Research


Allergies and Autoimmunity

Immunomodulatory proteins in colostrum

Plusa T: Department of Internal Medicine, Pneumonology and Allergology, Central Clinical Hospital of the Ministry of National Defense, Military Institute of Health Services in Warsaw, Poland. [email protected]: 2009 Mar;26(153):234-8.

The value of bovine colostrums is documented in clinical observations and supported by large database. An antibacterial effect and modulation of the immune response are accepted. The wide spectrum of the activity of a lactoferrin or a proline-rich polipeptide complex was confirmed in experimental and clinical studies. Moreover, a high concentration of immunoglobulins in bovine colostrum gives exceptional opportunity for use as a support in immunodeficiency treatment.

PMID: 19388540 [PubMed - indexed for MEDLINE]

Identification and quantification of innate immune system mediators in human breast milk.

Allergy Asthma Proc. 2004 Sep-Oct;25(5):297-304.; Armogida SA, Yannaras NM, Melton AL, Srivastava MD; Department of Allergy and Immunology, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195, USA.

Breast-feeding decreases the risk of breast cancer in mothers and infection, allergy, and autoimmunity in infants. The presence of mediators of the innate immune system in human milk, including soluble defensins, cathelicidins, and toll-like receptors (TLRs), has not been researched thoroughly. The whey fractions of colostrum and transitional and mature milk (n = 40) from normal mothers (n = 18) and from mothers with autoimmune or allergic diseases (n = 22) were analyzed for defensins by competitive enzyme-linked immunosorbent assay, and expression of messenger RNA (mRNA) for defensins, TLRs, and cathelicidin-derived antimicrobial peptide (LL-37) by cells in breast milk was determined by semiquantitative reverse-transcription-polymerase chain reaction. In whey, human neutrophil-derived a-defensin 1 (HNP-1) and human beta-defensin 2 (HBD-2) were present in the highest concentrations (median, 33.0 and 31.3 microg/mL, respectively), human alpha-defensin 6 (HD-6) was present in moderate amounts (3.1 microg/mL), and HD-5 and HBD-1 were present in the lowest concentrations (2.4 and 1.7 microg/mL, respectively). There was great variability of defensin levels between subjects, but there was no relation to autoimmune or allergic diagnosis. HNP-1, HD-5, and HD-6 were present in significantly higher levels in colostrum than in mature milk. Regarding defensin mRNA expression in the breast milk cells, 95% of the samples (n = 41) were positive for HBD-1, 68% were positive for HD-5, 22% were positive for HBD-3, 15% were positive for HBD-2, 5% were positive for HBD-4, and 2% were positive for HD-6; 88% (14/16) were positive for HNP-1. Breast milk cells also expressed mRNA for TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR9, CD14, and LL-37. Human breast milk contains high concentrations of multiple defensin proteins and cells in breast milk express mRNA for these defensins, multiple TLRs, and LL-37. The innate immune system in breast milk is complex and likely provides protection for maternal breast tissue and the developing digestive tract of newborns.

Colostrum and bioactive, colostral peptides differentially modulate the innate immune response of intestinal epithelial cells.

J Pept Sci. 2010 Jan;16(1):21-30.Department of Food Science, Aarhus University, Blichers Allé 20, DK-8830 Tjele, Denmark; Jørgensen AL, Juul-Madsen HR, Stagsted J.

Characterization and identification of peptides with bioactivity from food have received considerable interest recently since such bioactive components must be adequately documented if they are part of functional food claims. We have characterized peptides from colostrum or those generated by a simulated gastrointestinal digest (GI) and tested them for bioactivity using murine intestinal (mIC(c12)) cells and compared with bioactivity of intact colostrum. The peptides were recovered in the permeate after dialysis. The presence of peptides in the permeate was confirmed by C(18) RP-HPLC, determination of free amino termini and MALDI MS. The bioactivity of the intact colostrum and colostral peptides in the permeate was tested using mIC(c12) cells stimulated in the absence or presence of different bacterial ligands that mediate cellular activation through stimulation of Toll-like receptors (TLR). Whereas intact colostrum generally reduced TLR-mediated signaling, the isolated peptides seemed to either stimulate or reduce the immune response depending on the bacterial ligand used for stimulation. Interestingly, the most potent bioactive peptides originated from nondigested colostrum, which had only been subject to endogenous protease activity. Identified peptides in the nondigested colostrum originated exclusively from the casein fraction of colostrum as shown by MALDI MS/MS identification. Thus, multiple components with different bioactivities towards the innate immune response appear in bovine colostrum.

Potential immunoregulatory role of heme oxygenase-1 in human milk: a combined biochemical and molecular modeling approach.

Department of Biological Chemistry, Medical Chemistry and Molecular Biology, University of Catania, 95125 Catania, Italy; Li Volti G, Galvano F, Frigiola A, Guccione S,Di Giacomo C, Forte S, Tringali G, Caruso M, Adekoya OA, Gazzolo D.

Human milk contains biological factors that are involved in a newborn’s growth and immune system regulation. By integrating standard biochemical experimental protocols with computational methods, the present study investigates the presence of heme oxygenase-1 (HO-1), a cytoprotective enzyme, in human milk at different levels of maturation and in milk formulae. Furthermore, we evaluated cytokine and glutathione S-transferase (GSH) levels. Samples were collected from colostrum (on Day 1 after birth), from transition milk (on Postdelivery Days 7 and 14) and from mature milk (on Day 30 after delivery) in 14 healthy women. HO-1 protein, GSH and cytokines levels were measured using enzyme-linked immunosorbent assay and flow cytometry. HO-1 protein levels were significantly higher in colostrum (1.33 ng/ml; 5th centile 0.92; 95th centile 2.38) and in transition milk at 14 days (0.97 ng/ml; 5th centile 0.87; 95th centile 1.45) than in mature milk (0.9 ng/ml; 5th centile 0.8; 95th centile 1.38). Levels of HO-1 in milk formulae were similar to those in colostrum. No significant differences in GSH content were observed in mature milk, transition milk and colostrum, whereas significantly higher GSH levels were observed in milk formulae. No significant levels of cytokines, with the exception of interleukin-8, were found. Computational studies on the possible interactions between HO-1 and CD91 were carried out by a battery of softwares, namely, GRAMM (version 1.03), DALI, CLUSTALW (version 2.0), PatchDock and FireDock, mutually counterchecking and validating each other. The computational results, the strong convergence (to the same “solution”) of which finally leads to an “experimental-like” character, showed that HO-1 may bind to CD91, thus suggesting its major role as a new chaperokine in immune response regulation. These findings, which connect and integrate biochemical data and computational data interpretation, represent a synergistic and powerful means of conducting biological research.

PMID: 19879747 [PubMed - as supplied by publisher]

Cytokines in human milk.

Res Commun Mol Pathol Pharmacol. 1996 Sep;93(3):259-62. Srivastava MD,Srivastava A, Brouhard B, Saneto R, Groh-Wargo S, Kubit J;
Department of Pediatrics, Cleveland Clinic Foundation, OH 44195, USA.

