Michele Vaz dos Anjos, Eduarda Possa, Gisele da Silva Fonseca, Larissa Bergoza, Leandro Tasso
{"title":"Cefepime distribution by microdialysis in peritoneal fluid of rats with or without experimental peritonitis","authors":"Michele Vaz dos Anjos, Eduarda Possa, Gisele da Silva Fonseca, Larissa Bergoza, Leandro Tasso","doi":"10.1111/apm.13418","DOIUrl":"10.1111/apm.13418","url":null,"abstract":"<p>The aim of this study was to investigate the penetration of cefepime into rat peritoneal fluid by microdialysis and to determine the relationship between unbound drug plasma and tissue concentration in healthy animals and in a sepsis model established through cecal ligation and puncture-induced peritonitis. Probe recovery was performed by dialysis and retrodialysis. Cefepime was administered at a dose of 110 mg/kg intravenously. Samples were collected for about 4 h, and concentrations were determined by liquid chromatography-electrospray ionization-QTOF MS. Tissue penetration was also determined. Probe recovery <i>in vivo</i> was 38.78% ± 3.31% and 38.83% ± 2.74% in the control and peritonitis groups, respectively. Cefepime was rapidly distributed in the peritoneal fluid in both groups. The peritoneal fluid/plasma cefepime ratio was 0.38 and 0.32 for the control and peritonitis groups, respectively. Cefepime concentrations were above the MIC of 4 mg/L for the main enterobacteria. The infection model that was used had no apparent effect on the pharmacokinetics of cefepime in rats. This was the first study to determine free cefepime concentrations in the peritoneal fluid of healthy rats and rats with experimental peritonitis.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 12","pages":"1096-1105"},"PeriodicalIF":2.2,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140806665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fábio Cassola, Nedy Ramírez, Camila Delarmelina, Marta Cristina Teixeira Duarte
{"title":"In vitro determination of the susceptibility of Malassezia furfur biofilm to different commercially used antimicrobials","authors":"Fábio Cassola, Nedy Ramírez, Camila Delarmelina, Marta Cristina Teixeira Duarte","doi":"10.1111/apm.13419","DOIUrl":"10.1111/apm.13419","url":null,"abstract":"<p><i>Malassezia furfur</i> is a yeast known as the etiological agent of seborrheic dermatitis. We evaluated the action of five different antimicrobials (amphotericin B, chloramphenicol, ketoconazole, fluconazole, and nystatin) on inhibiting biofilm formation and removing biofilm already formed by <i>M. furfur</i>. The assays were carried out using the microdilution method, and scanning electron microscopy images were used to analyze the biofilm structure. According to the results obtained, the percentage of inhibition was higher for chloramphenicol, followed by ketoconazole, nystatin, and amphotericin B. Regarding the eradication of the biofilm formed, the highest percentage was chloramphenicol, followed by ketoconazole and nystatin. Amphotericin B did not affect biofilm eradication, whereas fluconazole did not cause significant changes inhibiting or removing <i>M. furfur</i> biofilm. Therefore, except for fluconazole, all evaluated antimicrobials had inhibiting effects on the biofilm of <i>M. furfur</i>, either in its formation and/or eradication. Although the results achieved with chloramphenicol have been highlighted, further <i>in vitro</i> and <i>in vivo</i> studies are still needed in order to include this antimicrobial in the therapy of seborrheic dermatitis due to its toxicity, especially to the bone marrow.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 12","pages":"1106-1114"},"PeriodicalIF":2.2,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140798226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"LncRNA SNHG1 serves as a biomarker for systemic lupus erythematosus and participates in the disease progression","authors":"Linsen Jiang, Anning Qi, Hongyu Yang, Shuping Wang, Fei Wang, Xuemei Bai, Juan Ren","doi":"10.1111/apm.13410","DOIUrl":"10.1111/apm.13410","url":null,"abstract":"<p>LncRNAs play an important role in autoimmune diseases. The purpose of this study was to explore the role of lncRNA SNHG1 in systemic lupus erythematosus (SLE), and laid a theoretical foundation for the study of SLE. The basic clinical information of all subjects was first collected for statistical analysis, and SNHG1 expression in the serum of all subjects was detected by RT-qPCR. The value of SNHG1 in the diagnosis of SLE was assessed by ROC. The correlation between SNHG1 and each blood sample index was analyzed by Pearson correlation analysis. The role of SNHG1 in primary peripheral blood mononuclear cells (PBMCs) apoptosis was explored. SNHG1 expression is relatively upregulated in patients with SLE compared to healthy people. SNHG1 expression was positively correlated with SLEDAI score, IgG, CRP, and ESR, and negatively correlated with C3 and C4. ROC indicated that SNHG1 has the potential to assist in the diagnosis of SLE. PBMCs apoptosis in SLE was higher than that in control group, the knockdown and overexpression of SNHG1 could correspondingly inhibit and promote PBMCs apoptosis. SNHG1 has the potential to be a diagnosis marker for SLE and may be involved in regulating PBMCs apoptosis.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 7","pages":"507-514"},"PeriodicalIF":2.8,"publicationDate":"2024-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140798266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anni Sjöblom, Lauri Jouhi, Pirjo Laakkonen, Reija Randén-Brady, Jussi Tarkkanen, Caj Haglund, Petri Mattila, Timo Carpén, Jaana Hagström, Antti Mäkitie
