Mucoprotective agents, such as eupatilin, are often prescribed to prevent gastrointestinal (GI) bleeding in addition to an acid suppressant despite the absence of a large-scale study. We evaluated ...the additional effect of eupatilin on the prevention of GI bleeding in both the upper and lower GI tract in concomitant aspirin and acid suppressant users using the nationwide database of national claims data from the Korean National Health Insurance Service (NHIS).
An aspirin cohort was constructed using the NHIS claims data from 2013 to 2020. Patients who manifested with hematemesis, melena, or hematochezia were considered to have GI bleeding. A Cox proportional hazards regression model was used to determine the risk factors for GI bleeding associated with the concomitant use of GI drugs and other covariates among aspirin users.
Overall, a total of 432,208 aspirin users were included. The concurrent use of an acid suppressant and eupatilin (hazard ratio HR = 0.85, p = 0.016, vs. acid suppressant only) was a statistically significant preventive factor for GI bleeding. Moreover, a more than 3-month duration (HR = 0.88, p = 0.030) of acid suppressant and eupatilin prescription (vs. acid suppressant only) was a statistically significant preventive factor for GI bleeding.
Eupatilin administration for ≥ 3 months showed additional preventive effect on GI bleeding in concomitant aspirin and acid suppressant users. Thus, cotreatment with eupatilin with a duration of 3 months or longer is recommended for reducing GI bleeding among aspirin plus acid suppressant users.
Long-term use of acid suppressants such as proton pump inhibitors (PPIs) and histamine 2 receptor antagonist (H2RA) has been associated with the risk of osteoporotic fracture. Acid suppressants and ...muco-protective agents (MPAs) are often used together as anti-ulcer agents. We evaluated the association between the risk of osteoporotic fracture and the combined use of these anti-peptic agents.
A population-based case-control study was conducted by analyzing the Korean National Health Insurance Data from 2014 to 2020. Patients who had been prescribed anti-peptic agents, such as PPI, H2RA, or MPA, were included. Considering the incidence of osteoporotic fractures, the case group (n = 14,704) and control group (n = 58,816) were classified by 1:4 matching based on age and sex.
The use of all types of anti-peptic agents was associated with an increased risk of osteoporotic fractures (PPI: hazard osteoratio HR, 1.31; H2RA: HR, 1.44; and MPA: HR, 1.33; all p < 0.001). Compared to PPI alone, the combined use of "PPI and H2RA" (HR, 1.58; p = 0.010) as well as "PPI, H2RA, and MPA" (HR, 1.71; p = 0.001) was associated with an increased risk of osteoporotic fracture. However, compared with PPI alone, "MPA and PPI or H2RA" was not associated with an increased risk of osteoporotic fracture.
This study found that the combined use of "PPI and H2RA" was associated with a higher risk of osteoporotic fractures. In cases where deemed necessary, the physicians may initially consider prescribing the combination use of MPA.
We investigated high-field terahertz (THz) responses and the nonlinear conductivities of n- and p-type GaAs thin films in the THz region. As the THz pulse intensity was increased to 59 μJ/cm2, the ...THz transmission of the n-type GaAs thin film was significantly increased, more than that of the p-type film. This result is correlated with the conductivity of the electronic system caused by scattering processes. Intervalley scattering was dominant in n-type GaAs, whereas hot–cold hole interactions and intervalence band transitions were the main factors reducing the conductivity in p-type GaAs. In addition, we extracted the frequency-domain conductivity of the n- and p-type GaAs thin films and used the Drude–Smith model to explain non-Drude-like behavior due to high-field excitation.
•High-field THz is useful to study carrier dynamics in intraband of semiconductor.•High-field carrier dynamics of n- and p-type GaAs thin films is investigated.•The dynamics of hot electrons and holes can be explained by scattering mechanisms.
Nuclear factor of activated T cells (NFAT5) is a well-known transcription factor that regulates the expression of genes involved in osmotic stress. However, the role of NFAT5 in inflammatory pain ...remains unknown. Here, we studied the function of NFAT5 in inflammatory pain using NFAT5-heterozygous (Het) mice. To study inflammatory pain, we injected 10 µL of 2% formalin into the right hind paws of mice and monitored pain behaviors, such as licking, lifting, and flinching, for 60 min. After the first 15 min (phase I), there were no significant differences in pain behaviors between wild-type (WT) and NFAT5-Het mice. However, from 15-60 min (phase II), NFAT5-Het mice displayed significantly fewer pain behaviors compared to WT mice. Further, the expression levels of inflammatory-pain-related factors, including c-Fos, phosphorylated extracellular signal-regulated kinase (p-ERK), and phosphorylated
-methyl-D-aspartate receptor subunit 2B (p-NR2B), were significantly elevated in the spinal dorsal neurons of formalin-treated WT mice but was not elevated in NFAT5-Het mice. Similarly, c-Fos, p-ERK, and p-NR2B levels were significantly higher in glutamate-treated PC12 neuronal cells but were not affected by Nfat5 silencing in glutamate-treated PC12 cells. Altogether, our findings suggest that NFAT5 deficiency may mitigate formalin-induced inflammatory pain by upregulating mammalian target of rapamycin (mTOR) expression and downregulating its downstream factors in spinal dorsal neurons. Therefore, NFAT5 is a potential therapeutic target for the treatment of inflammatory pain.