Breast feeding improves the health of children. The greatest significance is to host defense, prevention of autoimmunity, and development of the digestive system; however, the underlying mechanisms for these effects are not well understood. Based on recent evidence that cytokines might be important in these processes, we have used ELISA to quantitate the cytokines in human colostrum, transitional, and mature milk from mothers delivering preterm or at term. We also used reverse transcription PCR to test breast milk cells for the production of cytokine mRNA. No significant (< 10 pg/ml) GM-CSF, SCF, LIF, MIP-1 alpha, IL-2, IL-4, IL-11, IL-12, IL-13, IL-15, sIL-2R, or IFN-gamma was detected. And, in contrast to earlier studies using bioassays or RIA, no significant IL-1 beta, TNF-alpha, or IL-6 was present; nor was IL-10, which had been tested using less specific antibodies. We did confirm the presence of high levels of M-CSF, which remained high throughout lactation. Human milk contained latent, but not free, TGF-beta 1, and especially TGF-beta 2, both of which may be activated by gastric acid pH. High levels of IL-1RA were detected, and like activated TGF-beta, may protect against autoimmunity. Chemokines, particularly GRO-alpha and MCP-1, but also RANTES and IL-8, were present and could protect against infection. Maternal cells in breast milk expressed mRNA for MCP-1 (20/20), IL-8 (14/20), TGF-beta 1 (14/16), TGF-beta 2 (4/6), M-CSF (9/12), IL-6 (6/12) and IL-1 beta (7/12), and may be a source of these cytokines. mRNA for IL-2, IL-10, IFN-gamma, TNF-alpha was not detected and only weak expression was found for RANTES (1/18). There was considerable variability between individual women, and women delivering preterm had lower levels of several cytokines in colostrum than women delivering at term. Yet, cytokine levels remained high months to years into lactation, providing immunological benefit to the breastfed infant/child.

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Alzheimer’s

Colostral Proline-Rich Polypeptides - Immunoregulatory Properties and Prospects of Therapeutic Use in Alzheimer’s Disease.

Curr Alzheimer Res. 2009 Nov 26; Janusz M, Zablocka A.; Department of Immunochemistry, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 R.Weigla, 53-114 Wroclaw, Poland. [email protected].

A proline-rich polypeptide complex (PRP), subsequently called Colostrinin (CLN), was first isolated from ovine colostrum, was shown to possess immunoregulatory properties, including effects on the maturation and differentiation of murine thymocytes and humoral and cellular immune responses, both in vivo and in vitro. PRP seems to restore balance in cellular immune functions and is not species specific. PRP is a complex of peptides of molecular masses ranging from 500 to 3000 Da. The polypeptide contains 25% proline and 40% hydrophobic amino acids. PRP shows a regulatory activity in cytokine (IFN, TNF-alpha, IL-6, IL-10) induction and possesses the ability to inhibit the overproduction of oxygen reactive species and nitric oxide. Besides its immunoregulatory activity, PRP also showed psychotropic properties, improving cognitive activity and behavior of old rats, humans, and chickens. The properties of PRP prompted the authors to propose the complex for the treatment neurodegenerative disorders. Beneficial effects of PRP/Colostrinin were shown for the first time in double-blind placebo-controlled trials and long-term open-label studies. The results were confirmed in multicenter clinical trials. A very important property of PRP/Colostrinin is the prevention of Abeta aggregation and the disruption of already existing aggregates. The same properties were expressed by one of PRP’s components, a nonapeptide (NP). Moreover, PRP modulates neurite outgrowth, suppresses uncontrolled activation of cells, reduces 4-HNE-mediated cellular damage, and modulates expression in cellular redox regulation, cell proliferation, and differentiation. Its biological response modifying activity can play an important role in its use in the treatment of Alzheimer’s disease.

>PMID: 19939229 [PubMed - as supplied by publisher]

The protective effects of the nutraceutical, colostrinin, against Alzheimer’s disease, is mediated via prevention of apoptosis in human neurones induced by aggregated beta-amyloid.

J Nutr Health Aging. 2009 Jun;13(6):522-7.Douraghi-Zadeh D, Matharu B, Razvi A, Austen B.; Neurodegeneration Unit, Basic Medical Sciences, St. George’s, University of London, Cranmer Terrace, Tooting, London, UK.

OBJECTIVE: It has previously been demonstrated that oral administration of ovine Colostrinin (CLN), a proline-rich polypeptide isolated from ovine colostrum, can effectively treat Alzheimer’s disease patients. This study aims to determine whether CLN has effects on the aggregation and toxicity of synthetic beta-amyloid (Abeta), implicated as a causative agent of AD. DESIGN AND MEASUREMENTS: Using cell assays, we examined if pre-treatment of neuronal cells with CLN confers protection. RESULTS: The data from cytotoxicity assays (using MTT and LDH) demonstrated that pre-treatment of human neuronal SHSY-5Y cells with 5 microg/ml CLN, for 24 hours, confers neuroprotection against Abeta-induced neurotoxicity. Twenty-four hour pre-treatment with 5 microg/ml CLN was also shown to reduce Abeta 1-40-induced apoptosis in human neuronal cells as determined via qualitative and quantitative apoptosis assays. CONCLUSION: The neuroprotection conferred with CLN pre-treatment was reduced with the Fas ligand (FasL) binding antibody Nok1, suggesting that the effects of CLN may involve a Fas:soluble FasL interaction. These findings indicate that CLN could possibly play a role in the prevention of AD pathogenesis, though the inhibition of Fas-mediated apoptosis.

PMID: 19536420 [PubMed - indexed for MEDLINE]

A proline-rich polypeptide complex (PRP) isolated from ovine colostrum. Modulation of H2O2 and cytokine induction in human leukocytes

Department of Immunochemistry, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 R. Weigla, 53-114 Wroclaw, Poland; Agnieszka Zablocka, Maria Janusz, , Józefa Macalaa and Józef Lisowskia

Abstract: A proline-rich polypeptide complex (PRP) has immunoregulatory properties and also shows beneficial effects in Alzheimer’s disease (AD). It is known that the unregulated activation of microglial cells in AD may result in chronic inflammatory response. There is a link between the activation of immune cells on the periphery and in the central nervous system (CNS). Therefore, we studied the effect of the PRP on human peripheral blood mononuclear cells (PBMCs) stimulated by LPS with PHA (LP) or PMA as proinflammatory activators. PRP and its nonapeptide fragment (NP) inhibited by 40–60% production of H2O2 induced by PMA. The peptides also inhibited activity of superoxide dismutase. Both peptide preparations showed differential effects on the secretion of cytokines. NP induced TNF-α only while PRP induced IL-6, IL-10 and TNF-α. On the other hand, the release of TNF-α and IL-10 induced by LP in PBMCs was inhibited by PRP while NP inhibited the release of IFN-γ and IL-10. The results obtained showed that PRP may affect not only adaptive immunity but also innate immunity and thus may regulate secretions of mediators of inflammation. The regulatory effect of the PRP on the innate immunity may shed some light on understanding the beneficial effects of this polypeptide complex in AD patients.

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Antioxidant

Antioxidant and radical scavenging activity of human colostrum, transitional and mature milk.

J Clin Biochem Nutr. 2009 Sep;45(2):150-4. Epub 2009 Aug 28.Zarban A, Taheri F, Chahkandi T,Sharifzadeh G, Khorashadizadeh M.; Biochemistry department, Faculty of Medicine, Birjand University of Medical Sciences, Birjand 9717853577, Iran.

