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1.
Helicobacter ; 23(2): e12460, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29315971

ABSTRACT

BACKGROUND: Helicobacter pylori (H. pylori) infection causes elevation of lipid peroxidation product malondialdehyde (MDA) and this association may be due to the bacterium causing reactive oxygen species-mediated damage to DNA in the gastric epithelium. The aim of this study was to investigate the gastric juice MDA levels in relation to H. pylori infection and associated gastric diseases. METHODS: Gastric juice samples were obtained from 117 patients undergoing endoscopy, and gastric juice MDA levels were determined by high-performance liquid chromatography (HPLC) system. We compared the MDA levels between patients with and without H. pylori infection and assessed the differences of MDA levels between chronic gastritis, gastric intestinal metaplasia, and gastric cancer postsurgical resection. RESULTS: Malondialdehyde levels in gastric juice were significantly higher in chronic gastritis patients with H. pylori infection than in those without H. pylori infection (P < .0001). In patients without H. pylori infection, patients with gastric intestinal metaplasia and gastric cancer postsurgical resection had significantly higher gastric juice MDA level than patients with chronic gastritis. As a whole, patients with gastric intestinal metaplasia and gastric cancer postsurgical resection also had significantly higher MDA levels in gastric juice as compared to patients with chronic gastritis (P < .01). However, the difference of gastric juice MDA levels between gastric intestinal metaplasia and gastric cancer postsurgical resection was not significant. CONCLUSION: Malondialdehyde in gastric juice could be used as a potential diagnostic biomarker for H. pylori infection and associated gastric diseases. The gastric juice MDA levels increased proportionally with the severity of gastric diseases.


Subject(s)
Gastric Juice/metabolism , Helicobacter Infections/metabolism , Helicobacter pylori/pathogenicity , Malondialdehyde/metabolism , Aged , Female , Gastric Mucosa/metabolism , Gastric Mucosa/microbiology , Gastritis/metabolism , Gastritis/microbiology , Humans , Male , Middle Aged , Stomach Neoplasms/metabolism , Stomach Neoplasms/microbiology
2.
Stem Cells ; 35(10): 2115-2128, 2017 10.
Article in English | MEDLINE | ID: mdl-28782268

ABSTRACT

Reprogramming of cancer cells into induced pluripotent stem cells (iPSCs) is a compelling idea for inhibiting oncogenesis, especially through modulation of homeobox proteins in this reprogramming process. We examined the role of various long noncoding RNAs (lncRNAs)-homeobox protein HOXA13 axis on the switching of the oncogenic function of bone morphogenetic protein 7 (BMP7), which is significantly lost in the gastric cancer cell derived iPS-like cells (iPSLCs). BMP7 promoter activation occurred through the corecruitment of HOXA13, mixed-lineage leukemia 1 lysine N-methyltransferase, WD repeat-containing protein 5, and lncRNA HoxA transcript at the distal tip (HOTTIP) to commit the epigenetic changes to the trimethylation of lysine 4 on histone H3 in cancer cells. By contrast, HOXA13 inhibited BMP7 expression in iPSLCs via the corecruitment of HOXA13, enhancer of zeste homolog 2, Jumonji and AT rich interactive domain 2, and lncRNA HoxA transcript antisense RNA (HOTAIR) to various cis-element of the BMP7 promoter. Knockdown experiments demonstrated that HOTTIP contributed positively, but HOTAIR regulated negatively to HOXA13-mediated BMP7 expression in cancer cells and iPSLCs, respectively. These findings indicate that the recruitment of HOXA13-HOTTIP and HOXA13-HOTAIR to different sites in the BMP7 promoter is crucial for the oncogenic fate of human gastric cells. Reprogramming with octamer-binding protein 4 and Jun dimerization protein 2 can inhibit tumorigenesis by switching off BMP7. Stem Cells 2017;35:2115-2128.


Subject(s)
Cellular Reprogramming Techniques/methods , Homeodomain Proteins/genetics , RNA, Long Noncoding/genetics , Stomach Neoplasms/genetics , Bone Morphogenetic Protein 7/genetics , Bone Morphogenetic Protein 7/metabolism , Cell Line, Tumor , Cell Proliferation , Homeodomain Proteins/metabolism , Humans , Promoter Regions, Genetic , RNA, Long Noncoding/metabolism , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology
3.
J Dig Dis ; 18(9): 537-542, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28644575

