• renal replacement therapy
• gastrointestinal bleeding

• Aging
• Diet
• Microbiota
• Rats
• Sex
• high-fat

• UCHL-1
• aging
• calcium
• oxidative stress
• proteasome

• Helicobacter pylori
• atrophic gastritis
• eradication
• gastric microbiota
• intestinal metaplasia

• ArfGAP3
• Differentiation
• Mechanical stress
• Oxidative stress
• Pelvic floor dysfunction

Aging is a significant risk factor for gastrointestinal dysmotility, but aging-associated differences between different organs and the exact time to start degenerating have remained obscure. Here we evaluated alterations of interstitial cells of Cajal, enteric neurons and connexin43 expression in the stomach, jejunum and colon in 2-, 12-, 16-, 20- and 24-month-old mice, as well as in aged human colon. Interstitial cells of Cajal, cholinergic and nitrergic neurons within the whole digestive tract were reduced over time, but their loss first appeared in stomach, then in intestine, helping to understand that gastric function was first impaired during aging. The decrease of connexin43 expression occurred before interstitial cells of Cajal and neurons loss, suggesting that connexin43 might be the major target influenced during senescence. Furthermore, changes in expressions of pro-inflammatory cytokines (tumour necrosis factor-α, interleukin-1β, interleukin-6) and apoptosis-related proteins (B-cell lymphoma-2, caspase-3) which indicated “inflammaging”, might contribute to the loss of enteric neurons and interstitial cells of Cajal in aged gastrointestinal tract. Our results provide possible therapeutic time window for beneficial intervention for geriatric patients with gastrointestinal motility disorders.

• aging
• connexin43
• enteric nervous system
• gastrointestinal motility
• interstitial cells of Cajal

The incidence and predictors of bleeding after acute coronary syndrome are unclear within the real‐world setting. Our objective was to determine the incidence, types, timing, and predictors of bleeding complications following hospital discharge after acute coronary syndrome.

We used the Clinical Practice Research Datalink, with linkage to Hospital Episode Statistics, to determine the incidence, timing, and types of bleeding events within 12 months after hospital discharge for acute coronary syndrome. We assessed independent associations between postdischarge bleeding and baseline patient characteristics using a competing risk regression model, accounting for death as a competing event. Among 27 660 patients surviving to hospital discharge, 3620 (13%) experienced bleeding complications at a median time of 123 days (interquartile range, 45–223 days) after discharge. The incidence of bleeding was 162/1000 person‐years (95% CI, 157–167/1000 person‐years) within the first 12 months after hospital discharge. Bruising (949 bleeds [26%]) was the most common type of first bleeding event, followed by gastrointestinal bleed (705 bleeds [20%]), whereas intracranial bleed was relatively rare (81 bleeds [2%]). Significant predictors of postdischarge bleeding included history of bleeding complication, oral anticoagulant prescription, history of peripheral vascular disease, chronic obstructive pulmonary disease, and advanced age (>80 years). Predictors for postdischarge bleeding varied, depending on the anatomic site of the bleeding event.

Bleeding complications after hospital discharge for acute coronary syndrome are common. Patients who experience these bleeding events have distinct baseline characteristics, which vary by anatomic site of the bleed. These characteristics can inform risk‐benefit considerations in deciding on favorable combination and duration of secondary antithrombotic therapy.

• hemorrhage
• incidence
• postdischarge
• real world
• risk factors
• sites

• Anti-inflammatory agents, non-steroidal
• Aspirin
• Gastritis
• Irsogladine maleate
• Peptic ulcer

• Aged
• Aged, 80 and over
• Anti-Inflammatory Agents, Non-Steroidal/adverse effects
• Anti-Ulcer Agents/adverse effects
• Anti-Ulcer Agents/therapeutic use
• Double-Blind Method
• Female
• Gastric Mucosa/drug effects
• Gastric Mucosa/pathology
• Gastritis/chemically induced
• Gastritis/diagnosis
• Gastritis/prevention & control
• Humans
• Male
• Middle Aged
• Republic of Korea
• Risk Factors
• Stomach Ulcer/chemically induced
• Stomach Ulcer/diagnosis
• Stomach Ulcer/prevention & control
• Time Factors
• Treatment Outcome
• Triazines/adverse effects
• Triazines/therapeutic use

