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Background: We recently demonstrated that a female sex hormone, estrogen, suppressed esophageal epithelial injury in a reflux esophagitis model of rat, suggesting that estrogen may play an important role in controlling the progress of the gastro-esophageal reflux disease spectrum. However, the precise mechanism of the action is unclear., Aim: To investigate the potential role of estrogen in the esophageal barrier function., Methods: Male rabbits were pretreated with either continuous release 17β-estradiol or placebo, and the excised esophageal mucosa was subjected to Ussing chamber experiments after the 2-week pre-treatment. The mucosal side of the chamber was perfused with luminal irritants (HCl or acidified sodium nitrite), while the basal side was perfused by modified Krebs buffer. The epithelial barrier function was evaluated by the transmembrane resistance and the epithelial permeability. The intercellular space of the epithelium was investigated with transmission electron microscopy and the expression of tight junction protein, occludin, claudin-1, and claudin-4, with immunoblotting., Results: Estrogen pre-treatment significantly attenuated the decrease in the transmembrane resistance and the increase in the epithelial permeability induced by luminal irritants. Furthermore, the dilation of the intercellular space induced by luminal HCl was significantly alleviated by 17β-estradiol administration. The baseline occludin expression was significantly potentiated by 17β-estradiol administration., Conclusions: This is the first study showing an enhancement of the esophageal barrier function by 17β-estradiol administration. The lack of the protective effect of estrogen could be responsible for the male predominance of erosive reflux esophagitis.

Chronic infection with the bacterial Helicobacter pylori is a major cause of gastric and duodenal ulcer disease, gastric mucosal atrophy, and cancer. H. pylori-induced expression of the intestinal epithelial-specific transcription factor caudal-related homeobox 2 (Cdx2) contributes to intestinal metaplasia, a precursor event to gastric cancer. Given a role for the bacterial pattern recognition molecule nucleotide-binding oligomerization domain 1 (NOD1) in the innate immune response to bacterial infection, we investigated mechanisms used by NOD1 to regulate H. pylori infection and its propensity towards the development of intestinal metaplasia. We found that Cdx2 was induced by H. pylori infection in both normal and neoplastic gastric epithelial cells in a manner that was inversely related to NOD1 signaling. Mechanistic investigations revealed that Cdx2 induction relied upon activation of NF-κB but was suppressed by NOD1-mediated activation of TRAF3, a negative regulator of NF-κB. In vivo, prolonged infection of NOD1-deficient mice with H. pylori led to increased Cdx2 expression and intestinal metaplasia. Furthermore, gastric epithelial cells from these mice exhibited increased nuclear expression of the NF-κB p65 subunit and decreased expression of TRAF3. Overall, our findings illuminated a role for NOD1 signaling in attenuating H. pylori-induced Cdx2 expression in gastric epithelial cells, suggesting a rationale to augment NOD1 signaling in H. pylori-infected patients to limit their risks of accumulating precancerous gastric lesions., (©2016 American Association for Cancer Research.)

Aim: To clarify the pathogenesis of gastroesophageal reflux disease symptoms in non-erosive reflux disease (NERD) patients., Methods: Thirty-five NERD patients with persistent symptoms, despite taking rabeprazole 10 mg twice daily for at least 8 wk, were included in this study. All patients underwent 24 h combined impedance - pH on rabeprazole. The symptom index (SI) was considered to be positive if ≥ 50%, and proximal reflux episodes were determined when reflux reached 15 cm above the proximal margin of the lower esophageal sphincter., Results: In 14 (40%) SI-positive patients, with liquid weakly acid reflux, the occurrence rate of reflux symptoms was significantly more frequent in proximal reflux episodes (46.7%) than in distal ones (5.7%) (P < 0.001). With liquid acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes (38.5%) and distal ones (20.5%) (NS). With mixed liquid-gas weakly acid reflux, the occurrence rate of reflux symptoms in proximal reflux episodes was significantly more frequent (31.0%) than in distal reflux ones (3.3%) (P < 0.001). With mixed liquid-gas acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes (29.4%) and distal ones (14.3%) (NS)., Conclusion: The proximal extent of weakly acidic liquid and mixed liquid-gas reflux is a major factor associated with reflux perception in SI-positive patients on proton pump inhibitor therapy.

Background and Aim: Gastric acidic abnormalities are related to various types of diseases in Helicobacter pylori (H. pylori) infection status. However, no studies have shown correlations between many tiny endoscopic findings and the acid secretion level simultaneously. In the present study, we investigated predictive tiny endoscopic findings of hyperchlorhydria and hypochlorhydria., Methods: A total of 223 subjects without organic diseases who underwent esophagogastroduodenoscopy and endoscopic gastrin test (EGT) for estimating gastrin-stimulated gastric acid secretory response between 1999 and 2012 at our institution were retrospectively analyzed. Two blinded expert endoscopists reviewed the images independently and recorded the endoscopic findings., Results: According to the EGT values, the enrolled subjects were categorized into hyperchlorhydria, normal acid secretion, and hypochlorhydria groups. In all subjects, hematin (odds ratio [95% confidence interval] = 3.32 [1.40-7.84]) and antral erosion(2.88 [1.24-6.70]) were the predictive endoscopic findings for hyperchlorhydria, and swelling of areae gastricae (14.4 [5.74-36.1]) and open-type atrophy (15.1 [7.35-31.1]) were those for hypochlorhydria. In addition, the predictive endoscopic findings for hyperchlorhydria differed according to the H. pylori infection status, hematin in H. pylori-positive subjects and antral erosion in H. pylori-negative subjects, in contrast to those for hypochlorhydria, which were the same irrespective of the H. pylori infection status., Conclusions: We could predict the acid secretion status based on the endoscopic findings regardless of H. pylori infection status, which would be of some help for evaluating the risk for acid-related diseases., (© 2014 The Authors. Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society.)

Background and Aim: In Japan, after the revision of the gastrointestinal endoscopic guidelines for patients taking antithrombotics, endoscopic biopsies were permitted while continuing antithrombotic treatment. However, the risk of bleeding after the biopsy with or without cessation of antithrombotics has not been fully evaluated because bleeding events are very rare. The aim of this prospective study was to evaluate the risk for bleeding after upper gastrointestinal biopsy without cessation of antithrombotics., Methods: Consecutive patients who underwent upper gastrointestinal endoscopic biopsy from December 2011 to March 2014 were enrolled in this study. Antithrombotic medication and its cessation status was checked at enrollment. To confirm bleeding events associated with biopsy, medical examination at the hospital or direct confirmation by telephone was done within 1 month after the biopsy., Results: Among the 3758 patients who underwent endoscopic biopsies, 394 patients (10.5%) were medicated with antithrombotics, and 286 of them (72.6% of the total antithrombotics users) did not undergo cessation. Bleeding after the biopsy occurred in six cases (0.15%, 95% CI; 0.09%∼0.22%), but there was only one case that had continued taking antithrombotics. The incidence of bleeding after biopsy was not significantly higher in the patients who had continued taking antithrombotics compared with the others (0.35% vs 0.14%, P = 0.38)., Conclusion: This prospective study showed that continuation of antithrombotics did not increase the bleeding risk after upper gastrointestinal endoscopic biopsy., (© 2014 The Authors. Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society.)

