Genotoxicity and cytotoxicity of sevoflurane in two human cell lines in vitro with ionizing radiation / Genotoxicidad y citotoxicidad del sevoflurane en dos lineas celulares humanas in vitro con radiacion ionizante

Objective: To determine the in vitro toxicity of different concentrations of sevoflurane in cells exposed to X-ray. Methods: The genotoxic effects of sevofluorane were studied by means of the micronucleus test in cytokinesis-blocked cells of irradiated human lymphocytes. Subsequently, its cytotoxic effects on PNT2 (normal prostate) cells was determined using the cell viability test (MTT) and compared with those induced by different doses of X-rays. Results: A dose- and time-dependent cytotoxic effect of sevofluorane on PNT2 cells was determined (p >0.001) and a dose-dependent genotoxic effect of sevofluorane was established (p >0.001). Hovewer, at volumes lower than 30 μL of sevofluorane at 100%, a non-toxic effect on PNT2 cells was shown. Conclusion: sevofluorane demonstrates a genotoxic capacity as determined in vitro by micronucleus test in cytokinesis-blocked cells of irradiated human lymphocytes.

Objetivo: Determinar la capacidad genotóxica del anestésico sevofluorano en en células expuestas a radiación ionizante. Métodos: La genotoxicidad del sevofluorane se determinó mediante el test del bloqueo citocinético de linfocitos humanos irradiados bloqueados con citochalasina. La capacidad citotóxica se determinó mediante el test de viabilidad celular e inhibición del crecimiento celular (MTT) en células PNT2 (epiteliales de próstata), comparando sus resultados con los inducidos por diferentes dosis de rayos X. Resultados: Se ha determinado un efecto citotóxico del sevofluorane sobre las células PNT2 que presenta correlación con la dosis administrada y el tiempo de estudio utilizado (p >0.001), así como un efecto genotóxico con características dosis-dependientes (p >0.001). Sin embargo, con volúmenes de sevofluorane puro inferiores a 30 μL no encontramos efecto citotóxico sobre las células PNT2. Conclusión: Sevofluorane muestra una significativa capacidad genotóxica in vitro determinada mediante el test de micronúcleos en linfocitos humanos irradiados con bloqueados citocinético mediante citochalsina.

Zoledronic acid and radiation: toxicity, syergy or radiosensitization?

INTRODUCTION: Zoledronic acid (Z) is a bisphosphonate used in hypercalcaemia-related cancer, in complications for bone metastasis and in postmenopausal osteoporosis and it has been related to osteoradionecrosis, especially when associated with radiation to the head and neck structures.OBJECTIVES: To determine the radiosensitization capacity of zoledronic acid in the combined treatment with ionizing radiation (IR) by evaluating its genotoxic and cytotoxic capacities in non-tumoral cells. MATERIALS AND METHODS: The genotoxic effect of Z was studied by means of the micronucleus test in cytokinesis-blocked cells of human lymphocytes irradiated before and after a 2 Gy irradiation, while the cytotoxic effect was studied by a cell viability test in the PNT2 cell line before and after exposure to different X-ray doses (0-20 Gy) in four groups (Z alone, radiation alone, Z + IR and IR + Z). RESULTS: A dose-dependent and time-dependent cytotoxic effect of Z and IR on PNT2 cells in vitro (p > 0.001) was demonstrated. With the concentrations recommended for humans, the combined treatment had a more pronounced effect than individual treatments (p < 0.001). The effect was synergic (CI < 1), increasing the Z enhancement ratio (2.6) and sensitization factor (56 %); the effect of Z was always greater after IR exposure. In the genotoxic effect, only the administration of Z after irradiation (IR + Z) increased chromosome damage (p < 0.001) and the sensibilization factor (35.7 %). CONCLUSION: High concentrations of Z are toxic, but the concentrations recommended for clinical practice in humans give it the characteristics of a radiosensitization agent, whose effect is even greater when administered after IR (AU)

Zoledronic acid and radiation: toxicity, synergy or radiosensitization?

