Article

Use of Lactoferrin for Helicobacter pylori Eradication

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

One-week triple therapy is the most frequently recommended treatment for Helicobacter pylori infection. Eradication rate is satisfactory, nevertheless is advisable to look for more effective therapies. To test the efficacy of a standard triple therapy plus bovine lactoferrin in the eradication of H. pylori infection. One hundred and fifty consecutive H. pylori positive patients, suffering from dyspeptic symptoms were recruited in a 7-day triple therapy open randomised single centre study with rabeprazole, clarithromycin, tinidazole, bovine lactoferrin (group A) or rabeprazole, clarithromycin, tinidazole (group B), or a 10-day therapy with rabeprazole, clarithromycin, tinidazole (group C). H. pylori status was assessed 8 weeks after the end of the treatment by means of a 13C-urea breath test or a H. pylori stool antigen-test. Eradication rates (intention to treat/per protocol) were: group A (92.2/95.9%), group B (71.2/72.5%) and group C (70.2/75%). The efficacy of triple therapy added with lactoferrin was significantly higher than other two regimens (p=0.01, intention to treat analysis; p=0.005, per protocol analysis). These results suggest that lactoferrin tested in the present study was effective in curing H. pylori and could be a new agent to assist the antimicrobials in the eradication of the bacterium.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... and reduces side effects, thus resulting in better therapeutic compliance (statistically significant values for nausea, diarrhea, metallic taste, abdominal pain, and glossitis). Various other studies that assessed the combination of LF [33][34][35] and PB [9,36] with TT individually came up with contrasting results concerning the eradication rate. Di Mario et al. showed that LF administered in addition to TT (esomeprazole or rabeprazole + clarithromycin + tinidazole for 7 days) improved eradication (93 vs 78.3% [33] and 95.9 vs 72.5% [34]); however, there was no improvement in therapeutic compliance [33]. ...
... Various other studies that assessed the combination of LF [33][34][35] and PB [9,36] with TT individually came up with contrasting results concerning the eradication rate. Di Mario et al. showed that LF administered in addition to TT (esomeprazole or rabeprazole + clarithromycin + tinidazole for 7 days) improved eradication (93 vs 78.3% [33] and 95.9 vs 72.5% [34]); however, there was no improvement in therapeutic compliance [33]. Zullo et al. [35] evaluated TT (esomeprazole + clarithromycin + amoxicillin) for 7 days with and without the addition of LF and did not obtain significant improvement in the eradication rate. ...
... Considering the improvements enjoyed by adding adjuvants to TT [9,[32][33][34][35][36][37][49][50][51][52], we wanted to assess whether the same improvements are obtained both in side effects (as primary endpoint) and in eradication rates with ST. Evaluation of eradication was taken as a secondary endpoint because in view of the high success rates of ST, we expected no significant improvement by adding adjuvants. ...
Article
Sequential therapy (ST) seems to offer higher success rates than triple therapy (TT) in the eradication of Helicobacter pylori (H. pylori) infection. However, from the standpoint of therapeutic compliance, there is no difference between the two treatments. Adjuvant treatment (especially with probiotics (PB) and lactoferrin (LF)) has often improved compliance and eradication rates in patients subjected to TT, while ST had never been used in association with adjuvants. Over a period of 2 years, we randomized and divided 227 consecutive adult patients with H. pylori infection into three groups. The patients were given ST with the addition of adjuvants, as follows: group A (ST + placebo), group B (ST + LF + PB), and group C (ST + PB). Our goal was to assess therapeutic compliance, so we prepared a questionnaire to help determine the severity of the side effects. We also determined the eradication rates for the groups. Patients with ST + placebo had the worst compliance as compared with the other two groups in terms of the absence of symptoms (p < .001 between B and A; p = .001 between C and A) and the presence of intolerable symptoms (p = .016 between B and A; p = .046 between C and A). The differences between the values for the treated groups and those for the placebo group were statistically significant. On the other hand, there was no statistically significant difference in compliance between groups B and C. The eradication rate was similar for the three groups. Probiotics associated with ST provide optimum therapeutic compliance compared with the placebo and, despite the need to take a larger number of tablets, they should be taken into consideration as an adjuvant to therapy for H. pylori infection. The addition of LF to the PB did not bring about any further improvements in compliance. As compared with the placebo, the eradication rate of ST did not improve by adding LF + PB or by using PB alone.
... Diarrhea was seen with 44% of the subjects receiving the LF solution as opposed to 92% in the control group administered with a placebo. Bovine LF has also been used as an adjunct in the triple therapy against Helicobacter pylori in randomized control trials (RCTs) [33,34]. There was a higher rate of H. pylori eradication in the group receiving the clarithromycin/tinidazole/rabeprazole 7 day triple therapy combined with bovine LF (92.2 [34] and 90% [33] H. pylori eradication) than in the group receiving the triple therapy alone (71.2 [34] and 77% [33] H. pylori eradication). ...
... Bovine LF has also been used as an adjunct in the triple therapy against Helicobacter pylori in randomized control trials (RCTs) [33,34]. There was a higher rate of H. pylori eradication in the group receiving the clarithromycin/tinidazole/rabeprazole 7 day triple therapy combined with bovine LF (92.2 [34] and 90% [33] H. pylori eradication) than in the group receiving the triple therapy alone (71.2 [34] and 77% [33] H. pylori eradication). The positive effect of LF may be antibiotic specific as no additional benefit of bovine LF on H. pylori eradication was seen in another study using an esomeprazole/clarithromycin/amoxicillin 7 day triple therapy [140]. ...
... Bovine LF has also been used as an adjunct in the triple therapy against Helicobacter pylori in randomized control trials (RCTs) [33,34]. There was a higher rate of H. pylori eradication in the group receiving the clarithromycin/tinidazole/rabeprazole 7 day triple therapy combined with bovine LF (92.2 [34] and 90% [33] H. pylori eradication) than in the group receiving the triple therapy alone (71.2 [34] and 77% [33] H. pylori eradication). The positive effect of LF may be antibiotic specific as no additional benefit of bovine LF on H. pylori eradication was seen in another study using an esomeprazole/clarithromycin/amoxicillin 7 day triple therapy [140]. ...
Article
Many studies have demonstrated that milk protein consumption has benefits in terms of promoting human health. This review assesses the intervention studies which have evaluated potential health enhancing effects in humans following the ingestion of milk proteins. The impact of milk protein ingestion has been studied to asses their satiating, hypotensive, antimicrobial, anti-inflammatory, anticancer, antioxidant and insulinotropic properties as well as their impact on morphological modifications (e.g., muscle and fat mass) in humans. Consistent health promoting effects appear to have been observed in certain instances (i.e., muscle protein synthesis, insulinotropic and hypotensive activity). However, controversial outcomes have also been reported (i.e., antimicrobial, anti-inflammatory, anticancer and antioxidant properties). Several factors including interindividual differences, the timing of protein ingestion as well as the potency of the active components may explain these differences. In addition, processing conditions have been reported, in certain instances, to affect milk protein structure and therefore modify their bioactive potential. It is thought that the health promoting properties of milk proteins are linked to the release of bioactive peptides (BAPs) during gastrointestinal digestion. There is a need for further research to develop a more in-depth understanding on the possible mechanisms involved in the observed physiological effects. In addition, more carefully controlled and appropriately powered human intervention studies are required to demonstrate the health enhancing properties of milk proteins in humans. Copyright © 2015. Published by Elsevier Inc.
... They demonstrated in a recent multicenter study that bLf is an essential adjuvant to a one-week triple-combination therapy for H. pylori extermination. 13 Moreover, recombinant lactoferrin has been found to enhance the efficacy of triple-therapy regimens in H. pylori-infected mice. This is following our results. ...
... In addition, bLf exerts an effect against the attachment and colonization of H. pylori bacteria in the gastric mucosa, with a subsequent reduction in organism number as well as the associated inflammatory process. 13,20,21 In our study, the ST was more effective than the PpTT, a finding that matches previously reported data. The eradication rate for PpTT was less than the accepted threshold, while ST could be an effective and appropriate option for first-line H. pylori abolition therapy. ...
Article
Full-text available
Background: Bovine lactoferrin addition to regimens of Helicobacter pylori treatment has been tried, with conflicting results. Aim: To assess the effect of bovine lactoferrin in addition to the anti-H. pylori treatment. Methods: We enrolled 400 H. pylori-infected patients who were randomized into 4 equal groups: (A): proton-pump-based triple therapy (PpTT) for 2 weeks, (B): sequential therapy for 2 weeks, (C): proton-pump-based triple therapy plus bovine lactoferrin for 2 weeks, and (D): sequential therapy plus bovine lactoferrin for 2 weeks. Results: In the per-protocol analysis, the success in groups A, B, C, and D were 70.3%, 82.8%, 85.6%, and 94.5%, respectively (P < .001). The treatment success rate for the sequential therapy plus bovine lactoferrin regimen was significantly higher than that with sequential therapy alone (94.5% vs. 82.8%, P = .013). The same applied for proton-pump-based triple therapy (85.6% vs. 70.3%, P = .014). The addition of bovine lactoferrin and the presence of endoscopic corpus gastritis were independent predictors for successful eradication of H. pylori. Conclusion: Bovine lactoferrin could hasten the effectiveness of the proton-pump-based triple therapy or sequential therapy for H. pylori eradication.
... Several studies have revealed that LF plays a direct role in the body's defense against pathogens, including fi ndings that individuals more susceptible to infection have lower levels of neutrophil LF [Breton-Gorius et al., 1980;Boxer et al., 1982;Baker & Baker, 2005]. In an open, randomized, single-center study of 150 individuals with diagnosed H. pylori infection, patients were given antibiotics at varying doses and durations (range 7-10 days) in conjunction with 200 mg encapsulated LF [Di Mario et al., 2003]. Analysis of the study revealed 100%-eradication of H. pylori in the group using the seven-day antibiotic course with the addition of LF. ...
... Other research reported the anti-infective effects of oral LF in animals with H. pylori gastric infection, Staphylococcus aureus systemic infection and E. coli urinary tract infection [Wakabayas-hi et al., 2006]. LF also improves some symptoms of H. pylori gastric infection [Okuda et al., 2005] and increases the eradication rate of triple therapy against H. pylori in the stomach [Di Mario et al., 2003]. The suppressive effect of bovine LF against H. pylori was examined using two clinical tests. ...
Article
The functionalities of glycoprotein lactoferrin (LF) and glycomacropeptide (GMP) were discussed. LF is considered a multifunctional protein. Its absorption in the bowel; immune response; antioxidant, anti-carcinogenic and anti-infl ammatory properties; and protection against microbial infection, were the most widely studied functions to date. Besides, promotion of balanced intestinal fl ora by preventing growth of harmful bacteria and stimulating bifi dus, LF helps to secure a correct balance of the intestinal fl ora. Although, most of the proposed biological activities of LF are related to the binding of iron, the non-iron related functions have been described as well, such as regulation of iron metabolism, prevention of oxidation and control of cell or tissues damage (result of aging). Likewise, GMP, which is a carbohydrate-containing peptide formed from chymosin or pepsin digestion of κ-casein, exhibits several useful biological activities, including binding of cholera toxin and E. coli enterotoxins, inhibition of bacterial and viral adhesions, suppression of gastric secretions, promotion of bifi dobacterial growth, and modulation of immune responses. GMP contains no aromatic amino acids and is therefore used for phenylketonuria (PKU) suffering patients. The carbohydratic parts bound to such glycoprotein or glycopeptide, may act as prebiotics in the intestine and colon.
... Several studies have revealed that LF plays a direct role in the body's defense against pathogens, including fi ndings that individuals more susceptible to infection have lower levels of neutrophil LF [Breton-Gorius et al., 1980;Boxer et al., 1982;Baker & Baker, 2005]. In an open, randomized, single-center study of 150 individuals with diagnosed H. pylori infection, patients were given antibiotics at varying doses and durations (range 7-10 days) in conjunction with 200 mg encapsulated LF [Di Mario et al., 2003]. Analysis of the study revealed 100%-eradication of H. pylori in the group using the seven-day antibiotic course with the addition of LF. ...
... Other research reported the anti-infective effects of oral LF in animals with H. pylori gastric infection, Staphylococcus aureus systemic infection and E. coli urinary tract infection [Wakabayas-hi et al., 2006]. LF also improves some symptoms of H. pylori gastric infection [Okuda et al., 2005] and increases the eradication rate of triple therapy against H. pylori in the stomach [Di Mario et al., 2003]. The suppressive effect of bovine LF against H. pylori was examined using two clinical tests. ...
Article
The functionalities of glycoprotein lactoferrin (LF) and glycomacropeptide (GMP) were discussed. LF is considered a multifunctional protein. Its absorption in the bowel; immune response; antioxidant, anti-carcinogenic and anti-infl ammatory properties; and protection against microbial infection, were the most widely studied functions to date. Besides, promotion of balanced intestinal fl ora by preventing growth of harmful bacteria and stimulating bifi dus, LF helps to secure a correct balance of the intestinal fl ora. Although, most of the proposed biological activities of LF are related to the binding of iron, the non-iron related functions have been described as well, such as regulation of iron metabolism, prevention of oxidation and control of cell or tissues damage (result of aging). Likewise, GMP, which is a carbohydrate-containing peptide formed from chymosin or pepsin digestion of κ-casein, exhibits several useful biological activities, including binding of cholera toxin and E. coli enterotoxins, inhibition of bacterial and viral adhesions, suppression of gastric secretions, promotion of bifi dobacterial growth, and modulation of immune responses. GMP contains no aromatic amino acids and is therefore used for phenylketonuria (PKU) suffering patients. The carbohydratic parts bound to such glycoprotein or glycopeptide, may act as prebiotics in the intestine and colon.
