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Efficacy and tolerability of oral lactoferrin supplementation in mild to moderate acne vulgaris: An exploratory study

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Abstract

Lactoferrin, an innate defense iron-binding protein, possesses antimicrobial and anti-inflammatory activities. Beneficial systemic effects on inflammatory diseases have been proposed. The aim of the present study was to explore the efficacy and tolerability of oral bovine lactoferrin supplementation in subjects with mild to moderate facial acne vulgaris. In this open-label, single-arm study, 43 adolescents and young adults were enrolled to take a chewable tablet formulation of bovine lactoferrin twice daily for 8 weeks. The primary efficacy endpoint was the improvement in acne lesion counts compared with baseline. Tolerability was evaluated on the basis of adverse event frequencies. Thirty-nine subjects, aged 17.5 ± 3.8 years, completed the study per protocol. At the end of the study (week 8), a mean reduction in inflammatory lesion count of 20.2% (-2.2 ± 7.0, p = 0.054), in non-inflammatory lesion count of 23.5% (-6.2 ± 9.8, p < 0.001), and in total lesion count of 22.5% (-8.4 ± 13.1, p < 0.001) was observed as compared with baseline. At study conclusion, 76.9% (30 of 39) of subjects showed a reduction in total lesion count. The results for inflammatory acne lesions were variable over the study course. None of the subjects experienced a lactoferrin-related adverse event during the trial. Despite the limitations of an uncontrolled, open-label study, the results from this study indicate that lactoferrin in mild to moderate acne vulgaris is well tolerated and may lead to an overall improvement in acne lesion counts in the majority of affected adolescents and young adults when administered as a dietary supplement on a twice daily regimen. Further randomized, placebo-controlled trials of longer duration appear warranted.

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... [7][8][9] The effect of lactoferrin against acne has only been demonstrated in either small or noncontrolled open label trials. 10,11 Thus, we investigated the effect of an oral lactoferrin with vitamin E and zinc capsule formulation in an adequately powered, randomized, double-blind, placebo-controlled trial for mild to moderate acne vulgaris. ...
... To our knowledge, this is the lar- moderate acne, as well as a decrease in sebum levels. 10,11 However, these past studies failed to detect a gender effect of lactoferrin in the reduction in total and comedonal lesions. This may have been due to the small sample size, resulting in underpowered subgroup analyses. ...
... In contrast, other lactoferrin products only have 80% purity. 10,11 Indeed, we were able to show a better range of percent acne reduction versus baseline in our study (32.7-36% median reduction; 22.7-39% mean reduction) compared to a noncontrolled study (20)(21)(22)(23).5% mean reduction) at 8 weeks. 11 Despite these concerns, it is worth emphasizing that randomization remains the most powerful way to control for both known and unknown confounders. ...
Article
Lactoferrin is an iron-binding milk-derived protein that has shown antibacterial and anti-inflammatory effects in vitro and in vivo. The objective of this study was to determine the efficacy and safety of lactoferrin, combined with vitamin E and zinc, for mild to moderate acne vulgaris. In this randomized, double-blind, placebo-controlled trial, 168 subjects aged 13-40 years old were randomly assigned to take either a capsule formulation containing lactoferrin with vitamin E and zinc or placebo twice a day for 3 months. The primary outcome measure was a reduction in the number of acne lesions compared to placebo. A total of 164 subjects completed the study per protocol. The lactoferrin group (n = 82) showed a significant median percent reduction in total lesions as early as 2 weeks (14.5%, P = 0.0120), with the maximum reduction occurring at week 10 (28.5%, P < 0.0001) compared to placebo group (n = 82). Maximum reduction in comedones (32.5%, P < 0.0001) and inflammatory lesions (44%, P < 0.0001) was also seen at week 10 compared to placebo. Sebum scores were improved by week 12. No adverse events were observed during the trial. A twice daily regimen of lactoferrin with vitamin E and zinc significantly reduced acne lesions in people with mild to moderate acne vulgaris.
... The milk protein most commonly used as a supplement is lactoferrin, possibly due to its broad spectrum of proven biological properties (Section 2.4.1). This has been found to induce a significant improvement in the skin condition of patients with psoriasis and acne vulgaris, including a reduction in the number of inflammatory lesions and an overall improvement in the clinical picture [90,[170][171][172]. ...
... Twice daily administration of lactoferrin (100 mg) as a dietary supplement was found to result in an overall improvement in acne lesions in patients with mild to moderate common acne [170]. Twice daily administration of capsules containing lactoferrin with vitamin E and zinc for three months was found to reduce the number of acne lesions, reduce blackheads and inflammatory changes, and better regulate sebum secretion. ...
... reduction in erythema and pruritus; softening, moisturizing, soothing, and anti-inflammatory effects [177] liposomal gel containing 20% horse colostrum ulcerative skin lesions (n = 10) improvement of skin healing and repair [177] cosmetic formulations based on a combination of horse colostrum and horse milk healthy skin antiaging, moisturizing, protective, tensio-distensive, tonic, smoothing, anti-irritant, emollient, bleaching, decongestant, and sebostatic effects [177] fermented (by lactic acid bacteria) horse colostrum atopic dermatitis (atopy and psoriasis) alleviating symptoms; moisturizing and anti-inflammatory effects [178] fermented colostrum acne improvement related to the antibacterial effect [179] formulations containing bovine or equine colostrum (plus hyaluronic acid or its salt and olive oil or vitamin E) healthy skin of elderly volunteers improvement elasticity and tension; moisturizing and antioxidant effects; reduction in skin sagging and liver spots [180] cosmetic formulation based on colostrum albumin (plus arbutin) healthy skin with discoloration whitening properties [181] Milk-based products used as supplements fermented milk enriched with lactoferrin acne vulgaris (n = 18) reduction in inflammation, sebum content, and the severity of acne lesions [90] lactoferrin mild to moderate common acne overall improvement in acne lesions [170] capsules containing lactoferrin (plus vitamin E and zinc) acne reduction in the number of acne lesions, blackheads, and inflammatory changes; regulation of sebum secretion [173] 3. ...
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Milk and colostrum have high biological potential, and due to their natural origin and non-toxicity, they have many uses in cosmetics and dermatology. Research is ongoing on their potential application in other fields of medicine, but there are still few results; most of the published ones are included in this review. These natural products are especially rich in proteins, such as casein, β-lactoglobulin, α-lactalbumin, lactoferrin, immunoglobulins, lactoperoxidase, lysozyme, and growth factors, and possess various antibacterial, antifungal, antiviral, anticancer, antioxidant, immunomodulatory properties, etc. This review describes the physico-chemical properties of milk and colostrum proteins and the natural functions they perform in the body and compares their composition between animal species (cows, goats, and sheep). The milk- and colostrum-based products can be used in dietary supplementation and for performing immunomodulatory functions; they can enhance the effects of certain drugs and can have a lethal effect on pathogenic microorganisms. Milk products are widely used in the treatment of dermatological diseases for promoting the healing of chronic wounds, hastening tissue regeneration, and the treatment of acne vulgaris or plaque psoriasis. They are also increasingly regarded as active ingredients that can improve the condition of the skin by reducing the number of acne lesions and blackheads, regulating sebum secretion, ameliorating inflammatory changes as well as bestowing a range of moisturizing, protective, toning, smoothing, anti-irritation, whitening, soothing, and antiaging effects.