{"title":"IGSF3 tissue expression in squamous cell carcinoma of the oropharynx: a novel tool for prognosis assessment in HPV-related and HPV-unrelated disease","authors":"Anni Sjöblom, Lauri Jouhi, Pirjo Laakkonen, Reija Randén-Brady, Jussi Tarkkanen, Caj Haglund, Petri Mattila, Timo Carpén, Jaana Hagström, Antti Mäkitie","doi":"10.1111/apm.13417","DOIUrl":"10.1111/apm.13417","url":null,"abstract":"<p>Biomarkers are not broadly used in the management of head and neck cancers (HNCs). Biomarkers have been beneficial in the management of other cancers, however, not in HNCs. Therefore, we observed the immunopositivity of a novel biomarker called immunoglobulin superfamily member 3 (IGSF3) in tumor tissues in HPV-related and HPV-unrelated OPSCC. Two patient cohorts (C1 and C2) from separate time periods were available for this study (total <i>N</i> = 282). Both consisted of OPSCC patients treated at the Helsinki University Hospital (HUS, Helsinki, Finland) during 2000–2016. For HPV determination, HPV mRNA <i>in situ</i> hybridization was used. Immunohistochemistry was used to assess IGSF3 immunopositivity in cancer tissues. Overall survival (OS) was used as endpoint in the statistical analysis. In C1, stronger immunopositivity of IGSF3 in tumor-infiltrating lymphocytes (TILs) correlated with favorable OS (p = 0.005). Stronger IGSF3 immunopositivity in tumor cells (TCs) was associated with HPV negativity (p = 0.017). Stronger IGSF3 immunopositivity in TILs correlated with HPV positivity (p < 0.001). Elevated IGSF3 immunopositivity in TILs associates with HPV-related tumors and may signify favorable prognosis. The immunopositivity of IGSF3 differs between HPV-related and HPV-unrelated OPSCC.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 12","pages":"1061-1070"},"PeriodicalIF":2.2,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apm.13417","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140589412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adrian Jimenez San San Mauro, Niels Høiby, Oana Ciofu
{"title":"Increased susceptibility to azithromycin of Pseudomonas aeruginosa biofilms using RPMI 1640 testing media","authors":"Adrian Jimenez San San Mauro, Niels Høiby, Oana Ciofu","doi":"10.1111/apm.13413","DOIUrl":"10.1111/apm.13413","url":null,"abstract":"<p>Azithromycin (AZM) is efficient for treatment of chronic <i>Pseudomonas aeruginosa</i> biofilm lung infections, despite of resistance in conventional susceptibility testing. It has been shown that planktonic <i>P. aeruginosa</i> are more susceptible to AZM when tested in RPMI 1640 medium. The aim of the study was to test the susceptibility to AZM of <i>P. aeruginosa</i> biofilms in LB vs RPMI 1640 media. We investigated the effect of AZM on planktonic and biofilms of (WT) <i>P. aeruginosa</i> (PAO1), the hypermutable (Δ<i>mutS</i>) and the antibiotic-resistant phenotype(Δ<i>nfxB</i>) mutants. The effect of AZM on young and mature biofilms was investigated in the modified Calgary Biofilm Device by estimation of the minimal biofilm inhibitory concentration (MBIC). The AZM MBIC<sub>90</sub> in LB/RPMI1640 on young biofilms treated for 24 h was 16/4 μg/mL for PAO1, 32/8 μg/mL for Δ<i>mutS,</i> and 256/16 μg/mL for Δ<i>nfxB,</i> while in mature biofilms was 256/2 μg/mL for PAO1 and Δ<i>mutS</i> and 16/1 μg/mL for Δ<i>nfxB.</i> The effect of AZM was improved when the treatment was prolonged to 72 h, supporting the intracellular accumulation of AZM. An increased susceptibility of <i>P. aeruginosa</i> biofilms to AZM was observed in RPMI 1640 than in LB medium. Our results might improve susceptibility testing and dosing of AZM for treatment of biofilm infections.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 12","pages":"1086-1095"},"PeriodicalIF":2.2,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apm.13413","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140589531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rui Ji, Hong Yang, Jiamei Chen, Anna Zhao, Xia Chen, Yanli Niu