... Several studies have revealed that LF plays a direct role in the body's defense against pathogens, including fi ndings that individuals more susceptible to infection have lower levels of neutrophil LF [Breton-Gorius et al., 1980;Boxer et al., 1982;Baker & Baker, 2005]. In an open, randomized, single-center study of 150 individuals with diagnosed H. pylori infection, patients were given antibiotics at varying doses and durations (range 7-10 days) in conjunction with 200 mg encapsulated LF [Di Mario et al., 2003]. Analysis of the study revealed 100%-eradication of H. pylori in the group using the seven-day antibiotic course with the addition of LF. ...
... Other research reported the anti-infective effects of oral LF in animals with H. pylori gastric infection, Staphylococcus aureus systemic infection and E. coli urinary tract infection [Wakabayas-hi et al., 2006]. LF also improves some symptoms of H. pylori gastric infection [Okuda et al., 2005] and increases the eradication rate of triple therapy against H. pylori in the stomach [Di Mario et al., 2003]. The suppressive effect of bovine LF against H. pylori was examined using two clinical tests. ...
Article
Full-text available
The functionalities of glycoprotein lactoferrin (LF) and glycomacropeptide (GMP) were discussed. LF is considered a multifunctional protein. Its absorption in the bowel; immune response; antioxidant, anti-carcinogenic and anti-infl ammatory properties; and protection against microbial infection, were the most widely studied functions to date. Besides, promotion of balanced intestinal fl ora by preventing growth of harmful bacteria and stimulating bifi dus, LF helps to secure a correct balance of the intestinal fl ora. Although, most of the proposed biological activities of LF are related to the binding of iron, the non-iron related functions have been described as well, such as regulation of iron metabolism, prevention of oxidation and control of cell or tissues damage (result of aging). Likewise, GMP, which is a carbohydrate-containing peptide formed from chymosin or pepsin digestion of κ-casein, exhibits several useful biological activities, including binding of cholera toxin and E. coli enterotoxins, inhibition of bacterial and viral adhesions, suppression of gastric secretions, promotion of bifi dobacterial growth, and modulation of immune responses. GMP contains no aromatic amino acids and is therefore used for phenylketonuria (PKU) suffering patients. The carbohydratic parts bound to such glycoprotein or glycopeptide, may act as prebiotics in the intestine and colon.
... Some recent studies have shown that both recombinant and bovine lactoferrin (bLF) exert an anti-microbial effect against H. pylori in both in vitro and in vivo models. In particular, bLF inhibited the growth of H. pylori at concentrations >0.5 mg/ml [12], and in recent pilot studies bLF achieved an eradication rate of >90% when added to a seven-day clarithromycin-tinidazole-based triple therapy [13][14][15]. However, a more recent study failed to show a statistical improvement in curing H. pylori when bLF is added [16]. ...
... As far as its use in humans is concerned, the results of lactoferrin-containing anti-H. pylori treatment are contrasting [13][14][15][16]27]. ...
... Due to the expense of treatment and concern for antibiotic resistance, new treatments are being sought. In an open, randomised, single-centre study of 150 individuals with diagnosed H. Pylori infection, patients were given antibiotics at varying doses and durations (range 7-10 days) in conjunction with 200 mg encapsulated lactoferrin (Di Mario et al. 2003b). Analysis of the study revealed a 100% eradication of H. pylori in the group using the 7-day antibiotic course with the addition of lactoferrin. ...
... Several studies have revealed that LF plays a direct role in the body's defense against pathogens, including fi ndings that individuals more susceptible to infection have lower levels of neutrophil LF [Breton-Gorius et al., 1980; Boxer et al., 1982; Baker & Baker, 2005]. In an open, randomized, single-center study of 150 individuals with diagnosed H. pylori infection, patients were given antibiotics at varying doses and durations (range 7?10 days) in conjunction with 200 mg encapsulated LF [Di Mario et al., 2003]. Analysis of the study revealed 100%-eradication of H. pylori in the group using the seven-day antibiotic course with the addition of LF. ...
Article
Full-text available
The functionalities of glycoprotein lactoferrin (LF) and glycomacropeptide (GMP) were discussed. LF is considered a multifunctional protein. Its absorption in the bowel; immune response; antioxidant, anti-carcinogenic and anti-inflammatory properties; and protection against microbial infection, were the most widely studied functions to date. Besides, promotion of balanced intestinal flora by preventing growth of harmful bacteria and stimulating bifidus, LF helps to secure a correct balance of the intestinal flora. Although, most of the proposed biological activities of LF are related to the binding of iron, the non-iron related functions have been described as well, such as regulation of iron metabolism, prevention of oxidation and control of cell or tissues damage (result of aging). Likewise, GMP, which is a carbohydrate-containing peptide formed from chymosin or pepsin digestion of κ-casein, exhibits several useful biological activities, including binding of cholera toxin and E. coli enterotoxins, inhibition of bacterial and viral adhesions, suppression of gastric secretions, promotion of bifidobacterial growth, and modulation of immune responses. GMP contains no aromatic amino acids and is therefore used for phenylketonuria (PKU) suffering patients. The carbohydratic parts bound to such glycoprotein or glycopeptide, may act as prebiotics in the intestine and colon. © Copyright by Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences.
... Lactoferrin molecule is an 80 kDa glycosylated protein with iron-chelating property [2]. Lactoferrin acts as a multifunctional biomolecule and have been used in the treatment of bacterial and viral diseases [3][4][5]. Lactoferrin is known to interact with a variety of bio-molecules like DNA, RNA, polysaccharides and heparin [6][7][8]. ...
Article
Full-text available
Lactoferrin is one of the important nutraceutical with several physiological and biological functions. Bovine colostrum contains higher concentrations of lactoferrin than in the milk. The present work describes the use of two mixed mode sorbents, mercapto ethyl pyridine (MEP HyperCel™) and phenyl propyl amine (PPA HyperCel™), for the recovery of lactoferrin from bovine colostrum whey. The dynamic binding capacity study showed that, in MEP the mode of interaction of lactoferrin is similar to IgG and had a more or less same binding capacity of ~20 mg/mL of sorbent. In PPA, the interaction of lactoferrin was hydrophobic and was influenced by the addition of salt. The binding capacity of lactoferrin with PPA in absence and presence of salt was found to be ~17 and ~18 mg/mL sorbent respectively. The binding buffers used for the chromatographic experiments were 0.05 M sodium phosphate buffer, pH 7.4, with or without sodium chloride (0.15 M). A decreasing step pH gradient of pH 6.0, 5.5 and 4.0 was performed for elution. Both lactoferrin and immunoglobulin were obtained with high homogeneity. The recovered lactoferrin was confirmed by immunoblot analysis. The chro-matographic elution fractions obtained from MEP Hypercel did not exhibit lactoperoxidase activity. The highest recovery of lactoferrin (~91%) with 2.9 fold rise in purity was obtained when the MEP resin column was used with the binding buffer without sodium chloride. Thus, MEP HyperCel™ could be a potential alternative to existing systems for separation of lactoferrin from bovine colostrum whey.
... The above experimental evidence led to several human clinical trials. These are summarized in Table 5 [43,[51][52][53][54][55][56][57] . As presented, 5 (of 7 available) positive clinical trials and a meta-analysis appear to establish the beneficial effect of bLf (4%-17% as per meta-analysis) on H. pylori eradication fairly well [58] . ...
Article
Helicobacter pylori (H. pylori) eradication is considered a necessary step in the management of peptic ulcer disease, chronic gastritis, gastric adenocarcinoma and mucosa associated lymphoid tissue lymphoma. Standard triple therapy eradication regimens are inconvenient and achieve unpredictable and often poor results. Eradication rates are decreasing over time with increase in antibiotic resistance. Fermented milk and several of its component whey proteins have emerged as candidates for complementary therapy. In this context the current review seeks to summarize the current evidence available on their role in H. pylori eradication. Pertinent narrative/systematic reviews, clinical trials and laboratory studies on individual components including fermented milk, yogurt, whey proteins, lactoferrin, α-lactalbumin (α-LA), glycomacropeptide and immunoglobulin were comprehensively searched and retrieved from Medline, Embase, Scopus, Cochrane Controlled Trials Register and abstracts/proceedings of conferences up to May 2013. A preponderance of the evidence available on fermented milk-based probiotic preparations and bovine lactoferrin suggests a beneficial effect in Helicobacter eradication. Evidence for α-LA and immunoglobulins is promising while that for glycomacropeptide is preliminary and requires substantiation. The magnitude of the potential benefit documented so far is small and the precise clinical settings are ill defined. This restricts the potential use of this group as a complementary therapy in a nutraceutical setting hinging on better patient acceptability/compliance. Further work is necessary to identify the optimal substrate, fermentation process, dose and the ideal clinical setting (prevention/treatment, first line therapy/recurrence, symptomatic/asymptomatic, gastritis/ulcer diseases etc.). The potential of this group in high antibiotic resistance or treatment failure settings presents interesting possibilities and deserves further exploration.
... Dietary factors are reported to influence the severity of Helicobacter-induced gastritis and gastric cancer, low intake of vegetables and fruit, and high intakes of salt and processed meat being risk factors (Rocco andNardone 2007, Epplein et al. 2008). Bovine lactoferrin or lactoferrin plus probiotics added to triple therapy improved the eradication rates in the treatment of H. pylori infection (Di Mario et al. 2003, de Bortoli et al. 2007). Lysozyme and lactoperoxidase also act against pathogens (Pakkanen andAalto 1997, Zimecki andKruzel 2007). ...
... In patients, the ingestion of bLF as well as hLF has been reported to have beneficial effects on infections of both digestive and non-digestive tract tissues [69]. Clinical studies of LF therapy have been performed against hepatitis C virus7071, the gastric infection caused by Helicobacter pylori7273, and in tinea pedis caused by the fungus Trichophyton mentagrophytes [74]. In the digestive tract, intact and partially digested LF, which peptides can retain biological activity, bacteriostatic and bactericidal effects are exerted. ...
Chapter
Full-text available
Lactoferrin (LF) is a cationic iron-binding glycoprotein found in mucosal secretions and fluids of mammals such as those from respiratory, vaginal, digestive and intestinal tract, tears and saliva and is particularly abundant in colostrum and milk. LF is also produced by the secondary granules of neutrophils and secreted by these cells in blood and sites of infection. This glycoprotein of about 80 kDa is a component of the innate immune system devoted to capture ferric iron in order to be unavailable for pathogens growth when they try to colonize and invade a host. LF is truly a multifunctional molecule since is immunomodulator, anti-carcinogenic and microbicidal. The iron-free form of LF (apoLF) is active against numerous infective species of bacteria, fungi, virus, and protozoa. LF is digested by the gastric enzyme pepsin, producing N-terminal peptides named Lactoferricins (LFcins), which often are more potent antimicrobials than the native protein. Milk-derived bovine LF as well as the recombinant human and bovine LF has been utilized to treat microbial infections in animal models and in trials with patients,
... In addition, other potential mechanisms by which lactoferrin inhibits the growth of several microorganisms include structural changes in the microbial cell wall, complete loss of membrane integrity, indirect effects on enzyme activation, an increased generation of metabolic by-products of aerobic metabolism, iron deprivation and combination of these factors. [23] Honey Honey is a traditional remedy for dyspepsia and there have been a number of reports suggesting that honey can inhibit the growth of H. pylori. [24] The antimicrobial activity of honey has been attributed to hydrogen peroxide, osmolarity, acidity, aromatic acids and phenolic compounds. ...
Article
Full-text available
Abstract: Helicobacter pylori (H. pylori) is a worldwide infection that affects millions of people. Some people develop only minor symptoms or even no symptoms at all, whereas others complain of terrible stomach and chest pain, diarrhea, bloating, nausea, vomiting, heartburn, headaches, depression, anxiety and rashes. H. pylori can be eradicated by using conventional medical treatments or a natural approach. However, both approaches can also fail miserably due to patient incompliance and antimicrobial resistance of the infecting H. pylori strain. Therefore, a non-antibiotic agent that is both effective and free from side effects might be of considerable importance for the eradication of H. pylori.
... In addition, other potential mechanisms by which lactoferrin inhibits the growth of several microorganisms include structural changes in the microbial cell wall, complete loss of membrane integrity, indirect effects on enzyme activation, an increased generation of metabolic by-products of aerobic metabolism, iron deprivation and combination of these factors. [23] Honey Honey is a traditional remedy for dyspepsia and there have been a number of reports suggesting that honey can inhibit the growth of H. pylori. [24] The antimicrobial activity of honey has been attributed to hydrogen peroxide, osmolarity, acidity, aromatic acids and phenolic compounds. ...
Article
Full-text available
Helicobacter pylori (H. pylori) is a worldwide infection that affects millions of people. Some people develop only minor symptoms or even no symptoms at all, whereas others complain of terrible stomach and chest pain, diarrhea, bloating, nausea, vomiting, heartburn, headaches, depression, anxiety and rashes. H. pylori can be eradicated by using conventional medical treatments or a natural approach. However, both approaches can also fail miserably due to patient incompliance and antimicrobial resistance of the infecting H. pylori strain. Therefore, a non-antibiotic agent that is both effective and free from side effects might be of considerable importance for the eradication of H. pylori.
... The protective function of milk is known to be largely due to the presence of serum proteins in its composition where bLF plays a special role as a control growth factor and has antimicrobial, bifidogenic, antioxidant, anti-inflammatory, and immune-correcting activity (Kim et al., 2004;Yamauchi et al., 2006;Rahman et al., 2008 andHayakawa et al., 2009;Jenssen and Hancock, 2009;Montiel et al., 2015). Bovine lactoferrin is effective against such dangerous microorganisms like Streptococcus spp., Vibrio cholerae, Helicobacter pylori (Mario et al., 2003;Okuda et al., 2005;Sachdeva and Nagpal, 2009). It also resists a rather rare but very dangerous disease -listeriosis, leading to such consequences as the prenatal fetal death, malformations of newborns, children after listeria meningitis often suffer from paralysis and mental retardation (Ripolles et al., 2015). ...
