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IL-17A and IL-17F are both involved in the pathogenesis of neutrophilic inflammation observed in COPD and severe asthma. To explore this, mice deficient in both Il17a and Il17f and wild type (WT) mice were exposed to cigarette smoke or environmental air for 5 to 28 days and changes in inflammatory cells in bronchoalveolar lavage (BAL) fluid were determined. We also measured the mRNA expression of keratinocyte derived chemokine (Kc), macrophage inflammatory protein-2 (Mip2), granulocyte–macrophage colony stimulating factor (Gmcsf) and matrix metalloproteinase-9 (Mmp9 ) in lung tissue after 8 days, and lung morphometric changes after 24 weeks of exposure to cigarette smoke compared to air-exposed control animals. Macrophage counts in BAL fluid initially peaked at day 8 and again on day 28, while neutrophil counts peaked between day 8 and 12 in WT mice. Mice dual deficient with Il17a and 1l17f showed similar kinetics with macrophages and neutrophils, but cell numbers at day 8 and mRNA expression of Kc, Gmcsf and Mmp9 were significantly reduced. Furthermore, airspaces in WT mice became larger after cigarette smoke exposure for 24 weeks, whereas this was not seen dual Il17a and 1l17f deficient mice. Combined Il17a and Il17f deficiency resulted in significant attenuation of neutrophilic inflammatory response and protection against structural lung changes after long term cigarette smoke exposure compared with WT mice. Dual IL-17A/F signalling plays an important role in pro-inflammatory responses associated with histological changes induced by cigarette smoke exposure.

Rationale Severe eosinophilic asthma is characterized by airway eosinophilia and corticosteroid‐resistance, commonly overlapping with type 2 inflammation. It has been reported that chemokine (C‐C motif) ligand 5 (CCL5) is involved in the exacerbation of asthma by RNA virus infections. Indeed, treatment with a virus‐associated ligand and a T helper type 2 cell (Th2) cytokine can synergistically stimulate CCL5 production in bronchial epithelial cells. We aimed to evaluate the mechanisms underlying CCL5 production in this in vitro model and to assess the potential of Janus kinase 1 (JAK1) as a novel therapeutic target via the use of ruxolitinib. Methods We stimulated primary normal human bronchial epithelial (NHBE) cells and BEAS‐2B cells with poly(I:C) along with interleukin‐13 (IL‐13) or IL‐4, and assessed CCL5 production. We also evaluated the signals involved in virus‐ and Th2‐cytokine‐induced CCL5 production and explored a therapeutic agent that attenuates the CCL5 production. Results Poly(I:C) stimulated NHBE and BEAS‐2B cells to produce CCL5. Poly(I:C) and IL‐13 increased CCL5 production. Poly(I:C)‐induced CCL5 production occurred via the TLR3–IRF3 and IFNAR/JAK1–phosphoinositide 3‐kinase (PI3K) pathways, but not the IFNAR/JAK1–STATs pathway. In addition, IL‐13 did not augment poly(I:C)‐induced CCL5 production via the canonical IL‐13R/IL‐4R/JAK1–STAT6 pathway but likely via subsequent TLR3‐IRF3‐IFNAR/JAK1‐PI3K pathways. JAK1 was identified to be a potential therapeutic target for severe eosinophilic asthma. The JAK1/2 inhibitor, ruxolitinib, was demonstrated to more effectively decrease CCL5 production in BEAS‐2B cells than fluticasone propionate. Conclusion We have demonstrated that JAK1 is a possible therapeutic target for severe corticosteroid‐resistant asthma with airway eosinophilia and persistent Th2‐type inflammation, and that ruxolitinib has potential as an alternative pharmacotherapy., First, we focused on whether treatment with a virus‐associated ligand and type‐2 cytokine can synergistically stimulate CCL5 production in bronchial epithelial cells, in which we confirmed the synergistic effect. Second, we evaluated the mechanisms underlying the synergistical CCL5 production and found that the JAK1 is a novel therapeutic target for severe eosinophilic asthma. Finally, we have demonstrated that ruxolitinib is a potential therapeutic agent for severe corticosteroid‐resistant asthma with airway eosinophilia and persistent Th2‐type inflammation.

