Apmis

Kuo, Keng‐Liang; Chen, Chien‐Heng; Chen, Hsin‐I; Chung, Yen‐Yo; Chai, Chee‐Yin

doi: 10.1111/apm.12995pmid: 31520423

Meningiomas are common intracranial tumors, and most exhibit optimal prognosis; however, some meningiomas still recur and even develop malignant transformation in the following years, regardless of initial pathological grade. During these years, autophagy raises its significance in tumorigenesis and tumor suppression, both important for tumor development. The aim of this study was to elucidate the relationship between two autophagy markers, LC3B and beclin 1, with clinical and pathological parameters in patients with meningiomas. A total of 77 thin‐sectioned slides, retrospectively collected from meningioma patients, were analyzed and correlated with clinicopathological parameters. We found that expression of beclin 1 rather than LC3B correlated to better prognosis, lower pathological grade, and longer survival. Furthermore, intensity of beclin 1 was also found to be significantly related to the pathological grade. These findings indicated that beclin 1 as a protective factor predicts better prognosis and plays the role of tumor suppression in meningiomas.

Aghajani, Zahra; Rasooli, Iraj; Mousavi Gargari, Seyed Latif

doi: 10.1111/apm.12992pmid: 31512768

Iron uptake system is expressed in early stages of Acinetobacter baumannii infections under iron‐restricted conditions. This study is aimed at the evaluation of immuno‐protectivity of BfnH in comparison with BauA in both mature and selected fragmental proteins. The study was designed in single and combined forms of antigens. BfnH is presented in 3472 strains of A. baumannii with more than 97% identity. The preliminary immune‐informatics analysis of this protein indicated a region from the β‐barrel domain including exposed loops 2–5, with antigenic score comparable to that of BfnH. There was a significant rise in the specific IgG response in all test groups. The bacterial challenge with a lethal dose of A. baumannii demonstrated partial protection of whole proteins which coincides with a significant reduction in the bacterial population colonized in the main organs and an increase in the survival level. Passive immunization of the mice brought about 50% survival in the mice groups immunized with BfnH and with a combination of BfnH and BauA. The protectivity of siderophore receptors suggests their potential immunogenic role that could be considered as a component of multivalent subunit vaccine candidates against A. baumannii.

Paosen, Supakit; Jindapol, Sarunporn; Soontarach, Rosesathorn; Voravuthikunchai, Supayang Piyawan

doi: 10.1111/apm.12993pmid: 31512767

Pathogen resistance to conventional antibiotics has become a serious clinical and public health problem, making the development of an alternative mean a very urgent issue. Recently, biosynthesis of silver nanoparticles (AgNPs) was successfully accomplished in the presence of Eucalyptus citriodora leaf extract as a reducing agent. In this study, the antimicrobial mechanisms of AgNPs against important hospital‐acquired pathogens, including Gram‐positive, Gram‐negative bacteria, and fungi were further assessed. The results indicated that AgNPs could enhance a broad antimicrobial spectrum against drug‐resistant organisms, with a range of minimum inhibitory concentration from 0.02 to 0.36 μg/mL. Time‐kill assay showed that AgNPs produced bactericidal effects on the microorganisms. AgNPs could significantly reduce biofilm production in pathogens without affecting growth of the pathogens (p < 0.05). AgNPs inhibited cell viability and biofilm formation in a dose‐dependent manner. Cell membrane damage in microorganisms resulting from effects of AgNPs was observed. A significant increase in per cent uptake of crystal violet was observed in all isolates treated with AgNPs when compared with the control (p < 0.05). Upon treatment with AgNPs, the surface charge of the reference strains and clinical isolates of pathogens moved towards neutral. The alteration of surface potential after exposure to AgNPs could contribute to membrane disruption and cell viability. Scanning electron microscopy further confirmed morphological cell changes and disrupted the cell membrane. Increasing resistance to AgNPs was not induced by stepwise isolation of the bacteria after 45 passages on Luria‐Bertani agar supplemented with AgNPs. Furthermore, AgNPs was not toxic to red blood cells.