• Genistein
• HL-60 human leukemia cancer cells
• apoptosis
• endoplasmic reticulum stress
• mitochondria dysfunction

• Animals
• Anticarcinogenic Agents/pharmacology
• Apoptosis/drug effects
• Cell Cycle/drug effects
• DNA Damage
• Endoplasmic Reticulum Chaperone BiP
• Endoplasmic Reticulum Stress/drug effects
• Genistein/pharmacology
• HL-60 Cells
• Heterografts/drug effects
• Heterografts/pathology
• Humans
• Male
• Membrane Potential, Mitochondrial/drug effects
• Mice, Nude
• Reactive Oxygen Species/metabolism
• Xenograft Model Antitumor Assays

Patients with COPD are at higher risk of presenting with atrial fibrillation (AF). Information about clinical outcomes and optimal medical treatment of AF in the setting of COPD remains missing. We aimed to describe the prevalence of COPD in a sizeable cohort of real-world AF patients belonging to the same healthcare area and to examine the relationship between comorbid COPD and AF prognosis.

Prospective analysis performed in a specific healthcare area. Data were obtained from several sources within the “data warehouse of the Galician Healthcare Service” using multiple analytical tools. Statistical analyses were completed using SPSS 19 and STATA 14.0.

A total of 7,990 (2.08%) patients with AF were registered throughout 2013 in our healthcare area (n=348,985). Mean age was 76.83±10.51 years and 937 (11.7%) presented with COPD. COPD patients had a higher mean CHA₂DS₂-VASc (4.21 vs 3.46; P=0.02) and received less beta-blocker and more digoxin therapy than those without COPD. During a mean follow-up of 707±103 days, 1,361 patients (17%) died. All-cause mortality was close to two fold higher in the COPD group (28.3% vs 15.5%; P<0.001). Independent predictive factors for all-cause mortality were age, heart failure, diabetes, previous thromboembolic event, dementia, COPD, and oral anticoagulation (OA). There were nonsignificant differences in thromboembolic events (1.7% vs 1.5%; P=0.7), but the rate of hemorrhagic events was significantly higher in the COPD group (3.3% vs 1.9%; P=0.004). Age, valvular AF, OA, and COPD were independent predictive factors for hemorrhagic events. In COPD patients, age, heart failure, vasculopathy, lack of OA, and lack of beta-blocker use were independent predictive factors for all-cause mortality.

AF patients with COPD have a higher incidence of adverse events with significantly increased rates of all-cause mortality and hemorrhagic events than AF patients without COPD. However, comorbid COPD was not associated with differences in cardiovascular death or stroke rate. OA and beta-blocker treatment presented a risk reduction in mortality while digoxin use exerted a neutral effect.

• CHA2DS2-VASc
• COPD
• atrial fibrillation
• big data
• stroke

• LRP5
• Tie2
• VEGFR2
• aging
• angiogenesis
• lung

• Aging/physiology
• Animals
• Epithelial Cells
• Gene Knockdown Techniques
• Low Density Lipoprotein Receptor-Related Protein-5/genetics
• Low Density Lipoprotein Receptor-Related Protein-5/metabolism
• Lung/blood supply
• Lung/growth & development
• Mice
• Mice, Inbred C57BL
• Neovascularization, Physiologic
• Pneumonectomy
• Tissue Culture Techniques

• 18TPA34170129 American Heart Association-American Stroke Association
• R21 AG054830 NIA NIH HHS

