The H+/K+-ATPase of gastric parietal cell exchanges luminal K+ for cytoplasmic H+, of which outcome is gastric acidification with outflux of hydronium ion (H3O+). Secretion of gastric acid from the H+/K+-ATPase is stimulated by neuronal sensing and elaborately regulated various neuronal transmitters and hormones, consequently resulting in anchoring of the H+/K+-ATPase in canaliculi membrane of gastric parietal cell. Since hypersecretion of gastric acid or a defect of its barrier function is considered as a principal casual factor in the acid-related diseases such as duodenal and gastric ulcer, reflux esophagitis, and some types of gastritis, the development of anti-secretory agents including PPIs (proton pump inhibitors) and H2-RAs (histamine type 2 receptor antagonists) has revolutionized during the second millennium. Similar considerations applying to design of compounds substituting K+ led to the development of acid pump antagonists (APAs), of which advantages are independent of secretory status, no lag time required, reversible in actions allowing “on-demand dosage”. Our recent studies revealed that these inhibitors of H+/K+-ATPase could be extensively applied for the selective induction of cancer cell apoptosis, a significant anti-inflammatory and gastroprotective action far beyond acid suppression. In the current review, we described the mechanistic regulation of gastric acid secretion with pump inhibitor, the difference and characteristics between PPI and APA based on the molecular mechanism, and their new applications beyond acid suppression.
The distinguishing feature of the traditional Indian medicinal system, Ayurveda, is its emphasis on the maintenance of positive health. As per Ayurveda, Indian medicinal plants are rich sources of substances that have several therapeutic properties including cardioprotection. Globally, cardiovascular diseases are a leading cause of mortality. Several epidemiological studies suggest a correlation between antioxidant intake and occurrence of various cardiovascular diseases. This review deals with medicinal plants which possess cardiotonic, cardioprotective and antioxidant effects. It also includes our studies on the antioxidant properties of some of these plants such as Terminalia arjuna (arjun), Trigonella foenum-graecum (fenugreek), Curcuma longa (turmeric), Garcinia indica (kokum) and Vitis vinifera (grapes). Among these, Terminalia arjuna possesses the highest antioxidant potential and inhibit whole plasma oxidation in rats besides showing significant intestinal absorption. Other plants studied also exhibit radical scavenging effects as studied using various biochemical assays. These antioxidant effects may possibly be responsible for their known beneficial therapeutic effects including their use in cardioprotection.
Impaired cognitive function in the elderly with diabetes mellitus has been reported, and many, but not all, studies showed that diabetes mellitus is a risk factor for dementia. Although the mechanism of cognitive dysfunction in elderly diabetes mellitus subjects remains to be elucidated, several lines of evidence indicate that insulin and/or inflammation may be involved.
Objective: To investigate the difference in superoxide production from circulating neutrophils and Kupffer cells between in the mice after burn injury and mice suffering from bacterial septicemia. Background: Both severe burn injury and septicemia can result in a critical/fatal outcome for the patients even after initial resuscitation. Analyses of defense mechanisms in the host who survive after severe stress are thereby very important for improvement of intensive care. Method: Either burn injury or inoculations with Peudomonas aeruginosa were subjected to C57BL/6 mice. After 7 days, circulating neutrophils and Kupffer cells were obtained from the mice to examine superoxide or cytokine production. Results: Neither of the mouse groups showed any pathological changes in major organs or any elevations in the serum transaminase or TNF levels at 7 days after burn injury or bacterial inoculation. The burn injured mice showed significantly higher superoxide production from neutrophils by stimulation with phorbor myristate acetate (PMA) or opsonized zymosan (OZ) than that from Kupffer cells. In contrast, the bacterial challenged mice showed a significantly higher superoxide production from Kupffer cells than that from neutrophils. In addition, the burn injured mice showed a significantly higher production of IL-10, namely anti-inflammatory cytokine, from the Kupffer cells by LPS stimulation than the bacterial challenged mice while the bacterial challenged mice showed a significantly higher production of IL-12, namely proinflammatory cytokine, from Kupffer cells by LPS stimulation than the burn injured mice. Conclusions: Neutrophils might thus be activated to a greater degree than Kupffer cells in mice after burn injury, while Kupffer cells might be activated more than neutrophils after bacterial septicemia.
Ghrelin, a novel growth hormone releasing peptide, has been reported to accelerate food intake and gastrointestinal motility. The relationship between ghrelin secretion and emotional stress remains unknown. The present study was designed to investigate ghrelin dynamics in mice after the application of the emotional stress. To apply emotional stress in the mouse model, the communication box paradigm was used. Just after the communication box protocol, the mice were examined. The plasma and gastric ghrelin levels were measured by enzyme immunoassay and radioimmunoassay. Ghrelin immunohistochemistry and quantitative RT-PCR of preproghrelin mRNA in the stomach were performed. The plasma ghrelin levels were significantly increased in the stress-applied mice. Gastric ghrelin levels and the density of ghrelin-immunoreactive cells in the stress-applied mice tended to be decreased as compared with that in the control mice, but the difference was not statistically significant. There was no significant difference in the preproghrelin mRNA expression levels between the stress-applied mice and the control mice. The present study demonstrated for the first time that the plasma level of ghrelin increased in the association emotional stress.
Helicobacter pylori (H. pylori) is known to be associated with peptic ulcer, chronic gastritis, MALT lymphoma, and gastric cancer. In this study, we investigated the usefulness of a new E-plate serum antibody kit, developed in Japan using H. pylori strains isolated from Japanese patients, in the assessment of eradication, with an HM-CAP kit for comparison. The subjects were 100 H. pylori positive patients who underwent upper gastrointestinal endoscopy between October 1999 and June 2000. Eradication assessment performed using E-plate kit with the cut-off values for the delta value of the antibody titre set at −20%, −30%, and −40%, yielded sensitivity/specificity of 93.9%/85.7%, 92.4%/85.7%, and 72.7%/92.9%, respectively, for agreement rates with eradication assessments using endoscopic biopsy specimens at 2 months post-eradication therapy. Use of the HM-CAP kit with cut-off values of −5%, −10%, and −15% yielded sensitivity/specificity of 97.0%/28.6%, 83.3%/85.7%, and 53.0%/100%, respectively. These results indicated that the E-plate kit is more useful for eradication assessment in Japan.
We studied the salt taste change during pregnancy and investigated its meaning in normal pregnancy and preeclampsia female in salt restriction. 40 normal pregnant female, 35 pregnant female with preeclampsia and 64 healthy non-pregnant female were recruited to this study. Gustatory test was performed with the filter-paper disk method. Salt solutions, 0.1, 0.2, 0.4, 0.6, 0.8 and 1.0 weight % were made from reagent grade sodium chloride and distilled water. The threshold of salt taste in pregnant female was higher than that of non-pregnant female. The threshold of salt taste in preeclampsia female was higher than that of pregnant female. The threshold of salt taste in normal pregnant female was correlated with their weight gain during pregnancy however that in preeclampsia female was not correlated. The threshold of salt taste was decreased and the symptom of preeclampsia was improved when preeclampsia female took the salt restriction diet therapy. It is suggested that the change of salt taste was related to the increased need of sodium according to progress of normal pregnancy, and was also related to the improvement of the symptoms of preeclampsia in salt restriction. The salt taste may be an objective indicator of salt intake for preeclampsia.