Phylogeography of cliff-dwelling relicts with a highly narrow and disjunct distribution in the western Mediterranean.

PREMISE OF THE STUDY: The high biodiversity in the Baetic-Rifan hotspot of Mediterranean region is shaped by complex geological and climatic histories and has been a subject of recent intensive studies. However, very little is known about phylogenetic and biogeographic history of three rare and critically endangered cliff-dwelling species of Sonchus in section Pustulati in this region. METHODS: We investigated the genetic variation and phylogenetic relationships of populations based on nuclear (ITS/ETS) and plastid (3'trnL-ndhJ/psaI-accD) DNA sequences, and amplified fragment length polymorphisms (AFLPs). We performed a Bayesian relaxed molecular clock analysis with ITS data to estimate divergence times for major lineages. KEY RESULTS: ITS/ETS and AFLP phylogenies showed high concordance and contrasted with cpDNA data. The divergence between S. masguindalii and S. fragilis was dated at 5.48 Ma, between S. fragilis and S. pustulatus at 3.89 Ma, and between the Baetic and Rifan S. pustulatus at 1.18 Ma. Within each distribution area, AFLP data showed a relatively high genetic structuring and moderate genetic diversity, the latter being impoverished in the Baetic populations. CONCLUSIONS: Our results further confirm the hybrid origin of S. pustulatus, a critically endangered species. The origin and diversification of lineages appear to have occurred on the temporary land bridge that joined Iberian and North Africa during the Messinian Salinity Crisis (5.96-5.33 Ma) and the subsequent Zanclean flood that progressively refilled the Mediterranean Basin (5.33-3.60 Ma). The only Baetic populations of S. pustulatus most likely originated from the Rifan ones.

The correlation between the bronchial hyperresponsiveness to methacholine and asthma like symptoms by GINA questionnaires for the diagnosis of asthma.

BACKGROUND: In epidemiological studies of asthma, questionnaires to differentiate asthmatics from non-asthmatics have proven to be cost-effective and convenient. The aim of this study was to analyze the association between hyperresponsiveness to methacholine and the validity of five items for the asthma like questionnaire recommended by the Global Initiative for Asthma (GINA). METHODS: A total of 680 subjects who visited the pulmonology department with suspected symptoms of asthma were enrolled. All participants completed five items questionnaires and underwent methacholine bronchial provocation tests (MBPT). The diagnostic value of the questionnaire was assessed through analysis of the sensitivity, specificity, and positive and negative predictive values. RESULTS: Multivariate logistic regression analysis showed that questionnaires about wheezing, exercise induced dyspnea and pollution-induced dyspnea were useful for differentiating asthmatics from non-asthmatics (adjusted odds ratio (OR) =2.0, 95% confidence interval (CI) 1.3-3.0; OR =2.3, 95% CI 1.5-3.5; OR =2.0, 95% CI 1.3-3.0) respectively. A total symptom score of higher than 1 was associated with the highest sensitivity (98.4%) and lowest specificity (9.4%). In contrast, a total symptom score of more than 5 was associated with the highest specificity (91.9%) and lowest sensitivity (18.5%) CONCLUSIONS: Although questionnaires are not a sufficiently accurate method for diagnosing asthma, properly selected questionnaire can be used as effective strategies in situations such as private clinics or large population based epidemiologic studies.

Usefulness of N-terminal pro-B-type natriuretic peptide in patients admitted to the intensive care unit: a multicenter prospective observational study.

BACKGROUND: The role of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) as a prognostic factor in patients admitted to the intensive care unit (ICU) is not yet fully established. We aimed to determine whether NT-pro-BNP is predictive of ICU mortality in a multicenter cohort of critically ill patients. METHODS: A total of 1440 patients admitted to 22 ICUs (medical, 14; surgical, six; multidisciplinary, two) in 15 tertiary or university-affiliated hospitals between July 2010 and January 2011 were assessed. Patient data, including NT-pro-BNP levels and Simplified Acute Physiology Score (SAPS) 3 scores, were recorded prospectively in a web-based database. RESULTS: The median age was 64 years (range, 53-73 years), and 906 (62.9%) patients were male. The median NT-pro-BNP level was 341 pg/mL (104-1,637 pg/mL), and the median SAPS 3 score was 57 (range, 47-69). The ICU mortality rate was 18.9%, and hospital mortality was 24.5%. Hospital survivors showed significantly lower NT-pro-BNP values than nonsurvivors (245 pg/mL [range, 82-1,053 pg/mL] vs. 875 pg/mL [241-5,000 pg/mL], respectively; p < 0.001). In prediction of hospital mortality, the area under the curve (AUC) for NT-pro-BNP was 0.67 (95% confidence interval [CI], 0.64-0.70) and SAPS 3 score was 0.83 (95% CI, 0.81-0.85). AUC increment by adding NT-pro-BNP is minimal and likely no different to SAPS 3 alone. CONCLUSIONS: The NT-pro-BNP level was more elevated in nonsurvivors in a multicenter cohort of critically ill patients. However, there was little additional prognostic power when adding NT-pro-BNP to SAPS 3 score.

