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Helicobacter pylori

Scientific classification
Kingdom: Bacteria
Phylum: Proteobacteria
Class: Epsilon Proteobacteria
Order: Campylobacterales
Family: Helicobacteraceae
Genus: Helicobacter
Species: H. The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have The Proteobacteria are a major group ( Phylum) of Bacteria. They include a wide variety of Pathogens such as Escherichia, The Campylobacterales are an order of Proteobacteria. They make up the epsilon subdivision together with the small family Nautiliaceae. Helicobacter is a Genus of Gram-negative bacteria possessing a characteristic Helix shape Helicobacter is a Genus of Gram-negative bacteria possessing a characteristic Helix shape pylori
Binomial name
Helicobacter pylori
((Marshall et al. 1985) Goodwin et al. 1989)

ICD-9 code: 041. 86

Helicobacter pylori (pronounced /ˌhɛlɪkəˈbæktɚ paɪˈlɔəraɪ/) is a gram-negative, microaerophilic bacterium that infects various areas of the stomach and duodenum. Gram-negative bacteria are those Bacteria that do not retain Crystal violet dye in the Gram staining protocol Microaerophilic Organisms are a specific type of microorganism (especially bacteria that requires Oxygen to survive but requires environments containing lower levels The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have An infection is the detrimental Colonization of a host Organism by a foreign Species. In Human anatomy, the stomach is a J-shaped hollow muscular organ of the Gastrointestinal tract involved in the second phase of Digestion, following In Anatomy of the Digestive system, the duodenum is a hollow jointed tube about 25-30 cm (10-12 in long connecting the Stomach to the Jejunum Many cases of peptic ulcers, gastritis, duodenitis, and cancers are caused by H. A peptic ulcer, also known as PUD or peptic ulcer disease, is an Ulcer (defined as mucosal erosions equal to or greater than 0 Gastritis is an inflammation of the lining of the stomach There are many possible causes Duodenitis is Inflammation of the Duodenum. It may persist acutely or chronically Cancer bacteria (not Viruses) are infectious organisms which are known or suspected of causing cancer pylori infections. However, many who are infected do not show any symptoms of disease. A disease is an abnormal condition of an organism that impairs bodily functions and can be deadly H. pylori's helical shape (from which the genus name is derived) is thought to have evolved to penetrate and favor its motility in the mucus gel layer. A genus (plural genera from Γένος Latin genus "descent family type gender" is a low-level Taxonomic Motility is a biological term which refers to the ability to move spontaneously and actively consuming energy in the process In vertebrates mucus is a slippery secretion produced by and covering Mucous membranes It is a viscous Colloid containing Antiseptic enzymes (such as [1][2]

Contents

History

See also: Timeline of peptic ulcer disease and Helicobacter pylori

In 1875, German scientists found helical shaped bacteria in the lining of the human stomach. Wikipedia talkFeatured lists for an explanation of this and other inclusion tags below -->This is a timeline of the events relating to the discovery that peptic Germany, officially the Federal Republic of Germany ( ˈbʊndəsʁepuˌbliːk ˈdɔʏtʃlant is a Country in Central Europe. A helix (pl helixes or helices) from the Greek word έλιξ, is a special kind of Space curve, i The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have In Human anatomy, the stomach is a J-shaped hollow muscular organ of the Gastrointestinal tract involved in the second phase of Digestion, following The bacteria could not be grown in culture and the results were eventually forgotten. A microbiological culture, AKA microbial culture, is a method of multiplying microbial organisms by letting them reproduce in predetermined culture media under controlled laboratory [3] In 1893, the Italian researcher Giulio Bizzozero described helical shaped bacteria living in the acidic environment of the stomach of dogs. Italy (Italia officially the Italian Republic, (Repubblica Italiana is located on the Italian Peninsula in Southern Europe, and on the two largest Giulio Bizzozero (1846-1901 was an Italian doctor and medical researcher The dog ( Canis lupus familiaris) is a domesticated Subspecies of the gray wolf, a Mammal of the Canidae family of the order [4] Professor Walery Jaworski of the Jagiellonian University in Kraków investigated sediments of gastric washings obtained from humans in 1899. Walery Jaworski ( March 20, 1849 &ndash July 17, 1924) was one of the pioneers of Gastroenterology in Poland. For several academies alternatively called "Krakow Academy" see Education in Kraków The Jagiellonian University (Uniwersytet Kraków, in English also spelled Krakow or Cracow (ˈkrækaʊ M-W: krăk'ou krāk'ō is one of the largest and oldest cities in Poland In Human anatomy, the stomach is a J-shaped hollow muscular organ of the Gastrointestinal tract involved in the second phase of Digestion, following Among some rod-like bacteria, he also found bacteria with a characteristic helical shape, which he called Vibrio rugula. He was the first to suggest a possible role of this organism in the pathogeny of gastric diseases. This work was included in the "Handbook of Gastric Diseases", but it did not have much impact because it was written in Polish. Polish ( język polski, polszczyzna) is the Official language of Poland. [5]

