Combination therapy at an early stage of the novel coronavirus infection (COVID-19). Case series and design of the clinical trial “BromhexIne and Spironolactone for CoronаvirUs Infection requiring hospiTalization (BISCUIT)”

The article focuses on effective treatment of the novel coronavirus infection (COVID-19) at early stages and substantiates the requirement for antiviral therapy and for decreasing the viral load to prevent the infection progression. The absence of a specific antiviral therapy for the SARS-CoV-2 virus is stated. The authors analyzed results of early randomized studies using lopinavir/ritonavir, remdesivir, and favipiravir in COVID-19 and their potential for the treatment of novel coronavirus infection. Among the drugs blocking the virus entry into cells, the greatest attention was paid to the antimalaria drugs, chloroquine and hydroxychloroquine. The article addresses in detail ineffectiveness and potential danger of hydroxychloroquine, which demonstrated neither a decrease in the time of clinical recovery nor any improvement of prognosis for patients with COVID-19. The major objective was substantiating a possible use of bromhexine, a mucolytic and anticough drug, which can inhibit transmembrane serin protease 2 required for entry of the SARS-CoV-2 virus into cells. Spironolactone may have a similar feature. Due to its antiandrogenic effects, spironolactone can inhibit X-chromosome-related synthesis of ACE-2 receptors and activation of transmembrane serin protease 2. In addition to slowing the virus entry into cells, spironolactone decreases severity of fibrosis in different organs, including the lungs. The major part of the article addresses clinical examples of managing patients with COVID-19 at the University Clinic of the Medical Research and Educational Centre of the M. V. Lomonosov Moscow State University, including successful treatment with schemes containing bromhexine and spironolactone. In conclusion, the authors described the design of a randomized, prospective BISCUIT study performed at the University Clinic of the M. V. Lomonosov Moscow State University with an objective of evaluating the efficacy of this scheme.

Sensing of Prostate Spesific Antigen by Differential Pulse Anodic Stripping Voltammetry of Gold Nanoparticle - Silver Enhanced Labels

<div style="left: 78.8156px; top: 533.372px; font-size: 11.129px; font-family: sans-serif; transform: scaleX(0.968874);" data-canvas-width="302.2885949032258">Metode deteksi Antigen Spesifik Prostat (ASP) berdasarkan pemotongan peptide dengan menggunakan perak enhancer (AgEhn) pada nanopartikel emas (AuNP) sebagai penanda. ASP merupakan serin protease yang dihasilkan secara normal oleh sel jaringan prostat dan sel kanker prostat.ASP secara luas digunakan sebagai biomarker untuk kanker prostat.Aktivitas ASP dideteksi berdasarkan pemotongan peptida yang terikat pada dasar wellplate melalui interaksi biotin – avidin. Setelah proses pemotongan, peptida-SH yang terpotong akan terbuang dalam proses pembilasan, peptidayang terpotong pada dasar wellplate tidak dapat mengikat nanopartikel emas karena kehilangan gugus tiol (-SH) pada ujung peptida. Sisa peptide-SH yang tidak terpotong akan berikatan dengan AuNP, diikuti dengan reduksi secara autokatalitik pada larutan AgEhn menjadi Ag(s). Jumlah Ag yang terdapat pada permukaan AuNP ditentukan secara voltametri lucutan anodik (VLA) setelah mengoksidasi Ag (s) menjadi ion Ag+ menggunakan elektroda screen printed carbon (SPC). Optimasi dilakukan pada kondisi pengukuran dan kondisi immunoassay, sehingga penentuan PSA pada rentang 1–500 ng.mL-1 dihasilkan limit deteksi sebesar 152,204 ng.mL-1 dengan sensitivitas 0,003 μ A/ng.mL-1. Penentuan PSA dengan metode ini telah berhasil dilakukan, namun masih membutuhkan kajian lebih lanjut.</div>

Sensing of Prostate Spesific Antigen by Differential Pulse Anodic Stripping Voltammetry of Gold Nanoparticle - Silver Enhanced Labels

<div style="left: 78.8156px; top: 533.372px; font-size: 11.129px; font-family: sans-serif; transform: scaleX(0.968874);" data-canvas-width="302.2885949032258">Metode deteksi Antigen Spesifik Prostat (ASP) berdasarkan pemotongan peptide dengan menggunakan perak enhancer (AgEhn) pada nanopartikel emas (AuNP) sebagai penanda. ASP merupakan serin protease yang dihasilkan secara normal oleh sel jaringan prostat dan sel kanker prostat.ASP secara luas digunakan sebagai biomarker untuk kanker prostat.Aktivitas ASP dideteksi berdasarkan pemotongan peptida yang terikat pada dasar wellplate melalui interaksi biotin – avidin. Setelah proses pemotongan, peptida-SH yang terpotong akan terbuang dalam proses pembilasan, peptidayang terpotong pada dasar wellplate tidak dapat mengikat nanopartikel emas karena kehilangan gugus tiol (-SH) pada ujung peptida. Sisa peptide-SH yang tidak terpotong akan berikatan dengan AuNP, diikuti dengan reduksi secara autokatalitik pada larutan AgEhn menjadi Ag(s). Jumlah Ag yang terdapat pada permukaan AuNP ditentukan secara voltametri lucutan anodik (VLA) setelah mengoksidasi Ag (s) menjadi ion Ag+ menggunakan elektroda screen printed carbon (SPC). Optimasi dilakukan pada kondisi pengukuran dan kondisi immunoassay, sehingga penentuan PSA pada rentang 1–500 ng.mL-1 dihasilkan limit deteksi sebesar 152,204 ng.mL-1 dengan sensitivitas 0,003 μ A/ng.mL-1. Penentuan PSA dengan metode ini telah berhasil dilakukan, namun masih membutuhkan kajian lebih lanjut.</div>

Molecular characteristics of bap-positiveStaphylococcus aureusstrains from dairy cow mastitis

The biofilm-associated protein (Bap) ofStaphylococcus aureusis a high molecular weight cell-wall-anchored protein involved in biofilm formation, first described in bovine mastitis strains from Spain. So far, studies regarding Bap were mainly based on the Spanish strain V329 and its mutants, but no information on the genetic variability ofbap-positiveStaph. aureusstrains is yet available in the literature. The present study investigated the molecular characteristics of 8bap-positiveStaph. aureusstrains from subclinical bovine mastitis, isolated in 5 herds; somatic cell counts (SCC) of milk samples were also registered. Strains were characterised using MLST, SPA typing and microarray and the results were compared with V329. All isolates from this study and V329 were assigned to ST126, t605, but some molecular differences were observed. Only herd A and B strains harboured the genes for β-lactams resistance; the leukocidin D/E gene, a type I site-specific deoxyribonuclease subunit, 3rd locus gene and serin-protease A and B were carried by all strains, but not by V329, while serin-protease E was absent in V329 and in another isolate. Four isolates and V329 harboured the fibronectin-binding protein B gene. SCC showed the highest value in the milk sample affected by the only strain carrying all the virulence factors considered. Potential large variability of virulence was evidenced among V329 and allbap-positiveStaph. aureusstrains considered: the carriage offnbcould enhance the accumulation of biofilm, but the lack oflukD/EandsplA, BorEmight decrease the invasiveness of strain.