... In inflammatory regions, it inhibits the release of IL-8 by endothelial cells and reduces the expression of IL-8 mRNA. Mueller4 showed that oral LF could effectively relieve mild to moderate acne symptoms but failed to fully demonstrate LF's anti-inflammatory mechanism. Therefore, in this study, in vitro experiments were used to explore the effects of LF on the generation of pro-inflammatory cytokines in HaCaT cells induced by the inactivation of P. acnes. ...
... 4 and Han14 showed lactoferrin can significantly reduced acne lesions in people with mild to moderate acne vulgaris. However, the exact anti-inflammatory mechanism of LF inF I G U R E 4 Western blot analysis shows that the inhibitory effect of LF on the inflammation induced by P. acnes in mice skin through TLR2/NF-κB signaling pathway and the protein level of downstream molecule ICAM-1 of TLR/NF-κB pathway. ...
Article
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Lactoferrin (LF) is a monomer glycoprotein in the mammalian colostrum that has multiple biological activities and a high affinity for iron ions. Not only does it have strong antibacterial activity, it also can regulate the release of cytokines in inflammatory areas, activate immune cells, and inhibit inflammatory diseases caused by non‐pathogenic bacteria and the development of tumors. However, the anti‐inflammatory mechanism of LF in inflammatory skin diseases induced by Propionibacterium acnes (P. acnes) has not been elucidated in vitro and in vivo. In this study, we investigated the effects of LF on the generation of inflammatory cytokines in HaCaT cells induced by heat‐killed P. acnes. The expression of pro‐inflammatory cytokines IL‐8 increased after induction of HaCaT by heat‐killed P. acnes, but it decreased significantly after LF treatment. Western blotting was used to examine the levels of TLR2, nuclear factor (NF) κB and intercellular cell adhesion molecule 1 protein induced by P. acnes in HaCaT cells, and the results showed that the levels were inhibited by LF. In addition, activated P. acnes (1 × 107 CFU/mL) was injected into the ears of experimental mice, which induced inflammation 24 hours after the injection. However, immunohistochemical analysis showed a significant reduction in the inflammatory response after LF treatment in the right ear relative to the untreated left ear, and the same result was seen with western blotting. In summary, this study revealed the treatment effect of LF on P. acnes‐induced inflammation, thus providing support for the anti‐acne properties of LF.
... A few studies have reported that some of the patients with acne had acceptable therapeutic response with a reduction of acne lesions with use of LF in mild and moderate acne cases [9][10][11]. However, no studies have directly assessed serum LF level in patients with acne. ...
... Chan et al. [11] showed that daily intake of LF with vitamin E and zinc can significantly reduce acne lesions in patients with mild to moderate AV. Moreover, Mueller et al. [9] showed a statistically significant decrease in the mean noninflammatory and mean total lesion count from baseline with oral LF supplementation 100 mg twice daily for 8 weeks. Another study by Kim et al. [10] showed that intake of LF-enriched fermented milk resulted in significant reduction in inflammatory lesion, and acne grade, as compared with the placebo group. ...
Article
Background Acne vulgaris (AV) is a chronic inflammatory disease of the pilosebaceous units. Lactoferrin (LF) is an iron-binding glycoprotein, which is known to have a role in decreasing inflammation and microbial infection. A few studies have reported that many of the patients with acne had acceptable therapeutic response to LF supplementation. However, no studies have directly assessed serum LF level in patients with acne. Objective To evaluate serum LF level in patients with severe versus mild acne in comparison with healthy controls. Patients and methods Serum LF was assessed using enzyme-linked immunosorbent assay in 40 AV patients comprising two subgroups; 20 mild and 20 severe cases, versus 20 healthy controls. Levels were correlated with disease duration. Results Mean serum LF levels were significantly higher in patients with AV than in healthy controls (P
... Lactoferrin (100 mg) has a beneficial effect both in combination with vitamin E (11 IU as alpha-tocopherol) and zinc (5 mg as zinc gluconate), taken twice daily [6], as well as alone as 100 mg of lactoferrin-enriched (80%) whey milk protein powder, twice a day [13] and in the amount of 200 mg of lactoferrin alone-as described above [14]. ...
Article
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Acne vulgaris (AV) is a chronic disease that affects a significant percentage of the world’s population. Its development is influenced by both external and internal factors. The purpose of this review is to demonstrate the effect of basic nutrient intake on the exacerbation or alleviation of AV lesions. A retrospective review of publications in PubMed regarding diet therapy and the impact of individual nutrient intake on the skin condition of patients was conducted. Ingestion of products with a high glycaemic index may indirectly lead to sebum overproduction, which promotes infection with Cutibacterium acnes and causes inflammation. Consumption of certain dairy products may result in skin deterioration caused by the presence of hormones in these products, i.e., progesterone and testosterone precursors. The beneficial effect of fatty acids on the skin is manifested by the reduction in inflammation. Of significance in AV treatment are vitamins A, C, D, E and B, as well as mineral elements zinc and selenium. Proper nutrition may not only prevent or alleviate AV but also increase treatment efficacy.
... In previous clinical trials, the effects of LF on skin illnesses were reported; 2,7,9,12,13,16 however, this is the first report suggesting the positive effects of LF on skin conditions in health subjects. ...
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Hirotsugu Oda,1 Momoko Miyakawa,1 Masaru Mizuki,2 Yuka Misawa,3 Teruomi Tsukahara,2 Miyuki Tanaka,1 Koji Yamauchi,1 Fumiaki Abe,1 Tetsuo Nomiyama2 1Food Ingredients and Technology Institute, R&D Division, Morinaga Milk Industry Co., Ltd, Zama, Kanagawa 252-8583, Japan; 2Department of Preventive Medicine and Public Health, Shinshu University School of Medicine, Matsumoto, Nagano 390-8621, Japan; 3Department of Rehabilitation, Nagano Children’s Hospital, Nagano 399-8288, JapanCorrespondence: Hirotsugu OdaFood Ingredients and Technology Institute, R&D Division, Morinaga Milk Industry Co., Ltd., 5-1-83, Zama, Kanagawa 252-8583, JapanTel +81 46 252 3045Fax +81 46 252 3017Email h-oda@morinagamilk.co.jpObjective: To investigate the effects of lactoferrin (LF) on subjective skin conditions in winter.Design: A preliminary, randomized, double-blinded, placebo-controlled trial.Setting and subjects: Healthy adults in Japan.Interventions: Intake of placebo, 200 mg, or 600 mg of LF for 12 weeks in winter.Endpoints: Changes in the scores of subjective skin conditions.Results: Three hundred and forty-six subjects were randomized. Nine subjects (placebo, n=0; 200 mg, n=5; 600 mg, n=4) withdrew consent, and 7 subjects (placebo, n=4; 200 mg, n=2; 600 mg, n=1) were lost to follow-up, resulting in 330 for a full analysis set.Outcomes: Changes in the scores of moisture were greater in the 600 mg group than in the placebo group. Changes in the scores of moisture were greater in the 200 mg and 600 mg groups, and of texture were greater in the 600 mg group than in the placebo group in female subjects.Conclusion: Intake of LF may improve moisture or texture of skin in winter.Keywords: lactoferrin, winter, skin, moisture, texture
... 8 LF is present in myriad mucosal fluids, [9][10][11][12][13] but is most predominant in human milk, particularly in the colostrum during early lactation, where it has been suggested to promote the healthy growth and development of the gastrointestinal [GI] tract, 14 promote the growth of commensal bacteria, and deter the establishment of pathogenic bacteria and viruses. [15][16][17] LF has been previously used for its beneficial effects in several models of human health including dermal inflammation, 18,19 wound healing, 20 and infectious diseases. 19,21,22 Preclinical studies have shown the protective effects of orally administered human LF [hLF] in mice 23 and bovine LF [bLF] in rats in chemically induced models of colitis. ...