The bacterium was rediscovered in 1979 by Australian pathologist Robin Warren, who did further research on it with Australian physician Barry Marshall beginning in 1981; they isolated the organisms from mucosal specimens from human stomachs and were the first to successfully culture them. For a topic outline on this subject see List of basic Australia topics. Dr John Robin Warren AC (born 11 June[[ 937]] in Adelaide) is an Australian Pathologist and researcher who is credited with the 1979 For a topic outline on this subject see List of basic Australia topics. Barry James Marshall, AC FRS FAA (born 30 September 1951) is an Australian Physician, Nobel Prize [6] In their original paper,[7] Warren and Marshall contended that most stomach ulcers and gastritis were caused by infection by this bacterium and not by stress or spicy food as had been assumed before. A spice is a dried Seed, Fruit, Root, Bark or vegetative substance used in Nutritionally insignificant quantities as a Food additive [8]

The medical community was slow to recognize the role of this bacterium in stomach ulcers and gastritis, believing that no microorganism could survive for long in the acidic environment of the stomach. The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have A peptic ulcer, also known as PUD or peptic ulcer disease, is an Ulcer (defined as mucosal erosions equal to or greater than 0 Gastritis is an inflammation of the lining of the stomach There are many possible causes A microorganism (also spelled micro organism or micro-organism and also called a microbe) is an Organism that is Microscopic (usually The community began to come around after further studies were done, including one in which Marshall drank a Petri dish of H. pylori, developed gastritis, and the bacteria were recovered from his stomach lining, thereby satisfying three out of the four of Koch's postulates. Koch's postulates are four criteria designed to establish a causal relationship between a causative Microbe and a Disease. The fourth was satisfied after a second endoscopy ten days after inoculation revealed signs of gastritis and the presence of "H. pylori". Marshall was then able to treat himself using a fourteen day dual therapy with bismuth salts and metronidazole. Bismuth (ˈbɪzməθ is a Chemical element that has the symbol Bi and Atomic number 83 Metronidazole ( INN) (mɛtrəˈnaɪdəzoʊl is a Nitroimidazole anti-infective medication used mainly in the treatment of infections caused by susceptible Marshall and Warren went on to show that antibiotics are effective in the treatment of many cases of gastritis. In 1994, the National Institutes of Health (USA) published an opinion stating that most recurrent gastric ulcers were caused by H. "NIH" redirects here For other meanings of NIH see NIH (disambiguation. pylori, and recommended that antibiotics be included in the treatment regimen. In modern usage an antibiotic is a Chemotherapeutic agent with activity against Microorganisms such as Bacteria, fungi or Protozoa [9] Evidence has been accumulating to suggest that duodenal ulcers are also associated with H. A peptic ulcer, also known as PUD or peptic ulcer disease, is an Ulcer (defined as mucosal erosions equal to or greater than 0 pylori infection. [10][11] In 2005, Warren and Marshall were awarded the Nobel Prize in Medicine for their work on H. The Nobel Prize in Physiology or Medicine (Nobelpriset i fysiologi eller medicin is awarded once a year by the Swedish Karolinska Institute. pylori. [12]

Before the appreciation of the bacterium's role, stomach ulcers were typically treated with medicines that neutralize gastric acid or decrease its production. Medicine is the art and science of healing It encompasses a range of Health care practices evolved to maintain and restore Human Health by the Gastric acid is one of the main Secretions of the Stomach, together with several Enzymes and Intrinsic factor. While this worked well, the ulcers very often reappeared. At one time, bismuth subsalicylate was commonly used to treat gastritis and peptic ulcers. Bismuth subsalicylate, with a chemical formula C7H5BiO4 is a drug used to treat Nausea, Heartburn, Indigestion, It was often effective, but fell out of use, since its mechanism of action was a mystery. Nowadays it is quite clear that it is due to the bismuth salt acting as an antibiotic. Today, many stomach ulcers are treated with antibiotics effective against H. pylori.

