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Caustic ingestion can lead to structural changes in the upper gastro-intestinal tract. However, there is limited data on the effect of caustic ingestion on gastric secretion. This study was planned to determine changes in gastric acid output after sham feeding in patients with caustic induced esophageal stricture and to compare it with healthy controls. It was a prospective study done at tertiary care center in North India. Consecutive patients with caustic induced esophageal stricture were evaluated for the study. Gastric secretory function was estimated in the basal state and after modified sham feeding. These results were compared with age-matched controls. The mean age of the included patients (n = 18) was 30.11 ± 9.19 years and 13 patients were male. 16 (88%) patients had history of acid ingestion. Patients with caustic sequelae had significantly lower basal and stimulated acid secretion compared to controls (n = 10) (5.84 ± 2.44 mmol/hr; p < 0.01 and 17.16 ± 7.53 mmol/hr; p < 0.01; respectively). Patients with lower esophageal stricture (n = 8) had significantly lower increase in acid output compared to patients with stricture elsewhere in esophagus (0.20 ± 0.3 vs. 2.31 ± 1.74 mmol/hr, p < 0.01). Patients with lower esophageal involvement had significantly lower stimulated acid secretion and increase in acid secretion compared to controls (4.74 ± 4.67 vs. 17.16 ± 7.53 mmol/hr; p < 0.01 and 20 ± 0.3 vs. 2.09 ± 0.88 mmol/hr; p < 0.01; respectively). [ABSTRACT FROM AUTHOR]

Background: Caustic ingestion can lead to structural changes in the upper gastrointestinal tract. However, there are limited data on the effect of caustic ingestion on gastric secretion. This study was planned to determine the changes in gastric acid output in patients with caustic ingestion. Methods: It was a prospective study done at a tertiary care center in northern India. Twenty consecutive patients in chronic phase of caustic ingestion were evaluated for the study. The gastric secretory function was estimated in the basal state and following pentagastrin stimulation. These results were compared with normal values for our laboratory. Results: The mean age of the included patients (n = 20) was 27.35 ± 2.96 years and 14 patients were male. Sixteen (80%) patients had a history of acid ingestion. Patients with caustic ingestion had significantly lower mean gastric acid secretion (0.8 ± 0.4 mEq/h vs. 4 ± 0.4 mEq/h; p < 0.001) compared to controls. After pentagastrin stimulation, the mean gastric juice volume (31.8 ± 6 mL/h vs. 62.3 ± 11.7 mL/h; p < 0.01) and acidity (15.3 ± 5.1 mEq/L vs. 39.6 ± 9.3 mEq/L; p < 0.001) increased in patients with caustic ingestion, but were lower than those in control subjects. Patients with a lower esophageal stricture (n = 6) had decreased maximum acid output (0.62 ± 0.32 mEq/h vs. 6.05 ± 0.55 mEq/h; p < 0.05) compared to patients with stricture in the upper or middle esophagus. Conclusion: Caustic ingestion is associated with reduced gastric juice volume and acid output. Patients with stricture in the lower one third of the esophagus are at a higher risk of hypochlorhydria compared to patients with stricture in either the upper or middle esophagus. [ABSTRACT FROM AUTHOR]

Metabolite-protein interactions define the output of metabolic pathways and regulate many cellular processes. Although diseases are often characterized by distortions in metabolic processes, efficient means to discover and study such interactions directly in cells have been lacking. A stringent implementation of proteome-wide Cellular Thermal Shift Assay (CETSA) was developed and applied to key cellular nucleotides, where previously experimentally confirmed protein-nucleotide interactions were well recaptured. Many predicted, but never experimentally confirmed, as well as novel protein-nucleotide interactions were discovered. Interactions included a range of different protein families where nucleotides serve as substrates, products, co-factors or regulators. In cells exposed to thymidine, a limiting precursor for DNA synthesis, both dose- and time-dependence of the intracellular binding events for sequentially generated thymidine metabolites were revealed. Interactions included known cancer targets in deoxyribonucleotide metabolism as well as novel interacting proteins. This stringent CETSA based strategy will be applicable for a wide range of metabolites and will therefore greatly facilitate the discovery and studies of interactions and specificities of the many metabolites in human cells that remain uncharacterized. [ABSTRACT FROM AUTHOR]

Physiologically based absorption modeling has been attracting increased attention to study the interactions of weakly basic drug compounds with acid-reducing agents like proton-pump inhibitors and H2 blockers. Recently, standardized gastric and intestinal biorelevant media to simulate the achlorhydric and hypochlorhydric stomach were proposed and solubility and dissolution data for two model compounds were generated. In the current manuscript, for the first time, we report the utility of these recently proposed biorelevant media as input into physiologically based absorption modeling. Where needed, data collected with the biorelevant gastrointestinal transfer (BioGIT) system were used for informing the simulations in regard to the precipitation kinetics. Using two model compounds, a HCl salt and a semi-fumarate co-crystal which as expected dissolve to a greater extent in these media (and in gastric and intestinal human aspirates) compared to what the pH-solubility profile of the free form would suggest, we demonstrate successful description of the plasma concentration profiles and correctly predicted the lack of significant interaction after administration with pantoprazole or famotidine, respectively. Thus, the data reported in this manuscript represent an initial step towards defining biorelevant input for such simulations on interactions with acid-reducing agents. [ABSTRACT FROM AUTHOR]

Summary: Background: Although autoimmune gastritis (AIG) is generally considered relatively rare, we frequently encounter AIG among patients at to our hospital who have experienced at least two episodes of Helicobacter pylori eradication failure. Aims: We investigated the incidence of AIG in consecutive patients who consulted our department for H. pylori eradication with reference to eradication history. Methods: A total of 404 consecutive patients who visited the H. pylori‐specific out‐patient unit of our hospital from June 2015 to June 2017 were enrolled. Of these, 137 were treatment‐naive, 47 had failed treatment once (single failure), and 220 had failed treatment twice or more (multiple failures) by 13C‐UBT. Gastroscopy was performed in all patients. Culture tests of gastric mucosal samples were performed for H. pylori and other bacteria positive for urease activity. Anti‐parietal cell antibody (APCA) was measured. Patients with severe atrophy in the gastric corpus and positivity for APCA were diagnosed as having AIG. Results: A total of 43 patients were diagnosed as having AIG, of whom two were treatment‐naive (1.5%, 2/137), 1 failed eradication once (2.1% 1/47), and 40 failed treatment at least twice (18.2%, 40/220). The incidence of AIG was significantly higher in the multiple failure group than in the single failure or treatment‐naive groups. Urease‐positive bacteria, such as Klebsiella pneumoniae and alpha‐streptococcus, were identified in 33 of the 35 AIG patients who underwent culture testing. Conclusion: AIG patients were often misdiagnosed as refractory to eradication therapy, probably because achlorhydria in AIG might allow urease‐positive bacteria other than H. pylori to colonise the stomach, causing positive 13C‐UBT results. [ABSTRACT FROM AUTHOR]

Introduction: Diabetes mellitus is one of the metabolic disorders which is characterised by chronic hyperglycaemia due to insulin resistance or deficiency or both. Though a hydrotherapy text reported the use of Cold Abdominal Pack (CAP) for various metabolic disorders, there is a lack of scientific evidence for the use of CAP in a metabolic disorder like Type 2 Diabetes Mellitus (T2DM). Aim: To evaluate the immediate effect of CAP on blood glucose level and cardiovascular functions in patients with T2DM. Materials and Methods: In this prospective single group pretest and post-test study, a total of 20 male T2DM subjects with the mean age of 51.75±7.71 years were recruited from June 2016 to December 2016. Study was conducted in SVYASA University, Bengaluru, Karnataka, India. All the subjects underwent CAP for 20 minutes. Assessments were taken before and immediately after the intervention using standard methods. Statistical analysis was performed using Student's paired samples t-test with the use of Statistical Package for the Social Sciences (SPSS), version 16.0. Results: Results of this study showed a significant reduction in random blood glucose level (p=0.011), pulse rate/heart rate (p=0.028), systolic blood pressure (p=0.023), mean arterial pressure (p=0.010), rate pressure product (p=0.006), and double product (p=0.003) compared to its respective pre test and no such significant changes were observed in diastolic blood pressure (p=0.095) and pulse pressure (p=0.306). Conclusion: Results of this study suggest that 20 minutes of CAP might be effective in improving blood glucose level and cardiovascular functions of patients with T2DM. [ABSTRACT FROM AUTHOR]