Article
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Background and aims: Inflammatory bowel disease (IBD) is characterized by a disruption of immune homeostasis, which is tightly regulated to protect against harmful pathogens yet not react to commensal antigens. Animal studies indicate that regulatory T cells (Treg) modulate the immune response to prevent IBD development. Lactoferrin (LF), is an endogenous anti-inflammatory pleiotropic protein secreted at high concentrations in colostrum and at mucosal sites. However, the effect of LF on specific T lymphocyte populations has not been studied. Here, we identify a novel mechanism by which a recombinant human LF, VEN-120, regulates T cell populations in health and disease. Methods: Two murine models of intestinal inflammation, the Dextran sodium sulfate colitis model and the TNFΔARE/+ model of ileitis were used to study the anti-inflammatory and T cell modulating ability of VEN-120. Flow cytometry was used to evaluate T cell populations within the lamina propria and mesenteric lymph nodes, and to evaluate the effect of VEN-120 on CD4+ T cells in vitro. Results: VEN-120 reduced inflammation in both models of IBD, accompanied by increased Tregs in the intestinal lamina propria. Treatment of CD4+ T cells in vitro resulted in an upregulation of Treg genes and skewing towards a Treg population. This in vitro T cell skewing translated to an increase of Treg homing to the intestinal lamina propria and associated lymph tissue in healthy mice. Conclusions: These data provide a novel immunological mechanism by which VEN-120 modulates T cells to restrict inflammatory T cell-driven disease.
... It is a multifunctional protein involved in a wide range of activities, such as immunomodulation and promotion of cell proliferation (Vogel 2012). The effects of Lf on skin include promotion of wound healing (Takayama and Aoki 2012), improvement of inflammatory lesions of acne vulgaris (Kim et al. 2010;Mueller et al. 2011), up-regulation of the proliferation of dermal fibroblasts and keratinocytes (Engelmayer et al. 2008;Tang et al. 2010), and attenuation of UV-induced photo damage (Murata et al. 2014). Lf is known to penetrate skin (Ishii et al. 2012) and has high water solubility. ...
Article
Lactoferrin (Lf) is an iron-binding multifunctional protein, mainly present in external secretions. Lf is known to penetrate skin and may thus exert its multiple functions in skin. Sophorolipids (SLs) are glycolipid biosurfactants, which have been shown to enhance absorption of commercial bovine Lf (CbLf) in model skin via forming an assembly with CbLf. In this study, uptake and post-internalization localization of bovine Lf (bLf), CbLf, and human Lf (hLf) with or without forming assemblies with SLs in human dermal fibroblasts (HDFn) were determined using (125)I-labeled Lfs and confocal microscopy, respectively. Our results show that all 3 Lfs were internalized by HDFn; although SLs did not significantly affect the uptake of Lfs, it changed Lf localization by accumulating Lfs in the perinuclear region. Furthermore, microarrays were used to investigate transcriptional profiling in HDFn in response to CbLf, SLs, or CbLf-SLs-assembly treatments. Transcriptome profiling indicates that CbLf may play roles in the protection of skin from oxidative stress, immunomodulatory activities, and enhancement of wound healing. The assembly had similar effects but dramatically modulated the transcription of some genes. SLs alone modified signaling pathways related to lipid metabolism, as well as synthesis of sex hormones and vitamins. Thus, CbLf may exert beneficial effects on skin, and these effects may be modulated by SLs.
... Lactoferrin might be a good candidate for antimicrobial drug development (such as hLF1-11), because it kills almost all microbes very efficiently, has anti-inflammatory properties, and is safe in humans [15,42]. It has been found useful in acne given orally [17,24], but its mechanism of action is not understood. ...
Article
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In acne vulgaris, antimicrobial peptides (AMPs) could play a dual role; i.e., protective by acting against Propionibacterium acnes, pro-inflammatory by acting as signalling molecules. The cutaneous expression of 15 different AMPs was investigated in acne patients; furthermore, the impact of isotretinoin therapy on AMP expression was analysed in skin biopsies from 13 patients with acne vulgaris taken before, during and after a 6-month treatment cycle with isotretinoin using quantitative real-time polymerase chain reaction. Cutaneous expression of the AMPs cathelicidin, human β-defensin-2 (HBD-2), lactoferrin, lysozyme, psoriasin (S100A7), koebnerisin (S100A15), and RNase 7 was upregulated in untreated acne vulgaris, whereas α-defensin-1 (HNP-1) was downregulated compared to controls. While relative expression levels of cathelicidin, HBD-2, lactoferrin, psoriasin (S100A7), and koebnerisin (S100A15) decreased during isotretinoin treatment, only those of cathelicidin and koebnerisin returned to normal after 6 months of isotretinoin therapy. The increased expression of lysozyme and RNase 7 remained unaffected by isotretinoin treatment. The levels of granulysin, RANTES (CCL5), perforin, CXCL9, substance P, chromogranin B, and dermcidin were not regulated in untreated acne patients and isotretinoin had no effect on these AMPs. In conclusion, the expression of various AMPs is altered in acne vulgaris. Isotretinoin therapy normalizes the cutaneous production of distinct AMPs while the expression of others is still increased in healing acne. Considering the antimicrobial and pro-inflammatory role of AMPs, these molecules could serve as specific targets for acne therapy and maintenance of clinical remission.
... Skuteczność LF w leczeniu trądziku pospolitego potwierdziła także najnowsza próba kliniczna (n=39), w której młodym osobom podawano BLF (100 mg/dzień) w postaci tabletek do ssania. Stwierdzono redukcję ogólnej liczby zmian i zmian zapalnych, nie badano jednak innych parametrów, w tym dotyczących gospodarki lipidowej skóry [50]. ...
Obesity, dyslipidemia, hyperglycemia/type II diabetes and hypertension together constitute the so-called metabolic syndrome. Frequency of occurrence of these serious metabolic disturbances is associated with life style and is on the rise in prosperous industrialized countries. These diseases represent not only a serious health problem but also social and economic ones, and involve in prophylaxis and treatment various specialists (physicians, dieticians and psychologists). For about two decades research has been conducted on the possibility to apply milk-derived proteins in prevention and treatment of the above mentioned metabolic diseases. Lactoferrin (LF), a protein present in milk and excretory fluids of mammals, is one of the most intensively studied milk proteins for therapeutic application. Initial trials revealing an advantageous effect of LF on lipid metabolism and obesity enrolled only a few volunteers and were performed in Japan in 2003. Subsequent trials were conducted on animals as well as in clinics, and the positive results were supported by in vitro tests. After oral administration of LF, decreases of body weight, waist measurement, visceral fat tissue, plasma and liver fatty acid concentrations, triglycerides and cholesterol were registered. The mechanism of LF action may involve several processes, such as inhibition of adipogenesis, decrease of dietary triglyceride absorption, elevation of HDL cholesterol possessing anti-atherogenic properties, inhibition of accumulation of oxidized LDL cholesterol forms in macrophages and protection against formation of foam cells. LF also increases the susceptibility of cells to insulin action, including in conditions when the response to insulin is lowered (during inflammation). In addition, LF regulates activity of insulin-like growth factor (IGF). The data collected to date indicate that LF is a promising, completely nontoxic, natural remedy which (as for example a food supplement) may be applied in long-term prophylaxis and therapy of metabolic disturbances, such as dyslipidemia, obesity and insulin resistance/type II diabetes.
