Jacek Budzyński

Brain-gut axis in the pathogenesis of Helicobacter pylori infection.

Helicobacter pylori (H. pylori) infection is the main pathogenic factor for upper digestive tract organic diseases. In addition to direct cytotoxic and proinflammatory effects, H. pylori infection may also induce abnormalities indirectly by affecting the brain-gut axis, similar to other microorganisms present in the alimentary tract. The brain-gut axis integrates the central, peripheral, enteric and autonomic nervous systems, as well as the endocrine and immunological systems, with gastrointestinal functions and environmental stimuli, including gastric and intestinal microbiota. The bidirectional relationship between H. pylori infection and the brain-gut axis influences both the contagion process and the hosts neuroendocrine-immunological reaction to it, resulting in alterations in cognitive functions, food intake and appetite, immunological response, and modification of symptom sensitivity thresholds. Furthermore, disturbances in the upper and lower digestive tract permeability, motility and secretion can occur, mainly as a form of irritable bowel syndrome. Many of these abnormalities disappear following H. pylori eradication. H. pylori may have direct neurotoxic effects that lead to alteration of the brain-gut axis through the activation of neurogenic inflammatory processes, or by microelement deficiency secondary to functional and morphological changes in the digestive tract. In digestive tissue, H. pylori can alter signaling in the brain-gut axis by mast cells, the main brain-gut axis effector, as H. pylori infection is associated with decreased mast cell infiltration in the digestive tract. Nevertheless, unequivocal data concerning the direct and immediate effect of H. pylori infection on the brain-gut axis are still lacking. Therefore, further studies evaluating the clinical importance of these host-bacteria interactions will improve our understanding of H. pylori infection pathophysiology and suggest new therapeutic approaches.

Autonomic nervous function in Helicobacter pylori-infected patients with atypical chest pain studied by analysis of heart rate variability.

Objectives Cardiovascular autonomic neurous system (ANS) activity estimated by analysis of heart rate variability (HRV) was compared in Helicobacter pylori-positive and H. pylori-negative male patients suffering from atypical chest pain to verify the hypothesis that autonomic neural system might be the way linking chronic H. pylori infection with gastrointestinal tract disorders. Methods We have analysed data obtained from 101 male patients examined in our clinic due to atypical chest pain, without evidence of serious cardiovascular, respiratory and digestive tract or metabolic diseases. In each patient, besides interview and physical examination, were performed: gastroscopy with mucosa biopsy (for urease test and histology), oesophageal pH-metry and manometry, ultrasound abdomen examination, chest X-ray, exercise test on running track, 24-h ECG Holter monitoring with time-domain and frequency-domain HRV analysis, and echocardiography. Results In comparison with H. pylori-negative, in all H. pylori-infected patients (n = 63) a significantly greater low frequency power, an index of sympathetic activity, and higher values of vagal tone parameters [pNN50, percentage of differences between RR intervals that are greater than 50 ms; high-frequency power in HRV analysis (HF)] were observed. The relationship between H. pylori infection and the HF value was confirmed in multi-factorial analysis. The aforementioned ANS activity differences were accompanied by: significantly fewer gastro-oesophageal acid reflux episodes, lower gastric acidity and more effective and complete oesophageal peristalsis in H. pylori-positive patients. Conclusions H. pylori infection may affect ANS activity and via this way also contribute to gastro-oesophageal and cardiovascular pathology.

Effects of Nordic Walking and Pilates exercise programs on blood glucose and lipid profile in overweight and obese postmenopausal women in an experimental, nonrandomized, open-label, prospective controlled trial.

