How Helicobacter pylori urease may affect external pH and influence growth and motility in the mucus environment: evidence from in-vitro studies

BACKGROUND: Survival of Helicobacter pylori is dependent upon urease in the cytoplasm and at the bacterial surface. We have sought to clarify how alkaline ammonium salts, released from urea by this enzyme, might alter mucus pH and so affect growth and motility of the bacterium in the gastric mucus environment. METHODS: Experiments were conducted in vitro to determine how the growth and motility of H. pylori are affected by changes in external pH, and how the bacterium, by hydrolysing urea, alters the pH of the bicarbonate buffer that occurs at the gastric mucosal surface. These data were fitted into experimental models that describe how pH varies within the mucus layer in the acid-secreting stomach. RESULTS: H. pylori was motile between pH 5 and 8, with optimal motility at pH 5. It grew between pH 6 and 8, with optimal growth at pH 6. The bacterium had urease activity between pH 2.7 and 7.4, as evidenced by pH rises in bicarbonate-buffered solutions of urea. Changes in buffer pH were dependent upon initial pH and urea concentration, with the greatest rate of pH change occurring at pH 3. Modelling experiments utilizing these data indicated that (1) in the absence of urease, H. pylori growth and motility in the mucus layer would be restricted severely by low mucus pH in the acid-secreting stomach, and (2) urease will sometimes inhibit H. pylori growth and motility in the mucus layer by elevating the pH of the mucus environment above pH 8. CONCLUSIONS: Urease is essential to the growth and motility of H. pylori in the mucus layer in the acid-secreting stomach, but, paradoxically, sometimes it might suppress colonization by raising the mucus pH above 8. This latter effect may protect the bacteria from the adverse consequences of overpopulation.     

Management of nasal injuries: a postal questionnaire survey of UK ENT consultants

Nasal injuries are one of the commonest conditions seen in ENT out-patients. There is no uniform policy or protocol for the management of this condition. A postal questionnaire was sent to all UK-based ENT consultants. The aim of this study was to ascertain current practice in the management of this common problem. We were also interested to know if consultants believed that the septum should be addressed and dealt with at the same time as manipulation to improve cosmetic and functional results. Manipulation of nasal bones without anaesthesia, under local anaesthesia, and general anaesthesia with digital pressure or using instruments are all practised. The digital pressure under general anaesthesia with use of septal and nasal forceps, if needed, is practised by the majority of consultants (55.8 per cent). Only a minority considered the role of the septum to be important in the initial management of the patient.     

Human autologous dendritic cell-glioma fusions: feasibility and capacity to stimulate T cells with proliferative and cytolytic activity

Summary Gliomas are the most common primary neoplasm of the central nervous system. The failure of conventional treatment modalities to improve outcome over the last two decades has led to interest in alternative treatment modalities. Dendritic cell (DC)-based immunotherapy has utilized DC pulsed with tumor lysate or peptide to induce an antitumor immune response mediated largely by CD8 T cells. While this has been effective in preclinical studies, clinical efficacy remains unproven. Recently, hybrid cells produced by fusions of tumor and autologous DC have demonstrated remarkable efficacy for stimulating an anti-tumor immune response in both preclinical and clinical studies of extra-cranial neoplasms. The advantage of generating such hybrid cells is that the entire cellular material of the tumor is processed and presented in both endogenous and exogenous pathways. This leads to activation of both MHC class I restricted CD8 cells as well as MHC class II restricted CD4 T cells. Here, we examinedin vitro T cell stimulatory capacity of autologous human DC-glioma fusion in comparison to DC loaded with apoptotic glioma. DC fused with autologous tumor or loaded with apoptotic tumor cells (DC/apo) were first used to stimulate autologous non-adherent peripheral blood mononuclear cells (PBMC),in vitro. The PBMC were then examined for phenotype (CD3, CD4, CD8) and intracellular IFN-γ using flow cytometry. Lymphocyte proliferation and cytolytic responses were also assessed. Lymphocytes stimulatedin vitro with fusion or DC/apo cells showed significantly enhanced cytotoxicity and proliferation against autologous tumor cells compared with PBMC stimulated with tumor cells or DC alone. Both strategies had similar efficacy. Tumor-cytolytic responses were enhanced by the addition of CD40 ligand (CD40L), and partially blocked by anti-MHC class I antibody. Flow cytometric analysis detected CD3⁺CD8⁺ T cells, which also stained positive for intracellular IFN-γ. The study suggests that DC/glioma fusion and DC/apo have comparable efficacy for stimulation of CTL with cytolytic and proliferative activity against human malignant gliomas. These findings may have implications for future studies of DC-based immunotherapy in malignant gliomas.     