Article
Background: Adult Female acne (AFA) nowadays is a very common skin condition affecting mainly women aged between 25 - 40. The treatment of AFA could be challenging. Study aim: We evaluate and compare the efficacy and tolerability of a cream formulation containing two retinoid molecules (hydroxypinacolone/retinyl palmitate) combined with Iris Florentina root extract and a complex of three oligopeptides (C) applied twice a day (morning and evening) alone or in combination (C+O) with a food supplement containing a mixture of prebiotic molecules (FOS&GOS) zinc, lactoferrin and niacinamide. Subjects and methods: In a multicentre, randomized, assessor-blinded, 12-week trial we assessed the efficacy of these two regimens in the evolution of AFA lesions (non-inflammatory: NI-L; inflammatory: IL; and total number of lesions: TL). Additional efficacy endpoints were the evolution of the 6-point (from 0 to 5) GEA and Adult Female Acne Scoring Tool (AFAST) scores. Results: One hundred and eighty-four women (mean age 32±6 years) with AFA agreed to participate after obtaining informed consent. They were randomised (2:1) to the topical product (n=123) (Group C) or to the combination (n=61) (Group C+O) treatment. All enrolled patients concluded the trial with no drop-out. At baseline NI-L, IL and TL acne lesions count were 15±9, 9±5, and 24±14 in the Group C and 19±8, 9±4, and 29±10 in Group C+O. In comparison with the number of the acne lesions at the baseline, both treatment regimens induced a significant reduction (p=0.0001, ANOVA test) at week 12 in NI-L, IL, and TL by -54%, -63% and -59% in Group C and by -55%, -73% and -61% in the Group C+O, respectively. At week 12 the absolute IL count reduction vs. baseline was significantly (p=0.0158) greater in Group C+O (-7.0) in comparison with Group C (-5.5). The GEA absolute score reduction in Group C+O group was significantly greater in comparison with Group C (-1.5 vs. -1.1; p=0.0097). In the Group C+O a greater percentage of success treatment (defined as a GEA score of 0/1 at week 12) was observed in comparison with Group C (39% vs. 27%; p=0.06). AFAST score at baseline was 2.4±0.5 in group C and 2.8±0.6 in group C+O. AFAST score was reduced by 21% and by 51% after 6 and 12 weeks of treatment in group C and by 22% and 55% in group C+O, respectively. Both treatment regimens were well tolerated. Not relevant adverse events were recorded. Conclusion: A cream containing retinoids molecules and Iris Florentina root extract is effective and well tolerated in the management of AFA. The treatment combination with a prebiotic and anti-inflammatory food supplement offers an additional clinical benefit mainly in reducing inflammatory lesions and improving the severity acne score.
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Background: Lactoferrin (LF)is an innate-defence non-heme iron binding glycoprotein of 80 kDa able to support the immune system and influence immune cell activity by antioxidant, antibacterial and antiviral properties. This work focusses on the study of the in vitro anti-inflammatory activity of Bovine LF(bLF)on Lipopolysaccharide (LPS)-induced cytokines expression. Methods: We investigated the immunomodulatory effect of bLF on tumor necrosis factor alpha (TNF-α), interleukin-10 (IL-10) and interleukin-12 (IL-12) cytokines on human keratinocytes NCTC2544 and human myelomonocytic leukaemia cells, THP-1. Results: Bovine LF exerted an anti-inflammatory activity since early phase to 8h of treatment, by modulating cytokines expression and secretion. Conclusions: These data encourage the use of bLF as immunomodulatory agent in the treatment of different dermatological conditions linked to inflammatory processes.
Article
Lactoferrin is a glycoprotein widely present in mammalian secretions and possesses documented protective effects, including antimicrobial and anti-inflammatory properties. While its therapeutic use is being investigated for a myriad of diseases, there is increasing interest in its application for skin disease. Our objective was to systematically review the clinical evidence for the use and efficacy of lactoferrin for the treatment of dermatological conditions. Pubmed and Embase databases were searched for clinical studies evaluating lactoferrin for dermatological conditions. A total of 6 studies were reviewed. Of the current clinical trials, there is encouraging evidence to suggest that lactoferrin may be beneficial in acne, psoriasis, and diabetic ulcerations. Although the current evidence is promising, further research is necessary to establish lactoferrin as complementary therapy in the clinical setting.
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Introduction: Current acne treatment guidelines, as well as, treatment efficacy, safety, tolerability and patient preferences must all be considered in determining appropriate treatment regimes. Literature can assist physicians' evidence-based recommendations according to these factors. Areas covered: To determine the current and future direction of pharmacotherapy for treatment of acne, a PubMed search was conducted to identify all clinical trials involving the treatment of acne from 2009 to 2012. A total of 65 publications met inclusion criteria and were reviewed. Literature was heavily focused on the efficacy and tolerability of topical combination therapies and supported their use compared with monotherapy. A few studies on topical antiandrogens and antioxidants showed an alternative approach to targeting acne. Studies on oral monotherapy provided some evidence for the use of pulsed azithromycin for acne in adolescents. Literature also supports the use of low-dose isotretinoin for moderate acne, which was comparable in efficacy to high-dose regimes and better tolerated. Expert opinion: Combination acne therapy, whether it be combination topical therapy or combination oral and topical therapy, is well supported by recent studies. Given the multifactorial pathogenesis of acne and the hurdles of adherence to treatment, we anticipate greater development of and reliance on combination acne products in the future.
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Accumulative evidence supports the role of nutritional factors in acne. I report here 5 healthy male adult patients developing acne after the consumption of whey protein, a favorite supplement of those engaged in bodybuilding. These observations are in line with biochemical and epidemiological data supporting the effects of milk and dairy products as enhancers of insulin/insulin-like growth factor 1 signaling and acne aggravation. Further prospective studies are required to determine the possible role of dietary supplements in the fitness and bodybuilding environment.
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Acne vulgaris is a common dermatological condition characterized by hormonally-mediated sebum overproduction, follicular hyperkeratinization, and chronic inflammation of the pilosebaceous unit. Microbes, genetic susceptibilities, and various environmental factors have been linked to the pathogenesis of the condition. Over the last several years it has become apparent that patients with acne are under increased cutaneous and systemic oxidative stress. Moreover, the burden of oxidative stress may not be a mere consequence of acne; rather, the oxidative stress, lipid peroxidation in particular, may be an early event that helps to drive the acne process. Here, we explore the role of oxidative stress and review the preliminary research involving the administration of local and systemic antioxidants.
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Numerous studies were published over the last 50 years to investigate whether diet is associated with the etiology of acne. Although older studies well known by dermatologists that refute the association between acne and diet exist, their scientific foundation is weak. New articles have recently brought to light evidence contrary to previous findings. Therefore, we would like to investigate whether diet, directly or indirectly, influences one or more of the four fundamental etiopathogenic pillars of acne: (1) hyperproliferation of basal keratinocytes, (2) increase of sebaceous production, (3) colonization by Propionibacterium acnes, and (4) inflammation.