Human milk from healthy women contains numerous nutrients such as antioxidants which are necessary for newborns. The aim of this study was to evaluate the changes of total antioxidant capacity (TAC) and free radical scavenging activity in human milk during the first six month period of lactation and also its relationship to maternal plasma. A total of 505 milk samples (colostrum, transitional and mature milks) collected from 115 healthy women with full term newborns. Blood plasma was obtained from 58 women at 3 months postpartum. The TAC of samples were measured by Ferric Reducing/Antioxidant Power assay and free radical scavenging activity were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. TAC was obviously higher in colostrums than transitional and mature milks. Similar results were observed for DPPH radical scavenging activity of the samples. There was a high significant correlation between the results of these two methods. The relationship between the antioxidant content of human milk and maternal plasma was also significant. These data suggest that using colostrum, with high antioxidant potential during the first days of life is vital; moreover, reduction in total TAC during the course of lactation may needs more attention about nutritional status.

PMID: 19794922

Antioxidants in colostrum and milk of sows and cows.

Reprod Domest Anim. 2009 Aug;44(4):606-11.; Albera E, Kankofer M.; Department of Animal Biochemistry and Physiology, Faculty of Veterinary Medicine, Agricultural University, Lublin, Poland.

On account of the oxidative stress conditions that may appear during parturition, colostrum should provide with not only nutritional and immunological components but also antioxidative protection of newborn. There is evidence that apart from well-known antioxidative enzymes like glutathione peroxidase, superoxide dismutase, catalase or low molecular antioxidants, proteins like lactoperoxidase (LPO), lactoferrin (LF) and ceruloplasmin (CP) may exert antioxidative properties in colostrum. The aim of present study was to determine and to evaluate LPO, LF and CP activities in colostrum and milk of sows and cows. Samples were collected from 16 healthy cows five times: immediately after parturition, 12, 24 and 48 h, and 7 days postpartum as well as from 14 healthy sows five times: immediately after parturition, 6, 12, 24 and 36 h later. Examined parameters were determined spectrophotometrically at 412, 560 and 540 nm respectively. LPO activity was higher in sows as in cows and increased significantly within examined time. LF ability to inhibit superoxide radical generation was higher in sows as in cows and increased significantly within examined time. CP oxidase activity was higher in cows as in sows and decreased significantly during experimental period. In conclusion, antioxidative defence system in colostrum shows dynamic changes that allow for providing with necessary protection from oxidative stress conditions, which may appear after parturition.

PMID: 19642220 [PubMed - indexed for MEDLINE]

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Athletics


Bovine colostrum supplementation and exercise performance: potential mechanisms.

Sports Med. 2009;39(12):1033-54. doi: 10.2165/11317860-000000000-00000.Shing CM, Hunter DC,Stevenson LM.; School of Human Life Sciences, University of Tasmania, Launceston, Tasmania, Australia. [email protected]

Bovine colostrum (BC) is rich in immune, growth and antimicrobial factors, which promote tissue growth and the development of the digestive tract and immune function in neonatal calves. Although the value of bovine colostrum to human adults is not well understood, supplementation with BC is becoming increasingly popular in trained athletes to promote exercise performance. The combined presence of insulin-like growth factors (IGF), transforming growth factors, immunoglobulins, cytokines, lactoferrin and lysozyme, in addition to hormones such as growth hormone, gonadotrophin-releasing hormone, luteinizing hormone-releasing hormone and glucocorticoids, would suggest that BC might improve immune function, gastrointestinal integrity and the neuroendocrine system, parameters that may be compromised as a result of intensive training. A review of studies investigating the influence of bovine colostrum supplementation on exercise performance suggests that BC supplementation is most effective during periods of high-intensity training and recovery from high-intensity training, possibly as a result of increased plasma IGF-1, improved intramuscular buffering capacity, increases in lean body mass and increases in salivary IgA. However, there are contradicting data for most parameters that have been considered to date, suggesting that small improvements across a range of parameters might contribute to improved performance and recovery, although this cannot be concluded with certainty because the various doses and length of supplementation with BC in different studies prevent direct comparison of results. Future research on the influence of BC on sports performance will only be of value if the dose and length of supplementation of a well-defined BC product is standardized across studies, and the bioavailability of the active constituents in BC is determined.PMID: 20030905 [PubMed - as supplied by publisher]

Bovine colostrum supplementation attenuates the decrease of salivary lysozyme and enhances the recovery of neutrophil function after prolonged exercise.

Department of Sport and Exercise Science, Aberystwyth University, Carwyn James Building, Penglais Campus, Aberystwyth, Ceredigion SY23 3FD, UK; Davison G, Diment BC.

Oral supplementation with bovine colostrum (COL) has been shown to enhance immunity in human subjects. However, there is limited research on the use of bovine COL supplementation to counter exercise-induced immunodepression, as a model of stress-induced immunodepression, and previous research has focused primarily on salivary IgA. The aim of the present study was to determine the effects of bovine COL supplementation on exercise-induced changes in innate immunity (neutrophil function and salivary lysozyme) in addition to salivary IgA. Twenty healthy, active men cycled for 2 h at approximately 64 % maximal oxygen uptake after 4 weeks of daily bovine COL (n 10) or placebo (PLA, n 10) supplementation. Blood and saliva samples were obtained before and after supplementation, before and after exercise. Exercise induced significant increases in markers of physiological stress and stress to the immune system (circulating neutrophils, neutrophil:lymphocyte ratio, immature granulocytes, atypical lymphocytes and plasma cortisol), but there were no differences between the COL and PLA groups. Significant group x time interactions (two-way mixed model ANOVA) were observed for neutrophil function (stimulated degranulation) and salivary lysozyme concentration and release (P < 0.05). Significant exercise-induced decreases were observed in these parameters, and bovine COL supplementation either speeded the recovery (neutrophil function) or prevented the decrease (salivary lysozyme) in these measures of innate immunity. These results suggest that 4 weeks of bovine COL supplementation limits the immunodepressive effects induced by an acute prolonged physical stressor, such as exercise, which may confer some benefits to host defence.

PMID: 20030905 [PubMed - as supplied by publisher]

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Chronic Fatigue


Immune and hemorheological changes in Chronic Fatigue Syndrome.

J Transl Med. 2010 Jan 11;8(1):1; Brenu EW, Staines DR, Baskurt OK, Ashton KJ, Ramos SB, Christy RM, Marshall-Gradisnik SM.

ABSTRACT: BACKGROUND: Chronic Fatigue Syndrome (CFS) is a multifactorial disorder that affects various physiological systems including immune and neurological systems. The immune system has been substantially examined in CFS with equivocal results, however, little is known about the role of neutrophils and natural killer (NK) phenotypes in the pathomechanism of this disorder. Additionally, the role of erythrocyte rheological characteristics in CFS has not been fully expounded. The objective of this present study was to determine deficiencies in lymphocyte function and erythrocyte rheology in CFS patients. METHODS: Flow cytometric measurements were performed for neutrophil function, lymphocyte numbers, NK phenotypes (CD56dimCD16+ and CD56brightCD16-) and NK cytotoxic activity. Erythrocyte aggregation, deformability and fibrinogen levels were also assessed. RESULTS: CFS patients (n = 10) had significant decreases in neutrophil respiratory burst, NK cytotoxic activity and CD56brightCD16- NK phenotypes in comparison to healthy controls (n = 10). However, hemorheological characteristics, aggregation, deformability and fibrinogen, lymphocyte numbers and CD56dimCD16+ NK cells were similar between groups. CONCLUSION: Immune dysfunction may therefore be an important contributory factor to the mechanism of CFS, as indicated by decreases in neutrophil respiratory burst, NK cell activity and NK phenotypes. Thus, immune cell function and phenotypes are possible diagnostic markers for CFS.

