Copper and Its Complexes in Medicine: A Biochemical Approach

The fundamental role of copper and the recognition of its complexes as important bioactive compounds in vitro and in vivo aroused an ever-increasing interest in these agents as potential drugs for therapeutic intervention in various diseases. The vast array of information available for their bioinorganic properties and mode of action in several biological systems, combined with the new opportunities offered by the flourishing technologies of medicinal chemistry, is creating an exciting scenario for the development of a novel generation of highly active drugs with minimized side effects which could add significantly to the current clinical research and practice. In this paper we attempt to summarize all the available-to-date information on these issues

The state of research equipment in South Africa: towards best practice

The article makes the point that instrumentation is critical to the science and technology infrastructure. Furthermore, it reports the results of a relevant national survey. Information is available for three groups – (i) research councils, (ii) universities, and (iii) technikons, museums and government departments as one group. This level of aggregation has been chosen in order to assist in the development of recommendations related to national policy. In addition, the state of equipment in the country is compared and contrasted with those in a number of countries abroad. Although it emerges that the Research Councils in South Africa possess the largest quantity of equipment, for the purpose of this paper, focus is given to the results of the Universities group since it is felt this provides greater ease of comparison to other developing countries.Die artikel beklemtoon dat instrumentasie krities is tot die wetenskap- en tegnologieinfrastruktuur. Verder rapporteer dit resultate van ‘n toepaslike nasionale ondersoek. Informasie word verskaf volgens drie kategorië, naamlik – (i) Navorsingsrade, (ii) Universiteite en (iii) Universiteite van Tegnologie (Tegnikons), asook Museums en Staatsdepartemente. Hierdie samestelling is gekies om te help met die ontwikkeling van voorstelle t.o.v. ‘n nasionale riglyn. Die toestand van toerusting in die land word vergelyk met dié van verskeie internasionale lande. Alhoewel dit blyk dat die Navorsingsrade in Suid-Afrika die grootste hoeveelheid toerusting besit, vir die doel van hierdie dokument, is daar klem gelê op die Universiteitsgroep, omdat dit beskou word as meer vergelykbaar met die situasie in ander ontwikkelende lande.http://sajie.journals.ac.z

Genotoxic effect induced by hydrogen peroxide in human hepatoma cells using comet assay

Background: Hydrogen peroxide is a common reactive oxygen intermediate generated by variousforms of oxidative stress. Aims: The aim of this study was to investigate the DNA damage capacity ofH2O2 in HepG2 cells. Methods: Cells were treated with H2O2 at concentrations of 25 μM or 50 μM for5 min, 30 min, 40 min, 1 h or 24 h in parallel. The extent of DNA damage was assessed by the cometassay. Results: Compared to the control, DNA damage by 25 μM and 50 μM H2O2 increasedsignificantly with increasing incubation time up to 1 h, but it was not increased at 24 h. Conclusions:Our Findings confirm that H2O2 is a typical DNA damage inducing agent and thus is a good modelsystem to study the effects of oxidative stress. DNA damage in HepG2 cells increased significantlywith H2O2 concentration and time of incubation but later decreased likely due to DNA repairmechanisms and antioxidant enzyme

Base-pair resolution analysis of the effect of supercoiling on DNA flexibility and major groove recognition by triplex-forming oligonucleotides.

In the cell, DNA is arranged into highly-organised and topologically-constrained (supercoiled) structures. It remains unclear how this supercoiling affects the detailed double-helical structure of DNA, largely because of limitations in spatial resolution of the available biophysical tools. Here, we overcome these limitations, by a combination of atomic force microscopy (AFM) and atomistic molecular dynamics (MD) simulations, to resolve structures of negatively-supercoiled DNA minicircles at base-pair resolution. We observe that negative superhelical stress induces local variation in the canonical B-form DNA structure by introducing kinks and defects that affect global minicircle structure and flexibility. We probe how these local and global conformational changes affect DNA interactions through the binding of triplex-forming oligonucleotides to DNA minicircles. We show that the energetics of triplex formation is governed by a delicate balance between electrostatics and bonding interactions. Our results provide mechanistic insight into how DNA supercoiling can affect molecular recognition, that may have broader implications for DNA interactions with other molecular species

