Subjects with diabetes experience an increased risk of cerebrovascular disease and stroke compared with nondiabetic age-matched individuals. Increased formation of reactive physiological dicarbonyl compound methylglyoxal (MGO) seems to be implicated in the development of diabetic vascular complication due to its protein glycation and oxidative stress effect. Edaravone, a novel radical scavenger, has been reported to display the advantageous effects on ischemic stroke both in animals and clinical trials; however, little is known about whether edaravone has protective effects on diabetic cerebrovascular injury. Using cultured human brain microvascular endothelial cells (HBMEC), protective effects of edaravone on MGO and MGO enhancing oxygen-glucose deprivation (OGD) induced injury were investigated. Cell injury was measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) formation, cell account, lactate dehydrogenase (LDH) release and Rhodamine 123 staining. Advanced glycation end-products (AGEs) formation and receptor for advanced glycation end-products (RAGE) expression were measured by western blotting. Cellular oxidative stress was measured by reactive oxygen species (ROS) release. Treatment of MGO for 24 h significantly induced HBMEC injury, which was inhibited by pretreatment of edaravone from 10–100 µmol/l. What’s more, treatment of MGO enhanced AGEs accumulation, RAGE expression and ROS release in the cultured HBMEC, which were inhibited by 100 µmol/l edaravone. Finally, treatment of MGO for 24 h and then followed by 3 h OGD insult significantly enhanced cell injury when compared with OGD insult only, which was also protected by 100 µmol/l edaravone. Thus, edaravone protected HBMEC from MGO and MGO enhancing OGD-induced injury by inhibiting AGEs/RAGE/oxidative stress.

No abstract

Introduction: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is rapidly emerging as a life-threatening nosocomial infection. In this study, we aim to identify risk factors, especially antibiotic use, for CRKP infection among intensive care unit (ICU) patients. Methodology: This was a matched case-control study of a 67-bed ICU in a tertiary care teaching hospital from 1 January 2011 through 30 June 2013. The control cases were selected among the patients with carbapenem-susceptible Klebsiella pneumoniae (CSKP) and were matched with CRKP cases for year of ICU admission and site of infection. The clinical outcomes and antibiotic treatments were analyzed. Results: One hundred and thirty patients were included in the study (65 cases and 65 controls). Bivariable analysis showed that age of patients (p = 0.044), number of antibiotic groups (p = 0.001), and exposure to carbapenems (p < 0.001) were associated with CRKP infection. Using multivariate analysis adjusted for age, prior hospitalization, number of antibiotic groups, and previous exposure to carbapenems, previous carbapenem exposure (p < 0.001) was identified as an independent risk factor for CRKP infection. Conclusions: These data suggest that exposure to carbapenems is an independent risk factor for CRKP infection. Patients with this clinical factor should be targeted for interventions to reduce the subsequent risk of infection.

BackgroundSecondary prevention is important for reducing both mortality and morbidity of patients with coronary heart disease (CHD). Pharmacists can provide medication and also work on disease management for patients with CHD. This review has been carried out to evaluate the role of pharmacist care on mortality, morbidity, and the CHD management.MethodsThe PubMed, MEDLINE, EMBASE, Web of Science and Cochrane Central Register of Controlled Trials databases were searched for randomized controlled trials (RCTs) to evaluate the impact of pharmacist care interventions on patients with CHD (in both community and hospital settings). Primary outcomes of interest were mortality, cardiovascular events and hospitalizations. Secondary outcomes were medication adherence, blood pressure control, and lipid management.ResultsFive RCTs (2568 patients) were identified. The outcomes were mortality, cardiovascular events, and hospitalizations in one study (421 patients), medication adherence in five studies, blood pressure in two studies (1914 patients), and lipid management in three studies (932 patients). The interventions of pharmacists included patient education, medication management, feedback to health care professionals, and disease management. There was no significant effect of pharmacist care on mortality, recurrent cardiac events or hospitalization of CHD patients. Significant positive effects of pharmacist care were shown on medication adherence in three studies, on blood pressure control in one study and on lipid management in one study.ConclusionIn this study, we concluded that pharmacists have a beneficial role in the care of CHD patients, although the evidence supporting positive impacts on mortality and morbidity remains uncertain due to the unavailability of data in these areas. Further research is needed to discern the contribution of pharmacist care on hard endpoints of CHD.

