The Association Between Time-Varying Wall Shear Stress and the Development of Plaque Ulcerations in Carotid Arteries From the Plaque at Risk Study

Background and Purpose: Shear stress (WSS) is involved in the pathophysiology of atherosclerotic disease and might affect plaque ulceration. In this case-control study, we compared carotid plaques that developed a new ulcer during follow-up and plaques that remained silent for their exposure to time-dependent oscillatory shear stress parameters at baseline.Materials and Methods: Eighteen patients who underwent CTA and MRI of their carotid arteries at baseline and 2 years follow-up were included. These 18 patients consisted of six patients who demonstrated a new ulcer and 12 control patients selected from a larger cohort with similar MRI-based plaque characteristics as the ulcer group. (Oscillatory) WSS parameters [time average WSS, oscillatory shear index (OSI), and relative residence time (RRT)] were calculated using computational fluid dynamics applying the MRI-based geometry of the carotid arteries and compared among plaques (wall thickness>2 mm) with and without ulceration (Mann–Whitney U test) and ulcer-site vs. non-ulcer-site within the plaque (Wilcoxon signed rank test). More detailed analysis on ulcer cases was performed and the predictive value of oscillatory WSS parameters was calculated using linear and logistic mixed-effect regression models.Results: The ulcer group demonstrated no difference in maximum WSS [9.9 (6.6–18.5) vs. 13.6 (9.7–17.7) Pa, p = 0.349], a lower maximum OSI [0.04 (0.01–0.10) vs. 0.12 (0.06–0.20) p = 0.019] and lower maximum RRT [1.25 (0.78–2.03) Pa−1 vs. 2.93 (2.03–5.28) Pa−1, p = 0.011] compared to controls. The location of the ulcer (ulcer-site) within the plaque was not always at the maximal WSS, but demonstrated higher average WSS, lower average RRT and OSI at the ulcer-site compared to the non-ulcer-sites. High WSS (WSS>4.3 Pa) and low RRT (RRT < 0.25 Pa) were associated with ulceration with an odds ratio of 3.6 [CI 2.1–6.3] and 2.6 [CI 1.54–4.44] respectively, which remained significant after adjustment for wall thickness.Conclusion: In this explorative study, ulcers were not exclusively located at plaque regions exposed to the highest WSS, OSI, or RRT, but high WSS and low RRT regions had a significantly higher odds to present ulceration within the plaque even after adjustment for wall thickness.

Therapeutic Potency of Gallium verum Extract on Ethanol-Induced Gastric Ulcer in Rats

Gallium verum, lady's bedstraw is an herbaceous annual plant belonging to the genus Rubiaceae; it possessed antioxidant, cytotoxic for cancer cells, antimicrobial, protective and endocrine effects. This work aimed to investigate the curative effects of G. verum extract on gastric ulcers following absolute ethanol administration in the healthy rat. Eighteen rats were randomly divided into three main groups; rats were fastened for 24 hours before ethanol administration. All groups except control administered ethanol (5 ml/kg body weight; orally). The rats were administrated distilled water (Ulcer group) or G. verum extract (100mg/kg) one hour later. G. verum extract caused a significant decrease in ulcer index, gastric juice volume, malondialdehyde, and nitric oxide, while gastric juice pH, glutathione, glutathione-S-transferase, and catalase increased significantly. The histological lesion score showed a significant enhancement in group G. verum compared to the ulcer group that scored the highest pathological destruction score. Immunohistochemical markers of NF-κB p65 and TNF-α showed a significant decrease in G. verum group. G. verum extract is a promising treatment modality against gastric injury through its powerful antioxidant, acid neutralizing, healing promotion, and ant-inflammation effects.

