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The outer-membrane component of the multi-drug efflux system - a structural analysis based on hydrophobicity distribution

100%

Roterman I. , Konieczny L. , Stapor K.

tom Vol. 20, no. 1

1--14

Aim: The structure of a multi-drug efflux system (specifically the outer membrane part) is the focus of our analysis. The role of electrostatic interactions in the efflux process is well understood. Methods: Our analysis is made possible by the application of the fuzzy oil drop model in its modified form (FOD-M). Results: The distribution of hydrophobicity in the periplasmic and membrane domains plays a significant role in both stabilisation within the membrane and in tunnel formation, which facilitates the transport of antibiotics. Conclusions: The analysis presented in this paper reveals the specificity of hydrophobicity distribution in relation to biological activity, as well as a possible mechanism for the folding process of proteins involved in multi-drug efflux.

Influence of time, temperature, pH and inhibitors on bioaccumulation of radiocaesium - 137Cs by lichen Hypogymnia physodes

86%

Pipíška M. , Horník M. , Kočiová M. , Augustín J. , Lesný J.

2005

tom Vol. 50,suppl.1

39-44

Caesium bioaccumulation experiments were carried out at 4 to 60°C using natural samples of the lichen Hypogymnia physodes. Thalli were incubated in 2.5 mi mol.l 1 CsCl solutions labelled with 137CsCl for up to 24 h at pH values from 2 to 10. Bioaccumulation of Cs+ ions in the first phase of the lichen-CsCl solution interaction is rapid, neither pH, nor temperature dependent within the range 4 to 60°C and observed also with the lichen biomass thermally inactivated at 60°C or chemically by formaldehyde. The second phase of 137Cs bioaccumulation is time, temperature and pH dependent and is inhibited by formaldehyde and thermal inactivation. The process at the initial concentration C0 = 2.5 ěmol.l 1 CsCl and 20°C reached equilibrium within 12 hours. It can be described by the first order reaction kinetics equation: log [Ct] = 1.89 - 0.00153 t, R = 0.950. Maximal values of Cs-bioaccumulation were observed at 20°C with minimum at 4°C and 40°C and at pH 4 5 with minimum at pH 2 and pH 6. Low caesium efflux values from lichen thalli by water and 0.1 mol.l 1 neutral salts at 20°C and 24 h equilibrium were observed. Efflux characterized by distribution coefficients D = [Cs]solution/[Cs]biomass at biomass/solution ratio 1:25 (w/v, wet wt.), decreases in the order: Li+- 78 × 10 3 >NH4 + = K+ 15 × 10 3 > Cs+ = Na+ 11 × 10 3. Low extractability of caesium from lichen by water and salt solutions can explain long persistent times of radiocaesium contamination sorbed by lichens, observed by many authors in caesiumcontaminated forest and mountain regions. Hypothesis of the role of the lichen secondary metabolites as caesium binders is discussed.

Mechanizm oporności na leki platynowe oraz strategie pokonywania tego zjawiska

81%

Weiss-Gradzińska W. , Krzempek W. , Trynda-Lemiesz L.

tom [Z] 67, 11-12

1105--1128

Platinum drugs belong to one of the oldest [2] and best investigated groups of cytotoxic drugs. On account of their high efficacy and alkylating-like action [14] they are used in a treatment of various types of neoplasms [3–5]. Despite investigators’ best efforts survival time of patients diagnosed with cancer is still short. Responsible for the fact is high toxicity of used therapeutic methods and development of resistance to them [3–5, 19]. In this paper authors review reasons behind decreased sensitivity of neoplastic cells to platinum treatment and discuss the newest promising trends in its overcoming. Due to different properties of neoplastic cells, availability of a chemotherapeutic agent inside a tumour is limited [9–12]. Moreover continuous development of resistance to platinum drugs further decreases their cellular concentration and inactivates their functions. Also owing to increased activity of DNA repair systems, higher tolerance to genome deformations and numerous mechanisms that lead to impaired apoptosis, drug efficacy is reduced [3-5, 19]. In order to increase a potency of platinum agents new therapeutic strategies are investigated. Coadministration with resistance modulators [20, 22, 23] and combination therapy with other antineoplastic drugs [8, 24–30] have already proved their effectiveness. Additionally, newer generations of platinum drugs are developed [15–18]. Mostly platinum(IV) prodrug complexes often releasing axial ligands with their own pharmacological action [5, 6, 31], but also multi-nuclear platinum compounds that form more complex DNA-adducts [32–35]. Other strategies include the development of innovative dosage forms such as single walled carbon nanotubes (SWCNTs), multiwalled carbon nanotubes (MWCNTs) [38, 39] or encapsulation [36, 37]. Finally utilisation of oncolytic viruses could be a way to selectively destroy neoplastically transformed cells [40].