Divalent cations regulate acidity within the lumen and tubulovesicle compartment of gastric parietal cells. Childhood Helicobacter pylori infection, clinical presentations, endoscopic, histologic features and results of treatment. Notch activity acts as a sensor for extracellular calcium during vertebrate left-right determination. Rx drugs

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Gastroenterology. 2004 Jan;126(1):182-95.
Divalent cations regulate acidity within the lumen and tubulovesicle compartment of gastric parietal cells.

Gerbino A, Hofer AM, McKay B, Lau BW, Soybel DI.

Department of Surgery, Brigham and Women's Hospital, VA Boston Health Care System, Boston, MA 02115, USA.

Background & Aims: Until recently, it has not been possible to evaluate factors that regulate the acidity of the microenvironment within the tubulovesicles and luminal (TV/L) spaces of the gastric gland. The goal of this study was to develop a method for monitoring the mechanisms that regulate acidity in the TV/L compartment. Methods: Isolated rabbit gastric glands (intact or permeabilized with S. aureus alpha-toxin) were loaded with a recently characterized fluorescent dye, LysoSensor Yellow-Blue DND 160 (Molecular Probes, Eugene, OR), which localizes to highly acidic compartments and can be used to monitor acidity ratiometrically. Results: In resting glands, the pH of the TV/L compartment was approximately 3.4. Moderate alkalizations ( approximately 0.5 to 1.0 pH unit alkalization) were observed during exposure to inhibitors of the apical H(+)/K(+) ATPase (omeprazole and SCH28080), thereby unmasking a stable, low-level leak of H(+) ions from the TV/L compartment. Similar changes were observed in alpha-toxin permeabilized glands following depletion of ATP in the cytoplasm. In intact and permeabilized glands, we used the cell-permeant, divalent cation chelator, tetrakis-(2-pyridylmethyl)ethylenediamine (TPEN) to probe the effects of lowering divalent cation content of the TV/L compartment. Exposure to relatively low concentrations (20 micromol/L, 50 micromol/L) of TPEN reversibly promoted H(+) leakage. At these concentrations, simultaneous inhibition using SCH28080 led to marked enhancement of the rate of alkalization. Conclusions: The effects of low-dose TPEN suggests that acidity within the TV/L compartment of the gastric gland may be regulated, at least in part, by its content of divalent cations such as Zn(2+), for which TPEN has high affinity.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14699499&dopt=Abstract

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J Med Assoc Thai. 2003 Aug;86 Suppl 3:S600-4.
Childhood Helicobacter pylori infection, clinical presentations, endoscopic, histologic features and results of treatment.

Vithayasai N.

Gastroenterology and Nutrition Unit, Queen Sirikit National Institute of Child Health, Bangkok 10400, Thailand.

OBJECTIVE: To study childhood Helicobacter pylori infection concerning the clinical presentations, endoscopic, histologic features and results of treatment. MATERIAL AND METHOD: A retrospective study conducted at the Gastroenterology and Nutrition Unit, Queen Sirikit National Institute of Child Health (QSNICH) was done from January 1993 to December 2002. All patients presented with recurrent abdominal pain, upper GI bleeding (non-variceal bleeding) chronic vomiting and dyspeptic symptoms who underwent upper GI endoscopy were included in this study. Positive urease test verified by biopsied specimens from the gastric antrum and body and/or finding the organisms from the specimens were the criteria for diagnosis of H. pylori infection. Clinical presentations, endoscopic, histologic features and results of treatment in H. pylori infected cases were described. RESULT: A total of 144 patients who underwent upper GI endoscopy were included in the study. 22 out of 144 cases proved to be infected by H. pylori. Ages ranged from 2.6 to 14 years (mean age 9 years). The male/female ratio was 1:1.2. Vomiting and epigastric pain were the leading symptoms. Endoscopic findings were divided into inflammation in the stomach 12 cases, both stomach and duodenum 6 cases and duodenal ulcer 4 cases. Nodular hyperplasia of gastric antrum was found in 8 out of 22 cases. Histologic evidence of chronic gastritis was present in 12 cases, chronic gastroduodenitis 6 cases and chronic duodenitis in duodenal ulcer cases. Treatment regimen consisted of one H2 blocker (ranitidine) initially which was changed to omeprazole in 2001 combined with 2 antibiotics (amoxycillin and metronidazole) for 14 days. CONCLUSION: This study group represented middle and low income groups from around Bangkok and many parts of Thailand. The prevalence of H. pylori infection in the present study was 15.3 per cent which reflects that H. pylori infection is a common health problem in Thailand. However, because this was only a descriptive study, the authors cannot specify the association between symptoms, endoscopic findings, histologic features and disease.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14700155&dopt=Abstract

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Nature. 2004 Jan 8;427(6970):121-8.
Notch activity acts as a sensor for extracellular calcium during vertebrate left-right determination.

Raya A, Kawakami Y, Rodriguez-Esteban C, Ibanes M, Rasskin-Gutman D, Rodriguez-Leon J, Buscher D, Feijo JA, Izpisua Belmonte JC.

Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.

During vertebrate embryo development, the breaking of the initial bilateral symmetry is translated into asymmetric gene expression around the node and/or in the lateral plate mesoderm. The earliest conserved feature of this asymmetric gene expression cascade is the left-sided expression of Nodal, which depends on the activity of the Notch signalling pathway. Here we present a mathematical model describing the dynamics of the Notch signalling pathway during chick embryo gastrulation, which reveals a complex and highly robust genetic network that locally activates Notch on the left side of Hensen's node. We identify the source of the asymmetric activation of Notch as a transient accumulation of extracellular calcium, which in turn depends on left-right differences in H+/K+-ATPase activity. Our results uncover a mechanism by which the Notch signalling pathway translates asymmetry in epigenetic factors into asymmetric gene expression around the node.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14712268&dopt=Abstract

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