Etiologies, diagnostic strategies, and outcomes of diffuse pulmonary infiltrates causing acute respiratory failure in cancer patients: a retrospective observational study.

INTRODUCTION: Although previous studies have reported etiologies, diagnostic strategies, and outcomes of acute respiratory failure (ARF) in cancer patients, few studies investigated ARF in cancer patients presenting with diffuse pulmonary infiltrates. METHODS: This was a retrospective observational study of 214 consecutive cancer patients with diffuse pulmonary infiltrates on chest radiography admitted to the oncology medical intensive care unit for acute respiratory failure between July 2009 and June 2011. RESULTS: After diagnostic investigations including bronchoalveolar lavage in 160 (75%) patients, transbronchial lung biopsy in 75 (35%), and surgical lung biopsy in 6 (3%), the etiologies of diffuse pulmonary infiltrates causing ARF were identified in 187 (87%) patients. The most common etiology was infection (138, 64%), followed by drug-induced pneumonitis (13, 6%) and metastasis (12, 6%). Based on the etiologic diagnoses, therapies for diffuse pulmonary infiltrates were subsequently modified in 99 (46%) patients. Diagnostic yield (46%, 62%, 85%, and 100%; P for trend < 0.001) and frequency of therapeutic modifications (14%, 37%, 52%, and 100%; P for trend < 0.001) were significantly increased with additional invasive tests. Patients with therapeutic modification had a 34% lower in-hospital mortality rate than patients without therapeutic modification (38% versus 58%, P = 0.004) and a similar difference in mortality rate was observed up to 90 days (55% versus 73%, Log-rank P = 0.004). After adjusting for potential confounding factors, therapeutic modification was still significantly associated with reduced in-hospital mortality (adjusted OR 0.509, 95% CI 0.281-0.920). CONCLUSIONS: Invasive diagnostic tests, including lung biopsy, increased diagnostic yield and caused therapeutic modification that was significantly associated with better outcomes for diffuse pulmonary infiltrates causing ARF in cancer patients.

The adverse effect of emergency department crowding on compliance with the resuscitation bundle in the management of severe sepsis and septic shock.

INTRODUCTION: The aim of this study is to evaluate the effects of emergency department (ED) crowding on the implementation of tasks in the early resuscitation bundle during acute care of patients with severe sepsis and septic shock, as recommended by the Surviving Sepsis Campaign guidelines. METHODS: We analyzed the sepsis registry from August 2008 to March 2012 for patients presenting to an ED of a tertiary urban hospital and meeting the criteria for severe sepsis or septic shock. The ED occupancy rate, which was defined as the total number of patients in the ED divided by the total number of ED beds, was used for measuring the degree of ED crowding. It was categorized into three groups (low; intermediate; high crowding). The primary endpoint was the overall compliance with the entire resuscitation bundle. RESULTS: A total of 770 patients were enrolled. Of the eligible patients, 276 patients were assigned to the low crowding group, 250 patients to the intermediate crowding group, and 244 patients to the high crowding group (ED occupancy rate: ≤ 115; 116-149; ≥ 150%). There was significant difference in compliance rates among the three groups (31.9% in the low crowding group, 24.4% in the intermediate crowding group, and 16.4% in the high crowding group, P < 0.001). In a multivariate model, the high crowding group had a significant association with lower compliance (adjusted odds ratio (OR), 0.44; 95% confidence interval (CI), 0.26 to 0.76; P = 0.003). When the ED occupancy rate was included as a continuous variable in the model, it had also a negative correlation with the overall compliance (OR of 10% increase of the ED occupancy rate, 0.90; 95% CI, 0.84 to 0.96, P = 0.002). CONCLUSIONS: ED crowding was significantly associated with lower compliance with the entire resuscitation bundle and decreased likelihood of the timely implementation of the bundle elements.