• Artemisia capillaris
• Gastritis
• Interleukin-1?
• Interleukin-6
• MDA
• SOD

The aging-associated cellular and molecular changes in esophagus have not been established, yet. Thus we evaluated histological structure, interstitial cells of Cajal (ICCs), neuronal nitric oxide synthase (nNOS)-positive cells, and contractility in the esophagus of Fischer 344 rat at different ages (6-, 31-, 74-weeks, and 2-years). The lamina propria thickness and endomysial area were calculated. The immunoreactivity of c-Kit, nNOS and protein gene product (PGP) 9.5 was counted after immunohistochemistry. Expression of c-Kit, stem cell factor (SCF), nNOS and PGP 9.5 mRNA was measured by real-time PCR, and expression of c-Kit and nNOS protein was detected by Western blot. Isovolumetric contractile force measurement and electrical field stimulation (EFS) were conducted. The lamina propria thickness increased (6 week vs 2 year, P = 0.005) and the endomysial area of longitudinal muscle decreased with aging (6 week vs 2 year, P<0.001), while endomysial area of circular muscle did not significantly decrease. The proportions of NOS-immunoreactive cells and c-Kit-immunoreactive areas declined with aging (6 week vs 2 year; P<0.001 and P = 0.004, respectively), but there was no significant change of PGP 9.5-immunopositiviy. The expressions of nNOS, c-Kit and SCF mRNA also reduced with aging (6 week vs 2 year; P = 0.006, P = 0.001 and P = 0.006, respectively), while the change of PGP 9.5 mRNA expression was not significant. Western blot showed the significant decreases of nNOS and c-Kit protein expression with aging (6 week vs 2 year; P = 0.008 and P = 0.012, respectively). The EFS-induced esophageal contractions significantly decreased in 2-yr-old rat compared with 6-wk-old rats, however, L-NG-Nitroarginine methylester did not significantly increase the spontaneous and EFS-induced contractions in the 6-wk- and 2-yr-old rat esophagus. In conclusion, an increase of lamina propria thickness, a decrease of endomysial area, c-Kit, SCF and NOS expression with preserved total enteric neurons, and contractility in aged rat esophagus may explain the aging-associated esophageal dysmotility.

• Aging
• Animals
• Blotting, Western
• Esophagus/cytology
• Esophagus/metabolism
• Interstitial Cells of Cajal/cytology
• Interstitial Cells of Cajal/metabolism
• Male
• Neurons/enzymology
• Nitric Oxide Synthase Type I/metabolism
• Proto-Oncogene Proteins c-kit/metabolism
• Rats
• Rats, Inbred F344
• Real-Time Polymerase Chain Reaction
• Stem Cell Factor/genetics
• Stem Cell Factor/metabolism

To observe changes in gastric biomarker levels with age and effects of Helicobacter pylori (H. pylori) infection in a healthy population, and explore factors associated with gastric biomarkers.

Three hundred and ninety-five subjects were selected and underwent physical examinations, biochemical tests, and measurement of serum pepsinogen (PG) I and II, gastrin-17 (G-17) and H. pylori antibody levels. Analyses were made by Student’s t-test, ANOVA, Pearson’s correlation and multiple linear regressions.

PGII levels were higher in the ≥ 65-years-old age group (P < 0.05) and PGI/PGII were lower in the ≥ 75-years-old age group (P = 0.035) compared to the 35-44-years-old age group. Levels of low-density lipoprotein cholesterol (LDL-C) were higher (P = 0.009) in H. pylori-infected subjects that were male. LDL-C levels were higher in 55-74-years-old age group (P < 0.05) for H. pylori-infected subjects and 45-64-years-old age group (P < 0.05) for non-infected subjects compared to 35-44-years-old age group. Hp-IgG level positively correlated with PGI, PGII and G-17 (P < 0.001, P < 0.001, P = 0.006), and negatively correlated with PGI/PGII (P < 0.001). Creatinine positively correlated with PGI, PGII and G-17 (P < 0.001, P < 0.001, P < 0.001). Fasting blood glucose (FBG) positively correlated with PGI/PGII and G-17 (P < 0.001, P = 0.037). Age positively correlated with PGII and G-17 (P = 0.005, P = 0.026).

PGII levels increased while PGI/PGII declined with age in a healthy population. H. pylori infection had an effect on raising LDL-C levels to increase the risk of atherosclerosis in males, especially those of elderly age. Age, H. pylori infection, levels of renal function and FBG were associated with levels of pepsinogens and gastrin.