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Acne vulgaris is a common skin condition, one that is associated with significant psychological disability. The psychological impairments in acne include higher rates of depression, anxiety, anger and suicidal thoughts. Despite a paucity of clinical research, patients with skin conditions and/or mental health disorders are frequent consumers of dietary supplements. An overlap may exist between nutrients that potentially have both anti-acne and mood regulating properties; examples include omega-3 fatty acids from fish oil, chromium, zinc and selenium. Here we report on five cases of acne treated with eicosapentaenoic acid and antioxidant nutrients. Self-administration of these nutrients may have improved inflammatory acne lesions and global aspects of well-being; the observations suggest a need for controlled trials.
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Earlier studies revealed that oral administration of lactoferrin (LF), a multi-functional milk protein, facilitated curing of dermatophytosis in guinea-pigs and man by an unknown mechanism. The present study aimed to assess the effect of feeding bovine LF on the host antifungal defence systems in guinea-pigs infected or immunised with Trichophyton mentagrophytes, a dermatophytosis-causing fungus. The unbound iron-binding capacity (UIBC) of the plasma of individual animals varied, and plasma with higher UIBC inhibited growth of T. mentagrophytes in vitro. However, LF administration did not enhance plasma UIBC or the anti-T. mentagrophytes activity of plasma in infected or uninfected animals. Phagocytic activity and reactive oxygen (RO) production of blood neutrophil polymorphonuclear leucocytes (PMNLs) were estimated by flow cytometry. LF administration caused no significant effects on phagocytic activity or RO production of neutrophil PMNLs in infected or uninfected animals. The functions of mononuclear cells (MNC) from the spleen were investigated in guinea-pigs immunised with heat-killed T. mentagrophytes conidia. The MNC were cultured with concanavalin A or inactivated T. mentagrophytes. In the bromo-deoxyuridine incorporation assay, the stimulation index was higher for MNC derived from LF-treated animals than for those from control animals. The culture supernates of MNC enhanced the ability of macrophages to kill T. mentagrophytes conidia. Furthermore, stronger augmentation was observed with the culture supernate from LF-treated animals than with that from control animals. In conclusion, LF feeding may potentiate the host antifungal defence systems by modulating MNC function rather than plasma antifungal activity or peripheral blood neutrophil PMNL activity.
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Whey is a natural by-product of cheese making process. Bovine milk has about 3.5% protein, 80% of which are caseins and the remaining 20% are whey proteins. Whey proteins contain all the essential amino acids and have the highest protein quality rating among other proteins. Advances in processing technologies have led to the industrial production of different products with varying protein contents from liquid whey. These products have different biological activities and functional properties. Also recent advances in processing technologies have expanded the commercial use of whey proteins and their products. As a result, whey proteins are used as common ingredients in various products including infant formulas, specialized enteral and clinical protein supplements, sports nutrition products, products specific to weight management and mood control. This brief review intends to focus on scientific evidence and recent findings related to the therapeutic potential of whey proteins and peptides.
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Lactoferrin has long been recognized for its antimicrobial properties, initially attributed primarily to iron sequestration. It has since become apparent that interaction between the host and bacteria is modulated by a complex series of interactions between lactoferrin and bacteria, lactoferrin and bacterial products, and lactoferrin and host cells. The primary focus of this review is the interaction between lactoferrin and bacteria, but interactions with the lactoferrin-derived cationic peptide lactoferricin will also be discussed. We will summarize what is currently known about the interaction between lactoferrin (or lactoferricin) and surface or secreted bacterial components, comment on the potential physiological relevance of the findings, and identify key questions that remain unanswered.
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Milk and colostrum are rich in proteins and peptides which play a crucial role in development of the immune system in mammalian offspring. Immunotropic properties of these compounds prompted investigators to search for their utility in prevention and therapy of various disorders in humans. The following constituents of milk are of particular interest: 1) Lactoferrin (LF)--exhibits antibacterial, antifungal, antiviral, antiparasite and antitumor activities. It is protective with regard to intestinal epithelium, promotes bone growth and accelerates recovery of the immune system function in immunocompromised animal; 2) A Proline-Rich Polypeptide (PRP) shows a variety of immunotropic functions, including promotion of T-cell maturation and inhibition'of autoimmune disorders. PRP was recently found to improve or stabilize the Instrumental Activity of Daily Living status in Alzheimer's disease patients. 3) Casein--has been protective in experimental bacteremia by eliciting myelopoiesis. Casein hydrolyzates were also protective in diabetic animals, reduced the tumor growth and diminished colicky symptoms in infants. Casein-derived peptides have been found to have antihypertensive effects. Glycomacropeptide (GMP)--a peptide derived from kappa casein, exhibits antibacterial and antithrombotic activities. 4) Alpha lactalbumin (LA)--demonstrates antiviral, antitumor 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. 5) Lysozyme--is effective in treatment of periodentitis and prevention of tooth decay. Milk enriched in lysozyme was used in feeding premature infants suffering from concomitant diseases. 6) Lactoperoxidase--shows antibacterial properties. In conclusion, milk-derived proteins and peptides are bio-accessible and safe for the prevention and treatment of numerous disorders in humans.
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Lactoferrin (Lf), a natural defence iron-binding protein, is present in exocrine secretions that are commonly exposed to normal flora: milk, tears, nasal exudate, saliva, bronchial mucus, gastrointestinal fluids, cervicovaginal mucus and seminal fluid. Additionally, Lf is produced in polymorphonuclear leukocytes and is deposited by these circulating cells in septic sites. A principal function of Lf is that of scavenging non-protein-bound iron in body fluids and inflamed areas so as to suppress free radical-mediated damage and decrease accessibility of the metal to invading bacterial, fungal and neoplastic cells. Adequate sources of bovine and recombinant human Lf are now available for development of commercial applications. Among the latter are use of Lf in food preservation, fish farming, infant milk formula and oral hygiene. other readily accessible body compartments for Lf administration include skin, throat and small intestine. Further research is needed for possible medicinal use in colon and systemic tissues. Although Lf is a natural product and should be highly biocompatible, possible hazards have been documented.
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Acne is a multifactorial inflammatory disease affecting pilosebaceous follicles. The initial event in the development of an acne lesion is abnormal desquamation of the keratinocytes that line the sebaceous follicle, which creates a microplug or microcomedo, An increase in circulating androgens at the onset of puberty stimulates the production of sebum in to the pilosebaceous unit. These events combine to create an environment within the pilosebaceous unit that is favorable for the colonization of the commensal bacteria, Propionibacterium acnes. With proliferation, P acnes secretes various inflammatory molecules and chemotactic factors that initiate and perpetuate the local inflammatory response and possibly induce keratinocyte hyperproliferation as well.