Several conditions associated with reduced gastric acid secretion confer an altered risk of developing a gastric malignancy. Helicobacter pylori-induced atrophic gastritis predisposes to gastric adenocarcinoma, autoimmune atrophic gastritis is a precursor of type I gastric neuroendocrine tumours, whereas proton pump inhibitor (PPI) use does not affect stomach cancer risk. We hypothesised that each of these conditions was associated with specific alterations in the gastric microbiota and that this influenced subsequent tumour risk. 95 patients (in groups representing normal stomach, PPI treated, H. pylori gastritis, H. pylori-induced atrophic gastritis and autoimmune atrophic gastritis) were selected from a cohort of 1400. RNA extracted from gastric corpus biopsies was analysed using 16S rRNA sequencing (MiSeq). Samples from normal stomachs and patients treated with PPIs demonstrated similarly high microbial diversity. Patients with autoimmune atrophic gastritis also exhibited relatively high microbial diversity, but with samples dominated by Streptococcus. H. pylori colonisation was associated with decreased microbial diversity and reduced complexity of co-occurrence networks. H. pylori-induced atrophic gastritis resulted in lower bacterial abundances and diversity, whereas autoimmune atrophic gastritis resulted in greater bacterial abundance and equally high diversity compared to normal stomachs. Pathway analysis suggested that glucose-6-phospahte1-dehydrogenase and D-lactate dehydrogenase were over represented in H. pylori-induced atrophic gastritis versus autoimmune atrophic gastritis, and that both these groups showed increases in fumarate reductase. Autoimmune and H. pylori-induced atrophic gastritis were associated with different gastric microbial profiles. PPI treated patients showed relatively few alterations in the gastric microbiota compared to healthy subjects. [ABSTRACT FROM AUTHOR]

Caddisflies have been included in ecotoxicological studies because of their sensitivity and ecological relevance. The present study aimed to assess the sublethal effects of an anthranilic diamide insecticide, chlorantraniliprole (CAP), to Sericostoma vittatum. Used worldwide, CAP is a persistent compound that has been found in surface waters at concentrations from 0.1 μg/L to 9.7 μg/L. It targets the ryanodine receptors, and the present ecotoxicological assessment focused on biomarkers related to neurotransmission, biotransformation, oxidative stress damage, and endpoints related to energy processing (feeding, energy reserves, and cellular metabolism). Six days of exposure trials revealed that feeding activity was significantly decreased in S. vittatum larvae exposed to 0.9 μg/L CAP. Concomitantly, a reduction in cellular metabolism and a significant decrease in protein content were also observed in caddisfly larvae exposed to CAP, suggesting metabolic depression. The results show that sublethal concentrations of CAP can cause detrimental sublethal effects on S. vittatum total glutathione content at concentrations as low as 0.2 μg/L. Bioenergetics can be used to assess physiological effects of contaminants, and the present results show that exposure to low, environmentally relevant, concentrations of CAP alter energy acquisition and metabolism in nontarget aquatic insects with potential population level effects. Environ Toxicol Chem 2017;36:1584-1591. © 2016 SETAC [ABSTRACT FROM AUTHOR]

Purpose: Clinically relevant pharmacokinetic interactions exist between gastric acid-reducing agents and certain weakly basic drugs that rely on acidic environments for optimal oral absorption. In this study, we examine whether the administration of betaine hydrochloride under fed conditions can enhance the absorption of atazanavir, an HIV-1 protease inhibitor, during pharmacologically-induced hypochlorhydria. Methods: In this randomized, single-dose, 3 period, crossover study healthy volunteers received ritonavir-boosted atazanavir (atazanavir/ritonavir 300/100 mg) alone, following pretreatment with the proton pump inhibitor rabeprazole (20 mg twice daily), and with 1500 mg of betaine HCl after rabeprazole pretreatment. Atazanavir was administered with a light meal and gastric pH was monitored using the Heidelberg Capsule. Results: Pretreatment with rabeprazole resulted in significant reductions in atazanavir C ( p < 0.01) and AUC ( p < 0.001) (71 and 70%, respectively), and modest decreases in ritonavir C and AUC ( p < 0.01) (40% and 41%, respectively). The addition of betaine HCl restored 13% of ATV C and 12% of AUC lost due to rabeprazole. Conclusions: The co-administration of rabeprazole with atazanavir resulted in significant decreases in atazanavir exposure. The addition of betaine HCl did not sufficiently mitigate the loss of ATV exposure observed during RAB-induced hypochlorhydria. Meal effects lead to a marked difference in the outcome of betaine HCl on atazanavir exposure than we previously reported for dasatanib under fasting conditions. [ABSTRACT FROM AUTHOR]

ABSTRACT Efficient calcium absorption is essential for skeletal health. Patients with impaired gastric acidification display low bone mass and increased fracture risk because calcium absorption is dependent on gastric pH. We investigated fracture healing and post-traumatic bone turnover in mice deficient in Cckbr, encoding a gastrin receptor that affects acid secretion by parietal cells. Cckbr−/− mice display hypochlorhydria, calcium malabsorption, and osteopenia. Cckbr−/− and wildtype (WT) mice received a femur osteotomy and were fed either a standard or calcium-enriched diet. Healed and intact bones were assessed by biomechanical testing, histomorphometry, micro-computed tomography, and quantitative backscattering. Parathyroid hormone (PTH) serum levels were determined by enzyme-linked immunosorbent assay. Fracture healing was unaffected in Cckbr−/− mice. However, Cckbr−/− mice displayed increased calcium mobilization from the intact skeleton during bone healing, confirmed by significantly elevated PTH levels and osteoclast numbers compared to WT mice. Calcium supplementation significantly reduced secondary hyperparathyroidism and bone resorption in the intact skeleton in both genotypes, but more efficiently in WT mice. Furthermore, calcium administration improved bone healing in WT mice, indicated by significantly increased mechanical properties and bone mineral density of the fracture callus, whereas it had no significant effect in Cckbr−/− mice. Therefore, under conditions of hypochlorhydria-induced calcium malabsorption, calcium, which is essential for callus mineralization, appears to be increasingly mobilized from the intact skeleton in favor of fracture healing. Calcium supplementation during fracture healing prevented systemic calcium mobilization, thereby maintaining bone mass and improving fracture healing in healthy individuals whereas the effect was limited by gastric hypochlorhydria. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1914-1921, 2016. [ABSTRACT FROM AUTHOR]

Helicobacter pylori is the strongest risk factor for gastric adenocarcinoma, which develops within a hypochlorhydric environment. We sequentially isolated H. pylori (strain J99) from a patient who developed corpus-predominant gastritis and hypochlorhydia over a 6-year interval. Archival J99 survived significantly better under acidic conditions than recent J99 strains. H. pylori arsRS encodes a 2-component system critical for stress responses; recent J99 isolates harbored 2 nonsynonymous arsS mutations, and arsS inactivation abolished acid survival. In vivo, acid-resistant archival, but not recent J99, successfully colonized high-acid-secreting rodents. Thus, genetic evolution of arsS may influence progression to hypochlorhydia and gastric cancer. [ABSTRACT FROM AUTHOR]

