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Prof. Mohamed Ahmed El Assal

Academic Position: Professor

Current Administrative Position:

Ex-Administrative Position:

Faculty: Medicine

Department: INTERNAL MEDICINE

Edu-Mail: mohamed.alassal@fmed.bu.edu.eg

Alternative Email: Mohamedelassal500@hotmail.com

Mobile: Not Available

Scientific Name: **********

Publications [ Titles(15) :: Papers(2) :: Abstracts(9) ]

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Lactoferrin as an added therapy in the treatment of Helicobacter pylori [2018-02-18]
ORIGINAL ARTICLE Year : 2017 | Volume : 34 | Issue : 2 | Page : 119-122 Lactoferrin as an added therapy in the treatment of Helicobacter pylori Fawzy A Megahed, Mohammed A El-Assal, Ahmed S Dabour, Ramy A Samy, Mahmoud A Rizk, Soha H Al Adhm Gastroenterology and Hepatology Unit, Internal Medicine Department, Faculty of Medicine, Benha University, Benha, Egypt Date of Submission 14-Feb-2017 Date of Acceptance 28-Mar-2017 Date of Web Publication 20-Nov-2017 Correspondence Address: Soha H Al Adhm Gastroenterology and Hepatology Unit, Internal Medicine Department, Faculty of Medicine, Benha University, Benha, 13518 Egypt Source of Support: None, Conflict of Interest: None Check DOI: 10.4103/bmfj.bmfj_25_17 Abstract Background Bovine lactoferrin (bLF), an iron-binding glycoprotein, is a nonenzymatic antioxidant found in the whey fraction of fermented milk as well as in colostrum. The possibility that bLF may help improve the Helicobacter pylori eradication rate was first conceived in 1997 when an in-vitro study by Yamazaki and colleagues showed that bLF was bactericidal to H. pylori in Brucella broth. Later in-vitro studies have confirmed the same and yielded evidence of the possible mechanism of the bactericidal action of bLF, relating it to the high iron-binding affinity and prevention of iron utilization by H. pylori. Lactoferrin is used for treating stomach and intestinal ulcers, diarrhea, and hepatitis C. Aim The aim of the study was to verify the value of adding lactoferrin to the treatment of H. pylori infection. Patients and methods This study was conducted on 50 patients selected from Internal Medicine Department, Benha University Hospital. They were divided into group 1, which included 25 patients who were treated with traditional therapy (clarithromycin, omeprazole, amoxicillin, or metronidazole), and group 2, who were treated by traditional therapy plus lactoferrin (pravotin) for 1 week. H. pylori stool antigen testing was performed for both groups before and after therapy to assess the response to therapy. Results were statistically analyzed. Results Our results show that addition of lactoferrin improves the H. pylori infection eradication rate. Keywords: Helicobacter pylori infection, lactoferrin, stool antigen, traditional therapy How to cite this article: Megahed FA, El-Assal MA, Dabour AS, Samy RA, Rizk MA, Al Adhm SH. Lactoferrin as an added therapy in the treatment of Helicobacter pylori. Benha Med J 2017;34:119-22 How to cite this URL: Megahed FA, El-Assal MA, Dabour AS, Samy RA, Rizk MA, Al Adhm SH. Lactoferrin as an added therapy in the treatment of Helicobacter pylori. Benha Med J [serial online] 2017 [cited 2018 Feb 18];34:119-22. Available from: http://www.bmfj.eg.net/text.asp?2017/34/2/119/218830 Introduction Helicobacter pylori is a Gram-negative, spiral bacterium that locates itself on the epithelial surface of the stomach. It is thought to be the most common bacterial infection worldwide. Virtually all persons infected by this organism develop gastritis, a signature feature of which is the capacity to persist for decades, leading to chronic inflammation of the underlying mucosa. It has been recognized to be associated with increased risk for chronic gastritis, peptic ulcer disease (PUD) (gastric and duodenal), gastric mucosal-associated lymphoid tissue lymphoma, and gastric adenocarcinoma. The WHO has described H. pylori as a class 1 carcinogen for gastric carcinoma. Isolation of the organism by Warren and colleagues in 1983 has modified the management of PUD [1]. Eradication of H. pylori is considered a necessary step in the management of these diseases. First-line traditional therapy eradication regimens (proton pump inhibitor plus clarithromycin and amoxicillin or metronidazole) are inconvenient and achieve unpredictable and often poor results. Second-line therapy includes traditional therapy plus lactoferrin [2]. Bovine lactoferrin (bLF), an iron-binding glycoprotein, is a nonenzymatic antioxidant found in the whey fraction of fermented milk as well as in colostrum. The possibility that bLF may help improve the H. pylori eradication rate was first conceived in 1997 when an in-vitro study by Yamazaki et al. [3] showed that bLF was found to be bactericidal to H. pylori in Brucella More Details broth. Later in-vitro studies have confirmed the same and yielded evidence of the possible mechanism of the bactericidal action of bLF, relating it to the high iron-binding affinity and prevention of iron utilization by H. pylori [4]. Lactoferrin is used for treating stomach and intestinal