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Human lactoferrin (hLF), a member of the transferrin family, is known for its antimicrobial and anti-inflammatory effects. Recent studies on various nonskin cell lines indicate that hLF may have a stimulatory effect on cell proliferation. To study the potential role of hLF in wound re-epithelialization. The effects of hLF on cell growth, migration, attachment and survival were assessed, with a rice-derived recombinant hLF (holo-rhLF), using proliferation analysis, scratch migration assay, calcein-AM/propidium iodide staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) method, respectively. The mechanisms of hLF on cell proliferation and migration were explored using specific pathway inhibitors. The involvement of lactoferrin receptor low-density lipoprotein receptor-related protein 1 (LRP1) was examined with RNA interference technique. An in vivo swine second-degree burn wound model was also used to assess wound re-epithelialization. Studies revealed that holo-rhLF significantly stimulated keratinocyte proliferation which could be blocked by mitogen-activated protein kinase (MAPK) kinase 1 inhibitor. Holo-rhLF also showed strong promoting effects on keratinocyte migration, which could be blocked by either inhibition of the MAPK, Src and Rho/ROCK pathways, or downregulation of the LRP1 receptor. With cells under starving or 12-O-tetradecanoylphorbol-13-acetate exposure, the addition of holo-rhLF was found greatly to increase cell viability and inhibit cell apoptosis. Additionally, holo-rhLF significantly increased the rate of wound re-epithelialization in swine second-degree burn wounds. Our studies demonstrate the direct effects of holo-rhLF on wound re-epithelialization including the enhancement of keratinocyte proliferation and migration as well as the protection of cells from apoptosis. The data strongly indicate its potential therapeutic applications in wound healing.
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Lactoferrin (LF) is a member of the transferrin family that is expressed and secreted by glandular epithelial cells and is found in the secondary granules of neutrophils. Originally viewed as an iron-binding protein in milk, with bacteriostatic properties, it is becoming increasingly evident that LF is a multifunctional protein to which several physiological roles have been attributed. These include regulation of iron homeostasis, host defense against a broad range of microbial infections, anti-inflammatory activity, regulation of cellular growth and differentiation and protection against cancer development and metastasis. While iron binding is likely central to some of the biological roles of LF, other activities, including specific interactions with mammalian receptors and microbial components, also contribute to the pleoitropic functional nature of this protein. In this article, recent advances in the understanding of these functions at the cellular and molecular level are discussed.
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Lactoferrin, a whey milk protein after removing precipitated casein, has a prominent activity against inflammation in vitro and systemic effects on various inflammatory diseases have been suggested. The objective was to determine dietary effects of lactoferrin-enriched fermented milk on patients with acne vulgaris, an inflammatory skin condition. Patients 18 to 30 y of age were randomly assigned to ingest fermented milk with 200 mg of lactoferrin daily (n = 18, lactoferrin group) or fermented milk only (n = 18, placebo group) in a 12-wk, double-blind, placebo-controlled study. Acne lesion counts and grade were assessed at monthly visits. The condition of the skin by hydration, sebum and pH, and skin surface lipids was assessed at baseline and 12 wk. Acne showed improvement in the lactoferrin group by significant decreases in inflammatory lesion count by 38.6%, total lesion count by 23.1%, and acne grade by 20.3% compared with the placebo group at 12 wk. Furthermore, sebum content in the lactoferrin group was decreased by 31.1% compared with the placebo group. The amount of total skin surface lipids decreased in both groups. However, of the major lipids, amounts of triacylglycerols and free fatty acids decreased in the lactoferrin group, whereas the amount of free fatty acids decreased only in the placebo group. The decreased amount of triacylglycerols in the lactoferrin group was significantly correlated with decreases in serum content, acne lesion counts, and acne grade. No alterations in skin hydration or pH were noted in either group. Lactoferrin-enriched fermented milk ameliorates acne vulgaris with a selective decrease of triacylglycerols in skin surface lipids.
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Historically, the relationship between diet and acne has been highly controversial. Before the 1960s, certain foods were thought to exacerbate acne. However, subsequent studies dispelled these alleged associations as myth for almost half a century. Several studies during the last decade have prompted dermatologists to revisit the potential link between diet and acne. This article critically reviews the literature and discusses how dermatologists might address diet when counseling patients with acne. Dermatologists can no longer dismiss the association between diet and acne. Compelling evidence exists that high glycemic load diets may exacerbate acne. Dairy ingestion appears to be weakly associated with acne, and the roles of omega-3 fatty acids, antioxidants, zinc, vitamin A, and dietary fiber remain to be elucidated. This study was limited by the lack of randomized controlled trials in the literature. We hope that this review will encourage others to explore the effects of diet on acne.
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A survey of 1066 healthy women and 1089 healthy men aged 18-70 years, performed to determine the prevalence of facial acne, showed that clinical acne was not confined to adolescents. Though it was more prevalent among men than women at 18, beyond the age of 23 clinical acne was more prevalent among women as the prevalence in men gradually declined. At 40-49 years 3% of men and 5% of women still had definite, albeit mild, clinical acne, and at 50-59 years 6% of men and 8% of women had physiological acne. The surprisingly high prevalence of acne in adults may be related to antibiotic treatment or, in women, to the use of oral contraceptives or cosmetics, though this survey did not study their influence. Further studies in different populations are needed to establish the prevalence of acne in the community, and its distribution.
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Development of irritant contact reactions in a wash test, in a repeated open application test (ROAT) and in chamber tests were compared with each other in 14 atopic and 14 non-atopic Caucasian medical students. In the wash test, the students washed their upper arm skin with 10% dishwashing liquid for 1 min 2 x a day for 1 week. In the ROAT, they applied the same detergent solution to 1 antecubital fossa 2 x daily for 1 week. Chamber tests were performed with the same detergent using 8 mm, 12 mm and 18 mm Finn Chambers applied to the upper back skin for 48 h. Additional 4 h and 24 h occlusion times were used with the 12 mm Finn Chambers. Test results were evaluated on days 0, 2, 4 and 7 by eye and by using an Evaporimeter EP1 for transepidermal water loss and a Minolta Chroma Meter CR-200 for skin colour. No statistically significant differences between atopics and non-atopics were found in any of the tests. The results of the tests did not correlate with each other, with the exception of the 12 mm/48 h chamber test and the wash test in atopics (R = 0.61, p = 0.02). It seems that other individual factors in addition to atopy influence the development of irritant contact dermatitis. The results of the chamber test and ROAT predicted poorly the result of the wash test.
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Human or bovine lactoferrin (LF) and lactoferricin (LFcin), a peptide derived from the N-terminal region of LF, each have the ability to stimulate the release of neutrophil-activating polypeptide interleukin 8 (IL-8) from human polymorphonuclear leukocytes (neutrophils, PMNs). This finding suggests that LF and LFcin may both function as immunomediators for activating the host defense system. A basic peptide, protamine, exerted the same effect as that of LF and LFcin, suggesting the importance of the basic nature of LF and LFcin in acting as an inducer of IL-8 release from PMNs.
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Acne vulgaris, or acne, as it is generally called, is the most common skin disease, affecting nearly 80 percent of persons at some time between the ages of 11 and 30 years.1 It can persist for years and result in disfigurement and permanent scarring, and it can have serious adverse effects on psychosocial development, resulting in emotional problems, withdrawal from society, and depression.2 The pathogenesis of acne is multifactorial, and therapy can now be directed at many of these factors. This review summarizes current concepts of the rational treatment of acne vulgaris. Pathophysiology of Acne Acne vulgaris is the result . . .
