Helicobacter pylori is the first formally recognized bacterial carcinogen and is one of the most successful human pathogens, as over half of the world's population is colonized with this gram-negative bacterium. Unless treated, colonization usually persists lifelong. H. pylori infection represents a key factor in the etiology of various gastrointestinal diseases, ranging from chronic active gastritis without clinical symptoms to peptic ulceration, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Disease outcome is the result of the complex interplay between the host and the bacterium. Host immune gene polymorphisms and gastric acid secretion largely determine the bacterium's ability to colonize a specific gastric niche. Bacterial virulence factors such as the cytotoxin-associated gene pathogenicity island-encoded protein CagA and the vacuolating cytotoxin VacA aid in this colonization of the gastric mucosa and subsequently seem to modulate the host's immune system. This review focuses on the microbiological, clinical, immunological, and biochemical aspects of the pathogenesis of H. pylori.

Pathogenesis of Helicobacter pylori Infection

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(07)60464-4.pdf

Development of a rational scale to assess the harm of drugs of potential misuse

Development of a rational scale to assess the harm of drugs of potential misuse. Commentary

The discovery that Helicobacter pylori infection is the main cause of most gastroduodenal diseases has been a major breakthrough in gastroenterology It has dramatically changed the management of these diseases which are now considered as infectious diseases and are treated with antibiotics

Triple therapy, including two antibiotics, amoxicillin and clarithromycin, and a proton pump inhibitor given for a week has been recommended as the treatment of choice at several consensus conferences1–6 However, this treatment may fail for several reasons, as reported elsewhere7 In fact, the main reason for failure was found to be H pylori resistance to one of the antibiotics used (that is, clarithromycin) Other treatments have also been proposed, including metronidazole, a drug for which resistance is also a problem although to a lesser extent, as well as tetracycline, fluoroquinolones, and rifamycins for which resistance has become an emerging issue8,9

Our aim was to review the prevalence of H pylori resistance to these various antibiotics, their clinical importance, and methods of testing, especially in light of the resistance mechanism which allows application of molecular methods

Numerous studies have been performed to determine the prevalence of H pylori resistance to antibiotics However, many of them have drawbacks, in particular concerning the number and representativeness of the strains tested

Most of the studies were performed in specialised centres, with recruitment of special cases which are not always representative of patients as a whole and, because these studies are monocentric, the number of patients may be low, leading to wide confidence intervals of the prevalence rates obtained

Ideal studies involving patients who are representative of a given region are few An alternative has been to analyse prevalence data obtained from clinical trials aiming to evaluate new regimens As prevalence is in essence an evolving phenomenon, only …

https://gut.bmj.com/content/gutjnl/53/9/1374.full.pdf

H pylori antibiotic resistance: prevalence, importance, and advances in testing

A link between oral health and cardiovascular disease has been proposed for more than a century. Recently, concern about possible links between periodontal disease (PD) and atherosclerotic vascular disease (ASVD) has intensified and is driving an active field of investigation into possible association and causality. The 2 disorders share several common risk factors, including cigarette smoking, age, and diabetes mellitus. Patients and providers are increasingly presented with claims that PD treatment strategies offer ASVD protection; these claims are often endorsed by professional and industrial stakeholders. The focus of this review is to assess whether available data support an independent association between ASVD and PD and whether PD treatment might modify ASVD risks or outcomes. It also presents mechanistic details of both PD and ASVD relevant to this topic. The correlation of PD with ASVD outcomes and surrogate markers is discussed, as well as the correlation of response to PD therapy with ASVD event rates. Methodological issues that complicate studies of this association are outlined, with an emphasis on the terms and metrics that would be applicable in future studies. Observational studies to date support an association between PD and ASVD independent of known confounders. They do not, however, support a causative relationship. Although periodontal interventions result in a reduction in systemic inflammation and endothelial dysfunction in short-term studies, there is no evidence that they prevent ASVD or modify its outcomes.