ulcers, diarrhea, and hepatitis C. It is also used as an antioxidant and to protect against bacterial and viral infections. Other uses include stimulating the immune system, promoting healthy intestinal bacteria, preventing cancer, and regulating the way the body processes iron [5]. Patients and methods Inclusion criteria Patients of both sexes who were aged 12–60 years and positive for H. pylori antigen in their stool were eligible for participation in this study. Exclusion criteria Patients with GIT malignancy, those with iron deficiency anemia, and patients negative for H. pylori antigen in stool were exempted from the study. All patients were subjected to the following: history taking, including age, sex, occupation, address, marital status, habits, past history of any disease, family history, and any present complaint; and clinical examination, including general and systemic examination. Laboratory investigation Complete blood count, liver function tests [alanine aminotransferase (ALT), aspartate aminotransferase, and bilirubin], and H. pylori antigen test in stool samples (before and after treatment) were conducted. The clinical data were recorded on a report form. These data were tabulated and analyzed using the computer program statistical package for social science (SPSS, version 16; SPSS Inc., Chicago, Illinois, USA) to obtain the following. Statistical analysis Descriptive data Descriptive statistics were calculated for the data in the form of mean and SD for quantitative data and frequency and distribution for qualitative data. Analytical statistics In the statistical comparison between the different groups, the significance of difference was tested using one of the following tests: the paired t-test, which was used to compare the mean of variables before and after treatment in the same group; and the Student t-test, which was used to compare the mean of two groups of quantitative data. Intergroup comparison of categorical data was performed using the χ2-test. A P value less than 0.05 was considered statistically significant, whereas values more than 0.05 were considered statistically insignificant and values less than 0.01 were considered highly significant in all analyses. Results The comparison between the studied groups before treatment showed no significant statistical values, except for the ALT level. The comparison between the studied groups after treatment showed significant statistical values for hemoglobin level, mean corpuscular volume (MCV) level, ALT level, and H. pylori antigen in stool ([Table 1] and [Figure 1]). Table 1 Comparison between the studied groups after treatment showing significant statistical values for Helicobacter pylori antigen in stool samples Click here to view Figure 1 Comparison between the studied groups after treatment showing significant statistical values for Helicobacter pylori antigen in stool samples Click here to view Discussion bLF, an iron-binding glycoprotein, is a nonenzymatic antioxidant found in the whey fraction of fermented milk as well as in colostrum. The possibility that bLF may help to improve the H. pylori eradication rate was first conceived in 1997 when an in-vitro study by Yamazaki et al.found bLF to be bactericidal to H. pylori in Brucella broth. Later in-vitro studies have confirmed the same and yielded evidence of the possible mechanism of the bactericidal action of bLF, relating it to the high iron-binding affinity and prevention of iron utilization by H. pylori[4]. Lactoferrin is used for treating stomach and intestinal ulcers and diarrhea. It is also used as an antioxidant and to protect against bacterial and viral infections. Other uses include stimulating the immune system, promoting healthy intestinal bacteria, preventing cancer, and regulating the way the body processes iron [5]. H. pylori is a Gram-negative, spiral bacterium that locates itself on the epithelial surface of the stomach. It is thought to be the most common bacterial infection worldwide. Virtually all persons infected with this organism develop gastritis, a signature feature of which is the capacity to persist for decades, leading to chronic inflammation of the underlying mucosa. It has been recognized to be associated with increased risk for chronic gastritis, PUD (gastric and duodenal), gastric mucosal-associated lymphoid tissue lymphoma, and gastric adenocarcinoma. The WHO has described H. pylori as a class 1 carcinogen for gastric carcinoma. Isolation of the organism by Warren and colleagues in 1983 has modified the management of PUD [1]. Eradication of H. pylori is considered a necessary step in the management of these diseases. First-line traditional therapy eradication regimens (proton pump inhibitor plus clarithromycin and amoxicillin or metronidazole) are inconvenient and achieve unpredictable and often poor results. Second-line therapy may include traditional therapy plus lactoferrin [2]. In the present study, the results show that addition of lactoferrin improves the H. pylori infection eradication rate. In agreement with our results was that of di Mario et al. [6], who found that the addition of 200 mg of bLF twice a day