Background and purpose of the study: Pseudomonas aeruginosa commonly colonizes the airway of patients with chronic obstructive pulmonary disease (COPD) and exacerbates their symptoms. P. ae...

Neutrophilic airway inflammation plays a central role in chronic obstructive pulmonary disease (COPD). CXC chemokine ligand (CXCL)1 is a neutrophil chemokine involved in the pathogenesis of COPD. However, its clinical significance in COPD patients is poorly understood.To assess the production of CXCL1 by bronchial epithelial cells in response to lipopolysaccharide (LPS) and tumor necrosis factor (TNF)α.We measured sputum CXCL1 and CXCL8 levels in patients with COPD, asthma, and asthma-COPD overlap (ACO), and compared them to those of patients with interstitial pneumonia (IP). Using primary human bronchial epithelial cells and BEAS-2B cells, CXCL1 protein release and mRNA expression were measured after LPS or TNFα stimulation. We evaluated signal transduction mechanisms for CXCL1 production using nuclear factor-κ B (NF-kB) and mitogen-activated protein kinase (MAPK) inhibitors, and examined the effects of anti-inflammatory agents on CXCL1 production in BEAS-2B cells.Sputum CXCL1 levels in COPD and ACO patients were higher than in IP patients, whereas sputum CXCL8 levels were not. Sputum CXCL1 levels were not affected by inhaled corticosteroid usage, whereas sputum CXCL8 levels tended to be affected. LPS and TNFα stimulated CXCL1 production and mRNA expression in bronchial epithelial cells. NF-kB and MAPK p38 were involved in LPS-induced CXCL1 production. Therapeutic anti-inflammatory agents minimally attenuated CXCL1 production and considerably inhibited CXCL8 production in BEAS-2B cells.Sputum CXCL1 levels is a potentially better diagnostic marker for COPD than sputum CXCL8 levels, which is explained by that CXCL1 production in bronchial epithelial cells is less affected by therapeutic anti-inflammatory agents than CXCL8 production.

Background: Neutrophilic airway inflammation has been suggested to play a crucial role in chronic inflammatory airway diseases such as asthma and COPD, and airway epithelial cells are involved in their regulation. growth-related gene α (GROα) has been reported to be expressed in the sputum of COPD patients. However, the role and clinical significance of GROα are poorly understood. Aims: We investigated the regulation of GROα production in human bronchial epithelial cells in vitro . Methods: We stimulated human bronchial epithelial cell line BEAS-2B with exogenous agents such as LPS and house dust mite (HDM) derp1 as well as TNFα. GROα production and expression were determined by ELISA and qRT-PCR. Furthermore, we evaluated the inhibitory effect of therapeutic agents associated with its regulation. Results: LPS and TNFα showed significant concentration-dependent effects on GROα expression and production in human BEAS-2B cells, and fluticasone (FP) suppressed this production. HDM derp1 also showed a significant concentration-dependent effect on GROα production, but the effect was less potent compared with those by LPS and TNFα. Conclusions: LPS and TNFα showed a potent stimulatory effect on GROα expression and production in human BEAS-2B cells. FP suppressed this production, implying that GROα is involved in chronic inflammatory airway diseases where FP show therapeutic effects.

