A possible genotoxic effect of cytostatic drugs in occupationally exposed personnel

S obzirom na poznate citotoksične učinke citostatika, željelo se upozoriti na moguće mutagenetske implikacije profesionalne izloženosti ovim agensima. Obrađena je skupina od 21 medicinske sestre koje rade s citostaticima, kao i odgovarajuća kontrolna skupina. Korištena je konvencionalna metoda za testiranje kemijskih mutagena - metoda izmjena sestara kromatida, SCE. Iako se rezultati dobiveni u izloženoj skupini nisu statistički značajno razlikovali od kontrole, visoki rasponi SCE vrijednosti u ispitanica koje rade s citostaticima potvrđuju sumnju na genotoksični učinak ovih agenasa.The aim of the study was to determine possible mutagenic implications of occupational exposure to cytostatic agents. Twenty-one nurses handling antineoplastic drugs and a matching control group were examined. The conventional method for testing chemical mutagens, that of sister chromatid exchanges, SCE, was used. Although the results obtained in the exposed group did not significantly differ from those obtained for the controls, wide ranges of SCE values observed among the medical personnel handling cytostatic drugs confirm the suspicion of the genotoxic effect of those agents

Capillary abnormalities in workers occupationally exposed to ionizing and nonionizing radiations

Cilj studije je bio metodom kapilaroskopije upozoriti na mogući utjecaj ionizacijskog i neionizacijskog zračenja na periferni krvotok profesionalno izloženih osoba. Kapilaroskopski smo pregledali 100 osoba profesionalno izloženih ionizacijskom zračenju, 110 osoba profesionalno izloženih neionizacijskom zračenju i 80 kontrolnih, neizloženih osoba. U obje test-skupine oštećenja mikrocirkulacije su bila statistički značajno učestalija nego u kontrolnoj skupini.The aim of the study was to determine a possible effect of ionizing and nonionizing radiations on peripheral blood flow in occupationally exposed persons by means of capillaroscopic analysis. Altogether 290 subjects were examined. Of these 100 were occupationally exposed to ionizing radiation, 110 were occupationally exposed to nonionizing radiation and 80 control subjects never worked with radiation sources. Statistical analysis showed that microvascular abnormalities occurred significantly more frequently among occupationally exposed persons than in the control group

Activation of store-operated calcium entry in airway smooth muscle cells: insight from a mathematical model

Intracellular dynamics of airway smooth muscle cells (ASMC) mediate ASMC contraction and proliferation, and thus play a key role in airway hyper-responsiveness (AHR) and remodelling in asthma. We evaluate the importance of store-operated entry (SOCE) in these dynamics by constructing a mathematical model of ASMC signaling based on experimental data from lung slices. The model confirms that SOCE is elicited upon sufficient depletion of the sarcoplasmic reticulum (SR), while receptor-operated entry (ROCE) is inhibited in such conditions. It also shows that SOCE can sustain agonist-induced oscillations in the absence of other influx. SOCE up-regulation may thus contribute to AHR by increasing the oscillation frequency that in turn regulates ASMC contraction. The model also provides an explanation for the failure of the SERCA pump blocker CPA to clamp the cytosolic of ASMC in lung slices, by showing that CPA is unable to maintain the SR empty of . This prediction is confirmed by experimental data from mouse lung slices, and strongly suggests that CPA only partially inhibits SERCA in ASMC

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

A possible genotoxic effect of cytostatic drugs in occupationally exposed personnel

S obzirom na poznate citotoksične učinke citostatika, željelo se upozoriti na moguće mutagenetske implikacije profesionalne izloženosti ovim agensima. Obrađena je skupina od 21 medicinske sestre koje rade s citostaticima, kao i odgovarajuća kontrolna skupina. Korištena je konvencionalna metoda za testiranje kemijskih mutagena - metoda izmjena sestara kromatida, SCE. Iako se rezultati dobiveni u izloženoj skupini nisu statistički značajno razlikovali od kontrole, visoki rasponi SCE vrijednosti u ispitanica koje rade s citostaticima potvrđuju sumnju na genotoksični učinak ovih agenasa.The aim of the study was to determine possible mutagenic implications of occupational exposure to cytostatic agents. Twenty-one nurses handling antineoplastic drugs and a matching control group were examined. The conventional method for testing chemical mutagens, that of sister chromatid exchanges, SCE, was used. Although the results obtained in the exposed group did not significantly differ from those obtained for the controls, wide ranges of SCE values observed among the medical personnel handling cytostatic drugs confirm the suspicion of the genotoxic effect of those agents

