Diseases

242 KiB

Open AccessReview

Helicobacter pylori: A Brief History of a Still Lacking Vaccine

by Paolo Ruggiero and Stefano Censini

Diseases 2014, 2(2), 187-208; https://doi.org/10.3390/diseases2020187 - 16 Jun 2014

Cited by 5 | Viewed by 7359

Helicobacter pylori colonizes the gastric mucosa of more than half of the human population worldwide. Soon after its discovery, the causative relationships between H. pylori infection and chronic atrophic gastritis, peptic ulcer and gastric mucosa-associated lymphoid tissue lymphoma were evidenced. Then, a significantly [...] Read more.

Helicobacter pylori colonizes the gastric mucosa of more than half of the human population worldwide. Soon after its discovery, the causative relationships between H. pylori infection and chronic atrophic gastritis, peptic ulcer and gastric mucosa-associated lymphoid tissue lymphoma were evidenced. Then, a significantly increased risk of developing gastric cancer was found to be associated with H. pylori infection. The efficacy of the treatment for H. pylori, based on a proton pump inhibitor plus antibiotics, has dropped below 80%, mainly due to antibiotic resistance. Vaccination would overcome antibiotic resistance and would lead to the eradication of this pathogen; however, in spite of almost twenty-five years of investigation on H. pylori vaccine candidates and good protective results obtained in animal models, no vaccine is currently licensed. This review focuses on the studies on the efficacy of those H. pylori vaccine candidates that underwent clinical trials. Efficacy trials have given unsatisfactory results, so far, with bacterial colonization remaining unaffected by vaccination. However, a vaccine able to counteract H. pylori-induced diseases, such as gastric cancer, even without providing sterilizing immunity, could be considered valuable. Full article

(This article belongs to the Special Issue Helicobacter Pylori Infection)

226 KiB

Open AccessReview

Molecular Mechanism of Gastric Carcinogenesis in Helicobacter pylori-Infected Rodent Models

by Takeshi Toyoda, Masami Yamamoto, Shinji Takasu, Kumiko Ogawa, Masae Tatematsu and Tetsuya Tsukamoto

Diseases 2014, 2(2), 168-186; https://doi.org/10.3390/diseases2020168 - 12 Jun 2014

Cited by 1 | Viewed by 5917

Abstract

Since the discovery of Helicobacter pylori (H. pylori), many efforts have been made to establish animal models for the investigation of the pathological features and molecular mechanisms of gastric carcinogenesis. Among the animal models, Mongolian gerbils and mice are particularly useful [...] Read more.

Since the discovery of Helicobacter pylori (H. pylori), many efforts have been made to establish animal models for the investigation of the pathological features and molecular mechanisms of gastric carcinogenesis. Among the animal models, Mongolian gerbils and mice are particularly useful for the analysis of H. pylori-associated inflammatory reactions and gastric cancer development. Inhibitors of oxidative stress, cyclooxygenase-2 (COX-2) and nuclear factor-κB, exert preventive effects on chronic gastritis and the development of adenocarcinomas in H. pylori-infected gerbils. Genetically-modified mouse models, including transgenic and knockout mice, have also revealed the importance of p53, COX-2/prostaglandin, Wnt/β-catenin, proinflammatory cytokines, gastrin and type III mucin in the molecular mechanisms of gastric carcinogenesis. Microarray technology is available for comprehensive gene analysis in the gastric mucosa of mouse models, and epigenetics, such as DNA methylation, could be an alternative approach to correlate the observations in animal models with the etiology in humans. Full article

(This article belongs to the Special Issue Helicobacter Pylori Infection)

1747 KiB

Open AccessArticle

NF-κB Activation Exacerbates, but Is not Required for Murine Bmpr2-Related Pulmonary Hypertension

by Megha Talati, Haitham Mutlak, Kirk B. Lane, Wei Han, Anna Hemnes, Outi Mutlak, Tom Blackwell, Rinat Zaynagetdinov, Timothy S. Blackwell and James West

Diseases 2014, 2(2), 148-167; https://doi.org/10.3390/diseases2020148 - 30 May 2014

Cited by 4 | Viewed by 7022

Abstract

Aim: The present study investigates the role of NF-κB in Bmpr2-related pulmonary hypertension (PH) using a murine model of PH with inducible overexpression of a cytoplasmic tail Bmpr2 mutation. Methods and Results: Electrophoretic mobility shift assay for nuclear extracts in Bmpr2^R899X mouse [...] Read more.