INTRODUCTION: Zoledronic acid (Z) is a bisphosphonate used in hypercalcaemia-related cancer, in complications for bone metastasis and in postmenopausal osteoporosis and it has been related to osteoradionecrosis, especially when associated with radiation to the head and neck structures. OBJECTIVES: To determine the radiosensitization capacity of zoledronic acid in the combined treatment with ionizing radiation (IR) by evaluating its genotoxic and cytotoxic capacities in non-tumoral cells. MATERIALS AND METHODS: The genotoxic effect of Z was studied by means of the micronucleus test in cytokinesis-blocked cells of human lymphocytes irradiated before and after a 2 Gy irradiation, while the cytotoxic effect was studied by a cell viability test in the PNT2 cell line before and after exposure to different X-ray doses (0-20 Gy) in four groups (Z alone, radiation alone, Z + IR and IR + Z). RESULTS: A dose-dependent and time-dependent cytotoxic effect of Z and IR on PNT2 cells in vitro (p > 0.001) was demonstrated. With the concentrations recommended for humans, the combined treatment had a more pronounced effect than individual treatments (p < 0.001). The effect was synergic (CI < 1), increasing the Z enhancement ratio (2.6) and sensitization factor (56 %); the effect of Z was always greater after IR exposure. In the genotoxic effect, only the administration of Z after irradiation (IR + Z) increased chromosome damage (p < 0.001) and the sensibilization factor (35.7 %). CONCLUSION: High concentrations of Z are toxic, but the concentrations recommended for clinical practice in humans give it the characteristics of a radiosensitization agent, whose effect is even greater when administered after IR.

Chemical genoprotection: reducing biological damage to as low as reasonably achievable levels.

OBJECTIVES: The aim of this study was to evaluate the antioxidant substances present in the human diet with an antimutagenic protective capacity against genotoxic damage induced by exposure to X-rays in an attempt to reduce biological damage to as low a level as reasonably possible. METHODS: Ten compounds were assessed using the lymphocyte cytokinesis-block micronucleus (MN) cytome test. The compounds studied were added to human blood at 25 µM 5 min before exposure to irradiation by 2 Gy of X-rays. RESULTS: The protective capacity of the antioxidant substances assessed was from highest to lowest according to the frequency of the MN generated by X-ray exposure: rosmarinic acid = carnosic acid = δ-tocopherol = l-acid ascorbic = apigenin = amifostine (P < 0.001) > green tea extract = diosmine = rutin = dimetylsulfoxide (P < 0.05) > irradiated control. The reduction in genotoxic damage with the radiation doses administered reached 58%, which represents a significant reduction in X-ray-induced chromosomal damage (P < 0.001). This degree of protection is greater than that obtained with amifostine, a radioprotective compound used in radiotherapy and which is characterised by its high toxicity. CONCLUSION: Several antioxidant substances, common components of the human diet and lacking toxicity, offer protection from the biological harm induced by ionizing radiation. Administering these protective substances to patients before radiological exploration should be considered, even in the case of small radiation doses and regardless of the biological damage expected.

The status of Spain's dental practice following the European Union directive concerning radiological installations: 11 years on (1996-2007).

OBJECTIVES: The aim of this study was to assess the influence of European Union legislation on dental radiology practice in Spain and the reduction in doses administered in dental radiological installations 11 years after its introduction. METHODS: A total of 19 079 official reports on dental surgeries from 16 Spanish autonomous regions published between 1996 and 2007 were studied. We analysed the physical characteristics of the X-ray units, anomalies, film processing, exposure times and mean radiation doses administered in clinical situations. RESULTS: The dose applied to obtain a radiograph of an upper second molar had decreased by 37% up until 2007, the mean dose being 2.7 mGy, with 81.1% of installations using a dose of less than 4 mGy, with a reference dose for the 3(rd) quartile of 3.6 mGy. Of note was the incorporation of digital systems (50.1%), which are gradually replacing manual processing systems (45.3%). There were significant differences between the systems: direct digital radiology < indirect digital radiology = Insight = Ektaspeed = Ultraspeed (P < 0.001). In installations with digital systems, 6.3% used more than 4 mGy (20.5% with direct radiology and 3.2% with indirect radiology) and 7.4% a dose of less than 0.5 mGy, with a mean dose of 1.8 mGy and a reference dose for the 3(rd) quartile of 2.3 mGy. CONCLUSION: There has been a gradual improvement in dental radiology practices; however, the incorporation of digital systems has not resulted in all the benefits hoped for, and mistakes are frequent. Besides the physical parameters that have been established, anatomical and clinical image quality criteria should be established to convince dentists of the real benefits of incorporating quality guarantee procedures in their practices.

Collimator with filtration compensator: clinical adaptation to meet European Union recommendation 4F on radiological protection for dental radiography.