Background: Bronchial asthma (BA) is characterized by chronic airway inflammation. Although a majority of BA patients are controlled by standard treatment containing inhaled corticosteroids, some patients suffer acute exacerbation. Reactive oxygen species (ROS) such as hydrogen peroxide are generated by inflammatory cells which are involved in the pathogenesis of BA. However, the role of ROS levels as a biomarker in BA patients is not yet clear. Aims and objectives: We tried to determine the role of ROS levels as a biomarker in the clinical settings of BA. Methods: We enrolled patients with BA from 2013 through 2015 at the Department of Respiratory Medicine, Kyorin University Hospital. Pulmonary function tests, FeNO, serum reactive oxygen metabolite (ROM) levels and serum IL-6 and IL-8 were measured. Serum ROM levels were measured by d-ROMs test. Results: A total of 110 patients with BA were recruited. Serum ROM levels correlated with WBC (rs = 0.273, P = 0.004), neutrophil (rs = 0.235, P = 0.014), CRP (rs = 0.403, P P 1 (rs = -0.306, P = 0.001, rs = - 0.240, P = 0.012, respectively). Serum ROM levels were significantly higher in patients with severe exacerbation group than in patients without exacerbation group ( P = 0.025). Receiver-operating characteristics analysis showed that ROM levels associated with the occurrence of severe exacerbation (area under the curve: 0.699, 95% CI: 0.597 to 0.801, P = 0.025). Conclusions: ROM levels might reflect neutrophilic inflammation, and correlated with airway obstruction. This biomarker may be useful for predicting severe exacerbations of BA.

BACKGROUND: The viral infection is one of the main causes of bronchial asthma attack.It has been reported that the serum CCL5 levels during attack increase as compared to stable periods. The airway epithelial cell has a potential to release various chemical mediators as well as a barrier role from the outside world. CCL5, one of chemical mediators, is known to have strong chemotactic activity for eosinophils, and thus might be involved in asthma exacerbation. AIMS: To determine regulation of CCL5 production from the airway epithelial cell at the time of the viral infection. METHODS: BEAS-2B cells were stimulated by poly I:C. CCL5 mRNA levels were evaluated using RT-PCR method and concentrations of CCL5 in the supernatant were measured by ELISA method. A variety of endogenous agents such as IL-4, IL-13, IL-33, IL-37 and Clara cell 16 kD protein (CC16) were co-stimulated to investigate the roles of these factors in endogenouscontrol of CCL5 production. RESULTS: CCL5 production and mRNA levels were significantly increased by poly I:C stimulation (∼50-fold increase and∼80-fold increase, p DISCUSSION: Airway epithelial cells act as potent sources of CCL5 upon viral infection, and IL-13 was suggested to play a role in airway inflammatory exacerbation in coordinated fashion during viral infection. Therefore, targeting IL-13 might be useful for the management of the asthma exacerbation at the time of the viral infection.

Background and Purpose Bronchial asthma (BA) is a chronic airway disease characterized by airway hyperresponsiveness and remodeling, which are intimately linked to chronic airway inflammation. Reactive oxygen species (ROS) such as hydrogen peroxide are generated by inflammatory cells that are involved in the pathogenesis of BA. However, the role of ROS in the management of BA patients is not yet clear. We attempted to determine the role of ROS as a biomarker in the clinical setting of BA. Subjects and Methods We enrolled patients with BA from 2013 through 2015 and studied the degrees of asthma control, anti-asthma treatment, pulmonary function test results, fractional exhaled nitric oxide (FeNO), serum reactive oxygen metabolite (ROM) levels, and serum levels of interleukin (IL)-6 and IL-8. Results We recruited 110 patients with BA. Serum ROM levels correlated with white blood cell (WBC) count (rs = 0.273, p = 0.004), neutrophil count (rs = 0.235, p = 0.014), CRP (rs = 0.403, p < 0.001), and IL-6 (rs = 0.339, p < 0.001). Serum ROM levels and IL-8 and CRP levels negatively correlated with %FEV1 (rs = -0.240, p = 0.012, rs = -0.362, p < 0.001, rs = -0.197, p = 0.039, respectively). Serum ROM levels were significantly higher in patients who experienced severe exacerbation within 3 months than in patients who did not (339 [302–381] vs. 376 [352–414] CARR U, p < 0.025). Receiver-operating characteristics analysis showed that ROM levels correlated significantly with the occurrence of severe exacerbation (area under the curve: 0.699, 95% CI: 0.597–0.801, p = 0.025). Conclusions Serum levels of ROM were significantly associated with the degrees of airway obstruction, WBC counts, neutrophil counts, IL-6, and severe exacerbations. This biomarker may be useful in predicting severe exacerbations of BA.