Background and Aim: Dysphagia caused by pharyngo-upper esophageal stricture is a complication of treatment for head and neck cancer. Endoscopic balloon dilation (EBD) is in widespread use as an effective and safe treatment for stricture in many areas of the gastrointestinal tract. In the present study, we investigated the efficacy and safety of EBD for pharyngo-upper esophageal strictures that developed after treatment for head and neck cancer., Methods: From January 2010 to December 2013, the medical records and endoscopic findings of 19 consecutive patients with pharyngo-upper esophageal strictures occurring after surgery and/or chemoradiotherapy for head and neck cancer were retrospectively examined., Results: Mean number of EBD sessions per patient was 6.6 (1-30), and mean maximum diameter of dilation was 15.8 (11-20) mm. Technical success was achieved in 16 of 19 (84.2%) patients, and only two major complications (bleeding and pha ryngeal edema) occurred in a total of 125 dilatation sessions (1.6%). Regarding the influence of chemoradiotherapy on the outcome of EBD, patients who had undergone chemoradiotherapy plus surgery experienced significantly more restenosis during the follow-up period compared to those who had undergone surgery alone (50% vs 0%, P < 0.05)., Conclusions: This retrospective analysis demonstrated the efficacy and safety of exclusive EBD for pharyngo-upper esophageal strictures occurring after treatment for head and neck cancer, indicating that the therapeutic application of EBD could be extended to such strictures. Patients who underwent chemoradiotherapy and surgery experienced more restenosis; hence, such patients should be carefully followed up after EBD treatment., (© 2014 The Authors. Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society.)

Left atrial (LA) structural and functional abnormalities are vital steps on the pathway toward heart failure with preserved ejection fraction in asymptomatic patients. The purpose of this study was to assess the relationship of LA function, particularly reservoir function, with LA structural remodeling related to the left ventricular (LV) dysfunction in asymptomatic patients with hypertension (HT) using conventional, tissue Doppler, and 2-D speckle-tracking echocardiography. Fifty age-matched healthy individuals and 140 patients with HT, including 75 with LA volume index (LAVI)<29 ml/m2 (normal LA group) and 65 with LAVI≥29 ml/m2 (large LA group), were enrolled. We defined peak early diastolic transmitral flow velocity/peak early diastolic mitral annular motion velocity (E/e')/peak systolic LA strain (S-LAs) as LA diastolic stiffness. The LV mass index, relative LV wall thickness, peak atrial systolic transmitral flow velocity, LA total, active, and passive emptying volume indexes, and E/e'/S-LAs were greatest, and S-LAs, peak early diastolic LA strain, peak systolic LV longitudinal strain and circumferential strain rate, and peak early diastolic LV radial strain rate were lower in the large LA group compared with control and/or normal LA group. Multivariate linear regression analysis revealed that aging, LA remodeling, and LV systolic and diastolic dysfunction are defined as strong predictors related to increased LA diastolic stiffness in the large LA group. HT alters LA dynamics significantly, with resultant increased LA volume and diastolic stiffness related to LV diastolic and systolic dysfunction, even in asymptomatic patients. Earlier treatment with renin–angiotensin system inhibitors may improve abnormal LA-LV interaction in this patient population.

Sarcoidosis is a multi-systemic disease of unknown etiology that results in the development of non-caseating epithelioid granulomas. The liver is the third most frequently involved organ after the lymph nodes and the lungs. Most cases of liver sarcoidosis do not present with symptoms and involve minimal liver dysfunction, but some cases display progression to portal hypertension and liver cirrhosis, and finally to liver failure. The mechanism and the risk of progression in liver sarcoidosis are still unknown because of the diagnostic difficulty associated with this condition, and because follow-up examinations can only be done in an invasive manner. Here, we present an informative case of liver sarcoidosis with rapid progression of esophagogastric varices. Four months prior to the definitive diagnosis, no signs of varices were observed on endoscopy, and developmentof esophagogastric varices, rapid progression, and eventual rupture occurred in a short period of time. A liver biopsy, carried out after endoscopic sclerotherapy, revealed that granulomas primarily affected the portal area without fibrotic and cirrhotic changes, which is considered a primary cause of portal hypertension and esophagogastric varices. Following the liver biopsy, the patient was given systemic steroids and is currently receiving outpatient care. Thus, we should consider the possibility that liver sarcoidosis, even in the absence of cirrhotic changes, can cause serious events such as esophagogastric variceal rupture following rapid progression as a result of portal hypertension., (© 2013 The Authors. Digestive Endoscopy © 2013 Japan Gastroenterological Endoscopy Society.)

Objective: To determine the frequency of p53 gene mutation and protein expression in Oral Squamous Cell Carcinoma (OSCC) and to establish correlation between the two., Study Design: Analytical study., Place and Duration of Study: Histopathology Department and Molecular Biology Laboratory, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from May 2010 to May 2011., Methodology: Thirty diagnosed cases of OSCC were selected by consecutive sampling. Seventeen were retrieved from the record files of the AFIP, and 13 fresh/frozen sections were selected from patients reporting to the Oral Surgery Department, Armed Forces Institute of Dentistry (AFID). Gene p53 mutation was analyzed in all the cases using PCRSSCP analysis. DNA was extracted from the formalin-fixed and paraffin-embedded tissue sections and fresh/frozen sections. DNA thus extracted was amplified by polymerase chain reaction. The amplified products were denatured and finally analyzed by gel electrophoresis. Gene mutation was detected as electrophoretic mobility shift. The immunohistochemical marker p53 was applied to the same 30 cases and overexpression of protein p53 was recorded., Results: Immunohistochemical expression of marker p53 was positive in 67% [95% Confidence Interval (CI) 48.7-80.9] of the cases. Mutations of the p53 gene were detected in 23% (95% CI 11.5-41.2) of the OSCC. No statistically significant correlation was found between p53 gene mutation and protein p53 expression (rs=-0.057, p=0.765)., Conclusion: A substantial number of patients have p53 gene mutation (23%) and protein p53 expression (67%) in oral squamous cell carcinoma (OSCC).

Gastric acid measurement is useful in assessing the effectiveness of antisecretory drugs, however, the conventional tests involve invasive nasogastric intubation. Orally administered ¹³C-labeled calcium carbonate (Ca¹³CO₃) reacts with gastric acid to produce ¹³C-labeled carbon dioxide (¹³CO₂), which is then excreted in the breath. The objective of this study was to evaluate the suitability of Ca¹³CO3 breath test for estimating gastric acid secretion in human noninvasively. First, the Ca¹³CO₃ breath test and the measurement of pooled gastric acid under a fasting condition were performed in 6 healthy volunteers to evaluate the correlation between the two parameters. Next, endoscopic gastric acid collection and the Ca¹³CO₃ breath test were performed on different days after pentagastrin injection in 20 subjects to evaluate the correlation between the tests and the reproducibility. Finally, the same studies were repeated in 4 subjects before and after 1-week rabeprazole, a proton pump inhibitor, administration. The maximum CO₂ concentration (Cmax) correlated very well with the amount of pooled gastric acid (r = 0.95), suggesting that Ca¹³CO₃ breath test values well reflected the fasting intragastric acidity. The ¹³CO₂ concentration after pentagastrin injection correlated well with pentagastrin-stimulated maximal acid output (r = 0.79 at 20 min). The reproducibility of the Ca¹³CO₃ breath test under pentagastrin-stimulation was good (coefficient of variation = 0.11). Rabeprazole administration markedly reduced the values of the Ca¹³CO₃ breath test, suggesting that it can sensitively assess the efficacy of rabeprazole. The Ca¹³CO₃ breath test can potentially be a useful method for non-invasive estimation for gastric acid secretion in human.

Objectives: Few studies have simultaneously evaluated the long-term outcomes of endoscopic resection (ER) for squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the esophagus in Japan. The objective of this study was to evaluate the long-term outcomes of ER for superficial esophageal cancer in consecutive patients., Methods: This was a retrospective study from a single institution. From April 2001 to June 2012, 204 patients with SCC and 26 patients with AC were included from a total of 355 consecutive patients who were treated by esophageal ER at the Tohoku University Hospital. Patients with submucosal invasion deeper than 200 μm and lymphovascular involvement were excluded. The intervention followed was endoscopic therapy., Results: Overall survival, disease-free survival, and recurrence rates were evaluated as long-term outcomes. In the SCC group, during the median observation time of 36.5 months (range, 6-120 months), 22 (10.8%) patients experienced metachronous recurrence, 4 (2.0%) patients experienced local recurrence, and 27 (13.2%) patients died from causes unrelated to SCC. In the AC group, during the median observation time of 45.5 months (range, 6-131 months), one patient (3.8%) experienced metachronous recurrence and two (7.7%) died from causes unrelated to AC. The cumulative 5-year overall survival rates were not significantly different between SCC (75.9%) and AC (88.9%) (P=0.120). The cumulative 5-year disease-free survival rates of SCC (57.1%) were significantly lower than those of AC (85.2%; P=0.017). The cumulative 5-year recurrence rates of SCC (32.0%) were significantly higher than those of AC (4.2%; P=0.023)., Conclusions: The rate of recurrence after ER was higher in patients with SCC than that in patients with AC. These findings suggest that, by detecting AC of the esophagus earlier, a satisfactory prognosis without recurrence can be expected after ER in Japan, and more rigorous endoscopic follow-up is necessary after ER in patients with SCC than in those with AC.