for 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 twice daily), clarithromycin (500 mg twice daily), and tinidazole (500 mg twice daily) [6]. Similarly, Tursi et al. [7] reported that quadruple therapy is now recommended as a second-line therapy for H. pylori infection. It has been found that quadruple therapy is very effective in retreating H. pylori-positive patients with a failure of a first attempt to cure this infection, especially when Lactobacillus casei is added [7]. The present study as well agrees with that of Zou et al. [8], who mentioned that bLF improves the side effects and increases eradication rates when associated with triple therapy. It is possible that the combination of bLF with clarithromycin, amoxicillin, and esomeprazole provokes a synergistic effect by launching attacks from different directions against H. pylori that could lead to a better complete clearance of the bacterial infection [8]. Okuda et al. [9] proved that bLF-based therapy could potentially improve H. pylori eradication rates by ∼10% without any significant impact on the treatment-associated adverse effects. Ellison [10] found that lactoferrin appears to be an important factor in the host’s defense against a wide range of bacteria. Potential mechanisms through which bLF inhibits the growth of certain microorganisms (including H. pylori) have been hypothesized. These include antimicrobial activity (bacteriostatic and bactericidal effects), structural changes in the microbial cell wall, complete loss of membrane potential and integrity, indirect effects on enzyme activation, increased generation of the metabolic by-products of anaerobic metabolism, iron deprivation, and a combination of these factors [10]. In contrast to our results, Zullo et al. [11] reported no difference between standard triple therapy and triple therapy+bLF in a recent study performed in three centers. Opekum et al. [12] also found that lactoferrin is not efficacious against H. pylori infection as a single agent but must be added to the triple therapy to improve the result. In particular, they claimed that there was no enhanced efficacy when amoxicillin was combined with bLF. However, it should be noted that the only published data on the interaction between amoxicillin and bLF are based on animal models proposed by Dial et al. [13]. In conclusion, our results showed that addition of lactoferrin can improve the H. pylori infection eradication rate and the present study recommends adding bLF to traditional therapy eradication regimens. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. References 1. Peek RM Jr, Fiske C, Wilson KT. Role of innate immunity in Helicobacter pylori-induced gastric malignancy. Physiol Rev 2010; 90:831–858. 2. Garza-González E, Perez-Perez GI, Maldonado-Garza HJ, Bosques-Padilla FJ. A review of Helicobacter pylori diagnosis, treatment, and methods to detect eradication. World J Gastroenterol 2014; 20:1438–1449. 3. Yamazaki N, Yamauchi K, Kawase K, Hayasawa H, Nakao K, Imoto I. Antibacterial effects of lactoferrin and a pepsin-generated lactoferrin peptide against Helicobacter pylori in vitro. J Infect Chemother 1997; 3:85–89. 4. Serna H, Dial EJ, Hall LR. Antibiotic properties of bovine lactoferrin on Helicobacter pylori. Dig Dis Sci 1998; 12:2750–2756. 5. Defer MC, Dugas B, Picard O, Damais C. Impairment of circulating lactoferrin in HIV-1 infection. Cell Mol Biol (Noisy-le-grand) 1995; 41:417–421. 6. Di Mario F, Aragona G, Dal Bo N, Ingegnoli AV, Cavestro GM, Moussa A, Potential use of lactoferrin in a 7 days trip therapy for Helicobacter pylori eradication: a pilot study. J Clin Gastroenterol 2003; 36:396–398. 7. Tursi A, Brandimarte G, Giorgetti GM, Modeo ME. Effect of Lactobacillus casei supplementation on the effectiveness and tolerability of a new second-line 10-day quadruple therapy after failure of a first attempt to cure Helicobacter pylori infection. Med Sci Monit 2004; 10:CR662–CR666. 8. Zou J, Dong J, Yu XF. Meta-analysis: the effect of supplementation with lactoferrin on eradication rates and adverse events during Helicobacter pylori eradication therapy. Helicobacter 2009; 14:119–127. 9. Okuda M, Nakazawa T, Yamauchi K, Miyashiro E, Koizumi R, Booka M et al. Bovine lactoferrin is effective to suppress Helicobacter pylori colonization in the human stomach: a randomized, double blinded, placebo controlled study. J Infect Chemother 2005; 11:265–269. 10. Ellison RT. The effects of lactoferrin on gram-negative bacteria. Adv Exp Med Biol 1994; 357:71–90. 11. Zullo A, de Francesco V, Scaccianoce G, Hassan C, Panarese A, Piglionica D et al. Quadruple therapy with lactoferrin for Helicobacter pylori eradication: a randomised, multicentre study. Dig Liver Dis 2005; 37:496–500. 12. Opekum AR, El-Zaimaity HM, Osato MS, Gilger Ma, Malaty HM, Terry M et al. Novel therapies for H. pylori infection. Aliment Pharmacol Ther 1999; 13:35–42 13. Dial EJ, Romero JJ, Headon DR, Lichtenberger LM. Recombinant human lactoferrin is effective in the treatment of Helicobacter felis-infected mice. J Pharm Pharmacol 2000; 52:1541–1546. more

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