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4.
Biol Psychiatry ; 45(11): 1393-402, 1999 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-10356620

RESUMO

BACKGROUND: Structural MRI data indicate schizophrenics have reduced left-sided temporal lobe gray matter volumes, especially in the superior temporal gyrus (STG) and medial temporal lobe. Our data further suggest a specificity to schizophrenia spectrum disorders of STG volume reduction. Interpretation of research studies involving schizophrenics may be complicated by the effects of exposure to neuroleptics and chronic illness. Sharing the same genetic diathesis of schizophrenics, subjects with schizotypal personality disorder (SPD) offer a unique opportunity to evaluate commonalities between schizophrenia and SPD, particularly as SPD subjects are characterized by cognitive and perceptual distortions, an inability to tolerate close friendships, and odd behavior, but they are not psychotic and so have generally not been prescribed neuroleptics nor hospitalized. Evaluation of brain structure in SPD may thus offer insight into the "endophenotype" common to both disorders. In addition, differences between groups may suggest which are the brain structures of schizophrenics that contribute to the development of psychosis. METHODS: To test the hypothesis of whether SPD subjects might show similar STG abnormalities, STG and medial temporal lobe regions of interest (ROI) were manually drawn on high resolution coronal MRI 1.5 mm thick slices. Images were derived from 16 right-handed male SPD subjects, without regard to family history, and 14 healthy, right-handed, comparison males who did not differ from the SPD group on parental socio-economic status, age, or verbal IQ. RESULTS: As predicted, SPD subjects showed a reduction in left STG gray matter volume compared with age and gender matched comparison subjects. SPD subjects also showed reduced parahippocampal left/right asymmetry and a high degree of disordered thinking. Comparisons with chronic schizophrenics previously studied by us showed the SPD group had a similarity of left STG gray matter volume reduction, but fewer medial temporal lobe abnormalities. CONCLUSIONS: These abnormalities strengthen the hypothesis of a temporal lobe abnormality in SPD, and the similarity of STG findings in schizophrenia and SPD suggest that STG abnormalities may be part of the spectrum "endophenotype." It is also possible that presence of medial temporal lobe abnormalities may help to differentiate who will develop schizophrenia and who will develop the less severe schizophrenia spectrum disorder, SPD.


Assuntos
Transtorno da Personalidade Esquizotípica/patologia , Lobo Temporal/patologia , Adulto , Estudos de Casos e Controles , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Manifestações Neurocomportamentais , Esquizofrenia/patologia , Índice de Gravidade de Doença , Estatísticas não Paramétricas
5.
Arch Neurol ; 58(1): 115-21, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11176944

RESUMO

OBJECTIVE: To investigate the relationship between magnetic resonance imaging regional lesion burden and cognitive performance in multiple sclerosis (MS) over a 4-year follow-up period. DESIGN: Twenty-eight patients with MS underwent magnetic resonance imaging and took the Brief, Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis at baseline, 1-year, and 4-year follow-up. An automated 3-dimensional lesion detection method was used to identify MS lesions within anatomical regions on proton density T2-weighted images. The relationship between magnetic resonance imaging regional lesion volumes and the Brief, Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis results was examined using regression analyses. RESULTS: At all time points, frontal lesion volume represented the greatest proportion of total lesion volume, and the percentage of white matter classified as lesion was also highest in frontal and parietal regions. On neuropsychological testing, when compared with age- and educational level-matched control subjects, patients with MS showed significant impairment on tests of sustained attention, processing speed, and verbal memory (P<.001). Performance on these measures was negatively correlated with MS lesion volume in frontal and parietal regions at baseline, 1-year, and 4-year follow-up (R = -0.55 to -0.73, P<.001). CONCLUSIONS: Multiple sclerosis lesions show a propensity for frontal and parietal white matter. Lesion burden in these areas was strongly associated with performance on tasks requiring sustained complex attention and working verbal memory. This relationship was consistent over a 4-year period, suggesting that disruption of frontoparietal subcortical networks may underlie the pattern of neuropsychological impairment seen in many patients with MS.