ABSTRACT

OBJECTIVE: This was a prospective study aiming to investigate whether levofloxacin plus bismuth-based quadruple therapy was more effective than levofloxacin-based triple therapy after failed first-line eradication therapies for Helicobacter pylori (H. pylori) infection. METHODS: Sixty-seven patients infected with H. pylori were randomly assigned to two groups; the levofloxacin plus bismuth-based quadruple therapy group (RBAL [n = 33]; rabeprazole 20 mg twice daily, bismuth subcitrate 120 mg four times daily, amoxicillin 1 g twice daily and levofloxacin 500 mg once daily, for 10 days) and the levofloxacin-based triple therapy group (RAL [n = 34]; rabeprazole 20 mg twice daily, amoxicillin 1 g twice daily and levofloxacin 500 mg once daily, for 10 days). Endoscopy was performed 4-8 weeks after H. pylori eradication to assess treatment response. We followed up patient response and compliance and checked their resistance to antibiotics. RESULTS: Intention-to-treat analysis revealed that both groups had similar eradication rates (RBAL vs RAL: 84.8% [95% confidence interval {CI} 72.6-97.1%] vs 67.6% [95% CI 51.9-83.4%], P = 0.0987). No significant differences in compliance or adverse events were found (P = 0.9829 and 0.0720). Epsilometer test showed that most eradication failure cases were levofloxacin-resistant. CONCLUSIONS: Adding bismuth subcitrate to levofloxacin-based triple therapy was not more effective than not doing so, but no further side effects were noted. Both eradication therapies were equally safe and patients had the same tolerance to both regimens. Resistance rate to levofloxacin may be important when choosing second-line therapy.


Subject(s)
Antacids/therapeutic use , Anti-Bacterial Agents/therapeutic use , Helicobacter Infections/drug therapy , Helicobacter pylori , Levofloxacin/therapeutic use , Organometallic Compounds/therapeutic use , Adult , Aged , Amoxicillin/therapeutic use , Antacids/adverse effects , Anti-Bacterial Agents/adverse effects , Disk Diffusion Antimicrobial Tests , Drug Resistance, Bacterial , Drug Therapy, Combination/adverse effects , Female , Gastroscopy , Helicobacter Infections/diagnostic imaging , Helicobacter pylori/drug effects , Humans , Levofloxacin/adverse effects , Male , Medication Adherence , Middle Aged , Organometallic Compounds/adverse effects , Prospective Studies , Proton Pump Inhibitors/therapeutic use , Rabeprazole/therapeutic use , Retreatment
4.
Proteomics ; 17(11)2017 Jun.
Article in English | MEDLINE | ID: mdl-28493537

ABSTRACT

We reported an integrated platform to explore serum protein variant pattern in cancer and its utility as a new class of biomarker panel for diagnosis. On the model study of serum amyloid A (SAA), we employed nanoprobe-based affinity mass spectrometry for enrichment, identification and quantitation of SAA variants from serum of 105 gastric cancer patients in comparison with 54 gastritis patients, 54 controls, and 120 patients from other cancer. The result revealed surprisingly heterogeneous and most comprehensive SAA bar code to date, which comprises 24 SAA variants including SAA1- and SAA2-encoded products, polymorphic isoforms, N-terminal-truncated forms, and three novel SAA oxidized isotypes, in which the variant-specific peptide sequence were also confirmed by LC-MS/MS. A diagnostic model was developed for dimension reduction and computational classification of the 24 SAA-variant bar code, providing good discrimination (AUC = 0.85 ± 3.2E-3) for differentiating gastric cancer group from gastritis and normal groups (sensitivity, 0.76; specificity, 0.81) and was validated with external validation cohort (sensitivity, 0.71; specificity, 0.74). Our platform not only shed light on the occurrence and modification extent of under-represented serum protein variants in cancer, but also suggested a new concept of diagnostic platform by serum protein variant profile.


Subject(s)
Gastric Mucosa/metabolism , Gastritis/diagnosis , Serum Amyloid A Protein/metabolism , Stomach Neoplasms/diagnosis , Chromatography, Liquid , Diagnosis, Differential , Gastritis/metabolism , Humans , Protein Isoforms , Stomach Neoplasms/metabolism , Tandem Mass Spectrometry
5.
Stem Cells ; 34(11): 2613-2624, 2016 11.
Article in English | MEDLINE | ID: mdl-27341307

ABSTRACT

The network of stemness genes and oncogenes in human patient-specific reprogrammed cancer stem cells (CSCs) remains elusive, especially in liver cancer. HepG2-derived induced pluripotent stem cell-like cells (HepG2-iPS-like cells) were generated by introducing Yamanaka factors and the knockdown vector shTP53. They exhibited features of stemness and a higher tumorigenesis after xenograft transplantation compared with HepG2 cells. The cancerous mass of severe combined immunodeficiency (SCID) mice derived from one colony was dissected and cultured to establish reprogrammed HepG2-derived CSC-like cells (designated rG2-DC-1C). A single colony exhibited 42% occurrence of tumors with higher proliferation capacities. rG2-DC-1C showed continuous expression of the OCT4 stemness gene and of representative tumor markers, potentiated chemoresistance characteristics, and invasion activities. The sphere-colony formation ability and the invasion activity of rG2-DC-1C were also higher than those of HepG2 cells. Moreover, the expression of the OCT4 gene and the c-JUN oncogene, but not of c-MYC, was significantly elevated in rG2-DC-1C, whereas no c-JUN expression was observed in HepG2 cells. The positive-feedback regulation via OCT4-mediated transactivation of the c-JUN promoter and the c-JUN-mediated transactivation of the OCT4 promoter were crucial for promoting cancer development and maintaining cancer stemness in rG2-DC-1C. Increased expression of OCT4 and c-JUN was detected in the early stage of human liver cancer. Therefore, the positive feedback regulation of OCT4 and c-JUN, resulting in the continuous expression of oncogenes such as c-JUN, seems to play a critical role in the determination of the cell fate decision from iPS cells to CSCs in liver cancer. Stem Cells 2016;34:2613-2624.