Nearly spherical vesicle shapes calculated by use of spherical harmonics : axisymmetric and nonaxisymmetric shapes and their stability

A theoretical approach to determine nearly spherical shapes of phospholipid vesicles is developed. The method is general in the sense that it does not depend on any symmetry restrictions. Equilibrium shapes are assumed to correspond to the minimum of the membrane bending elastic energy at constant values of the membrane area, the vesicle volume and the difference of areas of the two leaflets of the phospholipid bilayer. The bending energy and the constraints are expanded up to fourth order terms in the deviation from a sphere, and in the subsequent calculations all terms up to the third order are included. The deviation is expressed as a series of spherical harmonics. It sis shown that the stability of the solutions can be tested by inspecting the eigenvalues of the matrix of second derivatives of the bending energy with respect to independent amplitudes of spherical harmonics expansion. The method is applied to the calculation of axisymmetric and nonaxisymmetric shapes, and the influences of different approximations are discussed. It is shown that at variations of the leaflet area difference stable oblate and stable prolate shapes are transformed into each other in a continuous manner.On développe une approche théorique pour déterminer la forme quasi sphérique des vésicules phospholipidiques. La méthode est générale, dans le sens qu'elle ne dépend pas d'une quelconque restriction de symétrie. On suppose que la forme à l'équilibre correspond au minimum d'énergie de tension de courbure de la membrane pour une valeur constante de la surface de la membrane, du volume des vésicules et de la différence de surface des doubles feuillets phospholipidiques de la membrane. L'énergie de courbure et les contraintes sont développées à l'ordre 4 en terme de la déviation de la forme par rapport à une sphère. Tous les termes jusqu'au troisième ordre sont inclus dans les calcules suivants. La déviation est exprimée en séries d'harmoniques sphériques. On montre que la stabilité des solutions peut être testée en regardant les valeurs propres de la matrice des dérivées secondes de l'énergie de courbure par rapport aux amplitudes indépendantes du développement en harmoniques sphériques. La méthode est appliquée aux calculs des formes à symétrie axiale ou non, et les influences des différentes approximations sont étudiées. On montre que pour des variations de la différence dans l'aire des feuillets, on peut transformer de manière continue une forme stable aplatie en une forme stable allongée et, réciproquement

Microspectroscopy of red blood cells.

Spectroscopic techniques have been widely employed to analyze properties of macromolecules and dynamics of intracellular events on bulk preparations of cells. The development of computer controlled microspectrophotometers has made possible the study of the same events in single cells, often providing significant and unexpected results. This paper briefly reviews experimental works carried out in our laboratories on single red blood cells. Microspectrophotometric techniques were applied which make use of the fact that ligand binding to intracellular haemoglobin is associated with optical changes. Information on the relative abundance of different haemoglobin components inside single erythrocytes of trout blood was obtained from spectra of air equilibrated samples, taking advantage of the extreme pH sensitivity of one of the four haemoglobin components. The kinetics of oxygen and carbon monoxide binding to haemoglobin has been followed and demonstrated to correspond to a zero order process, with a rate much slower than that characteristic for haemoglobin in solution. These results demonstrate that the process is diffusion limited; computer simulations suggest that ligand uptake is limited by the time required for the diffusion from the extracellular space of enough ligand molecules for total saturation of intraerythrocytic haemoglobin. Finally, oxygen dissociation curves in single red blood cells can be obtained by means of particular flow cell, with promising results for the study of physiological and pathological processes (namely red cell sickling in drepanocytosis)