Outcome and predictors of mortality in patients requiring invasive mechanical ventilation due to acute respiratory failure while undergoing ambulatory chemotherapy for solid cancers.

PURPOSE: Acute respiratory failure that requires invasive mechanical ventilation is a leading cause of death in critically ill cancer patients. The aim of this study was to evaluate the outcome and prognostic factors of patients requiring invasive mechanical ventilator for acute respiratory failure, within 1 month of ambulatory chemotherapy for solid cancer. METHODS: A retrospective observational study of patients who underwent ambulatory chemotherapy at Samsung Medical Center, between January of 2007 and April of 2009, was employed for this study. RESULTS: A total of 51 patients met the inclusion criteria and were included in the study. The median age was 65 years (25-87) and the majority of the patients were male (n = 38, 74.5%). There were 42 patients (82.3%) with lung cancer. The most common cause of acute respiratory failure was pneumonia (n = 24, 47.1%), followed by acute respiratory failure due to extra-pulmonary infection, drug-induced pneumonitis, alveolar hemorrhage, and cancer progression. The intensive care unit (ICU) mortality was 68.6% and the most common cause of death in the ICU was uncorrected cause of acute respiratory failure. Before adjustment for others factors, prechemotherapy Eastern Cooperative Oncology Group (ECOG) Performance Scale (PS) (P = 0.03), Sequential Organ Failure Assessment score (P = 0.01), and anemia (P = 0.04) were significantly associated with ICU mortality. However, when adjusted for age, sex, and Acute Physiologic and Chronic Health Evaluation II score, only poor ECOG PS (≥2) was significantly associated with ICU mortality [OR 6.36 (95% CI (1.02-39.5))]. CONCLUSIONS: The outcome of patients with acute respiratory failure needing invasive mechanical ventilation during ambulatory chemotherapy for solid cancer is poor. Prechemotherapy performance status is an independent predictor of mortality.

Validation of SAPS3 admission score and its customization for use in Korean intensive care unit patients: a prospective multicentre study.

BACKGROUND AND OBJECTIVE: To externally validate the simplified acute physiology score 3 (SAPS3) and to customize it for use in Korean intensive care unit (ICU) patients. METHODS: This is a prospective multicentre cohort study involving 22 ICUs from 15 centres throughout Korea. The study population comprised patients who were consecutively admitted to participating ICUs from 1 July 2010 to 31 January 2011. RESULTS: A total of 4617 patients were enrolled. ICU mortality was 14.3%, and hospital mortality was 20.6%. The patients were randomly assigned into one of two cohorts: a development (n = 2309) or validation (n = 2308) cohort. In the development cohort, the general SAPS3 had good discrimination (area under the receiver operating characteristics curve = 0.829), but poor calibration (Hosmer-Lemeshow goodness-of-fit test H = 123.06, P < 0.001, C = 118.45, P < 0.001). The Australasia SAPS3 did not improve calibration (H = 73.53, P < 0.001, C = 70.52, P < 0.001). Customization was achieved by altering the logit of the original SAPS3 equation. The new equation for Korean ICU patients was validated in the validation cohort, and demonstrated both good discrimination (area under the receiver operating characteristics curve = 0.835) and good calibration (H = 4.61, P = 0.799, C = 5.67, P = 0.684). CONCLUSIONS: General and regional Australasia SAPS3 admission scores showed poor calibration for use in Korean ICU patients, but the prognostic power of the SAPS3 was significantly improved by customization. Prediction models should be customized before being used to predict mortality in different regions of the world.

Antifactor Xa levels in critically ill Korean patients receiving enoxaparin for thromboprophylaxis: a prospective observational study.