Assuntos
Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Imageamento por Ressonância Magnética , Esclerose Múltipla/complicações , Esclerose Múltipla/diagnóstico , Adulto , Depressão/diagnóstico , Depressão/etiologia , Avaliação da Deficiência , Feminino , Lobo Frontal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/fisiopatologia , Vias Neurais/fisiopatologia , Testes Neuropsicológicos , Lobo Parietal/patologia , Análise de Regressão , Índice de Gravidade de Doença
6.
Environ Mol Mutagen ; 23(2): 137-42, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-8143702

RESUMO

Cytogenetical endpoints, i.e., chromosome aberration (CA), sister-chromatid exchange (SCE), and proliferative rate indexes (PRI), were measured in peripheral blood lymphocytes (PBL) of 42 workers exposed occupationally to low-dose benzene, and of 42 controls. The role of smoking habit as a confounding factor of genotoxic effects caused by occupational low-dose benzene exposure was also studied. The benzene concentrations in the ambient air samples varied from 3 to 20 mg/m3 (mean: 7 mg/m3). The continuous low-dose benzene exposure significantly increased the CA and SCE frequencies, but did not influence PRI. Smoking levels were characterized by subjective accounts and by serum thiocyanate concentrations (SCN). CA and SCE were not significantly increased in smokers compared to nonsmokers, but the differences were expressed to a greater extent in the case of measurement of SCN concentrations. Determination of SCN proved to be more objective in the assessment of genotoxic effects of smoking as a confounding factor of occupational low-dose benzene exposure.


Assuntos
Benzeno/toxicidade , Mutagênicos/toxicidade , Fumar , Tiocianatos/sangue , Adulto , Análise de Variância , Benzeno/administração & dosagem , Divisão Celular , Células Cultivadas , Aberrações Cromossômicas , Fatores de Confusão Epidemiológicos , Monitoramento Ambiental , Feminino , Humanos , Hungria , Masculino , Pessoa de Meia-Idade , Testes de Mutagenicidade , Exposição Ocupacional , Troca de Cromátide Irmã , Fumar/sangue
7.
Environ Mol Mutagen ; 27(2): 84-92, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8603670

RESUMO

Structural, and numeric chromosome aberrations (CA), sister-chromatid exchange (SCE), phytohemagglutinin stimulation (LI), proliferative rate index (PRI), and UV light-induced unscheduled DNA-synthesis (UDS) were investigated in peripheral blood lymphocytes (PBL) of 48 historical controls ("Controls"); of 14 hospital controls in Budapest, Hungary ("Budapest controls"); of 9 nurses occupationally exposed to low-dose ethylene-oxide in Budapest ("Budapest exposed"); of 10 hospital controls in Eger, Hungary ("Eger controls"); and of 27 high dose ETO-exposed nurses in Eger ("Eger exposed"), where neoplasias, mainly breast cancers, were observed. ETO concentrations in the ambient air samples varied from 5 to 20 mg/m3 in Budapest; and from 5 to 100 mg/m3 in Eger. Bothe LI and PRI were depressed in Budapest exposed, indicating ETO-induced cytotoxicity and, however, normal in Eger exposed. SCE was slightly elevated in Budapest exposed, but significantly increased in Eger exposed. The yields of cells with high frequency SCE (HFC) were only increased in Eger exposed. The expected low CA frequencies were found in Controls and in Budapest controls. ETO exposures significantly increased the CA frequencies in Budapest and Eger exposed. In Budapest exposed, as expected, we found deletions; in a lesser extent chromatid exchanges and dicentrics; but no rings were detected. These results are in a good accordance to the published data of other investigations carried out on ETO-exposed human populations. However, in Eger exposed, beside the increased yields of deletions, the frequencies of dicentrics and rings showed a significant excess compared to the reviewed data. An unexpected, significant increase of dicentric and ring frequencies was also detected among the hospital controls in Eger controls without known clastogenic exposure. The role of confounding factors (age, smoking and drinking habit, total leukocyte count and hematocrit) was investigated by an analysis of variance on CA and SCE frequencies in Controls and in Eger exposed. Leukocyte count and mean age showed only significant effects on CA in Eger exposed and on SCE in Controls, respectively. A possible active confounding factor could be the temporary natural radioactivity of the local tap water. UDS in Budapest exposed and in Eger control were significantly higher then in the Controls and in Budapest controls. In Eger exposed UDS was significantly decreased compared to the Budapest exposed and Eger control groups. The explanation of the present results is difficult on the basis of the reviewed data on ETO-induced CA frequencies in exposed human populations, and it raises an issue of an independent genotoxic effect in Eger, which is common both in Eger controls and in Eger exposed, such as natural radioactivity.


