RESUMO
The aim of this study was to characterize the quantitative analyzed EEG (electroencephalogram) findings (qEEG) in chronic solvent encephalopathy (CSE) patients and study whether the qEEG findings associate with the duration and intensity of the solvent exposure. Also, the diagnostic value of qEEG in CSE is discussed. The EEG of 47 male CSE patients was analyzed. The laboratory's own reference EEG values of 24 healthy male subjects formed the laboratory control group. We also used an age-matched control group of 100 male blue-collar workers without occupational solvent exposure. The main finding of our study was that the power of the frontal theta band is increased in the CSE patient group compared with the laboratory control group. This suggests that the frontal cortex may be susceptible to the noxious effects of solvents. However, this difference was not seen in comparison with the matched control group, and thus, the connection with solvent effects remains uncertain. The variables indicating the level of solvent exposure did not associate with the power of the theta activity in the frontal area. Because of the small amount and unspecificity of the observed abnormalities, qEEG cannot be recommended to be used in the clinical diagnostics of solvent encephalopathy.
Assuntos
Dano Encefálico Crônico/diagnóstico , Eletroencefalografia/métodos , Síndromes Neurotóxicas/diagnóstico , Doenças Profissionais/diagnóstico , Solventes/efeitos adversos , Adulto , Dano Encefálico Crônico/induzido quimicamente , Dano Encefálico Crônico/fisiopatologia , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/fisiopatologia , Doenças Profissionais/induzido quimicamente , Doenças Profissionais/fisiopatologia , Exposição Ocupacional , Valores de ReferênciaRESUMO
Somatosensory evoked potentials were measured prospectively in 38 children with acute lymphoblastic leukemia to evaluate the side effects of vincristine therapy on conduction of the peripheral nerves. Nineteen patients at standard risk received vincristine 12 mg/m2 during induction therapy and 19 patients at intermediate or high risk received 6 mg/m2 during induction therapy and an additional 6 mg/m2 during delayed intensification therapy. These latencies were compared with those of 38 age-, height-, and sex-matched controls. A prolongation in the peripheral conduction time of the posterior tibial nerve was found in the standard risk patients after induction compared with that of the controls, and a delay was found not only from the ankle to the popliteal fossa, but also from the popliteal fossa to the spinal cord (P < .01). The conduction times of the median nerve from the wrist to the plexus (P < .01) and from the wrist to the spinal cord (P < .01) were prolonged after delayed intensification therapy. There was a significant delay in the median and tibial nerve conduction between the intermediate and high risk patients and their controls after a total vincristine dose of 12 mg/m2. These delays were found along the entire length of the nerves, especially in the proximal part of the tibial nerve (P < .001).
Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Doenças Desmielinizantes/induzido quimicamente , Potenciais Somatossensoriais Evocados/efeitos dos fármacos , Condução Nervosa/efeitos dos fármacos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Vincristina/efeitos adversos , Adolescente , Criança , Pré-Escolar , Estudos de Avaliação como Assunto , Feminino , Seguimentos , Humanos , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatologia , Tempo de Reação/efeitos dos fármacos , Fatores de RiscoRESUMO
OBJECTIVES: The aim of this study was to explore the possible influence of radiofrequency (RF) radiation exposure on human brain function. METHODS: The electroencephalographic (EEG) activity of 19 volunteers was quantitatively analyzed. Ten of the subjects were men (28-48 years of age) and 9 were women (32-57 years of age). The sources of exposure were 5 different cellular phones (analogue and digital models) operating at a frequency of 900 MHz or 1800 MHz. The EEG activity was recorded in an awake, closed-eyes situation. Six 30-minute experiments, including 1 sham exposure, were made for each subject. The duration of a real exposure phase was 20 minutes. RESULTS: Exposure to one of the phones caused a statistically significant change in the absolute power at the delta band of the EEG recording. However, no difference was seen in the relative power of the same band, and no changes occurred during exposure to other phones at any frequency bands. CONCLUSIONS: The findings of this study suggest that exposure to radiofrequency fields emitted by cellular phones has no abnormal effects on human EEG activity. The observed difference in 1 parameter was probably caused by statistical chance.