Interleukin (IL)-10 is an anti-inflammatory cytokine, but its role in cigarette smoke (CS)-induced inflammation and chronic obstructive pulmonary disease (COPD) has not been fully elucidated. The purpose of this study was to investigate the effect of IL-10 deficiency on CS-induced pulmonary inflammation in mice in vivo and in vitro.IL-10-deficient and wild-type control mice with a C57BL6/J genetic background were exposed to CS, and inflammatory cells in bronchoalveolar lavage fluid (BALF) and mRNA of cytokines in lung were evaluated with enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR).During 12 days of daily CS exposure to wild-type mice, neutrophil counts in BAL fluid and tumor necrosis factor (TNF)-α mRNA expression were increased, peaked at day 8, and then declined on day 12 when the level of IL-10 reached its peak. In IL-10-deficient mice, neutrophil recruitment and TNF-α mRNA levels induced by CS exposure were significantly greater than those in wild-type mice. Keratinocyte-derived chemokine (KC; murine ortholog of human CXCL8) and granulocyte macrophage colony-stimulating factor (GM-CSF) mRNA levels or matrix metalloproteinase(MMP)-9 protein levels were not correlated with neutrophil count.IL-10 had a modulatory effect on CS-induced pulmonary neutrophilic inflammation and TNF-α expression in mice in vivo and therefore appears to be an important endogenous suppressor of airway neutrophilic inflammation.

Background: Asthma-COPD overlap syndrome (ACOS) phenotype is not yet well characterized, and its diagnosis is sometimes difficult. Aims and objectives: Because clinical markers might be useful to distinguish ACOS from asthma and COPD, we analyzed clinical data from each to discover such markers. Methods: We performed cross-sectional analysis on 100 patients with asthma, 23 with COPD, and 15 with ACOS at our center from January 2012 through November 2014 under an informed consent from each patient with an institutional approval. ACOS was defined as patients diagnosed with both asthma and COPD. Results: Age and Brinkman Index were significantly higher in the ACOS group versus the asthma group (p Conclusion: When comparing the phenotype of ACOS with asthma and COPD in clinical settings, our results nearly correspond to those of past reports. Although these reports showed lower respiratory function and more acute exacerbation in ACOS, our results did not show such tendencies. This study failed to find any useful markers for diagnosis of ACOS, and therefore, further investigation should be necessary.

Background: Bronchial asthma (BA) is a common disease that is characterized by airway inflammation. Recently many patients achieve good control with anti-inflammatory treatment. However some patients have persistent symptoms and airflow limitation even during such intervention. Therefore, pursuing appropriate biomarkers reflecting severity is crucial for disease monitoring. Oxidative stress is attracting attention as one of the important pathophysiological factors in BA. Aims and objectives: We investigated the magnitudes of oxidative stress and other biomarkers in patients with BA to clarify relationship between severity and various biomarkers. Methods: We enrolled patients who attended our hospital due to BA from January 2012 to January 2015. Oxidative stress was evaluated by reactive oxygen metabolite (ROM) levels using the d-ROMs test (Diacron International, Grosetto, Italy). We examined characteristics of clinical history and laboratory findings. Results: One hundred and six patients (67 women, mean age: 52.3±16.5, 12 current smokers, 23 ex-smokers) were included in this study. Thirty four patients had airflow limitation (FEV1/FVC < 0.7). ROM levels were negatively correlated with %FEV1 (r = -0.21, p < 0.05). Serum IL-8 concentrations were also negatively correlated with FEV1/FVC (r = -0.37, p < 0.05) and %FEV1 (r = -0.42, p < 0.05). WBC and eosinophil counts, FeNO levels were not correlated with FEV1/FVC and %FEV1. Conclusions: ROM levels and serum IL-8 concentrations had significantly negative correlation with degrees of airflow limitation. These biomarkers may be useful in the management of BA.