PMID: 20064266 [PubMed - as supplied by publisher]

Improving fatigue assessment in immune-mediated neuropathies: the modified Rasch-built fatigue severity scale.

Van Nes SI, Vanhoutte EK, Faber CG, Garssen M, van Doorn PA, Merkies IS; PeriNomS Study Group; Bennett D, van den Berg LH, Van den Bergh PY,Cornblath DR, Dalakas M, Devigili G, van Doorn PA, Faber CG, Gorson KC, Hadden RD,Hahn AF, Hartung HP,Hughes RA, Lauria G, Léger JM, Lewis RA, Lunn MP, Merkies IS, Nobile-Orazio E,Notermans NC,Padua L, Reilly MM, >Smith B.; Department of Neurology, Erasmus Medical Centre Rotterdam, Rotterdam, The Netherlands. [email protected]

Fatigue is a major disabling complaint in patients with immune-mediated neuropathies (IN). The 9-item fatigue severity scale (FSS) has been used to assess fatigue in these conditions, despite having limitations due to its classic ordinal construct. The aim was to improve fatigue assessment in IN through evaluation of the FSS using a modern clinimetric approach [Rasch unidimensional measurement model (RUMM2020)]. Included were 192 stable patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) or polyneuropathy associated with monoclonal gammopathy of undetermined significance (MGUSP). The obtained FSS data were exposed to RUMM2020 model to investigate whether this scale would meet its expectations. Also, reliability and validity studies were performed. The original FSS did not meet the Rasch model expectations, primarily based on two misfitting items, one of these also showing bias towards the factor ‘walking independent.’ After removing these two items and collapsing the original 7-point Likert options to 4-point response categories for the remaining items, we succeeded in constructing a 7-item Rasch-built scale that fulfilled all requirements of unidimensionality, linearity, and rating scale model. Good reliability and validity were also obtained for the modified FSS scale. In conclusion, a 7-item linearly weighted Rasch-built modified FSS is presented for more proper assessment of fatigue in future studies in patients with immune-mediated neuropathies.

PMID: 20021568 [PubMed - in process]

Digestive Tract Disorders

Bovine colostrum prevents bacterial translocation in an intestinal ischemia/reperfusion-injured rat model.

J Med Food. 2009 Feb;12(1):37-46; Choi HS,Jung KH, Lee SC, Yim SV, Chung JH, Kim YW, Jeon WK, Hong HP,Ko YG, Kim CH, Jang KH, Kang SA.; Department of Emergency Medicine, Kohwang Medical Research Institute, Kyung Hee University, Seoul, Republic of Korea.

This study evaluated whether or not bovine colostrum (BC) is able to treat or prevent intestinal barrier damage, bacterial translocation, and the related systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) in an intestinal ischemia/reperfusion (I/R)-injured rat model. Fifty Sprague-Dawley rats were used. The rats’ intestinal I/R injuries were induced by clamping the superior mesenteric artery for 30 minutes. After 3 hours of reperfusion and then twice daily reclamping during the experiment, the experimental group was given BC (4 mL/kg/day) perorally, and the other groups received 0.9% saline and low fat milk (LFM) after intestinal I/R injury. Seventy-two hours later we assessed (1) intestinal damage and intestinal permeability, (2) enteric bacterial count and bacterial translocation, (3) serum albumin, protein, and hepatic enzyme levels, (4) pathologic findings of ileum and lung, (5) activity of oxygen-free radical species, and (6) pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-1beta). Intestinal damage, intestinal permeability, and bacterial translocation to other organs were significantly reduced in rats fed with BC after I/R when compared to rats fed LFM/saline after I/R (P < .05). In the evaluation of acute lung injury, neutrophils were found only in the lungs of the saline-fed group after I/R, and the wet/dry ratio of the lung tissue was significantly reduced in the BC-fed group after I/R compared to other I/R groups. A marked difference was found between LFM/saline-fed groups and BC-fed groups regarding malondialdehyde (P < .05) and pro-inflammatory cytokines (P < .01). In conclusion, BC may have beneficial effects in treating and preventing intestinal barrier damage, bacterial translocation and the related SIRS and MODS in the intestinal I/R-injured rat model.

PMID: 19298194 [PubMed - indexed for MEDLINE]

Prebiotic effect of lacto-N-biose I on bifidobacterial growth.

Biosci Biotechnol Biochem. 2009 May;73(5):1175-9. Epub 2009 May 7; Kiyohara M, Tachizawa A, Nishimoto M, Kitaoka M, Ashida H, Yamamoto K.; Graduate School of Biostudies, Kyoto University, Kyoto, Japan. [email protected]

We demonstrated the prebiotic effect of lacto-N-biose I (Galbeta1-3GlcNAc) on bifidobacteria in vitro. Lacto-N-biose I, a building unit of the type-I milk oligosaccharides, enhanced the growth of many bifidobacteria, especially Bifidobacterium bifidum, B. breve, and B. longum, which are predominant in the intestines of breast-fed infants. It might be a substantial, natural prebiotic in human colostrums.

PMID: 19420691 [PubMed - indexed for MEDLINE]

Diet-dependent mucosal colonization and interleukin-1beta responses in preterm pigs susceptible to necrotizing enterocolitis.

J Pediatr Gastroenterol Nutr. 2009 Jul;49(1):90-8; Van Haver ER, Sangild PT,Oste M, Siggers JL; Department of Veterinary Medicine, University of Antwerp, Wilrijk, Belgium.

OBJECTIVES: Intestinal colonization challenges the neonatal innate immune system, especially in newborns with an immature immune response lacking the supportive bioactive components from mother’s milk. Accordingly, formula-fed preterm pigs frequently show bacterial overgrowth, mucosal atrophy, and gut lesions reflecting necrotizing enterocolitis (NEC) within the first days after birth. We hypothesized that NEC development is related to a diet-dependent bacterial adherence and a subsequent proinflammatory cytokine response in the gut mucosa immediately after introduction of enteral food. MATERIALS AND METHODS: Premature piglets (92% gestation) received 2 to 3 days of total parenteral nutrition followed by 0, 8, or 17 hours of enteral formula or sow’s colostrum feeding. RESULTS: Following 8 hours, but not 17 hours, of colostrum feeding, a reduced number of intestinal samples with adherent bacteria (both Gram-negative and Gram-positive bacteria) was counted compared with 0 or 8 hours of formula feeding. Besides a more dense colonization, formula feeding leads to higher intestinal interleukin-1beta (IL-1beta) levels and more NEC-like lesions from 8 hours onward. The load of adherent bacteria was especially high in NEC lesions. Toll-like receptor 4 was detected in enteroendocrine, neuronal, and smooth muscle cells, potentially mediating the increase in IL-1beta levels by Gram-negative bacteria. CONCLUSIONS: Formula feeding facilitates bacterial adherence and the development of a proinflammatory state of the intestine, which may be among the key factors that predispose formula-fed preterm neonates to NEC.