Aim: The present study investigates the role of NF-κB in Bmpr2-related pulmonary hypertension (PH) using a murine model of PH with inducible overexpression of a cytoplasmic tail Bmpr2 mutation. Methods and Results: Electrophoretic mobility shift assay for nuclear extracts in Bmpr2^R899X mouse lung and immunohistochemistry for NF-κB p65 in human PAH lung demonstrate that NF-κB is activated in end-stage disease. Acute inflammation or expression of a constitutively active NF-κB elicits a strong suppression of the BMP pathway in mice inversely correlating to activation of NF-κB targets. However, Bmpr2 mutation does not result in NF-κB activation in early disease development as assessed by luciferase reporter mice. Moreover, Bmpr2 mutant mice in which NF-κB activation is genetically blocked develop PH indistinguishable from that without the block. Finally, delivery of a virus causing NF-κB activation strongly exacerbates development of PH in Bmpr2 mutant mice, associated with increased remodeling. Conclusion: NF-κB activation exacerbates, but is not required for Bmpr2-related PH. Pulmonary vascular-specific activation of NF-κB may be a “second hit” that drives penetrance in heritable PH. Full article

(This article belongs to the Special Issue Pulmonary Arterial Hypertension (PAH))

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555 KiB

Open AccessReview

The Role of Exercise Testing in the Modern Management of Pulmonary Arterial Hypertension

by Martin K. Johnson and Stephen Thomson

Diseases 2014, 2(2), 120-147; https://doi.org/10.3390/diseases2020120 - 28 May 2014

Cited by 4 | Viewed by 7521

Abstract

A culture of exercise testing is firmly embedded in the management of pulmonary arterial hypertension (PAH) but its clinical relevance and utility have recently been under some debate. The six minute walk test (6MWT) has been used as a primary outcome measure to [...] Read more.

A culture of exercise testing is firmly embedded in the management of pulmonary arterial hypertension (PAH) but its clinical relevance and utility have recently been under some debate. The six minute walk test (6MWT) has been used as a primary outcome measure to enable the licensing of many of the medications used for this condition. Recent reviews have questioned the validity of this test as a surrogate of clinical outcomes. At the same time, other questions are emerging where exercise testing may be the solution. With the rise in understanding of genetic markers of idiopathic PAH (IPAH), the screening of an otherwise healthy population for incipient pulmonary hypertension (PH) will be required. The proliferation in treatment choices and identification of populations with PH where PAH treatment is not indicated, such as left heart and lung disease, requires more definitive differentiation from patients with PAH. There is a continuing question about the existence and clinical relevance of exercise induced PAH as a cause of unexplained dyspnoea and fatigue and as a latent phase of resting PH. This review presents a summary and critical analysis of the current role of exercise testing in PAH and speculates on future trends. Full article

(This article belongs to the Special Issue Pulmonary Arterial Hypertension (PAH))

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1656 KiB

Open AccessArticle

Keratoacanthoma Pathobiology in Mouse Models

by Katherine N. Gibson-Corley, Laura M. Rogers, Adam Goeken, Adam J. Dupuy and David K. Meyerholz

Diseases 2014, 2(2), 106-119; https://doi.org/10.3390/diseases2020106 - 23 May 2014

Cited by 2 | Viewed by 17224

Abstract

Recently we described skin tumors driven by skin-specific expression of Zmiz1 and here we define keratoacanthoma pathobiology in this mouse model. Similar to human keratoacanthoma development, we were able to segregate murine keratoacanthomas into three developmental phases: growth, maturation, and regression. These tumors [...] Read more.