OBJECTIVE: Our aim was to develop a compensated filtration collimator for use in paediatric patients undergoing cephalometric radiography that reduces the radiation dose administered and fulfils recommendation 4F of the European guidelines on radiation protection in dental radiology. METHODS: An easy to use filtration-compensated collimator was constructed of plastic, lead and aluminium and used randomly with a group of 32 children (mean age 11 years) undergoing cephalometric radiography before receiving orthodontic treatment. The radiation doses administered to patients (eye lens and thyroid, submandibular and parotid glands) and to the chassis of the radiographic equipment were determined. RESULTS: The filtration-compensated collimator is easily fixed to the external surface of the radiographic equipment and results in (a) as collimator, a reduction of 40% in the surface irradiated in the children and of 61.4% in the dose administered to the thyroid glands (P<0.001); (b) as filtration compensator, a reduction of 32.8% administered to the eye lens (P<0.001), 31.45% to the submaxillary gland (P<0.01) and 11.4% to the parotid gland (P<0.05); there was no difference in the dose determined on the radiographic film. CONCLUSIONS: A radiographic examination can be carried out with children using only a third of the dose normally used with no increase in the time or cost involved.

Liposoluble antioxidants provide an effective radioprotective barrier.

Ionising radiation causes the massive generation of reactive oxygen species and induces cellular DNA damage. The antioxidant, protective effects of several compounds against gamma-ray-induced chromosomal damage were determined by the micronucleus test, evaluating the reduction in the frequency of micronuclei in cytokinesis-blocked human lymphocytes. The compounds studied were added to human blood at 25 microM, 5 min before or after irradiation with 2 Gy of caesium-137. The results suggest that different protective mechanisms are operating in each case. When the phenolic compounds are added before gamma-irradiation, their protective antimutagenic activity is based on their scavenging capacity against superoxide anion (O(2)(.-)) and, especially, hydroxyl radical ((.)OH), regardless of whether they are oil- or water-soluble compounds. When the phenolic compounds are added after gamma-irradiation treatment, the protective effect relies on activity against reactive oxygen species present in cells, i.e. lipoperoxy radicals (R(-)OO(.)), which are mainly responsible for continuous chromosomal oxidative damage. In addition, ionising radiation enhances lysosomal enzyme secretion and arachidonate release from membranes through lipo-oxygenase, cyclo-oxygenase and phospholipase activities, thus increasing the inflammatory cell response. Only oil-soluble compounds, such as carnosic acid, carnosol and delta-tocopherol, provide a significant protective antimutagenic activity. The most powerful water-soluble antioxidants lack the capacity to protect against gamma-ray-induced damage. The difference between anti-radical and anti-lipoperoxidant activities could explain the different behaviour of the compounds tested in terms of protecting against the lipid peroxidative processes. This anti-lipoperoxidant activity depends on several factors, but it is clear that only the lipo-antioxidants are effective in protecting human cells against oxidative damage, even when administered after exposure to ionising radiation.

[Complications at the first month following various types of intracoronary stents, implanted with high pressure without intracoronary ultrasonography or anticoagulation]. / Complicaciones en el primer mes de varios tipos de stents intracoronarios, implantados a altas presiones sin ayuda de ultrasonidos intracoronarios ni anticoagulación.

BACKGROUND: Coronary stents have proved their efficacy in bail-out situations and restenosis. Nevertheless, the high incidence of subacute thrombosis and vascular and bleeding complications limits its use. OBJECTIVES: To evaluate the clinical complications during the first month of three different types of stents, implanted with high pressure, without ultrasound guidance or anticoagulation. PATIENTS AND METHODS: All stents were implanted in arteries of 3 mm or more. After implantation, all stents were dilated between 15-17 atmospheres, aiming to a residual stenosis lower than 10%. After implantation, all patients received aspirin indefinitely and ticlopidine 250 mg twice daily for one month. The initial success, the ischemic complications (death, myocardial infarction and emergency surgery), acute and subacute thrombosis and vascular and hemorrhagic complications were evaluated. The evaluation was done following the procedure, prior to discharge from the hospital and at 1 month follow-up. RESULTS: In 49 patients, 51 stents were implanted. 70% had unstable angina. In one case the stent was implanted after primary PTCA. In 17.6%, the stent was implanted in a bail-out situation. Of the 51 stents, 32 were Palmaz-Schatz, 12 Wiktor and 7 Gianturco-Roubin. The initial success was 100%. There were no deaths, AMI, nor emergency surgeries in the first month. There was no case of acute or subacute thrombosis. There were 2 minor complications; one vascular: a pseudoaneurysm, and another hemorrhagic: an inguinal hematoma. Neither case needed surgery nor blood transfusion. All patients were discharged within 48 hours. CONCLUSION: Implantation of stents with high pressures, in spite of not using guidance ultrasound nor anticoagulation, is safe and effective, with a clear decrease in vascular complications, and without an increase in the incidence of acute or subacute thrombosis.