A novel data calibration scheme for electrical impedance tomography

In electrical impedance tomography surface measurements of voltages and currents are recorded and the image reconstruction algorithm uses this set of boundary data to estimate internal electrical properties of the region under investigation. Therefore correct and accurate modelling of the current and voltage distributions (forward model) is an essential part of any reconstruction method. In this paper, we explored the root cause of a boundary layer effect in the reconstructed conductivity map and found it to be an artefact arising from 2D to 3D data-model mismatch within the imaging algorithm. We propose a data calibration scheme that improves the reconstruction results by removing these boundary or edge effects. We present both two-dimensional and three-dimensional images for agar phantoms using this data calibration scheme which are markedly better than their counterparts recovered when the measurement data are not calibrated with the procedure outlined herein.     

Long-term trend toward earlier breeding in an American bird: A response to global warming?

In regions with severe winters, global warming may be expected to cause earlier onset of breeding in most animals, yet no documentation of such a trend exists in North America. In a study of marked individuals of the Mexican jay (Aphelocoma ultramarina) in southeastern Arizona, from 1971 to 1998, the mean Julian date of first clutch in the population declined significantly by 10.1 days. The date of the first nest in the population also became earlier, by 10.8 days. These changes were associated with significant trends toward increased monthly minimum temperatures on the study area, traits that are associated with the onset of breeding in this population. Significant trends from 1971 to 1997 toward warmer minimum temperatures in the months before and during the initiation of breeding were observed. These trends parallel changes in minimum temperatures and community composition in a recent study of grassland ecology in the western United States. Together, they suggest that more attention should be given to the possible ecological importance of global change in minimum temperatures.     

(-)-Epigallocatechin Gallate Inhibits the Pacemaker Activity of Interstitial Cells of Cajal of Mouse Small Intestine

The effects of (-)-epigallocatechin gallate (EGCG) on pacemaker activities of cultured interstitial cells of Cajal (ICC) from murine small intestine were investigated using whole-cell patch-clamp technique at 30℃ and Ca²⁺ image analysis. ICC generated spontaneous pacemaker currents at a holding potential of -70 mV. The treatment of ICC with EGCG resulted in a dose-dependent decrease in the frequency and amplitude of pacemaker currents. SQ-22536, an adenylate cyclase inhibitor, and ODQ, a guanylate cyclase inhibitor, did not inhibit the effects of EGCG. EGCG-induced effects on pacemaker currents were not inhibited by glibenclamide, an ATP-sensitive K⁺ channel blocker and TEA, a Ca²⁺-activated K⁺ channel blocker. Also, we found that EGCG inhibited the spontaneous [Ca²⁺]_i oscillations in cultured ICC. In conclusion, EGCG inhibited the pacemaker activity of ICC and reduced [Ca²⁺]_i oscillations by cAMP-, cGMP-, ATP-sensitive K+ channel-independent manner.     

Evaluation of behavioural and antioxidant activity of <Emphasis Type="Italic">Cytisus scoparius</Emphasis> Link in rats exposed to chronic unpredictable mild stress

Background  

Various human diseases have oxidative stress as one of their component. Many herbs have been reported to exhibit properties that combat oxidative stress through their active constituents such as flavonoids, tannins, phenolic compounds etc. Cytisus scoparius (CS) Link, (Family: Leguminosae), also called Sarothamnus scoparius, has been shown in invitro experiments to be endowed with anti-diabetic, hypnotic and sedative and antioxidant activity. Therefore this study was carried out to evaluate CS for its anxiolytic, antidepressant and anti-oxidant activity in stressed rats.