肺癌病人医院内获得性肺炎34例临床分析

目的 探讨肺癌病人医院内获得性肺炎（HAP）的病原菌及其药敏情况,正确选择抗生素。方法 对34例肺癌病人合并HAP进行回顾性分析。结果 38株病原菌中,革兰阴性杆菌32例（84．21％）,其中大肠埃顽希氏菌9株,铜绿假单胞菌8株,肺炎克雷伯氏杆菌8株。阿米卡星、头孢他啶和头孢哌酮＋舒巴坦对上述三种菌株敏感性较高。结论 明确肺癌病人AHP的病原菌及其药敏结果,可指导临床合理应用抗生素。     

An in vitro study on antiproliferative and antiestrogenic effects of Boerhaavia diffusa L. extracts

Ethnopharmacological relevance

Boerhaavia diffusa L. (Nyctinaceae) is a plant of tropical region used in Indian traditional medicine for the treatment of human ailments including abdominal tumor, jaundice, dyspepsia, menstrual disorders, etc. This plant also has antilymphoproliferative, antimetastatic and immunomodulatory effects.

Aim of the study

This study aimed to assess the antiproliferative and antiestrogenic properties of methanol extract of Boerhaavia diffusa (BME) in MCF-7 breast cancer cell lines.

Materials and methods

The effective concentration range of BME on cell viability was analyzed using MTT assay. Hydroxylapatite assay (HAP) was carried out to confirm the competitive binding of BME to the estrogen receptor (ER). The effect of BME on the expression of a selected estrogen responsive gene pS2 was analyzed by RT-PCR. The ability of BME to alter the cell cycle phases and distributions were studied using FACS analysis.

Results

Treatment with varying concentrations of BME (20–320 μg/mL) resulted in moderate to very strong growth inhibition in MCF-7 cell lines. BME competed with [³H]-estradiol for binding to ER with IC₅₀ value of 320 ± 25 μg/mL. RT-PCR analysis revealed that BME reduced the mRNA expression of pS2 indicating the antiestrogenic action of BME. BME treatment for 48 h resulted in a remarkable increase in the number of MCF-7 cells in the G0-G1 fraction from 69.1% to 75.8%, with a reciprocal decrease of cells in all other phases indicating cell cycle arrest at G0-G1 phase.

Conclusions

The results demonstrate that Boerhaavia diffusa possess antiproliferative and antiestrogenic properties and suggest that it may have therapeutic potential in estrogen dependent breast cancers.     

DHCC受体检测方法的研究

本文采用葡聚糖包裹的活性炭石(DCC)法、羟基磷灰石(HAP)法及等电聚焦电泳(IEF)法,在各种条件下检测了1.25(OH)_2D_3(DHCC)受体的含量。这3种方法得到的表现解离常数(Kd)分别等于4.2×10~(-9)mol/L、2.3×10~(-9)mol/L和6.4×10~(-9)mol/L;该受体蛋白分别在10nmol/L、8nmol/L和30nmol/L浓度的〔~3H〕DHCC处被饱和。该受体对D_3类似物的结合能力依次为1,25(OH)_2D_3>>25(OH)D_3>D_3≈E_2。我们所测佝偻病鸡3种组织中该受体含量依次为肠>输卵管壳腺>>肝。用DCC法,在4℃孵育2～5h,结合最稳定。用KTED缓冲液测得的胞液DHCC受体含量比用TED缓冲液高(P<0.05)。     

Diagnostic accuracy of Gram staining when predicting staphylococcal hospital-acquired pneumonia and ventilator-associated pneumonia: a systematic review and meta-analysis