Assuntos
Encéfalo/efeitos da radiação , Eletroencefalografia , Campos Eletromagnéticos/efeitos adversos , Telefone , Adulto , Intervalos de Confiança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Probabilidade , Doses de Radiação , Radiação não Ionizante/efeitos adversos , Valores de Referência , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: Because the brain is the recognized target organ for aluminum toxicity, internal aluminum load and central nervous system functions were investigated among aluminum welders in a shipyard. METHODS: Seventeen male welders with a mean age of 37 (range 24-48) years and a history of about four years of metal inert-gas welding on aluminum were the subjects. Aluminum in serum (S-Al) and urine (U-Al) was analyzed with graphite-furnace atomic absorption spectrophotometry. Central nervous system functions were examined with neuropsychological tests, symptom and mood questionnaires, quantitative electroencephalography (QEEG), and P300 evoked responses. RESULTS: The mean S-Al concentration was 0.21 (range 0.03-0.64) mumol.l-1 and the mean U-Al was 2.8 (range 0.9-6.1) mumol.l-1. Although the welders performed normally on the neuropsychological tests, there was a negative association between all four memory tests and U-Al and a positive association between the variability of visual reaction times and S-Al. In the QEEG, the amount of delta and theta activity in the frontal region correlated positively and the amount of alpha activity in the frontal region correlated negatively with S-Al. CONCLUSIONS: The S-Al and U-Al measurements indicated increased internal loads of aluminum in most of the welders. This finding is compatible with slowly eliminated aluminum from tissues. The neuropsychological assessment suggested disturbing effects of aluminum on short-term memory, learning, and attention. In the QEEG, a corresponding exposure-effect relationship was found for activity in the frontal region. Further studies are needed on the possibility that exposure to aluminum welding fumes causes harm to human health.
Assuntos
Alumínio/efeitos adversos , Alumínio/metabolismo , Encéfalo/efeitos dos fármacos , Exposição Ocupacional/efeitos adversos , Adulto , Afeto/efeitos dos fármacos , Carga Corporal (Radioterapia) , Encéfalo/fisiopatologia , Eletroencefalografia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , SoldagemRESUMO
OBJECTIVES: The relationship between elevated internal aluminum loads and central nervous system function was studied among aluminum welders, and the threshold level for adverse effect was defined. METHODS: For 65 aluminum welders and 25 current mild steel welders body burden was estimated, and the aluminum concentrations in serum (S-Al) and urine (U-Al) were analyzed with graphite furnace atomic absorption spectrometry with Zeeman background correction. Referents and low-exposure and high-exposure groups were defined according to an aggregated measure of aluminum body burden, the group median S-Al levels being 0.08, 0.14, and 0.46 micromol/l, respectively, and the corresponding values for U-Al being 0.4, 1.8, and 7.1 micromol/l. Central nervous system functions were assessed with a neuropsychological test battery, symptom and mood questionnaires, a visual and quantitative analysis of electroencephalography (EEG), and P3 event-related potentials with pitch and duration paradigms. RESULTS: Subjective symptoms showed exposure-related increases in fatigue, mild depression, and memory and concentration problems. Neuropsychological testing revealed a circumscribed effect of aluminum, mainly in tasks demanding complex attention and the processing of information in the working memory system and in the analysis and recall of abstract visual patterns. The visual EEG analysis revealed pathological findings only for aluminum welders. Mild, diffuse abnormalities were found in 17% of the low-exposure group and 27% of the high-exposure group, and mild to moderate epileptiform abnormalities at a frequency of 7% and 17%, respectively. CONCLUSIONS: Both objective neurophysiological and neuropsychological measures and subjective symptomatology indicated mild but unequivocal findings dose-dependently associated with increased aluminum body burden. The study indicates that the body burden threshold for adverse effect approximates an U-Al value of 4-6 micromol/l and an S-Al value of 0.25-0.35 micromol/l among aluminum welders.
