Modulatory effect of a complex fraction derived from colostrum on fibroblast contractibility and consequences on repair tissue.

A complex compound (immune ('IM') fraction) from colostrum-derived whey was investigated for its potential wound healing properties. One of its most intriguing in vitro abilities was to significantly inhibit the contraction of collagen gel while fibroblast density remained as in control gels. This antagonist effect was dose dependent and fibroblasts in these gels did not exhibit any stress fibres. Subsequently, in vivo studies have been conducted in two wound models in guinea pigs. Daily application on full-thickness wounds of a liquid formulation of the IM fraction (first model) significantly delayed wound closure by contraction compared to what normally occurred in control wounds. In another wound model, a gel formulation of the IM fraction was applied on scar tissues, which resulted in a minimised residual scar on 5/8 wounds compared to corresponding wound areas seen prior to treatment. Conversely, most control wounds exhibited scar tissue from which 3/8 resembled hypertrophic scar tissue. Wound tissue treated with IM fraction covered a significantly larger area than in the control wounds, whereas the collagen deposition was unchanged as in the presence of α-smooth muscle actin. Thus, IM fraction may act by modulating the contraction rate and wound remodelling.

A bovine whey protein extract stimulates human neutrophils to generate bioactive IL-1Ra through a NF-kappaB- and MAPK-dependent mechanism.

Innate immunity depends on the efficiency of neutrophils to be activated rapidly to restore homeostasis. It can benefit from priming agents that enhance neutrophil capacity to respond more efficiently to a subsequent stimulation. Among natural products, a bovine whey protein extract (WPE) has been shown to prime normal human blood neutrophils by enhancing their chemotaxis, phagocytosis, oxidative burst, and degranulation. These leukocytes are also an important source of cytokines, some of which have antiinflammatory functions. We investigated the role of WPE, as well as its mechanisms of action, on the production of interleukin (IL)-1 receptor antagonist (IL-1Ra) by neutrophils in vitro. WPE dose-dependently stimulated de novo synthesis and release of IL-1Ra by normal human blood neutrophils. Among the major proteins present in WPE, beta-lactoglobulin (beta-LG) and alpha-lactalbumin (alpha-LA) were the only active components. They had additive effects that exactly reproduced those of WPE. Similarly to WPE, they also stimulated the accumulation of IL-1beta, IL-8, IL-6, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and tumor necrosis factor-alpha. However, neutrophils incubated with WPE, beta-LG, and alpha-LA produced IL-1Ra in excess of IL-1beta and the ratio IL-1Ra:IL-1beta increased linearly. The amounts of IL-1Ra stimulated by WPE or beta-LG + alpha-LA significantly reduced the IL-1 activity in EL4 cells. Inhibitors of p38 and extracellular signal-regulated kinases (ERK)1/2 mitogen-activated protein kinase, and nuclear factor-kappaB cascades reduced neutrophil production of IL-1Ra. Our data suggest that WPE, through beta-LG + alpha-LA, has immunomodulatory properties and the potential to increase host defenses.

A bovine whey protein extract can enhance innate immunity by priming normal human blood neutrophils.

Bovine milk-derived products, in particular whey proteins, exhibit beneficial properties for human health, including the acquired immune response. However, their effects on innate immunity have received little attention. Neutrophils are key cells of innate defenses through their primary functions of chemotaxis, phagocytosis, oxidative burst, and degranulation. A whey protein extract (WPE) purified from bovine lactoserum was evaluated for its direct and indirect effects on these primary functions of normal human blood neutrophils in vitro. Although WPE had no direct effects on primary functions, a 24-h pretreatment of neutrophils with WPE was associated with a significant and dose-dependent increase of their chemotaxis, superoxide production, and degranulation in response to N-formyl-methionine-leucine-phenylalanine, as well as of their phagocytosis of bioparticles. The pretreatment increased the surface expression of CD11b, CD16B, and CD32A receptors. The major WPE protein components beta-lactoglobulin (beta-LG) and alpha-lactalbumin (alpha-LA) were the main active fractions having an additive effect on human neutrophils that became more responsive to a subsequent stimulation. This effect on NADPH oxidase activity was associated with translocation of p47(phox) to plasma membrane. Glycomacropeptide, a peptide present in measurable amounts in WPE products, was able to enhance the individual effect of beta-LG or alpha-LA on neutrophils. The present data suggest that WPE, through beta-LG and alpha-LA, has the capacity to enhance or "prime" human neutrophil responses to a subsequent stimulation, an effect that could be associated with increased innate defenses in vivo.

A double-blind, placebo-controlled, randomized trial of XP-828L (800 mg) on the quality of life and clinical symptoms of patients with mild-to-moderate psoriasis.

In a placebo-controlled clinical trial, the dietary supplement XP-828L (commercialized as Dermylex) demonstrated potential to reduce symptoms associated with mild-to-moderate psoriasis at a dose regimen of 5 g daily for 56 days. However, recent in vivo data in humans and animals suggest a daily dose of 800 mg could be more efficient than a 5-g dose. However, no well-structured clinical study has confirmed this hypothesis. The goal of the present study is to examine the effect of XP-828L at a daily dose of 800 mg on the quality of life and disease severity in patients with mild-to-moderate psoriasis. XP-828L at 800 mg per day (n=16) or placebo (n=10) was given orally for 56 days. Efficacy was measured by the Dermatology Life Quality Index (DLQI), Psoriasis Area and Severity Index (PASI), and itching sensation scores at day 1 and day 56. The DLQI and PASI scores and itching sensation decreased significantly by day 56 in subjects taking XP-828L compared to placebo (p less than 0.05). In summary, daily administration of 800 mg XP-828L for 56 days is adequate to improve the quality of life and decrease disease severity in patients with mild-to-moderate psoriasis.