Background Cigarette smoking is considered to be one of major causes of acute worsening of asthma as well as chronic obstructive pulmonary disease (COPD). Macrolide antibiotics have been reported to reduce the risk of exacerbations of COPD, and possibly neutrophilic asthma. However, the effect of clarithromycin (CAM) on pulmonary inflammation caused by short term exposure to cigarette smoke still remains to be investigated. Methods C57BL/6J female mice were daily exposed to tobacco smoke using a tobacco smoke exposure system, or clean air for 8 days, while simultaneously treated with either oral CAM or vehicles. Twenty four hours after the last exposure, mice were anaesthetized and sacrificed, and bronchoalveolar lavage (BAL) fluids were collected. Cellular responses in BAL fluids were evaluated. Levels of cytokine mRNA in the lung tissues were measured by quantitative RT-PCR. Paraffin-embedded lung tissues were evaluated to quantitate degree of neutrophil infiltration. Results The numbers of total cells, macrophages and neutrophils in the BAL fluid of smoke-exposed mice were significantly increased as compared to clean air group. These changes were significantly ameliorated in CAM-treated mice. The lung morphological analysis confirmed decrease of neutrophils by CAM treatment. Studies by quantitative PCR demonstrated CAM treatment significantly reduced lung expression levels of IL-17A, keratinocyte-derived chemokine (KC), granulocyte-macrophage colony stimulating factor (GM-CSF) and MMP-9 induced by cigarette smoke. Conclusion We demonstrate that CAM administration resolves enhanced pulmonary inflammation induced by short term cigarette smoke exposure in mice.

Lafutidine, a newly developed histamine H(2)-receptor antagonist, inhibits daytime (i.e., postprandial) as well as nighttime gastric acid secretion in clinical studies. It also has gastroprotective activity that particularly affects mucosal blood flow in rats. This study focused on the efficacy of lafutidine on plasma concentrations of gastrointestinal peptides in humans. Six healthy male volunteers aged 23-32 years without Helicobacter pylori infection were orally administered either 10 mg lafutidine, 20 mg famotidine, or water only (control) 30 min after a standard meal (650 kcal). Plasma concentrations of lafutidine and famotidine were highest from 90 to 150 min after administration. Intragastric pH was elevated after both lafutidine and famotidine compared with the control. Plasma concentrations of calcitonin gene-related peptide (CGRP) and somatostatin were significantly increased after lafutidine at 60 and 90 min. We concluded that lafutidine increases plasma concentrations of CGRP and somatostatin in humans, which may result in inhibition of postprandial acid secretion and gastroprotective activity.

Rabeprazole achieves more potent acid suppression than other proton pump inhibitors. Therefore it is administered at reduced as well as high dosages in eradication therapy for Helicobacter pylori; however, there is incomplete assessment of the efficacy of a reduced dosage of rabeprazole as might be employed in therapy. In this study, we evaluated acid-suppressive efficacy of a reduced dosage of rabeprazole on day 7 by 24-hr pH-metry in 10 healthy male cytochrome P-450 2C19 extensive metabolizers without Helicobacterpylori infection and compared the results with those of high dosages of rabeprazole, lansoprazole, and omeprazole. Median intragastric pH value, pH3 holding time ratio (pH3HT), pH4HT, pH5HT, pH6HT, and pH7HT for 24 hr with rabeprazole, 10 mg twice daily, were not significantly different from those of rabeprazole, 20 mg twice daily, lansoprazole, 30 mg twice daily, and omeprazole, 20 mg twice daily. In conclusion, for acid-suppressive efficacy, a reduced dosage of rabeprazole is comparable to high dosages of rabeprazole, lansoprazole, and omeprazole.

In the pathogenesis of gastroesophageal reflux disease (GERD), gastric acid is considered to be one of the most important factors, but little is known about the degree of gastric acid secretion in GERD patients. In this study, we evaluated it in GERD patients and control subjects by 24-h intragastric pH, and serological and histological investigations, in relation to Helicobacter pylori (H. pylori) status. In H. pylori-negative GERD patients gastric acid secretion was similar to that in H. pylori-negative control subjects. In H. pylori-positive GERD patients, in particular, mild GERD patients, it decreased significantly compared to that in H. pylori-negative control subjects, but the degree of decrease was smaller than in H. pylori-positive control subjects. Results of serological and histological evaluation were supportive. In conclusion, in some GERD patients, gastric acid secretion was significantly decreased. Increased or maintained gastric acid secretion was not essential in the pathogenesis of mild GERD.

