AmyloGraph : a comprehensive database of amyloid-amyloid interactions

Information about the impact of interactions between amyloid proteins on their fibrillization propensity is scattered among many experimental articles and presented in unstructured form. We manually curated information located in almost 200 publications (selected out of 562 initially considered), obtaining details of 883 experimentally studied interactions between 46 amyloid proteins or peptides. We also proposed a novel standardized terminology for the description of amyloid-amyloid interactions, which is included in our database, covering all currently known types of such a cross-talk, including inhibition of fibrillization, cross-seeding and other phenomena. The new approach allows for more specific studies on amyloids and their interactions, by providing very well-defined data. AmyloGraph, an online database presenting information on amyloid-amyloid interactions, is available at (). Its functionalities are also accessible as the R package (). AmyloGraph is the only publicly available repository for experimentally determined amyloid-amyloid interactions

Totally implantable central venous access ports

Całkowicie implantowane systemy dożylnego podawania leków (tzw. porty dożylne) stanowią niezwykle dogodne rozwiązanie u chorych poddanych chemioterapii. Metoda ta znajduje coraz szersze zastosowanie. Rocznie 700-1000 dorosłym chorym w Polsce wszczepia się port donaczyniowy. Z inicjatywy krajowego konsultanta w dziedzinie onkologii klinicznej odbyło się spotkanie uzgodnieniowe w celu ustalenia zasad bezpiecznego stosowania portów w Polsce. W spotkaniu uczestniczyło 26 ekspertów z 17 ośrodków onkologicznych. Rezultatem spotkania stało się uzgodnienie zasad przedstawionych w formie standardów i zaleceń. Uzgodnienia dotyczyły wskazań do zastosowania portów, kwalifikacji chorych, warunków technicznych implantacji i okresu obserwacji po zabiegu, zapobiegania i leczenia powikłań infekcyjnych i powikłań zakrzepowych, szkolenia personelu obsługującego porty, informacji przekazywanej chorym.Totally implantable central venous access ports are very useful in chemotherapic treatment. It gains wider application. In Poland they are implanted in 700-1000 patient annually. National Consultant in Clinical Oncology at meeting with 26 experts from 17 oncologic centers established the principles of safe implantation of ports in Poland. The meeting resulted in report on standards and recommendations containing: recommendation on ports application, patients’ qualification, implantation technics and follow-up observation, prevention and treatment of infection and thrombotic complication, professional staff training and information for patients

Secondary school students’ knowledge on risk factors for cardiovascular diseases

Introduction: Cardiovascular diseases constitute the most frequent cause of death, even exceeding cancer. The so--called risk factors, both modifiable and non-modifiable, play a significant role in their development. methods: 200 secondary school students, aged 16–19 years, participated in the study (137 girls and 63 boys). The study was conducted by means of the authors’ own survey questionnaire. Results: The vast majority of respondents (187; 93.5%) appropriately indicated obesity, hypercholesterolemia and smoking as modifiable risk factors. Nearly half of the respondents (96; 48%) appropriately recognised abdominal obesity based on waist size measurements and in the vast majority (157; 78.5%) correctly marked body mass index (BMI) for proper body weight. Most (136; 68%) knew about arteriosclerosis, the aftermaths of excessive salt consumption (158; 79%), fast food (184; 92%) and alcohol (139; 69.5%). Definitely fewer students (63; 31.5%) indicated the sources of cholesterol in food and appropriately defined the notion of HDL (72; 36%) and BMI (73; 36.5%). Conclusion: Secondary school students’ knowledge on the risk factors for cardiovascular diseases is incomplete. There is a need to implement health education aimed at reducing the prevalence of risk factors at a young age and/or their elimination, and as a result preventing the development and progression of cardiovascular diseases.Wstęp: Choroby układu krążenia stanowią najczęstszą przyczynę zgonów, częstszą nawet niż choroby nowotworowe. W ich rozwoju istotne znaczenie mają zarówno modyfikowalne, jak i niemodyfikowalne czynniki ryzyka. METODY: Badaniem objęto 200 uczniów (137 dziewcząt i 63 chłopców) szkół licealnych w wieku 16–19 lat. Badanie przeprowadzono za pomocą autorskiego kwestionariusza ankiety. WYNIKI: Zdecydowana większość badanych (187; 93,5%) jako modyfikowalne czynniki ryzyka poprawnie wskazała otyłość, hipercholesterolemię i palenie tytoniu. Prawie połowa badanych (96; 48%) na podstawie obwodu pasa potrafiła rozpoznać otyłość brzuszną, a zdecydowana większość (157; 78,5%) poprawnie zaznaczyła zakres BMI (body mass index) dla prawidłowej masy ciała. Większość ankietowanych (136; 68%) wiedziała, czym jest miażdżyca, jakie są konsekwencje nadmiernego spożywania soli (158; 79%), posiłków typu fast food (184; 92%) oraz alkoholu (139; 69,5%). Zdecydowanie mniej ankietowanych (63; 31,5%) prawidłowo wskazało źródła cholesterolu w pokarmach oraz poprawnie zdefiniowało pojęcia HDL (72; 36%) i BMI (73; 36,5%). WNIOSKI: Wiedza uczniów szkół licealnych na temat czynników ryzyka chorób układu krążenia jest niepełna. Konieczne jest prowadzenie działalności w zakresie oświaty zdrowotnej, mającej na celu zmniejszenie rozpowszechnienia czynników ryzyka już w młodym wieku i/lub ich eliminację, a w konsekwencji zapobieganie rozwojowi i progresji chorób układu krążenia