BackgroundThere is no clear guidance on empirical antibiotic coverage against Staphylococcus aureus for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP).ObjectiveTo evaluate whether the presence of clusters of Gram-positive cocci in Gram staining of respiratory samples predicts S. aureus as HAP/VAP pathogen.MethodsData sources were MEDLINE, PubMed, Embase, Scielo, CINAHL and Scopus, from inception to 15/07/2017 (update on 31/10/2019), and original data from a single-centre database (PROSPERO: CRD42017072138). We included studies reporting the diagnostic accuracy of a Gram-staining evaluation suggestive of Staphylococcus compared with a positive culture for S. aureus in any type of lower respiratory tract sample. Participants were adult patients with HAP/VAP. The index test was morphological evaluation of Gram staining of respiratory samples. We followed PRISMA guidelines and assessed risk of bias and applicability with the QUADAS-2 tool. We conducted a meta-analysis using a bivariate random effects model.ResultsWe selected five studies that included only VAP and data from a single-centre database including VAP and HAP. We pooled six studies for VAP and analysed 1665 respiratory samples. Pooled sensitivity was 68% (95%CI 49–83 and specificity 95% (95%CI 86–98). The pooled positive likelihood ratio was 12.7 (95%CI 5.1–31.6), negative likelihood ratio 0.34 (95%CI 0.20–0.57), diagnostic odds ratio 38 (95%CI 13–106) and area under the summary receiver operating curve (SROC) 0.91 (95%CI 0.88–0.93). There was great heterogeneity between sensitivity and specificity. In scenarios in which the prevalence of S. aureus was between 5% and 20%, the positive and negative predictive values were 62% (95%CI 47–77) and 95% (95%CI 82–100), respectively.ConclusionsDetection of Gram-positive cocci in clusters in respiratory samples of patients with VAP has the potential to guide risk assessments of S. aureus for more personalized antibiotic coverage. Randomized clinical trials with patient-centred outcomes are needed for strong clinical recommendations.     

Evaluation of Plasmodium vivax HAP2 as a transmission-blocking vaccine candidate

Transmission-blocking vaccine (TBV) is a promising strategy to interfere with the transmission of malaria. To date, only limited TBV candidate antigens have been identified for Plasmodium vivax. HAP2 is a gamete membrane fusion protein, with homology to the class II viral fusion proteins. Herein we reported the characterization of the PvHAP2 for its potential as a TBV candidate for P. vivax. The HAP2/GCS1 domain of PvHAP2 was expressed in the baculovirus expression system and the recombinant protein was used to raise antibodies in rabbits. Indirect immunofluorescence assays showed that anti-PvHAP2 antibodies reacted only with the male gametocytes on blood smears. Direct membrane feeding assays were conducted using four field P. vivax isolates in Anopheles dirus. At a mean infection intensity of 72.4, 70.7, 51.3, and 15.6 oocysts/midgut with the control antibodies, anti-PvHAP2 antibodies significantly reduced the midgut oocyst intensity by 40.3, 44.4, 61.9, and 89.7%. Whereas the anti-PvHAP2 antibodies were not effective in reducing the infection prevalence at higher parasite exposure (51.3–72.4 oocysts/midgut in the control group), the anti-PvHAP2 antibodies reduced infection prevalence by 50% at a low challenge (15.6 oocysts/midgut). Multiple sequence alignment showed 100% identity among these Thai P. vivax isolates, suggesting that polymorphism may not be an impediment for the utilization of PvHAP2 as a TBV antigen. In conclusion, our results suggest that PvHAP2 could serve as a TBV candidate for P. vivax, and further optimization and evaluation are warranted.     

发热 咳嗽 头发稀疏

<正>患儿男,6月龄,因"发热伴咳嗽半个月"于2009-02-12由南京儿童医院重症监护室(ICU)转入呼吸科。患儿2009-01-28出现不明原因发热,热型不规则,体温最高     

Terapias intervencionistas en hipertensión pulmonar

Despite advances in drug therapy, pulmonary hypertension—particularly arterial hypertension (PAH)—remains a fatal disease. Untreatable right heart failure (RHF) from PAH eventually ensues and remains a significant cause of death in these patients. Lowering pulmonary input impedance with different PAH-specific drugs is the obvious therapeutic target in RHF due to chronically increased afterload. However, potential clinical gain can also be expected from attempts to unload the right heart and increase systemic output. Atrial septostomy, Potts anastomosis, and pulmonary artery denervation are interventional procedures serving this purpose. Percutaneous balloon pulmonary angioplasty, another interventional therapy, has re-emerged in the last few years as a clear alternative for the management of patients with distal, inoperable, chronic thromboembolic pulmonary hypertension. The current review discusses the physiological background, experimental evidence, and potential clinical and hemodynamic benefits of all these interventional therapies regarding their use in the setting of RHF due to severe pulmonary hypertension.     