The aim of this study was to investigate antifactor Xa (aFXa) levels after once daily dose of 40 mg of enoxaparin and to evaluate factors influencing aFXa levels among Korean intensive care unit (ICU) patients. This prospective observational study was conducted between August and December 2011 in medical ICUs at Samsung Medical Center. AFXa levels between 0.1 and 0.3 U/mL were considered to be effective for antithrombotic activity. Fifty-five patients were included. The median aFXa levels were 0.22 (IQR 0.17-0.26) at 4 hr, 0.06 (IQR 0.02-0.1) at 12 hr, and 0 U/mL (IQR 0-0.03) at 24 hr. The numbers of patients showing effective antithrombotic aFXa levels were 48 (87.3%), 18 (32.7%), and 0 (0%) at 4, 12 and 24 hr, respectively. At 12 hr, higher sequential organ failure assessment (SOFA) scores and hyperbilirubinemia were significantly associated with low aFXa levels (OR, 0.58; 95% CI, 0.36-0.93; P = 0.02 and 0.06; 0.003-0.87; 0.04, respectively). Once daily dose of 40 mg of enoxaparin is inadequate for maintaining effective antithrombotic aFXa levels, and the inadequacy is more salient for patients with high SOFA scores and hyperbilirubinemia.

Ultrahigh dielectric permittivity in oxide ceramics by hydrogenation.

Boosting dielectric permittivity representing electrical polarizability of dielectric materials has been considered a keystone for achieving scientific breakthroughs as well as technological advances in various multifunctional devices. Here, we demonstrate sizable enhancements of low-frequency dielectric responses in oxygen-deficient oxide ceramics through specific treatments under humid environments. Ultrahigh dielectric permittivity (~5.2 × 106 at 1 Hz) is achieved by hydrogenation, when Ni-substituted BaTiO3 ceramics are exposed to high humidity. Intriguingly, thermal annealing can restore the dielectric on-state (exhibiting huge polarizability in the treated ceramics) to the initial dielectric off-state (displaying low polarizability of ~103 in the pristine ceramics after sintering). The conversion between these two dielectric states via the ambient environment-mediated treatments and the successive application of external stimuli allows us to realize reversible control of dielectric relaxation characteristics in oxide ceramics. Conceptually, our findings are of practical interest for applications to highly efficient dielectric-based humidity sensors.

Posttuberculosis tracheobronchial stenosis: use of CT to optimize the time of silicone stent removal.

PURPOSE: To evaluate whether air pockets (tracheobronchial air columns in the space between the outer surface of the stent and the adjacent airway wall) discernible at computed tomography (CT) can help optimize the time of stent removal in patients with posttuberculosis tracheobronchial stenosis (PTTS). MATERIALS AND METHODS: The study was approved by the institutional review board, and informed consent was obtained from all patients. Data from 41 patients (five men, 36 women) with a median age of 39 years (range, 21-64 years) who underwent silicone stent placement owing to PTTS, followed by CT and stent removal 6-12 months after clinical stabilization, were investigated retrospectively. Two radiologists determined whether the extent of air pockets on CT scans was associated with clinical success, which was defined as maintenance of a prosthesis-free airway for more than 2 years after stent removal. Radiologic features were compared for outcome by using a Wilcoxon two-sample test or Fisher exact test. RESULTS: Stents were removed successfully in 31 patients (76%). Air pockets longer than 1 cm or longer than 2 cm were associated with successful stent removal (P = .04 and P = .006, respectively). The sensitivity and specificity of air pocket length in the prediction of successful stent removal were 84% and 50%, respectively, for air pockets longer than 1 cm and 68% and 70% for air pockets longer than 2 cm. CONCLUSION: The extent of air pockets at chest CT shows correlation with the success of stent removal, indicates regression of stenosis, and may help guide the optimal time for stent removal.

Early initiation of low-dose corticosteroid therapy in the management of septic shock: a retrospective observational study.