The bacterium was initially named Campylobacter pyloridis, then C. pylori (after a correction to the Latin grammar) and in 1989, after DNA sequencing and other data showed that the bacterium did not belong in the Campylobacter genus, it was placed in its own genus, Helicobacter. The grammar of Latin, like that of other ancient Indo-European languages, is highly inflected, which allows for a large degree of flexibility when choosing word order The term DNA sequencing encompasses biochemical methods for determining the order of the Nucleotide bases Adenine, Guanine, Cytosine The Genus Campylobacter, (meaning 'twisted bacteria' first discovered in 1963 describes Gram-negative, spiral Microaerophilic bacteria A genus (plural genera from Γένος Latin genus "descent family type gender" is a low-level Taxonomic Helicobacter is a Genus of Gram-negative bacteria possessing a characteristic Helix shape The name pylōri means "of the pylorus" or pyloric valve (the circular opening leading from the stomach into the duodenum), from the Greek word πυλωρός, which means gatekeeper. The pylorus (from Greek πυλωρος = "gate guard" is the region of the Stomach that connects to the Duodenum. In Anatomy of the Digestive system, the duodenum is a hollow jointed tube about 25-30 cm (10-12 in long connecting the Stomach to the Jejunum Greek (el ελληνική γλώσσα or simply el ελληνικά — "Hellenic" is an Indo-European language, spoken today by 15-22 million people mainly

While H. pylori remains the most medically important bacterial inhabitant of the human stomach, other species of the Helicobacter genus have been identified in other mammals and some birds, and some of these can infect humans. Medicine is the art and science of healing It encompasses a range of Health care practices evolved to maintain and restore Human Health by the The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have Mammals ( class Mammalia) are a class of Vertebrate Animals characterized by the presence of Sweat glands, including sweat glands Birds ( class Aves) are bipedal endothermic ( Warm-blooded) Vertebrate animals that lay eggs. [13] Helicobacter species have also been found to infect the livers of certain mammals and to cause liver disease. The liver is a vital organ in the human body and is present in Vertebrates and some other animals [14]

Structure

H. pylori is a helical shaped Gram-negative bacterium, about 3 micrometres long with a diameter of about 0. Gram-negative bacteria are those Bacteria that do not retain Crystal violet dye in the Gram staining protocol 5 micrometre. It has 4–6 flagella. A flagellum ( plural flagella) is a tail-like structure that projects from the Cell body of certain Prokaryotic and Eukaryotic cells and it It is microaerophilic, i. Microaerophilic Organisms are a specific type of microorganism (especially bacteria that requires Oxygen to survive but requires environments containing lower levels e. it requires oxygen but at lower levels than those contained in the atmosphere. Oxygen (from the Greek roots ὀξύς (oxys (acid literally "sharp" from the taste of acids and -γενής (-genēs (producer literally begetteris the Temperature and layers The temperature of the Earth's atmosphere varies with altitude the mathematical relationship between temperature and altitude varies among five It contains a hydrogenase which can be used to obtain energy by oxidizing molecular hydrogen (H2) that is produced by other intestinal bacteria. A hydrogenase is an Enzyme that catalyses the reversible oxidation of molecular Hydrogen (H2 Hydrogen (ˈhaɪdrədʒən is the Chemical element with Atomic number 1 [15] It tests positive for oxidase, catalase, and urease. The oxidase test is a test used in Microbiology to determine if a Bacterium produces certain Cytochrome c oxidases It uses disks impregnated with a Catalase is a common Enzyme found in nearly all living organisms where it functions to catalyze the decomposition of Hydrogen peroxide to Urease ( is an Enzyme that catalyzes the Hydrolysis of Urea into Carbon dioxide and Ammonia. It is capable of forming biofilms[16] and conversion from helical to coccoid form[17], both likely to favor its survival and be factors in the epidemiology of the bacterium. A biofilm is a structured community of Microorganisms encapsulated within a self-developed polymeric matrix and adherent to a living or inert surface Staphylococcus aureus Gramjpg|thumb|300px| Staphylococcus bacteria]] Cocci (singular - coccus, from the Latin coccinus (scarlet and derived from the Epidemiology is the study of factors affecting the Health and Illness of populations and serves as the foundation and Logic of interventions made in the The coccoid form of the organism has not been cultured, but has been found in the water supply in the US. This form has also been found to be able to adhere to gastric epithelial cells in vitro. In vitro ( Latin: within the glass refers to the technique of performing a given experiment in a controlled environment outside of a living Organism