Assuntos
Alumínio/sangue , Alumínio/urina , Doenças do Sistema Nervoso Central/induzido quimicamente , Exposição Ocupacional/análise , Soldagem , Adulto , Distribuição por Idade , Alumínio/efeitos adversos , Carga Corporal (Radioterapia) , Doenças do Sistema Nervoso Central/epidemiologia , Intervalos de Confiança , Transtorno Depressivo/induzido quimicamente , Eletroencefalografia , Monitoramento Ambiental , Monitoramento Epidemiológico , Fadiga/induzido quimicamente , Feminino , Finlândia/epidemiologia , Humanos , Incidência , Masculino , Concentração Máxima Permitida , Transtornos da Memória/induzido quimicamente , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Saúde Ocupacional , Probabilidade , Medição de RiscoRESUMO
Somatosensory potentials in the non-affected hemisphere evoked by simulation of both the median nerve (median nerve SEPs) and the posterior tibial nerve (tibial nerve SEPs) were studied in 40 patients with supratentorial nonhaemorrhagic cerebral infarction three times during a one-year follow-up period. The EP-N20 interpeak latencies (IPLs) of the median nerve SEPs were on average longer in the patient group than in the control group (especially in patients with evidence of mass displacements in the cerebral computed tomography), whereas no significant differences were observed in the amplitudes of the median nerve SEPs. The P57-N75 amplitudes of the tibial nerve SEPs were on average lower in the patient group than in the control group. During the follow-up period the peak latencies and the P40-N75 IPLs of the tibial nerve SEPs increased and the amplitudes of the tibial nerve SEPs diminished.
Assuntos
Infarto Cerebral/fisiopatologia , Potenciais Somatossensoriais Evocados/fisiologia , Nervo Mediano/fisiologia , Nervo Tibial/fisiologia , Eletromiografia , Humanos , Estudos Prospectivos , Valores de Referência , Fatores de TempoRESUMO
Somatosensory potentials evoked by stimulation of the median nerve (median nerve SEPs) were studied in a prospective and sequential series of 40 patients with first supratentorial and nonhaemorrhagic cerebral infarct. In 35 patients the SEPs were recorded three times during the first year after the stroke. The location of the infarcted zone was reflected in the number of detected abnormalities: most patients with infarct changes extending to the gray matter of the Rolandic cortex showed abnormalities in the median nerve SEPs, and all patients with involvement of both precentral and postcentral cortical gray matter had abnormal median nerve SEPs. In the entire patient group when both latency and amplitude abnormalities were included about half (48%) of the patients had abnormal median nerve SEPs a week after the stroke, 39% 2-3 months after the stroke and 29% about one year after the stroke. These changes were not significant. When separately surveying the changes in the numbers of latency and amplitude abnormalities the difference between the first and the third examinations was nearly significant only in the number of latency abnormalities. Furthermore, in the absolute latency and amplitude values, no significant changes could be seen within the first two-three months after the infarct; within the whole one-year follow-up period a nearly significant change was noted between the second and the third examination in only one parameter (P22 peak latency). Thus, the abnormalities in the median nerve SEPs, especially the amplitude abnormalities, were relatively permanent during the one-year period after cerebral infarct.
Assuntos
Infarto Cerebral/fisiopatologia , Potenciais Somatossensoriais Evocados/fisiologia , Nervo Mediano/fisiopatologia , Adulto , Idoso , Encéfalo/fisiopatologia , Estimulação Elétrica , Eletroencefalografia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de TempoRESUMO
A prospective 1-year follow-up examination was carried out in 35 patients with supratentorial cerebral infarction. The median nerve SEPs were performed 3-15 days and the tibial nerve SEPs 4-19 days after the stroke. The functional outcome was assessed 1 year after the stroke. The occupational outcome correlated most closely with the amplitude abnormalities (absence or attenuation) and with the overall abnormality in the tibial nerve SEPs. The ability to cope with activities of daily living was associated significantly with motor signs in the neurological examination performed during the acute stage, and nearly significantly with the presence or absence of the N60 wave in the median nerve SEPs. Both the tibial nerve SEPs and the motor signs correlated nearly significantly with the presence of neurologic signs or symptoms 1 year after the stroke. The prognostic information provided by the clinical examination and the SEPs is thus qualitatively different and complementary. More prognostic information could be gained by the use of both tibial nerve and median nerve SEPs than by the use of median nerve SEPs only; in the present series of patients the tibial nerve SEPs even had a greater prognostic value than the median nerve SEPs.