INTRODUCTION: The use of low-dose steroid therapy in the management of septic shock has been extensively studied. However, the association between the timing of low-dose steroid therapy and the outcome has not been evaluated. Therefore, we evaluated whether early initiation of low-dose steroid therapy is associated with mortality in patients with septic shock. METHODS: We retrospectively analyzed the clinical data of 178 patients who received low-dose corticosteroid therapy for septic shock between January 2008 and December 2009. Time-dependent Cox regression models were used to adjust for potential confounding factors in the association between the time to initiation of low-dose corticosteroid therapy and in-hospital mortality. RESULTS: The study population consisted of 107 men and 71 women with a median age of 66 (interquartile range, 54 to 71) years. The 28-day mortality was 44% and low-dose corticosteroid therapy was initiated within a median of 8.5 (3.8 to 19.1) hours after onset of septic shock-related hypotension. Median time to initiation of low-dose corticosteroid therapy was significantly shorter in survivors than in non-survivors (6.5 hours versus 10.4 hours; P=0.0135). The mortality rates increased significantly with increasing quintiles of time to initiation of low-dose corticosteroid therapy (P=0.0107 for trend). Other factors associated with 28-day mortality were higher Simplified Acute Physiology Score (SAPS) 3 (P<0.0001) and Sequential Organ Failure Assessment (SOFA) scores (P=0.0007), dose of vasopressor at the time of initiation of low-dose corticosteroid therapy (P<0.0001), need for mechanical ventilation (P=0.0001) and renal replacement therapy (P<0.0001), while the impaired adrenal reserve did not affect 28-day mortality (81% versus 82%; P=0.8679). After adjusting for potential confounding factors, the time to initiation of low-dose corticosteroid therapy was still significantly associated with 28-day mortality (adjusted odds ratio (OR) 1.025, 95% confidence interval (CI) 1.007 to 1.044, P=0.0075). The early therapy group (administered within 6 hours after the onset of septic shock, n=66) had a 37% lower mortality rate than the late therapy group (administered more than 6 hours after the onset of septic shock, n=112) (32% versus 51%, P=0.0132). CONCLUSIONS: Early initiation of low-dose corticosteroid therapy was significantly associated with decreased mortality.

The incidence, causes, and prognostic significance of new-onset thrombocytopenia in intensive care units: a prospective cohort study in a Korean hospital.

This study was designed to investigate the incidence, causes, and outcomes of new-onset thrombocytopenia (NOT) in Korean intensive care units (ICUs). A prospective cohort study was conducted in medical ICUs of Samsung Medical Center between August 2010 and February 2011. All newly admitted patients were included if they stayed in the ICU for more than 48 hr and did not have thrombocytopenia upon admission. A total of 186 patients were included. NOT developed in 37.1%. Most common cause of NOT was sepsis with disseminated intravascular coagulation (66.7%), followed by drug-induced thrombocytopenia (18.8%), and heparin-induced thrombocytopenia (2.9%). IgG-specific antibody to platelet factor 4/heparin was positive in 2.4% among patients treated with heparin, and thrombosis occurred in two patients. Twenty eight-day mortality was higher in patients that developed NOT compared to those that did not develop NOT (39.1% vs 12%, P < 0.001). NOT increased the odds ratio of 28-day mortality and was an independent risk factor for mortality (OR 3.52; 95% CI 1.32-9.38; P = 0.012). In conclusion, NOT is common and is an independent risk factor for mortality in Korean ICU patients. Therefore, clinicians should make every effort to correct the causes of NOT.

Factors predicting outcome following airway stenting for post-tuberculosis tracheobronchial stenosis.

BACKGROUND AND OBJECTIVE: Silicone airway stents are used to widen narrowed airways in patients with post-tuberculosis tracheobronchial stenosis (PTTS). After mechanical stabilization, stents can be removed from the majority of patients leaving restored airway patency. However, in a significant minority re-stenosis develops post-sten removal thus necessitating surgical intervention or long-term stenting. In this study, we sought to establish prognostic factors for successful airway intervention in PTTS. METHODS: We retrospectively investigated 71 patients who underwent silicone stenting due to PTTS. After stenting, bronchoscopic toileting and/or repositioning was performed during follow up. At 6-12 months after clinical stabilization, stents were planned to be removed. Patients with patent airways were followed if no further intervention was required. If restenosis developed, patients underwent re-stenting or operation. Clinical parameters were analysed to determine favourable prognostic factors. RESULTS: Stents were successfully removed in 40 patients at a median 12.5 months after insertion. In 27 patients, stent re-insertion was carried out and four patients underwent surgical management. Multivariate logistic regression analysis revealed that successful stent removal was independently associated with atelectasis <1 month before bronchoscopic intervention, and absence of complete lobar atelectasis. CONCLUSIONS: Airway intervention, including silicone stenting, can be successful in patients with PTTS, when the intervention is performed within 1 month of atelectasis and before complete lobar atelectasis.

Lactobacillus casei suppresses experimental arthritis by down-regulating T helper 1 effector functions.