H. pylori possesses five major outer membrane protein (OMP) families. Each OMP appears to have specific functions. [18] All gastric and enterohepatic Helicobacter species are highly motile due to a flagella. A flagellum ( plural flagella) is a tail-like structure that projects from the Cell body of certain Prokaryotic and Eukaryotic cells and it The characteristic sheathed flagellar filaments of helicobacters are composed of two copolymerized flagellins, FlaA and FlaB. Flagellar motility is essential for Helicobacter species to colonize the gastric mucus. [19]

Molecular model of H. pylori urease enzyme
Molecular model of H. pylori urease enzyme

Colonization

With its flagella, the bacterium moves through the stomach lumen and drills into the mucus gel layer of the stomach. A flagellum ( plural flagella) is a tail-like structure that projects from the Cell body of certain Prokaryotic and Eukaryotic cells and it In vertebrates mucus is a slippery secretion produced by and covering Mucous membranes It is a viscous Colloid containing Antiseptic enzymes (such as A gel (from the lat gelu &mdashfreezing cold ice or gelatus &mdashfrozen immobile is an apparently solid jelly-like material formed from a It then finds ways to live in various areas of the stomach. The known areas include: inside the mucus gel layer (with a preference for the superficial area), above epithelial cells, and inside vacuoles formed by H. Superficial is a general term meaning "regarding the Surface " often Metaphorically Both in the literal as in the metaphorical sense the term has often a In biology and medicine epithelium is a tissue composed of cells that line the cavities and surfaces of structures throughout the body The cell is the structural and functional unit of all known living Organisms It is the smallest unit of an organism that is classified as living and is often called In general vacuole functions include Removing unwanted structural debris Isolating materials that might be harmful or a threat to the cell Containing pylori in epithelial cells. It produces adhesins which bind to membrane-associated lipids and carbohydrates and help its adhesion to epithelial cells. Adherence is often an essential step in bacterial Pathogenesis or Infection, required for Colonizing a new host. Lipids are broadly defined as any fat- Soluble ( lipophilic) naturally-occurring Molecule, such as fats oils waxes cholesterol sterols fat-soluble Carbohydrates (from ' Hydrates of Carbon ' or saccharides ( Greek σάκχαρον meaning " Sugar " are the most An example of this is the Lewis b antigen. It produces large amounts of urease enzymes which are localized inside and outside of the bacterium. Urease ( is an Enzyme that catalyzes the Hydrolysis of Urea into Carbon dioxide and Ammonia. Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins Urease metabolizes urea (which is normally secreted into the stomach) to carbon dioxide and ammonia (which neutralizes gastric acid). Urea is an Organic compound with the Chemical formula ( N[[hydrogen H]]22 C[[oxygen O]] Carbon dioxide ( Chemical formula:) is a Chemical compound composed of two Oxygen Atoms covalently bonded to a single Ammonia is a compound with the formula N[[hydrogen H3]] It is normally encountered as a Gas with a characteristic pungent Odor The survival of H. pylori in the acidic stomach is dependent on urease, and it would eventually die without it. The ammonia that is produced is toxic to the epithelial cells, and, along with the other products of H. Toxicity is the degree to which a substance is able to damage an exposed organism pylori—including protease, catalase and certain phospholipases—causes damage to those cells. A protease is any Enzyme that conducts Proteolysis, that is begins protein Catabolism by Hydrolysis of the Peptide bonds that link Catalase is a common Enzyme found in nearly all living organisms where it functions to catalyze the decomposition of Hydrogen peroxide to A phospholipase is an enzyme that converts Phospholipids into Fatty acids and other Lipophilic substances

Some strains of the bacterium have a particular mechanism for "injecting" the inflammatory inducing agents peptidoglycan from their own cell wall into epithelial stomach cells. In biology strain is a low-level Taxonomic rank used in three related ways Inflammation ( Latin, inflamatio, to set on fire is the complex biological response of vascular tissues to harmful stimuli such as Pathogens Not to be confused with Glycoprotein. Peptidoglycan, also known as murein, is a Polymer consisting of sugars and amino A cell wall is a tough flexible and sometimes fairly rigid layer surrounding a cell, located external to the Cell membrane, which provides the cell with structural (See below for "cagA pathogenicity island" in the section Genome studies of different strains) This factor may play a role in allowing certain strains to invade host tissue. Helicobacter pylori ( is a Gram-negative, microaerophilic Bacterium that inhabits various areas of the stomach and Duodenum. In Biology, a host is an organism that harbors a Virus or Parasite, or a mutual or Commensal Symbiont, typically providing nourishment Tissue is a cellular organizational level intermediate between cells and a complete organism [20]

Causes of infection

H. pylori is a contagious bacterium. Many researchers think that H. pylori is transmitted orally by means of fecal matter through the ingestion of waste tainted food or water. A clean and hygienic environment can help decrease the risk of H. pylori infection.