Article
The purpose of this work was to solve the regulation problems of protection processes through biologically active proteins in the animal body, in particular, to study the role of the receptor mechanism in the effect of lactoferrin and its derivatives (peptides) on the cell proliferation. There are presented the results of studying the bovine milk lactoferrin effect on the dermal fibroblasts and human keratinocytes, the growth of Bifidobacterium adolescentis B-1, as well as the study of anti-ulcer and dysbacteriosis activity of bovine milk lactoferrin and its hydrolyzates in an experiment in vivo. Bovine milk lactoferrin in the same dose inhibits the keratinocytes proliferation much more actively than stimulates the proliferation of dermal fibroblasts that allowed considering the immortalized keratinocytes as targets in a model system with bovine lactoferrin to study the mechanism inhibiting the cell growth. The bifidobacteria strains, which are not sensitive to bovine lactoferrin, turned out to be inert toward its peptides that may indicate the possibility of implementing the action on the cellular target of bovine lactoferrin and products of its limited proteolysis through a single receptor mechanism. Peptides of bovine lactoferrin, the most active in reference to stimulating the bifidogenic property of beneficial microorganisms, proved to be more effective in protection the gastrointestinal tract from ulceration of the gastric mucosa and dysbiosis. The minimum dose (1 mg per 1 kg of the animal body weight), the mucosal ulcerous erosion was not diagnosed as a result of injecting the mixture, was ~ 300 mg for bovine milk lactoferrin, ~ 100 mg for hydrolysates (after 4 hours of proteolysis), and ~ 10 mg (after 24 hours of proteolysis). In the experiments in vitro and in vivo, the peptides of low molecular weight have a stronger biological effect than the native bovine lactoferrin in the same concentration.
... Lf binds to the lipopolysaccharide of bacterial walls, and may also damage bacteria via formation of peroxides catalyzed by Lf-bound iron (III) ions, affecting membrane permeability and resulting in bacterial cell lysis [19,35,36]. Since the pioneristic work of Bullen and co-workers [37] on the protective effect of Lf towards E. coli 0111 infection in newborn guinea-pigs, there are several experimental observations that oral administration of Lf reduces bacterial and fungal infections mainly in the gastro-intestinal tract (see, for example, [9,[38][39][40][41][42][43][44]). On the other hand, Lf promotes the growth of bacteria with low iron requirements such as Lactobacillus and Bifidobacteria, which are generally believed to be beneficial to the host [45]. ...
Article
Full-text available
Lactoferrin is an iron-binding protein present in large quantities in colostrum and in breast milk, in external secretions and in polymorphonuclear leukocytes. Lactoferrin's main function is non-immune protection. Among several protective activities shown by lactoferrin, those displayed by orally administered lactoferrin are: (i) antimicrobial activity, which has been presumed due to iron deprivation, but more recently attributed also to a specific interaction with the bacterial cell wall and extended to viruses and parasites; (ii) immunomodulatory activity, with a direct effect on the development of the immune system in the newborn, together with a specific antinflammatory effects; (iii) a more recently discovered anticancer activity. It is worth noting that most of the protective activities of lactoferrin have been found, sometimes to a greater extent, also in peptides derived from limited proteolysis of lactoferrin that could be generated after lactoferrin ingestion. Lactoferrin could therefore be considered an ideal nutraceutic product because of its relatively cheap production from bovine milk and of its widely recognized tolerance after ingestion, along with its well demonstrated protective activities. The most important protective activities shown by orally administered bovine lactoferrin are reviewed in this article.
... Bovine Lf (1mg/ml) used in formulas fed to premature infants or normal infants were shown to induce the growth of the beneficial bacteria Bifidobacterium and inhibited proliferation of Clostridium and E. coli [43]. BLf given to patients infected with H. pylori in combination with a triple therapy regime completely eradicated the infection from 78% to 100% [44]. However contradictory to these studies a clinical trial with rhLf administered orally over a period of 24 hours to H. pylori infected subjects showed no decrease in infection [45]. ...
Article
Full-text available
Lactoferrin (Lf) is a natural occurring iron binding protein present in many mammalian excretions and involved in various physiological processes. Lf is used in the transport of iron along with other molecules and ions from the digestive system. However its the modulatory functions exhibited by Lf in connection to immune response, disease regression and diagnosis that has made this protein an attractive therapeutic against chronic diseases. Further, the exciting potentials of employing nanotechnology in advancing drug delivery systems, active disease targeting and prognosis have also shown some encouraging outcomes. This review focuses on the role of Lf in diagnosing infection, cancer, neurological and infammatory diseases and the recent nanotechnology based strategies.
... In particular, after the pioneering study by Miehlke and colleagues [289], who demonstrated the in vitro bactericidal activity of rhLf against 13 clinical isolates of H. pylori, both bLf and rhLf were shown to promote bacterial growth and gastric inflammation in mice [290]. In the same field, inconclusive results have been obtained so far in humans, with two open randomized trials showing the efficacy [291,292] and one the inefficacy [293] of bLf in improving eradication rates of H. pylori when applied in combination therapies. Moreover, despite the abovementioned studies proving the efficacy of Lf on animal models of colitis, the failure of bLf in decreasing risk of sepsis and necrotizing enterocolitis (NEC) in preterm infants was recently reported [294]. ...
Article
Full-text available
The connection between inflammation and cancer is well-established and supported by genetic, pharmacological and epidemiological data. The inflammatory bowel diseases (IBDs), including Crohn’s disease and ulcerative colitis, have been described as important promoters for colorectal cancer development. Risk factors include environmental and food-borne mutagens, dysbalance of intestinal microbiome composition and chronic intestinal inflammation, with loss of intestinal epithelial barrier and enhanced cell proliferation rate. Therapies aimed at shutting down mucosal inflammatory response represent the foundation for IBDs treatment. However, when applied for long periods, they can alter the immune system and promote microbiome dysbiosis and carcinogenesis. Therefore, it is imperative to find new safe substances acting as both potent anti-inflammatory and anti-pathogen agents. Lactoferrin (Lf), an iron-binding glycoprotein essential in innate immunity, is generally recognized as safe and used as food supplement due to its multifunctionality. Lf possesses a wide range of immunomodulatory and anti-inflammatory properties against different aseptic and septic inflammatory pathologies, including IBDs. Moreover, Lf exerts anti-adhesive, anti-invasive and anti-survival activities against several microbial pathogens that colonize intestinal mucosa of IBDs patients. This review focuses on those activities of Lf potentially useful for the prevention/treatment of intestinal inflammatory pathologies associated with colorectal cancer development.
... The results of lactoferrin in the treatment of H. pylori infection in humans were observed to be inconclusive. Di Mario et al. (2003) demonstrated that the addition of 200 mg of BLf twice a day for a 7-day triple therapy had a superior eradication rate (92%) in comparison with the standard 7-or 10-day triple therapy (71% and 72%, respectively) using rabeprazole (20 mg B.I.D.), clarithromycin (500 mg B.I.D.) and tinidazole (500 mg B.I.D). ...
Article
Aims: To evaluate the efficacy of bovine lactoferrin (BLf), recombinant human lactoferrin (rHLf) and desferrioxamine against Helicobacter pylori in vitro and in mice and also to determine whether BLf or rHLf alter gastric inflammation. Methods and results: In vitro: Broth dilution susceptibility tests were performed using different concentrations of desferrioxamine, BLf and rHLf. Murine trials: In the prevention trial, C57BL/6 female mice were treated with BLf or rHLF, and then infected with the SS1 strain of H. pylori. In the treatment trial, mice were gavaged with either BLf, rHLf or desferrioxamine. In addition, gastric myeloperoxidase activity (MPO) was measured to assess gastric inflammation. Desferoxamine was found to have a direct bactericidal effect, while BLf and rHLf only partially suppressed H. pylori growth in vitro. However, in both prevention and treatment trials all three forms of treatment failed to reduce H. pylori load in mice. Gastric MPO activity and H. pylori load were noted to be higher with lactoferrin treatments. Conclusions: Our study does not support the use of BLf or rHLF in the treatment of human H. pylori infection. Interestingly, H. pylori growth and gastric inflammation appear to be enhanced by lactoferrin treatment. Significance and impact of the study: The mouse model is ideal for testing novel H. pylori eradicating agents.
... Other antimicrobial activity assays mentioned in the literature and can be used solely or as a complementary to the mentioned assays like -to name a few-bioluminescence (Pihlanto-Leppӓlӓ et al. 1999), fluorescent in situ hybridization (FISH) (Brück et al. 2002) and electron microscopy (Vorland et al. 1999). There are only a few in vivo antimicrobial studies reported in the literature on animal models or clinical trials in humans (Nakasone et al. 1994;Isamida et al. 1998;Kuwata et al. 1998a;Kuwata et al 1998b;Kawaguchi et al. 1989;Di Mario et al. 2003). Pratt et al. (1944) isolated the first antibacterial compound from the microalga Chlorella sp., which is a mixture of fatty acids, known as chlorellin, and was found to be responsible for that inhibitory activity against both Gram positive and Gram negative bacteria. ...
Thesis
Full-text available
High-value products from microalgae, which can be used in various applications (nutritional, pharmaceuticals and cosmetic) can considerably increase the commercial value of microalgal biomass. This research focuses on the following: - Green extraction of proteins from the marine diatom Nitzschia laevis (N. laevis) and comparing them with those obtained from well-studied species such as Spirulina (Arthrospira) platensis (S. platensis) and Chlorella vulgaris (C.vulgaris). - Protein extracts obtained were subjected to three different protease enzymes including Trypsin, Alcalase®CLEA and Flavourzyme® to produce “bioactive hydrolysates”. - Screening of anti-oxidative, anti-hypertension, anti-inflammatory and antimicrobial activities in vitro. - Fractionation and characterization of bioactive proteins and hydrolysates produced from the microalgal extracts using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Soluble proteins and other major constituents (lipids and carbohydrates) from N. laevis were extracted using ultrasound, then compared to other well-investigated microalgae (Spirulina and Chlorella). N. laevis cellular lysates contained 21.09±2.00% protein, whereas Spirulina contained 54.20±10.73%, and Chlorella 14.01±9.51% (w/w). The aqueous protein extracts of Nitzschia contained 11832.5±3.53 μmol/L α-amino groups and were of high nutritional valuable due to the presence of most of the essential amino acids. In addition, Nitzschia’s proteins exhibited high thermal stability (84.31°C) after Chlorella proteins (87.49°C) at neutral pH. Protein hydrolysates from these microalgae were produced using Alcalase®CLEATM from Bacillus subtilis, Flavourzyme® from Aspergillus oryzae, and trypsin from bovine pancreas, independently. During the first assessment of protein extract and their enzymatic hydrolysates, it was noticed that the antioxidant activities were enhanced by the hydrolysis process in most cases, , especially those obtained using the commercial enzymes Alcalase®CLEATM and Flavourzyme® at 1% enzyme to substrate ratio. N. laevis showed the highest (in a fixed concentration of 2 mg mL-1) total phenolic content/reducing capacity (2.40±0.02 mg Gallic Acid Equevalent (GAE) 100g-1) after 90 minutes of hydrolysis with Alcalase®CLEATM, followed by Spirulina after 90 minutes of hydrolysis and Chlorella after 120 minutes of hydrolysis (2.30±0.04 and 1.90±0.05 mg GAE 100g-1, respectively). In the second assessment, the starting concentration of protein extracts and hydrolysates were increased to 4 mg mL-1, then 2-fold diluted in all assays for IC50 studies. Only the most antioxiadtive hydrolysate were used in the second assessment. They include Alcalase®CLEATM hydrolysates at 120, 90, and 120 minutes from N. laevis, S. platensis and C. vulgaris, respectively; Flavoursome® hydrolysates at 30, 60, 120 minutes from N. laevis, S. platensis and C. vulgaris, respectively; and Trypsin hydrolysates at 90 minutes from N. laevis, 120 minutes from S. platensis and C. vulgaris. Antioxidant activities, including DPPH, ABTS, and superoxide anion scavenging potentials, Oxygen radical absorbance capacity (ORAC), and xanthine oxidase inhibition were tested on aqueous protein extracts and the selected hydrolysates from each enzyme. All protein extracts and hydrolysates showed dose-dependant scavenging activities of ABTS and DPPH stable radicals. Flavourzyme® hydrolysates of N. laevis and S. platensis produced the highest ABTS scavenging activities (84.37±2.09% and 80.77±3.08%, respectively), with IC50 0.85±0.00 and 0.92±0.03 mg mL-1, respectively. These were followed by Alcalase®CLEATM and trypsin hydrolysates, although the differences weren’t singinficant (p> 0.05). The protein extracts alone did not show significant ABTS scavenging acitvities. DPPH scavenging activities observed where mild, and Flavourzyme® hydrolysates from all species produced the most DPPH radical scavenging activities, although the differences were not significant between data sets. The highest DPPH scavenging activity was found in N. laevis hydrolysates obtained by Flavourzyme® (39.23±0.84%), followed by S. platensis (31.23±2.00%), with IC50 2.12±0.01 and 1.71±0.04 mg mL-1, respectively. ORAC values were measured for all samples and N. laevis protein extracts exhibited the highest GAE and TE (trolox equevalent) compared to S. platensis and C. vulgaris (4.06±2.89, 3.56±1.24 and 2.97±1.31 mg GAE g-1 sample, and 1989.17±579.3, 1806.17±249.7 and 1590.17± 263.9 μM TE g-1 sample, respectively) (p< 0.05). The calculated IC50 for protein extracts from N. laevis, S. platensis and C. vulgairs were 1.36±0.17, 5.96±2.49 and >6 μM TE respectively. The IC50 for N. laevis, S. platensis and C. vulgairs Alcalase®CLEATM hydrolysates were 0.67±0.05 , 0.13±0.05 and 1.03±0.04 μM TE respectively. The IC50 of Flavourzyme® hydrolysates of N. laevis, S. platensis and C. vulgairs were 0.34±0.05 , 1.38±0.08 and 1.66±0.06 μM TE and using trypsin hydrolysates, the IC50 were 0.67±0.05 , 7.17 and 2.89±0.06 μM TE, respectively. Superoxide anion radical scavenging activity of trypsin hydrolysates from N. laevis were the highest achieved (118.45±0.00% and IC50 was 0.24±0.00 mg mL-1), followed by Alcalase®CLEATM (112.62±0.01% and IC50 was 0.70±0.00 mg mL-1) and Flavourzyme® (93.84±0.00% and IC50 was 0.30±0.00 mg mL-1). S. platensis proteins and hydrolysates in this study did not show significant superoxide radical scavenging activities, and the highest scavenging activity achieved was with trypsin hydrolysates (58.99±0.06% and IC50 was 1.21±0.00 mg mL-1). C. vulgaris protein extracts showed better superoxide scavenging activity than hydrolysed samples (115.44±0.00% and IC50 was 0.24±0.00 mg mL-1), followed by trypsin hydrolysates (90.61±0.02% and IC50 was 0.30±0.00 mg mL- 1), Alcalase®CLEATM (88.68±0.01% and IC50 was 0.37±0.00 mg mL-1) and lastly Flavourzyme® hydrolysates (76.70±0.01% and IC50 was 0.24±0.00 mg mL-1). The highest xanthine oxidase inhibition activity was achieved by Flavourzyme® hydrolysates of N. laevis at 156.14±7.58% and IC50 was 2.12±0.00 mg mL-1. S. platensis protein extracts showed the highest xanthine oxidase inhibitory activity (103.48±6.90% and IC50 was 2.07±0.03 mg mL-1), C. vulgaris protein extracts also showed better xanthine oxidase inhibition activity compared to the hydrolysed samples (85.35±7.32%, IC50 was 2.01±0.06 mg mL-1) (p> 0.05). In addition, protein extracts and hydrolysates showed antagonist effect toward acetylcholinesterase (AChE) and angiotensin-I converting (ACE) enzymes. The highest inhibitory activity of AChE was of obtained for Spirulina proteins (46.30±0.03 %, IC50 2.05±0.03 mg mL-1) followed by Nitzschia (32.32±0.12 %, IC50 1.09±0.11 mg mL-1) and Chlorella (20.98±0.02 %, IC50 2.97±0.01 mg mL-1). Flavourzyme® hydrolysates showed better AChE inhibitory activity, especially those of N. laevis (52.64±0.61%, IC50 1.59±0.00 mg mL-1). ACE was highly inhibited by Nitzschia proteins (138.08±0.01 %, IC50 0.40±0.13 mg mL-1) followed by Chlorella (90.15±1.32 %, IC50 1.55±2.00 mg mL-1) and Spirulina (83.79±0.11 %, IC50 0.27±0.04 mg mL-1). Trypsin hydrolysates of protein extracts from all three phyla showed better ACE inhibitory activities compared to other enzyme hydrolysates (88.03±7.47 % and IC50 1.63±0.01, 95.17±12.82 and IC50 0.68±0.06, and 61.36±23.42 and IC50 2.63±0.01 mg mL-1 for N. laevis, S. platensis and C. vulgaris trypsin hydrolysates, respectively) (p> 0.05). Protein extracts and hydrolysates did not show antibacterial or bactericidal activities against the tested organisms with the used range of concentrations. Aqueous protein extracts and hydrolysates from Nitzschia, Spirulina and Chlorella have shown in vitro antioxidant, anti-angiotensin I-converting enzyme and anti-acetylcholinesterase activities, suggesting potential new sources of bioactive proteins and peptides of different phyla with nutraceutical and pharmaceutical potentials. Until now, most of the biological activities of microalgal-derived bioactive proteins and hydrolysates have been observed in vitro. Therefore, further ex vivo research studies are needed in order to investigate their potential market as nutraceuticals and pharmaceuticals based on their therapeutic potential shown in this study.