Summary Objectives Community-acquired pneumonia (CAP) is associated with high mortality when initial treatment fails. Early identification of these patients allows physicians to modify treatments earlier, increasing survival. Methods Ninety-one hospitalized patients with CAP were studied. Serum soluble ST2 levels were measured at diagnosis and at 3, 7, and 14 days (days 0, 3, 7, and 14) after the initiation of antimicrobial treatment. The predictive value of all-cause in-hospital mortality and the additive effect of soluble ST2 on the pneumonia severity index (PSI) were evaluated. Results In univariate analysis, high serum levels of soluble ST2 at days 0, 3, 7, and 14 were predictive of death (hazard ratios: 3.1, 10.0, 12.0, and 22.6, respectively). In multivariate analysis, a combination of soluble ST2 at day 3 (above 2700 pg/ml) and PSI were predictive of death with higher accuracy than PSI alone (net reclassification improvement, 0.44; integrated discrimination improvement, 0.17; P = 0.001 for both). Specifically, simultaneous presence of high soluble ST2 (day 3) and a PSI of 5 was suggestive of higher mortality risk than a PSI of 5 alone (mortality 78% vs. 39%, respectively). Conclusions Soluble ST2 is prognostic indicator of CAP and can add to the predictive value of the PSI.

Objective and design:The histone acetylation processes, which are believed to play a critical role in the regulation of many inflammatory genes, are reversible and regulated by histone acetyltransferases (HATs), which promote acetylation, and histone deacetylases (HDACs), which promote deacetylation. We studied the effects of lipopolysaccharide (LPS) on histone acetylation and its role in the regulation of interleukin (IL)-8 expression. Material:A human alveolar epithelial cell line A549 was usedinvitro.Methods:Histone H4 acetylation at the IL-8 promoter region was assessed by a chromatin immunoprecipitation (ChIP) assay. The expression and production of IL-8 were evaluated by quantitative polymerase chain reaction and specific immunoassay. Effects of a HDAC inhibitor, trichostatin A (TSA), and a HAT inhibitor, anacardic acid, were assessed. Results:Escherichia coli-derived LPS showed a dose- and time-dependent stimulatory effect on IL-8 protein production and mRNA expression in A549 cellsin vitro. LPS showed a significant stimulatory effect on histone H4 acetylation at the IL-8 promoter region by ChIP assay. Pretreatment with TSA showed a dose-dependent stimulatory effect on IL-8 release from A549 cells as compared to LPS alone. Conversely, pretreatment with anacardic acid inhibited IL-8 production and expression in A549 cells. Conclusion:These data suggest that LPS-mediated proinflammatory responses in the lungs might be modulated via changing chromatin remodeling by HAT inhibition.

Procalcitonin (PCT), a calcitonin precursor, is commonly measured in the setting of community-acquired pneumonia (CAP). However, the clinical significance of serial PCT changes has not been established. We conducted a prospective observational study of 122 patients with CAP. Thirty-day mortality was the primary endpoint. Secondary endpoints included: (1) initial treatment failure, (2) 30-day mortality and/or initial treatment failure, and (3) intensive care unit (ICU) admission. In subgroup analysis, we classified patients into pneumococcal pneumonia and non-pneumococcal pneumonia groups. The baseline frequency of 30-day mortality was 10.7%. Increases in serum PCT levels from admission to Day 3 were observed with statistically higher frequency in patients with 30-day mortality (P = 0.002). For secondary endpoints, only the 30-day mortality and/or initial treatment failure group was statistically significant (P = 0.007). Subgroup analysis revealed statistically significant changes in the non-pneumococcal pneumonia group (N = 85) across several endpoints, including 30-day mortality (P = 0.001), initial treatment failure (P = 0.013), and 30-day mortality and/or initial treatment failure (P 0.001). No significant changes in endpoint measurements were found in the pneumococcal pneumonia group (N = 28). Interestingly, serum PCT levels at the time of diagnosis were higher in patients with pneumococcal pneumonia than those with non-pneumococcal pneumonia (P = 0.006), and this positively correlated with disease severity scores for all patients (PCT vs. PSI: R = 0.380, P 0.001; PCT vs.R = 0.422, P 0.001) and for non-pneumococcal pneumonia (PCT vs. PSI: R = 0.468, P 0.001; PCT vs.R = 0.448, P 0.001), but not for pneumococcal pneumonia. In conclusion, serial quantification of PCT can predict clinical outcomes for patients with CAP.