Antineoplastic Drugs as a Potential Risk Factor in Occupational Settings: Mechanisms of Action at the Cell Level, Genotoxic Effects, and Their Detection Using Different Biomarkers

U članku je prikazana osnovna podjela antineoplastičnih lijekova prema mehanizmima djelovanja na razini stanice. Objašnjeni su mehanizmi genotoksičnosti najvažnijih vrsta lijekova koji se primjenjuju u okviru uobičajenih protokola za liječenje zloćudnih novotvorina. Navedena je važeća klasifi kacija antineoplastika prema kancerogenom potencijalu, podaci o mutagenom potencijalu te je prikazana njihova podjela u skladu s anatomsko-terapijsko-kemijskim sustavom klasifi kacije. Sustavno su prikazani najvažniji rezultati svjetskih i hrvatskih istraživanja na populacijama radnika izloženih antineoplasticima, provedenih u razdoblju 1980.-2009. s pomoću četiri najčešće primjenjivane metode: analize izmjena sestrinskih kromatida, analize kromosomskih aberacija, mikronukleus-testa i komet-testa. Objašnjena su osnovna načela navedenih metoda te raspravljene njihove prednosti i nedostaci. Biološki pokazatelji daju važne podatke o individualnoj osjetljivosti profesionalno izloženih ispitanika koji mogu poslužiti unaprjeđenju postojećih uvjeta rada i upravljanju rizicima pri izloženosti genotoksičnim agensima. Na osnovi prednosti i nedostataka citogenetičkih metoda zaključeno je da je mikronukleus-test, koji podjednako uspješno dokazuje klastogene i aneugene učinke, jedna od najboljih metoda dostupnih za otkrivanje štetnih djelovanja antineoplastičnih lijekova koji su u aktivnoj primjeni.This article brings an overview of the mechanisms of action of antineoplastic drugs used in the clinical setting. It also describes the genotoxic potentials of the most important classes of antineoplastic drugs involved in standard chemotherapy protocols. Classifi cation of antineoplastic drugs according to the IARC monographs on the evaluation of carcinogenic risks to humans is accompanied by data on their mutagenicity and the most recent updates in the Anatomical Therapeutic Chemical (ATC) Classifi cation System. We report the main fi ndings of biomonitoring studies that were conducted in exposed healthcare workers all over the world between 1980 and 2009 using four biomarkers: sister chromatid exchanges, chromosome aberrations, micronuclei. and the comet assay. The methods are briefl y explained and their advantages and disadvantages discussed. Biomarkers provide important information on individual genome sensitivity, which eventually might help to improve current working practices and to manage the risks related with exposure to genotoxic agents. Taking into consideration all known advantages and drawbacks of the existing cytogenetic methods, the micronucleus assay, which is able to detect both clastogenic and aneugenic action, is the most suitable biomarker for assessing harmful effects of antineoplastic drugs currently used in health care

Measuring the effects of pesticides on occupationally exposed humans with the comet assay

In this study we examine the effects of a mixture of pesticides on occupationally exposed agricultural workers. The study was performed on 149 people, 84 agricultural workers and 65 healthy men from the same area, who served as the control group. The exposed group was divided into a subgroup with 65 individuals moderately exposed (39 men and 26 women) and a highly exposed subgroup consisted of 19 men. The statistical analysis of the comet assay results showed that there were no significant differences in basal DNA damage between pesticide-exposed workers and the control group nor between moderately and highly exposed ones. In addition, exposure of peripheral blood lymphocytes to hydrogen peroxide or 7-irradiation led to a similar degree of DNA damage and subsequent repair for all the studied populations. © 2006 Wiley Periodicals, Inc