Subject(s)
Feedback, Physiological , Gene Expression Regulation, Neoplastic , JNK Mitogen-Activated Protein Kinases/genetics , Liver Neoplasms/genetics , Neoplastic Stem Cells/metabolism , Octamer Transcription Factor-3/genetics , Aged , Animals , Antineoplastic Agents/pharmacology , Cell Differentiation , Cellular Reprogramming , Cisplatin/pharmacology , Doxorubicin/pharmacology , Drug Resistance, Neoplasm/genetics , Female , Fluorouracil/pharmacology , Hep G2 Cells , Humans , Induced Pluripotent Stem Cells/drug effects , Induced Pluripotent Stem Cells/metabolism , Induced Pluripotent Stem Cells/pathology , JNK Mitogen-Activated Protein Kinases/metabolism , Liver Neoplasms/drug therapy , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Male , Mice , Mice, SCID , Middle Aged , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/pathology , Octamer Transcription Factor-3/metabolism , Signal Transduction , Spheroids, Cellular/drug effects , Spheroids, Cellular/metabolism , Spheroids, Cellular/pathology , Transcriptional Activation , Tumor Burden/drug effects , Xenograft Model Antitumor Assays
6.
J Cell Mol Med ; 20(5): 962-72, 2016 May.
Article in English | MEDLINE | ID: mdl-26945908

ABSTRACT

Epidemiologic data show the incidence of gastric cancer in men is twofold higher than in women worldwide. Oestrogen is reported to have the capacity against gastric cancer development. Endogenous oestrogen reduces gastric cancer incidence in women. Cancer patients treated with oestrogens have a lower subsequent risk of gastric cancer. Accumulating studies report that bone marrow mesenchymal stem cells (BMMSCs) might contribute to the progression of gastric cancer through paracrine effect of soluble factors. Here, we further explore the effect of oestrogen on BMMSCs-mediated human gastric cancer invasive motility. We founded that HBMMSCs notably secrete interleukin-8 (IL-8) protein. Administration of IL-8 specific neutralizing antibody significantly inhibits HBMMSCs-mediated gastric cancer motility. Treatment of recombinant IL-8 soluble protein confirmed the role of IL-8 in mediating HBMMSCs-up-regulated cell motility. IL-8 up-regulates motility activity through Src signalling pathway in human gastric cancer. We further observed that 17ß -estradiol inhibit HBMMSCS-induced cell motility via suppressing activation of IL8-Src signalling in human gastric cancer cells. 17ß-estradiol inhibits IL8-up-regulated Src downstream target proteins including p-Cas, p-paxillin, p-ERK1/2, p-JNK1/2, MMP9, tPA and uPA. These results suggest that 17ß-estradiol significantly inhibits HBMMSCS-induced invasive motility through suppressing IL8-Src signalling axis in human gastric cancer cells.


Subject(s)
Epithelial Cells/drug effects , Estradiol/pharmacology , Gene Expression Regulation, Neoplastic , Interleukin-8/genetics , Mesenchymal Stem Cells/drug effects , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins pp60(c-src)/genetics , Bone Marrow Cells/cytology , Bone Marrow Cells/drug effects , Bone Marrow Cells/metabolism , Cell Line, Tumor , Cell Movement/drug effects , Coculture Techniques , Crk-Associated Substrate Protein/antagonists & inhibitors , Crk-Associated Substrate Protein/genetics , Crk-Associated Substrate Protein/metabolism , Epithelial Cells/metabolism , Epithelial Cells/pathology , Female , Gastric Mucosa/metabolism , Humans , Interleukin-8/antagonists & inhibitors , Interleukin-8/metabolism , MAP Kinase Kinase 4/antagonists & inhibitors , MAP Kinase Kinase 4/genetics , MAP Kinase Kinase 4/metabolism , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Mitogen-Activated Protein Kinase 1/antagonists & inhibitors , Mitogen-Activated Protein Kinase 1/genetics , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/antagonists & inhibitors , Mitogen-Activated Protein Kinase 3/genetics , Mitogen-Activated Protein Kinase 3/metabolism , Paxillin/antagonists & inhibitors , Paxillin/genetics , Paxillin/metabolism , Phosphorylation/drug effects , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins pp60(c-src)/antagonists & inhibitors , Proto-Oncogene Proteins pp60(c-src)/metabolism , Signal Transduction , Stomach/pathology
7.
World J Gastroenterol ; 21(40): 11221-35, 2015 Oct 28.
Article in English | MEDLINE | ID: mdl-26523098