• Helicobacter pylori antibody
• Pepsinogen
• Gastrin
• Gastric ageing

• Adult
• Age Factors
• Aged
• Aged, 80 and over
• Aging/blood
• Asymptomatic Infections/epidemiology
• Atherosclerosis/blood
• Atherosclerosis/epidemiology
• Biomarkers/blood
• China/epidemiology
• Cholesterol, LDL/blood
• Cross-Sectional Studies
• Female
• Gastric Mucosa/microbiology
• Gastric Mucosa/pathology
• Gastrins/blood
• Healthy Volunteers
• Helicobacter Infections/blood
• Helicobacter Infections/epidemiology
• Helicobacter Infections/immunology
• Helicobacter Infections/microbiology
• Helicobacter pylori/immunology
• Helicobacter pylori/isolation & purification
• Humans
• Male
• Middle Aged
• Pepsinogen A/blood
• Pepsinogen C/blood
• Physical Examination
• Prevalence
• Risk Factors
• Sex Factors
• Stomach Diseases/blood
• Stomach Diseases/epidemiology
• Stomach Diseases/microbiology

The aim of this study was to evaluate the effect of the synthetic S-allyl-l-cysteine (SAC) PMK-S005 on gastric acid secretion, inflammation, and antioxidant enzymes in aging rats.

The rats were divided into four groups at 31 weeks of age and were continuously fed a diet containing a vehicle control, PMK-S005 (5 or 10 mg/kg), or lansoprazole (5 mg/kg). Gastric acid secretion and connective tissue thickness of the lamina propria were evaluated at 74 weeks and 2 years of age. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and COX-2 levels were measured by using enzyme-linked immunosorbent assays (ELISAs) or Western blot assays. Levels of antioxidant enzymes, including heme oxyganase 1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1), were also measured.

As the rats aged, gastric acid secretion significantly decreased, and the connective tissue of the lamina propria increased. However, 74-week-old rats in the PMK-S005 group exhibited greater levels of gastric acid secretion than those of the control and lansoprazole groups. The increase of TNF-α, IL-1β, and COX-2 expression in 74-week and 2-year-old control rats were inhibited by PMK-S005. In addition, the decrease in HO-1 and NQO-1 protein expression that occurred with aging was inhibited by PMK-S005 in the 74-week-old rats.

These results suggest that PMK-S005 has therapeutic potential as an antiaging agent to ameliorate age-related gastric acid secretion, inflammation, and oxidative stress in the stomach.

• Aging
• Anti-inflammation
• Antioxidants
• Gastric acid
• s-allyl-L-cysteine

To elucidate the epidemiological characteristics and associated risk factors of perforated peptic ulcer (PPU).

We retrospectively reviewed medical records of patients who were diagnosed with benign PPU from 2010 through 2015 at 6 Hallym university-affiliated hospitals.

A total of 396 patients were identified with postoperative complication rate of 9.1% and mortality rate of 0.8%. Among 174 (43.9%) patients who were examined for Helicobacter pylori (H. pylori) infection, 78 (44.8%) patients were positive for H. pylori infection, 21 (12.1%) were on non-steroidal anti-inflammatory drugs (NSAIDs) therapy, and 80 (46%) patients were neither infected of H. pylori nor treated by any kinds of NSAIDs. Multivariate analysis indicated that older age (OR = 1.09, 95%CI: 1.04-1.16) and comorbidity (OR = 4.11, 95%CI: 1.03-16.48) were risk factors for NSAID-associated PPU compared with non-H. pylori, non-NSAID associated PPU and older age (OR = 1.04, 95%CI: 1.02-1.07) and alcohol consumption (OR = 2.08, 95%CI: 1.05-4.13) were risk factors for non-H. pylori, non-NSAID associated PPU compared with solely H. pylori positive PPU.

Elderly patients with comorbidities are associated with NSAIDs-associated PPU. Non-H. pylori, non-NSAID peptic ulcer is important etiology of PPU and alcohol consumption is associated risk factor.