Hydroxyapatite nanoparticle‐induced mitochondrial energy metabolism impairment in liver cells: in vitro and in vivo studies

Hydroxyapatite nanoparticles (HAP‐NPs) have been extensively developed as drug carriers, bone implants, coating materials, etc. in the human body. However, research focusing on the potential side effects of HAP‐NPs on the mitochondria‐associated energy metabolism in liver cells is lacking. In this study, HAP‐NPs with a long diameter of 80 nm and a short diameter of 20 nm were evaluated for their ability to induce mitochondrial energy metabolism dysfunction in vitro and in vivo . In the in vitro system, the buffalo rat hepatocyte (BRL) cell line was directly exposed to the HAP‐NPs. The results of these experiments showed that the HAP‐NPs induced inhibition of mitochondrial dehydrogenase activity, which was accompanied by a decrease in the mitochondrial membrane potential (MMP). In addition, HAP‐NPs elevated the hepatic levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and decreased the levels of GSH and SOD. These data indicated that HAP‐NPs induced a lowered rate of electron transfer in the mitochondrial respiratory chain, accompanied by a decrease in the activity of the mitochondrial respiratory chain complexes I, II and III. Furthermore, HAP‐NPs induced a decline in the enzymatic expression in the Krebs cycle. We also investigated the role of Kupffer cells (KCs, rat‐derived) in the effects induced by the HAP‐NPs. The supernatant from the HAP‐NP‐treated KCs was used to stimulate the BRL cells. We observed that the HAP‐NPs had the ability to induce KC activation. The activation of KCs then led to the release of tumor necrosis factor‐α (TNF‐α), nitric oxide (NO) and reactive oxygen species (ROS), and induced the inhibition of mitochondrial respiratory chain complexes I, II and III in the BRL cells. In the in vivo study, the TEM examination revealed mitochondrial swelling and vacuolar degeneration in the HAP‐NP‐treated hepatocytes. In addition, the amount of succinate (Suc), an intermediate in the mitochondrial Krebs cycle, also declined in the ¹H NMR spectroscopic measurements. Copyright © 2017 John Wiley & Sons, Ltd.     

Murepavadin: a new antibiotic class in the pipeline

Introduction: With the increase in multi-drug resistant P. aeruginosa, antimicrobials with a novel mechanism of action are needed that can target these infections.

Areas covered: Intravenous murepavadin is in Phase 3 development for the treatment of HABP/VABP due to P. aeruginosa. This paper summarizes the available information on the discovery, the in vitro activity, pharmacokinetic and pharmacodynamic properties and the clinical pharmacology of murepavadin to date.

Expert commentary: P. aeruginosa has an intrinsic resistance to many antibiotics due to high cellular impermeability and efficient drug efflux mechanisms, and the recent increase in prevalence of multidrug-resistant P. aeruginosa infections are particularly threatening in ICU settings. Murepavadin is a pathogen specific antimicrobial peptidomimetic with a novel, non-lytic mechanism of action, and is the first in class of outer membrane protein targeting antibiotics which are being developed. Murepavadin displays a potent in vitro activity including carbapenemase-producing and colistin-resistant P. aeruginosa. Murepavadin is active in pre-clinical animal models including infections with XDR isolates. The Pharmacokinetics is well characterized including subjects with impaired renal function and patients with VABP. Intravenous murepavadin is currently under clinical development for the treatment of HABP/VABP due to P. aeruginosa infection.