XP-828L in the treatment of mild to moderate psoriasis: randomized, double-blind, placebo-controlled study.

BACKGROUND: XP-828L, a protein extract obtained from sweet whey, has demonstrated potential benefit for the treatment of mild to moderate psoriasis in an open-label study. OBJECTIVE: To study in a randomized, double-blind, placebo-controlled study the safety and efficacy of XP-828L in the treatment of mild to moderate psoriasis. DESIGN: XP-828L 5 g/d (group A, n=42) or placebo (group B, n=42) was given orally for 56 days followed by XP-828L 5 g/d in group A and by XP-828L 10 g/d in group B for an additional 56 days. RESULTS: Patients receiving XP-828L 5 g/d for 56 days had an improved Physician's Global Assessment (PGA) score compared with patients under placebo (p less than 0.05). Considering the data of group A only, the PGA score improved from day 1 to day 56 (p less than 0.01); the Psoriasis Area and Severity Index score improved as well, but to a lesser extent (p less than 0.05). CONCLUSION: Oral administration of 5 g/d XP-828L compared with a placebo significantly improved the PGA score of patients with mild to moderate psoriasis.

XP-828L (Dermylex), a new whey protein extract with potential benefit for mild to moderate psoriasis.

Natural health products (NHPs) or complementary and alternative medicine (CAM) are commonly used to prevent disorders or support the usual treatments of many diseases. XP-828L, a whey protein extract, has demonstrated potential benefits for the treatment of mild to moderate psoriasis. The aim of this study was to analyze further clinical data that demonstrated the clinical benefits and safety of the XP-828L in patients with psoriasis and the potential mechanism of action of this product in vitro. Oral administration (2.5 g, twice a day, over 112 days) of XP-828L in 42 human subjects with mild to moderate psoriasis improved their PGA scores (physician's global assessment). Moreover, no significant changes in haematology or hepatic and renal parameters were observed throughout the study period, indicating the safety of the product. In vitro experiments showed that XP-828L decreased the proliferation of concanavalin A (ConA)-stimulated murine splenocytes and their production of interleukin (IL)-2 and interferon (IFN)-gamma. Although the in vivo mechanism of action of XP-828L remains unknown, XP-828L represents an NHP to be used as an alternative or concomitant treatment for mild to moderate psoriasis and potentially for other immune-mediated diseases.

XP-828l in the treatment of mild to moderate psoriasis: randomized, double-blind, placebo-controlled study.

BACKGROUND: XP-828L, a protein extract obtained from sweet whey, has demonstrated potential benefit for the treatment of mild to moderate psoriasis in an open-label study. OBJECTIVE: To study in a randomized, double-blind, placebo-controlled study the safety and efficacy of XP-828L in the treatment of mild to moderate psoriasis. DESIGN: XP-828L 5 g/d (group A, n = 42) or placebo (group B, n = 42) was given orally for 56 days followed by XP-828L 5 g/d in group A and by XP-828L 10 g/d in group B for an additional 56 days. RESULTS: Patients receiving XP-828L 5 g/d for 56 days had an improved Physician's Global Assessment (PGA) score compared with patients under placebo (p < .05). Considering the data of group A only, the PGA score improved from day 1 to day 56 (p < .01); the Psoriasis Area and Severity Index score improved as well, but to a lesser extent (p < .05). CONCLUSION: Oral administration of 5 g/d XP-828L compared with a placebo significantly improved the PGA score of patients with mild to moderate psoriasis.

Swim training increases glucose output from liver perfused in situ with glucagon in fed and fasted rats.

The effect of endurance swim training (3 hours per day, 5 days/week, for 10 weeks) on hepatic glucose production (HGP) in liver perfused in situ for 60 minutes with glucagon and insulin was studied in Sprague-Dawley rats. The experiments were performed in fed rats and in rats fasted for 24 hours, but with lactate (8 mmol/L) added to the perfusion medium. Liver glycogen content was significantly lower in fasted than fed rats (fasted untrained and trained: 14 +/- 4 and 11 +/- 3 micromol glycosyl U/g of liver wet weight (WW); fed untrained and trained: 205 +/- 11 and 231 +/- 11 micromol glycosyl U/g of liver WW; not significantly different in trained and untrained rats). Glucagon increased HGP in the 4 experimental groups, but the increases were more rapid and pronounced in trained than in untrained rats in both fed and fasted states. HGP values (area under the curve [AUC] in micromol/g of liver WW) were significantly higher in trained fed (112.1 +/- 7.1 v 85.9 +/- 12.2 in untrained rats) than in trained fasted rats (50.8 +/- 4.4 v 34.7 +/- 3.6 in untrained rats). When compared with untrained rats, the total amount of glucose released by the liver in response to glucagon in trained rats was approximately 30% higher in the fed state and approximately 45% larger in the fasted state. These results indicate that endurance training increases the response of both glycogenolysis and gluconeogenesis to glucagon.