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Adapalene is a new chemical entity that exhibits tretinoin-like activities in the terminal differentiation process. We evaluated a dose range effect of two concentrations of adapalene gel as acne treatment and compared adapalene 0.1% gel with tretinoin 0.025% gel in the treatment of acne patients in two large multicenter studies. Multicenter, investigator-masked, parallel group studies including 89 acne patients in the dose range study and 591 patients in the concurrent controlled studies were conducted. Adapalene gel 0.1% was significantly more effective in treating acne lesions than 0.03% adapalene gel. Adapalene gel 0.1% was significantly more effective than 0.025% or tretinoin gel in one study and of the same effectiveness in the other study. Adapalene gel was always better tolerated than tretinoin gel. Adapalene 0.1% gel is a safe and effective treatment of acne vulgaris.
Article
To investigate the effect of a triphasic low-dose oral contraceptive pill containing gestodene on acne severity and hormone levels in young women over 13 menstrual cycles. A total of 33 subjects aged 16-25 years with moderate facial acne were enrolled in the study. The primary efficacy end-points used in the clinical assessment of acne were the overall severity and number of lesions, sebum secretion and superficial follicular biopsy. Both physicians and patients evaluated acne status. Blood levels of sex hormone binding globulin (SHBG), estradiol, progesterone and androgens were monitored. By cycle 13, the total lesion count had been reduced by 80%. Physicians and patients assessed acne status in 90% and 95% of cases, respectively, as better or much better (p < 0.001). At the end of the study, SHBG levels had increased by 229% and total and free testosterone levels had decreased by 41% and 70%, respectively. An oral contraceptive containing triphasic gestodene has a beneficial effect on the severity ofacne, decreases major circulating androgen levels and is well tolerated.
Article
Lactoferrin is a multifunctional member of the transferrin family of nonheme iron-binding glycoproteins. Lactoferrin is found at the mucosal surface where it functions as a prominent component of the first line of host defense against infection and inflammation. The protein is also an abundant component of the specific granules of neutrophils and can be released into the serum upon neutrophil degranulation. While the iron-binding properties were originally believed to be solely responsible for the host defense properties ascribed to lactoferrin, it is now known that other mechanisms contribute to the broad spectrum anti-infective and anti-inflammatory roles of this protein. In this article, current information on the functions and mechanism of action of lactoferrin are reviewed, with particular emphasis on the activities that contribute to this protein's role in host defense. In addition, studies demonstrating that lactoferrin inhibits allergen-induced skin inflammation in both mice and humans, most likely secondary to TNF-alpha (tumor necrosis factor alpha) production, are summarized. Collectively, these results suggest that lactoferrin functions as a key component of mammalian host defense at the mucosal surface.
Article
Acne vulgaris is a distressing condition related to the pilo sebaceous follicle and which is considered as an ‘adolescent’ disorder. It is characterized by spontaneous resolution in the late teens or early twenties in the majority of cases. The first publication about the epidemiology of acne was in 1931 by Bloch [1]. Already at this time, the onset of acne was noted slightly earlier in girls (12.1 ± 1.5) compared to boys (12.8 ± 1.7 years), retentional lesions being the earliest lesions (13&percnt; at 6 years and 32&percnt; at 7 years of age). Since this publication, no significant evolution has been noted concerning the age of onset of acne. According to different studies of the literature performed in different countries in the world, the mean onset of acne is 11 years in girls and 12 years in boys, remaining earlier in girls (1 or 2 years) with mainly retentional lesions (open and closed comedones). However, adult acne has also been described recently.
Article
Oral administration of lactoferrin (LF), an innate-defense protein present in exocrine secretions such as milk and in neutrophils, is reported to improve host-protection against infections with microorganisms including pathogenic fungi, possibly due to an immunomodulatory effect. This study aimed to evaluate the effect of bovine LF feeding on peritoneal macrophage activities in mice intraperitoneally injected with inactivated Candida albicans. Time course analysis during the 14 days following Candida-priming revealed that LF administration slightly increased the number of peritoneal exudate cells, and significantly enhanced the production of superoxide anion (O2(-)) and nitric oxide (NO) by peritoneal macrophages at day 7. LF administration facilitated NO production and Candida hyphal-growth inhibition by macrophages derived from Candida-primed mice but not non-primed mice, suggesting that the action of LF is dependent on the immune status of the host. LF administration altered the kinetics of cytokines in the peritoneal lavage fluid of Candida-primed mice. Enhancement of cytokine levels by LF was observed for IL-12 at day 5 and IFN-gamma at day 9, but not for TNF-alpha or IL-10. In conclusion, LF feeding augmented the activities of macrophages in a manner dependent on Candida-priming and these effects may be related to enhanced cytokine levels.
Article
Lactoferrin (Lf), a natural defence iron-binding protein, is present in exocrine secretions that are commonly exposed to normal flora: milk, tears, nasal exudate, saliva, bronchial mucus, gastrointestinal fluids, cervicovaginal mucus and seminal fluid. Additionally, Lf is produced in polymorphonuclear leukocytes and is deposited by these circulating cells in septic sites. A principal function of Lf is that of scavenging non-protein-bound iron in body fluids and inflamed areas so as to suppress free radical-mediated damage and decrease accessibility of the metal to invading bacterial, fungal and neoplastic cells. Adequate sources of bovine and recombinant human Lf are now available for development of commercial applications. Among the latter are use of Lf in food preservation, fish farming, infant milk formula and oral hygiene. Other readily accessible body compartments for Lf administration include skin, throat and small intestine. Further research is needed for possible medicinal use in colon and systemic tissues. Although Lf is a natural product and should be highly biocompatible, possible hazards have been documented.
Article
We investigated the transfer of dietary bovine lactoferrin (LF) and its functional lactoferricin (LFcin) B-containing fragments to the portal blood of healthy adult rats by using several techniques. After a single administration of (125)I-labeled LF, radioactive bands were detected in autoradioluminograms of the portal blood, but similar bands were also observed after the administration of [(125)I]NaI. Although ovalbumin was detected by ELISA at 3-18 ng/ml in the portal blood plasma after an overnight administration, no LF was detected (< or =1.5 ng/ml). The antibody-captured ovalbumin fragments, but not the LF fragments, were detected in the plasma by surface-enhanced laser desorption/ionization affinity mass spectrometry (SELDI affinity MS). We finally attempted to detect the LFcin B-containing fragments by SELDI affinity MS with on-chip LFcin B-conversion, but could not detect them (< or =1 ng/ml) in the portal blood after the LF ingestion. The level of LF or its functional fragments transferred to the portal blood was therefore extremely low, if any.
Article
It has been reported previously that oral administration of lactoferrin (LF) provides some host-protective effects against infections, cancers, and inflammations. In this review, we focus on the effect of oral LF on various infectious diseases and discuss the mechanism as elucidated in animal models. In the case of infections occurring at sites other than the digestive canal, it is unclear whether oral LF is absorbed from the intestine and exerts its protective effect at the site of infection. In preterm human infants, neonatal pigs, and rats with colitis, it was reported that LF is detectable in various body fluids after oral administration. We could not detect the transport of oral bovine LF into the blood of adult rats without gastrointestinal illness using several techniques, suggesting that there is an extremely low level of transport of LF, if any. Orally administered LF may act at the oro-gastro-intestinal mucosa and aid the defense system against infections through a network of mucosal immunity and systemic immunity. Indeed, it is reported that oral LF increases the number of cells in the leukocyte subset and cytokine (IFN-gamma and IL-18) production in the intestinal mucosa of mice. Regarding systemic immunity, we have observed an increase of leukocyte number, cytokine (IFN-gamma, TNF-alpha, IL-12, and IL-18) production, and effector activity of macrophages in response to LF administration in several animal models. These enhanced immune responses may contribute to eradication of the pathogen, resolution of the symptoms, and maintenance of the homeostasis during infectious diseases.