There is experimental evidence, however, to show that Heliobacter species are not, in fact transmitted via the fecal-oral route, but rather through oral-oral contact. [21]

Diagnosis of infection

Immunohistochemical staining of H. pylori from a gastric biopsy.
Immunohistochemical staining of H. Immunohistochemistry or IHC refers to the process of localizing proteins in cells of a tissue section exploiting the principle of antibodies binding specifically pylori from a gastric biopsy. In Human anatomy, the stomach is a J-shaped hollow muscular organ of the Gastrointestinal tract involved in the second phase of Digestion, following A biopsy (in Greek: βίος life and όψη look/appearance is a Medical test involving the removal of cells or tissues

Diagnosis of infection is usually made by checking for dyspeptic symptoms and then doing tests which can suggest H. Dyspepsia (from the Greek "δυς-" (Dys- and "πέψη" (Pepse known in plain English as indigestion, meaning hard pylori infection. One can test noninvasively for H. pylori infection with a blood antibody test, stool antigen test, or with the carbon urea breath test (in which the patient drinks 14C- or 13C-labelled urea, which the bacterium metabolizes producing labelled carbon dioxide that can be detected in the breath). Blood is a specialized Bodily fluid that delivers necessary substances to the body's cells such as nutrients and oxygen—and transports Waste products Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily An antigen (from antibody-generating) or immunogen is a substance that prompts the generation of Antibodies and can cause an immune response A stool test is one where fecal matter is collected for analysis to diagnose the presence or absence of a medical condition The urea breath test is a rapid diagnostic procedure used to identify Infections by Helicobacter pylori, a spiral Bacterium implicated Carbon-14, 14C, or radiocarbon, is a Radioactive isotope of Carbon discovered on February 27, 1940, by Carbon-13 ( 13C) is a natural stable Isotope of Carbon and one of the Environmental isotopes. Urea is an Organic compound with the Chemical formula ( N[[hydrogen H]]22 C[[oxygen O]] Carbon dioxide ( Chemical formula:) is a Chemical compound composed of two Oxygen Atoms covalently bonded to a single However, the most reliable method for detecting H. pylori infection is a biopsy check during endoscopy with a rapid urease test, histological examination, and microbial culture. A biopsy (in Greek: βίος life and όψη look/appearance is a Medical test involving the removal of cells or tissues Endoscopy means looking inside and typically refers to looking inside the body for medical reasons using an instrument called an endoscope. Rapid urease test is a rapid test for diagnosis of Helicobacter pylori. Histology (from the Greek = 'tissue' is the study of the microscopic anatomy of cells and tissues of Plants and None of the test methods is completely failsafe. Even biopsy is dependent on the location of the biopsy. Blood antibody tests, for example, range from 76% to 84% sensitivity. Some drugs can affect H. pylori urease activity and give "false negatives" with the urea-based tests.

Infection may be symptomatic or asymptomatic (without perceptible ill effects). It is estimated that up to 70% of infection is asymptomatic and that about 2/3 of the world population are infected by the bacterium, making it the most widespread infection in the world. Actual infection rates vary from nation to nation - the West (Western Europe, North America, Australasia) having rates around 25% and much higher in the Third World. In the latter, it is common, probably due to poor sanitary conditions, to find infections in children. In the United States, infection is primarily in the older generations (about 50% for those over the age of 60 compared with 20% under 40 years) and the poorest. The United States of America —commonly referred to as the

This is largely attributed to higher hygiene standards and widespread use of antibiotics. However, antibiotic resistance is appearing in H. Antibiotic resistance is the ability of a Microorganism to withstand the effects of Antibiotics. pylori. [22] There are already many metronidazole resistant strains in Europe, the United States, and developing countries. Metronidazole ( INN) (mɛtrəˈnaɪdəzoʊl is a Nitroimidazole anti-infective medication used mainly in the treatment of infections caused by susceptible The United States of America —commonly referred to as the

The bacteria have been isolated from feces, saliva and dental plaque of infected patients, which suggests gastro-oral or fecal-oral as possible transmission routes. Feces, faeces, or fæces (see spelling differences) is a waste product from an animal's digestive tract expelled through the Anus For the band see Saliva (band; for the village in Azerbaijan see Səliva. Dental plaque is Biofilm (usually colorless that builds up on the Teeth.