Previous studies have examined the negative impacts of individual cardiovascular risk (CVR) factors on left atrial (LA)-left ventricular (LV) interaction, whereas the combined effects of these risk factors are insufficiently elucidated. We studied 176 asymptomatic patients with CVR factors and age-matched 50 healthy individuals by conventional and 2-dimensional speckle-tracking echocardiography. The patients were classified into 2 groups according to the number of CVR factors: one risk factor (single) group (n = 79) and 2 or more risk factors (comorbid) group (n = 97). The peak early diastolic transmitral flow velocity (E)/peak early diastolic mitral annular motion velocity (e')/peak systolic LA strain (S-LAs) was used as a surrogate for LA stiffness during ventricular systole. The E/e'/S-LAs was greatest in the comorbid group. The peak systolic LV circumferential and radial strains, peak early diastolic LV radial strain rate, and peak early diastolic LA strain and strain rate were lower in the comorbid group than in the single group. Multivariate regression analysis identified age, body mass index, systolic blood pressure, end-systolic LV diameter, peak systolic mitral annular motion velocity (s'), and peak systolic LV radial strain in the comorbid group, and peak atrial systolic transmitral fl ow velocity and s' in the single group, as independent predictors of E/e'/S-LAs. Subtle LA and LV dysfunction with individual CVR factors were more aggravated with the comorbid conditions in asymptomatic patients.

Heart failure with preserved ejection fraction (HFPEF) is a syndrome that frequently occurs in older people and patients with cardiovascular risk factors, particularly hypertension. This syndrome is not a specific disease process, whereas is associated with high morbidity and mortality in patients with heart failure with reduced ejection fraction (HFREF) as well. Therefore, a "one size fits all" diagnosis strategy is unlikely to operate for patients with HFPEF. Assessment of left atrial (LA)-left ventricular (LV)-arterial coupling seems to have a clinical impact on hypertensive patients, because HF signs and symptoms have been found to be significantly related to inappropriate LA-LV interaction during diastole and LV-arterial interaction during systole. Two-dimensional speckle tracking echocardiography (2DSTE) is a new tool that may have a role in earlier detecting the impaired LA, LV, and arterial function in asymptomatic patients. This review explored the impact of LA-LV-arterial coupling in understanding the pathophysiology of hypertension as a road to HFPEF, and the possibilities of clinical application by using 2DSTE.

Hypertension and obesity each are well known to result in heart failure with preserved ejection fraction. Therefore, it is clinically important to clarify the mechanisms of further deterioration of left atrial (LA)-left ventricular (LV) interaction in asymptomatic patients with obesity in the presence of hypertension. Data on conventional and two-dimensional speckle-tracking echocardiography (2DSTE) were obtained from 134 asymptomatic hypertensive patients. The study sample was divided into two groups: non-obese (n = 80; body mass index [BMI] <25 kg/m(2)] and obese (n = 54; BMI ≥25 kg/m(2)). The end-diastolic LV diameter, ratio of early transmitral flow to mitral annular motion velocity (E/e'), peak systolic LV circumferential strain rate, and E/e'/peak systolic LA strain (S-LAs) were greater in the obese group. Among the significantly correlated variables with BMI and E/e'/S-LAs in univariate analyses, multivariate analyses revealed that BMI is independently associated with end-diastolic LV diameter and peak systolic LV radial strain in all hypertensive patients, and that age, systolic blood pressure, relative LV wall thickness, peak systolic mitral annular motion velocity (s'), peak systolic LV radial strain, and peak early diastolic LV longitudinal strain rate are identified as independent predictors related to E/e'/S-LAs in the obese patients, whereas only s' contributes to the E/e'/S-LAs in the non-obese patients. Impaired LA-LV interaction was accelerated with obesity in the presence of hypertension. Assessment of the LA and LV function using 2DSTE provided additional information to the negative effects of cardiovascular risk factors on the LA and LV function in patients without clinical symptoms., (Copyright © 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

The elucidation of heat tolerance mechanisms is required to combat the challenges of global warming. This study aimed to determine the antioxidant enzyme responses to heat stress, at the enzymatic activity and gene expression levels, and to investigate the antioxidative alterations associated with heat tolerance in the stems and roots of squashes using three genotypes differing in heat tolerance. Plants of heat-tolerant "C. moschata", thermolabile "C. maxima" and moderately heat-tolerant interspecific inbred line "Maxchata" genotypes were exposed to moderate (37 °C) and severe (42 °C) heat shocks. "C. moschata" exhibited comparatively little oxidative damage, with the lowest hydrogen peroxide (H2O2), superoxide (O2(-)) and malondialdehyde (MDA) contents in the roots compared to stems, followed by "Maxchata". The enzyme activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT) and peroxidase (POD) were found to be increased with heat stress in tolerant genotypes. The significant inductions of FeSOD, MnSOD, APX2, CAT1 and CAT3 isoforms in tolerant genotypes suggested their participation in heat tolerance. The differential isoform patterns of SOD, APX and CAT between stems and roots also indicated their tissue specificity. Furthermore, despite the sequence similarity of the studied antioxidant genes among "C. maxima" and "Maxchata", most of these genes were highly induced under heat stress in "Maxchata", which contributed to its heat tolerance. This phenomenon also indicated the involvement of other unknown genetic and/or epigenetic factors in controlling the expression of these antioxidant genes in squashes, which demands further exploration.

Phospholipid vesicles (liposomes) formed in pharmaceutically acceptable nonaqueous polar solvents such as propylene glycol are of interest in drug delivery because of their ability to improve the bioavailability of drugs with poor aqueous solubility. We have demonstrated a stabilizing effect of cholesterol on lamellar phases formed by dispersion of distearoylphosphatidylcholine (DSPC) in water/propylene glycol (PG) solutions with glycol concentrations ranging from 0 to 100%. The stability of the dispersions was assessed by determining the effect of propylene glycol concentration on structural parameters of the lamellar phases using a complementary combination of X-ray and neutron scattering techniques at 25 °C and in the case of X-ray scattering at 65 °C. Significantly, although stable lamellar phases (and liposomes) were formed in all PG solutions at 25 °C, the association of the glycol with the liposomes' lamellar structures led to the formation of interdigitated phases, which were not thermostable at 65 °C. With the addition of equimolar quantities of cholesterol to the dispersions of DSPC, stable lamellar dispersions (and indeed liposomes) were formed in all propylene glycol solutions at 25 °C, with the significant lateral phase separation of the bilayer components only detectable in propylene glycol concentrations above 60% (w/w). We propose that the stability of lamellar phases of the cholesterol-containing liposomes formed in propylene glycol concentrations of up to 60% (w/w) represent potentially very valuable drug delivery vehicles for a variety of routes of administration.