Assuntos
Infarto Cerebral/fisiopatologia , Potenciais Somatossensoriais Evocados , Nervo Mediano/fisiologia , Nervo Tibial/fisiologia , Atividades Cotidianas , Adulto , Fatores Etários , Infarto Cerebral/diagnóstico por imagem , Estimulação Elétrica , Eletroencefalografia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Ocupações , Prognóstico , Estudos Prospectivos , Tempo de Reação/fisiologia , Tomografia Computadorizada por Raios XRESUMO
Somatosensory potentials evoked by stimulation of the posterior tibial nerve (tibial nerve SEPs) were studied in 40 patients with supratentorial non-haemorrhagic cerebral infarction and in 25 control subjects, SEPs were recorded twice in 39 patients and thrice in 35 patients. The first examination was carried out 4-19 days after the onset of the symptoms, the second examination 56-100 days after the stroke, and the third examination 348-393 days after the stroke. Increased side-to-side differences in the P57 and N75 peak latencies and absence of the P40 peak were the most frequent abnormal findings. The latency abnormalities were associated with involvement of the subcortical white matter of the rolandic region. The absence of the P40 peak was, in contrast, closely related to the extension of the infarcted area into the cortical gray matter of the rolandic region. When all SEP abnormalities were taken into account 55% of patients showed at least one abnormality in the tibial nerve SEP during the acute stage, 51% of patients had abnormal SEPs in the second examination and 43% of patients in the third examination. A nearly significant decrease was observed in the number of latency abnormalities, but the number of amplitude abnormalities, including absent responses, did not change during the 1 year follow-up period.
Assuntos
Infarto Cerebral/fisiopatologia , Potenciais Somatossensoriais Evocados/fisiologia , Nervo Tibial/fisiologia , Adolescente , Adulto , Idoso , Afasia/fisiopatologia , Córtex Cerebral/fisiopatologia , Infarto Cerebral/diagnóstico , Transtornos da Consciência/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Movimento/fisiologia , Exame Neurológico , Estudos Prospectivos , Tempo de Reação/fisiologia , Tomografia Computadorizada por Raios XRESUMO
During vaccinia virus (VV) assembly a major polypeptide migrating with an apparent MW of 35K, designated Ag35, is expressed as an early function and becomes an integral component of the lipoprotein envelope surrounding the mature virion. In a previous study evaluating humoral immunity to VV, a prominent response against Ag35 was invariably detected in immunized mice. In the context of our continuing investigations of the structure and function of the vaccinia envelope, with a view to alteration in antigenicity of this agent when used as a vaccine vector for foreign antigens, we carried out detailed mapping of the Ag35 gene, as well as determination of the nucleotide sequence. Use of hybridization-arrested translation, coupled with immunoprecipitation, located this gene within a 2.7-kbp EcoRI fragment of the larger 8.7-kbp HindIII H fragment. By means of S1 endonuclease resistance analysis a viral transcript was identified at the site of the Ag35 gene, where the occurrence of an open reading frame (ORF), corresponding to the transcript, was deduced from DNA sequence determination. However, the ORF encodes a polypeptide of only 22,300 Da predicted MW, which is much lower than the apparent MW estimated from SDS-polyacrylamide gel electrophoresis. The size discrepancy is not due to glycosylation or phosphorylation of Ag35 but may result from a proline-rich sequence which occurs in this polypeptide. To confirm that the ORF recognized in this study does, indeed, encode Ag35, the gene was expressed as a beta-galactosidase fusion protein in pUC19; Escherichia coli transformed with the relevant clones expressed a polypeptide of the appropriate molecular weight and antigenicity, when tested by Western blots. Regarding secondary structure and hydropathicity it can be predicted from the DNA sequence that Ag35 is highly hydrophilic but contains a hydrophobic region at the carboxy terminus, perhaps providing the stretch involved in membrane insertion. Computer search of a bank of protein sequences revealed an unusually strong similarity of 68% between the Ag35 at amino acid positions 44-121 and the G glycoprotein of respiratory syncytial virus at positions 189-264.