It is widely believed that in the absence of treatment, H. pylori infection—once established in its gastric niche—persists for life. In the elderly, however, it is likely infection can disappear as the stomach's mucosa becomes increasingly atrophic and inhospitable to colonization. The proportion of acute infections that persist is not known, but several studies that followed the natural history in populations have reported apparent spontaneous elimination. [23][24]

Treatment of infection

H. pylori colonized on the surface of regenerative epithelium (image from Warthin-Starry's silver stain)
H. pylori colonized on the surface of regenerative epithelium (image from Warthin-Starry's silver stain)

In peptic ulcer patients where infection is detected, the normal procedure is eradicating H. A peptic ulcer, also known as PUD or peptic ulcer disease, is an Ulcer (defined as mucosal erosions equal to or greater than 0 An infection is the detrimental Colonization of a host Organism by a foreign Species. pylori to allow the ulcer to heal. Ulcers are healing wounds that develop on the skin mucous membranes or eye The standard first-line therapy is a one week triple therapy. The Sydney gastroenterolgist Thomas Borody invented the first triple therapy in 1987. Gastroenterology ( MeSH heading is the branch of Medicine whereby the Digestive system and its disorders are studied Thomas Borody is an Australian gastoenterologist based in Sydney who is noted for his work in novel therapies for gastrointestinal disorders [25] Today, the standard triple therapy is amoxicillin, clarithromycin and a proton pump inhibitor such as omeprazole. Amoxicillin ( INN) or amoxycillin ( BAN) is a moderate-spectrum bacteriolytic β-lactam antibiotic used to treat Bacterial Infections Clarithromycin is a Macrolide Antibiotic used to treat Pharyngitis, Tonsillitis, acute maxillary Sinusitis, acute bacterial exacerbation Proton pump inhibitors (or "PPI"s are a group of drugs whose main action is pronounced and long-lasting reduction of Gastric acid production Omeprazole ( INN) (oʊˈmɛprəzoʊl is a Proton pump inhibitor used in the treatment of Dyspepsia, peptic ulcer disease (PUD Gastroesophageal [26] Variations of the triple therapy have been developed over the years, such as using a different proton pump inhibitor, as with pantoprazole or rabeprazole, or using metronidazole instead of amoxicillin in those allergic to penicillin. Proton pump inhibitors (or "PPI"s are a group of drugs whose main action is pronounced and long-lasting reduction of Gastric acid production Pantoprazole (brand names Pantopan in Italy Protium; Protonix; Pantozol; Pantor; Pantoloc; Astropan; Controloc Rabeprazole is an antiulcer drug in the class of Proton pump inhibitors It was developed by Eisai Co Metronidazole ( INN) (mɛtrəˈnaɪdəzoʊl is a Nitroimidazole anti-infective medication used mainly in the treatment of infections caused by susceptible Allergy is a disorder of the Immune system often also referred to as Atopy. Penicillin (sometimes abbreviated PCN or pen) is a group of Beta-lactam antibiotics used in the treatment of Bacterial Infections [27] Such a therapy has revolutionised the treatment of peptic ulcers and has made a cure to the disease possible, where previously symptom control using antacids, H2-antagonists or proton pump inhibitors alone was the only option. A disease is an abnormal condition of an organism that impairs bodily functions and can be deadly An antacid is any substance generally a base or Basic salt, which counteracts stomach acidity. The H2-receptor antagonists (H2RA often shortened to H2 antagonist) are a class of drugs used to block the action of Histamine Proton pump inhibitors (or "PPI"s are a group of drugs whose main action is pronounced and long-lasting reduction of Gastric acid production [28][29]

A meta-analysis of randomized controlled trials suggests that supplementation with probiotics can improve eradication rates and reduce adverse events. In Statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses A randomized controlled trial (RCT is a type of scientific Experiment most commonly used in testing the Efficacy or Effectiveness of Healthcare Probiotics are Dietary supplements containing potentially beneficial Bacteria or Yeasts According to the currently adopted definition by FAO / [30]

Unfortunately, an increasing number of infected individuals are found to harbour antibiotic-resistant bacteria. Antibiotic resistance is the ability of a Microorganism to withstand the effects of Antibiotics. This results in initial treatment failure and requires additional rounds of antibiotic therapy or alternative strategies such as a quadruple therapy. Bismuth compounds are also effective in combination with the above drugs. Bismuth (ˈbɪzməθ is a Chemical element that has the symbol Bi and Atomic number 83 For the treatment of clarithromycin-resistant strains of H. Clarithromycin is a Macrolide Antibiotic used to treat Pharyngitis, Tonsillitis, acute maxillary Sinusitis, acute bacterial exacerbation pylori the use of levofloxacin as part of the therapy has been suggested. Levofloxacin is a 3rd-generation fluoroquinolone Antibiotic, marketed by Ortho-McNeil under the trade name Levaquin in the United States