Non-steroidal anti-inflammatory drugs (NSAIDs) can cause dyspeptic symptoms, including abdominal pain. Gastric mucus is important as the first line of defense against luminal irritants. In the present study, we investigated whether gastric mucus secretion could influence the severity of gastric mucosal injuries or NSAID-induced dyspeptic symptoms. Fifteen Helicobacter pylori-negative, healthy males were administered two types of NSAIDs, a non-selective cyclooxygenase inhibitor, naproxen (300 mg, twice a day), or a cyclooxygenase-2-selective inhibitor, etodolac (200 mg, twice a day), for 1 week in a crossover study, with an interval of ≥ 4 weeks. Study participants underwent endoscopic examinations before and after treatment. Pentagastrin-stimulated gastric secretions were collected for 10 min during endoscopic examinations, and were analyzed for gastric acid levels (mEq/10 min) and mucus output (mg hexose/10 min). The grade of gastric mucosal injury was assessed endoscopically. Among 29 subjects who completed the crossover study, 11 individuals reported abdominal pain following the administration of naproxen or etodolac for 1 week, as judged by elevated pain scores, while 18 individuals did not report abdominal pain. The occurrence of symptoms was not associated with the type of NSAIDs administered or the occurrence of erosive injury visualized by endoscopy. Gastric mucus secretion was significantly increased in subjects without drug-induced abdominal pain (P < 0.05), whereas it was significantly reduced in those with drug-induced abdominal pain (P < 0.05). In conclusion, the occurrence of NSAID-induced abdominal pain is associated with reduced levels of gastric mucus secretion rather than the occurrence of endoscopic mucosal injury.

In the present paper, we report a case of rare collagenous gastritis. The patient was a 25-year-old man who had experienced nausea, abdominal distention and epigastralgia since 2005. Esophagogastroduodenoscopy (EGD) carried out at initial examination by the patient's local doctor revealed an extensively discolored depression from the upper gastric body to the lower gastric body, mainly including the greater curvature, accompanied by residual mucosa with multiple islands and nodularity with a cobblestone appearance. Initial biopsies sampled from the nodules and accompanying atrophic mucosa were diagnosed as chronic gastritis. In August, 2011, the patient was referred to Tohoku University Hospital for observation and treatment. EGD at our hospital showed the same findings as those by the patient's local doctor. Pathological findings included a membranous collagen band in the superficial layer area of the gastric mucosa, which led to a diagnosis of collagenous gastritis. Collagenous gastritis is an extremely rare disease, but it is important to recognize its characteristic endoscopic findings to make a diagnosis., (© 2012 The Authors. Digestive Endoscopy © 2012 Japan Gastroenterological Endoscopy Society.)

Background: Two-dimensional speckle tracking echocardiography (2DSTE) has recently been applied to evaluate left atrial (LA) function in addition to left ventricular (LV) function. However, whether 2DSTE can provide insight into LA-LV interaction related to an increase in LV pressure overload remains unknown., Methods: One hundred five asymptomatic patients with hypertension were studied by conventional, pulsed and tissue Doppler, and 2DSTE. Hypertensive patients were classified into 2 groups according to the ratio of early diastolic to atrial systolic velocity (E/A) of transmitral flow: E/A ≥ 1 (n = 37) and E/A < 1 (n = 68). We used (E/peak early diastolic mitral annular motion velocity [e'])/peak systolic LA strain (S-LAs) and E/e', as parameters of LA stiffness during ventricular systole and LV diastolic stiffness, respectively., Results: The peak early diastolic LV longitudinal strain rate, and peak early diastolic LA strain and strain rate were lower in the E/A < 1 group than in the E/A ≥ 1 group. The E/e'/S-LAs and E/e' were greater in the E/A < 1 group. In the E/A < 1 group, systolic blood pressure (SBP) correlated with LV wall thickness parameters, A, e', E/e', peak early diastolic LV longitudinal strain rate, and E/e'/S-LAs. Multivariate regression analysis indicated that A, E/e', and E/e'/S-LAs were defined as strong predictors related to SBP., Conclusion: In patients with hypertension, an elevation in SBP leads to increased LA stiffness during ventricular systole and LV diastolic stiffness, in association with continued and further advanced LV diastolic dysfunction. 2DSTE is considered a sensitive tool for detecting abnormal LA-LV coupling related to an increased LV pressure overload., (© 2013, Wiley Periodicals, Inc.)

Our aim was to investigate the relationships between left atrial (LA) structural and functional changes and left ventricular (LV) dysfunction related to LV pressure overload in asymptomatic patients with hypertension. One hundred and twenty-six asymptomatic patients with hypertension and LV ejection fraction (EF) ≥ 60% were studied. Conventional, pulsed and tissue Doppler, and two-dimensional speckle-tracking echocardiography (2DSTE) were performed to seek the independent determinants for alterations in LA structure and function. LA volume index (LAVI) correlated with age, body mass index (BMI), end-diastolic ventricular septal thickness (VSth), end-diastolic LV posterior wall thickness, relative LV wall thickness (RWT), LV mass index, peak A velocity of transmitral flow, E/e', and peak systolic and early diastolic LA strains and strain rates. Peak LA strain during ventricular systole (S-LAs) correlated with age, BMI, heart rate (HR), end-systolic LV diameter, LAVI, VSth, RWT, LVEF, e', E/e', peak systolic LV radial strain, and peak early diastolic LV longitudinal strain rate. Multivariate regression analyses indicated that LV mass index, peak A velocity, E/e', and S-LAs are defined as strong predictors related to LAVI, and that BMI, HR, LAVI, and peak systolic LV radial strain are defined as strong predictors related to S-LAs. In conclusion, 2DSTE demonstrated that alterations in LA structure and function are mainly associated with LV diastolic and systolic dysfunction, respectively, in preclinical patients with hypertension., (Copyright © 2013 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Increased arterial stiffness is becoming an increasing health care problem as the population ages. Our aim was to detect the vascular aging of common carotid artery (CCA) and abdominal aorta (AAO) more easily and earlier using two-dimensional speckle-tracking echocardiography, and to evaluate the regional differences in mechanical properties related to changes in aging between the two arteries in preclinical patients. Twenty-nine clinically normal individuals and 68 preclinical patients with cardiovascular risk factors were examined. The peak circumferential strains were measured from the short-axis views of the CCA and AAO, and each stiffness β was determined. The CCA and AAO diameters increased with advanced age, and the latter diameter was widely distributed in patients of 50 years or older. The mean strain and stiffness index of the AAO were greater and lower, respectively, than those of the CCA at all ages. The CCA and AAO strains decreased with age, expressing dramatic declines before the fifth decade of life. The CCA and AAO stiffness indices increased with age, expressing rapid ascents after the fifth decade of life, particularly in the AAO. The best markers of subclinical arterial aging were strain in younger persons and stiffness in older individuals. Two-dimensional speckle-tracking echocardiography is a new tool that can be used to directly and easily evaluate arterial function.

Objective: There is a strong male predominance of oesophageal adenocarcinoma, which might be related to the higher prevalence of precursor lesions such as erosive reflux oesophagitis in men compared with women. This experiment investigated the gender difference in a reflux oesophagitis model of rats and explored the potential role of oestrogen in controlling oesophageal tissue damage., Design: An acid-reflux oesophagitis model was surgically produced in male and female rats, and ascorbic acid in the diet and sodium nitrite in the drinking water were administered to half of either group to provoke luminal exogenous nitric oxide (NO) as an exacerbating agent. Seven days after the surgery, the oesophagus was excised, and the injury area, myeloperoxidase activity and pro-inflammatory cytokine levels were measured. Furthermore, 17β-oestradiol was administered to ovariectomised female rats or male rats, which then underwent reflux oesophagitis surgery., Results: While there was no gender difference in oesophageal damage in the baseline model, oesophageal damage was more intensively observed in males than in females in the presence of exogenous NO administration. While oesophageal damage was increased in ovariectomised rats compared with sham ovariectomised, exacerbated oesophageal damage was attenuated by the replacement of 17β-oestradiol. In addition, exacerbated oesophageal damage in male rats was suppressed by 17β-oestradiol., Conclusion: This is the first study showing the prominent gender difference in the severity of oesophageal tissue damage in a gastro-oesophageal reflux disease-related animal model, highlighting the critical involvement of oestrogen in controlling gastro-oesophageal reflux disease-related oesophageal epithelial injury.

