RESUMEN
We provide the most accurate results for the QCD transition line so far. We optimize the definition of the crossover temperature T_{c}, allowing for its very precise determination, and extrapolate from imaginary chemical potential up to real µ_{B}≈300 MeV. The definition of T_{c} adopted in this work is based on the observation that the chiral susceptibility as a function of the condensate is an almost universal curve at zero and imaginary µ_{B}. We obtain the parameters κ_{2}=0.0153(18) and κ_{4}=0.00032(67) as a continuum extrapolation based on N_{t}=10, 12, 16 lattices with physical quark masses. We also extrapolate the peak value of the chiral susceptibility and the width of the chiral transition along the crossover line. In fact, both of these are consistent with a constant function of µ_{B}. We see no sign of criticality in the explored range.
RESUMEN
We present possible indications for flavor separation during the QCD crossover transition based on continuum extrapolated lattice QCD calculations of higher order susceptibilities. We base our findings on flavor-specific quantities in the light and strange quark sector. We propose a possible experimental verification of our prediction, based on the measurement of higher order moments of identified particle multiplicities. Since all our calculations are performed at zero baryochemical potential, these results are of particular relevance for the heavy-ion program at the LHC.
RESUMEN
PURPOSE: To examine the possible late complications of splenectomy or spleen autotransplantation in large laboratory animal model, in which we need non-invasive or minimal-invasive methods for long-term monitoring of the experimental animals. METHODS: Experimental groups of beagle dogs were: non-operated control, sham-operated control, splenectomy, spleen autotransplantation with 5 or 10 spleen-chips taken into the greater omentum (Furka's technique). Prior to operations, on the 1(st) postoperative week, monthly till the 6(th) as well as in the 9(th) and 12(th) month, hemorheological examinations were performed. In postoperative 12(th) month colloid scintigraphy and diagnostic laparoscopy were carried out. At the end of the investigation comparative morphological examinations were performed, too. RESULTS: From the 4(th)-5(th) postoperative month filtration function of spleen-autotransplants showed particular restoration compared to splenectomy group. However, the functional results did not reach the values of the control or sham-operated groups. Sham-operated control's scintigraphy nicely showed activity in the spleen. In spleen autotransplantation-groups scintigraphy indicated well the activity of spleen-chips. During diagnostic laparoscopy spleen-chips with their blood supply were found. Histologically, the structure of spleen-autotransplants was similar to normal splenic tissue. CONCLUSIONS: The autotransplants are regenerated, their functions have been partly restored, and thus spleen autotransplantation may prevent the possible complications of splenectomy. These parameters and the presented investigative protocol are suitable for long-term following-up of viability of the spleen-autotransplants.
Asunto(s)
Modelos Animales , Bazo/trasplante , Esplenectomía/efectos adversos , Animales , Coloides , Perros , Estudios de Factibilidad , Femenino , Laparoscopía , Masculino , Periodo Posoperatorio , Cintigrafía , Regeneración , Bazo/diagnóstico por imagen , Bazo/fisiología , Factores de Tiempo , Trasplante Autólogo/efectos adversos , Trasplante Autólogo/métodos , Resultado del TratamientoRESUMEN
PURPOSE: To examine the possible late complications of splenectomy or spleen autotransplantation in large laboratory animal model, in which we need non-invasive or minimal-invasive methods for long-term monitoring of the experimental animals. METHODS: Experimental groups of beagle dogs were: non-operated control, sham-operated control, splenectomy, spleen autotransplantation with 5 or 10 spleen-chips taken into the greater omentum (Furka's technique). Prior to operations, on the 1st postoperative week, monthly till the 6th as well as in the 9th and 12th month, hemorheological examinations were performed. In postoperative 12th month colloid scintigraphy and diagnostic laparoscopy were carried out. At the end of the investigation comparative morphological examinations were performed, too. RESULTS: From the 4th-5th postoperative month filtration function of spleen-autotransplants showed particular restoration compared to splenectomy group. However, the functional results did not reach the values of the control or sham-operated groups. Sham-operated control's scintigraphy nicely showed activity in the spleen. In spleen autotransplantation-groups scintigraphy indicated well the activity of spleen-chips. During diagnostic laparoscopy spleen-chips with their blood supply were found. Histologically, the structure of spleenautotransplants was similar to normal splenic tissue. CONCLUSIONS: The autotransplants are regenerated, their functions have been partly restored, and thus spleen autotransplantation may prevent the possible complications of splenectomy. These parameters and the presented investigative protocol are suitable for long-term following-up of viability of the spleen-autotransplants.
