Genetic and evolutionary implications in peptic ulcer disease

The evidence for a genetic component in peptic ulcer disease has been based on twin, family, and blood group studies. A polygenic model for the inheritance of peptic ulcers has been displaced by a genetic heterogeneity model based on several lines of evidence, some of the most powerful being recent work using subclinical markers. One marker in particular, an elevated level of serum pepsinogen I (PG I), a pepsin precursor produced by the gastric mucosa, secreted into the stomach lumen and also appearing in the bloodstream, has been found to be associated with a subgroup of duodenal ulcer patients. Segregation analysis of elevated serum PG I in duodenal ulcer sibships demonstrates familial aggregation consistent with autosomal dominant inheritance. Elevated PG I is also accompanied by gastric hyperacidity and presumably indicates those individuals with an increased mass of chief and parietal cells, and thus an increased capacity for peptic activity, an important element in the pathogenesis of ulcer disease. An evolutionary hypothesis based on selection for peptic activity and acidity is offered to explain several of the epidemiologic and genetic elements of this group of chronic diseases.     

Submitting articles to the BMJ

ObjectiveTo determine whether people whose marital partners have depression, diabetes, hypertension, ischaemic heart disease, stroke, hyperlipidaemia, peptic ulcer disease, or asthma or chronic obstructive pulmonary disease are at increased risk of the same disease.DesignCross sectional study.Setting10 practices from the Trent Focus Collaborative Research Practice Network.Participants8386 married couples (16 772 individuals) from a population of 29 014 participants aged 30-74 years.OutcomesRisk of disease in participants whose marital partner had that disease compared with those whose partner did not.ResultsAfter both partners'' age, smoking, and obesity and which general practice they attend were adjusted for, participants whose marital partner had asthma, depression, hypertension, hyperlipidaemia, and peptic ulcer disease were at increased risk of having the same disease. The adjusted odds ratios were 1.69 (95% confidence interval 1.43 to 2.98) for asthma, 2.08 (1.71 to 2.54) for depression, 1.32 (1.04 to 1.67) for hypertension, 1.44 (1.19 to 1.75) for hyperlipidaemia, and 2.01 (1.48 to 2.73) for peptic ulcer disease.ConclusionPartners of people with specific diseases are at increased risk of the disease themselves—at least 70% increased risk for asthma, depression, and peptic ulcer disease. This implicates shared environmental causes in some diseases in addition to any genetic or distant exposure or shared behaviours with respect to seeking health care.

What is already known on this topic

People whose spouses have hypertension are at increased risk of hypertensionLittle is known about the risks of disease for spouses of patients with diseases other than hypertension

What this study adds

People whose marital partner had asthma, depression, and peptic ulcer disease were at increased risk of having the same diseaseShared environmental factors contribute to the risk of diseasesThe costs and benefits of screening people for diseases of their spouses needs to be considered     

Host Determinants of Helicobacter pylori Infection and Its Clinical Outcome

Greater than one-half of the world's population harbors Helicobacter pylori. The majority of infected individuals, however, remain asymptomatic, with only 10% to 20% developing diseases, including peptic ulcer disease, gastric cancer, and gastric mucosa–associated lymphoid tissue lymphoma. This article reviews host factors that may predispose an individual to both the acquisition of H. pylori infection and subsequent clinical outcome. Individuals with specific blood group antigens and human leukocyte antigen genotypes may be more susceptible to H. pylori infection. Additional factors, such as the age of acquisition, the host immune response, the site of infection, acid secretion, and interactions with nonhost factors (including bacterial virulence factors and environmental influences) may play a role in determining clinical outcome. Further investigation is required to clarify the mechanisms by which these interactions occur and, more critically, to determine their relative importance. This knowledge will enable the identification of individuals at risk of developing clinical disease with H. pylori infection.     