Background:  The aim of the present study was to detect earlier the negative effect of cardiovascular risk (CVR) factors on left atrial (LA) and left ventricular (LV) function related to abdominal aortic (AAO) stiffness using 2-dimensional speckle-tracking echocardiography (2DSTE) in asymptomatic patients., Methods and Results:  One hundred and twelve patients with CVR factors and 56 healthy individuals were studied. 2DSTE data were acquired for determination of LA and LV myocardial and AAO wall deformations. LA volume index, LV mass index, ratio of early diastolic transmitral flow to mitral annular velocity (E/e')/peak systolic LA strain (S-LAs), and AAO stiffness were greater, and peak early diastolic LV longitudinal strain rate (SR-LVe) was lower in the patient group. Among the significantly correlated variables with AAO stiffness on univariate analysis, multivariate linear regression analysis identified SR-LVe and (E/e')/S-LAs in the patient group, and only age in the healthy group, as independent predictor of AAO stiffness., Conclusions:  Structural and functional changes in the LA and LV and AAO stiffening were accelerated with CVR factors, and higher AAO stiffness was associated with deteriorated LA compliance and impaired LV relaxation in asymptomatic patients with CVR factors. 2DSTE has a potential for earlier detection of abnormal LA and LV function related to increased AAO stiffness.

Background: The association of Helicobacter pylori infection with aspirin-induced gastropathy is controversial. H. pylori infection exerts diverse effects on gastric acid secretion. In this study, the interaction between H. pylori infection and aspirin was investigated with reference to the individual gastric acid secretion level in H. pylori-positive subjects., Methods: Ninety-three (81 men, mean age: 70 years) long-term low-dose aspirin takers were prospectively enrolled. H. pylori infection was evaluated by serum IgG antibody determination, and gastrin-stimulated acid output was assessed with the endoscopic gastrin test. H. pylori-positive aspirin-takers were classified into 2 subgroups (hyposecretors and non-hyposecretors). The grade of gastric mucosal injury was assessed endoscopically according to the modified Lanza score; intensive aspirin-induced gastropathy was defined as a modified Lanza score of ≥4. Multiple logistic regression analyses were used to adjust for potential confounders., Results: With H. pylori-negative patients taken as the reference, H. pylori infection was found to be positively associated with intensive gastropathy among non-hyposecretors, with an odds ratio (OR) (95 % confidence interval [CI]) of 4.2 (1.1-17.1), while the infection was negatively associated with gastropathy among hyposecretors, with an OR (95 % CI) of 0.3 (0.08-0.9). Aspirin-induced gastropathy occurred preferentially in the antrum among H. pylori-positive non-hyposecretors, while it affected the fundus among H. pylori-positive hyposecretors., Conclusion: The effect of H. pylori infection on the aspirin-induced gastropathy was biphasic depending on the individual gastric acid secretion level. In the presence of sufficient amounts of gastric acid, H. pylori infection and aspirin could synergistically damage gastric mucosal integrity, while in the absence of sufficient amounts of gastric acid, the synergistic effect could be completely counteracted and the infection could even suppress the aspirin-induced gastropathy.

Mucosa-associated lymphoid tissue (MALT) lymphomas are extra-nodal B-cell lymphomas arising from MALT, and the most commonly affected organ is the stomach. Helicobacter pylori (H. pylori) eradication therapy with proton-pump inhibitors and antibiotics is the first-line therapy for H. pylori-positive gastric MALT lymphomas, but the effectiveness of the therapy for H. pylori-negative gastric MALT lymphomas remains controversial. Hence, we aimed to evaluate the effectiveness of this eradication therapy for H. pylori-negative MALT lymphomas. The H. pylori infection status of 158 gastric MALT lymphoma patients followed in our unit was judged by urea breath test, rapid urease test, histology of the biopsy specimen taken from the stomach during endoscopy, and serum antibody against H. pylori. Seventeen patients that were negative for all four tests and did not have gastric mucosal atrophy were treated with antibiotic eradication therapy. The average age at diagnosis was 56.8 years old (range: 36-73 years), and the median follow-up period after H. pylori eradication in all 17 patients was 5.3 years (range: 0.3-12.7 years). Five patients (29.4%) achieved complete remission (CR) by eradication therapy alone. Comparison between the responding and non-responding patients revealed that the patients endoscopically diagnosed to have a single lesion of gastric MALT lymphoma were seen only in the responding group, whereas all non-responding patients had multiple lesions (P < 0.05). In conclusion, H. pylori eradication therapy achieved a favorable CR rate in H. pylori-negative gastric MALT lymphoma patients and could be considered as a first-line therapy, especially for patients with a single lesion.

Background: The Activity in GEriatric acute CARe (AGECAR) is a randomised control trial to assess the effectiveness of an intrahospital strength and walk program during short hospital stays for improving functional capacity of patients aged 75 years or older., Methods/design: Patients aged 75 years or older admitted for a short hospital stay (≤ 14 days) will be randomly assigned to either a usual care (control) group or an intervention (training) group. Participants allocated in the usual care group will receive normal hospital care and participants allocated in the intervention group will perform multiple sessions per day of lower limb strength training (standing from a seated position) and walking (10 min bouts) while hospitalized. The primary outcome to be assessed pre and post of the hospital stay will be functional capacity, using the Short Physical Performance Battery (SPPB), and time to walk 10 meters. Besides length of hospitalization, the secondary outcomes that will also be assessed at hospital admission and discharge will be pulmonary ventilation (forced expiratory volume in one second, FEV1) and peripheral oxygen saturation. The secondary outcomes that will be assessed by telephone interview three months after discharge will be mortality, number of falls since discharge, and ability to cope with activities of daily living (ADLs, using the Katz ADL score and Barthel ADL index)., Discussion: Results will help to better understand the potential of regular physical activity during a short hospital stay for improving functional capacity in old patients. The increase in life expectancy has resulted in a large segment of the population being over 75 years of age and an increase in hospitalization of this same age group. This calls attention to health care systems and public health policymakers to focus on promoting methods to improve the functional capacity of this population., Trial Registration: ClinicalTrials.gov ID: NCT01374893.

Background: The relative contribution of gastric acid secretion and Helicobacter pylori infection to low-dose aspirin-induced gastropathy remains to be clarified. This is partly because the capability of the infection to modify gastric acid secretion complicates the interaction. The aim of this study was to estimate the association of aspirin-induced mucosal injury, as well as H. pylori infection, with gastric acid output., Methods: A total of 186 male outpatients, comprising 60 aspirin takers, on 100 mg of enteric-coated aspirin daily and 126 non-aspirin takers were prospectively enrolled in this study. Gastrin-stimulated acid output was estimated by the endoscopic gastrin test. The grade of gastric mucosal injury was assessed endoscopically according to the modified Lanza score. Multiple logistic regression analyses were used to adjust for potential confounders., Results: The gastric acid secretion level, with an odds ratio (OR) (95% confidence interval [CI]) of 10.5 (3.0-36.9) and aspirin administration, with an OR (95% CI) of 7.4 (3.0-18.3) were independently associated with gastric mucosal injury, and the co-existence of both factors greatly elevated the risk of mucosal injury, with an OR (95% CI) of 77.0 (13.5-440.0). H. pylori infection, itself, did not show any significant effect on the aspirin-induced mucosal injury after adjusting for gastric acid secretion., Conclusions: This study has demonstrated that aspirin-induced gastropathy is directly associated with gastric acid secretion. In addition, it also suggested that the gastric acid secretion level modulates the association between H. pylori infection and aspirin-induced gastropathy.