Objective:In chronic atrophic gastritis (CAG), destruction of gastric parietal cells causes anacidity and hypergastrinemia. Use of proton pump inhibitors, which also induces gastric anacidity, is associated with increased fracture rates. Our objectives were to study possible differences in bone mineral density (BMD) and bone quality in patients with CAG compared to controls. Material and methods:We performed a cross-sectional study on 17 CAG patients aged 54 ± 13 years and 41 sex- and age-matched controls. Lumbar and femoral BMD and bone quality assessed by lumbar trabecular bone score (TBS) were measured by DXA, and bone material strength (BMS) by microindentation of the tibia. Serum bone markers (CTX, P1NP, sclerostin, osteocalcin, OPG, RANKL) were analyzed. Results:We found lower lumbar BMDZ-score (−0.324 ± 1.096 versus 0.456 ± 1.262,p = 0.030), as well as a higher frequency of osteoporosis at the lumbar spine (p = 0.046) and osteopenia at total hip (p = 0.019) in patients compared to controls. In a post hoc subgroup analysis, we observed that the differences were confined to the male patients. TBS also tended to be lower in male patients (p = 0.059), while BMS did not differ between the groups. Osteocalcin, sclerostin, OPG, and OPG/RANKL ratio were lower in patients compared to controls, while CTX and P1NP did not differ between the groups. Conclusions:We observed lower lumbar BMD, increased frequency of osteopenia and osteoporosis in male, but not female patients with CAG. Bone markers suggest a decrease in bone formation and increased bone resorption in CAG patients compared to controls. [ABSTRACT FROM PUBLISHER]

Objective: Evaluate the impact of reduced gastric acid secretion after administration of two acid-reducing agents on the physicochemical characteristics of contents of upper gastrointestinal lumen of fasted adults. Materials and Methods: Eight healthy male adults, fasted from food for 12 h, participated in a three-phase crossover study. Phase 1: No drug treatment prior to aspirations. Phase 2: Oral administration of 40 mg pantoprazole at ~9 am the last 3 days prior to aspirations and at ~7 am on aspiration day. Phase 3: Oral administration of 20 mg famotidine at ~7 pm prior to aspirations and at ~7 am on aspiration day. Samples from the contents of upper gastrointestinal lumen were aspirated for 50 min, after administration of 240 ml table water at ~9 am. Results: Reduction of gastric acid secretion was accompanied by reduced buffer capacity, chloride ion concentration, osmolality and surface tension in stomach and by increased pH (up to ~0.7 units) in upper small intestine during the first 50 min post-water administration. The mechanism of reduction of acid secretion seems to be important for the buffer capacity in stomach and for the surface tension in upper gastrointestinal lumen. Conclusions: Apart from gastric pH, reduced acid secretion affects physicochemical characteristics of contents of upper gastrointestinal lumen which may be important for the performance of certain drugs/products in the fasted state. [ABSTRACT FROM AUTHOR]

Background Helicobacter pylori infection has been associated with an imbalance of iron homeostasis. IL-1β has been related with iron absorption disturbances through a variety of mechanisms. The aim of this study was to evaluate the presence of polymorphic variants for IL-1β cluster and gastric IL1β mRNA expression in H. pylori-infected children and their relationship with hypochlorhydria and iron deficiency (ID). Patients and Methods Prospective study of 123 symptomatic children. At endoscopy, antral biopsies were taken for urease test, pathology and culture and blood for analysis of ferritin, transferrin, serum iron, and total iron-binding capacity. Polymorphisms in the IL-1β cluster (positions −511, −31, +3954, ILRN) were determined by PCR-RFLP. Gastric mucosal expression of IL-1β mRNA was determined by RT-PCR. Results After exclusions, of 105 patients, 33 (31.4%) were H. pylori positive. Nine (8.6%) children were classified as iron deficient (ID). Helicobacter pylori positivity was associated with ID (OR: 5.1; 95% CI: 1.2-21.9) ( p = .04). No significant differences were found in allele frequency for IL1β gene cluster polymorphisms between infected and uninfected children. Helicobacter pylori-infected children with ID had significantly increased gastric IL1β mRNA in comparison with infected children without ID. In addition, a significant positive correlation was observed between mucosal IL-1β mRNA and fasting gastric juice pH. Gastric pH values were significantly increased in H. pylori-infected patients with ID compared to uninfected children. Conclusions The established association between H. pylori infection and ID in children may be mediated by increased gastric mucosal IL-1β. [ABSTRACT FROM AUTHOR]

We present the case of a 52-year-old male patient, hospitalized on an emergency basis in the University Emergency Hospital in Bucharest, after being diagnosed with pneumoperitoneum acute abdomen, for which emergency surgery was mandatory. A 3,5-4 cm malignant gastric perforation, ascitis and peritoneal carcinomatosis were found. The histopathological exam revealed infiltrative mucinous gastric carcinoma with epiploic metastasis. Due to the lack of available gastric material, an atypical surgical solution was performed: gastric packing with epiploic material by means of transgastric traction. The solution proved to be successful for short-term recovery. The underlying condition was not focused on, the patient being directed to the Oncology Department. Acute gastric perforation is a rare complication of gastric cancer, and the association with gastric linitis is uncommon. This specific histopathological condition made the classical surgical repair techniques unsuitable for the presented case and an atypical solution had to be performed. [ABSTRACT FROM AUTHOR]

The purpose of this work is to use biorelevant media to evaluate the robustness of a poorly water soluble weakly basic drug to variations along the gastrointestinal tract (GIT) after incorporation in liquisolid compacts and to assess the success of these models in predicting thein vivoperformance. Liquisolid tablets were prepared using mosapride citrate as a model drug. A factorial design experiment was used to study the effect of three factors, namely: drug concentration at two levels (5% and 10%), carriers at three levels (avicel, mannitol and lactose) and powder excipients ratio (R) of the coating material at two levels (25 and 30). Thein vitrodissolution media utilized were 0.1 N HCl, hypoacidic stomach model and a transfer model simulating the transfer from the stomach to the intestine. All compacts released above 95% of drug after 10 min in 0.1 N HCl. In the hypoacidic model, the compacts with R 30 were superior compared to R 25, where they released >90% of drug after 10 min compared to 80% for R 25. After the transfer of the optimum compacts from Simulated gastric fluid fast (SGFfast) to fasted state simulated intestinal fluid, slight turbidity appeared after 30 min, and the amount of drug dissolved slightly decreased from 96.91% to 90.59%. However, after the transfer from SGFfast to fed state simulated intestinal fluid, no turbidity or precipitation occurred throughout time of the test (60 min).In vivopharmacokinetic study in human volunteers proved the success of thein vitromodels with enhancement of the oral bioavailability (121.20%) compared to the commercial product. [ABSTRACT FROM PUBLISHER]

Purpose: To assess gastric pH and its relationship with urease-test positivity and histological findings in children with Helicobacter pylori infection. Methods: Fasting gastric juices and endoscopic antral biopsy specimens were collected from 562 children and subjected to the urease test and histopathological examination. The subjects were divided into 3 age groups: 0-4, 5-9, and 10-15 years. The histopathological grade was assessed using the Updated Sydney System, while the gastric juice pH was determined using a pH meter. Results: The median gastric juice pH did not differ significantly among the age groups (p=0.655). The proportion of individuals with gastric pH >4.0 was 1.3% in the 0-4 years group, 6.1% in the 5-9 years group, and 8.2% in 10-15 years (p=0.101). The proportions of moderate and severe chronic gastritis, active gastritis, and H. pylori infiltration increased with age (p<0.005). Urease-test positivity was higher in children with hypochlorhydria (77.8%) than in those with normal gastric pH (31.7%) (p<0.001). Chronic and active gastritis were more severe in the former than the latter (p<0.001), but the degree of H. pylori infiltration did not differ (20.9% vs. 38.9%; p=0.186). Conclusion: Gastric pH while fasting is normal in most children regardless of age. Urease-test positivity may be related to hypochlorhydria in children, and hypochlorhydria is in turn related to H. pylori infection. [ABSTRACT FROM AUTHOR]