PMID: 19516189 [PubMed - indexed for MEDLINE]

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The structural basis for the prevention of nonsteroidal antiinflammatory drug-induced gastrointestinal tract damage by the C-lobe of bovine colostrum lactoferrin.

Biophys J. 2009 Dec 16;97(12):3178-86; Mir R, Singh N,Vikram G, Kumar RP,Sinha M, Bhushan A, Kaur P, Srinivasan A, Sharma S, Singh TP; Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India.

Nonsteroidal antiinflammatory drugs (NSAIDs), due to their good efficacy in the treatment of pain, inflammation, and fever, are among the most prescribed class of medicines in the world. The main drawback of NSAIDs is that they induce gastric complications such as peptic ulceration and injury to the intestine. Four NSAIDs, indomethacin, diclofenac, aspirin, and ibuprofen were selected to induce gastropathy in mouse models. It was found that the addition of C-terminal half of bovine lactoferrin (C-lobe) reversed the NSAID-induced injuries to the extent of 47-70% whereas the coadministration of C-lobe prevented it significantly. The C-lobe was prepared proteolytically using serine proteases. The binding studies of C-lobe with NSAIDs showed that these compounds bind to C-lobe with affinities ranging from 2.6 to 4.8 x 10(-4) M. The complexes of C-lobe were prepared with the above four NSAIDs. All four complexes were crystallized and their detailed three-dimensional structures were determined using x-ray crystallographic method. The structures showed that all the four NSAID molecules bound to C-lobe at the newly identified ligand binding site in C-lobe that is formed involving two alpha-helices, alpha10 and alpha11. The ligand binding site is separated from the well known iron binding site by the longest and the most stable beta-strand, betaj, in the structure. Similar results were also obtained with the full length lactoferrin molecule. This novel, to our knowledge, binding site in C-lobe of lactoferrin shows a good complementarity for the acidic and lipophilic compounds such as NSAIDs. We believe this indicates that C-lobe of lactoferrin can be exploited for the prevention of NSAID-induced gastropathy.

PMID: 20006955

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Healing


Bovine colostrum promotes growth and migration of the human keratinocyte HaCaT cell line.

Growth Factors. 2009 Dec;27(6):448-55; Kovacs D, Cardinali G, Aspite N, Picardo M.; San Gallicano Dermatological Institute, IRCCS, Rome, Italy.

Bovine colostrum represents a rich source of growth factors, which are known to play a central role in wound healing. The aim of our study was to investigate the possible mitogenic and motogenic effects induced by colostrum on human keratinocytes. Cell proliferation evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide test and 5-Bromo-2′-deoxyuridine incorporation revealed that colostrum exerts a growth promoting activity. Scratch assay and immunofluorescence of actin cytoskeleton showed its effectiveness also in inducing cell migration. Furthermore, colostrum treatment increases the levels of tyrosine phosphorylated proteins and the activated forms of the extracellular signal-regulated kinases 1 and 2 and such effects appear to be repressed by the tyrosine kinase inhibitor genistein. Our results indicate that the biological activities of colostrum are specifically mediated by the growth factor-induced activation of tyrosine kinase receptors and underline the relevance of the synergistic action exerted by the growth factors in stimulating keratinocyte proliferation and migration essential for tissue repair.

PMID: 19919532

Mare’s colostrum globules stimulate fibroblast growth in vitro: a biochemical study.

J Med Food. 2009 Aug;12(4):836-45; Zava S, Barello C, Pessione A, Garoffo LP, Fattori P, Montorfano G, Conti A, Giunta C, Pessione E, Berra B, Giuffrida MG; Institute of General Physiology and Biological Chemistry, University of Milan, Milan, Turin, Italy.

The wound repair function of mare’s milk and colostrum was investigated. Mare’s colostrum improved wound healing in vivo; thus fibroblast growth activation by mare’s milk and colostrum was examined. As expected, colostrum was more effective than milk. To establish the biochemical nature of the bioactive molecules involved, colostrum was fractionated into whey, casein, and fat globules, and the efficacy of these fractions on fibroblast proliferation was studied. The fat globule fraction provided the strongest stimulation; its composition was studied and compared with the less-active milk fat globule fraction. The lipid pattern highlighted several differences between mare’s colostrum and milk; in particular, total lipid, linoleic acid, linolenic acid, ganglioside, and glycolipid contents were higher in colostrum. A proteomic investigation revealed some differences between the protein composition of colostrum and milk fat globules. Adipophylin and lactadherin were significantly overexpressed in colostrum fat globules. The role of specific lipids on skin wound repair and that of the epidermal growth factor-like domain, embedded within the lactadherin molecule and probably released in conditions stimulating proteolysis, are discussed.

PMID: 19735185 [PubMed - indexed for MEDLINE]


Immunity


Bovine Colostrum: its dietary supplementation role in improvement and modulation of human immune indices

Nutrition and Food Science Department; Home Economics Faculty; Food Hygiene Department; National Institute of Nutrition; Cairo; Sherif S. Ragab and Effat A. A. Afif.

Oral ingestion of bovine colostrum lozenges student subjects has been shown to be effective in improvement and modulation of humoral and cell-mediated immune indices during the feeding (two weeks) and post-feeding (two weeks) duration’s. Both of circulate serum immunoglobulins IgG, IgM and IgA as a some parameters of humoral immunity and T-lymphocytes CD4 and CD8 as a some parameters of cell-mediated immunity in all of examined human subjects has been significantly influenced by oral supplementation by bovine colostrum lozenges. There was a direct positive correlation between the daily-received colostrum dose and the observed influence on the titters of measured immunity indices. A daily dose of 400 mg bovine colostrum supplementation has more improvement and increase effects on estimated parameters rather than 200 mg daily dose which indicate that the improvement and modulation roles of bovine colostrum supplementation on immunity status was carried out through a dose - dependant fashion. All of the student cases of this study were having a low to moderate levels of all measured immunity indices which improved and modulated significantly as a result of daily consumption of bovine colostrum supplement.

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Factors associated with serum immunoglobulin levels in beef calves from Alberta and Saskatchewan and association between passive transfer and health outcomes.

Can Vet J. 2009 Mar;50(3):275-81; Waldner CL, Rosengren LB; Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan S7N 5B4, Canada. [email protected]

Inadequate consumption of colostrum can negatively affect calf health and survival. The serum immunoglobulin G (IgG) concentrations of 935 beef calves from 152 herds in Alberta and Saskatchewan have been described, using radial immunodiffusion. The determinants and health effects of serum IgG concentrations were studied in 601 calves sampled between 2 and 8 days of age. Of these calves, 6% had failure of passive transfer and an additional 10% had marginal passive transfer. Serum IgG concentrations were lower in calves born to a heifer, as a twin, or experiencing dystocia. The odds of both calf death and treatment were increased in calves with serum IgG concentrations below 24 g/L; a threshold notably higher than the 16 g/L usually considered as providing adequate passive transfer. The finding of 1/3 of calves with serum IgG concentrations less than 24 g/L suggests that calfhood treatments and mortality could be decreased by ensuring that high risk calves consume colostrum.

PMID: 19436479 [PubMed - indexed for MEDLINE]

Enterocin C, a class IIb bacteriocin produced by E. faecalis C901, a strain isolated from human colostrum.