Long-Term Outcomes in Patients with Post-Bulbar Ulcer Bleeding Compared to Bulbar Ulcer Bleeding in the Duodenum

<b><i>Background:</i></b> Duodenal ulcers are classified into bulbar and post-bulbar ulcers. The aim of this study is to compare the long-term outcomes of patients with post-bulbar ulcer bleeding and those with bulbar ulcer bleeding. <b><i>Methods:</i></b> A total of 272 patients with hemorrhagic duodenal ulcers requiring hospitalization were included. Their medical records were retrospectively reviewed. <b><i>Results:</i></b> All patients were categorized as bulbar or post-bulbar bleeding ulcer groups. The post-bulbar ulcer group had more patients of advanced age, concurrent malignancy, diabetes mellitus, hypertension, cirrhosis, and chronic kidney disease undergoing hemodialysis. We performed long-term follow-up for an average of 2.6 years. The mortality rate during the follow-up period in the post-bulbar ulcer group was significantly higher than that in the bulbar ulcer group (<i>p</i> &#x3c; 0.001). The PNED score was a better predictor of 30-day mortality compared to the complete Rockall score and the Glasgow-Blatchford Score. Predictors of mortality were evaluated using a Cox proportional hazards regression model. In multivariate analysis, post-bulbar ulcer, concurrent malignancy, cirrhosis, antiplatelet/anticoagulant use, and transfusion were significant predictors of mortality. <b><i>Conclusions:</i></b> Patients with post-bulbar ulcers have a poorer prognosis than those with bulbar ulcers. After the diagnosis of hemorrhagic post-bulbar duodenal ulcer, close follow-up is necessary.

Characteristics of peptic ulcer bleeding in cirrhotic patients with esophageal and gastric varices

Upper gastrointestinal bleeding (UGIB) is common in liver cirrhosis. Although esophageal and gastric varices (EGV) is the main bleeding source, there were still a proportion of patients with peptic ulcer bleeding. Thus, this study aimed to analyze the characteristic of variceal bleeding and peptic ulcer bleeding in liver cirrhosis. Cirrhotic patients with confirmed UGIB by urgent endoscopy from July 2012 to June 2018 were enrolled, and classified into peptic ulcer bleeding group (n = 248) and variceal bleeding group (n = 402). Clinical and endoscopic characteristics, therapeutic efficacy and prognosis were evaluated, and independent risk factors for 42-day morality were determined. The mean age and gender ratio of peptic ulcer bleeding group were higher than those in variceal bleeding group (55.58 ± 11.37 vs. 52.87 ± 11.57, P < 0.01; 4.51:1 vs. 2.87:1, P = 0.023). Variceal bleeding group most commonly presented as red blood emesis and coffee grounds (67.16%), while peptic ulcer group primarily manifested as melena (62.10%). Hepatocellular carcinoma was more prevalent in peptic ulcer group (141 vs. 119, P < 0.01). Albumin level in variceal bleeding group was lower higher (P < 0.01), but serum bilirubin, creatinine and prothrombin time were significantly higher (all P < 0.01). Success rate of endoscopic hemostasis for variceal bleeding and peptic ulcer bleeding was 89.05% and 94.35% (P = 0.021). Univariate and multivariate analysis identified prothrombin time (P = 0.041, OR [95% CI] 0.884 [0.786–0.995]), MELD score (P = 0.000, OR [95% CI] 1.153 [1.073–1.240]), emergency intervention (P = 0.002, OR [95% CI] 8.656 [2.219–33.764]), hepatic encephalopathy before bleeding (P = 0.003, OR [95% CI] 8.119 [2.084–31.637]) and hepatic renal syndrome before bleeding (P = 0.029, OR [95% CI] 3.877 [1.152–13.045]) as the independent predictors for 42-day mortality. Peptic ulcer bleeding should be distinguished from variceal bleeding by clinical and endoscopic characteristics.