ABSTRACT

Accurate diagnosis of Helicobacter pylori (H. pylori) infection is a crucial part in the effective management of many gastroduodenal diseases. Several invasive and non-invasive diagnostic tests are available for the detection of H. pylori and each test has its usefulness and limitations in different clinical situations. Although none can be considered as a single gold standard in clinical practice, several techniques have been developed to give the more reliable results. Invasive tests are performed via endoscopic biopsy specimens and these tests include histology, culture, rapid urease test as well as molecular methods. Developments of endoscopic equipment also contribute to the real-time diagnosis of H. pylori during endoscopy. Urea breathing test and stool antigen test are most widely used non-invasive tests, whereas serology is useful in screening and epidemiological studies. Molecular methods have been used in variable specimens other than gastric mucosa. More than detection of H. pylori infection, several tests are introduced into the evaluation of virulence factors and antibiotic sensitivity of H. pylori, as well as screening precancerous lesions and gastric cancer. The aim of this article is to review the current options and novel developments of diagnostic tests and their applications in different clinical conditions or for specific purposes.


Subject(s)
Helicobacter Infections/diagnosis , Helicobacter pylori/isolation & purification , Antibodies, Bacterial/blood , Antigens, Bacterial/analysis , Bacteriological Techniques , Biomarkers/blood , Biopsy , Breath Tests , Endoscopy, Gastrointestinal , Feces/microbiology , Helicobacter Infections/microbiology , Helicobacter Infections/therapy , Helicobacter pylori/genetics , Helicobacter pylori/immunology , Humans , Molecular Diagnostic Techniques , Predictive Value of Tests , Prognosis , Reproducibility of Results , Serologic Tests
8.
Biomed Res Int ; 2014: 513725, 2014.
Article in English | MEDLINE | ID: mdl-25548772

ABSTRACT

OBJECTIVE: This study was designed to compare the effect of Helicobacter pylori (H. pylori) infection treatment on serum zinc, copper, and selenium levels. PATIENTS AND METHODS: We measured the serum zinc, copper, and selenium levels in H. pylori-positive and H. pylori-negative patients. We also evaluated the serum levels of these trace elements after H. pylori eradication. These serum copper, zinc, and selenium levels were determined by inductively coupled plasma mass spectrometry. RESULTS: Sixty-three H. pylori-positive patients and thirty H. pylori-negative patients were studied. Serum copper, zinc, and selenium levels had no significant difference between H. pylori-positive and H. pylori-negative groups. There were 49 patients with successful H. pylori eradication. The serum selenium levels were lower after successful H. pylori eradication, but not significantly (P = 0.06). There were 14 patients with failed H. pylori eradication. In this failed group, the serum selenium level after H. pylori eradication therapy was significantly lower than that before H. pylori eradication therapy (P < 0.05). The serum zinc and copper levels had no significant difference between before and after H. pylori eradication therapies. CONCLUSION: H pylori eradication regimen appears to influence the serum selenium concentration (IRB number: KMUH-IRB-20120327).


Subject(s)
Copper/blood , Helicobacter Infections/blood , Selenium/blood , Zinc/blood , Adult , Aged , Amoxicillin/administration & dosage , Female , Helicobacter Infections/drug therapy , Helicobacter Infections/microbiology , Helicobacter pylori/drug effects , Humans , Lansoprazole/administration & dosage , Male , Middle Aged , Trace Elements/blood
9.
BMC Gastroenterol ; 14: 91, 2014 May 13.
Article in English | MEDLINE | ID: mdl-24884853

ABSTRACT

BACKGROUND: The acid-suppressive agents have been linked with an increased risk of infectious disease. The relationship between these drugs and Mycobacterium Tuberculosis (TB) was not been reported. METHODS: We conducted a case-control study using data from National Health Insurance research database of Taiwan. From 1996 till 2008, and 6541 cases were defined as TB infection/activation (ICD-9 coding plus prescription two of four first-line anti-TB regimen for at least one month). Control subjects who were matched to the TB cases by age and sex were selected with 10:1 ratio. Medical records including acid-suppressive agent prescription and comorbidity, and socioeconomic status were analyzed. RESULTS: TB infection/activation was more frequent to comorbidity with chronic diseases, alcohol abuse, malignancy, immune deficient/suppression status and acid-related disease (peptic ulcer, reflux esophagitis). Among the TB cases, there was higher exposure record to acid-suppressive agents within 3 months before TB index date (OR 2.43(2.06-2.88) and 1.90 (1.68-2.14) for proton pump inhibitor (PPI) and histamine 2 receptor antagonist (H2RA) respectively). After adjusting confounding factors, PPIs prescription 3 months before TB index date had an association of TB infection/activation (adjusted OR 1.63(1.61-1.63)). Similar result was found in H2RA user (adjusted OR 1.51(1.50-1.52)). The association of acid-suppressive agents in TB infection/activation was fade gradually when the drug prescription period extended. CONCLUSIONS: Recent prescription of acid-suppressive agent seems to associate the TB infection/activation. In the society where TB was prevalent, evaluation of pulmonary TB before prescription of PPI or H2RA is warranted.