Objectives: To assess the effects of an 8-week exercise training program with a special focus on light- to moderate-intensity resistance exercises (30-70% of one repetition maximum, 1RM) and a subsequent 4-week training cessation period (detraining) on muscle strength and functional capacity in participants aged 90 and older., Design: Randomized controlled trial performed during March to September 2009., Setting: Geriatric nursing home., Participants: Forty nonagenarians (90-97) were randomly assigned to an intervention or control group (16 women and 4 men per group)., Intervention: Eight-week muscle strength exercise intervention focused on lower limb strength exercises of light to moderate intensity., Primary Outcome: 1RM leg press., Secondary Outcomes: handgrip strength, 8-m walk test, 4-step stairs test, Timed Up and Go test, and number of falls., Results: A significant group by time interaction effect (P=.02) was observed only for the 1RM leg press. In the intervention group, 1RM leg press increased significantly with training by 10.6 kg [95% confidence interval (CI)=4.1-17.1 kg; P=.01]. Except for the mean group number of falls, which were 1.2 falls fewer per participant in the intervention group (95% CI=0.0-3.0; P=.03), no significant training effect on the secondary outcome measures was found., Conclusion: Exercise training, even of short duration and light to moderate intensity, can increase muscle strength while decreasing fall risk in nonagenarians., (© 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.)

Atrophic gastritis (AG) is a well-recognized high-risk condition for developing gastric cancer (GC). Gastrin 17 (G17), a hormone secreted from antral G cells, regulates gastric acid secretion, and its serum level is a possible indicator of antral atrophy. Serum pepsinogen is well established as the indicator of AG involving the corpus. Here we investigated whether serum PG and G17 levels would be useful for determining the topographic pattern of AG and estimating the risk of GC. Enrolled were 122 Japanese patients with early GC (114 well- to moderate-differentiated cancers and 8 poorly-differentiated cancers). In addition, 178 subjects without GC were recruited as control from those undergoing endoscopic examination (non-GC group). All subjects were histologically assigned to the following four groups: non-AG, antrum-predominant AG, corpus-predominant AG, and multifocal AG, affecting the antrum and corpus. Serum concentrations of pepsinogen and G17 were determined using ELISA. Multifocal AG was more frequent in the GC group than in the adjusted non-GC group, and had the highest risk of GC (OR 25.1). Serum G17 was significantly decreased with the exacerbation of antral atrophy in the coexistence of corpus atrophy. Serum biomarker profiles showed that the low levels of pepsinogen and G17 could discriminate between multifocal AG and other types of AG, but not with pepsinogen level alone. Serologically defined multifocal AG had the highest cancer risk among other serologically defined AG groups (OR 26.9). In conclusion, the low serum levels of pepsinogen and G17 are predictive of extensive gastric atrophy with high-risk of early GC.

Background: Eosinophilic esophagitis (EoE) has been a rarely recognized condition in Asian populations, and its clinical manifestation is rarely documented. Our aim was to describe clinically, endoscopically, and pathologically the features of patients with esophageal eosinophilia, including EoE., Methods: Twelve patients histologically proven to have esophageal eosinophilia were investigated. The histological diagnostic cutoff value was defined as a peak of ≥15 eosinophils/high-power field (HPF) in esophageal biopsies. Symptoms, endoscopic and pathological findings, and treatment outcome were evaluated., Results: Nine of the 12 patients were male and the 12 patients had a mean age of 47.7 years. Allergic conditions were concurrent in a total of 3 patients. Mild peripheral eosinophilia was observed in only 2 patients. The predominant symptom was solid-food dysphagia, but some patients complained of heartburn, or chest, epigastric, or back pain. Three asymptomatic subjects were also incidentally diagnosed during endoscopic screening. Linear furrows, concentric rings, and white exudates in the esophagus were frequently observed. In 4 of 5 patients who were administered a proton pump inhibitor (PPI), esophageal eosinophilia was histologically decreased or disappeared with symptom relief and endoscopic improvement. In 2 patients unresponsive to PPI, topical steroid therapy, administered by the swallowing of fluticasone propionate, led to symptomatic and histological remission., Conclusions: The endoscopic recognition of linear furrows, concentric rings, and white exudates is important in the diagnosis of eosinophilic esophageal inflammation. In a subset of patients this condition improves clinicopathologically with PPI treatment, and typical EoE, as strictly defined by unresponsiveness to PPI, appears to be a rather rare condition.

Exposure of the esophageal mucosa to refluxed gastroduodenal contents is recognized to be an important risk factor for Barrett's esophagus (BE). At the human gastroesophageal junction, nitric oxide is generated luminally through the enterosalivary recirculation of dietary nitrate, and in cases with gastroesophageal reflux, the site of luminal nitric oxide generation could shift to the distal esophagus. The aim of this study is to investigate whether exogenous luminal nitric oxide could promote the development of BE in rats. Sodium nitrite plus ascorbic acid were administered to a rat surgical model of BE, in which the gastroduodenal contents were refluxed into the esophagus to generate exogenous luminal nitric oxide in the esophagus by the acid-catalyzed chemical reaction between the 2 reagents. The emergence of BE was evaluated histologically in the early phase (several weeks) after the surgery with or without exogenous nitric oxide administration. To elucidate the histogenesis of BE, CDX2, MUC2 and MUC6 expressions were investigated immunohistochemically. Coadministration of sodium nitrite plus ascorbic acid significantly accelerated the timing of emergence and increased the area of BE compared with controls. Administration of either reagent alone did not show any promotive effects on BE formation. Immunohistochemically, the columnar epithelium thus induced was similar to the specialized intestinal metaplasia in human BE. The results of this animal model study suggest that exogenous luminal nitric oxide could be involved in the pathogenesis of the columnar transformation of the esophagus. Further studies in human are warranted.

We studied the A55T, E164K, I225T, K153R and P198A variants in the myostatin (GDF8) gene, muscle strength and mass, and physical function during daily living in 41 nonagenarians [33 women, age range, 90, 97]. No participant carried a mutant allele of the aforementioned variants, except three participants (all women), who carried the R allele of the K153R polymorphism, with one of them (woman aged 96 years) being homozygous. Overall, in KR women muscle phenotype values (1RM leg press and estimated muscle mass) were low-to-normal compared to the whole group (approximately 25th-50th percentile), and their functional capacity (Barthel and Tinetti tests) was normal. In the woman bearing the RR genotype, values of muscle mass and functional capacity were below the 25th percentile. She is the first RR Caucasian whose phenotype has been characterised specifically. In summary, heterozygosity for the GDF8 K153R polymorphism does not seem to exert a negative influence on the muscle phenotypes of women who are at the end of the human lifespan, yet homozygosity might do so. More research on larger cohorts of nonagenarians is needed to corroborate the present findings.

Purpose: We determined the effects of a 3-month low-moderate-intensity strength training program (2 sessions/week) on functional capacity, muscular strength, body composition, and quality of life (QOL) in 22 young (12-16 yrs) anorexic outpatients., Methods: Patients were randomly assigned to a training or control group (n=11 [10 females] each). Training sessions were of low intensity (loads for large muscle groups ranging between 20%-30% and 50%-60% of six repetitions maximum [6RM] at the end of the program). We measured functional capacity by the time up and go and the timed up and down stairs tests. Muscular strength was assessed by 6RM measures for seated bench and leg presses. We estimated percent body fat and muscle mass. We assessed patients' QOL with the Short Form-36 items., Results: The intervention was well tolerated and did not have any deleterious effect on patients' health, and did not induce significant losses in their body mass. The only studied variable for which a significant interaction (group x time) effect was found (p=.009) was the 6RM seated lateral row test., Conclusions: Low-moderate-intensity strength training does not seem to add major benefits to conventional psychotherapy and refeeding treatments in young anorexic patients., (Copyright 2010 Society for Adolescent Medicine. Published by Elsevier Inc. All rights reserved.)