OBJETIVO: Examinar as possíveis complicações tardias da esplenectomia ou do autotransplante de baço em modelo animal de grande porte, no qual faz-se necessário o uso de métodos não invasivos ou minimamente invasivos para monitorizar os animais de experimentação. MÉTODOS: Grupos experimentais de cães beagle foram: não-operados controle, sham-operados controle, esplenectomia, autotransplante de baço com 5 ou 10 fatias de baço colocados no grande omento (técnica de Furka). Antes das operações, na 1ª semana de pósoperatório, mensalmente até 6o.assim como no 9º. e 12º. mês, foram realizados exames hemorreológicos. No 12º. mês de pós-operatório, cintilografia colóide e laparoscopia diagnóstica foram realizadas. Ao final do experimento, exames morfológicos comparativos foram realizados também. RESULTADOS: A partir do 4º-5º mês pós-operatório, a função de filtração dos baços autotransplantados mostraram particular restauração comparados ao grupo esplenectomia. Entretanto, os resultados funcionais não alcançaram os valores dos grupos controle ou sham-operados. A cintilografia dos controles sham-operados mostraram atividade no baço. Nos grupos de autotransplante, a cintilografia indicou bem a atividade das fatias de baço. Durante a laparoscopia diagnóstica, as fatias de baço com seu suprimento sanguíneo foram encontrados. Histologicamente, a estrutura dos autotransplantes de baço foi similar ao tecido normal de baço. CONCLUSÕES: Os autotransplantes são regenerados, suas funções foram parcialmente restauradas, e então ao autotransplantate esplênico pode prevenir as possíveis complicações da esplenectomia. Estes parâmetros e o protocolo experimental são adequados para o seguimento em longo prazo da viabilidade de autotransplantes esplênicos.
Asunto(s)
Animales , Perros , Femenino , Modelos Animales , Bazo/trasplante , Esplenectomía/efectos adversos , Coloides , Estudios de Factibilidad , Laparoscopía , Periodo Posoperatorio , Regeneración , Bazo/fisiología , Bazo , Factores de Tiempo , Resultado del Tratamiento , Trasplante Autólogo/efectos adversos , Trasplante Autólogo/métodosRESUMEN
The aim of our study was to investigate the immunotoxicity of occupational cytostatic drug exposure, and to assess the possible effect of confounding factors, such as age and smoking. In this human study, the immunotoxic effect of antineoplastic drugs was investigated among 306 nurses working in oncology chemotherapy units. Results were compared to 98 non-exposed women. The immune status of the subjects was characterized by immune phenotyping of peripheral blood lymphocytes by flow cytometry, using monoclonal antibodies against surface antigens (CD3, CD4, CD8, CD19, CD25, CD45, CD56 and CD71). The killing ability of neutrophil leukocytes was assessed by the measurement of reactive oxygen intermediate production. Occupational exposure to antineoplastic drugs caused shifts in the major lymphocyte subpopulations, resulting in a statistically significant increase in the ratio of B cells. Cytostatic drug exposure also manifested itself in a decreased frequency of CD25 positive, activated T lymphocytes, and increased oxidative burst of neutrophil granulocytes, both of which may have a functional impact on the immune system of exposed subjects. In the younger subjects exposure also caused a shift in T cell subpopulations: a reduction in the cytotoxic T cell population lead to an elevated Th/Tc ratio. In the exposed group, smoking increased activation of T lymphocyte subpopulations. In conclusion, we have demonstrated that low dose occupational cytostatic drug exposure is immunotoxic, and age and smoking modify the effect of exposure.