Crohn's disease is associated with altered body composition, such as low muscle mass, which can affect clinical outcomes. However, there are few studies regarding the effect of sarcopenia on ...prognosis of Crohn's disease. In this study, we evaluated the body composition at the initial diagnosis of Crohn's disease and analyzed the clinical meaning of sarcopenia.
We conducted a retrospective review of medical records of patients who were diagnosed as Crohn's disease and underwent computed tomography within 3 months after diagnosis. Sarcopenia was defined as an L3 skeletal muscle index (SMI) of < 49 cm2/m2 for men and < 31 cm2/m2 for women. Outcomes such as need for hospitalization, surgery, use of steroids, immunomodulators and biologics were analyzed.
A total of 79 patients (male, 73.4%; mean age, 29.9 years) were included and 40 patients (51%) were diagnosed as sarcopenia. C-reactive protein (CRP) level was correlated with sarcopenia (P= 0.044). Erythrocyte sedimentation rate (ESR) showed a tendency to decrease inversely with SMI (r = -0.320, P= 0.008) and hemoglobin and albumin tended to increase in proportion to SMI (hemoglobin: r = 0.271, P= 0.016 and albumin: r = 0.350, P= 0.002). However, there was no statistically significance in time-to-first-event analysis in aspects of sarcopenia.
Approximately 50% of patients with newly diagnosed as Crohn's disease had sarcopenia. CRP levels were higher in the sarcopenia group and SMI correlated with ESR, hemoglobin, and albumin. However, none of prognostic values were demonstrated.
Purpose
Corneal lymphangiogenesis is known to play an important role in the pathogenesis of dry eye disease (DED). And the low‐grade inflammation associated with DED is known as an inducer of ...lymphangiogenesis without accompanying hemangiogenesis. This study is to evaluate the expression of known factors related with lymph‐/hem‐angiogenesis in the cornea and conjunctiva in the murine DED model.
Methods
DED was induced by housing 8‐week‐old female C57BL/6 mice in a controlled environmental chamber that allowed for the relative low humidity (< 25%), continuous regulation of airflow, and temperature (21 to 23ºC) for 3 weeks. Corneal fluorescein score was evaluated to confirm the efficacy of DED induction. Fluorescence images from the corneal whole mounts after immunohistochemical stain for lymphatic vessel endothelial hyaluronan receptor (lyve)‐1 were used for analysis. The expression of m‐RNA of the VEGF‐A, VEGF‐C, VEGF‐D (Figf), Angiopoietin‐2 (Angpt2), and VEGFR3 (flt4) were evaluated by real‐time PCR in the cornea and conjunctiva.
Results
Percentage of the area of lyve‐1+ area of the whole corneal area increased significantly in DED group (5.55 ± 1.45% in DED group versus 3.88 ± 0.74% in control, P=0.015, Mann‐Whitney U test). The expression of Angiopoietin‐2 increased significantly in the cornea (1.38 folds, 95% confidence interval CI: 1.03~1.84) and in the conjunctiva (1.36 folds, 95% CI: 1.04~1.77). And the expression of VEGF‐C increased significantly only in the conjunctiva (1.64 folds, 95% CI: 1.21~2.21). However, the expression of VEGF‐D significantly decreased both in the cornea (0.40 folds, 95% CI: 0.32~0.49) and in the conjunctiva (0.44 folds, 95% CI: 0.37~0.52).
Conclusions
Unique lymphangiogenesis without hemangiogenesis in DED may be associated with increased expression of Angiopoietin‐2 and VEGF‐C and decreased expression of VEGF‐D. However, the exact interaction of these key factors should be studied further.
This study aimed to complement previous studies on the risk of herpes zoster in the asthmatic adult population.
The Korean Health Insurance Review and Assessment Service-National Sample Cohort ...(HIRA-NSC) from 2002 through 2013 was used. A total of 64,152 participants with herpes zoster were matched for age, sex, income, region of residence, hypertension, diabetes, and dyslipidemia with 239,780 participants who were included as a control group. In both the herpes zoster and control groups, previous history of asthma were investigated. The crude and adjusted odds ratios (ORs) and 95% confidence intervals (CI) of asthma for herpes zoster were analyzed using unconditional logistic regression analysis. Subgroup analyses were conducted according to age and sex.