Int J Food Microbiol. 2009 Jul 31;133(1-2):105-12. Epub 2009 May 9; Caballero-Guerrero B, Jiménez E, Jiménez-Díaz R, Ruiz-Barba JL, Rodríguez JM; Departamento de Nutrición, Bromatología y Tecnología de Alimentos, Universidad Complutense de Madrid, Spain. [email protected]

Enterocin C (EntC), a class IIb bacteriocin was purified from culture supernatants of Enterococcus faecalis C901, a strain isolated from human colostrum. Enterocin C consists of two distinct peptides, named EntC1 and EntC2, whose complementary action is required for full antimicrobial activity. The structural genes entC1 and entC2 encoding enterocins EntC1 and EntC2, respectively, and that encoding the putative immunity protein (EntCI) are located in the 9-kb plasmid pEntC, harboured by E. faecalis C901. The N-terminal sequence of both antimicrobial peptides revealed that EntC1 (4284 Da) is identical to Ent1071A, one of the two peptides that form enterocin 1071 (Ent1071), a bacteriocin produced by E. faecalis BFE 1071. In contrast, EntC2 (3867 Da) presents the non-polar alanine residue at position 17 (Ala(17)) instead of the polar threonine residue (Thr(17)) in Ent1071B, the second peptide constituting Ent1071. In spite of peptide similarities, EntC differs from Ent1071 in major aspects, including the complementary activity among its constitutive peptides and its wider inhibitory spectrum of activity. Different amphiphilic alpha-helical conformations between EntC2 and Ent1071B could explain both, acquired complementary activity and increased antimicrobial spectrum.

PMID: 19501421 [PubMed - indexed for MEDLINE]

Seric and secretory antibodies reactive to alpha, beta and gamma intimins of Escherichia coli in healthy Brazilian adults.

FEMS Immunol Med Microbiol. 2009 Oct;57(1):32-9. Epub 2009 Jun 15; Zapata-Quintanilla LB, Tino-De-Franco M, Nuñez SP, Carbonare CB, Vulcano AB, Carbonare SB. Laboratório de Imunogenética, Instituto Butantan, São Paulo, SP, Brazil.

Intimin is essential for attaching and effacing lesions by pathogens such as enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC), and the antigenic polymorphism of intimin determines distinct subtypes. Our aim was to investigate the presence of immunoglobulin G (IgG) and IgA antibodies reactive to alpha, beta and gamma intimins in serum and colostrum from healthy Brazilian adults. We found seric IgG and secretory IgA antibodies reactive to conserved and variable regions of alpha, beta and gamma intimins and a positive correlation between the concentrations of these antibodies in both serum and colostrum that suggested cross reactivity among anti-intimin antibodies, as was confirmed by immunoblotting and absorption. The concentrations of anti-conserved region antibodies were higher than those of variable region antibodies. The presence of antibodies reactive to EHEC antigens could result from contact with EPEC or with other bacteria of the environment even though this bacterium is not frequent in Brazil, and suggests possible protection against EHEC.

PMID: 19583778 [PubMed - indexed for MEDLINE]

A novel immunoregulatory protein in human colostrum, syntenin-1, for promoting the development of IgA-producing cells from cord blood B cells.

Int Immunol. 2009 Sep;21(9):1013-23. Epub 2009 Jul 10; Sira MM, Yoshida T, Takeuchi M, Kashiwayama Y, Futatani T, Kanegane H, Sasahara A, Ito Y, >Mizuguchi M, Imanaka T, Miyawaki T.; Department of Pediatrics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, Toyama 930-0194, Japan.

Human colostrum contains many bioactive factors that must promote the development of intestinal mucosal immunity in infants. Especially, the presence of certain cytokines such as transforming growth factor (TGF)-beta or IL-10 has been of great interest for IgA production as a function of mucosal immune response. In the present study, we attempted to investigate whether unidentified factors inducing generation of IgA-producing cells from naive B cells might exist in colostrum. For this purpose, colostrum samples were directly added to a culture consisting of naive B cells and dendritic cells from cord blood and CD40 ligand-transfected L cells, comparing with recombinant IL-10 (rIL-10) and/or rTGF-beta. It was noted that most colostrum samples alone were able to induce IgA-secreting cells at higher levels than rIL-10 and/or rTGF-beta. IgA-inducing activity of colostrum was abolished by neither anti-neutralizing mAbs against IL-10 nor TGF-beta, though partially by anti-IL-6 mAb. We prepared partially purified fractions from both pooled colostrums with and without IgA-inducing activity and comparatively performed quantitative proteomic analysis by two-dimensional difference gel electrophoresis followed by liquid chromatography-mass spectrometry. As a result, syntenin-1 was identified as a candidate for IgA-inducing protein in colostrum. Western blot analysis indicated that levels of syntenin-1 in colostrum samples were correlated with their IgA-inducing activities. Moreover, we demonstrated that recombinant syntenin-1 could induce preferentially IgA production from naive B cells. These results suggest that syntenin-1 serves as one of IgA-inducing factors for B cells.

PMID: 19592421 [PubMed - indexed for MEDLINE]

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Feeding heat-treated colostrum or unheated colostrum with two different bacterial concentrations to neonatal dairy calves.

J Dairy Sci. 2009 Sep;92(9):4565-71.; J Dairy Sci. 2009 Sep;92(9):4565-71; Elizondo-Salazar JA, Heinrichs AJ; Department of Dairy and Animal Science, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.

The objective of this study was to determine the effects of feeding heat-treated colostrum or unheated colostrum of different bacterial counts on passive transfer of immunity in neonatal dairy calves. First milking colostrum was collected from Holstein cows, frozen at -20 degrees C, and then thawed and pooled into a single batch. One-third of the pooled colostrum was transferred into plastic containers and frozen at -20 degrees C until needed for feeding (unheated-low bacteria). Another third was heat-treated at 60 degrees C for 30 min and then frozen at -20 degrees C until needed for feeding (heat-treated). The final third of colostrum was transferred into plastic containers, stored at 20 degrees C for bacteria to grow for 24 h (unheated-high bacteria), and then frozen at -20 degrees C until needed for feeding. A total of 30 Holstein bull calves weighing >or=30 kg at birth were systematically enrolled into 1 of the 3 treatment groups. Calves were separated from their dams at birth before suckling occurred. Before colostrum was fed, a jugular blood sample was collected from each calf. The first feeding consisted of 3.8 L of colostrum containing, on average, 68 g of IgG/L using an esophageal feeder between 1.5 and 2 h after birth. For the second and third feeding pasteurized whole milk at 5% of birth weight was fed. Blood samples were collected before colostrum feeding and at 24 and 48 h of age to determine serum total protein (STP) and IgG concentrations. Heat treatment of colostrum at 60 degrees C for 30 min reduced colostrum bacteria concentration yet maintained colostral IgG concentration and viscosity at similar levels to the control treatment. Calves fed heat-treated colostrum had significantly greater STP and IgG concentrations at 24 h and greater apparent efficiency of absorption (AEA) of IgG (STP = 62.5 g/L; IgG = 26.7 g/L; AEA = 43.9%) compared with calves fed unheated-low bacteria colostrum (STP = 57.0 g/L; IgG = 20.2 g/L; AEA = 35.4%) or unheated-high bacteria colostrum (STP = 56.2 g/L; IgG = 20.1 g/L; AEA = 32.4%). High bacteria load in colostrum did not interfere with total protein or IgG absorption or AEA.