/pdf/periodontal-disease-and-atherosclerotic-vascular-disease-5dzvnap7v8.pdf

Periodontal Disease and Atherosclerotic Vascular Disease: Does the Evidence Support an Independent Association? A Scientific Statement From the American Heart Association

Gradual withdrawal of diazepam after long-term therapy

A novel PCR detection assay that amplifies the Helicobacter pylori-specific vacuolating cytotoxin gene (vacA) and thus enables rapid diagnosis of infection is described Additionally, a real-time probe hybridization melting point analysis assay to detect all three mutations in the 23S rRNA gene associated with clarithromycin resistance was applied directly to antral gastric biopsy samples Comparison with culture and an alternative PCR assay targeting the 16S rrn gene showed that the vacA assay was sensitive and specific when tested on biopsy samples from 121 patients Clarithromycin susceptibilities could be determined in the majority (923%) of culture-positive gastric biopsy samples analyzed, four of which generated melting peaks indicative of clarithromycin resistance by either an A→G or A→C mutation The presence of the mutations correlated with the clarithromycin disk diffusion sensitivities of matched cultures This PCR-based system was simple to perform and could be completed in 3 to 4 h, thereby overcoming the delays associated with conventional culture methods for H pylori identification and susceptibility testing

https://jcm.asm.org/content/jcm/39/4/1217.full.pdf

PCR-Based Diagnosis of Helicobacter pylori Infection and Real-Time Determination of Clarithromycin Resistance Directly from Human Gastric Biopsy Samples

Helicobacter pylori in dental plaque

Disruption of bone remodelling by diseases such as osteoporosis results in an imbalance between bone formation by osteoblasts and resorption by osteoclasts. Research into these metabolic bone disorders is primarily performed in vivo; however, in the last decade there has been increased interest in generating in vitro models that can reduce or replace our reliance on animal testing. With recent advances in biomaterials and tissue engineering the feasibility of laboratory-based alternatives is growing; however, to date there are no established in vitro models of bone remodelling. In vivo, remodelling is performed by organised packets of osteoblasts and osteoclasts called bone multicellular units (BMUs). The key determinant of whether osteoclasts form and remodelling occurs is the ratio between RANKL, a cytokine which stimulates osteoclastogenesis, and OPG, its inhibitor. This review initially details the different circumstances, conditions, and factors which have been found to modulate the RANKL:OPG ratio, and fundamental factors to be considered if a robust in vitro model is to be developed. Following this, an examination of what has been achieved thus far in replicating remodelling in vitro using three-dimensional co-cultures is performed, before overviewing how such systems are already being utilised in the study of associated diseases, such as metastatic cancer and dental disorders. Finally, a discussion of the most important considerations to be incorporated going forward is presented. This details the need for the use of cells capable of endogenously producing the required cytokines, application of mechanical stimulation, and the presence of appropriate hormones in order to produce a robust model of bone remodelling.

/pdf/in-vitro-models-of-bone-remodelling-and-associated-disorders-3rzc5s094r.pdf

In vitro Models of Bone Remodelling and Associated Disorders

Polymerised High Internal Phase Emulsions (PolyHIPEs) are manufactured via emulsion templating and exhibit a highly interconnected microporosity. These materials are commonly used as thin membranes for 3D cell culture. This study uses emulsion templating in combination with microstereolithography to fabricate PolyHIPE scaffolds with a tightly controlled and reproducible architecture. This combination of methods produces hierarchical structures, where the microstructural properties can be independently controlled from the scaffold macrostructure. PolyHIPEs were fabricated with varying ratios of two acrylate monomers (2-ethylhexyl acrylate (EHA) and isobornyl acrylate (IBOA)) and varying nominal porosity to tune mechanical properties. Young's modulus, ultimate tensile stress (UTS) and elongation at failure were determined for twenty EHA/IBOA compositions. Moduli ranged from 63.01±9.13 to 0.36±0.04MPa, UTS from 2.03±0.33 to 0.11±0.01MPa and failure strain from 21.86±2.87% to 2.60±0.61%. Selected compositions were fabricated into macro-porous woodpile structures, plasma treated with air or acrylic acid and seeded with human embryonic stem-cell derived mesenchymal progenitor cells (hES-MPs). Confocal and two-photon microscopy confirmed cell proliferation and penetration into the micro- and macro-porous architecture. The scaffolds supported osteogenic differentiation of mesenchymal cells and interestingly, the stiffest IBOA-based scaffolds that were plasma treated with acrylic acid promoted osteogenesis more strongly than the other scaffolds.

https://eprints.whiterose.ac.uk/90942/1/Emulsion%20templated.pdf

Robert Owen

Papers

Gradual withdrawal of diazepam after long-term therapy

PCR-Based Diagnosis of Helicobacter pylori Infection and Real-Time Determination of Clarithromycin Resistance Directly from Human Gastric Biopsy Samples

Helicobacter pylori in dental plaque

In vitro Models of Bone Remodelling and Associated Disorders

Emulsion templated scaffolds with tunable mechanical properties for bone tissue engineering