Assuntos
Óxido de Etileno/efeitos adversos , Linfócitos/efeitos dos fármacos , Enfermeiras e Enfermeiros , Exposição Ocupacional , Adulto , Análise de Variância , Aneuploidia , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/fisiologia , Células Cultivadas , Aberrações Cromossômicas/genética , Estudos de Coortes , DNA/biossíntese , DNA/efeitos dos fármacos , DNA/efeitos da radiação , Feminino , Humanos , Hungria , Cinética , Estilo de Vida , Linfócitos/citologia , Linfócitos/metabolismo , Troca de Cromátide Irmã/efeitos dos fármacos , Troca de Cromátide Irmã/genética , Raios Ultravioleta/efeitos adversos
8.
Environ Mol Mutagen ; 31(4): 301-10, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9654238

RESUMO

In order to investigate the genotoxic effects of occupational acrylonitrile (ACN) and dimethylformamide (DMF) exposures, clinical serum and urine parameters and genotoxicological endpoints such as chromosome aberration (CA), sister chromatid exchange (SCE), high frequency SCE (HFC), cell cycle kinetics, and UV-induced unscheduled DNA synthesis (UDS) were followed up three times during a 20-month period in peripheral blood lymphocytes (PBL) of 26 workers (13 maintainers and 13 fiber producers) occupationally exposed to ANC and/or DMF in a viscose rayon plant, 26 matched control subjects, and six industrial controls (all males). Six of the 26 exposed subjects were hospitalized because of liver dysfunction that had developed due to inhalative DMF exposure. The rate of smoking was estimated on the basis of serum thiocyanate (SCN) levels. Average peak air ACN and DMF concentrations were over the maximum concentration limits at the time of both investigations. Urine ACN and monomethyl-formamide (MMF) excretions of the exposed subjects were almost doubled after work shifts. An increase in lymphocyte count (in months 0 and 7), and severe alterations in the liver function were observed in the exposed subjects. In PBLs the proliferative rate index (PRI) was already increased in month 0 compared with the controls. In each study, significant increases in CA and SCE frequencies, as well as increases in UDS were found in PBLs of the exposed subjects. The frequencies of chromatid breaks and acentric fragments further increased in month 7 and remained constantly elevated in month 20. Increased yields of both chromatid and chromosome-type exchange aberrations first appeared in month 20, when HFCs were 2.72 times more frequent in fiber producers than in maintainers. The role of some important biological confounding factors (age, white blood cell count, and hematocrit) and lifestyle confounding factors (smoking and drinking habits) were subjected to an analysis of variance during the second study. Increased CA, SCE, and UDS were found both in control and exposed smokers when current smoking was established on the basis of the serum SCN levels. The cytogenetic data suggest that occupational exposures to ACN and DMF induce considerable genotoxic consequences and may increase the cancer risk in the exposed human populations.


Assuntos
Acrilonitrila/toxicidade , Aberrações Cromossômicas , Dimetilformamida/toxicidade , Mutagênicos , Exposição Ocupacional , Têxteis , Estudos de Casos e Controles , Ciclo Celular , Humanos , Masculino , Medição de Risco , Troca de Cromátide Irmã , Fumar
9.
Pathol Oncol Res ; 5(2): 117-21, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10393363

RESUMO

An unusual cluster of 8 breast cancer and 8 other malignant tumor cases (ovarian, uterus, lung, colon and brain tumors and malignant melanoma) developed in a period of 12 years among 98 nurses exposed to ethylene oxide (EtOx) for 5 15 years in a unit using gas sterilizer in a hospital of the archiepiscopal city of Eger, Hungary. EtOx concentration in air samples of the working area varied from 5 to 150 mg/m3. The question was, if there was any causal relationship between the elevated incidence of breast cancer and the EtOx exposure, the other possibility was, that this cluster appeared accidentally. EtOx is a human carcinogen, however, no increased breast cancer incidence in EtOx-exposed subjects was reported in the literature. We followed up for two consecutive years the 27 non cancer patients, EtOx-exposed nurses and 11 unexposed hospital controls with the aid of a multiple genotoxicology monitor including chromosomal aberration, sister-chromatide exchange, HPRT point mutation and DNA repair studies. The results were compared with data from 30 local historical controls, 48 historical controls from Budapest, 14 hospital controls and 9 EtOx exposed nurses from Budapest. Significantly high chromosome aberration yields (especially chromosome type exchanges) were alike detected in EtOx-exposed and the two other control groups in Eger. These results could not be interpreted as a consequence of EtOx exposure only, since in the EtOx-exposed group from Budapest, beside an increased total aberration frequency, the obtained exchange type aberration yields were as low as the historical controls. A plausible explanation can be the natural low dose radioactivity (222Rn) of the local tap-water due to a specific geological situation in Eger. The spontaneous breast cancer incidence in Hungary doubled in the last 10 years compared with the previous 20 years (1960 1980), especially in Eger. The appearance of the high breast cancer incidence in the hospital of Eger indicates the combined effect of EtOx and a more common local etiologic factor, such as the naturally radioactive tap-water. However, since the reported studies did not involve the investigation either of the genetic predisposition, or the effects of other possible environmental, occupational, and/or life style confounding factors, further studies (partly in progress) are necessary to clarify the importance of these factors.