... Bovine lactoferrin was also effective in curing H pylori in human patients. [28][29][30] In addition, probiotic-containing yogurt decreased H pylori colonization in the stomachs of human subjects. 31,32 A previous study in Turkey did not find H pylori in sheep milk, 33 in cow milk in the USA, 34 and in cow milk in Italy. ...
Article
Background and Aim Helicobacter pylori inhabits the gastric mucosa of humans and causes 89% of all gastric cancers. This is the first study of the seroprevalence, spatial distribution, and risk factors for H pylori in Jordan. Materials and Methods This is a cross‐sectional study of 460 healthy participants (aged between 15 and 81 years) proportionately sampled across each region of Jordan. Sera samples were tested for H pylori using Enzygnost® anti‐H pylori immunoglobulin G enzyme‐linked immunosorbent assay. Participants completed a validated questionnaire about potential risk factors including food consumption habits and environmental and animal exposure. Multivariate generalized linear models identified risk factors for infection. Results The results showed a high seroprevalence (88.6%; 95% confidence interval [CI]: 85.3‐91.2) of H pylori in the study population. After adjusting for possible confounders, age, consumption of raw milk, and location of residence were significantly associated with seropositivity. Older participants aged 30‐49 years had an 11% greater risk of seropositivity compared to participants aged 15‐29 years. Participants who consume raw milk and dairy products have a 9% decreased risk in seropositivity (prevalence ratio = 0.92; 95% CI: 0.84‐0.99) compared to those who do not consume these products. Conclusion This study reports a negative association between consumption of raw milk and seropositivity, and this is in line with several studies that report consumption of raw milk may be protective against H pylori. However, because of the risk of other serious pathogens associated with the consumption of raw dairy products, this study recommends pasteurization of raw milk. Future studies on the effect of fermented dairy products on H pylori colorization in gastric mucosa are recommended.
... In the past 5 years in China, there have been comparatively few publications regarding its antibacterial activity. One report showed that Lf has anti-Helicobacter pylori function (Yuan et al. 2015), in agreement with previous studies (Di Mario et al. 2003;Sachdeva and Nagpal 2009;de Bortoli et al. 2007). Another study demonstrated that apo-Lf or Lf hydrolysate inhibited the growth of foodborne pathogens, including E. coli, Salmonella typhimurium, Staphylococcus aureus, and Enterococcus faecalis, and inhibited some probiotic strains such as Lactobacillus acidophilus ATCC 4356, L. salivarius ATCC 11741, L. rhamnosus ATCC 53103, Bifidobacterium longum ATCC 15707, and B. lactis BCRC 17394 . ...
Article
Full-text available
Lactoferrin (Lf), a multifunctional glycoprotein, is an important antimicrobial and immune regulatory protein present in neutrophils and most exocrine secretions of mammals. Lactoferricin (Lfcin) is located in the N-terminal region of this protein. In this review, the current state of research into Lf and Lfcin in China is described. Searching with HistCite software in Web Sci located 118 papers published by Chinese researchers from 2011-2015, making China one of the top 3 producers of Lf research and development in the world. The biological functions of Lf and Lfcin are discussed, including antibacterial, antiviral, antifungal, anticarcinogenic, and anti-inflammatory activities; targeted drug delivery, induction of neurocyte, osteoblast, and tenocyte growth, and possible mechanisms of action. The preparation and heterologous expression of Lf in animals, bacteria, and yeast are discussed in detail. Five Lf-related food additive factories and 9 Lf-related health food production companies are certified by the China Food and Drug Administration (CFDA). The latest progress in the generation of transgenic livestock in China, the safety of the use of transgenic animals, and future prospects for the uses of Lf and Lfcin are also covered.
... In a study by de Bortoli et al., 56 the addition of bovine lactoferrin to a triple therapy with esomeprazole, amoxicillin and clarithromycin increased the success rate by 16% (ITT and PP analysis). In a similar study adding bovine lactoferrin to a therapy with rabeprazole, tinidazole and clarithromycin, Di Mario et al. 57 were able to increase the eradication rate by 21%, with total eradication in 92.2% (ITT analysis) and 95.2% (PP analysis) of treated cases. In our study the addition of bovine lactoferrin to a triple therapy that included esomeprazole, amoxicillin and levofloxacin for H. pylori infection significantly increased the eradication rate compared with that of the non-supplemented regimen, with a therapeutic gain of 21%. ...
Article
Full-text available
Objectives To evaluate the in vitro antimicrobial/antivirulence action of bovine lactoferrin and its ability to synergize with levofloxacin against resistant Helicobacter pylori strains and to analyse the effect of levofloxacin, amoxicillin and esomeprazole with and without bovine lactoferrin as the first-line treatment for H. pylori infection. Methods The bovine lactoferrin antimicrobial/antivirulence effect was analysed in vitro by MIC/MBC determination and twitching motility against six clinical H. pylori strains and a reference strain. The synergism was evaluated using the chequerboard assay. The prospective therapeutic trial was carried out on two separate patient groups, one treated with esomeprazole/amoxicillin/levofloxacin and the other with esomeprazole/amoxicillin/levofloxacin/bovine lactoferrin. Treatment outcome was determined with the [¹³C]urea breath test. Results In vitro, bovine lactoferrin inhibited the growth of 50% of strains at 10 mg/mL and expressed 50% bactericidal effect at 40 mg/mL. The combination of levofloxacin and bovine lactoferrin displayed a synergistic effect for all strains, with the best MIC reduction of 16- and 32-fold for levofloxacin and bovine lactoferrin, respectively. Bovine lactoferrin at one-fourth MIC reduced microbial motility significantly for all strains studied. In the in vivo study, 6 of 24 patients recruited had treatment failure recorded with esomeprazole/amoxicillin/levofloxacin (75% success, 95% CI 57.68%–92.32%), and in the group with esomeprazole/amoxicillin/levofloxacin/bovine lactoferrin, 2 out of 53 patients recruited had failure recorded (96.07% success, 95% CI 90.62%–101.38%). Conclusions Bovine lactoferrin can be considered a novel potentiator for restoring susceptibility in resistant H. pylori strains. Bovine lactoferrin added to a triple therapy in first-line treatment potentiates the therapeutic effect.
... As a multifunctional protein, LF is widely used for various clinical conditions. For instance, it is utilized for treating stomach and intestinal ulcers [11,12]. It is also applied as an antioxidant to protect against infections or tissue damage associated with aging [13][14][15]. ...
Article
Full-text available
Lactoferrin (LF) is a soluble glycoprotein of the transferring family found in most biological fluids, functioning as a major first line defense molecule against infection in mammals. It also shows certain anti-tumor activity, but its clinical application in tumor therapy is limited because high dosage is required. In this study, we demonstrate that M860, a monoclonal antibody against human LF (hLF), could significantly increase the anti-tumor potential of low dosage hLF by forming LF-containing immune complex (IC). Human monocytes primed with LF-IC, but not hLF or M860 alone, or control ICs, showed strong tumoricidal activity on leukemia cell lines Jurkat and Raji through induction of secreted Granzyme B (GzB). LF-IC is able to colligate membrane-bound CD14 (a TLR4 co-receptor) and FcγRIIa (a low affinity activating Fcγ receptor) on the surface of human monocytes, thereby triggering the Syk-PI3K-AKT-mTOR pathway leading to GzB production. Our work identifies a novel pathway for LF-mediated tumoricidal activity and may extend the clinical application of LF in tumor therapy.
Article
• Dairy derivatives have recently become the focus of much scientific investigation • Lactoferrin has antibacterial, antiviral, antifungal, antiparasitic, immunomodulatory and antitumour properties • Colostrum is antibacterial and antiviral and may enhance exercise performance • Whey protein concentrates may have ergogenic effects and may also improve satiety and bloodglucose levels • Other bioactive peptides appear to have wide-ranging antimicrobial and immunomodulatory properties.
Chapter
Buffaloes are the second largest milk source in the world after cows (92.5 and 599.6 billion liters with contributions of 12.8% and 83.2%, respectively). Because buffalo milk has a higher total solids content compared with cow milk, it accounts for about twice the food contribution implied by the volume of buffalo milk produced yearly. This milk is a richer source of fat, protein, lactose and minerals as compared to cow milk, so it can be considered as more nutritious for humans as well. This chapter includes (i) dairy buffalo population, breeds, production, socioeconomic importance for humans and commercial dairy products; (ii) description of major and minor constituents of buffalo milk along with their nutritional impacts on human health; and (iii) specific health benefits of buffalo milk and its products along with effects of buffalo health on its milk. It is important to know how the major and minor constituents of buffalo milk play a role in the development of some typical buffalo milk products and how their superior nutrition give them preference over the other milks for future research studies.
Article
Lactoferrin is an iron-binding glycoprotein present in milk as well as other exocrine secretions and neutrophil granules in mammals. Lactoferrin is considered to be an important host defense molecule and has a diverse range of physiological functions such as antimicrobial/antiviral activities, immunomodulatory activity, and antioxidant activity. During the past decade, it has become evident that oral administration of lactoferrin exerts several beneficial effects on the health of humans and animals, including anti-infective, anticancer, and anti-inflammatory effects. This has enlarged the application potential of lactoferrin as a food additive. The technology of producing bovine lactoferrin on a factory scale was established over 20 years ago. Bovine lactoferrin is purified by cation-exchange chromatography from bovine skim milk or whey, and is commercially available from several suppliers. Recombinant human lactoferrin is produced by Aspergillus niger, transgenic cows, and rice, and its efficacy is being evaluated. In this article, we review basic research and technological aspects of the application of lactoferrin.
Article
Helicobacter pylori infection is a widespread disease causing significant morbidity and mortality, with a relevant economic impact. To cure such an infection, the use of a 7-day triple therapy (a proton pump inhibitor together with two antibiotics) is suggested in those areas in which clarithromycin resistance rate is < 20%, whereas a 7-day quadruple therapy or a 14-day triple therapy should be used where clarithromycin resistance is higher. However, no existing therapies achieve bacterial eradication in all treated patients, the eradication rate can actually reach values as low as 70 – 80%. Therefore, new drugs are vital within this field. Surprisingly, very few patents have been claimed in the last three years. Quinolone derivatives probably remain the most investigated drugs, gemifloxacin being proposed most recently. New pleuromutilin derivatives (I-valnemulin) showed a very powerful bacteriocidal activity against H. pylori isolates, but in vivo data are still lacking. A novel proton pump inhibitor – the (-)-enantiomer of tenatoprazole – with reduced nocturnal acid breakthrough values has been claimed. This compound might improve activity of the antibiotic dose administered at bedtime.