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Citostáticos/efectos adversos , Subgrupos Linfocitarios/efectos de los fármacos , Subgrupos Linfocitarios/inmunología , Enfermeras y Enfermeros , Exposición Profesional/efectos adversos , Adulto , Separación Celular , Femenino , Citometría de Flujo , Hospitales , Humanos , InmunofenotipificaciónRESUMEN
P-glycoprotein (Pgp, ABCB1) is one of the active efflux pumps that are able to extrude a large variety of chemotherapeutic drugs from the cells, causing the phenomenon of multidrug resistance. It has been shown earlier that the combined application of a class of Pgp modulators (e.g. cyclosporine A and SDZ PSC 833) used at low concentrations and UIC2 antibody is a novel, specific, and effective way of blocking Pgp function (Goda et al., 2007). In the present work we study the UIC2 antibody mediated Pgp inhibition in more detail measuring the accumulation of tumor diagnostic radiotracers, 2-[(18)F]fluoro-2-deoxy-d-glucose ((18)FDG) and [(99m)Tc]hexakis-2-methoxybutyl isonitrile ((99m)Tc-MIBI), into Pgp(+) (A2780AD) and Pgp(-) (A2780) human ovarian carcinoma cells. Co-incubation of cells with UIC2 and cyclosporine A (CSA, 2µM) increased the binding of UIC2 more than 3-fold and reverted the rhodamine 123 (R123), daunorubicin (DNR) and (99m)Tc-MIBI accumulation of the Pgp(+) 2780AD cells to approx. the same level as observed in Pgp(-) cells. Similarly, 50µM paclitaxel (Pacl) increased UIC2 binding, and consequently reinstated the uptake of R123, DNR and (99m)Tc-MIBI into the Pgp(+) cells. Blocking Pgp by combined treatments with CSA+UIC2 or Pacl+UIC2 also decreased the glucose metabolic rate of the A2780AD Pgp(+) cells measured in (18)FDG accumulation experiments suggesting that the maintenance of Pgp activity requires a considerable amount of energy. Similar treatments of the A2780 Pgp(-) cells did not result in significant change in the R123, DNR, (99m)Tc-MIBI and (18)FDG accumulation demonstrating that the above effects are Pgp-specific. Thus, combined treatment with the UIC2 antibody and Pgp modulators can completely block the function of Pgp in human ovarian carcinoma cells and this effect can be followed in vitro by using tumor-diagnostic radiotracers, (99m)Tc-MIBI and (18)FDG.
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Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Anticuerpos Monoclonales/metabolismo , Ciclosporina/metabolismo , Fluorodesoxiglucosa F18/farmacocinética , Tecnecio Tc 99m Sestamibi/farmacocinética , Anticuerpos Monoclonales/farmacología , Antineoplásicos/farmacocinética , Transporte Biológico/efectos de los fármacos , Ciclosporina/farmacología , Daunorrubicina/farmacología , Resistencia a Múltiples Medicamentos , Femenino , Glucosa/metabolismo , Humanos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/metabolismo , Paclitaxel/farmacocinética , Unión Proteica , Rodamina 123/farmacocinética , Células Tumorales CultivadasRESUMEN
In the present study genotoxicological and immunotoxicological follow-up investigations were made on 811 donors including 94 unexposed controls and 717 nurses with various working conditions from different hospitals (The Hungarian Nurse Study). The nurses were exposed to different chemicals: cytostatic drugs, anesthetic, and sterilizing gases, such as ethylene oxide (ETO) and formaldehyde. The measured biomarkers were: clinical laboratory routine tests, completed with genotoxicological (chromosome aberrations [CA], sister chromatid exchange [SCE]), and immune-toxicological monitoring (ratio of lymphocyte subpopulations, lymphocyte activation markers, and leukocyte oxidative burst). The highest rate of genotoxicologically affected donors (25.4%) was found in the group of cytostatic drug-exposed nurses. Comparing geno- and immunotoxicological effect markers, we found that among genotoxicologically affected donors the frequency of helper T cell (Th) lymphocytes, the ratio of activated T and B cells increased, whereas the oxidative burst of leukocytes decreased. In hospitals with lack of protective measures increased CA yields were observed compared to those with ISO 9001 quality control or equivalent measures. Anemia, serum glucose level, thyroid dysfunctions, benign, and malignant tumors were more frequent in the exposed groups than in controls. The hygienic standard of the working environment is the basic risk factor for the vulnerability of nurses. On the basis of these results, it is suggested, that the used cytogenetic and immunological biomarkers are appropriate to detect early susceptibility to diseases. The Hungarian Nurse Study proved that the use of safety measures could protect against occupational exposure at work sites handling cytostatic drugs, anesthetic, and sterilizing gases.