Objective:Cardiometabolic effects of physical exercise depend on its intensity, duration, and type. The aim of this study was to compare the effects of two exercise models, Nordic Walking (NW) and Pilates, on postmenopausal women. Methods:The study comprised 196 overweight or obese women: 20 were advised to maintain their previous level of physical activity (control group) whereas the others started either an NW exercise program (n = 88) or a Pilates exercise program (n = 88). Blood was collected twice for testing: before the program commenced and after it had ended. Results:Of the 196 women who enrolled in the study, 147 (75%) completed the study; among those women, 69 (47%) completed a 10-week NW exercise program, 58 (39%) completed a 10-week Pilates exercise program, and 20 (14%) were in the control group. After 10 weeks, women in the NW group showed a significant reduction in body weight (6.4%), body mass index (6.4%), blood glucose (3.8%), total cholesterol (10.4%), non-high-density lipoprotein (HDL) cholesterol (16.7%), low-density lipoprotein cholesterol (12.8%), and triglycerides (10.6%), as well as an increase in HDL cholesterol (9.6%). Significantly smaller—although still favorable—changes, except for glucose and HDL cholesterol levels, were observed in the Pilates group (decreases of 1.7%, 1.7%, 1.6%, 5.3%, 8.3%, 7.5%, and 6% and an increase of 3.1%, respectively). Nevertheless, at the end of the study, the percentage of women with target concentrations of the lipid fractions had significantly increased in both exercise groups. No significant changes in the studied parameters were found in the control group. On multiple regression analysis, type of exercise program was an independent predictor of amplitude changes in most of the studied parameters. Conclusions:Exercise training in accordance with the NW model causes statistically and clinically more significant changes in glucose and basic blood lipid levels than do Pilates and dietary intervention alone.

The favourable effect of Helicobacter pylori eradication therapy in patients with recurrent angina-like chest pain and non-responsive to proton pump inhibitors – a preliminary study

Introduction The outcome of Helicobacter pylori (Hp) eradication therapy from the aspect of prevention of chest pain recurrence is still uncertain. The aim of this study was to assess the influence of Hp eradication therapy on the risk of hospitalization due to acute coronary syndrome. Material and methods The analysis was carried out in 63 consecutive patients with recurrent retrosternal symptoms: 28 (44%) with significant coronary artery narrowing in coronarography not qualified for revascularization by an invasive cardiologist, and 35 (56%) with no obstructive coronary artery lesions. In 33 (52%) of the patients, Hp infection was found and standard eradication therapy with omeprazole (2 × 20 mg), amoxicillin (2 × 1 g) and metronidazole (2 × 500 mg) was recommended. The mean follow-up period was 977 ±249 days. Results Chest pain requiring hospitalization because of unstable angina within the follow-up period was observed in 9 (27%) of the Hp-infected individuals and in 15 (50%) subjects in whom a urease test and histology did not confirm this infection (p = 0.055). The recommendation of Hp-eradication treatment was a significant factor prolonging the hospitalization-free period, both in the two Kaplan-Meier curve analyses (Cox’s F test = 1.96; p = 0.049) and the Cox proportional hazard model (beta = –1.18; p = 0.045), but was weaker than the effect of the non-obstructive coronary angiogram (beta = –1.45; p = 0.03). Conclusions The recommendation of Hp-eradication therapy may prolong the hospitalization-free period for patients with recurrent chest pain.

Clinical significance of Helicobacter pylori infection in patients with acute coronary syndromes: an overview of current evidence.

Although Helicobacter pylori (Hp) primarily colonizes gastric mucosa, it can occasionally inhabit in atherosclerotic plaques. Both forms of Hp infection may be involved in the pathogenesis of atherosclerosis via activation of a systemic or local inflammatory host reaction and induction of plaque progression and/or instability, possibly leading to coronary syndromes. The association between Hp infection and cardiovascular endpoint prevalence remains uncertain; however, it has been reported in many epidemiological investigations and may be reasonably explained by pathophysiological mechanisms. Besides the inflammatory pathway, Hp infection may trigger acute coronary syndromes by enhanced platelet reactivity and increased risk of gastrointestinal bleeding (type 2 myocardial infarction). The former seems to be predominantly related to the stimulatory effect of Hp infection on von Willebrand factor-binding and P-selectin activation, and the latter results from cytotoxic bacteria properties and aggravation of digestive tract injury related to aspirin or dual antiplatelet therapy. Despite these premises, the role of Hp infection in cardiovascular syndromes should still be recognized as controversial and requiring randomized, controlled trials to evaluate the outcome of Hp eradication in both cardiac and gastroenterological endpoints. Such need is also justified by potential bias of previous studies resulting from (1) using different diagnostic methods for identification of Hp infection, since only a small number of studies required confirmation of active Hp infection; and from (2) common lack of adjustment for important confounders such as socioeconomic status, smoking and effectiveness of eradication therapy, as well as the genetic characteristics of both the host and the bacterium.