Assuntos
Neoplasias da Mama/etiologia , Exposição Ambiental , Recursos Humanos de Enfermagem Hospitalar , Exposição Ocupacional , Distribuição por Idade , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/mortalidade , Desinfetantes/efeitos adversos , Óxido de Etileno/efeitos adversos , Feminino , Predisposição Genética para Doença , Humanos , Hungria/epidemiologia , Estilo de Vida , Pessoa de Meia-Idade , Radiação Ionizante
10.
Mutat Res ; 304(2): 159-65, 1994 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-7506358

RESUMO

The genotoxic effects of benzene were assessed in peripheral blood lymphocytes of 49 workers occupationally exposed to benzene (3-68.7 mg/m3 in the work environment) for 0-2, 2-10 and more than 10 years (10, 22 and 17 workers, respectively). Chromosomal aberrations, SCEs and UV-induced DNA synthesis were used as indicators of genotoxic effects. Most of the workers were followed up in 1991 and 1992, while the benzene concentrations were reduced to 1-18.4 mg/m3 air. Considered overall, in the "exposed" groups, the frequencies of chromosomal aberrations were significantly higher than in controls thus providing evidence for the clastogenic effects of benzene. However, there seems to be no correlation between aberration frequencies and the duration of prior exposure to benzene. In 1991 and 1992, when the benzene concentrations were brought down, there was a concomitant decrease in the frequencies of chromosomal aberrations; in 1992 the decrease reached one third to one half of the initial frequencies, values still higher than in the controls. With the other genotoxic end-points, the changes were small and not consistent.


Assuntos
Poluentes Ocupacionais do Ar/análise , Benzeno/efeitos adversos , Aberrações Cromossômicas , Monitoramento Ambiental , Exposição Ocupacional/efeitos adversos , Benzeno/análise , Indústria Química , DNA/biossíntese , DNA/efeitos da radiação , Reparo do DNA , Relação Dose-Resposta a Droga , Feminino , Humanos , Linfócitos/efeitos dos fármacos , Masculino , Petróleo , Estudos Retrospectivos , Troca de Cromátide Irmã , Raios Ultravioleta
11.
Mutat Res ; 412(1): 9-16, 1998 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-9508360

RESUMO

We studied the effects of chronic low dose exposure to environmental pollutants on the peripheral blood lymphocytes (PBL) of subjects living in the green belts and the inner town, and/or working in the surrounding of industrial estates of Greater Budapest agglomeration, Hungary. The effects of some biological (gender, age, hematocrit and white blood cell counts), lifestyle (smoking, drinking habits and residential areas), and seasonal confounding factors were also considered. PBLs of 175 Hungarian donors of Budapest agglomeration, i.e. 45 subjects living in the green belts without significant genotoxic exposure (C1), 43 donors living in the inner town (C2), and 87 individuals living and/or working near chemical industrial estates (C3), were analysed for structural and numeric chromosome aberrations (CA), sister-chromatid exchanges (SCE), cell proliferation indices (lectine stimulation, LI; and proliferation rate index, PRI), and UV-light-induced unscheduled DNA synthesis (UDS). Each subject was interviewed personally and also investigated clinically. The three populations were matched for age, smoking and drinking habits. We excluded all donors with acute infectious and/or chronic non-infectious diseases, and/or with exposure to any known chemical hazard. For C1s, the base line CA and SCE frequencies were 0.25% and 6.41 per mitosis, respectively; in C2, these frequencies were 0.48% and 6.07 per mitosis, respectively, and in C3, these data were 1.60% and 5.71 per mitosis, respectively. A significant increase of CA due to chromosome type acentric fragments was demonstrated in the donors living in the inner town (C2), compared to those living in the green belts (C1). In C3s, significant (p < 0.05) elevations were found in the frequencies of gaps, aberrant cells, total aberrations (excluding gaps), chromatid and chromosome type aberrations, and in UDS, compared to C1s. Results indicate an increased genotoxicologic risk in donors living and/or working in industrial areas. Gender-related differences in SCE frequencies were demonstrated in C2 and C3; in the latter smoking-induced changes in UDS were also found. Light drinking did not appear to influence the results.