PMID: 19700719 [PubMed - indexed for MEDLINE]


Inflammation

Bovine colostrum inhibits nuclear factor kappaB-mediated proinflammatory cytokine expression in intestinal epithelial cells.

Nutr Res. 2009 Apr;29(4):275-80; An MJ, Cheon JH, Kim SW, Park JJ, Moon CM, Han SY, Kim ES, Kim TI, Kim WH; Department of Internal Medicine and Institute of Gastroenterology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.

Colostrum, a nutrient-rich fluid produced by female mammals immediately after giving birth, is loaded with several immune, growth, and tissue repair factors. However, it remains unknown whether bovine colostrum has anti-inflammatory effects on intestinal epithelial cells (IEC). In this study, we aimed to investigate the anti-inflammatory effects of colostrum on IEC and to elucidate its molecular mechanisms. Human colon cancer HT-29 cells were stimulated with interleukin (IL)-1beta with or without bovine colostrum. The effects of colostrum on nuclear factor kappaB (NF-kappaB) signaling in HT-29 cells were examined using real-time reverse transcriptase-polymerase chain reaction detect IL-8 and intracellar adhesion molecule-1 mRNA expression using a NF-kappaB-dependent reporter gene assay and an electrophoretic mobility shift assay. Furthermore, we assessed the expression levels of inhibitor protein of NF-kappaB-alpha, cyclooxygenase-2, and p65 proteins by Western blotting. Bovine colostrum significantly inhibited IL-1beta-induced IL-8 and intracellar adhesion molecule-1 mRNA expression. Moreover, it suppressed IL-1beta-induced NF-kappaB activation, including NF-kappaB dependent reporter gene expression in a dose-dependent manner. Finally, Western blotting revealed that colostrum decreased the cyclooxygenase-2 protein expression level, inhibited inhibitor protein of NF-kappaB-alpha degradation, and blocked translocation of p65 into the nucleus. These data demonstrated that bovine colostrum might protect against IEC inflammation by inhibiting the NF-kappaB pathway, suggesting colostrum has a therapeutic potential for intestinal inflammation.

PMID: 19410980 [PubMed - indexed for MEDLINE]

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Pain & Fibromyalgia

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Oral immunoglobulin induces mononuclear cell apoptosis in patients suffering from idiopathic chronic pain syndrome: results from a pilot study.

Int J Clin Pharmacol Ther. 2009 Jul;47(7):421-33; Gasser M, Stock M, Grimm M, Sprotte G.; Department of Surgery I, Molecular Oncology and Immunology, University of Wuerzburg, Germany.

OBJECTIVE: The objective of this clinical pilot study was to examine the induction of apoptosis in mononuclear cells on treatment of patients with chronic pain syndrome with oral immunoglobulin produced from bovine colostrum (BCC). DESIGN: The 4 patients suffering from chronic idiopathic pain (idiopathic facial pain, CRPS or fibromyalgia) who were enrolled in the study had previously successfully been treated with BCC (varying individual doses). Mononuclear cells from peripheral blood were analyzed for representative cytokines in the serum as well as by TUNEL-assay to detect apoptotic cellular events 14 days after the last treatment with BCC and 14 days after restarting the treatment protocol with BCC. The clinical response (pain and quality of life parameters using a visual analogue scale (VAS)) were determined regularly in each patient. RESULTS: The findings showed a disturbed apoptosis homeostasis in 3 of the 4 patients. These results were accompanied by a relief of the pain symptoms. The 4th patient was found not to need any further analgetic treatment since she demonstrated only nonsignificant changes in her laboratory screening and immunological parameters and by the end of the study she was also completely free of pain (long-term treatment with BCC). CONCLUSIONS: In spite of the low patient number, the results were obtained with a sufficiently high degree of control because of the study design. The agreement of the clinical data with our laboratory measurements suggests that the induction of apoptotic events in mononuclear cells is the result of the dominant immunological effects of BCC treatment.

PMID: 19640348 [PubMed - indexed for MEDLINE]


Weight Loss

Leptin concentrations are a predictor of overweight reduction in a lifestyle intervention.

Int J Pediatr Obes. 2009;4(4):215-23; Reinehr T, Kleber M, de Sousa G, Andler W.; Vestische Hospital for Children and Adolescents, University of Witten/Herdecke, Datteln, Germany. [email protected]

OBJECTIVE: Leptin resistance is discussed to be involved in the genesis of obesity. Therefore, we hypothesized that leptin levels were negatively associated with degree of weight loss in obese children participating in a lifestyle intervention. METHODS: We studied 248 obese children aged 8-14 years attending the “Obeldicks” lifestyle intervention (mean age 10.6+/-0.2 years, 53% female, 48% pubertal, mean body mass index (BMI) 27.8+/-0.3 kg/m2, and mean standard deviation score [SDS]-BMI 2.43+/-0.03). Baseline leptin concentrations were correlated with change of weight status, waist circumference, and percentage body fat, as calculated from skinfold measurements in the one-year intervention by Pearson correlation and multiple linear regression analyses. Furthermore, the relationship between leptin and cardiovascular risk factors (insulin, insulin resistance index HOMA, blood pressure, lipids, and glucose) were analyzed. RESULTS: A total of 212 children (85%) reduced their overweight, 9 children (4%) dropped out, and 27 children (11%) did not reduce their overweight in the lifestyle intervention “Obeldicks”. The mean reduction of SDS-BMI was 0.34+/-0.02. The reduction of SDS-BMI (r=- 0.27), waist circumference (r=- 0.64), and percentage body fat (r=- 0.26) were significantly negatively associated with baseline leptin levels both in univariate analyses and in multiple regression analyses, adjusted to baseline age, BMI, gender and pubertal stage. Baseline leptin concentrations were significantly associated with BMI, pubertal stage, gender, waist circumference, and insulin, but not to any other cardiovascular risk factors in multiple regression analyses. CONCLUSIONS: The finding that baseline leptin concentrations were significantly negatively correlated with the degree of weight loss in a lifestyle intervention supports the hypothesis of leptin resistance in obesity. This study is registered at clinicaltrials.gov (NCT00435734).

PMID: 19922035

Leptin is essential in maintaining normal vascular compliance independent of body weight.

Int J Obes (Lond). 2009 Oct 6; Sikka G, Yang R, Reid S, Benjo A, Koitabashi N, Camara A, Baraban E, O’Donnell CP, Berkowitz DE, Barouch LA.; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

The adipocytokine leptin centrally regulates body weight by enhancing metabolic rate and signaling satiety, but it also has wide-ranging peripheral effects. Leptin receptors are expressed on vascular smooth muscle cells and have a role in maintaining vascular tone. We investigated the vascular effects of leptin repletion or calorie restriction on leptin-deficient mice (ob/ob) and a leptin antagonist on wild-type (WT) mice. Aortic compliance was assessed by the measurement of pulse wave velocity by noninvasive Doppler; blood pressure was measured by left ventricular catheterization. We found that ob/ob mice have much stiffer aortas than WT mice and that reduction in aortic stiffness was greater in ob/ob mice treated with leptin vs calorie restriction, despite similar weight loss. Interestingly, treating WT mice with a leptin antagonist increases aortic stiffness with no change in weight. Thus, we conclude that leptin is essential for maintaining normal aortic compliance independent of body weight.International Journal of Obesity advance online publication, 6 October 2009; doi:10.1038/ijo.2009.208.