Some studies show that consumption of broccoli sprouts can be effective at inhibiting H. Broccoli is a plant of the Cabbage family Brassicaceae (formerly Cruciferae pylori growth[31] with sulforaphane being at least one of the active agents[32]. Sulforaphane is an anti Cancer, Antidiabetic, and Antimicrobial compound that can be obtained by eating Cruciferous vegetables such as

Some studies show that mastic gum can destroy H. Mastic ( Greek:μαστίχα( Pistacia lentiscus) is an Evergreen Shrub or small Tree of the Pistacio family growing pylori in vitro, but studies done in vivo have shown it to be ineffective in short trials. In vitro ( Latin: within the glass refers to the technique of performing a given experiment in a controlled environment outside of a living Organism In vivo ( Latin: within the living means that which takes place inside an organism. [33]

A study done on Mongolian gerbils indicates that green tea extract can suppress H. Green tea is a type of Tea made solely with the leaves of Camellia sinensis, that has undergone minimal Oxidation during processing pylori growth. [34] Another study done in South Korea suggests that an acidic polysaccharide found in green tea is significantly effective in preventing adhesion of H. Polysaccharides are relatively complex Carbohydrates They are Polymers made up of many Monosaccharides joined together by Glycosidic bonds pylori to human cultures of epithelial cells. [35]

As explained below, some authors suggest that some strains of H. pylori may be protective against certain diseases of the esophagus and cardia. Therefore, a more cautious approach than complete eradication may be necessary in some cases.

Helicobacter and cancer

Two related mechanisms by which H. pylori could promote cancer are under investigation. Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled One mechanism involves the enhanced production of free radicals near H. In Chemistry, radicals (often referred to as free radicals) are atoms molecules or ions with Unpaired electrons on an otherwise Open shell pylori and an increased rate of host cell mutation. In biology mutations are changes to the Nucleotide sequence of the Genetic material of an organism The other proposed mechanism has been called a "perigenetic pathway"[36] and involves enhancement of the transformed host cell phenotype by means of alterations in cell proteins such as adhesion proteins. Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl Cellular adhesion is the binding of a cell to another cell or to a Surface or matrix. It has been proposed that H. pylori induces inflammation and locally high levels of TNF-alpha and/or interleukin 6. Inflammation ( Latin, inflamatio, to set on fire is the complex biological response of vascular tissues to harmful stimuli such as Pathogens Tumor necrosis factor ( TNF, cachexin or cachectin and formally known as Tumor necrosis factor-alpha) is a Cytokine involved in systemic According to the proposed perigenetic mechanism, inflammation-associated signaling molecules such as TNF-alpha can alter gastric epithelial cell adhesion and lead to the dispersion and migration of mutated epithelial cells without the need for additional mutations in tumor suppressor genes such as genes that code for cell adhesion proteins. A tumor suppressor gene, or antioncogene is a Gene that protects a cell from one step on the path to cancer History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance

Acid reflux and esophageal cancer

As the incidence of gastric cancer has decreased, the incidences of gastroesophageal reflux disease and esophageal cancer have increased dramatically. Gastroesophageal reflux disease ( American English and Canadian English) or Gastro-oesophageal reflux disease ( British English, Hiberno-English Esophageal cancer is malignancy of the Esophagus. There are various subtypes In 1996, Martin J. Blaser put forward the theory that H. Martin J Blaser, MD is the Frederick H King Professor of Internal Medicine Chairman Department of Medicine and Professor of Microbiology pylori might also have a beneficial effect: by regulating the acidity of the stomach contents, it lowers the impact of regurgitation of gastric acid into the esophagus. [3] While some favorable evidence has been accumulated, as of 2005 the theory is not universally accepted.