Tøttrup, Mikkel; Søballe, Kjeld; Bibby, Bo M.; Hardlei, Tore F.; Hansen, Peter; Fuursted, Kurt; Birke‐Sørensen, Hanne; Bue, Mats

doi: 10.1111/apm.12996pmid: 31515843

Cefuroxime is widely used as antibiotic prophylaxis for orthopaedic procedures. We evaluated bone, subcutaneous tissue (SCT) and plasma pharmacokinetics of cefuroxime in male patients undergoing total knee replacement (TKR) after both traditional short‐term infusion (STI) and continuous infusion (CI). Eighteen male patients undergoing TKR were randomly assigned to STI or CI of 1.5 g of cefuroxime. Measurements were obtained in plasma, SCT, cancellous and cortical bone every 30 min for 8 h following surgery. For sampling in solid tissues, microdialysis was applied. Population pharmacokinetic modelling was performed in order to estimate pharmacokinetic parameters, and to assess the probability of attaining cefuroxime concentrations above clinically relevant minimal inhibitory concentrations (MICs) for 65% and 90% of the 8 h dosing interval. Low SCT and cortical bone penetration were found in both the STI and the CI group, but the findings were only significant in the STI group. Irrespective of MIC, tissue and target, CI leads to improved probability of attaining relevant pharmacokinetic targets compared with STI. For the Staphylococcus aureus MIC breakpoint (4 μg/mL), STI leads to inadequate probability of target attainment. CI of 1.5 g of cefuroxime leads to improved probability of attaining relevant pharmacokinetic targets in male TKR patients compared with traditional STI. These findings suggest that application of CI may improve antibiotic prophylaxis for male TKR patients.

Andersen, Thomas; Østgård, René Drage; Aspari, Maithri Prasad; Kragstrup, Tue Wenzel; Glerup, Henning; Jurik, Anne Grethe; Johansen, Claus; Hvid, Malene; Deleuran, Bent Winding

doi: 10.1111/apm.12994pmid: 31512766

The aim was to examine anti‐tumor necrosis factor α (anti‐TNFα) therapy influence changes on Th17 and Th22 cells in patients with spondyloarthritis (SpA), and its correlation with changes in clinical and magnetic resonance imaging (MRI) activity and chronicity scores. The Th17 and Th22 cells were assessed at baseline, after 12 and 52 weeks of anti‐TNFα therapy by flow cytometry (ClinicalTrials.gov NCT4682724). The percentages of both Th17 and Th22 cells were increased by 70% at baseline compared with healthy controls (both p < 0.01). During treatment, these two subsets increased further to be 170% (Th17) and 123% (Th22) above levels in healthy controls (both p < 0.01). The same subsets decrease their expression of IL‐23R significantly during the observation period (p < 0.05). High levels of Th17 and Th22 cells at baseline were associated with the degree of chronic changes in the sacroiliac joints on MRI and a good clinical response to anti‐TNFα treatment after one year. Plasma levels were not associated with clinical changes. Th17 cells, and Th22 subsets, increased during one year of anti‐TNF‐α therapy in SpA, regardless of their clinical improvement. This supports that both the Th17 and Th22 subsets could be involved in the progression in SpA.

Bagheri Nejad, Ramin; Yahyaraeyat, Ramak; Es‐haghi, Ali; Nayeri Fasaei, Bahar; Zahraei Salehi, Taghi

doi: 10.1111/apm.12997pmid: 31514254

Brucellosis is a worldwide bacterial zoonosis caused by Brucella spp. No approved vaccine is available for human use against the disease. In this study, outer membrane vesicles (OMVs) from a Brucella melitensis biovar 1 human isolate obtained in Iran were used to immunize BALB/c mice (n = 12) by 2 intramuscular injections with a 2‐week interval. Another group of 12 mice was used as non‐vaccinated controls. Two weeks after the last vaccination, six mice of each group were sacrificed, and proliferation and interferon gamma (IFNγ) production responses of their splenocytes were evaluated following in vitro stimulation with killed Brucella cells. The other mice were challenged with the virulent B. melitensis isolate. Two weeks later, mice were killed and spleens were cultured to determine the number of the challenge strain. The results showed proliferative response and IFNγ production of splenocytes from vaccinated mice (stimulation index: 2.18 ± 0.57, and 1519.35 ± 10.70 pg/mL, respectively) were significantly higher than those of control mice (stimulation index: 1.02 ± 0.02, and 210.01 ± 17.58 pg/mL, respectively). Numbers of the challenge strain in spleens of vaccinated mice were also significantly less than those in the controls with 1.6 units of protection. Our study revealed vaccination with OMVs of the B. melitensis isolate could induce specific immune responses and protection against infection in the mouse model suggesting their potential application for active immunization against brucellosis.