In COPD patients a reduced daily activity has been well documented, resulting from both respiratory and non-respiratory manifestations of the disease. An evaluation by multisensory armband has confirmed that daily physical activity is mainly associated with dynamic hyperinflation, regardless of COPD severity. This aspect is crucial, since exercise capacity is closely correlated to life expectancy. Notwithstanding the causal key role of lung impairment in the patient's symptoms, some authors have suggested that other factors, such as systemic inflammation and co-morbidities, have an important role, particularly as mortality risk factors. Many studies suggest the efficacy of bronchodilators and rehabilitation in improving exercise capacity, and, speaking in terms of daily life, in increasing the number of days in which patients are able to perform their usual activities. On this evidence, the first aim in the management of COPD should be to improve exercise capacity and daily activity since these outcomes have direct effects on patients’ quality of life, co-morbidities (heart and metabolic diseases), and prognosis. Thus, improving physical activity represents a modern approach aimed at dealing with both pulmonary and systemic manifestations of the disease. It is however worth of notice to remember that in patients affected by COPD the relationship between the improvement of “potential” exercise capacity and daily physical activity has been found to be only moderate to weak. Obtaining a significant behavior modification with regard to daily physical activity, together with the optimization of therapy thus represents currently the true challenge. [ABSTRACT FROM AUTHOR]

Background: HIV and Helicobacter pylori are common chronic infections in sub-Saharan Africa. Both conditions can predispose to gastric hypochlorhydria that may be a risk factor for enteric infections and reduced drug absorption. We have investigated to what extent HIV and H. pylori infections are associated with hypochlorhydria in a Malawian cohort of patients undergoing endoscopy. Methods: 104 sequential symptomatic adults referred for gastroscopy at Queen Elizabeth Central Hospital, Blantyre, Malawi, had blood taken for rapid HIV testing and fasting serum gastrin analysis. Gastric fluid was aspirated for pH testing, and gastric biopsies were taken. Results: After 9/104 HIV-infected patients who were already established on anti-retroviral therapy were excluded, 17/95 (25.0%) were seropositive for untreated HIV, and 68/95 (71.6%) patients were H. pylori positive by histology. Hypochlorhydria (fasting gastric pH>4.0) was present in 55.8% (53/95) of patients. H. pylori infection was significantly associated with hypochlorhydria (OR 2.91, [1.02-7.75], p=0.046). While single infection with HIV was not significantly independently associated with hypochlorhydria. H. pylori and HIV co-infection was more strongly associated with hypochlorhydria (OR 6.25, [1.33-29.43], p=0.020) than either infection alone, suggesting an additive effect of co-infection. HIV infection was associated with higher serum gastrin levels (91.3pM vs. 53.1pM, p=0.040), while H. pylori infection was not (63.1pM vs. 55.1pM, p=0.610). Irrespective of H. pylori and HIV status, most patients (>90%) exhibited pangastritis. Only three patients had histological evidence of gastric atrophy, of which only one was HIV-infected. Conclusion: H. pylori infection was associated with fasting hypochlorhydria, while HIV was not independently associated. HIV and H. pylori co-infection, however, was more strongly associated with hypochlorhydria than H. pylori infection alone. The mechanism of this apparent additive effect between HIV and H. pylori remains unclear, but appears to be related to chronic pangastritis rather than gastric atrophy, and associated with hypergastrinaemia in HIV-infected individuals. [ABSTRACT FROM AUTHOR]

We re-evaluated the old hypothesis that gastritis-induced achlorhydria is a cause of iron deficiency anemia (IDA) in humans. First, we analyzed the currently available research on the association between achlorhydria and IDA. When gastric acid secretion was measured after maximal stimulation, the frequency of achlorhydria (or severe hypo-chlorhydria) was 44% in patients with idiopathic IDA and 1.8% in healthy controls. In some patients with pernicious anemia, presumed achlorhydria preceded the development of IDA in time. However, we found no credible evidence that IDA caused gastritis or that IDA preceded the development of achlorhydria. Thus, correlational results favor achlorhydria as the causal factor in the association between achlorhydria and IDA. Second, we sought to determine whether gastritis and achlorhydria cause negative iron balance. When biosynthetic methods were used to isotopically label iron in food, achlorhydric patients were found to have severe malabsorption of nonheme iron, which persisted after the development of IDA. In 1 study, achlorhydria reduced the normal increase in heme-iron absorption from hemoglobin in response to iron deficiency. After an injection of isotopic iron into normal men, the physiologic loss of iron from the body was found to be 1 mg/d. Patients with chronic gastritis had excess fecal loss of isotopically tagged plasma iron. Calculations based on these results indicate that the absorption of iron from a typical Western diet by achlorhydric patients would be less than physiologic iron losses, creating a negative iron balance that could not be overcome by the adaptive increase in duodenal iron absorptive capacity that occurs in response to iron deficiency. The combination of results from these correlational and pathophysiologic studies supports the hypothesis that gastritis-induced achlorhydria can be an independent cause of IDA. [ABSTRACT FROM AUTHOR]

Background and study aims: We developed a novel magnetic-controlled capsule endoscopy (MCE) system for use in the human stomach. The aim of the current study was to compare the diagnostic accuracy of MCE with that of standard gastroscopy for gastric diseases. Patients and methods: A total of 68 patients were enrolled in this self-controlled trial. Patients were evaluated by both MCE and gastroscopy. Gastroscopy was performed 4-24 hours after completion of the MCE examination. Results: The positive percent agreement between MCE and gastroscopywas 96.0 %, and the negative percent agreement was 77.8 %. The overall agreement was 91.2% with a kappa value of 0.765 (P< 0.001). A total of 68 pathological findings were detected, of which 53 were identified by both methods. The MCE and standard gastroscopymissed seven and eight findings, respectively. Conclusions: MCE showed a diagnostic accuracy similar to that of standard gastroscopy. These results suggest that MCE is a promising alternative to gastroscopy for noninvasive screening of gastric diseases. [ABSTRACT FROM AUTHOR]

Vitamin B12 is a water-soluble vitamin naturally present in some foods, added to others as a dietary supplement. Vitamin B12 exists in several forms and contains mineral cobalt. Compounds with Vitamin B12 activity are collectively called cobalamins and active forms are Methylcobalamin and 5 deoxyadenosylcobalamin. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the prognostic value of lymphovascular invasion (LVI) in gastric cancer patients without lymph node metastasis. Methods: A total of 699 patients with primary tumor pT1-3/pN0-1 gastric adenocarcinoma who underwent curative resection from 2001 to 2010 were categorized into 3 groups: One-hundred and eleven patients with pN0/LVI(+), 475 with pN0/LVI(−), and 103 with pN1. Results: The tumors in patients with N0/LVI(+) had more aggressive clinicopathologic features than those in patients with N0/LVI(−). However, there was no significant difference in patient characteristics between patients with pN0/LVI(+) and those with pN1, except for histologic grade. There were no significant differences in the overall survival rate in patients with pN0/LVI(+) compared to those with pN0/LVI(−) or the pN1 stage. However, the recurrence-free survival rate of the pN0/LVI(+) group was lower than that of the pN0/LVI(−) group ( p < 0.001), while no significant difference was observed between the pN0/LVI(+) and the N1 groups ( p = 0.216). In multivariate analysis, LVI was identified as a poor prognostic factor related to recurrence-free survival in node-negative gastric cancer patients. pT3 stage and less than D2 lymphadenectomy were poor prognostic factors affecting recurrence-free survival, and less than D2 lymphadenectomy was an independent poor prognostic factor for overall survival in pN0/LVI(+) patients. Conclusions: LVI could be an indicator of biological aggressiveness and may be a reliable prognostic factor for node-negative gastric cancer. LVI should be considered in postoperative management of gastric cancer. [ABSTRACT FROM AUTHOR]