PMID: 19806156 [PubMed - as supplied by publisher]

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Methylnaltrexone potentiates body weight and fat reduction with leptin.

J Opioid Manag. 2009 Nov-Dec;5(6):373-8; Yuan CS, Sun S, Attele A, Wang CZ, Tong R, Israel RJ; Department of Anesthesia & Critical Care, Pritzker School of Medicine, University of Chicago, Illinois, USA

OBJECTIVE: Leptin increases energy expenditure by enhancing systemic and brown adipose metabolism. In a neonatal rat model, retroperitoneal fat pad weight decreased significantly in leptin-treated animals, which reduced body weight. As opioids increase feeding, opioid antagonists may decrease food intake and body weight. However, interactions between leptin and the activity of peripheral opioids on body weight and fat accumulation have not been investigated. In this study, the authors evaluated the effects of naloxone (a nonselective opioid antagonist) and methylnaltrexone (a peripherally acting opioid antagonist) on the action of leptin in neonatal rats. RESULTS: Compared with control, the weight gain of pups given a single daily intraperitoneal injection of leptin 0.5 mg/kg, leptin 0.5 mg/kg plus naloxone 0.3 mg/kg, or leptin 0.5 mg/kg plus methylnaltrexone 3.0 mg/kg for 8 consecutive days was significantly reduced (all p < 0.01). Naloxone or methylnaltrexone significantly potentiated leptin’s effect on body weight (p < 0.05 or p < 0.01, respectively). After coadministration of leptin plus naloxone or leptin plus methylnaltrexone, weight reduction in the right retroperitoneal fat pads was also significant compared with the reduction after leptin alone (p < 0.05 or p < 0.01, respectively). CONCLUSIONS: The data suggest the existence of a peripheral opioid-related mechanism in leptin-active modulation of body weight.

PMID: 20073411 [PubMed - in process]

Endogenous leptin signaling in the caudal nucleus tractus solitarius and area postrema is required for energy balance regulation.

Cell Metab. 2010 Jan;11(1):77-83; Hayes MR, Skibicka KP, Leichner TM, Guarnieri DJ, DiLeone RJ, Bence KK, Grill HJ; University of Pennsylvania, Philadelphia, 19104, USA. [email protected]

Medial nucleus tractus solitarius (mNTS) neurons express leptin receptors (LepRs), and intra-mNTS delivery of leptin reduces food intake and body weight. Here, the contribution of endogenous LepR signaling in mNTS neurons to energy balance control was examined. Knockdown of LepR in mNTS and area postrema (AP) neurons of rats (LepRKD) via adeno-associated virus short hairpin RNA-interference (AAV-shRNAi) resulted in significant hyperphagia for chow, high-fat, and sucrose diets, yielding increased body weight and adiposity. The chronic hyperphagia of mNTS/AP LepRKD rats is likely mediated by a reduction in leptin potentiation of gastrointestinal satiation signaling, as LepRKD rats showed decreased sensitivity to the intake-reducing effects of cholecystokinin. LepRKD rats showed increased basal AMP-kinase activity in mNTS/AP micropunches, and pharmacological data suggest that this increase provides a likely mechanism for their chronic hyperphagia. Overall these findings demonstrate that LepRs in mNTS and AP neurons are required for normal energy balance control. 2010 Elsevier Inc.

PMID: 20074530

Non-categorized

Bringing evidence to complementary and alternative medicine in children with cancer: Focus on nutrition-related therapies.

Kelly KM; Pediatr Blood Cancer. 2008 Feb;50(2 Suppl):490-3; discussion 498; Division of Pediatric Oncology, Columbia University Medical Center, New York, New York, USA. [email protected]

Children with cancer frequently use complementary and alternative medicine (CAM), especially in conjunction with conventional therapy. Dietary supplements are a commonly used CAM modality, with the prevalence of supplement use ranging from 35% to 50% of children with cancer in surveys completed in the United States. Less is known about the use of dietary supplements in developing countries. The evidence for some dietary supplements providing some benefit to children with cancer is reviewed. Preliminary studies have shown that antioxidant status may affect chemotherapy tolerance in children with acute lymphoblastic leukemia. Other supplements, including TRAUMEEL S, glutamine, vitamin E, Immunocal, colostrum, and probiotics, may help to reduce gastrointestinal toxicities of chemotherapy and radiation. However, more definitive evidence is needed. Most dietary supplements have not been tested adequately to determine their safety and efficacy, with even less understood about their potential interactions with conventional chemotherapy and radiation. With the greater use of dietary supplements by patients with cancer, increasing scientific attention is being paid to the investigation of these therapies. But research on dietary supplements is complex and usually more difficult than that on conventional medications. Strong research designs are critical in obtaining information that will ultimately influence clinical practice and public awareness. (c) 2007 Wiley-Liss, Inc.

PMID: 18064645 [PubMed - indexed for MEDLINE]

Therapeutic properties of proteins and peptides from colostrum and milk

Zimecki M, Artym J.; Zaklad Terapii Doswiadczalnej Instytutu Immunologii i Terapii Doswiadczalnej PAN im. Ludwika Hirszfelda we Wroclawiu. [email protected]

Colostrum and milk are rich in proteins and peptides which play a crucial role in innate immunity when transferred to the offspring and may accelerate maturation of the immune system in neonates. The immunotropic properties of these proteins prompted investigators research their potential application in prevention and therapy. Lactoferrin (LF) exhibits antibacterial, antifungal, antiviral, antiparasitice, and antitumoral activities. It is protective with regard to intestinal epithelium, promotes bone growth, and accelerates the recovery of immune system function in immunocompromised animals. LF was tried in the treatment of hepatitis C infection and the intestinal form of graft-versus-host disease (GvHD). A proline-rich polypeptide (PRP) demonstrated a variety of immunotropic functions, including the promotion of T-cell maturation and inhibition of autoimmune disorders. PRP, in the form of chewable tablets (Colostrinin) was recently found to improve or stabilize the health status of Alzheimer’s disease patients. Casein and casein-derived peptides showed protective activities in enamel demineralization and as caries-preventing agents. The protein hydrolyzates were also protective in diabetic animals, reduced tumor growth, had antihypertensive activity and diminished colicky symptoms in infants. Glycomacropeptide (GMP), a peptide derived from kappa-casein, exhibited various antibacterial and antithrombotic activities. Alpha-lactalbumin (LA) demonstrated antiviral, antitumoral and anti-stress properties. LA-enriched diets were anxiolytic, lowered blood pressure in rats, prevented diarrhea, and led to a better weight gain in malnourished children. HAMLET, a complex of LA and oleic acid, was effective in patients with cutaneous papillomas. Lysozyme found application in infant formulas, the treatment of periodentitis, and the prevention of tooth decay. Milk enriched in lysozyme was used in feeding premature infants suffering from concomitant diseases. Interesting, antibacterial properties were exhibited by lactoperoxidase. Both lysozyme and lactoperoxidase required cooperative action with LF in combating bacteria. In conclusion, preparations derived from milk and colostrum are effective, easily bioaccessible, and safe, finding wide application in prevention and therapy for newborns and adults.

PMID: 15995598 [PubMed - indexed for MEDLINE]

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