Peptic ulcers result from in imbalance of aggressive (e.g., acid-pepsin) and protective factors (e.g., mucosal blood flow, bicarbonate secretion). Most ulcers are etiologically related to infection with Helicobacter pylori or use of nonsteroidal anti-inflammatory drugs (NSAIDs). Mechanisms resulting in improved anti-H. pylori therapy include better delivery of antimicrobials to the sites of infection (e.g., changing dose, formulation, duration or the use of adjuvants), enhancing local immunity or by reducing the mucus barrier to topical therapy. Mechanisms to prevent NSAID ulcers include less damaging NSAIDs (e.g., COX-2 selective NSAIDs, nitric oxide-donating NSAIDs), reduction in acid secretion or replacement of mucosal prostaglandins.
Article
Helicobacter pylori infection is a widespread disease causing significant morbidity and mortality, with relevant economic impact. A 7-day triple regimen (proton pump inhibitor together with two antibiotics) is currently suggested as first-line treatment, but the success rate following such a therapy is decreasing. Therefore, new drugs or novel therapeutic approaches are needed. Patents of new antibiotics have been claimed, such as both erythromycin and rifamycin derivatives, and new polycyclic compounds, showing a very powerful antibacterial activity in vitro. Patents of either H. pylori urease inhibitors or new proton pump inhibitors are also of great interest. Several attempts have been made to create vaccines for H. pylori infection, with interesting results in animal models. Experimentation in humans is ongoing.
Article
Background: The optimal duration for Helicobacter pylori (H. pylori) eradication therapy is controversial, with recommendations ranging from 7 to 14 days. Several systematic reviews have attempted to address this issue but have given conflicting results and limited their analysis to proton pump inhibitor (PPI), two antibiotics (PPI triple) therapy. We performed a systematic review and meta-analysis to investigate the optimal duration of multiple H. pylori eradication regimens. Objectives: The primary objective was to assess the relative effectiveness of different durations (7, 10 or 14 days) of a variety of regimens for eradicating H. pylori. The primary outcome was H. pylori persistence. The secondary outcome was adverse events. Search methods: The Cochrane Library, MEDLINE, EMBASE, and CINAHL were searched up to December 2011 to identify eligible randomised controlled trials (RCTs). We also searched the proceedings of six conferences from 1995 to 2011, dissertations and theses, and grey literature. There were no language restrictions applied to any search. Selection criteria: Only parallel group RCTs assessing the efficacy of one to two weeks duration of first line H. pylori eradication regimens in adults were eligible. Within each regimen, the same combinations of drugs at the same dose were compared over different durations. Studies with at least two arms comparing 7, 10, or 14 days were eligible. Enrolled participants needed to be diagnosed with at least one positive test for H. pylori on the basis of a rapid urease test (RUT), histology, culture, urea breath test (UBT), or a stool antigen test (HpSA) before treatment. Eligible trials needed to confirm eradication of H. pylori as their primary outcome at least 28 days after completion of eradication treatment. Trials using only serology or a polymerase chain reaction (PCR) to determine H. pylori infection or eradication were excluded. Data collection and analysis: Study eligibility and data extraction were performed by two independent review authors. Data analyses were performed within each type of intervention, for both primary and secondary outcomes. The relative risk (RR) and number needed to treat (NNT)/number needed to harm (NNTH) according to duration of therapy were calculated using the outcomes of H. pylori persistence and adverse events. A random-effects model was used. Subgroup analyses and sensitivity analyses were planned a priori. Main results: In total, 75 studies met the inclusion criteria. Eight types of regimens were reported with at least two comparative eligible durations. They included: PPI + two antibiotics triple therapy (n = 59), PPI bismuth-based quadruple therapy (n = 6), PPI + three antibiotics quadruple therapy (n = 1), PPI dual therapy (n = 2), histamine H2-receptor antagonist (H₂RA) bismuth quadruple therapy (n = 3), H₂RA bismuth-based triple therapy (n = 2), H₂RA + two antibiotics triple therapy (n = 3), and bismuth + two antibiotics triple therapy (n = 2). Some studies provided data for more than one regimen or more than two durations.For the PPI triple therapy, 59 studies with five regimens were reported: PPI + clarithromycin + amoxicillin (PCA); PPI + clarithromycin + a nitroimidazole (PCN); PPI + amoxicillin + nitroimidazole (PAN); PPI + amoxicillin + a quinolone (PAQ); and PPI + amoxicillin + a nitrofuran (PANi). Regardless of type and dose of antibiotics, increased duration of PPI triple therapy from 7 to 14 days significantly increased the H. pylori eradication rate (45 studies, 72.9% versus 81.9%), the RR for H. pylori persistence was 0.66 (95% CI 0.60 to 0.74), NNT was 11 (95% CI 9 to 14). Significant effects were seen in the subgroup of PCA (34 studies, RR 0.65, 95% CI 0.57 to 0.75; NNT 12, 95% CI 9 to 16); PAN (10 studies, RR 0.67, 95% CI 0.52 to 0.86; NNT = 11, 95% CI 8 to 25); and in PAQ (2 studies, RR 0.37, 95% CI 0.16 to 0.83; NNT 3, 95% CI 2 to 10); but not in PCN triple therapy (4 studies, RR 0.87, 95% CI 0.71 to 1.07). Significantly increased eradication rates were also seen for PPI triple therapy with 10 versus 7 days (24 studies, 79.9% versus 75.7%; RR 0.80, 95% CI 0.72 to 0.89; NNT 21, 95% CI 15 to 38) and 14 versus 10 days (12 studies, 84.4% versus 78.5%; RR 0.72, 95% CI 0.58 to 0.90; NNT 17, 95% CI 11 to 46); especially in the subgroup of PAC for 10 versus 7 days (17 studies, RR 0.80, 95% CI 0.70 to 0.91) and for 14 versus 10 days (10 studies, RR 0.69, 95% CI 0.52 to 0.91). A trend towards increased H. pylori eradication rates was seen with increased duration of PCN for 10 versus 7 days, and of PAN for 10 versus 7 days and 14 versus 10 days, though this was not statistical significant. The proportion of patients with adverse events, defined by authors, was marginally significantly increased only between 7 days and 14 days (15.5% versus 19.4%; RR 1.21, 95% CI 1.06 to 1.37; NNTH 31, 95% CI 18 to 104) but not for other duration comparisons. The proportion of patients discontinuing treatment due to adverse events was not significantly different between treatment durations.Only limited data were reported for different durations of regimens other than PPI triple therapy. No significant difference of the eradication rate was seen for all regimens according to different durations except for H₂RA bismuth quadruple therapy, where a significantly higher eradication rate was seen for 14 days versus 7 days, however only one study reported outcome data. Authors' conclusions: Increasing the duration of PPI-based triple therapy increases H. pylori eradication rates. For PCA, prolonging treatment duration from 7 to 10 or from 10 to 14 days is associated with a significantly higher eradication rate. The optimal duration of therapy for PCA and PAN is at least 14 days. More data are needed to confirm if there is any benefit of increasing the duration of therapy for PCN therapy. Information is limited for regimens other than PPI triple therapy; more studies are needed to draw meaningful conclusions for optimal duration of other H. pylori eradication regimens.
Article
The utilization of live microorganisms as therapeutics has been gaining increasing attention over the last years with the addition of scientific knowledge on their traditional uses. Probiotics are defined as "live micro-organisms which when administered in adequate amounts, confer a health benefit on the host". The normal intestinal microbiota prevents the colonization of pathogenic bacteria and has important immune functions. It has been hypothesized that the sudden change in the intestinal microbiota that parallels the modern life practices of humans might have contributed to the rise in the incidence of particular diseases. Bacteria and yeasts may be used as probiotics either in the form of a single strain or combination of microorganisms or mixed with prebiotics. Probiotics have been used for various disease states from gastrointestinal diseases to infections and even to diabetes and atopic diseases. Drawing firm conclusions about the clinical efficacy of probiotics is hard because of the heterogeneity of patient populations, probiotic strains, dosages, and commercial preparations. However, probiotics represent a very exciting and promising area of research due to the ever-increasing antibiotic resistance rates and the ability of some probiotics to modify the course of diseases.
Chapter
Full-text available
Casein and whey proteins have various functionalities on human health. These are expressed mainly through the peptides that are released when these proteins are digested and include antithrombotic and antihypertasive action, positive effects on the human nervous system and a stimulative effect on the human immune system, antimicrobial action and controlling effects on chronic diseases. Much research has been focused on the use of casein and whey proteins for the production of functional peptides useful for human health. This contribution reviews the discovered effects of casein and whey proteins on human health and the techniques used to isolate bioactive peptides from them.
Article
Scope Lactoferrin (Lf) has a protective potential to liver, but whether it can prevent alcoholic liver injury (ALI) remains unclear. Methods and results Four groups of male C57BL/6J mice were fed with different diets, namely, AIN-93G diet for control (CON) and ethanol (EtOH) groups, and AIN-93G diet with 0.4% and 4% casein replaced by Lf for low-dose Lf (LLf) and high-dose Lf (HLf) groups, respectively. ALI was induced by giving 20% ethanol ad libitum combined with four “binges”. Lf could remarkably decrease EtOH-induced mortality. Lf promoted aldehyde dehydrogenase-2 (ALDH2) expression and suppressing cytochrome P450 2E1 (CYP2E1) overexpression, resulting in the reduced hepatic superoxide and inflammation levels, which ultimately led to the hepatic injury alleviation. However, HLf increased acetyl-CoA carboxylase and fatty acid synthase protein levels, which suggested that excessive intake might weaken the beneficial effects of Lf. Moreover, LLf increased the relative abundances of Akkermansia and Lactobacillus. Additionally, we found that Lf likely exerted action in its digestive product forms rather than intact Lf molecular in normal condition. Conclusion LLf could ameliorate ALI, which was associated with the regulation of hepatic alcohol metabolism and the modulation of gut microbiota. However, excessive Lf intake might result in a diminished benefit. This article is protected by copyright. All rights reserved
Article
AIM: To systematically evaluate whether adding lactoferrin to H pylori eradication regimens could improve eradication rates and reduce side effects during anti-H pylori treatment. METHODS: Eligible articles were identified by searching electronic databases. We included all randomized trials comparing lactoferrin supplementation to placebo or no treatment during anti-H pylori regimens. Statistical analysis was performed with Review Manager 5.0.10. Subanalysis/Sensitivity analysis was also performed. RESULTS: We identified 9 randomized trials (n = 1343). Pooled H pylori eradication rates for patients with and without lactoferrin were 86.57% (95% CI: 83.99%-89.15%) and 74.44% (95% CI: 71.14%-77.74%) by intention-to-treat analysis, respectively, and the odds ratio (OR) was 2.26 (95% CI: 1.70-3.00); the occurrence of total side effects, especially nausea, for groups with or without lactoferrin were 9.05% (95% CI: 6.83%-11.27%) and 16.28% (95% CI: 13.43%-19.13%), respectively; the summary OR was 0.15 (95% CI: 0.04-0.54). CONCLUSION: Our review suggests that supplementation with lactoferrin could be effective in increasing eradication rates of anti-H pylori therapy, and could be considered helpful for patients with eradication failure.
Article
Lactoferrin is a milk protein credited with an impressive list of multifunctional health benefits. Separation of LF from other ingredients of milk requires several complex steps of protein engineering. Despite high purity, proteins isolated from such processes may harbor microbial and endotoxin contaminants that could compromise LF functionality and applications in vivo. A novel treatment for contaminant reduction (TCR) to enhance the protein quality during commercial-scale LF production has been developed. LF-(TCR), based on this cutting-edge protein technology, contains ultra-clean LF that could offer the highest standards of microbiological quality and functional assurance for nutraceutical applications.
Conference Paper
Ingestion of bovine lactoferrin (bLF) has been reported to show anti-infective, anti-cancer, and anti-inflammatory effects. In particular, it has become evident that oral bLF had a beneficial effect on infections of both digestive and nondigestive tract tissue in various animal models. Furthermore, the effects of bLF have been indicated in clinical studies on patients with Helicobacter pylori infection, chronic hepatitis C, tinea pedis, and other diseases. Immunomodulation in the intestine and systemic sites has been suggested to mediate the protective effects of oral bLF against infection. Recently, we demonstrated the beneficial effects of oral bLF in influenza virus infected mice. BLF administration reduced the lung consolidation score and the number of infiltrating leukocytes in bronchoalveolar lavage fluid. We also investigated the effect of oral bLF on the transcription of genes related to immunity in the small intestine of mice using the quantitative RT-PCR method. We found that intake of bLF increased the expression of IL-12p40, IFN-beta, and NOD2. Thus, oral bLF activates the transcription of important immune-related genes in the small intestine, and such transcriptional activation may promote systemic host immunity.
Article
Full-text available
Milk is an important component of a balanced diet and contains numerous valuable constituents. Considerable acclaimed health benefits of milk are related to its proteins, not only for their nutritive value but also for their biological properties. Scientific evidence suggests that anticarcinogenic activities, antihypertensive properties, immune system modulation, and other metabolic features of milk, are affiliated with its proteins (intact proteins or its derivatives). In this article, the main health-related aspects of milk proteins, such as anticarcinogenic, immunomodulatory, antimicrobial, anticariogenic, antihypertensive, and hypocholesterolemic effects are reviewed. Collectively, the findings indicate the effectiveness of milk proteins on reduction of risk factors for cancer, cardiovascular diseases and overall improvement of health aspects.