Approximately 16.2% (9728/59,945) and 12.8% (30,752/239,780) of participants in the herpes zoster and control groups, respectively, had a previous history of asthma (P < 0.001). The herpes zoster group demonstrated a 1.32-times higher odds of asthma than the control group (95% CI 1.28-1.35, P < 0.001). The increased odds of asthma in the herpes zoster group persisted in all the age and sex subgroups.
The odds for asthma were higher in the herpes zoster group.
Clusterin is a secretory glycoprotein, which is highly up-regulated in a variety of normal and injury tissues undergoing apoptosis including infarct region of the myocardium. Here, we report that ...clusterin protects H9c2 cardiomyocytes from H2O2-induced apoptosis by triggering the activation of Akt and GSK-3β. Treatment with H2O2 induces apoptosis of H9c2 cells by promoting caspase cleavage and cytochrome c release from mitochondria. However, co-treatment with clusterin reverses the induction of apoptotic signaling by H2O2, thereby recovers cell viability. The protective effect of clusterin on H2O2-induced apoptosis is impaired by PI3K inhibitor LY294002, which effectively suppresses clusterin-induced activation of Akt and GSK-3β. In addition, the protective effect of clusterin is independent on its receptor megalin, because inhibition of megalin has no effect on clusterin-mediated Akt/GSK-3β phosphoylation and H9c2 cell viability. Collectively, these results suggest that clusterin has a role protecting cardiomyocytes from oxidative stress and the Akt/GSK-3β signaling mediates anti-apoptotic effect of clusterin.
Streptococcus pneumoniae causes the most severe form of the bacterial meningitis which is the major cause of bacterial meningitis. Virulence factors produced by S. pneumoniae have been known to ...contribute significantly to the disease process. ClpP protease (ClpP) which is essential for virulence and survival under stress conditions in S. pneumoniae was examined for the ability to induce apoptosis and the mechanism of the induction of apoptosis in human neuron-like cells, SK-N-SH neuroblastoma cells. ClpP inhibited cell growth and induced apoptosis in SK-N-SH cells. Treatment with ClpP resulted in hypodiploid DNA contents, increased Bax/Bcl-2 ratio and induction of reactive oxygen species (ROS) production. The release of cytochrome c from mitochondria into the cytosol, which is an initiator of the activation of caspase cascades, was not observed in ClpP-treated cells. In addition, pretreatment with Z-Val–Ala–Asp–fluoromethylketone (Z-VAD-fmk), a broad spectrum caspase inhibitor, could not rescue apoptotic cells from ClpP toxicity. Coincidently, caspase-3 and -8 activation and cleavage of PARP were not detected. Moreover, caspase independent apoptosis-inducing factor (AIF) was released from mitochondria and translocated to the nucleus in response to ClpP. We also found that ClpP treatment resulted in the increase of p53 activity and cytoplasmic p53 levels were increased by ClpP, suggesting that functional activation of p53 is intact despite increased cytoplasmic accumulation. Taken together, these data suggest that ClpP contributes to neuronal damage in meningitis and provide further insight into the mechanisms underlying action of pneumococcal virulence factors during bacterial pathogenesis.
•We examined the mechanism of neuron-like cell cytotoxicity induced by Streptococcus pneumoniae ClpP.•ClpP induced a caspase-independent apoptotic pathway through mitochondria-mediated AIF translocation into the nucleus.•The apoptosis is associated with functional activation of p53 which occurs despite increased cytoplasmic accumulation.
Capsule endoscopy (CE) has shown that low-dose aspirin occasionally causes small bowel (SB) bleeding. We herein evaluated the protective effects of mucoprotective agents (MPAs) on SB bleeding in ...aspirin users using the nationwide database of claims data from the National Health Insurance Service (NHIS).
As CE is an insured procedure, we constructed an aspirin-SB cohort using NHIS claims data, with a maximum follow- up period of 24 months. Patients with anemia, melena, or hematochezia that occurred within 4 weeks before and after performing CE were suspected to have SB bleeding. A Cox proportional hazards regression model was used to determine the risk factors for SB bleeding. Subgroup analyses were conducted among patients who used acid suppressants, such as proton pump inhibitors (PPIs) and histamine-2 receptor antagonists.
A total of 15,542 aspirin users were included. Anticoagulant use (hazard ratio HR, 3.22), high Charlson comorbidity index score (≥ 2) (HR, 3.54), and PPI use (HR, 2.85) were significantly associated with SB bleeding, whereas eupatilin use (HR, 0.35) was a preventive factor. SB bleeding occurred more frequently in concurrent users of acid suppressants than in nonusers (1.3% vs. 0.5%). Subgroup analysis revealed that eupatilin significantly reduced the risk of SB bleeding in aspirin users with concurrent use of acid suppressants (HR, 0.23 vs. 2.55).
Eupatilin was associated with a reduced risk of SB bleeding in both aspirin users and those with concomitant use of acid suppressants. Eupatilin use should be considered for aspirin users, especially for those concomitantly taking acid suppressants.
PDF