• Helicobacter pylori
• Non-steroidal anti-inflammatory drugs
• Peptic ulcer perforation
• Stomach ulcer
• Duodenal ulcer

• Adult
• Age Factors
• Aged
• Alcohol Drinking/adverse effects
• Alcohol Drinking/epidemiology
• Anti-Inflammatory Agents, Non-Steroidal/adverse effects
• Comorbidity
• Duodenal Ulcer/diagnosis
• Duodenal Ulcer/epidemiology
• Duodenal Ulcer/mortality
• Duodenal Ulcer/surgery
• Female
• Helicobacter Infections/epidemiology
• Helicobacter Infections/microbiology
• Helicobacter pylori/isolation & purification
• Hospitals, University
• Humans
• Logistic Models
• Male
• Middle Aged
• Multivariate Analysis
• Odds Ratio
• Peptic Ulcer Hemorrhage/diagnosis
• Peptic Ulcer Hemorrhage/epidemiology
• Peptic Ulcer Hemorrhage/mortality
• Peptic Ulcer Hemorrhage/surgery
• Peptic Ulcer Perforation/diagnosis
• Peptic Ulcer Perforation/epidemiology
• Peptic Ulcer Perforation/mortality
• Peptic Ulcer Perforation/surgery
• Postoperative Complications/epidemiology
• Republic of Korea/epidemiology
• Retrospective Studies
• Risk Factors
• Stomach Ulcer/diagnosis
• Stomach Ulcer/epidemiology
• Stomach Ulcer/mortality
• Stomach Ulcer/surgery
• Time Factors
• Treatment Outcome

• Acute kidney injury
• Anti-ulcer drugs
• Endoscopy
• Gastrointestinal bleeding
• Hemodialysis
• Non-steroidal anti-inflammatory drugs

The gastric accommodation reflex is an important mechanism in gastric physiology. However, the aging-associated structural and functional changes in gastric relaxation have not yet been established. Thus, we evaluated the molecular changes of interstitial cell of Cajal (ICC) and neuronal nitric oxide synthase (nNOS) and the function changes in the corpus of F344 rats at different ages (6-, 31-, 74-wk and 2-yr). The proportion of the c-Kit-positive area in the submucosal border (SMB) and myenteric plexus (MP) layer was significantly lower in the older rats, as indicated by immunohistochemistry. The density of the nNOS-positive immunoreactive area also decreased with age in the SMB, circular muscle (CM), and MP. Similarly, the percent of nNOS-positive neuronal cells per total neuronal cells and the proportion of nNOS immunoreactive area of MP also decreased in aged rats. In addition, the mRNA and protein expression of c-Kit and nNOS significantly decreased with age. Expression of stem cell factor (SCF) and the pan-neuronal marker PGP 9.5 mRNA was significantly lower in the older rats than in the younger rats. Barostat studies showed no difference depending on age. Instead, the change of volume was significantly decreased by L-NG63-nitroarginine methyl ester in the 2-yr-old rats compared with the 6-wk-old rats (P = 0.003). Taken together, the quantitative and molecular nNOS changes in the stomach might play a role in the decrease of gastric accommodation with age.

• Chronic obstructive pulmonary disease (COPD)
• Recurrent peptic ulcer bleeding (PUB)
• Steroids

• Adolescent
• Adult
• Aged
• Databases, Factual
• Female
• Glucocorticoids/therapeutic use
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Multivariate Analysis
• Peptic Ulcer Hemorrhage/epidemiology
• Proportional Hazards Models
• Pulmonary Disease, Chronic Obstructive/drug therapy
• Pulmonary Disease, Chronic Obstructive/epidemiology
• Recurrence
• Risk Factors
• Taiwan/epidemiology
• Young Adult

Arsenic trioxide has shown the excellent therapeutic efficiency for acute promyelocytic leukemia. Nowadays, more and more research focuses on the design of the arsenic drugs, especially organic arsenicals, and on the mechanism of the inducing cell death. Here we have synthesized some organic arsenicals with Schiff base structure, which showed a better antitumor activity for three different kinds of cancer cell lines, namely HL-60, SGC 7901 and MCF-7. Compound 2a (2-(((4-(oxoarsanyl)phenyl)imino)methyl)phenol) and 2b (2-methoxy-4-(((4-(oxoarsanyl)phenyl)imino)methyl)phenol) were chosen for further mechanism study due to their best inhibitory activities for HL-60 cells, of which the half inhibitory concentration (IC₅₀) were 0.77 μM and 0.51 μM, respectively. It was illustrated that 2a or 2b primarily induced the elevation of reactive oxygen species, decrease of glutathione level, collapse of mitochondrial membrane potential, release of cytochrome c, activation of Caspase-3 and apoptosis, whereas all of the phenomena can be eliminated by the addition of antioxidants. Therefore, we concluded that compound 2a and 2b can induce the oxidative stress-mediated intrinsic apoptosis in HL-60 cells. Both the simplicity of structure with Schiff base group and the better anticancer efficiency demonstrate that organic arsenicals are worthy of further exploration as a class of potent antitumor drugs.