Research
Full-text available
Peynir altı suyu, daha önceleri, peynir yapımının bir atık ürünü olarak ele alınmakta idi, fakat son yıllarda bileşimi ortaya konularak, içeriği oluşturan aminoasit, immünglobulin, büyüme faktörleri gibi maddelerin antimikrobiyal, antiviral, antifungal, epitelizan, immün stimülan, rejeneratif gibi birçok tera-pötik etkileri tanımlanmıştır. Beşerî hekimlikte peynir altı suyu immün stimülasyon amacıyla özellikle yaş-lılarda iskemik atakta, " human immunodeficiency virus " (HIV) enfeksiyonunda, pek çok hastalıkta antimikrobiyal amaçlı (Escherichia coli, Salmonella typhimurium, Shigella dysenteriae, Listeria monocy-togenes, Bacillus stearothermophilus, Bacillus subtilis, Micrococcus luteus, Pseudomonas aeruginosa, Listeria monocytogenes, Candida albicans ve Helicobacter pylori), egzersiz ve sporcularda kas yapımında, gastrointestinal sistem hastalıklarında, kanser hastalarında, osteoporözde, ağız ve diş sağlığında, depres-yon, stres ve kozmetik sektörü gibi pek çok alanda kullanılmaktadır. Oysa güncel literatür tarandığında, bu ürünün maalesef veteriner hekimlik alanında çok fazla araştırılmamış, özellikle de rutin kullanıma gir-mekten çok uzak olduğu görülmektedir. Doğal ve maliyeti düşük olan peynir altı suyunun, ister toz hâ-linde, ister taze sıvı hâlde; barsak hastalıkları, köpeklerin parvoviral enteritisi, yangısal barsak hastalığı, yenidoğan ve gelişme geriliği gösteren yavrular, viral, bakteriyel, paraziter hastalıklar, geriatri, kanser hastalığı gibi durumlarda destek ve rejeneratif tedavi yönünden değerlendirilmesi ile terapi başarısına önemli ölçüde katkı sağlayacağı kanaatindeyiz. Bu çalışmada, peynir altı suyunun içeriği, beşerî ve vete-riner hekimlik sahasında kullanım alanları özetlenmiştir. A An na ah h t ta ar r K Ke e l li i m me e l le er r: : Vey protein; veterinerlik bilimi; tedavi A AB BS S T TR RA AC CT T Whey was a waste product of cheese manufacturing previously, but in the last decades with the identification of its content, it is used in many areas of human medicine as a supportive element because of the antimicrobial, antiviral, antifungal, epithelialing, immune stimulant, regeneratif effects due to its amino acid, immune globuline, growth factors etc. components. Major areas whey proteins are used in human medicine are immune stimulation, ischemic attack especially in elderly, , human immunodeficiency virus (HIV) infection, in many disorders as antimicrobials (Escherichia coli, Salmonella typhimurium, Shigella dysenteriae, Listeria monocytogenes, Bacillus stearothermophilus, Bacillus subtilis, Micrococcus luteus, Pseudomonas aeruginosa, Listeria monocytogenes, Candida albi-cans and Helicobacter pylori), exercise and by sportsmen for muscle protein synthesis, gastrointestinal system disorders, neoplastic disorders, osteoporesis, oral and dental health, depression and stress and cozmetic areas. Unfortunately, current literature shows that this product has not been invesitigated and very far from clinical application in veterinary medicine. The authors opinion is that, this economically available and natural product must be a part of supportive and regenerative therapy in gas-trointestinal disorders, canine parvoviral enteritis, inflammatory bowel disease, neonates and puppy and kittens with inproper development, viral, bacterial and parasitic infections, geriatry and cancer. This review summarizes the content and therapeutic applications of whey proteins in human and veterinary medicine. K Ke ey y W Wo or rd ds s: : Whey protein; veterinary medicine; therapy T Tu ur rk ki iy ye e K Kl li in ni ik kl le er ri i J J V Ve et t S Sc ci i 2 20 01 16 6; ;7 7((2 2)): :6 60 0-4 4
Article
Full-text available
Milk is an important component of a balanced diet and contains numerous valuable constituents. Considerable acclaimed health benefits of milk are related to its proteins, not only for their nutritive value but also for their biological properties. Scientific evidence suggests that anticarcinogenic activities, antihypertensive properties, immune system modulation, and other metabolic features of milk, are affiliated with its proteins (intact proteins or its derivatives). In this article, the main health-related aspects of milk proteins, such as anticarcinogenic, immunomodulatory, antimicrobial, anticariogenic, antihypertensive, and hypocholesterolemic effects are reviewed. Collectively, the findings indicate the effectiveness of milk proteins on reduction of risk factors for cancer, cardiovascular diseases and overall improvement of health aspects.
Chapter
Whey protein is one of the two major protein types of bovine milk, accounting for 20 percent of milk protein, while casein accounts for the remaining 80 percent. Human breast milk contains less methionine, phenylalanine, and lysine compared to bovine milk and more cysteine and tryptophan. Branched chain amino acids (BCAAs) are highly valued amino acids due to their high solubility in the digestive tract and therefore, faster rate of absorption compared to other proteins that require pre‐digestion to remain soluble in the gut. The protein digestibility corrected amino acid score (PDCAAS) is currently the most accepted and widely used method for measurement of the protein value in human nutrition as it takes into account true fecal digestibility of proteins. Clinical trials have shown that whey protein has beneficial effects in the treatment of cancer, human immunodeficiency virus (HIV), hepatitis B, cardiovascular disease, osteoporosis and serves well as an antimicrobial agent.
Article
Nowadays, Helicobacter pylori is the unique biological carcinogenic agent. The search for antimicrobial alternatives to antibiotics against this pathogen has been categorized as priority due to the drastic failure associated to currently applied antibiotic therapy. The present research work assess the bioactive antimicrobial capability of fucoidan (“Generally Recognized as Safe” approval – European Comission December 2017)1 from different species of Phaeophyceae algae (Fucus vesiculosus, Undaria pinnnatifida, Macrocystis pyrifera) against this pathogen. All studied fucoidans showed bacteriostatic and bactericidal effect at the studied concentrations [5-100] µg/ml, and exposure time [0-7] days. The most effective anti-H. pylori fucoidan was validated in Caernohabditis elegans as in vivo model. C. elegans feed was supplemented with Undaria pinnatifida fucoidan [0-100] µg/ml revealing a significant improvement of lifespan, lowering H. pylori concentration at digestive tract, and increasing egg-laying pattern. New research lines proposing this compound as active agent in nutraceutical and preventive novel therapies should be opened
Article
Recent progress in protein-based nanomedicine, inspired by the success of Abraxane® albumin-paclitaxel nanoparticles, have resulted in novel therapeutics used for treatment of challenging diseases like cancer and viral infections. However, absence of specific drug targeting, poor pharmacokinetics, premature drug release, and off-target toxicity are still formidable challenges in the clinic. Therefore, alternative protein-based nanomedicines were developed to overcome those challenges. In this regard, lactoferrin (Lf), a glycoprotein of transferrin family, offers a promising biodegradable well tolerated material that could be exploited both as an active therapeutic and drug nanocarrier. This review highlights the major pharmacological actions of Lf including anti-cancer, antiviral, and immunomodulatory actions. Delivery technologies of Lf to improve its pries and enhance its efficacy were also reviewed. Moreover, different nano-engineering strategies used for fabrication of drug-loaded Lf nanocarriers were discussed. In addition, the use of Lf for functionalization of drug nanocarriers with emphasis on tumor-targeted drug delivery was illustrated. Besides its wide application in oncology nano-therapeutics, we discussed the recent advances of Lf-based nanocarriers as efficient platforms for delivery of anti-parkinsonian, anti-Alzheimer, anti-viral drugs, immunomodulatory and bone engineering applications.
Article
Several milk proteins, such as immunoglobulins, lactoperoxidase, lysozyme and lactoferrin, have long been recognised for promoting health benefits in both newborns and adults. However, it has been shown that not only intact milk proteins but also derivatives thereof can participate in the host defence by exerting many kinds of biological functions. This review focuses on the use of technological processes to induce protein modifications aimed at the enhancement or generation of antibacterial activity. This includes the release of antibacterial peptides by enzymatic digestion, and proteins that exert antibacterial activity by acquiring a new conformation, such as the folding variant of α-lactalbumin or the lysozyme molecule. Current knowledge of antibacterial peptides is evaluated, paying special attention to the formation of these peptides by different proteolytic enzymes, their antibacterial effect, and, where relevant, the methods designed for their production. Finally, the contributions that demonstrate the in vivo health benefits of these compounds are also considered.
Article
Full-text available
X-ray structure analyses of four different forms of human lactoferrin (diferric, dicupric, an oxalate-substituted dicupric, and apo-lactoferrin), and of bovine diferric lactoferrin, have revealed various ways in which the protein structure adapts to different structural and functional states. Comparison of diferric and dicupric lactoferrins has shown that different metals can, through slight variations in the metal position, have different stereochemistries and anion coordination without any significant change in the protein structure. Substitution of oxalate for carbonate, as seen in the structure of a hybrid dicupric complex with oxalate in one site and carbonate in the other, shows that larger anions can be accommodated by small side-chain movements in the binding site. The multidomain nature of lactoferrin also allows rigid body movements. Comparison of human and bovine lactoferrins, and of these with rabbit serum transferrin, shows that the relative orientations of the two lobes in each molecule can vary; these variations may contribute to differences in their binding properties. The structure of apo-lactoferrin demonstrates the importance of large-scale domain movements for metal binding and release and suggests that in solution an equilibrium exists between open and closed forms, with the open form being the active binding species. These structural forms are shown to be similar to those seen for bacterial periplasmic binding proteins, and lead to a common model for the various steps in the binding process.
Article
Full-text available
Previous studies have demonstrated a direct iron-irreversible inhibition of a variety of microorganisms by human apolactoferrin. The present study compared the bactericidal effects of lactoferrin on Streptococcus mutans with the bacteriostatic effects of iron deprivation. Growth (as determined by change in optical density) and macromolecular synthesis, as determined by incorporation of (14)C-labeled uracil, thymidine, and lysine, were inhibited by incubation of washed exponential-phase S. mutans NCTC 10449 with purified human apolactoferrin. Similarly, apolactoferrin inhibited glucose uptake and metabolism. Iron-saturated lactoferrin had no effect on bacterial growth or metabolism and was capable of serving as a source of iron in iron-depleted medium. S. mutans failed to grow, and there was no indication of macromolecular synthesis in iron-depleted partially defined medium; however, glucose metabolism continued, though at a reduced rate, and viability was retained for 72 h. There was no detectable metabolism of glucose by cells maintained for 18 h in iron-free medium. Metabolism was restored by transfer of iron-depleted S. mutans to iron-complete medium. This was in contrast to the irreversible inhibition by lactoferrin after 1 h of incubation. Inhibition could not be reversed by removal of cell surface-associated lactoferrin as detected by rhodamine isothiocyanate-labeled antilactoferrin. This inhibition of metabolism and rapid loss in viability observed with lactoferrin treatment suggest that lactoferrin has a direct bactericidal effect on S. mutans that cannot be attributed to simple iron deprivation.
Article
Full-text available
Lactoferrin containing physiological amounts of iron is an inhibitor of lipid peroxidation induced by iron(III) salts and ascorbic acid. It might therefore help to protect neutrophils, inflammatory foci and secretions from metal-ion-dependent oxidative damage.
Article
Full-text available
Lactoferrin is a 703-amino acid glycoprotein originally isolated from milk. Plasma lactoferrin is predominantly neutrophil derived but indications are that it may also be produced by other cells. Lactoferrin in body fluids is found in the iron-free form, the monoferric form and in the diferric form. Three isoforms of lactoferrin have been isolated, ie two with RNase activity (lactoferrin-beta and lactoferrin-gamma) and one without RNase activity (lactoferrin-alpha). Receptors for lactoferrin can be found on intestinal tissue, monocytes/macrophages, neutrophils, lymphocytes, platelets, and on certain bacteria. A wide spectrum of functions are ascribed to lactoferrin. These range from a role in the control of iron availability to immune modulation. More research is necessary however to obtain clarity with regard to the exact mechanism of action of lactoferrin.
Article
Full-text available
Lactoferrin is an iron-binding protein which is synthesized by mucosal epithelium and neutrophils and released by these cells in response to inflammatory stimuli. It promotes neutrophil aggregation and manifests iron-dependent and -independent antimicrobial properties in vitro. Since lactoferrin binds to glycosaminoglycans (GAGs) and sulfated polysaccharides can inhibit its clearance in vivo and in vitro, we sought to examine its interaction with the GAGs chondroitin sulfate and heparin. Amino-terminal sequencing of proteolytic fragments of human lactoferrin that were fractionated by GAG chromatography suggested that the amino-terminal 6 kDa of the secreted protein mediates its interaction with GAGs. Synthetic peptides were used to show that the first 33 residues of human lactoferrin can bind well to solid-phase or solution-phase GAGs. The first 33 residues bound fluoresceinamine-labeled heparin with an IC50 (611 nM) which approximated that of the intact protein (124 nM). In contrast, when the first six residues (GRRRRS) were removed from this peptide, it then bound poorly to heparin (IC50 = 49 microM). Our results suggest that the GRRRRS sequence at the amino terminus of human lactoferrin acts synergistically with an RKVR sequence at positions 28-31 to form the predominate functional GAG-binding site of human lactoferrin. Molecular modeling of the crystalline structure of lactoferrin supports a synergistic activity between these two sites since it shows that they juxtapose each other on the surface of the folded protein. Solid docking calculations indicate that they can form a cationic cradle as a binding site for chondroitin sulfate.
Article
Full-text available
Antimicrobial factors form one arm of the innate immune system, which protects mucosal surfaces from bacterial infection. These factors can rapidly kill bacteria deposited on mucosal surfaces and prevent acute invasive infections. In many chronic infections, however, bacteria live in biofilms, which are distinct, matrix-encased communities specialized for surface persistence. The transition from a free-living, independent existence to a biofilm lifestyle can be devastating, because biofilms notoriously resist killing by host defence mechanisms and antibiotics. We hypothesized that the innate immune system possesses specific activity to protect against biofilm infections. Here we show that lactoferrin, a ubiquitous and abundant constituent of human external secretions, blocks biofilm development by the opportunistic pathogen Pseudomonas aeruginosa. This occurs at lactoferrin concentrations below those that kill or prevent growth. By chelating iron, lactoferrin stimulates twitching, a specialized form of surface motility, causing the bacteria to wander across the surface instead of forming cell clusters and biofilms. These findings reveal a specific anti-biofilm defence mechanism acting at a critical juncture in biofilm development, the time bacteria stop roaming as individuals and aggregate into durable communities.