Environmental changes during seed production are important drivers of lot-to-lot variation in seed behaviour and enable wild species to time their life history with seasonal cues. Temperature during seed set is the dominant environmental signal determining the depth of primary dormancy, although the mechanisms though which temperature changes impart changes in dormancy state are still only partly understood., We used molecular, genetic and biochemical techniques to examine the mechanism through which temperature variation affects Arabidopsis thaliana seed dormancy., Here we show that, in Arabidopsis , low temperatures during seed maturation result in an increase in phenylpropanoid gene expression in seeds and that this correlates with higher concentrations of seed coat procyanidins. Lower maturation temperatures cause differences in coat permeability to tetrazolium, and mutants with increased seed coat permeability and/or low procyanidin concentrations are less able to enter strongly dormant states after exposure to low temperatures during seed maturation., Our data show that maternal temperature signalling regulates seed coat properties, and this is an important pathway through which the environmental signals control primary dormancy depth. [ABSTRACT FROM AUTHOR]

The aim of the present study was to search the effective ratio of whole plant of Fumaria vaillantii Loisel (Fumaria vaillantii L.) and fruit of Benincasa hispida Thunb. (Benincasa hispidaT.) in composite form, namely "FVBH" for the management of hypochlorhydria along with iron deficiency in male albino rats. Hypochlorhydria refers to suppression of hydrochloric acid secretion by the stomach. Hypochlorhydria was induced by ranitidine in this study. We used four composite extracts of the mentioned plant and fruit with different ratios (1:1, 1:2, 2:1, and 3:2) for searching the most effective composite extract for the correction of hypochlorhydria. Gastric acidity is an important factor for iron absorption. Thus, hypochlorhydria causes iron deficiency in rat and it was prevented significantly by the extract treatment at the ratio of 1:1 of the said plant and fruit. The correction of iron deficiency by the composite extract was compared with iron supplementation to hypochlorhydric rat. It was found that preadministration followed by coadministration of FVBH-1 (1:1) able to prevent the ranitidine-induced hypochlorhydria and iron deficiency. The composite extract, FVBH-1 (1:1) significantly (P<0.05) increased the pepsin concentration, chloride level in gastric juice, iron levels in serum and liver along with blood hemoglobin level than other ratios used here. Hence, it can be concluded that FVBH-1 (1:1) is an effective herbal formulation for the management of hypochlorhydria and related iron deficiency. [ABSTRACT FROM AUTHOR]

Ménétrier's disease (MD) is a rare type of hypertrophic gastropathy involving the body of the stomach, which is characterized by thickening of the mucous membrane in the form of giant rugal folds, hypochlorhydria and protein loss. The potential for malignant transformation of this lesion remains a controversial topic. Therefore, in the present study, a case of a 51-year-old male exhibiting MD with coexisting advanced gastric cancer is described; a review of the literature is also presented. The present case emphasized that MD requires particular attention and should be regarded as a premalignant condition due to the previously documented cases of its coexistence with gastric cancer, in addition to the lack of knowledge regarding its pathogenesis and effective therapeutic management. [ABSTRACT FROM AUTHOR]

Long-term decrease of gastric acid secretion by omeprazole leads to increase of TBA-active products level, activity of glutathione peroxidase, activity of glutathione transferase and to reduction of ?????? ???????????????? ?????????? and glutathione reductase activity in blood serum of rats. Simultaneous introduction to the rats of omeprazole and multiprobiotic "Apibact®" reduce the activity of lipide peroxidation and has a modulatory effect on functioning of glutathione dependent system of antioxidant defense in rat blood serum as compared to administration of omeprazole alone. [ABSTRACT FROM AUTHOR]

The present study aimed to correlation of nitric oxide system and cytokine levels in rat's liver cells under prolonged hypochlorhydria. Nitrite ions accumulation attached to increase nitric oxide synthase activity in the liver cells under reducing gastric acid secretion. Currently proved nitric oxide key role in the regulation of immune responses, so, prolonged hypochlorhydria accompanied by the synthesis of proinflammatory cytokines (tumor necrosis factor a, interleukin-6). [ABSTRACT FROM AUTHOR]

Background: The human stomach, when healthy, is not a suitable host for microorganisms, but in pathological conditions such as gastritis, when gastric acid secretion is impaired, microbial overgrowth can be observed. Apart from Helicobacter pylori, the composition of microbiota, resident or exogenously introduced during neutral/high pH conditions, has not been investigated thoroughly. Thus, it is possible that Bifidobacteriaceae, important autochthonous and beneficial bacteria of human gastrointestinal microbiota, could over-colonize the stomach of hypochlorhydria patients suffering from autoimmune atrophic gastritis (AAG) or omeprazoletreated (OME) gastritis. This prompted us to characterize the Bifidobacteriaceae in such patients' gastric microbiota and to study its abnormal colonization. Methods: Samples of gastric juices, and antrum and corpus mucosa from 23 hypochlorhydria patients (13 AAG and 10 OME) and from 10 control volunteers with base-line normochlorhydria, were cultivated in Brain Heart Infusion (BHI) and selective Bifidobacterium-Tryptone-Phytone-Yeast extract (Bif-TPY) media. The isolates were characterized by the fructose-6-phosphate phosphoketolase (F6PPK) test, electrophoresis of cellular proteins, the fermentation test, guanine-cytosine% DNA content, and DNA-DNA hybridization. Negative F6PPK isolates were characterized by order-specific polymerase chain reaction (PCR). Results: A total of 125 isolates, assigned to the Bifidobacteriaceae family on the basis of their morphology, were obtained from AAG and OME patients, but not from normal subjects. Of these isolates, 55 were assigned to the Bifidobacteriaceae family on the basis of their fructose-6-phosphoketolase (PPK) activity, PPK being the key taxonomic enzyme of this family. The remaining 70 isolates, which were PPK-negative, were attributed to the Actinomycetales order following specific primer PCR analysis. We observed a significantly higher abundance of Bifidobacteriaceae (Bifidobacterium dentium, Scardovia inopinata, and Parascardovia denticolens) in OME group than the AAG group. Furthermore, the Actinomycetales distribution was homogeneous for both hypochlorhydria patient groups. Conclusions: This study suggests that the Bifidobacteriaceae species, typically found in the oral cavity, readily colonizes the hypochlorhydria stomach of OME patients. The clinical relevance and the mechanism underlying this Bifidobacteriaceae presence in OME gastritis requires further functional studies. [ABSTRACT FROM AUTHOR]

Objective. We compared the characteristics of patients with Cushing's disease alone with those of patients with Cushing's disease and hyperprolactinemia. Methods. Eighty-four patients were enrolled between 2002 and 2011, in a hospital in China. Clinical, endocrinological, and histopathological data, MRI scans, and surgical outcomes were reviewed throughout the follow-up period. Results. Patients with Cushing's disease and hyperprolactinemia had a younger age at diagnosis (30.28 ± 14.23 versus 36.08 ± 10.91 years; P = 0.037) and a larger adenoma maximal diameter (2.44 ± 1.32 versus 1.44 ± 1.05 cm; P < 0.001) than patients with Cushing's disease alone. Menstrual disorders (P = 0.027) and visual field defects (P = 0.021) were more common and progressive obesity (P = 0.009) and hypertension (P < 0.001) were less common in patients with Cushing's disease and hyperprolactinemia. The rate of normalization of hormonal levels was lower (41.7% versus 91.7%; P < 0.001) and the recurrence rate was higher (36.1% versus 8.3%; P < 0.001) in patients with Cushing's disease and hyperprolactinemia. Conclusions. Careful long-term follow-up is needed of patients with Cushing's disease and hyperprolactinemia. [ABSTRACT FROM AUTHOR]

