Drug interference in Trinder reaction

Our recent research of drug interference in Trinder reaction – a widely used chromogenic reaction in the field of clinical biochemistry, was focused on comparison of various drugs and the impact on determination of several biochemical parameters with validated diagnostic kits utilizing Trinder reaction. Our results showed significant alteration of results in therapeutic concentrations of ACC®, Dicynone® and Novalgin® in comparison to the control samples. Dobutamine, Tensamin and ascorbic acid showed significant interference only in samples containing 1 mmol/l of drug.V našem posledním výzkumu lékové interference v Trinderově reakci, široce rozšířené chromogenní reakci v oboru klinické biochemie, jsme se zaměřili na porovnání různých leků a jejich dopad na měření několika biochemických paramerů pomocí validovaných diagnostických souprav využívající Trinderovu reakci. Naše výsledky ukázaly významnou změnu výsledků při terapeutických koncentracích ACC, Dicynonu a Novalginu ve srovnání s kontrolními vzorky. Dobutamin, Tensamin a kyselina askorbová projevovaly významnou interferenci až u vzorků obsahujícíc koncentraci léku 1 mmol/l

Interference Dicynone v Trinderově reakci – porovnání produktů dodavatelů IVD

V této části našeho výzkumu jsme se zaměřili na porovnání interference Trinderovy reakce lékem Dicynone, u reagenčních setů různých výrobců in vitro diagnostiky působící v České republice. Trinderova reakce je v klinické biochemii poměrně rozšířená chromogenní reakce a Dicynone je široce užívané hemostatikum. Na výsledcích ukazujeme jednak to, že žádný z výrobců tuto interferenci zatím spolehlivě nevyřešil, ale také to, že se dá do značné míry omezit, jak lze uvést na příkladu fy Erba Lachema.This section of our Dicynone interference in Trinder reaction research was focused on performance of different in vitro diagnostic providers and their reagent sets from located in Czech Republic. Trinder reaction is a widely used chromogenic reaction and Dicynone is a abundantly used hemostatic medication. The results show that the interference is universal in all reagent kits utilizing Trinder reaction and also that the interference effect could be reduced as is shown in Erba Lachema company results

A new approach to the study of toxicity of polyphenol-rich compounds

Raw data gathered by Proteon Pharmaceuticals were further analyzed by co-workers of the Medical University of Lodz.Proteon Pharmaceuticals and one of the co-authors (Magdalena Lukasiak) were responsible mainly for cell culture and for performing of HCS analysis. Raw data gathered by Proteon Pharmaceuticals were further analyzed by co-workers of the Medical University of Lodz).The toxicity of in vitro tested compounds is usually evaluated based on EC50 values calculated from dose-response curves. However, there is a large group of compounds for which a standard four-parametric sigmoid curve fitting may be inappropriate for estimating EC50. In the present study, 22 polyphenol-rich compounds were prioritized from the least to the most toxic based on the total area under and over the dose-response curves (AUOC) in relation to baselines. The studied compounds were ranked across three key cell indicators (mitochondrial membrane potential, cell membrane integrity and nuclear size) in a panel of five cell lines (HepG2, Caco-2, A549, HMEC-1, and 3T3), using a high-content screening (HCS) assay. Regarding AUOC score values, naringin (negative control) was the least toxic phenolic compound. Aronox, spent hop extract and kale leaf extract had very low cytotoxicity with regard to mitochondrial membrane potential and cell membrane integrity, as well as nuclear morphology (nuclear area). Kaempferol (positive control) exerted strong cytotoxic effects on the mitochondrial and nuclear compartments. Extracts from buckthorn bark, walnut husk and hollyhock flower were highly cytotoxic with regard to the mitochondrion and cell membrane, but not the nucleus. We propose an alternative algorithm for the screening of a large number of agents and for identifying those with adverse cellular effects at an early stage of drug discovery, using high content screening analysis. This approach should be recommended for series of compounds producing a non-sigmoidal cell response, and for agents with unknown toxicity or mechanisms of action.Proteon Pharmaceuticalsinfo:eu-repo/grantAgreement/[European Regional Development Fund Innovative Economy Operational Programme]/UDA-POIG.01.03.01-10-129/08-00/[Production of polyphenol extracts of plant origin with antiplatelet and cardioprotective properties – FLAWOPIRYNA