Subject(s)
Anti-Ulcer Agents/therapeutic use , Histamine H2 Antagonists/therapeutic use , Proton Pump Inhibitors/therapeutic use , Tuberculosis/epidemiology , Adult , Aged , Case-Control Studies , Comorbidity , Female , Humans , Male , Middle Aged , Odds Ratio , Retrospective Studies , Risk Factors , Taiwan/epidemiology , Time Factors
10.
World J Gastroenterol ; 20(12): 3343-9, 2014 Mar 28.
Article in English | MEDLINE | ID: mdl-24695835

ABSTRACT

AIM: To evaluate the utility of the string test to detect genotypic clarithromycin-resistant Helicobacter pylori (H. pylori) by polymerase chain reaction (PCR)-restriction fragment length polymorphism. METHODS: Patients undergoing endoscopic examinations were enrolled in the present study. String tests were done on the next day of endoscopy. Segments of 23S rRNA were amplified from DNA obtained from string tests. PCR-restriction fragment length polymorphism was accomplished by restriction enzymes BbsI and BsaI recognizing the mutation site A to G at 2143 or at 2142 of 23S rRNA domain V, respectively. RESULTS: One hundred and thirty-four patients with H. pylori infection underwent string tests. To compare phenotypic resistance, 43 isolates were successfully cultured in 79 patients in whom 23S rRNA was successfully amplified. Of five patients with clarithromycin-resistant H. pylori, 23S rRNA of H. pylori isolates from four patients could be digested by BsaI. In 38 susceptible isolates, 23S rRNA of H. pylori isolates from 36 patients could not be digested by either BsaI or BbsI. The sensitivity and specificity of the string test to detect genotypic clarithromycin resistance were 66.7% and 97.3%, respectively. Positive and negative predictive values were 80% and 94.7%, respectively. CONCLUSION: String test with molecular analysis is a less invasive method to detect genotypic resistance before treatment. Further large-scale investigations are necessary to confirm our results.


Subject(s)
Clarithromycin/pharmacology , Drug Resistance, Bacterial , Helicobacter Infections/drug therapy , Helicobacter pylori/drug effects , Helicobacter pylori/genetics , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Endoscopy , Genotype , Helicobacter Infections/genetics , Humans , Microbiological Techniques , Mutation , Phenotype , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , RNA, Ribosomal, 23S/genetics
11.
Int J Med Sci ; 11(1): 7-16, 2014.
Article in English | MEDLINE | ID: mdl-24396281

ABSTRACT

Gender differences in terms of mortality among many solid organ malignancies have been proved by epidemiological data. Estrogen has been suspected to cast a protective effect against cancer because of the lower mortality of gastric cancer in females and the benefits of hormone replacement therapy (HRT) in gastric cancer. Hence, it suggests that 17ß-estradiol (E2) may affect the behavior of cancer cells. One of the key features of cancer-related mortality is metastasis. Accumulating evidences suggest that human bone marrow mesenchymal stem cells (HBMMSCs) and its secreted CCL-5 have a role in enhancing the metastatic potential of breast cancer cells. However, it is not clear whether E2 would affect HBMMSCs-induced mobility in gastric cancer cells. In this report, we show that CCL-5 secreted by HBMMSCs enhanced mobility in human AGS gastric cancer cells via activation of Src/Cas/Paxillin signaling pathway. Treatment with specific neutralizing antibody of CCL-5 significantly inhibited HBMMSCs-enhanced mobility in human AGS gastric cancer cells. We further observe that 17ß-estradiol suppressed HBMMSCs-enhanced mobility by down-regulating CCL5-Src/Cas/paxillin signaling pathway in AGS cells. Collectively, these results suggest that 17ß-estradiol treatment significantly inhibits HBMMSCS-induced mobility in human AGS gastric cancer cells.


Subject(s)
Chemokine CCL5/metabolism , Estradiol/pharmacology , Mesenchymal Stem Cells/pathology , Paxillin/metabolism , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , src-Family Kinases/metabolism , Antibodies, Neutralizing/pharmacology , Bone Marrow Cells/cytology , Bone Marrow Cells/metabolism , Cell Line, Tumor/drug effects , Cell Movement/drug effects , Chemokine CCL5/genetics , Chemokine CCL5/immunology , Crk-Associated Substrate Protein/metabolism , Down-Regulation/drug effects , Enzyme Inhibitors/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Humans , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Signal Transduction/drug effects , Stomach Neoplasms/metabolism , src-Family Kinases/antagonists & inhibitors
12.
Biochem Res Int ; 2013: 594561, 2013.
Article in English | MEDLINE | ID: mdl-24349780