• EGR1
• NF-κB
• apoptosis
• follicular atresia
• granulosa cell
• ovarian aging

• aging gastric mucosa
• angiogenesis
• growth factors
• healing
• injury
• serum response factor

• Aging/pathology
• Aging/physiology
• Bone Marrow Cells
• Cyclooxygenase 2/physiology
• Early Growth Response Protein 1/metabolism
• Endothelial Progenitor Cells/physiology
• Gastric Mucosa/blood supply
• Gastric Mucosa/pathology
• Gastric Mucosa/physiology
• Humans
• Karyopherins/physiology
• Neovascularization, Pathologic/genetics
• Nitric Oxide/physiology
• PTEN Phosphohydrolase/metabolism
• Prostaglandins/physiology
• Regeneration/genetics
• Regeneration/physiology
• Serum Response Factor/physiology
• Stomach Ulcer/pathology
• Stomach Ulcer/physiopathology
• Vascular Endothelial Growth Factor A/metabolism
• Vascular Endothelial Growth Factor A/physiology

This review updates the current views on aging gastric mucosa and the mechanisms of its increased susceptibility to injury. Experimental and clinical studies indicate that gastric mucosa of aging individuals-“aging gastropathy”-has prominent structural and functional abnormalities vs young gastric mucosa. Some of these abnormalities include a partial atrophy of gastric glands, impaired mucosal defense (reduced bicarbonate and prostaglandin generation, decreased sensory innervation), increased susceptibility to injury by a variety of damaging agents such as ethanol, aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), impaired healing of injury and reduced therapeutic efficacy of ulcer-healing drugs. Detailed analysis of the above changes indicates that the following events occur in aging gastric mucosa: reduced mucosal blood flow and impaired oxygen delivery cause hypoxia, which leads to activation of the early growth response-1 (egr-1) transcription factor. Activation of egr-1, in turn, upregulates the dual specificity phosphatase, phosphatase and tensin homologue deleted on chromosome ten (PTEN) resulting in activation of pro-apoptotic caspase-3 and caspase-9 and reduced expression of the anti-apoptosis protein, survivin. The imbalance between pro- and anti-apoptosis mediators results in increased apoptosis and increased susceptibility to injury. This paradigm has human relevance since increased expression of PTEN and reduced expression of survivin were demonstrated in gastric mucosa of aging individuals. Other potential mechanisms operating in aging gastric mucosa include reduced telomerase activity, increase in replicative cellular senescence, and reduced expression of vascular endothelial growth factor and importin-α-a nuclear transport protein essential for transport of transcription factors to nucleus. Aging gastropathy is an important and clinically relevant issue because of: (1) an aging world population due to prolonged life span; (2) older patients have much greater risk of gastroduodenal ulcers and gastrointestinal complications (e.g., NSAIDs-induced gastric injury) than younger patients; and (3) increased susceptibility of aging gastric mucosa to injury can be potentially reduced or reversed pharmacologically.

• Aging gastric mucosa
• Injury
• Phosphatase and tensin homologue deleted on chromosome ten-PTEN
• Survivin
• Apoptosis
• Hypoxia

• Age Factors
• Aging/metabolism
• Aging/pathology
• Animals
• Gastric Mucosa/drug effects
• Gastric Mucosa/metabolism
• Gastric Mucosa/pathology
• Gastrointestinal Agents/therapeutic use
• Humans
• Risk Factors
• Signal Transduction
• Stomach Diseases/drug therapy
• Stomach Diseases/etiology
• Stomach Diseases/metabolism
• Stomach Diseases/pathology
• Treatment Outcome