Recently we described skin tumors driven by skin-specific expression of Zmiz1 and here we define keratoacanthoma pathobiology in this mouse model. Similar to human keratoacanthoma development, we were able to segregate murine keratoacanthomas into three developmental phases: growth, maturation, and regression. These tumors had areas with cellular atypia, high mitotic rate, and minor local invasion in the growth phase, but with development they transitioned to maturation and regression phases with evidence of resolution. The early aggressive appearance could easily be misdiagnosed as a malignant change if the natural pathobiology was not well-defined in the model. To corroborate these findings in the Zmiz1 model, we examined squamous skin tumors from another tumor study in aging mice, and these tumors followed a similar biological progression. Lastly, we were able to evaluate the utility of the model to assess immune cell infiltration (F4/80, B220 Granzyme B, CD3 cells, arginase-1) in the regression phase; however, because inflammation was present at all phases of development, a more comprehensive approach will be needed in future investigations. Our study of keratoacanthomas in selected murine models suggests that these squamous tumors can appear histologically aggressive during early development, but with time will enter a regression phase indicating a benign biology. Importantly, studies of squamous skin tumor models should be cautious in tumor diagnosis as the early growth distinction between malignant versus benign based solely on histopathology may not be easily discerned without longitudinal studies to confirm the tumor pathobiology. Full article

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Open AccessArticle

The Impact of Economic Crisis on Chronic Patients’ Self-Rated Health, Health Expenditures and Health Services Utilization

by Anastasios Skroumpelos, Elpida Pavi, Katerina Mylona and John Kyriopoulos

Diseases 2014, 2(2), 93-105; https://doi.org/10.3390/diseases2020093 - 22 May 2014

Cited by 9 | Viewed by 6152

Abstract

There is evidence that the economic crisis in Greece has substantially affected patients and health care services, with chronic patients forming a particularly vulnerable group. The aim of this study was to investigate whether and in what way the current economic environment has [...] Read more.

There is evidence that the economic crisis in Greece has substantially affected patients and health care services, with chronic patients forming a particularly vulnerable group. The aim of this study was to investigate whether and in what way the current economic environment has affected patients with selected chronic conditions. A cross sectional study was carried out with a sample size of 1200 patients suffering from hypertension, diabetes and chronic obstructive pulmonary disease (COPD). Following a large family income decrease (35.4%) in the last 3 years, chronic patients reported decreased spending for various expenditure categories in order to maintain their ability to finance their health care needs. Among the disease groups studied, statistically significant differences were found for self-rated heath (SRH), out-of pocket health expenditures, health services utilization and the perceived need for physician services. Although need for physician visits for issues related to the chronic condition has largely been reported as met, this was achieved by increased out-of-pocket expenditures and large family budget cuts for essential household goods and services. Austerity measures and reduction of public health expenditure by the state appear to have led to high private expenditures and to de jure or de facto insurance coverage loss for primary care services. Full article

(This article belongs to the Special Issue Impact of Economic Crisis in Primary Health Care (PHC))

612 KiB

Open AccessFeature PaperReview

Intercalated Cells: More than pH Regulation

by Ensaf Y. Almomani, Sumanpreet Kaur, R. Todd Alexander and Emmanuelle Cordat

Diseases 2014, 2(2), 71-92; https://doi.org/10.3390/diseases2020071 - 8 Apr 2014

Cited by 3 | Viewed by 18265

Abstract

The renal collecting duct is the nephron segment where the final urine content of acid equivalents and inorganic ions are determined. The role of two different cell types present in this nephron segment has been determined many years ago: principal cells that express [...] Read more.

The renal collecting duct is the nephron segment where the final urine content of acid equivalents and inorganic ions are determined. The role of two different cell types present in this nephron segment has been determined many years ago: principal cells that express the epithelial sodium channel ENaC and aquaporin 2, regulate electrolyte reabsorption, while intercalated cells, which express acid-base transporters and vacuolar H⁺-ATPase, maintain an apropriate acid-base balance. Recent evidence challenges this historical view. Rather than having independent and non-overlapping functions, the two cell types in the collecting duct appear to functionally cooperate to regulate acid-base and volume homeostasis via complex paracrine and endocrine interplay. This review summarizes these recent findings. Full article

(This article belongs to the Special Issue Feature Papers)

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Diseases, Volume 2, Issue 2 (June 2014) – 7 articles , Pages 71-208

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