ABSTRACT

Background. The suppression of Helicobacter pylori (H. pylori) decreases H. pylori-related diseases. The probiotics have an inhibitory effect on H. pylori. Aim. We investigated the effects of long-term use of yogurt on H. pylori based on Mongolian gerbils' model. Materials and Methods. Yogurt (containing a supplement of Lactobacillus acidophilus, Bifidobacterium lactis, etc.) was used. Forty-six gerbils were divided into five groups. All groups were inoculated with H. pylori for 5 to 8 weeks. The yogurt was given as follows: Group (Gr.) A: from 1st to 4th week; Gr. B from 5th to 8th week; Gr. C: from 17th week to sacrifice; Gr. D: from 5th week to sacrifice. Gerbils were sacrificed on the 52nd week. Histology was evaluated according to the Sydney system. Results. The positive rates of H. pylori were 60% (Gr. A), 75% (Gr. B), 67% (Gr. C), 44% (Gr. D), and 100% (Gr. E). Gr. D showed lower inflammatory score. Only Gr. E (60%) had intestinal metaplasia. Gr. D showed higher IL-10 and lower TNF- α expression than Gr. E. Conclusion. Long-term intake of yogurt could decrease H. pylori infection. The long-term use of yogurt would be an alternative strategy to manage H. pylori infection.

13.
Gastroenterol Res Pract ; 2013: 390967, 2013.
Article in English | MEDLINE | ID: mdl-24348534

ABSTRACT

Background. Chronic Helicobacter pylori infection and iron-deficiency anemia (IDA) are common in adults. Although the most common causes of IDA usually arise from the gastrointestinal tract, the association between chronic Helicobacter pylori infection and anemia remains unclear. Aim. To evaluate the association of chronic Helicobacter pylori infection and IDA. Materials and Methods. We enrolled 882 patients from January 2010 to April 2013. The status of Helicobacter pylori (H.p) infection was confirmed and blood samples from the same participants were taken on the same day to check the level of hemoglobin, serum iron, ferritin, and total iron-binding capacity (TIBC). Results. No significant difference was noted from the demographic data. The average level of hemoglobin (Hb) was not different between negative and positive groups, pos 13.57 g/dL versus neg 13.65 g/dL (P = 0.699). Although the levels of serum IDA related parameters were expected in positive group (lower serum iron and ferritin and higher TIBC) these differences did not reach statistical significance (P = 0.824 for iron, P = 0.360 for ferritin, and P = 0.252 for TIBC). Conclusion. Chronic Helicobacter pylori infection is not attributed to IDA. The levels of hemoglobin, serum iron and ferritin, and TIBC remain unaffected after chronic H.p infection. Large-scale clinical studies are needed to prove the association.

14.
Kaohsiung J Med Sci ; 29(12): 691-4, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24296059

ABSTRACT

Terlipressin, an analogue of vasopressin, is frequently used for the management of esophageal varices bleeding and hepatorenal syndrome. Terlipressin therapy in portal hypertensive patients is frequently associated with hyponatremia, but is rarely accompanied with serious neurological manifestations. A 39-year-old female with pancreatic neuroendocrine tumor, liver metastasis, main portal vein thrombosis, and a history of esophageal varices presented to the emergency room because of hematemesis. Terlipressin was given with a loading dose of 2 mg followed by 1 mg every 6 hours. After a total of 6 mg terlipressin injection, she suffered from acute delirium. Pertinent examinations showed there was no gross brain lesion by computed tomography, whereas her serum sodium level dropped from baseline (136 mmol/L) to 116 mmol/L with a serum osmolality of 256 mOsm/kg. At that time, urine sodium and urine osmolality were 142 mmol/L and 488 mOsm/kg, respectively. Under the tentative diagnosis of terlipressin-induced hyponatremic encephalopathy, terlipressin was withheld and hypertonic saline infusion was given. Within 12 hours, her serum sodium level recovered to 130 mmol/L and she gradually regained her cognitive functions. Although symptomatic hyponatremic encephalopathy is a rare complication of terlipressin treatment, close monitoring of serum electrolyte level is warranted in patients receiving terlipressin.


Subject(s)
Brain Diseases/chemically induced , Hyponatremia/chemically induced , Lypressin/analogs & derivatives , Adult , Female , Humans , Liver Cirrhosis , Lypressin/adverse effects , Terlipressin
15.
Gastroenterol Res Pract ; 2013: 983653, 2013.
Article in English | MEDLINE | ID: mdl-23878534

ABSTRACT

Gastroesophageal reflux disease (GERD), a common disorder with troublesome symptoms caused by reflux of gastric contents into the esophagus, has adverse impact on quality of life. A variety of medications have been used in GERD treatment, and acid suppression therapy is the mainstay of treatment for GERD. Although proton pump inhibitor is the most potent acid suppressant and provides good efficacy in esophagitis healing and symptom relief, about one-third of patients with GERD still have persistent symptoms with poor response to standard dose PPI. Antacids, alginate, histamine type-2 receptor antagonists, and prokinetic agents are usually used as add-on therapy to PPI in clinical practice. Development of novel therapeutic agents has focused on the underlying mechanisms of GERD, such as transient lower esophageal sphincter relaxation, motility disorder, mucosal protection, and esophageal hypersensitivity. Newer formulations of PPI with faster and longer duration of action and potassium-competitive acid blocker, a newer acid suppressant, have also been investigated in clinical trials. In this review, we summarize the current and developing therapeutic agents for GERD treatment.