蜂蜜的抗菌机理及其抗菌效果的影响因素

利用蜂蜜的抗菌特性治疗各种疾病或创伤是蜂蜜开发中一个比较热门的方向。本文对蜂蜜可能的抗菌机理以及蜂蜜中的抗菌组分作了阐述,对影响蜂蜜抗菌效果的因素以及蜂蜜抗菌特性的医学应用进行了探讨。     

成人口腔黏膜念珠菌病的多因素分析

为探讨影响成人口腔黏膜念珠菌病发生的因素,选取口腔黏膜念珠菌病、复发性阿弗他溃疡、扁平苔藓、舍格伦综合征、白斑、天疱疮、类天疱疮患者及口腔黏膜健康者为研究对象,详细记录731个样本的年龄、性别、吸烟、口腔卫生情况、抗生素使用、义齿、口腔黏膜疾病、全身疾病,对结果进行多元Logistic回归分析,得到影响口腔黏膜念珠菌病发生的因素有4类,分别为发病前使用抗生素、口腔卫生情况、口腔黏膜疾病、全身疾病,即多种因素的作用导致口腔黏膜念珠菌病的发生。     

Experimental gastric mucosal injury: laboratory models reveal mechanisms of pathogenesis and new therapeutic strategies.

Gastric ulcer is a multifaceted, pluricausal illness. Knowledge of the pathophysiology of gastric ulcer disease remains incomplete. Current pharmacological management of gastric ulceration is directed primarily at the reduction or neutralization of gastric acid secretion despite evidence that patients with this disease often exhibit normal gastric secretory activity. Attempts have been made to prevent or reduce gastric mucosal injury by cytoprotective agents without diminishing gastric acidity. We review several alternate explanations for the cause of gastric ulcers by examining various experimental models of gastric mucosal damage, including ethanol-, stress-, and nonsteroidal antiinflammatory drug-induced gastric lesions. We also discuss possible new strategies for the treatment of ulcer disease, particularly novel pharmacological targets arising from research conducted with these models. Growing realization that factors other than gastric secretion contribute significantly to the development of gastric ulcer disease prompts the conclusion that these same factors represent viable treatment alternatives.     

Glutathione system of erythrocyte and plasma in peptic ulcer

A complex study of the blood glutathione system has been carried out for the first time in patients with peptic (gastric and duodenal) ulcer. In erythrocytes and blood plasma of patients with the complicated peptic ulcer and postgastroresection syndromes there was the increase of conjugated dienes (and in the second group the increase in antioxidant activity). Under these conditions the main change was the sharp and identical decrease in glutathione peroxidase activity. In patients with uncomplicated peptic ulcer there was sharp increase in erythrocite and plasma glutathione reductase activity and plasma GSH. In operated but basically healthy patients plasma glutathione peroxidase remained decreased but plasma GSH sharply increased. Evidently complicated peptic ulcer is characterized by decreased functioning of the glutathione system. Activation of this system and the decrease or disappearance of manifestations of oxidative stress are associated with a favorable course of this disease, especially at uncomplicated peptic ulcer. The revealed changes significantly differ from those observed in patients with viral hepatitis, blle excretory diseases and strokes.     

The therapeutic lead potential of metabolites obtained from natural sources for the treatment of peptic ulcer

For over a century, ulcer has been a major cause of morbidity and mortality. Its treatment has progressed from vagotomy to proton pump inhibitors. However, the drugs used produce many adverse effects and are less effective than they ought to be. Therefore, there is a growing interest in alternative therapies and the use of natural products. This review emphasizes recent studies involving naturally occurring antiulcer metabolites, categorized according to their chemical structure. Both terrestrial and marine sources are included. More than a hundred and fifty different compounds are presented, and where possible, their main mechanisms of action are summarized. Considering that Helicobacter pylori is an important causal factor in the pathogenesis of ulcer disease, an overview of some natural compounds with anti-H. pylori activity is presented.     

Problems in the genetics of peptic ulcer. II. An analysis of the associations of the disease with certain simply heritable traits]

The research of distribution of blood group ABO, Rhesus, Lewis, Secretor, C5+-component of choline esterase and the ability to taste PTC among Moscow population patients suffering from duodenal ulcer is carried out in comparison with the control. Statistically authentic association of the disease with 0(I) blood group, unsecretor and the association of joint signs (coefficients of association are 1.32, 2.17 and 2.62 respectively) is found. Authenticity of relation with disease is not proved during the investigation of other signs. The values of risk to fall ill for the patients possessing and not possessing the signs of duodenal ulcer are obtained (concerning separate factors and joint factors). It is established that the combination of 0(I) blood group and unsecretor increases the risk of the diseases in 2.4 times as compared with the patients possessing A, B, AB blood groups and secretors.     