Although the beneficial effects of probiotics on wide variety of diseases have been shown, little is known about how probiotics modulate the immune system. In this study we elucidated the underlying mechanisms how Lactobacillus casei (L. casei) protects against rheumatoid arthritis (RA) progression by investigating the effector functions of CD4(+) T cells. Oral administration of L. casei suppressed collagen-induced arthritis (CIA) and reduced paw swelling, lymphocyte infiltration and destruction of cartilage tissue. L. casei administration reduced type II collagen (CII)-reactive proinflammatory molecules (IL-1beta, IL-2, IL-6, IL-12, IL-17, IFN-gamma, TNF-alpha and Cox-2) by CD4(+) T cells. L. casei administration also reduced translocation of NF-kappaB into nucleus and CII-reactive Th1-type IgG isotypes IgG2a and IgG2b, while up-regulating immunoregulatory IL-10 levels. Our results suggest that oral administration of L. casei suppresses the type II collagen-reactive effector function of Th1-type cellular and humoral immune responses in arthritic inflammation.

Foxp3 induces IL-4 gene silencing by affecting nuclear translocation of NFkappaB and chromatin structure.

The forkhead family protein Foxp3 is a unique marker of regulatory T cells and plays a crucial role in the development and function of those cells. Ectopic expression of Foxp3 abolishes the expression of many cytokines in uncommitted cells but there is little information about whether it causes gene silencing in differentiated cells. In this study, we showed that ectopic expression of Foxp3 in primary T helper 2 cells abolished IL-4 gene expression. Foxp3 inhibited nuclear translocation of NFkappaB by increasing the stability of the NFkappaB inhibitor IkappaBalpha, which in turn reduced in vivo binding of NFkappaB to the IL-4 promoter region. Moreover, Foxp3 over-expression induced inactive chromatin structure by decreasing in vivo binding levels of acetylated histone 3 while increasing methylated histone 3 at lysine 9 in the IL-4 genomic locus. Our results suggest that Foxp3 could induce gene silencing by inhibiting NFkappaB activity and by causing its target loci to adopt an inactive chromatin configuration.

Pharmacokinetic Alteration of Paclitaxel by Ferulic Acid Derivative.

P-glycoprotein (P-gp) is known to be involved in multidrug resistance (MDR) and modulation of pharmacokinetic (PK) profiles of substrate drugs. Here, we studied the effects of synthesized ferulic acid (FA) derivatives on P-gp function in vitro and examined PK alteration of paclitaxel (PTX), a well-known P-gp substrate drug by the derivative. Compound 5c, the FA derivative chosen as a significant P-gp inhibitor among eight FA candidates by in vitro results, increased PTX AUCinf as much as twofold versus the control by reducing PTX elimination in rats. These results suggest that FA derivative can increase PTX bioavailability by inhibiting P-gp existing in eliminating organs.

Ethanol extract of Inonotus obliquus inhibits lipopolysaccharide-induced inflammation in RAW 264.7 macrophage cells.

Inonotus obliquus (Pers.:Fr.) Pil. is a white rot fungus that belongs to the family Hymenochaetaceae of Basidiomycetes. Extracts and fractions of this fungus have been known to have biological activities, including antimutagenic, anticancer, antioxidative, and immunostimulating effects. Recently, there have been reports that the anti-inflammatory and antinociceptive properties of the methanol extract of I. obliquus may be due to the inhibition of inducible nitric oxide (NO) synthase (iNOS) and cyclooxygenase-2 (COX-2) expression via the down-regulation of nuclear factor kappaB (NF-kappaB) binding activity. However, the effects of I. obliquus on Akt and mitogen-activated protein kinase (MAPK) activation of inflammatory mediator production have not yet been elucidated. In the present study, a 70% ethanol extract of I. obliquus (IOE70) showed antioxidative effects. We also tested the ability of the I. obliquus extract to inhibit the inflammatory cascades in lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells. The NO inhibition of IOE70 was better than that of other ethanol extracts from I. obliquus. To investigate the mechanism by which IOE 70 inhibits NO production and iNOS and COX-2 expression, we examined the activations of IkappaBalpha, Akt, and c-Jun NH(2) -terminal kinase (JNK) in LPS-activated macrophages. IOE70 markedly inhibited the phosphorylation of IkappaBalpha, Akt, and MAPKs in dose-dependent manners in LPS-activated macrophages. Taken together, these experiments demonstrated that IOE70 inhibition of LPS-induced expression of iNOS and COX-2 protein is mediated by Akt and JNK. Based on our findings, the most likely mechanism that can account for this biological effect of IOE70 involves the inhibition of NF-kappaB through the phosphatidylinositol 3-kinase/Akt/IkappaB pathway and the inhibition of JNK activation. Thus, IOE70 might have useful clinical applications in the management of inflammatory diseases and may also be useful as a medicinal food.