Acid formation in gastroenterological patients with colonization of the stomach with virulent and non-virulent strains of helicobacter

Objective. To prove that increased acid production in patients with gastric ulcer and duodenal ulcer is associated with the impact of the virulent strains of Helicobacter pylori but due not to the persistence of non-virulent strains.Materials and methods. Patients with active gastroduodenal ulcer and patients with active chronic pancreatitis accompanied by the gastritis were compared in the respect of the level of pH in the antrum and corpus gastricum, as well as Helicobacter pylori virulence according to the presence cagA gene, especially in combination with vacA allele s1 / m1 (if any of the strains were found in gastric biopsy specimen).Results. In patients with gastric ulcer the average values of pH were significantly lower, both in the antrum and corpus gastricum, than in patients with chronic pancreatitis accompanied by gastritis. Helicobacter pylori strains were found only in half of the patients, either in the gastric ulcer group or in the group of chronic pancreatitis accompanied by the gastritis. Significant difference was revealed after virulent genes identification: virulent strains prevailed in patients with gastric ulcer and in contrast to the prevalence of non-virulent strains in patients with chronic pancreatitis accompanied by the gastritis (Mann-Whitney test, p = 0.001). Since there is no available data that Helicobacter has an affinity for a highly acidic medium in comparison with moderately acidic medium, it is concluded that just primary colonization of the stomach with virulent strains results in hyperacidity (as the consequence of cytotoxicity) and that persistence of non-virulent strains hardly effects hyperacidity.

Up-Regulation of Mir-21 and Mir-130a and Serum Leptin Levels on Leg Ulcers Development in Sickle Cell Anemia

Introduction: Leg ulcers (LUs) are a cutaneous complication of sickle cell anemia (SCA), whose etiology is considered multifactorial. In the search for new candidates for modulators of SCA clinical events, recent evidence suggests the significant role of mechanisms related to post-transcriptional regulation, especially microRNAs (miRNAs). Thus, the analysis of miRNAs miR-21 and miR-130a differential expression in patients with SCA becomes an interesting approach, since both act in the regulation of several biological mechanisms related to the pathophysiology of LU, especially the tissue repair process. In addition, these miRNAs have already been related to the regulation of serum leptin levels, a strong angiogenic pleiotropic hormone that acts in the healing process of skin lesions. Therefore, the aim of the study was to investigate the influence of miR-21 and miR-130a and serum leptin levels on the development of LUs in SCA patients. Methods: After analyzing medical records, 60 SCA patients were selected. Patients who presented some of the main clinical manifestations that may have etiology due to the underlying disease (for example: osteonecrosis, stroke, priapism and acute chest syndrome) were not included. Patients with a history of LU were considered cases, and those who did not develop this complication (n=20), were considered control (median age: 26 years, range: 19-61, 50% males). The control group was called "HbSS-Control" and the case group was divided into two subgroups: Active leg ulcer group, composed of 19 patients with active LU at the time of blood collection (median age: 35 years, range: 24-56, 68% males), and healed leg ulcer group, composed of 21 patients with healed LU at the time of blood collection (median age: 34 years, range: 22-52, 43% males). In addition, it was analyzed a group of 10 donors with normal hemoglobin profile (median age: 25 years, range: 20-30, 50% males), identified as "HbAA-Control". Expression levels of miRNAs extracted from peripheral blood, using mirVanaTM PARIS Kit (Invitrogen™) were evaluated by RT-qPCR technique utilizing TaqMan® probes. Serum leptin levels of the patients were evaluated employing the ELISA method (Human Leptin ELISA Kit, Millipore®). Mann-Whitney and Kruskal-Wallis tests were applied to compare continuous variables. Results: Up-regulation of both miRNAs was observed in the active leg ulcer group in contrast to the healed leg ulcer (miR-21: P&lt;0.0001, Figure 1A, Fold change [FC]=14,2; miR-130a: P=0.0004, FC=18,8, Figure 1B) and Control-HbSS groups (miR-21: P&lt;0.0001, FC=34,4, Figure 1A; miR-130a: P=0.0006, FC=15,3, Figure 1B) and the HbAA-Control group (miR-21: P&lt;0.0001, FC=5,8, Figure 1C; miR-130a: P=0.0009, FC=10,9, Figure 1D). However, there was no significant difference between the healed leg ulcer, HbSS-Control and HbAA-Control groups (miR-21: P=0.1829, Figure 1E; miR-130a: P=0.3537; Figure 1F). Furthermore, the active leg ulcer group had lower serum leptin levels when compared to the healed leg ulcer and Control-HbSS groups (P=0.0058; Figure 2A). The levels of leptin in the healed leg ulcer group did not differ from the Control-HbSS group (P=0.5929; Figure 2B). Conclusion: Our results demonstrated an inverse relation between the miRNAs miR-21 and miR-130a expression with serum leptin levels, suggesting that the up-regulation of these miRNAS may be related to the chronicity and healing of LUs in individuals with SCA through decreased of serum leptin levels. Disclosures No relevant conflicts of interest to declare.