Vitamin B2 functionalized iron oxide nanozymes for mouth ulcer healing

Mouth ulcer is associated with inflammation and high risk of bacterial infection, which aggravates the patient's condition.Currently, there is no effective treatment for mouth ulcer. Herein, we report that vitamin-modified iron oxide nanoparticles improve the healing of mouth ulcer through anti-inflammation and antibacterial activities. We discovered that vitamin B_2(VB_2)modified iron oxide nanoparticles performed enhanced peroxidase-like, catalase-like, and superoxide dismutase(SOD)-like activities, acting as typical iron oxide nanozymes(IONzymes) with triad activities. In particular, VB_2 modification significantly improved the SOD-like activity, thus providing a reactive oxygen species(ROS)-scavenging ability. Cellular antioxidant experiments showed that vitamin B_2 modified IONzymes(VB_2-IONzymes) protect human oral keratinocytes(HOK) and BALB/3 T3 cells from hydrogen peroxide(H_2O_2), and these cells have high biocompatibility to eukaryotic cells. In addition, VB_2-IONzymes exerted an antibacterial activity against Streptococcus mutans, Staphylococcus aureus, and Escherichia coli. Importantly, VB2-IONzymes accelerated the recovery of mouth ulcer and reduced the local secretion of inflammatory factors in mouse ulcer model via ROS scavenging and antibacterial activity. Taken together, our work demonstrates that vitamin B_2 modification endows iron oxide nanoparticles with enhanced enzyme-like activities and VB_2-IONzymes may be a promising reagent in the treatment of mouth ulcer because of their intrinsic anti-inflammation and antibacterial capabilities.     

良性中心气道狭窄支气管镜介入治疗术后近远期再狭窄相关因素分析

目的探讨良性中心气道狭窄支气管镜介入治疗术后近远期再狭窄相关因素。方法对2011年2月~2015年2月我院收治的60例良性中心气道狭窄患者经支气管镜下介入治疗,治疗方式包括高频电刀、冷冻、球囊扩张、金属覆膜支架置入等。治疗后对患者的治疗时机、局部感染情况、治疗方法、气道狭窄病因、年龄、性别、基础疾病等情况进行分析,随访观察评估术后疗效、出现再狭窄的时间,探讨近远期再狭窄的危险因素。结果 Cox回归分析表明,患有基础疾病(高血压、糖尿病)、球囊扩张、支架置入、治疗时机不当(溃疡坏死增值阶段)、局部感染是良性气管狭窄支气管镜下腔内介入治疗术后近期再狭窄的相关危险因素,其对再狭窄影响的风险比(OR值)依次为6.715、2.197、5.820、6.914、5.345。支架置入和治疗时机不当(溃疡坏死增值阶段)是良性气管狭窄支气管镜下腔内介入治疗术后远期再狭窄的相关危险因素,其对再狭窄影响的风险比(OR值)分别为6.706,7.154。结论良性中心气道狭窄患者支气管镜下腔内介入治疗术后近期再狭窄的危险因素是基础疾病、球囊扩张、支架置入、局部感染、治疗时机不当,远期再狭窄危险因素是支架置入和治疗时机不当。     

Virulence factors of Helicobacter pylori: implications for vaccine development

Helicobacter pylori is one of the most common infectious diseases in humans and causes gastritis, peptic ulcer disease and malignant tumours of the stomach. This review discusses how H. pylori can colonize the human stomach, an ecological niche that is protected against all other bacteria. Knowledge about the virulence factors of H. pylori has accumulated rapidly over the last decade. Together with the information contained in the complete H. pylori genome sequence, this knowledge is now being applied in the search for a vaccine against this global pathogen.     

Infectious animal disease and its control

The control of infectious diseases in the main food-producing animals is considered and the main factors involved in the epizootiology of disease are presented. The properties of infectious agents and their natural history together with factors that influence the spread and development of disease are summarized. The factors in intensive animal husbandry that affect the occurrence of infectious disease and its control are considered. These include population density, population movement, management, hygiene and genetic constitution of the host. They encourage the appearance of new diseases, changes in the character of established diseases and the development of pathogenicity in infectious agents that were previously of no importance. Intensive animal husbandry has also increased the importance of multifactorial disease, which includes diseases that require more than one infectious agent or one or more infectious agents plus other factors for their cause. The methods of control of infectious disease currently available are described and the success and difficulties of their control on a global, national and local (farm or enterprise) basis are considered. Examples of diseases of global importance where national and world programmes of control and eradication have been of varying success are described. Examples of diseases that are enzootic throughout the world and the procedures used for their control are also described. The technological opportunities for the improvement of the control of infectious disease in the future are discussed. It is considered that developments in molecular biology and immunology will provide improvements in diagnostic tools and will revolutionize the development of animal resistance to disease and the production and use of vaccines.     