Water insoluble faintly alkaline drugs often have potential absorption problem in gastrointestinal tract in oral administration for patients with gastric anacidity. The purpose of the present study is to develop a novel method to improve the absorption of the water insoluble faintly alkaline drug in peroral administration. This method is based on ion exchange of ion-exchange fibers. Water-insoluble faintly alkaline drug ketoconazole was used as a model drug. Ketoconazole and the active groups of the ion-exchange fibers combined into ion pairs based on the acid-base reaction. This drug carrier did not release drugs in deionized water, but in water solution containing other ions it would release the drugs into the solution by ion exchange. Confirmed by the X-ray diffraction and the differential scanning calorimetry (DSC), the ketoconazole combined onto the ion-exchange fibers was in a highly molecular level dispersed state. The improved dissolution of ketoconazole ion-exchange fiber complexes is likely to originate from this ketoconazole's highly dispersed state. Furthermore, due to this ketoconazole's highly dispersed state, ketoconazole ion-exchange fiber complexes significantly decreased the individual difference of absorption in oral administration of ketoconazole caused by the fluctuation of the acid degree in the gastric fluid. [ABSTRACT FROM AUTHOR]

The increasing of Chga gene's expression in rat's duodenal villus and crypt epithelial cells upon gastric hypoacidic conditions were shown. The level of Chga mRNA was similar to the control value both in villus and crypt epitheliocytes upon treatment of hypoacidic rats with multiprobiotic Symbiter. [ABSTRACT FROM AUTHOR]

Background/Aims: H. pylori CagL amino acid polymorphisms such as Y58/E59 can increase integrin α5β1 expression and gastric cancer risk. Hypochlorhydria during chronic H. pylori infection promotes gastric carcinogenesis. The study test whether CagL-Y58/E59 isolates may regulate integrin α5β1 to translocate CagA via the type IV secretory system even under adverse pH conditions, and whether the integrin α5β1 expression primed by H. pylori is a pH-dependent process involving hypochlorhydria in a vicious cycle to promote gastric carcinogenesis. Methods: The expressions of integrin α5 and β1, CagA phosphorylation, IL-8, FAK, EGFR, and AKT activation of AGS cells exposed to CagL-Y58/E59 H. pylori, isogenic mutants, and different H. pylori CagL amino acid replacement mutants under different pH values were determined. Differences in the pepsinogen I/II ratio (indirectly indicating gastric acidity) and gastric integrin α5β1 expression were compared among the 172 H. pylori-infected patients with different cancer risks. Results: Even under adversely low pH condition, H. pylori CagL-Y58/E59 still keep active integrin β1 with stronger binding affinity, CagA translocation, IL-8, FAK, EGFR, and AKT activation than the other mutants (p<0.05). The in vitro assay revealed higher priming of integrin α5β1 by H. pylori under elevated pH as hypochlorhydria (p<0.05). In the H. pylori-infected patients, the gastric integrin α5β1 expressions were higher in those with pepsinogen I/II ratio <6 than in those without (p<0.05). Conclusions: H. pylori CagL-Y58/E59 prime higher integrin under adverse pH and may involve to enhance hypochlorhydria vicious cycle for gastric carcinogenesis, and thus require an early eradication. [ABSTRACT FROM AUTHOR]

Acute Helicobacter pylori infection produces hypochlorhydria. The decrease in acid facilitates survival of the bacterium and its colonization of the stomach. The present study was designed to identify the pathways in oxyntic mucosa by which acute H. pylori infection inhibits acid secretion. In rat fundic sheets in an Ussing chamber, perfusion of the luminal surface with H. pylori in spent broth (10³-108 cfu/ml) or spent broth alone (1:105 to 1:100 final dilution) caused a concentration-dependent increase in somatostatin (SST; maximal: 200 ± 20 and 194 ± 9% above basal; P < 0.001) and decrease in histamine secretion (maximal: 45 ± 5 and 48 ± 2% below basal; P < 0.001); the latter was abolished by SST antibody, implying that changes in histamine secretion reflected changes in SST secretion. Both responses were abolished by the axonal blocker tetrodotoxin (TTX), the sensory neurotoxin capsaicin, or the CGRP antagonist CGRP8-37, implying that the reciprocal changes in SST and histamine secretion were due to release of CGRP from sensory neurons. In isolated rabbit oxyntic glands, H. pylori inhibited basal and histaminestimulated acid secretion in a concentration-dependent manner; the responses were not affected by TTX or SST antibody, implying that H. pylori can directly inhibit parietal cell function. In conclusion, acute administration of H. pylori is capable of inhibiting acid secretion directly as well as indirectly by activating intramural CGRP sensory neurons coupled to stimulation of SST and inhibition of histamine secretion. Activation of neural pathways provides one explanation as to how initial patchy colonization of the superficial gastric mucosa by H. pylori can acutely inhibit acid secretion. [ABSTRACT FROM AUTHOR]

Patient: 52-year-old African-American male. Chief Complaint: Severe abdominal pain and difficulty eating. History of Present Illness: The patient presented to the emergency room (ER) with severe abdominal pain. Approximately 3 months prior to his visit, the patient stopped taking his metformin for diabetes and monitoring his glucose. For the next 3 months, the patient experienced rapid weight loss, a rash on the center of his tongue, genital skin sloughing, and sharp lower back pain. The patient then decided to resume his medication. Subsequently, the rash on his tongue cleared, the sloughing decreased but did not clear, and his back pain subsided. The patient began experiencing occasional pain when swallowing food, but dismissed the symptoms. On the morning prior to his ER visit, when the patient swallowed food he had mild discomfort in the upper esophagus and it felt as though food was lodged in his esophagus after the meal. Eating lunch increased the patient's discomfort to a moderate level of pain that seemed to move with the food to the lower portion of his esophagus over a 2 hour period. Finally, an afternoon snack escalated the patient's pain in the upper abdominal region to a severe level. Once again the patient described the pain as following the food as it traveled into the abdominal region. Past Medical and Surgical History: The patient had type 2 diabetes mellitus for approximately 10 years and hypercholesterolemia for at least 27 years. The patient had a hemorrhoidectomy 8 years earlier. Social History: No tobacco use, no alcohol use, and no intravenous drug abuse. Family History: The patient's mother died at age 62 from type 2 diabetes mellitus complications that included 5 years of blindness accompanied by occasional seizures. The patient is a retired civil service employee. Physical Exam and Vital Signs: Upon admission, the patient's temperature was 98.8°F; blood pressure 132/84 mmHg; respirations 18/minute; and pulse 72 beats per minute (bpm). The patient presented with severe epigastric pain with difficulty swallowing, acute localized lower abdomen pain, and a genital rash. He had no signs of blurred vision, sloughing of skin elsewhere on the body, chest pain, coughing, shortness of breath, or abdominal distention. He had no nausea, vomiting, hematemesis, melena, or hematochezia. He had no dysuria or pyuria. He did not have any swelling, ulcers, or numbness in his feet or legs.MD. [ABSTRACT FROM AUTHOR]

Background: Achlorhydria caused by e.g. atrophic gastritis allows for bacterial overgrowth, which induces chronic inflammation and damage to the mucosal cells of infected individuals driving gastric malignancies and cancer. Enterococcus faecalis (E. faecalis) can colonize achlohydric stomachs and we therefore wanted to study the impact of E. faecalis infection on inflammatory response, reactive oxygen species (ROS) formation, mitochondrial respiration, and mitochondrial genetic stability in gastric mucosal cells. Methods: To separate the changes induced by bacteria from those of the inflammatory cells we established an in vitro E. faecalis infection model system using the gastric carcinoma cell line MKN74. Total ROS and superoxide was measured by fluorescence microscopy. Cellular oxygen consumption was characterized non-invasively using XF24 microplate based respirometry. Gene expression was examined by microarray, and response pathways were identified by Gene Set Analysis (GSA). Selected gene transcripts were verified by quantitative real-time polymerase chain reaction (qRT-PCR). Mitochondrial mutations were determined by sequencing. Results: Infection of MKN74 cells with E. faecalis induced intracellular ROS production through a pathway independent of oxidative phosphorylation (oxphos). Furthermore, E. faecalis infection induced mitochondrial DNA instability. Following infection, genes coding for inflammatory response proteins were transcriptionally up-regulated while DNA damage repair and cell cycle control genes were down-regulated. Cell growth slowed down when infected with viable E. faecalis and responded in a dose dependent manner to E. faecalis lysate. Conclusions: Infection by E. faecalis induced an oxphos-independent intracellular ROS response and damaged the mitochondrial genome in gastric cell culture. Finally the bacteria induced an NF-κB inflammatory response as well as impaired DNA damage response and cell cycle control gene expression. Transcript profiling: Array Express accession number E-MEXP-3496. [ABSTRACT FROM AUTHOR]