Article
Lactoferrin is an 80-kDa, iron-binding glycoprotein present in milk and, to a lesser extent, in exocrine fluids such as bib and tears. It consists of a single-chain polypeptide with two gobular lobes and is relatively resistant to proteolysis. The complete cDNAs for lactoferrin from human milk, neutrophils, and bovine milk have been reported, and recombinant proteins have been produced. Owing to its iron-binding properties, lactoferrin has been proposed to play a role in iron uptake by the intestinal mucosa and to act as a bacteriostatic agent by withholding iron from iron-requiring bacteria. Its presence in neutrophils and its release during inflammation suggest that lactoferrin is also involved in phagocytic killing and immune responses. Additionally, lactoferrin may function in ways not related to iron-binding, e.g. as a growth factor and as a bactericidal agent. This review attempts to evaluate these proposed functions and their biological significance in more detail.
Article
Significant progress and new insights have been gained in the 4 years since the first Maastricht Consensus Report, necessitating an update of the original guidelines. To achieve this, the European Helicobacter Pylori Study Group organized a meeting of specialists and experts from around the world, representatives from National Gastroenterology Societies and general practitioners from Europe to establish updated guidelines on the current management of Helicobacter pylori infection. The meeting took place on 21–22 September 2000.
Article
Aims. To evaluate prevalence of primary Helicobacter pylori antibiotic resistances in Northeast Italy and to identify risk factors associated with this resistance.Materials and methods. A total of 248 patients undergoing upper gastrointestinal endoscopy were enrolled from 19 Endoscopy Units over a 6-month period. From each patient, 4 gastric biopsies were taken for histology and 2 were sent to the Central Referral Microbiological Laboratory for culture and determination of antibiotic activity against Helicobacter pylori by means of E-test. Strains were considered resistant when minimum inhibitory concentration was >8 μg/ml for metronidazole and > 1 μg/ml for clarithromycin. No cut-off value was predefined for amoxycillin.Results. Culture of Helicobacter pylori was successfully performed in 167 patients. Primary resistance to metronidazole, clarithromycin or amoxycillin was 14.9%, 1.8% and 0.%, respectively. Patients infected with Helicobacter pylori strains resistant to antibiotics were more frequently females than males (70.3% vs 41.4%), had a significantly lower coffee intake (66.6% vs 86.6%) and lower body mass index (23.7±2.6 vs 25.3±3.6) than patients with susceptible Helicobacter pylori strains. Age, smoking, alcohol use, family history of Helicobacter pylori infection, concomitant diseases and treatments, endoscopic diagnoses, Helicobacter pylori density and histological activity of chronic gastritis were not associated with antibiotic resistance. Multivariate analysis confirmed that female gender (odds ratio = 2.74, 95% confidence interval = 1.03–7.27) was the only significant risk factor associated with antibiotic resistance.Conclusions. In this population, primary Helicobacter pylori resistance to metronidazole was higher than resistance to clarithromycin, and female gender was significantly associated with this resistance. The low prevalence of resistance to metronidazole, clarithromycin and amoxycillin identified in this geographical area suggests that proton pump inhibitor-based triple regimens including these antibiotics may still be used as first line therapies against Helicobacter pylori infection.
Article
X-ray structure analyses of four different forms of human lactoferrin (diferric, dicupric, an oxalate-substituted dicupric, and apo-lactoferrin), and of bovine diferric lactoferrin, have revealed various ways in which the protein structure adapts to different structural and functional states. Comparison of diferric and dicupric lactoferrins has shown that different metals can, through slight variations in the metal position, have different stereochemistries and anion coordination without any significant change in the protein structure. Substitution of oxalate for carbonate, as seen in the structure of a hybrid dicupric complex with oxalate in one site and carbonate in the other, shows that larger anions can be accommodated by small side-chain movements in the binding site. The multidomain nature of lactoferrin also allows rigid body movements. Comparison of human and bovine lactoferrins, and of these with rabbit serum transferrin, shows that the relative orientations of the two lobes in each molecule can vary; these variations may contribute to differences in their binding properties. The structure of apo-lactoferrin demonstrates the importance of large-scale domain movements for metal binding and release and suggests that in solution an equilibrium exists between open and closed forms, with the open form being the active binding species. These structural forms are shown to be similar to those seen for bacterial periplasmic binding proteins, and lead to a common model for the various steps in the binding process.
Background. Population Helicobacter pylori screening and treatment has been advocated as a means of reducing mortality from gastric cancer. The optimum Helicobacter pylori eradication therapy to use in this setting is uncertain.Aims. To compare efficacy of seven days of omeprazole, clarithromycin and either metronidazole, or amoxycillin in Helicobacter pylori positive subjects detected by population screening.Patients. Helicobacter pylori positive patients from the placebo group of a population screening and treatment trial were invited to take part in the investigation.Methods. Patients were randomised to receive either omeprazole, clarithromycin and metronidazole or omeprazole, clarithromycin and amoxycillin, and Helicobacter pylori eradication was verified with a 13C-urea breath test at least four weeks after completion of therapy.Results. A total of 221 patients took part in the study and 210 completed the protocol. Treatment was successful in (84%) patients allocated to omeprazole, clarithromycin and metronidazole and in (87%) allocated to omeprazole, clarithromycin and amoxycillin in an intention-to-treat analysis (p=0.46). Per protocol eradication rates were (87%) in the metronidazole, and (93%) amoxycillin group (p=0.129).Conclusions. There was no significant difference between the two regimens. The eradication rates achieved are comparable with previous studies in both dyspepsia and peptic ulcer patients.
Article
Various immunoregulatory and anti-infective roles have been proposed for lactoferrin, the iron-binding protein present in external secretions and neutrophil secondary granules. A recent meeting1 updated current knowledge of the structure and function of this unusual protein.
Article
Lactoferrin is an iron-binding protein found in human mucosal secretions as well as the specific granules of polymorphonuclear leukocytes. A variety of functions have been ascribed to the protein, and it appears to contribute to antimicrobial host defense. In particular, it has been shown to have direct effects on pathogenic microorganisms including bacteriostasis and the induction of microbial iron uptake systems. Still its overall physiologic role remains to be defined. It has appeared logical that antimicrobial activity of the protein arises from sequestration of environmental iron thereby causing nutritional deprivation in susceptible organisms. This argument is buttressed by the finding that selected highly virulent pathogens have evolved techniques to subvert this effect and use the protein as an iron source. However, recent observations indicate that the protein has additional properties that contribute to host defense. Work by several groups has shown that the protein synergistically interacts with immunoglobins, complement, and neutrophil cationic proteins against Gram-negative bacteria. Further, both the whole protein and a cationic N-terminus peptide fragment directly damage the outer membrane of Gram-negative bacteria suggesting a mechanism for the supplemental effects. This review will summarize these diverse observations with a consideration of how the in vitro work relates to the physiological role of the protein.
Article
Lactoferricin B (LF-B) is a peptide derived from acid-pepsin digestion of bovine lactoferrin, which has antimicrobial properties. In order to assess the antimicrobial spectrum of LF-B and its possible in vivo uses, the minimum inhibitory and microbicidal concentrations of pure lactoferricin B were determined for a range of bacterial species and under varying conditions of growth including growth phase and size of the inoculum, pH and ionic strength of the medium. Lactoferricin B was bactericidal against a wide range of bacteria and Candida albicans. Proteus spp., Pseudomonas cepacia and Serratia spp. were resistant. The bactericidal activity of LF-B was inhibited by increasing ionic strength and bacterial inoculum and at acid pH. The activity of lactoferricin B was completely inhibited by the addition of 5% whole cow's milk and was reduced in the presence of increasing concentrations of mucin. These results indicate the potential of LF-B to reduce the numbers of organisms in a simple medium, but raise doubts about its role in vivo because of its sensitivity to changes in physical variables. It may be that lactoferricin exerts a transient antimicrobial effect at mucosal surfaces.
Article
All Helicobacter pylori strains tested produced extracellular siderophores, detected by a modified Universal Detection medium, but growth on this medium was poor. By using the iron chelating compound, 2,2'-dipyridyl, outer membrane proteins of 78 and 40 kDa were detected in some, but not all strains examined. No direct binding of lactoferrin or transferrin (the mechanism used by Neisseria to obtain iron) could be demonstrated for H. pylori. Some other techniques for the study of iron-limitation on bacteria were found to be unsuitable for H. pylori.
Article
Lactoferrin is an 80-kDa, iron-binding glycoprotein present in milk and, to a lesser extent, in exocrine fluids such as bile and tears. It consists of a single-chain polypeptide with two gobular lobes and is relatively resistant to proteolysis. The complete cDNAs for lactoferrin from human milk, neutrophils, and bovine milk have been reported, and recombinant proteins have been produced. Owing to its iron-binding properties, lactoferrin has been proposed to play a role in iron uptake by the intestinal mucosa and to act as a bacteriostatic agent by withholding iron from iron-requiring bacteria. Its presence in neutrophils and its release during inflammation suggest that lactoferrin is also involved in phagocytic killing and immune responses. Additionally, lactoferrin may function in ways not related to iron-binding, e.g. as a growth factor and as a bactericidal agent. This review attempts to evaluate these proposed functions and their biological significance in more detail.
Article
Many of the currently used Helicobacter pylori eradication regimens fail to cure 5-20% of the patients. Those patients will remain at risk of developing a potentially fatal complication of peptic ulcer disease. Therefore, a new attempt to cure H. pylori infection after initial failure of therapy is indicated. We studied the efficacy of three retreatment regimens after initial failure of omeprazole-amoxicillin dual therapy. Fifty-three patients whose treatment failed were randomly assigned to receive retreatment with the same regimen of omeprazole 20 mg b.i.d. (group I) or omeprazole 40 mg t.i.d. (group II) plus amoxicillin 750 mg t.i.d. for 14 days. Forty patients in whom the omeprazole-amoxicillin retreatment failed were assigned to receive omeprazole 20 mg b.i.d., amoxicillin 750 mg t.i.d., and metronidazole 500 mg t.i.d. for 14 days (group III) or omeprazole 20 mg b.i.d. plus clarithromycin 500 mg t.i.d. for 14 days (group IV). H. pylori infection was assessed by culture and histology of gastric biopsies before and 4-6 wk after cessation of therapy. Susceptibility of H. pylori to amoxicillin, clarithromycin, and metronidazole was determined by the E test. In groups I (n = 28) and II (n = 25), cure of H. pylori infection was achieved in 21% and 28% of patients, respectively (not significant). In groups III (n = 20) and IV (n = 20), H. pylori infection was cured in 75% and 70%, respectively. Retreatment with an identical omeprazole-amoxicillin dual regimen is of limited benefit, a result that is independent of the omeprazole dose. In contrast, a third H. pylori eradication attempt with omeprazole-clarithromycin dual therapy or omeprazole-amoxicillin-metronidazole triple therapy provides reasonable cure rates after failure of omeprazole-amoxicillin dual therapy.
Article
To investigate a potential new treatment for gastric Helicobacter pylori infection, we have examined the use of the natural antibiotic lactoferrin, found in bovine milk, for activity against Helicobacter species both in vitro and in vivo. Lactoferrin was bacteriostatic to H. pylori when cultured at concentrations > or =0.5 mg/ml. Growth of H. pylori was not inhibited by another milk constituent, lysozyme, or by a metabolite of lactoferrin, lactoferricin B, but growth was inhibited by the iron chelator deferoxamine mesylate. Lactoferrin inhibition of growth could be reversed by addition of excess iron to the medium. Lactoferrin in retail dairy milk was found to be more stable intragastrically than unbuffered, purified lactoferrin. Treatment of H. felis-infected mice with lactoferrin partially reversed mucosal disease manifestations. It is concluded that bovine lactoferrin has significant antimicrobial activity against Helicobacter species in vitro and in vivo. Bovine lactoferrin should be further investigated for possible use in H. pylori infections in man.
Article
Increasing antibiotic resistance has begun to impair our ability to cure Helicobacter pylori infection. To evaluate orally administered novel therapies for the treatment of H. pylori infection. Healthy H. pylori infected volunteers received: (a) hyperimmune bovine colostral immune globulins, (b) an oligosaccharide containing an H. pylori adhesion target, Neu5Aca2-3Galb1-4Glc-(3'-sialyllactose), or (c) recombinant human lactoferrin. Outcome was assessed by urea breath test or histological assessment of the number of H. pylori present. None of the novel therapies appeared effective and no adverse events occurred. Although in vitro data appeared promising, in vivo results were disappointing. Higher doses, longer duration of therapy, adjunctive acid suppression, or a combination could possibly yield better results.
Article
It remains unclarified whether bovine lactoferrin (bLF) can exert a therapeutic effect on the host infected with Helicobacter pylori. Germfree BALB/c mice were orally inoculated with H. pylori to induce infection. Three weeks after infection the mice were given bLF orally once daily for 2 or 4 weeks and were then killed to examine the bacterial number in the stomach and the serum antibody titer to H. pylori. To count the number of epithelium-bound H. pylori, the resected stomach was agitated in phosphate-buffered saline to remove non-bound H. pylori before bacterial enumeration. The administration of 10 mg bLF for 3 to 4 weeks decreased the number of H. pylori in the stomach to one-tenth and also exerted a significant inhibitory effect on the attachment of H. pylori to the stomach. As a result, the serum antibody titer to H. pylori, whose level is presumed to represent the size of the immune response by the host, thereby reflecting the degree of bacterial attack, decreased to an undetectable level. These findings suggest that bLF exerts an inhibitory effect on colonizing H. pylori by detaching the bacterium from the gastric epithelium and by exerting a direct anti-bacterial effect.