A review of spontaneous ulcer disease in domestic animals: chickens, cattle, horses, and swine.

The human species is perhaps unique for its high incidence of spontaneous, chronic ulcer of the glandular mucosa of the stomach and duodenum. Nevertheless, spontaneous ulcers, usually of the stomach, commonly occur in many domestic animals. Some of these lesions are chronic and they may occur in either the glandular or squamous-lined regions of the stomach. As with the human disease(s) the pathogenesis in domestic animals is multifactorial, poorly understood, and variable between and within species. Some parallelisms exist in aggressive and defensive factors, but parasitic factors, via gastrinemia, and a histaminic factor via diet may occur in some animal ulcers. Underlying environmental stresses, of debated importance with the human disease but of proven importance in several rat ulcer models, may play a key role in some spontaneous gastric ulcer situations in swine and cattle. This is manifest in crowding and transporting situations. Seasonal, age, and weaning factors also alter the incidence of ulcer in cattle. Psychologic/environmental stress-related factors, as well as drug and physiologic stress factors appear to upset the balance in the horse between resistance and aggressive mucosal factors. Dietary factors which are highly important in ulcer disease in swine and chickens, have not yet been incriminated in spontaneous, equine ulcer disease. More investigation of the pathogenesis of domestic animal ulcers will prove useful for both human and veterinary medicine in terms of a) elucidating pathogenetic mechanisms for all species, b) may provide new animal models for study, and c) may enhance prevention of such lesions in domestic animals for economic and humanitarian reasons.     

The effect of climate change on the occurrence and prevalence of livestock diseases in Great Britain: a review

There is strong evidence to suggest that climate change has, and will continue to affect the occurrence, distribution and prevalence of livestock diseases in Great Britain (GB). This paper reviews how climate change could affect livestock diseases in GB. Factors influenced by climate change and that could affect livestock diseases include the molecular biology of the pathogen itself; vectors (if any); farming practice and land use; zoological and environmental factors; and the establishment of new microenvironments and microclimates. The interaction of these factors is an important consideration in forecasting how livestock diseases may be affected. Risk assessments should focus on looking for combinations of factors that may be directly affected by climate change, or that may be indirectly affected through changes in human activity, such as land use (e.g. deforestation), transport and movement of animals, intensity of livestock farming and habitat change. A risk assessment framework is proposed, based on modules that accommodate these factors. This framework could be used to screen for the emergence of unexpected disease events.     

The impact of age on genetic risk for common diseases

Inherited genetic variation contributes to individual risk for many complex diseases and is increasingly being used for predictive patient stratification. Previous work has shown that genetic factors are not equally relevant to human traits across age and other contexts, though the reasons for such variation are not clear. Here, we introduce methods to infer the form of the longitudinal relationship between genetic relative risk for disease and age and to test whether all genetic risk factors behave similarly. We use a proportional hazards model within an interval-based censoring methodology to estimate age-varying individual variant contributions to genetic relative risk for 24 common diseases within the British ancestry subset of UK Biobank, applying a Bayesian clustering approach to group variants by their relative risk profile over age and permutation tests for age dependency and multiplicity of profiles. We find evidence for age-varying relative risk profiles in nine diseases, including hypertension, skin cancer, atherosclerotic heart disease, hypothyroidism and calculus of gallbladder, several of which show evidence, albeit weak, for multiple distinct profiles of genetic relative risk. The predominant pattern shows genetic risk factors having the greatest relative impact on risk of early disease, with a monotonic decrease over time, at least for the majority of variants, although the magnitude and form of the decrease varies among diseases. As a consequence, for diseases where genetic relative risk decreases over age, genetic risk factors have stronger explanatory power among younger populations, compared to older ones. We show that these patterns cannot be explained by a simple model involving the presence of unobserved covariates such as environmental factors. We discuss possible models that can explain our observations and the implications for genetic risk prediction.     