Aims Acute Helicobacter pylori infection is associated with transient hypochlorhydria. In H pylori-associated atrophy, hypochlorhydria has a role in iron deficiency (ID) through changes in the physiology of iron-complex absorption. The aims were to evaluate the association between H pylori-associated hypochlorhydria and ID in children. Methods Symptomatic children (n=123) were prospectively enrolled. Blood, gastric juice and gastric biopsies were taken, respectively, for haematological analyses, pH assessment and H pylori determination, and duodenal biopsies for exclusion of coeliac disease. Stool samples were collected for parasitology/microbiology. Thirteen children were excluded following parasitology and duodenal histopathology, and five due to impaired blood analysis. Results Ten children were hypochlorhydric (pH>4) and 33 were H pylori positive. In H pylori-positive children with pH>4 (n=6) serum iron and transferrin saturation levels % were significantly lower ( p<0.01) than H pylori-positive children with pH≤4. No differences in ferritin, or total iron binding capacity, were observed. In H pylori-negative children with pH>4, iron and transferrin saturation were not significantly different from children with pH≤4. Conclusions Low serum iron and transferrin in childhood H pylori infection is associated with hypochlorhydria. In uninfected children, hypochlorhydria was not associated with altered serum iron parameters, indicating a combination of H pylori infection and/or inflammation, and hypochlorhydria has a role in the aetiology of ID. Although H pylori-associated hypochlorhydria is transient during acute gastritis, this alters iron homeostasis with clinical impact in developing countries with a high H pylori prevalence. [ABSTRACT FROM AUTHOR]

Introduction: Zollinger-Ellison syndrome is characterized by recurrent peptic ulcers and diarrhea that result from gastrin-secreting neuroendocrine tumors of the gastrointestinal tract; nevertheless, severe hypergastrinemia may also have alternative pathogenetic explanations.Case Presentation: A 61-year-old woman of Caucasian origin presented with a history of epigastric pain and early satiety, severe hypergastrinemia (approximately 2000 pg/mL) and a neuroendocrine polyp in the corpus of her stomach. Chronic atrophic gastritis and intestinal metaplasia was present, but she denied use of acid suppressant drugs and the results of tests for Helicobacter pylori as well as gastric parietal cell and intrinsic factor antibodies were negative. She underwent a radical gastric tangential resection. Six months later, serum gastrin was still elevated despite lack of recurrence of tumor.Conclusion: The clinical picture was suggestive for a hypochlorhydria-related hypergastrinemia with subsequent development of a non-secreting carcinoid. We suggest a periodic endoscopic follow-up in patients with severe hypochlorhydria-related hypergastrinemia in order to earlier detect neuroendocrine polyps. [ABSTRACT FROM AUTHOR]

Background: Gender and gastric acid have been suggested to be independently involved in the pathophysiology of functional dyspepsia, but the interrelationship among gender, dyspeptic symptoms, and gastric acid secretion remains to be evaluated. We sought to explore this issue in dyspeptic patients. Methods: A total of 89 outpatients (male, 36; mean age, 55.6 years) with dyspeptic symptoms were analyzed. The degree of dyspeptic symptoms was evaluated and scored using a symptom questionnaire consisting of 3 subcategories: dysmotility-related symptoms, reflux-related symptoms, and epigastric pain-related symptoms. Stimulated gastric acid secretion was directly measured using an endoscopic gastrin test. Results: The total symptom scores and the epigastric pain-related symptom scores were significantly higher in female patients than in male patients. The dysmotility-related and reflux-related symptom scores were also higher, but not significantly, in the female patients. Multiple regression analysis of age, gender, habitual drinking, smoking, Helicobacter pylori infection, and gastric acid secretion revealed that gender and gastric hypochlorhydria, defined as less than 2.1 mEq/10 min in the endoscopic gastrin test, were significantly associated with higher dyspeptic symptom scores. The total scores and the dysmotility-related scores were significantly higher in the patients with gastric hypochlorhydria than in those with gastric non-hypochlorhydria, and this difference was found to be present only in females. Conclusions: Gastric hypochlorhydria in female dyspeptic patients may be involved in the exacerbation of dyspeptic symptoms. Differences in the responsiveness to gastric hypochlorhydria between males and females may be partly responsible for the gender differences in the prevalence and severity of dyspeptic symptoms. [ABSTRACT FROM AUTHOR]

Background Patients with chronic atrophic gastritis have long-term gastric hypoacidity, and secondary hypergastrinaemia. Some also develop gastric ECL cells carcinoids (type 1 GC). Most type 1 GC remain indolent, but some metastasise. Patients undergo surveillance, and some are treated with somatostatin analogues, endoscopic resection or surgery. Netazepide ( YF476) is a highly selective, potent and orally active gastrin receptor antagonist, which has anti-tumour activity in various rodent models of gastric neoplasia driven by hypergastrinaemia. Netazepide has been studied in healthy volunteers. Aim To assess the effect of netazepide on type 1 GC. Methods Eight patients with multiple type 1 GC received oral netazepide once daily for 12 weeks, with follow-up at 12 weeks in an open-label, pilot trial. Upper endoscopy was performed at 0, 6, 12 and 24 weeks, and carcinoids were counted and measured. Fasting serum gastrin and chromogranin A (CgA) and safety and tolerability were assessed at 0, 3, 6, 9, 12 and 24 weeks. Results Netazepide was well tolerated. All patients had a reduction in the number and size of their largest carcinoid. CgA was reduced to normal levels at 3 weeks and remained so until 12 weeks, but had returned to pre-treatment levels at 24 weeks. Gastrin remained unchanged throughout treatment. Conclusions The gastrin receptor antagonist netazepide is a promising new medical treatment for type 1 gastric carcinoids, which appear to be gastrin-dependent. Controlled studies and long-term treatment are justified to find out whether netazepide treatment can eradicate type 1 gastric carcinoids. [ABSTRACT FROM AUTHOR]

In a mouse model for juvenile obesity, we investigated how the age of onset of voluntary exercise affects factors of the metabolic syndrome. One exercise group had access to running wheels from 3 weeks (representing childhood) and another one from 9 weeks on (early adulthood). Both groups were compared to mice without exercise. The investigations were performed under 2 diets (standard maintenance and highfat diet). Average daily running activity was independent of diet and exercise. On both diets, mice with exercise from 3 weeks on gained 10 g body weight and 5 g fat mass less than mice without exercise. The highest body weight difference between mice on HFD without exercise and mice on standard maintenance diet with exercise was 24 g. Despite the higher energy expenditure during exercise, young mice did not increase their energy intake adjusted for lean mass, while mice with exercise from 9 weeks had an increased energy intake of 6 kJ per day and therefore could not reduce fat mass on both diets. However, mice with exercise from 9 weeks had better glucose tolerance at 20 weeks than mice with exercise from childhood on. Independently of the age of exercise onset, triglycerides were reduced from 2.4 to 1.7 mmol/l on both diets and insulin levels from 1.5 to 0.3 and 4.5 to 1.8 μg/ml on standard maintenance and high-fat diet, respectively, which represents a considerable improvement. Physical activity seems to have long-lasting effects on body composition and health, but they are different depending on when exercise has begun. [ABSTRACT FROM AUTHOR]