No abstract

A selective, sensitive and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of tigecycline (TGC) in human plasma, using tigecycline-d as an internal standard (IS). Analytical samples were prepared using a protein precipitation method coupled with a concentration process. The analyte and IS were separated on a reversed-phase Waters Acquity UPLC BEH-C column (2.1 × 50 mm i.d., 1.7 μm) with a flow rate of 0.25 mL/min. The mobile phase consisted of water, containing 0.2% formic acid (v/v) with 10 mm ammonium formate (A) and acetonitrile (B). The mass spectrometer was operated in selected reaction monitoring mode through electrospray ionization ion mode using the transitions of m/z 586.2 → 513.1 and m/z 595.1 → 514.0 for TGC and IS, respectively. The linearity of the method was in the range of 10-5000 ng/mL. Intra- and inter-batch precision (CV) for TGC was <9.27%, and the accuracy ranged from 90.06 to 107.13%. This method was successfully applied to the analysis of samples from hospital-acquired pneumonia patients treated with TGC, and a validated population pharmacokinetic model was established. This developed method could be useful to predict pharmacokinetics parameters and valuable for further pharmacokinetics/pharmacodynamics studies.

Abstract. Heat shock protein 27 (HSP27) is an important regulator involved in the development of lung cancer. However, limited evidence exists concerning the underlying molecular mechanisms of its action. The results of the present study revealed that HSP27 was highly expressed in the lung cancer tissues of mice. In an in vitro model, the overexpression of HSP27 promoted cell proliferation, while HSP27 knockdown inhibited cell proliferation. HSP27 promoted cell proliferation in vitro by directly upregulating the expression of HSP27 target genes, which required the activation of the activator protein-1 (AP-1) signaling pathway. This was evaluated by the phosphorylation status of an important pathway component, c-Jun in lung cancer tissue and cells. These results suggested that HSP27 has a promotional role in lung cancer, and therefore indicated a novel mechanism involving lung cancer cell proliferation, which may underlie poor responses to therapy. Therefore, HSP27 may be a suitable therapeutic target for the treatment of lung cancer. IntroductionLung cancer is the leading cause of cancer-associated mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for ~85% of all mortalities associated with lung cancer. The overall five-year survival rate for patients remains poor (1-3). The poor prognoses of lung cancer patients primarily result from early relapse, metastasis and unsuccessful responses to treatment strategies, including surgery, chemotherapy and radiotherapy (4-6). In addition, the lack of effective prognostic biomarkers that are able to predict treatment response and prognosis affects treatment regimens and patient outcomes.Heat shock proteins (HSPs) are a large family of proteins that function as molecular chaperones under physiological conditions (7). The ability of radiofrequency ablation to induce the expression of HSPs, including HSP70, in small animal models suggests that HSPs may be involved in rescuing damaged cells in close proximity to the ablation zone and, therefore, limiting the therapeutic effects (8,9). In addition, HSPs have been identified to promote carcinogenesis by inhibiting apoptosis (10-14) and enhancing resistance to treatment (15,16). However, it has been established that HSPs function differently in different tumors (10,15).HSP27 is a 27-kDa protein that regulates apoptosis by interacting with key components of apoptotic signaling pathways, particularly those involved in the activation of caspases. Increasing evidence has indicated that HSP27 may play an important role in cancer (17). The expression of HSP27 has been associated with poor prognoses in ovarian (18), breast (10,19), gastric (20) and prostate cancers (21), as well as in osteoscarcomas (14). In addition, HSP27 has been reported to be associated with poor prognoses in patients with lung cancer (22). However, whether the expression of HSP27 has a prognostic role in lung cancer remains controversial. Zimmermann et al (22) reported that the level of serum HSP27 was positively correlated with advanced lung...

Background Infection is the leading cause of morbidity and mortality among burn patients, and bloodstream infection (BSI) is the most serious. This study aimed to evaluate the epidemiology and clinical outcomes of BSI in severe burn patients. Methods Clinical variables of all patients admitted with severe burns (≥ 20% total body surface area, %TBSA) were analyzed retrospectively from January 2013 to December 2018 at a teaching hospital. The Kaplan–Meier method was utilized for plotting survival curves. Multivariate logistic regression and Cox regression model were also performed. Results A total of 495 patients were evaluated, of whom 136 (27.5%) had a BSI. The median time from the patients being burned to BSI was 8 days. For BSI onset in these patients, 47.8% (65/136) occurred in the first week. The most frequently isolated causative organism was A. baumannii (22.7%), followed by methicillin-resistant Staphylococcus aureus (18.7%) and K. pneumoniae (18.2%), in patients with BSI. Multivariate logistic regression analysis showed that %TBSA (p = 0.023), mechanical ventilation (p = 0.019), central venous catheter (CVC) (p < 0.001) and hospital length of stay (27d vs 50d, p < 0.001) were independent risk factors associated with BSI. Cox regression model showed that acute kidney injury (HR, 12.26; 95% CI 2.31–64.98; p = 0.003) and septic shock (HR, 4.36; 95% CI 1.16–16.34; p = 0.031) were identified as independent predictors of 30-day mortality of BSI in burn patients. Conclusions Multidrug resistant gram-negative bacteria were the main pathogens of BSI in severe burn patients. Accurate evaluation of risk factors for BSI and the mortality of BSI in severe burn patients may improve early appropriate management.