We examined the frequency of multiple vertebral fractures (MVFs) and esophageal hiatal hernia (HH) in 18 Japanese postmenopausal women (74.1 +/- 9.9 years, mean +/- SD), with refractory reflux esophagitis (RRE) that had needed a proton pump inhibitor for more than 6 months to suppress symptoms such as heartburn and acid regurgitation, as well as in 57 control subjects without RE (71.4 +/- 5.9 years). MVFs (two or more VFs), HH, and both features were found in 11 (61%), 16 (89%), and 11 (61%) subjects, respectively, in the RRE group. All 11 patients with MVFs also had HH, suggesting their strong association. On the other hand, MVFs, HH, and both were found in 15 (26%), 23 (40%), and 8 (14%) subjects, respectively, in those without RE. The differences in frequencies of MVFs, HH, and both between the two groups were significant (chi2 = 7.3, 12.9, and 16.0; P = 0.015, 0.0009, and 0.0002, respectively). When univariate logistic regression analysis was performed with the presence of RRE as a dependent variable and the presence of MVFs, HH, and both as independent variables, MVFs, HH, and both were selected as indices affecting the presence of RRE (age-adjusted odds ratios: 4.34, 11.07, and 10.30; 95% confidential intervals: 1.40-13.45, 2.30-53.22, and 2.96-35.86; P = 0.0109, 0.0027, and 0.0002, respectively). These results show that the presence of MVFs is associated with the presence of RRE in Japanese postmenopausal women, and this association becomes more significant when HH is present. Thus, a kyphotic lumbar spine with MVFs may cause HH and RE by raising the intraabdominal pressure. As recent therapeutic agents for osteoporosis, alendronate and risedronate, are known to be very effective for suppressing the occurrence of new VFs, these agents may also prevent gastrointestinal disorders such as HH and RRE in osteoporotic women when administered to subjects without VFs.
Summary Objective: A number of clinical trials have reported that proton-pump inhibitors are efficacious in the treatment of upper abdominal symptoms, but most of these trials have been carried out in Caucasians. This study investigated the type of upper abdominal symptoms reported by Japanese patients with reflux esophagitis and the efficacy of omeprazole for treating their symptoms.Methods: A total of 234 patients aged ≥20 years with grade A to D reflux esophagitis were enrolled in this multicenter, open study. Patients received omeprazole 10 or 20 mg/day for 4 weeks. Symptom and quality of life questionnaires were administered at baseline, week 2 and week 4.Results: Among the 221 evaluable patients, almost 70% reported reflux-type symptoms (e.g. regurgitation and heartburn). Ulcer-and dysmotility-type symptoms (e.g. stomach pain and belching) were also common, occurring in 38-62% of patients. After 4 weeks of omeprazole *To whom correspondence should be addressed. Tel: +81-853-20-2190 Fax: +81-853-20-2187 E-mail: kadachi@med.shimane-u.ac.jp Abbreviations: ARD, acid-related disease; FD, functional dyspepsia; GSRS, Gastrointestinal Symptoms Rating Scale; PPIs, proton pump inhibitors; PU, peptic ulcer; QOL,quality of life; RE, reflux esophagitis; SD, standard deviation. Conclusion: Reflux-type symptoms as well as ulcer-and dysmotility-type symptoms were seen frequently in Japanese patients with reflux esophagitis. However, omeprazole improved all symptom types and quality of life in this patient population.