Article
Although the currently most effective treatment regimens cure about 90% of infections, 10% of patients remain Helicobacter pylori positive. Several factors contribute to treatment failure. These include patient compliance, bacterial resistance to antibiotics, and treatment related issues. Treatment failure leads to the development of bacterial resistance to metronidazole and clarithromycin. Retreatment can be undertaken after considering several different strategies: to repeat the same regimen with full doses of medications and a longer treatment duration, or to choose different regimens to avoid the antibiotic previously used, or to switch to proton pump inhibitor (PPI) based quadruple therapy or ranitidine bismuth citrate (RBC) based triple therapy. In principle, full doses and longer treatment durations are advisable. As retreatment is always difficult, choosing the best available first line treatment regimen is still the best "rescue" treatment.
Article
Rabeprazole sodium is a proton pump inhibitor. To evaluate the efficacy and safety of 1-week triple therapy with rabeprazole, amoxycillin and clarithromycin for the eradication of Helicobacter pylori. A total of 100 subjects with H. pylori were randomly divided into two groups of 1-week triple therapy with rabeprazole 10 mg b.d., amoxycillin 750 mg b.d. and either clarithromycin 200 mg b.d. (RAC400, n=50) or clarithromycin 400 mg b. d. (RAC800, n=50). Endoscopic examination with four biopsies (two specimens from the antrum and two from the gastric body) was performed. The status of H. pylori infection was determined using culture and histology (Giemsa stain) of the biopsy specimens. Sensitivity to clarithromycin was determined using the E-test: MIC > 8 g/mL was considered to be resistant, whereas MIC < 2 g/mL was considered to be sensitive. Cure was defined as no evidence of H. pylori infection 1 month after completion of treatment. There were no significant differences in the clinical characteristics of the two groups. Eradication rates (intention-to-treat and per protocol, respectively) were: RAC400: 86% (95% CI: 76-95%) and 89% (95% CI: 80-97%); RAC800: 94% (95% CI: 87-100%) and 97% (95% CI: 94-100%). There was no significant difference between the eradication rates of either regimen. Three subjects with failed eradication in the RAC400 group were all infected with a clarithromycin-resistant strain before beginning the therapy. Haemorrhagic colitis was the only severe adverse event, which was observed in one patient in the RAC800 group. One-week triple therapy with rabeprazole, amoxycillin and low-dose clarithromycin is effective for the eradication of H. pylori infection.
Article
A third line treatment is needed in roughly 5% of patients infected with Helicobacter pylori. Few data have been reported on efficacy of treatment regimens in these patients. A prospective trial was designed to study the effectiveness of third line treatment of H. pylori infection in ulcer patients. Two-week quadruple, culture-guided, combinations were used in 31 consecutive patients. Susceptibility to metronidazole and clarithromycin were studied by E-test, and thereafter a predetermined treatment regimen was used. Compliance was evaluated by pill count, and eradication defined by negative urea breath test at 6 weeks. Two main quadruple regimens were used in 29 patients. In spite of good compliance, the combination of omeprazole, tetracycline, bismuth and clarithromycin (OTBC) showed an eradication rate (per protocol analysis) of 36% (five out of 14; CI: 12.8-64.9), and if amoxycillin was used (OTBA) the rate was 67% (eight out of 12; CI: 34.9-90.1). The difference was not significant. No clinical factor was found to be associated with failure to eradicate. Third line treatment often fails to eradicate H. pylori infection. New strategies need to be developed and tested for this common clinical situation.
Article
One-week low-dose proton pump inhibitor-based triple therapies have usually proved to be effective treatments for Helicobacter pylori infection. To investigate the eradication efficacy, safety profile and patient compliance of two triple therapies containing a standard dose of rabeprazole and a new fluoroquinolone, levofloxacin. One hundred patients referred to us for gastroscopy, who were H. pylori-positive, were consecutively recruited in a prospective, open-label study. The enrolled patients were randomised to receive a seven-day course of rabeprazole 20 mg o.d. plus levofloxacin 500 mg o.d. and either amoxycillin 1 g b.d. (RLA group) or tinidazole 500 mg b.d. (RLT group). Their H. pylori status was assessed by means of histology and rapid urease test at entry, and by 13C-urea breath test 8 weeks after the end of treatment. All 100 enrolled patients completed the study. Forty-six of 50 patients treated with RLA (both PP and ITT analysis: 92%; 95% CI: 81-98%) and 45 of 50 with RLT (both PP and ITT analysis: 90%: 95% CI: 78-97%), became H. pylori-negative. Slight or mild side-effects occurred in 4 (8%) patients of the RLA group and in 5 (10%) of the RLT group. This study demonstrates the efficacy of two 1-week rabeprazole-based triple therapies including levofloxacin to eradicate H. pylori. These regimens prove to be safe, well-tolerated, and achieved good eradication rates. Levofloxacin may be an effective alternative to clarithromycin in triple therapy regimens.
Article
Acid suppression plus two antibiotics is considered the reference anti-Helicobacter pylori treatment. Reported eradication rates are around 65-80%. Human Lactobacillus acidophilus shows an in vitro inhibitory effect on the attachment of H. pylori to gastric epithelial cell lines. Culture supernatant of this bacillus seems to decrease the in vitro viability of H. pylori. To evaluate whether the supplementation with an inactivated preparation of L. acidophilus could improve the efficacy of a standard anti-H. pylori therapy. One-hundred and twenty H. pylori-positive patients were randomly assigned to a 7-day triple therapy based on rabeprazole (20 mg b.d.), clarithromycin (250 mg t.d.s.) and amoxicillin (500 mg t.d.s.) (RCA group: 60 subjects), or to the same regimen supplemented with a lyophilized and inactivated culture of Lactobacillus acidophilus (t.d.s.) (RCAL group: 60 subjects). In the RCA group, eradication was successful in 72% (42 out of 58 patients) from a per protocol (PP) analysis, or 70% (42 out of 60 patients) using an intention-to treat (ITT) analysis. In the RCAL group a significant increase in the eradication rate was observed: 88% (52 out of 59 patients) from PP analysis (P=0.03), 87% (52 out of 60 patients) from ITT analysis (P=0.02). These results seem to confirm the in vitro anti-H. pylori effect of L. acidophilus, suggesting that the inactivated L. acidophilus could be effective in increasing eradication rates of a standard anti-H. pylori therapy.
Article
To evaluate prevalence of primary Helicobacter pylori antibiotic resistances in Northeast Italy and to identify risk factors associated with this resistance. A total of 248 patients undergoing upper gastrointestinal endoscopy were enrolled from 19 Endoscopy Units over a 6-month period. From each patient, 4 gastric biopsies were taken for histology and 2 were sent to the Central Referral Microbiological Laboratory for culture and determination of antibiotic activity against Helicobacter pylori by means of E-test. Strains were considered resistant when minimum inhibitory concentration was >8 microg/ml for metronidazole and >1 microg/ml for clarithromycin. No cut-off value was predefined for amoxycillin. Culture of Helicobacter pylori was successfully performed in 167 patients. Primary resistance to metronidazole, clarithromycin or amoxycillin was 14.9%, 1.8% and 0%, respectively Patients infected with Helicobacter pylori strains resistant to antibiotics were more frequently females than males (70.3% vs 41.4%), had a significantly lower coffee intake (66.6% vs 86.6%) and lower body mass index (23.7+/-2.6 vs 25.3+/-3.6) than patients with susceptible Helicobacter pylori strains. Age, smoking, alcohol use, family history of Helicobacter pylori infection, concomitant diseases and treatments, endoscopic diagnoses, Helicobacter pylori density and histological activity of chronic gastritis were not associated with antibiotic resistance. Multivariate analysis confirmed that female gender (odds ratio = 2.74, 95% confidence interval = 1.03-7.27) was the only significant risk factor associated with antibiotic resistance. In this population, primary Helicobacter pylori resistance to metronidazole was higher than resistance to clarithromycin, and female gender was significantly associated with this resistance. The low prevalence of resistance to metronidazole, clarithromycin and amoxycillin identified in this geographical area suggests that proton pump inhibitor-based triple regimens including these antibiotics may still be used as first line therapies against Helicobacter pylori infection.
growth of several microorganisms have been suggested, Tytgat GN. Therapeutic options after failed Helicobacter pylori including structural changes in the microbial cell wall, eradication therapy
  • Hulst Rw
  • Jf
  • Van
  • Ten A Ende
  • Kate Fj
  • Dankert
V an der Hulst RW, Weel JF, Van der Ende A, Ten Kate FJ, Dankert J, growth of several microorganisms have been suggested, Tytgat GN. Therapeutic options after failed Helicobacter pylori including structural changes in the microbial cell wall, eradication therapy. Am J Gastroenterol 1996;9:2333–7.
The effect of human serum
  • Jenny Er Da
  • Aisen
B aldwin DA, Jenny ER, Aisen P. The effect of human serum
Iron acquisition by transferrin and milk lactoferrin on hydroxyl radical formation from Helicobacter pylori: Importance of human lactoferrin. Infect Immun superoxide and hydrogen peroxide
  • H Mo
  • D Legrand
  • G Spik
  • Leclere
H usson MO, Legrand D, Spik G, LeClere H. Iron acquisition by transferrin and milk lactoferrin on hydroxyl radical formation from Helicobacter pylori: Importance of human lactoferrin. Infect Immun superoxide and hydrogen peroxide. J Biol Chem 1984;259:13391–4. 1993;61:2694–7.
Lac-production and iron-regulated envelope proteins of Helicobacter toferrin a new antimicrobial peptide
  • D K Walter
  • Barclay R Siderophore
  • Em A Smart
  • Burgess G L Bloomberg
  • Millar
I llingworth D, Walter K, Griffiths P, Barclay R. Siderophore [31] J ones EM, Smart A, Bloomberg G, Burgess L, Millar MR. Lac-production and iron-regulated envelope proteins of Helicobacter toferrin a new antimicrobial peptide. J Appl Bacteriol 1994;77:208– pylori.
Therapy and drug resistance in Helicobacter pylori infection. Dig bacterium, clarithromycin, tinidazole and bLf exert an
  • F L Olivieri
  • De L Luca
  • Lehours P P Pozzato
  • Megraud
B azzoli F, Olivieri L, De Luca L, Pozzato P, Lehours P, Megraud F. Therapy and drug resistance in Helicobacter pylori infection. Dig bacterium, clarithromycin, tinidazole and bLf exert an Liver Dis 2000;32:S207–10.
The role of lactoferrin as an This schedule, therefore, could be proposed for wider anti-inflammatory molecule
  • B Be
  • Js Serody
  • Cohen
B ritigan BE, Serody JS, Cohen MS. The role of lactoferrin as an This schedule, therefore, could be proposed for wider anti-inflammatory molecule. Adv Exp Med Biol 1994;335:143–56.
Neutralization of endotoxin in culture of Lactobacillus acidophilus increases Helicobacter pylori vitro and in vivo by a human lactoferrin-derived peptide. Infect eradication rates
  • Z Gh
  • Dm Mann
  • Tsai
Z hang GH, Mann DM, Tsai CM. Neutralization of endotoxin in culture of Lactobacillus acidophilus increases Helicobacter pylori vitro and in vivo by a human lactoferrin-derived peptide. Infect eradication rates. Aliment Pharmacol Ther 2000;14:1625–9.
therapeutic agent to assist antimicrobials in the eradication Norris GE, Rumball SV, Smith CA. Structure, function and flexibili-of H. pylori to produce a combination that maximises ty of human lactoferrin
  • B En
  • Anderson Bf Baker Hm
  • Haridas M Jameson
  • Gb
B aker EN, Anderson BF, Baker HM, Haridas M, Jameson GB, therapeutic agent to assist antimicrobials in the eradication Norris GE, Rumball SV, Smith CA. Structure, function and flexibili-of H. pylori to produce a combination that maximises ty of human lactoferrin. Int J Biol Macromol 1991;13:122–9.
innate immunity prevents bacterial biofilm development
  • O Ar
  • Hm
  • Osato Ms
  • Ma Gilger
  • Malaty
  • Hm
O pekun AR, El-Zaimaity HM, Osato MS, Gilger MA, Malaty HM, innate immunity prevents bacterial biofilm development. Nature Terry M, Headon DR, Graham DY. Novel therapies for Helicobacter 2002;417:552–5.
Lactoferrin: a general review. Haematologica compliance to the schedule and the low price of the bLf
  • P Viljoen
L evay P, Viljoen M. Lactoferrin: a general review. Haematologica compliance to the schedule and the low price of the bLf 1995;80:252–67.
Lactoferrin: molecular structure and biological respectively, the low rate of minor side effects, the good function
  • B Lyer
according to intention-to-treat and per protocol analyses, [15] L onnerdal B, Lyer S. Lactoferrin: molecular structure and biological respectively, the low rate of minor side effects, the good function. Annu Rev Nutr 1995;15:93–110.
jects, with one more long-lasting therapy or with concomi-Third line treatment for Helicobacter pylori: a prospective, culture-tant acid-suppressing therapy; moreover, it is controversial guided study in peptic ulcer patients
  • F B Sicilia
  • Ducons Ja E Sierra
  • Revillo Mj Ferrero
G omollon F, Sicilia B, Ducons JA, Sierra E, Revillo MJ, Ferrero M. jects, with one more long-lasting therapy or with concomi-Third line treatment for Helicobacter pylori: a prospective, culture-tant acid-suppressing therapy; moreover, it is controversial guided study in peptic ulcer patients. Aliment Pharmacol Ther whether human lactoferrin is inhibitory to H. pylori. 2000;14:1335–8.
Appropriate statistical analysis for 2 × 2 tables
  • G Leandro
  • Md Mazzara
  • Og Manghisi
Leandro G, Mazzara MD, Manghisi OG. Appropriate statistical analysis for 2 × 2 tables. Ital J Gastroenterol 1986;18:284.