Cordycepin inhibits lipopolysaccharide-induced inflammation by the suppression of NF-kappaB through Akt and p38 inhibition in RAW 264.7 macrophage cells.

Cordyceps militaris, a caterpillar-grown traditional medicinal mushroom, produces an important bioactive compound, cordycepin (3'-deoxyadenosine). Cordycepin is reported to possess many pharmacological activities including immunological stimulating, anti-cancer, anti-virus and anti-infection activities. The molecular mechanisms of cordycepin on pharmacological and biochemical actions of macrophages in inflammation have not been clearly elucidated yet. In the present study, we tested the role of cordycepin on the anti-inflammation cascades in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. In LPS-activated macrophage, nitric oxide (NO) production was inhibited by butanol fraction of C. militaris and the major component of C. militaris butanol faction was identified as cordycepin by high performance liquid chromatography. To investigate the mechanism by which cordycepin inhibits NO production and inducible nitric oxide synthase (iNOS) expression, we examined the activation of Akt and MAP kinases in LPS-activated macrophage. Cordycepin markedly inhibited the phosphorylation of Akt and p38 in dose-dependent manners in LPS-activated macrophage. Moreover, cordycepin suppressed tumor necrosis factor (TNF-alpha) expression, IkappaB alpha phosphorylation, and translocation of nuclear factor-kappaB (NF-kappaB). The expressions of cycloxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were significantly decreased in RAW 264.7 cell by cordycepin. Taken together, these results suggest that cordycepin inhibits the production of NO production by down-regulation of iNOS and COX-2 gene expression via the suppression of NF-kappaB activation, Akt and p38 phosphorylation. Thus, cordycepin may provide a potential therapeutic approach for inflammation-associated disorders.

Mirtazapine treatment for pathological laughing and crying after stroke.

Selective serotonin reuptake inhibitors (SSRIs) have been recognized as the treatment of choice for pathological laughing and crying (PLC), which is a common, distressing condition that follows stroke. There have been few reports about other treatment options for PLC. Here, the authors report rapid responses to mirtazapine in two patients with poststroke PLC who failed to respond to SSRIs or bupropion. In the first case, a 63-year-old woman with severe long-standing crying spells that had persisted for 3 months responded well to low-dose mirtazapine within a few days; she could not tolerate citalopram or sertraline. In the second case, both the laughing and crying spells of a 64-year-old woman were improved within a few days of mirtazapine administration, after they had not responded to bupropion. This is one of the first reports to suggest that mirtazapine may be an alternative to SSRIs for treating poststroke PLC.

Prevalence of colorectal adenomatous polyps in patients with chronic obstructive pulmonary disease.

BACKGROUND: Colorectal adenomatous polyps are precancerous lesions of colorectal cancer. The aim of this study was to assess the prevalence of colorectal adenomatous polyps in chronic obstructive pulmonary disease (COPD) patients and determine whether COPD is associated with colorectal malignant potential. METHODS: Subjects who had undergone post-bronchodilator spirometry and colonoscopy and were 40 years or older were selected from the hospital database. COPD was defined as a spirometry in which the ratio of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) is <0.7 in post-bronchodilator spirometry. The non-COPD group was matched for both age and sex, and were defined as having an FEV1, FVC, and FEV1/FVC ≥0.7 in spirometry. Finally, 333 patients were retrospectively reviewed; of this group, 82 patients had COPD. RESULTS: Among the subjects, 201 patients (60%) were nonsmokers, while 78 (23%) were current smokers. The prevalence of colorectal adenomatous polyps was 39% (98/251) in the non-COPD group and 66% (54/82) in the COPD group. Among 54 patients with adenomatous polyps in the COPD group, 47 had tubular adenoma and seven had villous adenoma. Multiple logistic regression analyses revealed that only COPD patients whom matched to the criteria of COPD by pulmonary function test (odds ratio 2.1, 95% confidence interval: 1.1-3.8; P=0.019) were independently associated with colorectal malignant potential. CONCLUSION: The risk of colorectal malignant potential in the COPD group was higher than in the non-COPD group. We may suggest that COPD patients should consider regular colonoscopic evaluation to screen for premalignant colon polyps regardless of smoking.