New RAPMYCOI SensititreTM Antimicrobial Susceptibility Test for Atypical Rapidly Growing Mycobacteria (RGM)

Rapidly growing mycobacteria (RGM) cause an increasing international concern, mainly due to their natural resistance to many antibiotics. The aim of this study was to conduct species identification and determine the antimicrobial susceptibility profiles of RGM isolated in Poland. Antimicrobial susceptibility was tested using broth microdilution and the RAPMYCOI panel. A total of 60 strains were analysed, including the following species: M. fortuitum complex (30), M. abscessus subsp. abscessus (16), M. abscessus subsp. massiliense (7), M. chelonae (5), and M. mucogenicum (2). For 12 M. abscessus subsp. abscessus strains, the presence of the erm 41T28 genotype associated with inducible macrolide resistance and a functional erm gene was confirmed. A MUT2 mutation in the rrl gene (constitutive resistance) was identified for two strains from the subtype M. abscessus subsp. massiliense. Among the 15 tested antibiotics, amikacin and linezolid had the strongest antimycobacterial activity. Most of the tested strains were resistant to doxycycline and trimethoprim/sulfamethoxazole. Tigecycline MICs were low for all tested strains. Findings from our study highlight the importance of correct identification of clinical isolates and antimicrobial susceptibility testing

Antiatherosclerotic effects of 1-methylnicotinamide in apolipoprotein E/low-density lipoprotein receptor-deficient mice : a comparison with nicotinic acid

1-Methylnicotinamide (MNA), the major endogenous metabolite of nicotinic acid (NicA), may partially contribute to the vasoprotective properties of NicA. Here we compared the antiatherosclerotic effects of MNA and NicA in apolipoprotein E (ApoE)/ low-density lipoprotein receptor (LDLR)-deficient mice. ApoE/ LDLR2/2 mice were treated with MNA or NicA (100 mg/kg). Plaque size, macrophages, and cholesterol content in the brachiocephalic artery, endothelial function in the aorta, systemic inflammation, platelet activation, as well as the concentration of MNA and its metabolites in plasma and urine were measured. MNA and NicA reduced atherosclerotic plaque area, plaque inflammation, and cholesterol content in the brachiocephalic artery. The antiatherosclerotic actions of MNA and NicA were associated with improved endothelial function, as evidenced by a higher concentration of 6-keto-prostaglandin F1a and nitrite/nitrate in the aortic ring effluent, inhibition of platelets (blunted thromboxane B2 generation), and inhibition of systemic inflammation (lower plasma concentration of serum amyloid P, haptoglobin). NicA treatment resulted in an approximately 2-fold higher concentration of MNA and its metabolites in urine and a 4-fold higher nicotinamide/MNA ratio in plasma, compared with MNA treatment. In summary; MNA displays pronounced antiatherosclerotic action in ApoE/LDLR2/2 mice, an effect associated with an improvement in prostacyclin- and nitric oxide-dependent endothelial function, inhibition of platelet activation, inhibition of inflammatory burden in plaques, and diminished systemic inflammation. Despite substantially higher MNA availability after NicA treatment, compared with an equivalent dose of MNA, the antiatherosclerotic effect of NicA was not stronger. We suggest that detrimental effects of NicA or its metabolites other than MNA may limit beneficial effects of NicA-derived MNA