Association between Bacterial Infection and Peripheral Vascular Disease: A Review

There are an increasing number of data showing a clinically important association between bacterial infection and peripheral artery disease (PAD). Bacteria suspected of being involved in PAD pathogenesis are: periodontal bacteria, gut microbiota, Helicobacter pylori, and Chlamydia pneumoniae. Infectious agents may be involved in the pathogenesis of atherosclerosis via activation of a systemic or local host immunological response to contamination of extravascular tissues or the vascular wall, respectively. A systemic immunological reaction may damage vascular walls in the course of autoimmunological cross-reactions between anti-pathogen antibodies and host vascular antigens (immunological mimicry), pathogen burden mechanisms (nonspecific activation of inflammatory processes in the vascular wall), and neuroendocrine-immune cross-talk. Besides activating the inflammatory pathway, bacterial infection may trigger PAD progression or exacerbation by enhancement of platelet reactivity, by a stimulatory effect on von Willebrand factor binding, factor VIII, fibrinogen, P-selectin activation, disturbances in plasma lipids, increase in oxidative stress, and resistance to insulin. Local inflammatory host reaction and induction of atherosclerotic plaque progression and/or instability result mainly from atherosclerotic plaque colonization by microorganisms. Despite these premises, the role of bacterial infection in PAD pathogenesis should still be recognized as controversial, and randomized, controlled trials are required to evaluate the outcome of periodontal or gut bacteria modification (through diet, prebiotics, and probiotics) or eradication (using antibiotics) in hard and surrogate cardiovascular endpoints.

Improvement in health-related quality of life after therapy with omeprazole in patients with coronary artery disease and recurrent angina-like chest pain. A double-blind, placebo-controlled trial of the SF-36 survey

BackgroundMany patients with coronary artery disease (CAD) have overlapping gastroenterological causes of recurrent chest pain, mainly due to gastroesophageal reflux (GER) and aspirin-induced gastrointestinal tract damage. These symptoms can be alleviated by proton pump inhibitors (PPIs). The study addressed whether omeprazole treatment also affects general health-related quality of life (HRQL) in patients with CAD.Study48 patients with more than 50% narrowing of the coronary arteries on angiography without clinically overt gastrointestinal symptoms were studied. In a double-blind, placebo-controlled, cross-over study design, patients were randomized to take omeprazole 20 mg bid or a placebo for two weeks, and then crossed over to the other study arm. The SF-36 questionnaire was completed before treatment and again after two weeks of therapy.ResultsPatients treated with omeprazole in comparison to the subjects taking the placebo had significantly greater values for the SF-36 survey (which relates to both physical and mental health), as well as for bodily pain, general health perception, and physical health. In comparison to the baseline values, therapy with omeprazole led to a significant increase in the three summarized health components: total SF-36; physical and mental health; and in the following detailed health concept scores: physical functioning, limitations due to physical health problems, bodily pain and emotional well-being.ConclusionsA double dose of omeprazole improved the general HRQL in patients with CAD without severe gastrointestinal symptoms more effectively than the placebo.

Orexin in Patients with Alcohol Dependence Treated for Relapse Prevention: A Pilot Study

AIM The aim of the study was to assess the blood concentration of orexin and its association with other clinical factors in patients with alcohol dependence. METHODS Thirty-two males hospitalized on an addiction treatment ward due to alcohol dependence and 23 healthy men as a control group were enrolled in the study. The measurement of orexin in the blood was made at the beginning of the treatment (after withdrawal symptoms had stopped) and again after 4 weeks of observation. RESULTS At the beginning of the observation, the alcohol-dependent patients had significantly greater orexin blood concentration than the control group. After 4 weeks of treatment for relapse prevention, the blood orexin level decreased significantly to a value similar to that in the control group. At the beginning of the study, more severely alcohol-dependent patients (Short Alcohol Dependence Data [SADD] score range: 20-45) had significantly greater orexin blood concentration than individuals with moderate addiction severity (SADD score range: 10-19). However, after 4 weeks of abstinence, the peptide blood concentration was similar in both groups of alcoholic patients. CONCLUSIONS Orexin or its receptor is a potential target for relapse prevention treatment, but further study with long-term observation is needed to verify the usefulness of blood orexin determination as a marker of alcohol relapse risk.