Protective Role of Casuarinin from Melaleuca leucadendra against Ethanol-Induced Gastric Ulcer in Rats

Gastric ulcer is a major health problem. Current treatment options of gastric ulcer, including antagonists of histamine H2 receptor and inhibitors of the proton pump, do not cure gastric ulcers, but only provide temporary relief of symptoms and can be associated with severe side effects. The lack of effective and safe medications for this global health problem urges for the discovery of novel classes of compounds with potent activity and an acceptable safety profile. Ethanol-induced ulceration in rats was used to evaluate the gastroprotective activity of casuarinin, an ellagitannin isolated from Melaleuca leucadendra. Casuarinin (25, 50, and 100 mg/kg) reduced the ulcer area by 45, 78, and 99%, respectively, compared with the ulcer group. Casuarinin (100 mg/kg) increased mucin content by 1.8-fold and reduced acidity by 42%. At the same dose, it also increased the levels of reduced glutathione by 194%, catalase by 586%, and prostaglandin E2 to its normal level. In contrast, it attenuated the ethanol-increased levels of malondialdehyde by 56%, TNF-α by 58%, and caspase-3 by 87%. Histological findings demonstrated that casuarinin exhibited a protective effect against tissue alterations in response to the ethanol-induced ulcer. Casuarinin suppressed the immunoexpression of nuclear factor-kappa B, cyclooxygenase-2, and inducible nitric oxide synthase to their normal values. It also induced the expression of heat shock protein-70, reaching up to 4.9-fold in comparison with the ulcer group. The potent gastroprotective effect of casuarinin was thus attributed to its anti-inflammatory, antioxidant, and antiapoptotic effects. Our results suggest the potential application of casuarinin as an antiulcer agent from natural sources.

ANXIETY, DEPRESSION AND PERSONALITY TYPES IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: COMPARISONS WITH PEPTIC ULCER AND THE GENERAL POPULATION

Aim: To explore corellation of anxiety, depression ant type of personality in inflammatory bowel disease (IBD) and compare with peptic ulcer (PU).Subjects and methods: In this study, prevalence of anxiety, depression and type of personality was investigated in 362 cases divided into three groups: 112 of IBD patients, 122 of peptic ulcer patients and 128 of control group who didn't have any gastrointestinal or psychic complaints. IBD and peptic ulcer diagnosis were established by standard diagnostic procedures (anamnesis, clinical manifestations, laboratory, endoscopy and biopsy in IBD and upper endoscopy in peptic ulcer). Anxiety and depression wereestablished by Hamilton anxiety rating scale (HAM-A) and Hamilton rating test for depression (HAM-D). Type of A/B personality was established by Bortner scale and D type of personality by Denollet scale (DS14).Results: Anxiety was found in 47 (41.9%) and depression in 44 (38.3%) of a total of 112 IBD cases. In group with peptic ulcer anxiety was found in 40 (32.8%) and depression aalso in 40 (32.8%) of total 122 cases. In control group anxiety was diagnosed in 21 (16.4%) and depression in 20 (15.6%) of total 128 cases. Anxiety and depresson were significantly higher in both groups than in control group but anxiety and depression were significantly higher in IBD group than peptic ulcer group. D type of personality was statistically significant in peptic ulcer group.Conclusion: Anxiety and depression in IBD and peptic ulcer cases have a greater prevalence compared to the normal population and surprisingly are higher in IBD than peptic ulcer group. D type of personality is associated with peptic ulcer.