Lansoprazole is a new proton pump inhibitor that was synthesized and developed in Japan. In study 1, we compared the acid secretion inhibitory effects of intravenous bolus injection and intravenous drip infusion of 30 mg twice daily of lansoprazole injection. In study 2, we compared 60 mg once daily and 30 mg twice daily of lansoprazole administered by intravenous bolus injection. Comparisons were made by the crossover method using 24-h intragastric pH monitoring in 10 healthy adult males. In both studies, lansoprazole significantly inhibited gastric acid secretion in comparison with control values. In comparison of administration methods, both intravenous bolus injection and intravenous drip infusion showed the same effectiveness. In the dose comparison, a single daily dose and two daily doses were both considered acceptable, but more reliable effects were achieved with two daily doses.

Summary We studied the risk factors associated with resistance to imipenem, levofloxacin and gentamicin in Pseudomonas aeruginosa isolated from blood cultures of 175 patients in a hospital in Japan. Imipenem resistance was associated with transfer from another hospital, and receiving antifungal medication. Gentamicin resistance was associated with previous administration of a penicillin. No specific risk factors were associated with levofloxacin resistance.

Background and Objectives To improve clinical outcomes of the initial therapy for gastroesophageal reflux disease, intragastric pH should be above 4.0 for more than 20 hours a day (83.3%) and nocturnal gastric acid breakthrough, defined as 60 continuous minutes of intragastric pH below 4.0 at night, should be inhibited. A “step-down” therapy sometimes fails because of insufficient acid suppression. Therefore we compared the acid-suppressive effects of proton pump inhibitors. Methods This was a prospective, randomized, open-label, 8-way crossover study. In 9 healthy Helicobacter pylori–negative cytochrome P450 (CYP) 2C19 homozygous extensive metabolizers, intragastric pH was measured for 24 hours on day 7 of treatment with rabeprazole, omeprazole, and lansoprazole orally administered once daily at reduced and standard doses. Results Compared with baseline data (7% [range, 5%-20%]), the median values of the 24-hour percent of time that intragastric pH was above 4.0 significantly increased but did not exceed 83.3% under any of the 7 regimens, which were as follows: 10 mg rabeprazole (51% [range, 28%-78%], P

Ouren-Gedoku-To (OGT) and San'ou-Syashin-To (SST), traditional Chinese prescriptions, have been used to treat peptic ulcer. In order to elucidate the mechanism of the protective effects of OGT and SST on the gastric mucosa, we studied their effects on gastric mucosal lesions, ion permeability and prostaglandin synthesis using ulcer experimentally induced in rats by saturation with acidic test solution after taurocholate treatment. Both OGT and SST inhibited taurocholate-induced gastric mucosal lesions in a dose-related manner. These prescriptions dose-dependently inhibited not only the increase of hydrogen and sodium ion net fluxes but also possible hydrogen ion back diffusion into the gastric mucosa during saturation with acidic test solution. SST induced a significant increase in gastric mucosal prostaglandins synthesized from 14C labeled arachidonate. These results suggest that both OGT and SST by strengthening the gastric mucosal barrier demonstrate their protective effects on the gastric mucosa and that this effect of SST is attributable to the increased ability of the gastric mucosa to synthesize prostaglandin.

The latest portable tape recorders must be more compact, light-weight, and operate on a lower power supply, no more than a single 1.5V dry battery. Some of the latest integrated circuits for play-only tape recorders can operate on a single 1.5V dry battery, but integrated circuits for record-and-play cassette tape recorders still require two such batteries.