16.
Eur J Clin Invest ; 43(9): 949-56, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23879740

ABSTRACT

BACKGROUND: Although the association between chronic Helicobacter pylori infection and type 2 diabetes has been suggested, findings have been inconsistent. This study evaluated the association between chronic H. pylori infection and glucose regulation. MATERIALS AND METHODS: We evaluated H. pylori infection status of participants recruited from the gastroenterology clinic at our hospital. At baseline, we performed blood tests including fasting plasma glucose, insulin, glycated haemoglobin A1c (HbA1c) and other biochemical measurements. Insulin resistance and beta-cell function were assessed by homoeostasis model assessment (HOMA-IR and HOMA-B, respectively). RESULTS: A total of 2070 participants were recruited. Those who had H. pylori infections had higher serum HbA1c levels and lower HOMA-B than those who did not (5.78% vs. 5.69%, P = 0.01 and 53.85 + 38.43 vs. 60.64 + 43.40, P = 0.009, respectively). They also had a significantly higher prevalence of type 2 diabetes (8.97% vs. 5.57%, P= 0.02). Chronic H. pylori infection was significantly associated with high levels of HbA1c and type 2 diabetes in participants above 65 years old (P = 0.001) and decreased insulin secretion and sensitivity in those under 45 years (P = 0.05). CONCLUSIONS: Long-term H. pylori infection is significantly associated with high levels of HbA1c and decreased insulin secretion in this Chinese population. Proper screening for H. pylori infection combined with regular monitoring of blood glucose and HbA1c levels might be effective for the early detection of glucose dysregulation and prevention of type 2 diabetes.


Subject(s)
Diabetes Mellitus, Type 2/complications , Glycated Hemoglobin/metabolism , Helicobacter Infections/complications , Helicobacter pylori , Adult , Aged , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/prevention & control , Early Diagnosis , Female , Helicobacter Infections/blood , Helicobacter Infections/diagnosis , Homeostasis/physiology , Humans , Longitudinal Studies , Male , Middle Aged
17.
Clin Chim Acta ; 424: 123-30, 2013 Sep 23.
Article in English | MEDLINE | ID: mdl-23719625

ABSTRACT

BACKGROUND: The ability to determine the virulence of a Helicobacter pylori strain would be helpful for predicting the development of gastrointestinal disease and suggesting medical treatment. METHODS: A protocol based on matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI-TOF MS) was established for the efficient detection of peptides and proteins in extracts of H. pylori cells. Two multivariate statistical methods-principal component analysis (PCA) and hierarchical clustering analysis-were used to analyze the resulting MALDI mass spectra of reference strains and clinical isolated/inoculated strains. RESULTS: Based on differences in their peptide and protein profiles, H. pylori strains having similar virulence genotypes were grouped together on the PCA score plot. Hierarchical cluster analysis revealed high conformity between the protein profiles and the respective virulence genotypes. The inoculated H. pylori strain, which was clustered in the same group with the high-virulence reference strains, also resulted in severe histopathological lesions in gerbils. CONCLUSIONS: MALDI-TOF MS combined with multivariate analyses shows the ability to rapidly differentiate H. pylori strains in terms of their virulence.


Subject(s)
Bacterial Proteins/isolation & purification , Gerbillinae/microbiology , Helicobacter Infections/diagnosis , Helicobacter Infections/veterinary , Helicobacter pylori/pathogenicity , Animals , Bacterial Typing Techniques , Genetic Variation , Helicobacter Infections/microbiology , Helicobacter pylori/chemistry , Humans , Multivariate Analysis , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Virulence
18.
J Antimicrob Chemother ; 68(1): 222-8, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22984204

ABSTRACT

OBJECTIVES: This prospective study was designed to compare the efficacies of levofloxacin-containing and high-dose metronidazole-containing quadruple therapies after failure of standard triple therapies. METHODS: A total of 150 Helicobacter pylori-infected patients were enrolled in our study and randomly assigned to levofloxacin-containing quadruple therapy (EBTL group) (40 mg of esomeprazole twice daily, 300 mg of bismuth subcitrate four times daily, 500 mg of tetracycline four times daily and 500 mg of levofloxacin once daily for 10 days) (n = 76) or high-dose metronidazole-based quadruple therapy (EBTM group) (40 mg of esomeprazole twice daily, 300 mg of bismuth subcitrate four times daily, 500 mg of tetracycline four times daily and 500 mg of metronidazole four times daily for 10 days) (n = 74). Follow-up endoscopy or urea breath test was done 16 weeks later to assess the treatment response. Patients' responses, CYP2C19 genotypes and antibiotic resistances were also examined. All participants, caregivers and those assessing the outcomes were blinded to group assignment. RESULTS: Intention-to-treat analysis revealed that both groups showed similar eradication rates: EBTL, 78.9% (60/76) (95% CI 69.7%-88.1%) and EBTM, 79.7% (59/74) (95% CI 70.5%-88.7%) [risk ratio (RR) 0.97, 95% CI 0.44-2.14]. Per-protocol results were EBTL = 87.0% (60/69) (95% CI 79.4%-94.9%) and EBTM = 90.8% (59/65) (95% CI 83.8%-97.8%) (RR 0.68, 95% CI 0.23-2.0). We did not find significant differences in compliance (RR 0.5, 95% CI 0.54-2.3) and adverse events (RR 1.11, 95% CI 0.54-2.3) between the two groups. Logistic regression analysis showed that only compliance was an important predictor for eradication failure. CYP2C19 polymorphism did not influence the eradicating effect. CONCLUSIONS: The 10 day bismuth quadruple therapies with high-dose metronidazole or levofloxacin were effective even in areas with high resistance. These two therapies were equally safe and tolerated. Besides this, the metronidazole-containing therapy was cheaper. So it is persuasive that high-dose metronidazole-containing quadruple therapy could be a good choice for second-line H. pylori eradication in areas with high resistance.