Heat Shock Protein 70 Gene Single Nucleotide Polymorphism and Diabetic Foot Ulcer. Is There Any Relationship?

Objective: The study aims to investigate the potential role of C2437T (Met493Thr) single nucleotide polymorphism (SNP) of the heat shock protein (HSP) 70 in diabetic foot ulcer patients. Methods: In this prospective cohort study, SNP of the HSP70 hom gene, also called HSPA1L, was studied among diabetic patients with an ulcer (Group A: n = 50), diabetic patients without an ulcer (Group B: n = 50), and healthy subjects (Group C: n = 50). Results: There was a higher frequency of T/T genotype in group A (76%) as compared to group B (44%) and group C (14%). Moreover, the frequency of T allele was 7.3% in group A, 5.5% in group B, and 3.9% in group C. C allele frequency was 2.6%, 4.4%, and 6.1% in group A, group B, and group C, respectively. In group A, the odds ratio and risk ratio were 19-fold and 5-fold, respectively, for the HSP70 hom T/T homozygous gene compared to B (OR 19.45; RR 5.42; X2 38.8, p < 0.0001). Moreover, 4-fold and 1.75-fold ratios have been compared with group C (OR 4.03; RR 1.72; X2 10.6, p < 0.001). No significant difference in genotype was observed in group B and group C. Conclusions: There is a significant and positive association of hspHSP70 hom polymorphism restricted to T allele in homozygous and heterozygous states among diabetic foot ulcer (DFU) patients.

Clinical significance of Serum Pepsinogen I/II and gastrin-17 determination in gastric cancer diagnosis and prognosis

Currently, the diagnosis of atrophic gastritis and gastric cancer are mainly made by endoscopy and histopathology. Our study aimed to explore the practical value of Serum Pepsinogen I/II and gastrin-17 in gastric cancer diagnosis and prognosis. We collected 60 cases of gastric ulcer from February 2015 to November 2016 as gastric ulcer group, and 40 cases of gastric cancer treated in the same period as gastric cancer group. In 3 years after gastric cancer, 20 patients were served as postoperative gastric cancer group, and 70 healthy subjects as control group. The results showed that serum Pepsinogen I/II, gastrin-17, and other serum gastric function indexes were tested by enzyme-linked immunosorbent assay (ELISA). The serum PGI level of gastric ulcer group was higher than control group ( P < 0.05). The serum G-17 concentrations in gastric ulcer group, gastric cancer group, and postoperative gastric cancer group were all higher than control group ( P < 0.05). The area under receiver operating characteristic (ROC) curve of PGI screening was 0.905 and the best cutoff point was PGI < 75 µg/L. Their sensitivity and specificity were 87.2% and 75.1%; the area under ROC curve of PGI/PGII rate screening was 0.761 and the best cutoff point was PGI/PGII < 4. Their sensitivity and specificity were 88.9% and 62.3%. Multi logistical regression showed that the level of serum PGI, PGI, and G-17 and the odds ratio (OR) level of gastric cancer risk were 2.093, 2.653, and 0.494 ( P < 0.05). The examination of Serum Pepsinogen I/II, gastrin-17, and other serum gastric function indexes can be used in the diagnosis and prognosis of gastric cancer and has a rather high practical value in monitoring recurrence in postoperative gastric cancer patients.