Beyond genetic factors in familial amyloidotic polyneuropathy: protein glycation and the loss of fibrinogen's chaperone activity

Familial amyloidotic polyneuropathy (FAP) is a systemic conformational disease characterized by extracellular amyloid fibril formation from plasma transthyretin (TTR). This is a crippling, fatal disease for which liver transplantation is the only effective therapy. More than 80 TTR point mutations are associated with amyloidotic diseases and the most widely accepted disease model relates TTR tetramer instability with TTR point mutations. However, this model fails to explain two observations. First, native TTR also forms amyloid in systemic senile amyloidosis, a geriatric disease. Second, age at disease onset varies by decades for patients bearing the same mutation and some mutation carrier individuals are asymptomatic throughout their lives. Hence, mutations only accelerate the process and non-genetic factors must play a key role in the molecular mechanisms of disease. One of these factors is protein glycation, previously associated with conformational diseases like Alzheimer's and Parkinson's. The glycation hypothesis in FAP is supported by our previous discovery of methylglyoxal-derived glycation of amyloid fibrils in FAP patients. Here we show that plasma proteins are differentially glycated by methylglyoxal in FAP patients and that fibrinogen is the main glycation target. Moreover, we also found that fibrinogen interacts with TTR in plasma. Fibrinogen has chaperone activity which is compromised upon glycation by methylglyoxal. Hence, we propose that methylglyoxal glycation hampers the chaperone activity of fibrinogen, rendering TTR more prone to aggregation, amyloid formation and ultimately, disease.     

Identification of the pathogens associated with skin ulceration and peristome tumescence in cultured sea cucumbers Apostichopus japonicus (Selenka)

The aquaculture of sea cucumbers Apostichopus japonicus (Selenka) has developed rapidly in China in recent years, but is increasingly affected by diseases such as skin ulceration and peristome tumescence. Previous studies on the pathogens causing these diseases focused largely on bacterial causes. In December 2008, we isolated four dominant bacterial species from lesions present in A. japonicus with the aforementioned diseases, from a farm in Yangkou (Qingdao, China). With two of these bacterial species, experimental infection of healthy A. japonicus resulted in the same disease symptoms that occurred in naturally infected A. japonicus. These two species were identified as Pseudoalteromonas sp. and Pseudoalteromonas tetraodonis. The early symptoms of infection for these bacterial species were ulcer spots on the dorsal skin and abdominal parapodia, followed by an increase in the number of ulcer spots or their merging into larger spots. Additionally, we isolated a spherical virus 100-250 nm in diameter and with a bilayer capsule, from A. japonicus with another disease from four different farms. By experimental infection with crude extracts of the virus, healthy laboratory-acclimatized A. japonicus developed the same symptoms as in natural infected cases. The early symptoms of viral infection comprised a decrease in tentacle activity, decay of dorsal papillate podia, peristome tumescence and abdominal ulceration. Our study demonstrates that the bacteria and virus were both responsible for skin ulceration and peristome tumescence in A. japonicus, but resulted in different early disease symptoms.     

哈尔滨市儿童医院收治口腔粘膜病患儿的构成情况调查

目的:统计20l3年哈尔滨市儿童医院全年就诊口腔黏膜病患儿的病历资料,分析目前儿童口腔粘膜病的病种构成和临床治疗情况。方法:收集哈尔滨市儿童医院2013年全年口腔粘膜病例22257例,按病因分成四大类疾病,针对其就诊性别、年龄、各病种的伴发全身疾病和相关影响因素等进行统计分析。结果:22257病例中,感染性疾病的构成比最高,除鹅口疮外均在幼儿期高发,上皮珠主要发生在新生儿期,婴儿期创生性溃疡的构成比最高。复杂病因疾病随年龄增加构成比呈上升趋势。女孩发育性疾病构成比率更高,而男孩外伤性疾病的构成比更高。外伤性疾病伴发全身疾病比率最低(7%),而疱疹性口炎和疱疹性咽峡炎100%伴发上呼吸道感染。复杂病因疾病患儿有家族史的比例较高,城市患儿创伤性溃疡的患病率较低。结论:对儿童口腔粘膜病统计分析可以掌握就诊患儿的口腔粘膜病种类型及变化,有助于医生开展疾病的诊治和预防工作。