Subject(s)
Helicobacter Infections/drug therapy , Helicobacter pylori/drug effects , Levofloxacin , Metronidazole/administration & dosage , Ofloxacin/administration & dosage , Organometallic Compounds/administration & dosage , Adult , Aged , Anti-Bacterial Agents/administration & dosage , Drug Administration Schedule , Drug Therapy, Combination , Female , Follow-Up Studies , Helicobacter Infections/epidemiology , Humans , Male , Middle Aged , Surveys and Questionnaires , Treatment Outcome , Young Adult
19.
J Dig Dis ; 14(3): 147-52, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23216875

ABSTRACT

OBJECTIVE: Target-controlled infusion (TCI) of propofol is an effective way of delivering propofol during endoscopy. However, the ideal effect-site concentration (Ce) of propofol has not yet been defined in an Asian population. This study aimed to determine the ideal Ce of propofol in painless gastrointestinal endoscopy in a Taiwanese population. METHODS: A total of 121 consecutive patients undergoing diagnostic endoscopy were recruited for this study. The endoscopic procedure was carried out within 1 h. TCI of propofol was utilized during the procedure. All patients received the same regimen to induce conscious sedation, including a bolus of midazolam (0.04 mg/kg) and fentanyl (0.5 µg/kg). The Ce of propofol was calculated using the Schneider model. Patients were randomly assigned to either the low Ce group (1.5-2.5 µg/mL) or high Ce group (3.0-4.0 µg/mL). Their cardiovascular and respiratory events were monitored during the procedure and the patients' post-procedure satisfaction was evaluated. RESULTS: The mean requirement for propofol was 232.02 mg in the low Ce group and 329.56 mg in the high Ce group, respectively (P < 0.0001). No unexpected event was observed in either group. However, more episodes of hypotension were observed in the high Ce group (P = 0.026). The post-procedure satisfaction rate between the two groups was comparable. CONCLUSION: A low Ce of propofol TCI (1.5-2.5 µg/mL) achieved adequate anesthesia, reduced the risk of hypotension, and attained a high satisfaction rate in a Taiwanese population undergoing diagnostic painless endoscopy.


Subject(s)
Anesthetics, Intravenous/administration & dosage , Endoscopy, Gastrointestinal/adverse effects , Hypnotics and Sedatives/administration & dosage , Hypotension/prevention & control , Propofol/administration & dosage , Adult , Aged , Anesthetics, Intravenous/adverse effects , Conscious Sedation/methods , Dose-Response Relationship, Drug , Drug Administration Schedule , Endoscopy, Gastrointestinal/methods , Female , Humans , Hypnotics and Sedatives/adverse effects , Hypotension/etiology , Infusions, Intravenous , Male , Middle Aged , Patient Satisfaction , Propofol/adverse effects
20.
Gastroenterol Res Pract ; 2012: 674324, 2012.
Article in English | MEDLINE | ID: mdl-22829808

ABSTRACT

Background and Study Aims. To compare the effectiveness of two regimens, single-dose esomeprazole- and pantoprazole-based triple therapy, for Helicobacter pylori (H. pylori) eradication. Patients and Methods. A total of 453 patients were enrolled for H. pylori eradication. They were randomly assigned to either EAC group (Esomeprazole 40 mg once daily, Amoxicillin 1 g twice daily, Clarithromycin 500 mg twice daily for 7 days) or PAC group (Pantoprazole 40 mg twice daily, Amoxicillin 1 g twice daily, Clarithromycin 500 mg twice daily for 7 days). Follow-up endoscopy or urea breath test was scheduled 12-16 weeks after the eradication to evaluate the therapeutic response. Results. Higher eradication rate in EAC group than PAC group was shown by intention-to-treat analysis (EAC 72% versus PAC 55%, P < 0.05) and per-protocol analysis (EAC 91% versus PAC 72%, P < 0.05). The incidence of adverse effects (EAC 19% versus PAC 17%, P = 0.712) and the compliance (EAC 87% versus PAC 91%, P = 0.083) were comparable between these 2 groups. Conclusions. Single-dose esomeprazole-based triple therapy is effective for H. pylori eradication.

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