A significant proportion of groundwater in south Asia is contaminated with arsenic. Pakistan has low levels of arsenic in groundwater compared with China, Bangladesh and India. A representative multi-stage cluster survey conducted among 3874 persons > or = 15 years of age to determine the prevalence of arsenic skin lesions, its relation with arsenic levels and cumulative arsenic dose in drinking water in a rural district (population: 1.82 million) in Pakistan. Spot-urine arsenic levels were compared among individuals with and without arsenic skin lesions. In addition, the relation of age, body mass index, smoking status with arsenic skin lesions was determined. The geographical distribution of the skin lesions and arsenic-contaminated wells in the district were ascertained using global positioning system. The total arsenic, inorganic and organic forms, in water and spot-urine samples were determined by atomic absorption spectrophotometry. The prevalence of skin lesions of arsenic was estimated for complex survey design, using surveyfreq and surveylogistic options of SAS 9.1 software.The prevalence of definitive cases i.e. hyperkeratosis of both palms and soles, was 3.4 per 1000 and suspected cases i.e. any sign of arsenic skin lesions (melanosis and/or keratosis), were 13.0 per 1000 among > or = 15-year-old persons in the district. Cumulative arsenic exposure (dose) was calculated from levels of arsenic in water and duration of use of current drinking water source. Prevalence of skin lesions increases with cumulative arsenic exposure (dose) in drinking water and arsenic levels in urine. Skin lesions were 2.5-fold among individuals with BMI <18.5 kg/m2. Geographically, more arsenic-contaminated wells and skin lesions were alongside Indus River, suggests a strong link between arsenic contamination of groundwater with proximity to river.This is the first reported epidemiological and clinical evidence of arsenic skin lesions due to groundwater in Pakistan. Further investigations and focal mitigation measures for arsenic may be carried out alongside Indus River.

The leaves extract of Catharanthus roseus was investigated for hypotensive and hypolipidemic effects in adrenaline-induced hypertensive rats (AIHR) and compared with those of Atenolol in a crossover design. The pharmacologically Active components responsible for hypotensive activities were isolated from plant using bioassay guided purification approach and the structure of the compounds was proposed by spectroscopic methods. Catharanthus roseus leaves extract and commercial drug Atenolol were administered through intraperitoneal (i.p) route for one week. Different biochemical parameters such as heart weight, blood glucose level, serum cholesterol level, serum triglyceride level, body weight and the relationships between them were measured. Catharanthus roseus leaves extract at a dose of 30 mg/155+/-15 gm of body weight was injected in rat at every morning during the treatment period. The dose of Atenolol was determined according to its pharmacokinetic parameters. Clinically effective plasma concentration as a hypotensive drug was obtained after the injection of 0.1 mg/155+/-15 gm of body weight of the drug. The Catharanthus roseus leaves extract made significant changes in each cardiovascular parameter after investigation. Catharanthus roseus leaves extract treated animals have shown the hypotensive effects. Hypotensive effects were also shown by Atenolol.

Background: The Health Enhancing Strength Training in Nonagenarians (STRONG) is a randomised control trial to assess the effectiveness of an aerobic and strength training program for improving muscle strength, functional capacity and quality of life in nonagenarians., Methods: Sixty (51 women) nonagenarians (age range: 90-102 years) who live in a geriatric nursing home will be randomly assigned to either a usual care (control) group (n = 30) or an intervention (training) group (n = 30). Participants allocated in the usual care group will receive general physical activity guidelines and participants allocated in the intervention group will also enroll in three weekly non-consecutive individualized training sessions (approximately 45-50 min each) during 8 weeks. The exercise program will consist of muscular strength [with a special focus on leg press at 30% (start of the program) to 70% 1 repetition maximum (end)] and aerobic exercises (cycle-ergometry during 3-5 to 15 minutes at 12-14 points in the rate of perceived exertion scale)., Results: Results from STRONG will help to better understand the potential of regular physical activity for improving the well-being of the oldest population groups., Conclusion: The increase in life expectancy together with the dramatic decrease in birth rates in industrialized countries calls the attention to health care systems and public health policymakers to focus attention on promoting healthy lifestyle in the highest sector of the population pyramid. Our study attempts to improve functional capacity and QOL of nonagenarians by implementing an individualised aerobic and strength training program in a geriatric residential care. Results from STRONG will help to better understand the potential of regular physical activity for improving the well being even in persons aged 90 years or over.

Nitric oxide produced endogenously in vagal neurons modulates gastrointestinal motor activity as an important non-adrenergic and non-cholinergic neurotransmitter. Other than through endogenous biosynthesis, a high concentration of nitric oxide also occurs by chemical reactions within the stomach in the presence of gastric acid through the entero-salivary re-circulation of dietary nitrate. Although dietary nitrate can be a potential source of nitric oxide in the human stomach, there has been no report on the effect of dietary nitrate on gastric motor function. The aim of this study is to investigate the effect of dietary nitrate on gastric emptying, one of the major parameters for the gastric motor function. Fifteen healthy volunteers underwent a placebo-controlled (310 mg sodium nitrate or placebo), double-blind, crossover trial. Since a sufficient amount of gastric acid is essential for dietary nitrate-derived nitric oxide generation in the stomach, the same protocol was repeated after 1-week treatment with a proton pump inhibitor, rabeprazole. Gastric emptying was evaluated by (13)C-octanoate breath test. The sodium nitrate ingestion did not affect gastric emptying either prior to or during rabeprazole treatment, although rabeprazole treatment itself significantly delayed gastric emptying, being independent of the dietary nitrate load. Confirmation of the delayed gastric emptying with rabeprazole indicates the sensitivity of the breath test employed in the present study. In conclusion, despite the potential nitrogen source of exogenous nitric oxide, the ingestion of 310 mg sodium nitrate, which is equivalent to the average daily intake of Japanese adults, does not affect gastric emptying in healthy volunteers.

The research was conducted to investigate the in vitro antimicrobial and cytotoxic activities of leaves and flowers extract extracted from Lippia alba. Disc diffusion technique was used for in vitro antibacterial and antifungal screening. Zones of inhibition were observed in disc diffusion for antibacterial screening against 4 Gram-positive pathogenic and 6 Gram-negative pathogenic bacteria. Among crude extracts chloroform extract showed good activity against all test organisms. A Large zone of inhibition was observed (18 mm) against Vibrio parahaemolyticus. In antifungal screening, the compound showed mild to moderate zones of inhibition against four tested organisms. A Large zone of inhibition was observed against Aspergillus niger (13 mm). Cytotoxic activities of crude extracts were determined using Brine shrimp lethality Bioassay and LC50 values of standard Vincristin sulphate as positive control, n-hexane and crude ethanol extracts were found to be 5, 15 and 20 microg mL(-1), respectively.

Objective: Cytotoxic concentrations of nitric oxide are generated luminally at the gastroesophageal junction through the entero-salivary recirculation of dietary nitrate in humans. The site of luminal nitric oxide generation shifts to the lower esophagus when gastric acid is refluxed into the esophagus. The aim of this study was to investigate the influence of persistent administration of exogenous nitric oxide on esophageal damage., Material and Methods: 0.1% sodium nitrite and/or 1% ascorbic acid was administered in an established rat acid-refluxed esophagitis model. Co-administration of both reactants in this model is thought to induce high concentrations of nitric oxide luminally in the esophagus by an acid-catalyzed chemical reaction when refluxed gastric acid is present. The tissue damage was evaluated by a macroscopic lesion index and myeloperoxidase activity. Nitrotyrosin was assessed immunohistochemically as a footprint of peroxynitrite formation., Results: Co-administration of sodium nitrite and ascorbic acid induced a 4- to 5-fold increase in the esophageal damage compared with baseline reflux esophagitis, while the damage was unchanged when either of the reagents alone was given. Nitrotyrosine was strongly stained in the tissue from the co-administration. Treatment of superoxide scavengers efficiently prevented the exacerbation of esophageal damage by exogenous nitric oxide exposure, suggesting an essential role of superoxide in esophageal damage., Conclusions: Exogenous luminal nitric oxide greatly exacerbated the tissue damage of reflux esophagitis. Diffusion of the luminal nitric oxide into the adjacent superoxide-enriched inflamed tissue of the esophagus could lead to the production of the highly toxic agent peroxynitrite, thus causing exacerbation of the esophageal damage.