Synthesis and Biological Activity of Piperidinothiosemicarbazones Derived from Aminoazinecarbonitriles

To investigate how structural modifications affect tuberculostatic potency, we synthesized seven new piperidinothiosemicrabazone derivatives 8–14, in which three of them had a pyrazine ring replacing the pyridine ring. Derivatives 8–9 and 13–14 exhibited significant activity against the standard strain (minimum inhibitory concentration (MIC) 2–4 μg/mL) and even greater activity against the resistant M. tuberculosis strain (MIC 0.5–4 μg/mL). Additionally, the effects of compounds 8–9 were entirely selective (MIC toward other microorganisms ≥ 1000 μg/mL) and non-toxic (IC50 to HaCaT cells 5.8 to >50 μg/mL). The antimycobacterial activity of pyrazine derivatives 11–12 was negligible (MIC 256 to >500 μg/mL), indicating that replacing the aromatic ring was generally not a promising line of research in this case. The zwitterionic structure of compound 11 was determined using X-ray crystallography. Absorption, distribution, metabolism, and excretion (ADME) calculations showed that all compounds, except 11, could be considered for testing as future drugs. An analysis of the structure–activity relationship was carried out, indicating that the higher basicity of the substituent located at the heteroaromatic ring might be of particular importance for the antituberculous activity of the tested groups of compounds

Synthesis and Structure–Activity Relationship of 2,6-Disubstituted Thiosemicarbazone Derivatives of Pyridine as Potential Antituberculosis Agents

In this study, six new 2,6-disubstituted thiosemicarbazone derivatives of pyridine were synthesized (4–9), and their tuberculostatic activity was evaluated. All of them showed two- to eightfold higher activity (minimum inhibitory concentration (MIC) 0.5–4 µg/mL) against the resistant strain compared with the reference drug. Compounds 5 and 7, which contained the most basic substituents—pyrrolidine and piperidine—in their structure, strongly inhibited the growth of the standard strain (MIC 2 µg/mL). Furthermore, the same derivatives exhibited activity comparable to that of the reference drugs against some types of Gram-positive bacteria (MIC 0.49 µg/mL) and showed no cytotoxicity (IC50 > 50 µg/mL) in HaCaT cells. The zwitterionic structure of each compound was determined using X-ray crystallography. Absorption, distribution, metabolism, and excretion analyses showed that all compounds are good drug candidates. Thus, compounds 5 and 7 were identified as leading structures for further research on antituberculosis drugs with extended effects

Menthol- and thymol-based ciprofloxacin derivatives against Mycobacterium tuberculosis: in vitro activity, lipophilicity, and computational studies

Abstract In this work, we investigated the antitubercular properties of Ciprofloxacin derivatives conjugated with menthol and thymol moieties. For the sixteen derivatives, we established minimal inhibitory concentrations (MIC) using isolates of Mycobacterium tuberculosis that were resistant or susceptible to other antibiotics. For the most potent compound 1‐cyclopropyl‐6‐fluoro‐7‐{4‐[6‐((1R,2S,5R)‐2‐isopropyl‐5‐methylcyclohexyloxy)‐6‐oxohexyl]piperazin‐1‐yl}‐4‐oxo‐1,4‐dihydroquinoline‐3‐carboxylic acid (6), we determined fractional inhibitory concentration index (FICI) values to confirm antibacterial susceptibility and synergistic effects with other reference drugs. In addition, chromatographic studies of all the derivatives demonstrated a significant three to four-fold increase in lipophilicity and affinity to phospholipids compared to Ciprofloxacin. Finally, we conducted structure-based studies of the investigated compounds using molecular docking and taking into account protein target mutations associated with fluoroquinolone resistance. In summary, our findings indicate that the investigated compounds possess tuberculostatic properties, with some showing similar or even better activity against resistant strains compared to reference drugs. Increased lipophilicity and affinity to phospholipids of the new derivatives can offer several advantages for new drug candidates, beyond just improved cell membrane penetration. However, further studies are needed to fully understand their safety, efficacy, and mechanism of action