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Sustancias Peligrosas , Personal de Enfermería en Hospital , Citometría de Flujo , Humanos , Hungría , Sistema Inmunológico/efectos de los fármacos , Inmunofenotipificación , Mutágenos/toxicidad , Estallido RespiratorioRESUMEN
Statistical data indicate a chronic shortage of work-force due to overwork, ill health state and increased risk of chronic noninfectious diseases in Hungarian health care personnel, which needs investigations in order to decrease the risk. Nurses of oncology units, often exposed to carcinogens when preparing and handling cytostatic drugs, are especially at high risk. In the present publication we report a complex clinical, geno- and immunotoxicology risk assessment of altogether 500 nurses, performed during the last 10 years at various oncology units in Hungary. The obtained results indicate that the health status of nurses at oncology units is better than the Hungarian average, especially of hypertonia and type II diabetes. However, the prevalence of iron deficiency anemia and different thyroid gland diseases is significantly higher than those of the controls matched for sex and age. The results suggest that iron deficiency can potentiate the resistance to insulin, i.e. the persistence of iron deficiency may increase the serum glucose levels and thus the risk of diabetes. Among the studied geno- and immunotoxicology biomarkers, the frequency of chromosome aberrations, sister chromatid exchange and B lymphocytes was significantly increased compared to the matched controls. The obtained alterations demonstrate the occupational exposure of the nurses to cytostatic drugs, thus the introduction of more strict hygienic controls and compliance with the European Union chemical safety regulations is necessary.
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Anemia Ferropénica/epidemiología , Antineoplásicos/efectos adversos , Estado de Salud , Enfermeras y Enfermeros/estadística & datos numéricos , Enfermedades Profesionales/epidemiología , Exposición Profesional/efectos adversos , Enfermería Oncológica , Enfermedades de la Tiroides/epidemiología , Adulto , Anemia Ferropénica/complicaciones , Anemia Ferropénica/metabolismo , Linfocitos B , Glucemia/metabolismo , Estudios de Casos y Controles , Aberraciones Cromosómicas , Dislipidemias/epidemiología , Europa (Continente) , Femenino , Guías como Asunto , Departamentos de Hospitales , Humanos , Hungría/epidemiología , Resistencia a la Insulina , Enfermedades Profesionales/complicaciones , Enfermedades Profesionales/metabolismo , Prevalencia , Estudios Retrospectivos , Intercambio de Cromátides Hermanas , Recursos HumanosRESUMEN
Chemoprevention with chelating agent Humetta for three months was performed, due to anaemia and other haematologic disorders, immunotoxicological alterations and/or increased chromosome aberration rate among galvanisers and goldsmiths occupationally exposed to precious and heavy metals. Twenty-two of altogether 47 subjects took part voluntarily in the chemoprevention, and the rest of the subjects served as untreated controls. Complex clinical laboratory testing including detailed anamneses; genotoxicological and immunotoxicological monitoring were performed before and after administration of chemopreventive agent. After chemoprevention a significant improvement was observed in anaemia and serum glucose levels, while a less marked improvement was found in serum cholesterol levels and liver functions. Altered chromosome aberration and apoptotic cell fraction also tended to normalise after treatment. Immunological parameters were not affected by the treatment. The obtained results may suggest that chemoprevention with chelating agents as Humetta can help in the prevention of harmful effects of occupational exposures to metals.