Assuntos
Ciclo Celular/fisiologia , Exposição Ambiental , Monitoramento Ambiental/métodos , Poluentes Ambientais , Indústrias , Linfócitos/citologia , Testes de Mutagenicidade , Troca de Cromátide Irmã , População Suburbana , População Urbana , Adulto , Consumo de Bebidas Alcoólicas , Células Cultivadas , Feminino , Humanos , Hungria , Hidroxiureia/farmacologia , Cinética , Linfócitos/efeitos dos fármacos , Linfócitos/efeitos da radiação , Masculino , Índice Mitótico , Seleção de Pacientes , Fumar , Raios Ultravioleta
12.
Mutat Res ; 445(2): 241-9, 1999 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-10575433

RESUMO

Premature (early) centromere division (PCD, i.e., the separation of centromeres during the prometaphase/metaphase of the mitotic cycle) seems to be a possible manifestation of chromosome instability in human chromosome-breakage syndromes. Chromosome instability also frequently occurs in the peripheral blood lymphocytes (PBL) of humans occupationally exposed to clastogenic agents, and is considered an etiologic factor of neoplastic diseases. In order to investigate the importance of PCD in cancer risk assessment, we studied the frequency of PCDs in PBL of 400 Hungarian subjects. The various groups comprised 188 control donors and 212 subjects occupationally exposed to different genotoxic chemicals, such as acrylonitrile (ACN) and/or dimethylformamide (DMF), benzene, cytostatic drugs, ethylene oxide (ETO), mixed exposure in the rubber industry, mixed organic solvents including CCl4, hot oil-mist, bitumen, and polychlorinated biphenyls (PCB). Data were compared with chromosomal aberration frequencies determined in the same samples. PCD yields are significantly higher in populations exposed to mixed chemicals, crude oil and cytostatic drugs, compared with controls. PCDs involving more than three chromosomes are also more frequent in ETO- and oil mist-exposed groups than in the others. The results indicate that the induction of PCDs is neither incidental nor artificial. As a consequence, we suggest that PCD can be developed into a new, exposure-related cytogenetic biomarker for a more adequate occupational cancer risk assessment. A further, follow-up epidemiological and cytogenetic investigation of PCD is in progress.


Assuntos
Centrômero/efeitos dos fármacos , Mutagênicos/efeitos adversos , Exposição Ocupacional/efeitos adversos , Adulto , Biomarcadores/análise , Indústria Química , Aberrações Cromossômicas , Dano ao DNA , Indústria Farmacêutica , Monitoramento Ambiental , Feminino , Substâncias Perigosas/efeitos adversos , Humanos , Cariotipagem , Linfócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Serviço Hospitalar de Enfermagem , Petróleo
13.
Mutat Res ; 465(1-2): 61-8, 2000 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-10708970