Increasing incidence of various cancers has been reported in diabetic patients. O‐linked N‐acetylglucosamine (O‐GlcNAc) modification of proteins at serine/threonine residues (O‐GlcNAcylation) is an essential post‐translational modification that is upregulated in diabetic patients and has been implicated in tumor growth. However, the mechanisms by which O‐GlcNAcylation promotes tumor growth remain unclear. Given that AMP‐activated kinase (AMPK) has been thought to play important roles in suppressing tumor growth, we evaluated the involvement of AMPK O‐GlcNAcylation on the growth of LoVo cells, a human colon cancer cell line. Results revealed that treatment with Thiamet G (TMG), an inhibitor of O‐GlcNAc hydrolase, increased both anchorage‐dependent and ‐independent growth of the cells. O‐GlcNAc transferase overexpression also increased the growth. These treatments increased AMPK O‐GlcNAcylation in a dose‐dependent manner, which led to reduced AMPK phosphorylation and mTOR activation. Chemical inhibition or activation of AMPK led to increased or decreased growth, respectively, which was consistent with the data with genetic inhibition of AMPK. In addition, TMG‐mediated acceleration of tumor growth was abolished by both chemical and genetic inhibition of AMPK. To examine the effects of AMPK O‐GlcNAcylation in vivo, the LoVo cells were s.c. transplanted onto the backs of BALB/c‐nu/nu mice. Injection of TMG promoted the growth and enhanced O‐GlcNAcylation of the tumors of the mice. Consistent with in vitro data, AMPK O‐GlcNAcylation was increased, which reduced AMPK phosphorylation and resulted in activation of mTOR. Collectively, the higher colon cancer risk of diabetic patients could be due to O‐GlcNAcylation‐mediated AMPK inactivation and subsequent activation of mTOR.
The cholecystokinin (CCK)-B/gastrin receptor binds two brain-gut hormones, CCK and gastrin, with high affinities. These peptides have a trophic effect on gastrointestinal cells expressing the receptor in vivo as well as in vitro. Recently, this receptor mRNA was reported to be expressed in immunocytes localized in the lamina propria of normal rat stomach mucosa. Here, we studied the receptor expression in human hematopoietic cells in order to determine whether they play a role in cell growth. The CCK-B/gastrin receptor mRNA was detectable in the polymorphonuclear (PMN) cells but not in the mononuclear cells of normal peripheral white blood cells by reverse transcription-polymerase chain reaction. The receptor transcript was, however, expressed in human leukemia cell lines (14 of 18 cell lines tested) derived from not only myeloid, but also T- and B-lymphoid lineages. The CCK-B/gastrin receptors on several leukemia cell lines were shown to be biologically active by demonstrating ligand-dependent cell proliferation in serum-deprived medium. Interestingly, a human CCK-B/gastrin receptor specific antagonist, YM022, but not its stereotype isoform, selectively inhibited the DNA synthesis of THP-1, MOLT-16, MOLT-14, and CCRF-CEM in the absence of exogenous peptide ligands. Further investigation revealed that these leukemia cell lines and normal PMN cells also expressed gastrin mRNA. These results suggest that growth of human leukemia cells is promoted by an autocrine mechanism through the CCK-B/gastrin receptors.
Cholecystokinin (CCK)‐B and gastrin receptors are expressed on a variety of human tumor cells. Recently, we have demonstrated that the human brain CCK‐B receptors are identical to the gastrin receptors derived from the stomach mucosa, and that the brain‐gut peptides, CCK‐8 and gastrin I are mitogenic for mouse NIH 3T3 fibroblasts expressing human CCK‐B/gastrin receptors (N‐hCCKBR). In this report, we evaluated the antiproliferative potency of CCK‐B/gastrin receptor antagonists by using N‐hCCKBR cells. Among several antagonists, a benzodiazepine derivative, YM022 had the most potent activities in competing with [125I]CCK‐8 or [125I]gastrin I binding, inhibition of CCK‐8‐ or gastrin I‐induced phosphoinositide hydrolysis and increasing cytoplasmic free calcium. Interestingly, a potent antagonist for rat CCK‐B/gastrin receptors did not have such activities in N‐hCCKBR cells. YM022 inhibited the CCK‐8‐ or gastrin I‐induced [methyl‐3H]thymidine incorporation of N‐hCCKBR cells in a dose‐dependent manner. In the absence of exogenous peptide ligands, YM022 also inhibited the proliferation of several human cancer cell lines expressing the genes for both gastrin and its receptor. These results suggest that YM022 could intervene in the autocrine stimulation of human tumor cell lines through CCK‐B/gastrin receptors. N‐hCCKBR cells are an excellent tool to screen for novel human CCK‐B/gastrin receptor antagonists possessing antiproliferative activity for human cancer cells.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.