic hepatitis those with chronic hepatitis C should be performed.

Anticancer Research 20: 4785-4792, 2000.

21- WHEY PROTEIN CONCENTRATE (WPC) AND GLUTATHIONE MODULATION

    IN CANCER TREATMENT

    Gustavo Bounous, M.D., F.R.C.S. (C)

    ABSTRACT - The glutathione (GSH) antioxidant proteins also exhibit anti-carcinogenesis and system is foremost among the cellular protective anticancer activity. They do this via their effect on mechanisms. Depletion of this small molecule is a increasing GSH concentration in relevant tissues, common consequence of increased formation of and may have anti-tumor effect on low volume of reactive oxygen species during increased cellular tumor via stimulation of immunity through the activities. This phenomenon can occur in the GSH pathway. It is considered that oxygen radical lymphocytes during the development of the generation is frequently a critical step in immune response and in the muscular cells during carcinogenesis, hence the effect of GSH on free strenuous exercise. It is not surprising that so much radicals as well as carcinogen detoxification, could research has been done, and is still being done on be important in inhibiting carcinogenesis induced this small tripeptide molecule. Whey protein by a number of different mechanisms. Case reports concentrate has been shown to represent an are presented which strongly suggest an anti-tumor effective and safe cysteine donor for GSH effect of a whey protein dietary supplement in some replenishment during GSH depletion in immune urogenital cancers. This non toxic dietary deficiency states. Cysteine is the crucial limiting intervention, which is not based on the principles of amino acid for intracellular GSH synthesis. Animal current cancer chemotherapy, will hopefully attract experiments showed that the concentrates of whey the attention of laboratory and clinical oncologists.

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ACCEPTED FOR PUBLICATION IN NUTRITION AND CANCER, VOL 38, ISSUE #2

    22- ENHANCING EFFECT OF PATENTED WHEY PROTEIN ISOLATE

    (IMMUNOCAL) ON THE CYTOTOXICITY OF ANTI-CANCER DRUG

    Wayne Y. Tsai, Wen-Huei Chang, Ching-Hsein Chen, and Fung-Jou Lu

    Department of Biochemistry, College of Medicine National Taiwan University, Taipei, Taiwan, R.O.C.

    ABSTRACT To determine the enhancing effect there was no significant difference on survival rate. of a whey protein isolate on the cytotoxicity of a In the investigation of apoptosis. compared to the potential anti-cancer drug. baicalein, human cells in baicalein medium, cells in combined hepatoma cell line HepG2 was assigned to grow in medium showed a higher phosphatidylserine different media for four days, followed by the exposure, lower rnitochondrial transmembrane investigation of cell growth and apoptosis. potential and nearly 13 times more cells were Excluding the control group with normal medium, detected undergoing apoptosis. We also other three treatment media included whey protein demonstrated that Immunocal was able to reduce

    isolate (marketed as Immunocal) medium, glutathione in HepG2 by 20% to 40% and regulated baicalein medium, and combined medium the elevation of glutathione, which was in response containing both Irnmunocal and baicalein. MTT to baicalein. In conclusion, Immunocal seemed to

    assay indicated that cells grew in combined enhance the cytotoxicity of baicalein by inducing medium had a significantly lower survival rate more apoptosis, this increase in apoptotic cells may compared to the cells grew in baicalein medium; in be in association with the depletion of GSH in

    HepG2. This is the first study to demonstrate, in contrast, for the cells grew in Immunocal group,

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