RESUMO

Somatostatin receptors are supposed to be important in the regulation of apoptosis. In this study, we measured apoptosis occurring spontaneously, or induced by the synthetic somatostatin analogue, the peptide TT-232. We examined isolated human peripheral blood lymphocytes (PBL) from 32 nurses exposed bedside to cytostatic drugs, 12 chronic lymphoid leukaemia (CLL) patients prior to treatment, and 19 unexposed, healthy donors without anamnestic occupational exposure to genotoxic agents. Cells were stimulated by phytohaemagglutinin-P (PHA) and cultured for 69 h with or without 15 microg/ml TT-232, respectively. Cell kinetic parameters and apoptosis were determined by flow cytometry after staining with FITC-labeled anti-BrdU and propidium iodide (PI) and the results on spontaneous and peptide-induced apoptosis were compared with the obtained chromosome aberration frequencies (CA). The peptide TT-232 unexpectedly induced chromosome breakage in addition to apoptosis. The mean spontaneous apoptotic fractions were 6.65+/-0.89%, 6.46+/-0. 53%, and 3.07+/-0.57%, and the mean CA yields in the samples without TT-232 were 1.74+/-0.46%, 2.44+/-0.40%, and 4.50+/-1.05%, for healthy subjects, nurses, and CLL patients, respectively. A total of 15 microg/ml TT-232 treatment in healthy subjects increased the mean CA frequency (10.38+/-1.57%), as well as the apoptotic cell fraction (2.63+/-0.45 times higher than the corresponding untreated sample). In TT-232-treated PBLs of nurses, CA remained unchanged and the mean apoptotic cell fraction showed only a slight increase (1.24+/-0.11 times higher than the untreated). Among CLL patients, TT-232 treatment significantly increased both CA (up to 17.83+/-4.04%) and the ratio of apoptotic cells (21.78+/-11.00 times higher than the untreated). These results demonstrated significant differences in apoptosis sensitivity in controls, nurses and CLL donors, after 15 microg/ml TT-232 treatment. Data also indicate that the induced CA yields in CLL donors with high CA are in correlation with TT-232-induced apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Quebra Cromossômica , Peptídeos Cíclicos/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Estudos de Casos e Controles , Células Cultivadas , Aberrações Cromossômicas , DNA/metabolismo , Humanos , Técnicas In Vitro , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/patologia , Linfócitos/citologia , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Enfermeiras e Enfermeiros , Exposição Ocupacional , Somatostatina/análogos & derivados
14.
J Toxicol Environ Health A ; 62(5): 307-18, 2001 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-11261894

RESUMO

Most of the antineoplastic drugs used in the treatment of tumors are carcinogenic to humans. Hospital nurses are often subject to possible occupational carcinogen exposure. Exposure may occur during handling and administration of infusion solutions containing cytostatics. A genotoxicological monitoring system to detect genotoxic changes was developed in our laboratory, helping to improve working conditions and subserving primary prevention. Multiple-endpoint follow-up genotoxicological monitoring was performed in peripheral blood lymphocytes (PBLs) among 4 groups of 95 nurses (152 investigations) occupationally exposed to cytostatics. The results were compared to those of historical and industrial controls. The genotoxicological endpoints were the determination of the frequency of sister chromatid exchanges (SCEs) and the cells with high-frequency SCEs (HFC), the frequency of structural and numerical chromosome aberrations. and the measurement of ultraviolet-light-induced unscheduled DNA-repair synthesis (UDS). In Hospital 1, where nurses worked without a safety cabinet, the percentage of cells with chromosome aberrations (AC) was significantly higher than that of the controls. In Hospital 2, where nurses used inadequate safety cabinets (with horizontal airflow), significantly elevated levels of AC, SCE, HFC, and UDS were detected. During follow-up, in Hospital 2 at the time of the second investigation AC was still significantly higher, although safety conditions had been improved. The results indicate the presence of genotoxic damage in hospital nurses working with no or inadequate safety equipment. In Hospitals 3 and 4 where nurses using biological safety cabinets, the results were lower than those in the previous two groups. In Hospital 3 in the first year of the study AC was as at the level of industrial controls. During follow-up in the course of the repeated investigations a fluctuation in AC above the control level and an increase in HFC in yr 4 and 6 of the study were observed. In this group, the fluctuation in AC and HFC during the study points to the possibility of genotoxic exposure with cytostatics despite of the use of suitable safety cabinets, drawing attention to other possible routes of exposure. In Hospital 4, both AC and HFC were elevated. These data corroborate the need to maintain safety measures to avoid exposure, and the necessity of intervention in the case of exposure when using and handling hazardous carcinogenic agents. The results also indicate a certain expression time for genotoxic changes, which can lead to late somatic mutations as well as to a possible higher risk of cancer.


