الفهرس 
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Abstract
VI. Summary and recommendations
VI.1. Summary
Helicobacter pylori are gram negative bacteria that can inhabit various areas of the stomach, particularly the antrum. It causes low-level inflammation of the stomach lining and is strongly linked to the development of duodenal and gastric ulcers and stomach cancer. The standard first-line therapy is a one week ”triple therapy” consisting of proton pump inhibitor (PPI) such as omeprazole, lansoprazole or rabeprazole and 2 antibiotics such as clarithromycin and amoxicillin .
Proton pump inhibitors are metabolized in the liver by the cytochrome P450 system (CYP) mainly through Cytochrome P450 2C19 (CYP2C19).
Polymorphism of CYP2C19 gene affects pharmacokinetics and pharmacodynamics of PPIs with a consequent effect on the intragastric pH and this is considered to be one of the causes for treatment failure for H. pylori linking the cure rate with CYP2C19 gene polymorphism that is different among different populations. CYP2C19*2 and CYP2C19*3 are the most common mutant variants of CYP2C19.
The objective of this study was to check the influence of CYP2C19 polymorphism on PPI–based triple therapy for H. pylori infection among Egyptian children presenting with gastritis from the Nile Delta region of Egypt, Also applying the use of the relatively simple and accurate methods of molecular biology techniques as PCR – Restriction Fragment Length Polymorphism (PCR-RFLPs) for mutation identification.
The participant in this study included 100 children (39 males and 61 females) of an age mean ± SD of 11.45 ± 3.0 years. These were diagnosed clinically with dyspepsia due to gastritis and underwent an upper gastrointestinal endoscopy at Mansoura University Pediatric Hospital, Department of Gastroenterology. They had not previously received H. pylori treatment. Cases were classified according to their stomach pathology and being positive to the H. pylori stool antigen into mild (25 cases), moderate (65 cases) and severe (10 cases). Treatment was in the form of lansoprazole (0.6 mg/kg twice a day), amoxicillin (30 mg/kg twice a day), and clarithromycin (15 mg/kg twice a day) for 14 days. More than one month after the treatment, a stool antigen test for H. pylori was performed to assess the cure rate.
Detection of CYP2C19 gene mutations related to CYP2C19*2 and CYP2C19*3 was done using ”PCR- RFLP” (Polymerase Chain Reaction – Restriction Fragment Length Polymorphism) technique.
The results of the present study showed the following:
Genotyping children treated for H. pylori infection related to their metabolic capability linked to CYP2C19 polymorphism showed that the total frequency of RMs (CYP2C19*1*1) was 65%, the frequency of IMs (CYP2C19*1*2 and CYP2C19*1*3) was equal to 26%, while that of PMs (CYP2C19*2*2 and CYP2C19*2*3) was 9% (Table 1). Testing genetic equilibrium between the observed and expected genotypes using the Hardy Weinberg equilibrium showed that the CYP2C19*3 genetic variants were conforming to the law (Chi square =3.40, p >0.05). On the other hand, the CYP2C19*2 polymorphism showed a non-fitting pattern (Chi square =16.4, p <0.001) probably due to the relative higher frequency of the homozygous *2*2 genotype .
Cure rates using the triple therapy for 2 weeks showed that cases with the IMs genotypic status of CYP2C19 had a higher cure rate of H. pylori when compared with those with the RMs genotypic status (84.6 vs. 69.2, OR=2.4 95% CI=0.8-7.8) although it was statistically non-significant probably due to the relatively small sample size. In addition, cases with the PMs genotypic status had reasonable higher cure rate compared with those of the RMs genotypic status (77.8 vs. 69.2, OR=1.6 95% CI=0.3-8.1) which was also statistically non-significant. The combination of CYP2C19 IMs and PMs had a higher cure rate relative to RMs (OR=2.15, 95% CI=0.8-5.9). Comparing the cure rates of cases subgroups with different CYP2C19 genetic polymorphism related to age, gender and severity of infection did not show a significant difference.
In conclusion, there was an influence of CYP2C19 genetic polymorphism in in eradication of Helicobacter pylori among Egyptian children. This might warrant adoption of screening program for H.pylori patients treated with triple therapy including CYP2C19 genetic screening.
VI.2. Recommendations
1. Routine screeninig for CYP2C19 mutations for H.pylori patients undergo triple therapy treatment.
2. another wide spectrum study including a large and multi-centered sample for a full analysis of all factors presumably affecting the cure rate of H. pylori infection.
We also recommend some precautions to avoid infection of H.pylori:
1. Eating cranberries, red grapes, and blueberries make H. Pylori grow much more slowly, and changes the shape of the bacterium into a coccoid form, so that it is no longer a helicobacter (Matsushima et al., 2008)
2. Broccoli sprouts inhibit H. Pylori (Yanaka et al., 2009).
3. Try to work in a ventilated area. If you don’t, keep the doors open to allow for a fresh air flow.
4. Wash your hands frequently and properly: wash in the hottest temperature that you can tolerate (don’t push it or you’ll get scalded) and use warm water for children.
5. Try not to touch your face, especially around your mouth and nose areas.
6. Wash hands after covering a cough or sneeze; or after blowing your nose.
7. Try not to eat food that has been prepared in an ”unhygienic” setting; observe how the food preparation is being done, how clean an area appears etc. If in doubt, don’t eat it.
8. Only drink clean water from a reputable source. Use filters or other means of decontaminating water if you are traveling or camping.
9. Wash your hands before cooking or preparing food. Wash them when you have finished preparations also, as bacteria could be sitting on meats or dirt on vegetables etc.
10. Wash your hands when visiting hospital and when leaving the hospital. If you are tending to a sick person, keep everything as clean as possible, including your hands.
11. Wash your hands after touching pets and other animals. This includes petting farms, your own pets and visiting animals. You don’t know where they’ve been and without thinking you might pop your fingers into your mouth.