Background Proton pump inhibitors ( PPIs) are potent inhibitors of gastric acid secretion and give hypergastrinemia secondary to gastric hypoacidity. PPI treatment therefore induces enterochromaffin-like ( ECL) cell hyperplasia. Long-term hypergastrinemia in rodents and man also leads to ECL cell neoplasia. Whether long-term PPI treatment will induce ECL cell neoplasia in man has been disputed. Aim To describe gastric carcinoids in two patients with a history of long-term PPI use. Results Two patients had been taking PPI for 12-13 years due to gastro-oesophageal reflux disease. At routine upper gastrointestinal endoscopy a solitary tumour was found in the oxyntic mucosa of both patients. Histology from the tumours showed in both cases a well-differentiated neuroendocrine tumour. Biopsies from flat oxyntic mucosa showed no signs of atrophic gastritis and a normal presence of parietal cells in both cases, but hyperplasia of ECL cells. The tumour in patient 1 was resected endoscopically. After cessation of PPI treatment the tumour regressed in patient 2 and the ECL cell hyperplasia regressed in both patients. In patient 2 serum gastrin and chromogranin A were elevated during PPI treatment, and normalised after cessation of treatment. In patient 1, unfortunately, we had serum only after treatment, and at that time both parameters were normal. Conclusion These cases show that hypergastrinemia secondary to proton pump inhibitors treatment, like other causes of hypergastrinemia, may induce enterochromaffin-like cell carcinoids in man. [ABSTRACT FROM AUTHOR]

Ménétrier's disease (MD) is a rare, acquired, premalignant disorder of the stomach characterized by enlarged gastric folds with foveolar hyperplasia, the phenotype of antralization of gastric glands, hypochlorhydria and hypoproteinemia. The etiology of MD is unknown, but both increased signaling by transforming growth factor-α and infection with Helicobacter pylori ( H. pylori) have been implicated. Here, a case involving 70-year-old man who lost weight after developing anorexia and diarrhea is reported. He was diagnosed as MD without H. pylori infection, and in spite of intensive care, he died 40 days after admission. An autopsy confirmed MD. Immunohistochemistry revealed overexpression of transforming growth factor-α in the foveolar region of the gastric mucosa. The autopsy also distinguished this H. pylori-negative MD from hyperplastic polyp of the stomach, which is important in clarifying the entity of H. pylori-negative MD. [ABSTRACT FROM AUTHOR]

Infection of the human stomach mucosa by Helicobacter pylori induces strong inflammatory responses and a transitory hypochlorhydria which can progress in ~2 % of patients to atrophic gastritis, dysplasia, or gastric adenocarcinoma. H. pylori infection of gastric biopsies or cultured gastric epithelial cells in vitro represses the activity of endogenous or transfected promoter of the alpha-subunit (HKα) of gastric H,K-adenosine triphosphatase (H,K-ATPase), the parietal cell enzyme mediating acid secretion. Some mechanistic details of H. pylori-mediated repression of HKα and ensuing hypochlorhydria have been recently elucidated. H. pylori strains expressing a type IV secretion system (T4SS) encoded by the cag pathogenicity island are known to upregulate the transcription factor nuclear factor (NF)-κB. The NF-κB-binding regions in the HKα promoter were identified and shown to repress its transcriptional activity. Interaction studies have indicated that although active phosphorylated NF-κB p65 is present in infected cells, an NF-κB p50/p65 heterodimeric complex fails to bind to the HKα promoter. Point mutations at −159 and −161 bp in the HKα promoter NF-κB binding sequence prevent the binding of NF-κB p50 and prevent H. pylori repression of point-mutated HKα promoter activity. The T4SS factors CagL, CagE, CagM, and possibly CagA and the lytic transglycosylase Slt, are mechanistically involved in NF-κB activation and repression of HKα transcription. CagL, a T4SS pilus component, binds to the integrin αβ to mediate translocation of virulence factors into the host cell and initiate signaling. During acute H. pylori infection, CagL dissociates ADAM 17 (a disintegrin and a metalloprotease 17) from the integrin αβ complex and stimulates ADAM17-dependent release of heparin-binding epidermal growth factor (HB-EGF), EGF receptor (EGFR) stimulation, ERK1/2 kinase activation, and NF-κB-mediated repression of HKα. These studies suggest that H. pylori inhibits HKα gene expression by an integrin αβ → ADAM17 → HB-EGF → EGFR → ERK1/2 → NF-κB pathway mediating NF-κB p50 homodimer binding to the HKα promoter. Here we review the molecular basis and recent progress of this novel pathogen-dependent mechanism of H,K-ATPase inhibition, which contributes significantly to our current understanding of H. pylori pathophysiology. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 49-year-old man with high levels of thyroid-stimulating hormone (TSH) despite increased doses of levothyroxine. It states that the patient's treatment-refractory hypothyroidism was not connected to gastric hypochlorhydria-related levothyroxine maldigestion. It adds that a bowel endoscopic biopsy shown celiac disease and low-gluten diet was advised resulting to normal levels of TSH. Discussion on serum TSH as bases for thyroxine dosage is also presented.

Background and aims. Atrophic gastritis (AG) results most often from Helicobacter pylori (H. pylori) infection. AG is the most important single risk condition for gastric cancer that often leads to an acid-free or hypochlorhydric stomach. In the present paper, we suggest a rationale for noninvasive screening of AG with stomach-specific biomarkers. Methods. The paper summarizes a set of data on application of the biomarkers and describes how the test results could be interpreted in practice. Results. In AG of the gastric corpus and fundus, the plasma levels of pepsinogen I and/or the pepsinogen I/pepsinogen II ratio are always low. The fasting level of gastrin-17 is high in AG limited to the corpus and fundus, but low or non-elevated if the AG occurs in both antrum and corpus. A low fasting level of G-17 is a sign of antral AG or indicates high intragastric acidity. Differentiation between antral AG and high intragastric acidity can be done by assaying the plasma G-17 before and after protein stimulation, or before and after administration of the proton pump inhibitors (PPI). Amidated G-17 will rise if the antral mucosa is normal in structure. H. pylori antibodies are a reliable indicator of helicobacter infection, even in patients with AG and hypochlorhydria. Conclusions. Stomach-specific biomarkers provide information about the stomach health and about the function of stomach mucosa and are a noninvasive tool for diagnosis and screening of AG and acid-free stomach. [ABSTRACT FROM AUTHOR]

Hypochlorhydria is a common problem in any age of people like other gastric disorders. It has so many etiologies such as sympathetic dominance, antiseretory drug use, excess sugar and refined foods, etc. In the present study, our objective was to search out the effective solvent extract of fruit of Benincasa hispida T. for the management of hypochlorhydria in model male albino rats. Hypochlorhydria was induced in rat as per standard method by oral administration of ranitidine. Different solvent extracts (Hydromethanol, ethyl acetate, and aqueous) of ripe fruit of B. hispida were prepared following the standard protocol. Various parameters in this concern like free acidity, total acidity, pH, pepsin concentration, chloride and vitamin C levels in gastric juice were measured by standard biochemical and titrimetric methods. It was found that pre-administration followed by co-administration of aqueous extract of B. hispida (ABH) resulted significant correction of ranitidine-induced hypochlorhydria in rat. This aqueous extract-treated group showed increased levels of vitamin C, pepsin, and chloride concentration in gastric juice as well as the antioxidant status significantly (P<0.05) in respect to other extract-treated groups. From the results, it can be concluded that the ABH has most effective anti-hypochlorhydric and antioxidative efficacy than other solvent extracts of said plant fruit. [ABSTRACT FROM AUTHOR]