Assuntos
Antineoplásicos/efeitos adversos , Mutagênicos/efeitos adversos , Enfermeiras e Enfermeiros , Exposição Ocupacional/efeitos adversos , Adolescente , Adulto , Fatores Etários , Aberrações Cromossômicas , Reparo do DNA/efeitos dos fármacos , Determinação de Ponto Final , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Troca de Cromátide Irmã/efeitos dos fármacos , Fumar/genética
15.
J Toxicol Environ Health A ; 62(5): 319-31, 2001 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-11261895

RESUMO

Multiple-endpoint follow-up genotoxicology monitoring was performed in a group of 22 Hungarian road pavers between 1996 and 1999. The studied endpoints were the determination of structural and numeric chromosome aberration (CA), sister chromatid exchange (SCE), high-frequency SCE and HPRT mutation frequencies, and ultraviolet (UV)-light-induced unscheduled DNA synthesis in peripheral blood lymphocytes (PBLs). The workers (8 hand pavers and 14 finishers, mean age 37 yr) used tar-free asphalt. The results were compared with those of 6 work-site controls (35 yr), 101 historical controls (38 yr), and 87 industrial controls (38 yr). The most marked changes were found in the CA frequencies. In the control, the mean CA frequency was 1.6%. In the first study, increased CA frequencies were found in the donors that either had been exposed to hot asphalt fumes or had cleaned the equipment with crude oil. The mean CA frequency of the 14 finishers working in closed cabins was 3.67% in 1996. The increased CA frequency was attributed to the high level of hot asphalt fumes due to insufficient ventilation. By 1999 the mean CA frequency decreased to 1.23%. For the 8 hand pavers working in open air the mean CA frequency was 3.6% in 1996. The obtained data suggested that the increase in CA frequencies was due to the use of petroleum and crude oil; therefore, these substances were replaced with harmless detergents. By 1999 the mean CA frequency decreased to 1%. In finishers the mean CA frequency returned to the control level 1 yr later (1999) than in the case of hand pavers. The chromosome-type aberrations remained predominant during the follow-up. The individual variations observed were attributed to smoking and inadequate personal protection. The obtained results suggest that the use of tar-free asphalt and harmless detergents with adequate personal protection does not increase the frequencies of the genotoxicological parameters compared to controls. Consequently, an improvement in working conditions can prevent further exposures and thus decrease the cancer risk of road pavers.


Assuntos
Hidrocarbonetos/toxicidade , Mutagênicos/toxicidade , Exposição Ocupacional/efeitos adversos , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Ciclo Celular/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Determinação de Ponto Final , Indicadores Básicos de Saúde , Humanos , Hungria , Hipoxantina Fosforribosiltransferase/genética , Indústrias , Masculino , Troca de Cromátide Irmã/efeitos dos fármacos , Fumar/genética , Raios Ultravioleta
16.
J Ethnopharmacol ; 150(1): 85-94, 2013 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-23978659

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Mongolian medicine (TMM) uses preparations from herbs as one form of medication for the treatment of a diversity of diseases including diabetes mellitus (DM). We evaluated the effect of extracts from the plant Leonurus sibiricus L. (LS), used in TMM to treat typical symptoms of type 2 DM, on insulin secretion, electrophysiological properties, intracellular calcium concentration and cell proliferation of INS-1E insulinoma cells under standard cell culture conditions (SCC; 11.1mM glucose). MATERIALS AND METHODS: Insulin secretion was measured by ELISA, electrical properties were assessed by whole cell patch clamping, intracellular calcium concentration (Cai) by Fluo-4 time lapse imaging, insulin receptor expression was verified by RT-PCR and cell proliferation assessed by CellTiter-Glo® cell viability assay. RESULTS: Insulin released from INS-1E cells into the culture medium over 24h was significantly increased in presence of 500 mg/L aqueous LS extract (LS OWE) as well as methanolic LS extract (LS MeOH/H2O) but not in the presence of the butanol-soluble extract (LS MeOH/BuOH). Acute application of LS OWE resulted in a depolarization of the cell membrane potential paralleled by an initial increase and subsequent decline and silencing of action potential frequency, by KATP channel inhibition, persisting depolarization and an increase in Cai. The electrophysiological effects were comparable to those of 100 µM tolbutamide, which, however failed to elevate insulin secretion under SCC. Furthermore all LS extracts stimulated INS-1E cell proliferation. CONCLUSIONS: The finding that extracts from Leonurus sibiricus L. enhance insulin secretion and/or foster cell proliferation may provide possible explanations for the underlying therapeutic principles in the empirical use of LS-containing formulations in DM and DM-related disorders as applied in TMM.