Background: We recently reported the expansion of the acid-secreting mucosa following Helicobacter pylori eradication with Congo red chromoendoscopy for a short-term follow-up of up to 7 months. We aimed to extend the observation period and to clarify the characteristic features of acid-secreting and non-acid-secreting mucosa., Methods: In 24 H. pylori-positive patients with fundic atrophy, Congo red chromoendoscopy was performed prior to, 1 month, 7 months, and finally more than 2 years after the eradication. The areas of the acid-secreting mucosa were evaluated semiquantitatively. Two gastric biopsy specimens were taken from the acid-secreting and non-acid-secreting areas at the final chromoendoscopy and were subjected to histologic evaluation and immunohistochemistry for Ki-67 as a proliferation index., Results: After a gradual increase in acid-secreting areas for up to 7 months after eradication, they further increased in 79% subjects between 7 months and the final observation at a mean follow-up of 62 months. However, there still existed non-acid-secreting mucosa in the fundic area in all subjects, indicating that the expansion of acid-secreting mucosa remained partial. Compared with the neighboring acid-secreting area, the non-acid-secreting area was characterized histologically by higher degrees of residual inflammation, mucosal atrophy, and intestinal metaplasia, and by sustained hyperproliferation as well., Conclusions: Functionally irreversible (non-acid-secreting) gastric mucosa after eradication was associated with extensive intestinal metaplasia and sustained hyperproliferation, suggesting that such mucosa still possesses malignant potential. Congo red chromoendoscopy may be useful for estimating the risk of subsequent development of gastric cancer following successful H. pylori eradication by determining the distribution of functionally irreversible mucosa.

Background: Tuberculosis is prevailing in both urban and rural areas of Pakistan. Knowledge, attitude and practice (KAP) of private practitioners (PPs) regarding tuberculosis management have been reported only in urban areas of Pakistan. This survey was conducted for the first time in a rural area of Sindh, Pakistan., Methods: This survey was conducted in January 2007 at Thatta, a rural district of Sindh, Pakistan. Study subjects were twenty-two allopathic qualified (MBBS) doctors of district Thatta, who were practicing in private setups for at least last one year. Before TB-DOTS training PPs had filled the KAP questionnaire regarding tuberculosis (TB) diagnosis and management through DOTS. Survey data was analysed through SPSS version 11.05 software., Results: On average, five TB suspects per month were seen by each PP. Only 14% of PPs advised sputum microscopy solely for pulmonary TB diagnosis, while 86% of PPs used different combination of tests (chest x-ray/sputum microscopy/ESR/tuberculin test) for TB diagnosis. Over 40% PPs did not prescribe TB treatment regimen according to TB-DOTS category. Majority PPs (85%) did not follow the treatment through sputum microscopy and instead relied on clinical improvement and x-ray clearance. Nearly 60% of TB patients at PPs clinic did not show compliance to the TB treatment and none of PPs were following the retrieval of default cases., Conclusions: A gross lack of PPs knowledge and right practice regarding TB diagnosis and management through DOTS was identified and needed to be addressed through providing DOTS training.

Purpose: The measurement of serum pepsinogens is clinically useful to represent gastric acid secretion. Since both serum pepsinogens and gastric acid secretion are considerably altered by H. pylori eradication, the correlation between these two parameters could be different prior to and after eradication. In this study, we investigated the correlation between the two parameters prior to and after eradication., Methods: One hundred eighteen H. pylori-positive patients with peptic ulcers or chronic gastritis were enrolled in this retrospective analysis. In all participants both the measurement of serum pepsinogens and the determination of gastric acid secretion were performed prior to and at 1 month after successful eradication. In 85 subjects, the same assessments were repeated at 7 months. Correlations between serum pepsinogens and gastric acid secretion were assessed using linear regression analysis., Results: The pepsinogen I/II ratio (r = 0.56) was a better indicator of gastric acid secretion in H. pylori-infected subjects than pepsinogen I itself (r = 0.31). Eradication of H. pylori altered the association, causing pepsinogen I (r = 0.55) to become a better indicator of gastric acid secretion compared with the pepsinogen I/II ratio (r = 0.40) at 1 month after eradication, followed by similar tendencies at 7 months., Conclusion: Using different serum biomarkers (pepsinogen I/II ratio prior to eradication or pepsinogen I after eradication), the measurement of serum pepsinogens is useful for predicting the individual gastric acid secretion level not only in H. pylori-infected subjects, but also in subjects with histories of eradication of the infection.

Objective: To determine the prevalence of cigarette smoking and to obtain information on socio-demographic factors and attitude regarding cigarette smoking among adult women in a rural district of Sindh Province, Pakistan., Methods: A cross sectional community based survey was done in a rural district of Sindh province of Pakistan using a two stage cluster sampling design. A pre tested questionnaire was used to interview 502 adult women (aged 18- 60 years) from the study site. The study was approved by the ethical research committee and informed consent was taken from participants., Results: A total of 502 women were interviewed for this study. Approximately 71% of women were illiterate and 44% of women were in the age group of 18-24 years. A high number (10%) of adult women were smokers. Age at initiation among women (18-24 years) was 42%. A significant difference for questions regarding smoking effects on health (p = 0.02) and knowledge regarding smoking causes respiratory disease (p = 0.02) was observed in this survey., Conclusion: It was concluded that the prevalence of smoking among women is on the rise in this rural district of Pakistan. Young age at initiation is an important finding that needs to be addressed.

Objectives: Very few studies have examined mental health morbidity in Bangladesh. This community-based study of rural Bangladesh in 2000-2001 estimated the burden of mental morbidity among rural people of working age., Study Design and Methods: Community surveys were conducted with one respondent from each household of three selected villages in the service provision area of a non-profit public health organization. General Health Questionnaire 60 (GHQ-60) was used as a screening tool in Stage I, and clinical examination by a Western-trained psychiatrist was undertaken for concurrent validation in Stage II., Results: The overall prevalence of psychiatric disorders in this rural area was 16.5%. Depressive disorders and anxiety disorders constituted about one-half and one-third of the total cases, respectively. A significantly higher prevalence of mental disorders was found in the economically poor respondents, those over 45 years of age, and women from large families., Conclusion: There is a high prevalence of psychiatric disorders in rural Bangladesh. These findings should aid the planning of locally relevant and appropriate mental healthcare programmes. There is an urgent need for a national mental healthcare policy that strengthens primary mental healthcare services.

Among the consequences of the increasing prolongation of lifespan is a worldwide increase in the number of cases of dementia or impaired cognition. In the present study, to test the hypothesis that mechanisms independent of high blood pressure are involved in maintaining cognitive function, we assessed the effects of long-term dilazep treatment on cognitive dysfunction in normotensive Dahl salt-sensitive (Dahl S) rats fed a low-salt diet, using the standard passive avoidance test. Normotensive Dahl S rats fed a 0.3% NaCl diet were treated for 6 months with low-dose dilazep (2.5 microg/ml in drinking water) or high-dose dilazep (12.5 microg/ml). Systolic blood pressure was within normotensive range throughout the study and did not differ among the experimental groups. The results of the passive avoidance test revealed that dilazep treatment attenuated the decline of latency time relative to that in the untreated control rats (control latency time, 235 s; low-dilazep group, 389 s; high-dilazep group, 397 s), suggesting that the cognitive function of normotensive Dahl S rats was improved by dilazep treatment. This improvement of cognition was associated with significant increases in the number of neuronal cells in the hippocampal region and with an increase in capillary length in dilazep-treated Dahl rats. In addition, the dilazep treatments significantly attenuated arteriolar injury of glomeruli in the kidney. These data suggest that dilazep treatment, through vascular and non-vascular effects, maintains the brain function in Dahl S rats susceptible to vascular injury and organ dysfunction.

A pilot study was carried out in Bangladesh during August and September, 1995, using a "snowball" technique with 30 male multiple drug users in order to investigate buprenorphine use, characteristics of the users, their reasons for its use and the drug's effects.