{"title":"The role of hsa_circ_0042260/miR-4782-3p/LAPTM4A axis in gestational diabetes mellitus","authors":"Rui Ji, Hong Yang, Jiamei Chen, Anna Zhao, Xia Chen, Yanli Niu","doi":"10.1111/apm.13407","DOIUrl":"10.1111/apm.13407","url":null,"abstract":"<p>Gestational diabetes mellitus (GDM) is a common metabolic condition during pregnancy, posing risks to both mother and fetus. CircRNAs have emerged as important players in various diseases, including GDM. We aimed to investigate the role of newly discovered circRNA, hsa_circ_0042260, in GDM pathogenesis. Using GSE194119 dataset, hsa_circ_0042260 was identified and its expression in plasma, placenta, and HG-stimulated HK-2 cells was examined. Silencing hsa_circ_0042260 in HK-2 cells assessed its impact on cell viability, apoptosis, and inflammation. Bioinformatics analysis revealed downstream targets of hsa_circ_0042260, namely miR-4782-3p and LAPTM4A. The interaction between hsa_circ_0042260, miR-4782-3p, and LAPTM4A was validated through various assays. hsa_circ_0042260 was upregulated in plasma from GDM patients and HG-stimulated HK-2 cells. Silencing hsa_circ_0042260 improved cell viability, suppressed apoptosis and inflammation. Hsa_circ_0042260 interacted with miR-4782-3p, which exhibited low expression in GDM patient plasma and HG-stimulated cells. MiR-4782-3p targeted LAPTM4A, confirmed by additional assays. LAPTM4A expression increased in GDM patient plasma and HG-induced HK-2 cells following hsa_circ_0042260 knockdown or miR-4782-3p overexpression. In rescue assays, inhibition of miR-4782-3p or overexpression of LAPTM4A counteracted the effects of hsa_circ_0042260 downregulation on cell viability, apoptosis, and inflammation. In conclusion, the hsa_circ_0042260/miR-4782-3p/LAPTM4A axis plays a role in regulating GDM progression in HG-stimulated HK-2 cells.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 6","pages":"465-476"},"PeriodicalIF":2.8,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140575745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pathophysiological microenvironments in oral candidiasis","authors":"Mette Rose Jørgensen","doi":"10.1111/apm.13412","DOIUrl":"10.1111/apm.13412","url":null,"abstract":"<p>Oral candidiasis (OC), a prevalent opportunistic infection of the oral mucosa, presents a considerable health challenge, particularly in individuals with compromised immune responses, advanced age, and local predisposing conditions. A considerable part of the population carries <i>Candida</i> in the oral cavity, but only few develop OC. Therefore, the pathogenesis of OC may depend on factors other than the attributes of the fungus, such as host factors and other predisposing factors. Mucosal trauma and inflammation compromise epithelial integrity, fostering a conducive environment for fungal invasion. Molecular insights into the immunocompromised state reveal dysregulation in innate and adaptive immunity, creating a permissive environment for <i>Candida</i> proliferation. Detailed examination of <i>Candida</i> species (spp.) and their virulence factors uncovers a nuanced understanding beyond traditional <i>C. albicans</i> focus, which embrace diverse <i>Candida</i> spp. and their strategies, influencing adhesion, invasion, immune evasion, and biofilm formation. Understanding the pathophysiological microenvironments in OC is crucial for the development of targeted therapeutic interventions. This review aims to unravel the diverse pathophysiological microenvironments influencing OC development focusing on microbial, host, and predisposing factors, and considers <i>Candida</i> resistance to antifungal therapy. The comprehensive approach offers a refined perspective on OC, seeking briefly to identify potential therapeutic targets for future effective management.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 12","pages":"956-973"},"PeriodicalIF":2.2,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apm.13412","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140575732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The microenvironment in antibiotic susceptibility testing","authors":"Niels Høiby, Claus Moser, Oana Ciofu","doi":"10.1111/apm.13405","DOIUrl":"10.1111/apm.13405","url":null,"abstract":"<p>Antibiotic susceptibility testing (AST) by agar diffusion has been repeatedly standardized and, in most cases, gives results which predict clinical success when antibiotic treatment is based on such results. The formation of the inhibition zone is due to a transition from planktonic to biofilm mode of growth. The kinetics of the interaction of antibiotics with bacteria is similar during AST by agar diffusion and during administration of antibiotics to the patients. However, the Mueller-Hinton agar (MHA) recommended for AST agar diffusion test is fundamentally different from the composition of the interstitial fluid in the human body where the infections take place and human cells do not thrive in MH media. Use of RPMI 1640 medium designed for growth of eucaryotic cells for AST of <i>Pseudomonas aeruginosa</i> against azithromycin results in lower minimal inhibitory concentration, compared to results obtained by MHA. The reason is that the RPMI 1640 medium increases uptake and reduces efflux of azithromycin compared to MHA. During treatment of cystic fibrosis patients with azithromycin, mutational resistance occur which is not detected by AST with MHA. Whether this is the case with other antibiotics and bacteria is not known but it is of clinical importance to be studied.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 12","pages":"985-991"},"PeriodicalIF":2.2,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apm.13405","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140575735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}