Assuntos
Hipoglicemiantes/farmacologia , Insulina/metabolismo , Leonurus , Extratos Vegetais/farmacologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Secreção de Insulina , Insulinoma , Medicina Tradicional da Mongólia , Neoplasias Pancreáticas , Ratos
17.
Int J Food Microbiol ; 150(2-3): 95-102, 2011 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-21864930

RESUMO

A study tracking thermotolerant campylobacters from the setting of the broilers throughout the whole rearing period, slaughter and sale of chicken products in five consecutive broiler rotations of the same henhouse as well as in two different other farms was conducted in a well-defined geographic area (Hajdú-Bihar county, Hungary) between March 2006 and Feb 2007. All notified cases of human campylobacteriosis in this area during the study period were also included. One hundred and one, 44, 23 and 282 Campylobacter jejuni and 13, 15, 20 and 60C. coli were isolated from broiler houses, slaughterhouses, retail shops and human samples, respectively. Sixty-two isolates collected from broilers or their environment selected from different flocks (57C. jejuni, 5C. coli), 92 isolates collected from abattoirs and retail shops (72C. jejuni, 20C. coli), as well as 85 randomly selected human isolates (74C. jejuni, 11C. coli) were subjected to PFGE analysis using restriction enzymes KpnI and SmaI. Sixty-six of the isolates produced unique Sma-Kpn profiles; the majority (46) of these were of human origin. The remaining isolates formed PFGE clusters of between 2-25 isolates with 14 (12C. jejuni and 2C. coli) main clusters comprised of five or more isolates with identical KpnI-SmaI patterns. Two genetic clones of C. jejuni (clone A, n=25; clone B, n=20) included 18% of isolates from different sources. Generally, isolates from one cluster were found in 1-3 different flocks, notably, clone B was present in three rotations including those from the two independent farms. Six of the seven investigated flocks had one or two characteristic prevalent clones. Transmission of clones between consecutive flocks was frequently seen. Spread of both C. jejuni and C. coli was traced multiple times along the food chain; eight C. jejuni, but no C. coli clones were detected both in broilers and humans. These data suggest that broilers were the major source for C. jejuni but not for C. coli in the studied area and period. For C. jejuni the carryover of strains between consecutive flocks may be a common event, but the strain is eventually replaced by another and consecutive carryover events seem to be infrequent. The majority of the human disease was due to nonepidemic strains; some clones were transmitted from more than one broiler flocks (including epidemiologically unrelated flocks) to humans multiple times.


Assuntos
Infecções por Campylobacter/microbiologia , Campylobacter/classificação , Microbiologia de Alimentos , Matadouros/estatística & dados numéricos , Adaptação Fisiológica , Animais , Biodiversidade , Campylobacter/genética , Campylobacter/isolamento & purificação , Infecções por Campylobacter/epidemiologia , Infecções por Campylobacter/transmissão , Infecções por Campylobacter/veterinária , Campylobacter jejuni/classificação , Campylobacter jejuni/genética , Campylobacter jejuni/isolamento & purificação , Galinhas/microbiologia , Eletroforese em Gel de Campo Pulsado , Seguimentos , Geografia/estatística & dados numéricos , Humanos , Hungria/epidemiologia , Carne/microbiologia , Prevalência , Temperatura
18.
Exp Suppl ; 102: 51-9, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21299061

RESUMO

The skin, the largest organ of the body, functions as a barrier between the body proper and the external environment, as it is constantly exposed to noxious stressors. During the last few years, the concept of an interactive network involving cutaneous nerves, the neuroendocrine axis, and the immune system has emerged. The neuroendocrine system of the skin is composed of locally produced neuroendocrine mediators that interact with specific receptors. Among these mediators are neuropeptides, including members of the galanin peptide family--galanin, galanin-message associated peptide, galanin-like peptide, and alarin--which are produced in neuronal as well as nonneuronal cells in the skin. Here, we review the expression of the galanin peptides and their receptors in the skin, and the known functions of galanin peptides in different compartments of the skin. We discuss these data in light of the role of the galanin peptide family in inflammation and cell proliferation.


Assuntos
Galanina/fisiologia , Fenômenos Fisiológicos da Pele , Animais , Proliferação de Células , Dermatite/imunologia , Dermatite/fisiopatologia , Humanos , Pele/imunologia , Cicatrização
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