Impact of type 2 diabetes on the plasma levels of vascular endothelial growth factor and its soluble receptors type 1 and type 2 in patients with peripheral arterial disease

ObjectiveType 2 diabetes coexistent with lower extremity artery disease (peripheral arterial disease (PAD)) can be observed in numerous patients. The mechanism compensating for ischemia and contributing to healing is angiogenesis—the process of forming new blood vessels. The purpose of this study was to assess the likely impact of type 2 diabetes on the plasma levels of proangiogenic factor (vascular endothelial growth factor A (VEGF-A)) and angiogenesis inhibitors (soluble VEGF receptors type 1 and type 2 (sVEGFR-1 and sVEGFR-2)) in patients with PAD.MethodAmong 46 patients with PAD under pharmacological therapy (non-invasive), we identified, based on medical history, a subgroup with coexistent type 2 diabetes (PAD-DM2+, n=15) and without diabetes (PAD-DM2−, n=31). The control group consisted of 30 healthy subjects. Plasma levels of VEGF-A, sVEGFR-1, and sVEGFR-2 were measured using the enzyme-linked immunosorbent assay (ELISA) method.ResultsThe subgroups of PAD-DM2+ and PAD-DM2−revealed significantly higher concentrations of VEGF-A (P=0.000 007 and P=0.000 000 1, respectively) and significantly lower sVEGFR-2 levels (P=0.02 and P=0.000 01, respectively), when compared with the control group. Patients with PAD and coexistent diabetes tended to have a lower level of VEGF-A and higher levels of sVEGFR-1 and sVEGFR-2 comparable with non-diabetic patients.ConclusionsThe coexistence of type 2 diabetes and PAD is demonstrated by a tendency to a lower plasma level of proangiogenic factor (VEGF-A) and higher levels of angiogenesis inhibitors (sVEGFR-1 and sVEGFR-2) at the same time. Regardless of the coexistence of type 2 diabetes, hypoxia appears to be a crucial factor stimulating the processes of angiogenesis in PAD patients comparable with healthy individuals, whereas hyperglycemia may have a negative impact on angiogenesis in lower limbs.中文概要目 的研究2 型糖尿病对外周动脉疾病患者血浆内的血管内皮生长因子(VEGF-A)及其水溶性受体(sVEGFR-1 和sVEGFR-2)浓度的影响。创新点首次研究了2 型糖尿病对外周动脉疾病患者血浆内sVEGFR-1 和sVEGFR-2 浓度的影响。方 法选取46 个外周动脉疾病患者, 根据有无2 型糖尿病分为糖尿病组(15 例)和无糖尿病组(31 例), 另选30 个健康志愿者为正常对照组。采用酶联免疫吸附法(ELISA)检测他们血浆中VEGF-A及sVEGFR-1 和sVEGFR-2 的浓度, 然后通过对比各组浓度研究2 型糖尿病的影响。结 论与正常对照组相比, 外周动脉疾病患者具有较高的VEGF-A 浓度(2 型糖尿病组 P=0.000 007, 非糖尿病组 P=0.000 000 1)以及较低的sVEGFR-2浓度(2 型糖尿病组 P=0.02, 非糖尿病组 P=0.000 01)。同时, 2 型糖尿病组比非糖尿病组具有较低的VEGF-A 浓度及较高的sVEGFR-1 和sVEGFR-2 浓度。研究结果表明: 无论2 型糖尿病是否共存, 缺氧是导致血管生成的一个关键的刺激因素; 同时, 高血糖状态对下肢的血管生成有抑制作用。

The Effect of Two Different Cognitive Tests on Gait Parameters during Dual Tasks in Healthy Postmenopausal Women

Introduction. The paper aims to evaluate the influence of two different demanding cognitive tasks on gait parameters using BTS SMART system analysis. Patients and Methods. The study comprised 53 postmenopausal women aged 64.5 ± 6.7 years (range: 47–79). For every subject, gait analysis using a BTS SMART system was performed in a dual-task study design under three conditions: (I) while walking only (single task), (II) walking while performing a simultaneous simple cognitive task (SCT) (dual task), and (III) walking while performing a simultaneous complex cognitive task (CCT) (dual task). Time-space parameters of gait pertaining to the length of a single support phase, double support phase, gait speed, step length, step width, and leg swing speed were analyzed. Results. Performance of cognitive tests during gait resulted in a statistically significant prolongation of the left (by 7%) and right (by 7%) foot gait cycle, shortening of the length of steps made with the right extremity (by 4%), reduction of speed of swings made with the left (by 11%) and right (by 8%) extremity, and reduction in gait speed (by 6%). Conclusions. Performance of cognitive tests during gait changes its individual pattern in relation to the level of the difficulty of the task.