• aging
• colon
• inbred F344
• interstitial cells of Cajal
• neuronal nitric oxide synthase
• rats

• aging
• epithelial barrier function
• estradiol
• gut mucosa
• hormones
• menopause
• microbial translocation
• mucosal injury

• Adult
• Aged
• Comorbidity
• Diabetic Nephropathies/epidemiology
• Female
• Hospitalization/statistics & numerical data
• Humans
• Kidney Failure, Chronic/epidemiology
• Kidney Failure, Chronic/therapy
• Male
• Middle Aged
• Peptic Ulcer Hemorrhage/epidemiology
• Peptic Ulcer Hemorrhage/prevention & control
• Peritoneal Dialysis
• Proportional Hazards Models
• Renal Dialysis
• Renal Insufficiency, Chronic/epidemiology
• Risk Factors
• Taiwan/epidemiology

Cochinchina momordica seed extract (SK-MS10) has a gastric protective effect. We aimed to assess the effect of SK-MS10 on gastric acid secretion with morphologic changes in the aged rat.

Acid secretions were evaluated in the male F344 rats of four different ages (6-, 31-, 74-week, and 2-year). The 31-week-old rats were divided to three groups and continuously administered chow containing vehicle, SK-MS10 and lansoprazole, respectively. At the age of 74 weeks and 2 years, basal and stimulated acid was measured and the expression of mRNA and protein of H⁺-K⁺-ATPase were determined. The area of connective tissue of lamina propria was measured.

Basal and stimulated gastric acid significantly decreased and connective tissue of lamina propria increased with age. The expression of mRNA and protein of H⁺-K⁺-ATPase significantly decreased with age. However, 74-week-old rats in the SK-MS10 group had higher stimulated gastric acid secretion than those in the vehicle and lansoprazole groups. In 2-year-old rats of SK-MS10 group, there was no increase of connective tissue.

As SK-MS10 kept the capacity of acid secretion as well as connective tissue area to comparable to young rats, it might valuable to perform further research regarding mechanism of SK-MS10 as an antiaging agent in the stomach.

• Aging
• Cochinchina momordica seed
• Connective tissue
• Gastric acid
• Hydrogen-potassium-activated ATPase

• VEGF
• aging
• angiogenesis
• endostatin
• gastric mucosa
• mucosal healing

• Age Factors
• Aging/metabolism
• Alcohol-Induced Disorders/etiology
• Alcohol-Induced Disorders/genetics
• Alcohol-Induced Disorders/metabolism
• Alcohol-Induced Disorders/physiopathology
• Animals
• Disease Models, Animal
• Down-Regulation
• Endostatins/metabolism
• Ethanol
• Gastric Mucosa/blood supply
• Gastric Mucosa/injuries
• Gastric Mucosa/metabolism
• Male
• Matrix Metalloproteinase 9/metabolism
• Neovascularization, Physiologic
• RNA, Messenger/metabolism
• Rats
• Rats, Inbred F344
• Re-Epithelialization
• Time Factors
• Up-Regulation
• Vascular Endothelial Growth Factor A/genetics
• Vascular Endothelial Growth Factor A/metabolism

Although the effects of sanguinarine, a benzophenanthridine alkaloid, on the inhibition of some kinds of cancer cell growth have been established, the underlying mechanisms are not completely understood. This study investigated possible mechanisms by which sanguinarine exerts its anticancer action in cultured human bladder cancer cell lines (T24, EJ, and 5637). Sanguinarine treatment resulted in concentration-response growth inhibition of the bladder cancer cells by inducing apoptosis. Sanguinarine-induced apoptosis was correlated with the up-regulation of Bax, the down-regulation of Bid and XIAP, the activation of caspases (-3, -8, and -9), and the generation of increased reactive oxygen species (ROS). The ROS scavenger N-acetyl cysteine (NAC) completely reversed the sanguinarine-triggered apoptotic events. In addition, sanguinarine effectively increased the activation of the c-Jun N-terminal kinase (JNK) and the expression of the early growth response gene-1 (Egr-1), which was recovered by pretreatment with NAC. Furthermore, knockdown of Egr-1 expression by small interfering RNA attenuated sanguinarine-induced apoptosis, but not the JNK inhibitor, indicating that the interception of ROS generation blocked the sanguinarine-induced apoptotic effects via deregulation of the expression of Egr-1 proteins. Taken together, the data provide evidence that sanguinarine is a potent anticancer agent, which inhibits the growth of bladder cancer cells and induces their apoptosis through the generation of free radicals.