Article
Acne vulgaris is a common skin disorder among children and young adults that carries enormous financial and psychosocial impact. Contemporary therapies attempt to address factors underlying acne as a disorder of the pilosebaceous unit. These longstanding paradigms regarding pathogenesis and treatment continue to evolve in light of recent work on this ubiquitous disease. This review focuses on new literature that has emerged regarding the biology of the folliculosebaceous unit, the identification of particular mediators responsible for inflammatory acne, the use of topical and systemic retinoids in acne therapy, and approaches to address the emergence of antibiotic-resistant Propionibacterium acnes strains. In addition, the use of several novel therapeutic avenues is discussed, including combination therapies, lipoxygenase inhibitors, and lasers. As the understanding of the factors that initiate and exacerbate acne vulgaris continues to increase, so does the diversity of therapeutic options. Rational use of available treatment options based on the type and severity of acne lesions is a key component of successful acne therapy and allows the physician who treats adolescents with acne to provide optimum care.
Article
Acne is a multifactorial inflammatory disease affecting pilosebaceous follicles. The initial event in the development of an acne lesion is abnormal desquamation of the keratinocytes that line the sebaceous follicle, which creates a microplug or microcomedo. An increase in circulating androgens at the onset of puberty stimulates the production of sebum into the pilosebaceous unit. These events combine to create an environment within the pilosebaceous unit that is favorable for the colonization of the commensal bacteria, Propionibacterium acnes. With proliferation, P acnes secretes various inflammatory molecules and chemotactic factors that initiate and perpetuate the local inflammatory response and possibly induce keratinocyte hyperproliferation as well.
Article
Lactoferrin (LF) is a member of the transferrin family that is expressed and secreted by glandular epithelial cells and is found in the secondary granules of neutrophils. Originally viewed as an iron-binding protein in milk, with bacteriostatic properties, it is becoming increasingly evident that LF is a multifunctional protein to which several physiological roles have been attributed. These include regulation of iron homeostasis, host defense against a broad range of microbial infections, anti-inflammatory activity, regulation of cellular growth and differentiation and protection against cancer development and metastasis. While iron binding is likely central to some of the biological roles of LF, other activities, including specific interactions with mammalian receptors and microbial components, also contribute to the pleoitropic functional nature of this protein. In this article, recent advances in the understanding of these functions at the cellular and molecular level are discussed.
Article
Cost limitations, adverse effects or lack of efficacy limit the use of current topical therapies in mild to moderate acne vulgaris. To determine the safety and efficacy of picolinic acid, a novel zinc finger therapy, in the treatment of mild to moderate acne vulgaris. Twenty subjects with mild to moderate acne vulgaris were treated at our centre during an open-label study with 10% picolinic acid gel (PCL-016) twice daily to the face over 12 weeks. Fifteen patients completed the 12-week open-label study. A reduction of 58.2% (P < 0.001) in mean total lesion count, 55.5% (P < 0.001) in mean inflammatory lesion count and 59.7% (P < 0.005) in noninflammatory lesion count was seen in this population. No serious adverse events or clinically significant changes in laboratory values were noted. Results from this study suggest that 10% picolinic acid gel applied twice daily may be safe and effective in the treatment of mild to moderate acne vulgaris.
Article
R115866 (Rambazole; Barrier Therapeutics NV, Geel, Belgium), a new-generation retinoic acid metabolism-blocking agent, is a nonretinoid compound enhancing intracellularly the endogenous levels of all-trans-retinoic acid by blocking its catabolism. By virtue of this property, and the proven positive effects of retinoids in the treatment of acne, R115866 could potentially be a useful drug for acne. To explore the efficacy, safety and tolerability of systemic R115866 in male patients with moderate to severe facial acne vulgaris (at least 15 papules and/or pustules and at least two nodulocystic lesions). In this exploratory trial, 17 patients were treated with oral R115866 1 mg once daily for 12 weeks, followed by a 4-week treatment-free period. At the end of treatment (week 12, n = 16) a mean reduction in inflammatory lesion count of 77.4% (P < 0.001), in noninflammatory lesion count of 58.3% (P < 0.001) and in total lesion count of 76.0% (P < 0.001) was observed as compared with baseline. All lesion counts were significantly reduced from week 4 onwards. Mild side-effects were reported occasionally. The current data indicate that treatment with oral R115866 1 mg once daily for 12 weeks in patients with moderate to severe facial acne vulgaris is efficacious and well tolerated and merits further investigation.
Article
Microcomedones representing the clinically non-visible central precursor lesions of acne are induced by sebaceous hyperplasia as well as altered follicular growth and differentiation, and evolve into both comedones and inflammatory lesions. Thus, targeting microcomedone formation is essential in the prevention and therapeutic control of acne. The aim of this study was to assess the capacity of adapalene gel, 0.1%, to control the number of microcomedones after a combination treatment followed by a maintenance treatment. This was a single-site exploratory study in subjects with a diagnosis of mild to moderate acne vulgaris and the presence of at least 250 microcomedones per cm(2) at screening visit, counted via cyanoacrylate strips (CyASt). During the first 8 weeks, a combination of adapalene gel (0.1%) and benzoyl peroxide gel (2.5%) was applied. During the randomized, investigator-blinded, and vehicle-controlled 12-week maintenance phase, adapalene once daily (QD), or adapalene alternately with its vehicle once daily every other day (QoD), or vehicle QD were applied to the face. CyASt sampling on the forehead was done at baseline, week 8, and week 20. Lesion counting allowing calculating a defined success rate was done at all visits. A total of 54 subjects entered the combination phase, and 49 subjects were randomized into the maintenance phase: 16 in both the adapalene QD and the QoD group and 17 subjects receiving the vehicle. The microcomedone median count decreased for all groups until week 8 (end of combination phase) from 319 to 157. Microcomedone counts at the end of the maintenance phase (week 20) showed a significant percent difference (P = 0.04) between adapalene QoD (-53.5) and the vehicle (-42.1) and between adapalene QD (-50.6) and the vehicle (P = 0.037) compared with baseline. The application of adapalene gel, 0.1% monotherapy daily, or alternately every other day, significantly helps to control the microcomedone count during a 12-week maintenance treatment after a previous combination therapy with benzoyl peroxide in patients with mild to moderate acne.
Article
Acne vulgaris remains one of the most common conditions affecting adolescents. The pediatric practitioner is the first to evaluate adolescent acne, making familiarity with the condition and its management essential. This review covers some of the recent literature regarding acne to help practitioners stay current on the issues regarding this topic. The pathogenesis of acne is multifactorial and complex, but recent advances in molecular genetics have provided additional information on the actions of Proprionibacterium acnes. Nutritional studies have reevaluated a possible role for diet and lifestyle factors in acne development. Many therapies are available to control acne and to limit associated scarring. Their appropriate use requires an understanding of not only the benefits but also the possible risks and adverse effects involved. Recent concerns regarding the use of antibiotics and isotretinoin will be addressed. This study reviews the recent literature regarding teenage acne, focusing on pathogenesis, associations, and controversies and considerations in therapy.