Differentiation of polyvalent bacteriophages specific to uropathogenic Proteus mirabilis strains based on the host range pattern and RFLP

Artykuł opublikowany pod nazwiskiem Piątkowska (Grzejdziak)Urinary tract infections (UTIs) caused by P. mirabilis are difficult to cure because of the increasing antimicrobial resistance of these bacteria. Phage therapy is proposed as an alternative infection treatment. The aim of this study was to isolate and differentiate uropathogenic P. mirabilis strain specific polyvalent bacteriophages producing polysaccharide depolymerases (PDs). 51 specific phages were obtained. The plaques of 29 bacteriophages were surrounded by halos, which indicated that they produced PDs. The host range analysis showed that, except phages 58B and 58C, the phage host range profiles differed from each other. Phages 35 and 45 infected all P. mirabilis strains tested. Another 10 phages lysed more than 90% of isolates. Among these phages, 65A, 70, 66 and 66A caused a complete lysis of the bacterial lawn formed by 62% to 78% of strains. Additionally, phages 39A and 70 probably produced PDs. The phages' DNA restriction fragment length polymorphism (RFLP) analysis demonstrated that genomes of 51 isolated phages represented 34 different restriction profiles. DNA of phage 58A seemed to be resistant to selected EcoRV endonuclease. The 33 RFLP-EcoRV profiles showed a Dice similarity index of 38.8%. 22 RFLP patterns were obtained from single phage isolates. The remaining 12 restriction profiles consisted of 2 to 4 viruses. The results obtained from phage characterization based on the pattern of phage host range in combination with the RFLP method enabled effective differentiation of the studied phages and selection of PD producing polyvalent phages for further study

The role of glacier mice in the invertebrate colonisation of glacial surfaces: the moss balls of the Falljökull, Iceland

Glacier surfaces have a surprisingly complex ecology. Cryoconite holes contain diverse invertebrate communities while other invertebrates, such as Collembola often graze on algae and windblown dead organic on the glacier surface. Glacier mice (ovoid unattached moss balls) occur on some glaciers worldwide. Studies of these glacier mice have concentrated on their occurrence and mode of formation. There are no reports of the invertebrate communities. But, such glacier mice may provide a suitable favourable habitat and refuge for a variety of invertebrate groups to colonise the glacier surface. Here we describe the invertebrate fauna of the glacier mice (moss balls) of the Falljökull, Iceland. The glacier mice were composed of Racomitrium sp. and varied in size from 8.0 to 10.0 cm in length. All glacier mice studied contained invertebrates. Two species of Collembola were present. Pseudisotoma sensibilis (Tullberg, 1876) was numerically dominant with between 12 and 73 individuals per glacier mouse while Desoria olivacea (Tullberg, 1871) occurred but in far lower numbers. Tardigrada and Nematoda had mean densities of approximately 200 and 1,000 respectively. No Acari, Arachnida or Enchytraeidae were observed which may be related to the difficulty these groups have in colonizing the glacier mice. We suggest that glacier mice provide an unusual environmentally ameliorated microhabitat for an invertebrate community dwelling on a glacial surface. The glacier mice thereby enable an invertebrate fauna to colonise an otherwise largely inhospitable location with implications for carbon flow in the system

Digoxin, an Overlooked Agonist of RORγ/RORγT

Digoxin was one of the first identified RORγT receptor inverse agonists inhibiting the differentiation of Th17 cells. However, this compound exhibits inhibitory activity at relatively high concentrations that mediate cytotoxic effects. We previously identified several cardenolides that are structurally similar to digoxin that were able to induce RORγ/RORγT-dependent transcription. These observations encouraged us to reanalyze the effects of digoxin on RORγ/RORγT-dependent transcription at low, noncytotoxic concentrations. Digoxin induced RORγ/RORγT-dependent transcription in HepG2 and Th17 cells. Furthermore, analysis of the transcriptomes of Th17 cells cultured in the presence of digoxin revealed the induction of the expression of numerous Th17-specific genes, including IL17A/F, IL21, IL22, IL23R, CCR4, and CCR6. Thus, our study, which includes data obtained from intact cells, indicates that digoxin, similar to other cardenolides, is a potent RORγ/RORγT receptor activator and that its structure may serve as a starting point for the design of dedicated molecules that can be used in the development of adoptive cell therapy (ACT)