• Antineoplastic Agents/pharmacology
• Apoptosis/drug effects
• Apoptosis/genetics
• BH3 Interacting Domain Death Agonist Protein/genetics
• BH3 Interacting Domain Death Agonist Protein/metabolism
• Benzophenanthridines/pharmacology
• Caspases/genetics
• Caspases/metabolism
• Cell Line, Tumor
• Cell Survival/drug effects
• Cell Survival/genetics
• Down-Regulation/drug effects
• Early Growth Response Protein 1/genetics
• Early Growth Response Protein 1/metabolism
• Humans
• Isoquinolines/pharmacology
• JNK Mitogen-Activated Protein Kinases/genetics
• JNK Mitogen-Activated Protein Kinases/metabolism
• Reactive Oxygen Species/metabolism
• Up-Regulation/drug effects
• Up-Regulation/genetics
• Urinary Bladder Neoplasms/drug therapy
• Urinary Bladder Neoplasms/genetics
• Urinary Bladder Neoplasms/metabolism
• X-Linked Inhibitor of Apoptosis Protein/genetics
• X-Linked Inhibitor of Apoptosis Protein/metabolism
• bcl-2-Associated X Protein/genetics
• bcl-2-Associated X Protein/metabolism

• Aging/physiology
• Animals
• Anti-Inflammatory Agents, Non-Steroidal/adverse effects
• Indomethacin/adverse effects
• Male
• Stomach/drug effects
• Stomach/physiology

• Aged
• Aging/physiology
• Colon/cytology
• Colon/physiology
• Constipation/physiopathology
• Deglutition Disorders/physiopathology
• Enteric Nervous System/physiology
• Gastroesophageal Reflux/physiopathology
• Gastrointestinal Tract/physiology
• Humans
• Interstitial Cells of Cajal/physiology
• Intestines/physiology
• Neurons/physiology
• Parkinson Disease/complications
• Parkinson Disease/physiopathology
• Postprandial Period
• Sensation/physiology
• Stomach/cytology
• Stomach/physiology
• Stomach Diseases/complications
• Stomach Diseases/physiopathology

• Aging/physiology
• Animals
• Anti-Inflammatory Agents, Non-Steroidal/adverse effects
• Indomethacin/adverse effects
• Male
• Stomach/drug effects
• Stomach/physiology

• Aging
• digestive system
• ethanol
• oxidative stress
• rats

Aging gastric mucosa is known to have decreased mucosal defenses and increased susceptibility to injury by nonsteroidal anti-inflammatory drugs. Depending on the type of nonsteroidal anti-inflammatory drug (NSAID), the underlying mechanisms and the extent of damage to the stomach or intestine may differ. This study was performed to evaluate the acute gastric damage caused by different doses of indomethacin, diclofenac and aspirin in rats of various ages.

For the acute models, indomethacin (10, 20 or 40 mg/kg), diclofenac (40 or 80 mg/kg) or aspirin (100 mg/kg) was given to 7- and 25-week-old and 1-year-old Sprague-Dawley rats by intragastric gavage. The gross ulcer index, damage area as assessed by imaging, histological index, myeloperoxidase (MPO) activity, and cytosolic phospholipase A₂ (cPLA₂) levels were measured after 24 hours.

The gross ulcer index and damage area increased with age in the presence of three NSAIDs (p<0.05). The increases in MPO levels induced by diclofenac and aspirin were significantly higher in 1-year-old than 7-week-old rats (p<0.05). cPLA₂ expression induced by indomethacin (10 and 40 mg/kg) was greater in the 1-year-old rats, compared with 7-week-old rats (p<0.05).

NSAID-induced acute gastric damage increased in a dose- and age-dependent manner.

• Aging
• Aspirin
• Gastric damage
• Nonsteroidal anti-inflammatory drugs