Genome studies of different strains

EM photograph of H. pylori
EM photograph of H. pylori

Several strains are known, and the genomes of two have been completely sequenced. In classical genetics the genome of a Diploid Organism including Eukarya refers to a full set of chromosomes or genes in a Gamete, thereby For the sense of "sequencing" used in Electronic music, see the Music sequencer article [37][38] The genome of the strain "26695" consists of about 1. 7 million base pairs, with some 1550 genes. In Molecular biology, two Nucleotides on opposite complementary DNA or RNA strands that are connected via Hydrogen bonds are called The two sequenced strains show large genetic differences, with up to 6% of the nucleosides differing. See also Adenosine triphosphate (ATP

Study of the H. pylori genome is centered on attempts to understand pathogenesis, the ability of this organism to cause disease. The term pathogenesis means step by step development of a disease due to a series of changes in the structure and /or function of a cell/tissue/organ being caused by a microbial, chemical or physical There are 62 genes in the "pathogenesis" category of the genome database. Both sequenced strains have an approximately 40 kb long Cag pathogenicity island (a common gene sequence believed responsible for pathogenesis) that contains over 40 genes. Pathogenicity islands (PAIs are a distinct class of Genomic islands which are acquired by horizontal transfer. This pathogenicity island is usually absent from H. pylori strains isolated from humans who are carriers of H. pylori but remain asymptomatic.

The cagA gene codes for one of the major H. pylori virulence proteins. Virulence (also called pestiferousness) refers to the degree of Pathogenicity of a Microbe, or in other words the relative ability of a Microbe Bacterial strains that have the cagA gene are associated with an ability to cause severe ulcers. The cagA gene codes for a relatively long (1186 amino acid) protein. In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this The CagA protein is transported into human cells where it may disrupt the normal functioning of the cytoskeleton. cytoskeleton (also CSK is a cellular " Scaffolding " or " Skeleton " contained within the Cytoplasm. The cag pathogenicity island has about 30 genes part of which code for a complex type IV secretion system. After attachment of H. pylori to stomach epithelial cells, the CagA protein is injected into the epithelial cells by the type IV secretion system. The CagA protein is phosphorylated on tyrosine residues by a host cell membrane-associated tyrosine kinase. Phosphorylation is the addition of a Phosphate (PO4 group to a Protein molecule or a small molecule A protein kinase is a Kinase Enzyme that modifies other Proteins by chemically adding Phosphate groups to them ( Phosphorylation) A tyrosine kinase is an Enzyme that can transfer a Phosphate group from ATP to a Tyrosine residue in a Protein. Pathogenic strains of H. pylori have been shown to activate the epidermal growth factor receptor (EGFR), a membrane protein with a tyrosine kinase domain. The epidermal growth factor receptor (EGFR ErbB-1 HER1 in humans is the cell-surface receptor for members of the Epidermal growth factor family (EGF-family Activation of the EGFR by H. pylori is associated with altered signal transduction and gene expression in host epithelial cells that may contribute to pathogenesis. In Biology, signal transduction refers to any process by which a cell converts one kind of signal or stimulus into another Gene expression is the process by which inheritable information from a Gene, such as the DNA sequence, is made into a functional Gene product, such It has also been suggested that a c-terminal region of the CagA protein (amino acids 873–1002) can regulate host cell gene transcription independent of protein tyrosine phosphorylation. The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal end, or It is thought, due to cagA's low GC content relative to the rest of the helicobacter genome, that the gene was acquired by horizontal transfer from another cagA+ bacterial species.

See also

Notes

  1. ^ Chapter 23: Campylobacter and Helicobacter from Medical Microbiology, 4th ed., by Samuel Baron (editor), 1996
  2. ^ Yamaoka Y (editor). Gastritis is an inflammation of the lining of the stomach There are many possible causes A peptic ulcer, also known as PUD or peptic ulcer disease, is an Ulcer (defined as mucosal erosions equal to or greater than 0 In Human anatomy, the stomach is a J-shaped hollow muscular organ of the Gastrointestinal tract involved in the second phase of Digestion, following (2008). Helicobacter pylori: Molecular Genetics and Cellular Biology. Caister Academic Press. ISBN 978-1-904455-31-8 .  
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  6. ^ Barry Marshall biography, The Tall Poppy Campaign. Accessed 9 September 2006.
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  12. ^ The Nobel Prize in Physiology or Medicine 2005 awarded to Barry J. Marshall and J. Robin Warren "for their discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease".
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  38. ^ The Pylori Gene website allows access to genome information for the H. pylori 26695 and J99 strains. Another genome interface is provided by the National Center for Biotechnology Information; 26695, J99. In classical genetics the genome of a Diploid Organism including Eukarya refers to a full set of chromosomes or genes in a Gamete, thereby The National Center for Biotechnology Information ( NCBI) is part of the United States National Library of Medicine (NLM a branch of the National Institutes

References

External links


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