Assuntos
Antígenos Virais/genética , DNA Viral/genética , Genes Virais , Vaccinia virus/imunologia , Proteínas do Envelope Viral/genética , Sequência de Bases , Clonagem Molecular , Epitopos , Regulação da Expressão Gênica , Dados de Sequência Molecular , Estrutura Molecular , Proteínas Recombinantes de Fusão/genética , Mapeamento por Restrição , Solubilidade , Fatores de Tempo , Proteínas do Envelope Viral/imunologiaRESUMO
Caldesmon is a widely distributed contractile protein that occurs in both a high molecular weight [120-150-kilodalton (kDa)] and a low molecular weight (71-80-kDa) form, depending on the tissue. The structural relationship between these two forms was examined by mapping techniques. Partial cyanogen bromide cleavage in conjunction with sodium dodecyl sulfate gel electrophoresis was used to construct a map of the cleavage points and determine the relative position of the fragments in a high molecular weight caldesmon from chicken gizzard (caldesmon125). By use of this map, markers for different regions of the protein were obtained: Antibodies directed toward certain areas were prepared by affinity purification, and specific 125I-labeled tryptic peptides were found to originate from terminal cyanogen bromide fragments. Mapping of a lower molecular weight form of caldesmon (caldesmon72 from chicken liver) revealed the presence of sequences located in both ends of caldesmon125. A terminal 38-kDa fragment of both proteins was apparently identical on the basis of arrangement of cleavage sites, antibody reactivity, and iodopeptide mapping. Fragments from the other end of both proteins exhibited an identical pattern of peptides. These results show that it is sequences located in the central area of caldesmon125 which are missing in caldesmon72, indicating that the smaller molecule is not simply a proteolytic product of the larger. The two forms of caldesmon may be derived from separate genes or by alternative splicing from a single gene.
Assuntos
Proteínas de Ligação a Calmodulina/isolamento & purificação , Animais , Sítios de Ligação , Proteínas de Ligação a Calmodulina/genética , Galinhas , Brometo de Cianogênio , Eletroforese em Gel de Poliacrilamida , Peso Molecular , Fragmentos de Peptídeos/isolamento & purificaçãoRESUMO
In 40 patients with supratentorial non-haemorrhagic cerebral infarct, the findings in the tibial nerve SEPs recorded during the acute stage correlated significantly with the development of seizures during a 1 year follow-up period. Abnormality in the side-to-side difference of the P40-N48 amplitude was the finding with the highest correlation with the development of seizures: 87.5% of the patients were classified correctly as to the risk of seizures.
Assuntos
Infarto Cerebral/fisiopatologia , Eletroencefalografia , Epilepsia do Lobo Temporal/fisiopatologia , Potenciais Somatossensoriais Evocados/fisiologia , Nervo Tibial/fisiologia , Adulto , Córtex Cerebral/fisiopatologia , Infarto Cerebral/complicações , Epilepsia do Lobo Temporal/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The aim of the study was to examine the role of serotonergic (5-HT) and noradrenergic mechanisms in the regulation of wakefulness and sleep. For this purpose, adult cats with implanted electrodes for EEG, EOG and EMG were exposed to the 5-HT uptake blocker citalopram (0.1, 0.5 and 5.0 mg/kg intraperitoneally) and the noradrenaline uptake blocker prindamine (5 mg/kg intraperitoneally) at the start of continuous 16-hour sleep-wake recordings. Citalopram increased deep slow wave sleep and decreased REMS. Also prindamine decreased REMS but initially increased the proportion of time spent in the state of active wakefulness. Furthermore, to examine the interactions between 5-HT-nergic and noradrenergic mechanisms in the regulation of sleep, the administration of citalopram was preceded by intraperitoneal injections of phentolamine (10 mg/kg), an alpha-antagonist, and propranolol (5 mg/kg), a beta-antagonist. Phentolamine was totally ineffective against citalopram whereas propranolol partially counteracted the effects of citalopram on sleep. Prindamine was combined with the alpha-antagonists yohimbine (1 mg/kg), phentolamine (10 mg/kg) and prazosin (1 mg/kg) or with the beta-antagonist propranolol (5 mg/kg). Yohimbine was without any effect on REMS, phentolamine partly antagonized prindamine-induced decrease in the percentage of REMS, and prazosin only prolonged REMS latency and reduced deep SWS as well. Propranolol partially antagonized the prindamine-induced initial increase in active wakefulness time.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Norepinefrina/metabolismo , Antagonistas da Serotonina/farmacologia , Sono/efeitos dos fármacos , Vigília/efeitos dos fármacos , Animais , Gatos , Citalopram , Eletroencefalografia , Indanos/farmacologia , Masculino , Fentolamina/farmacologia , Prazosina/farmacologia , Propranolol/farmacologia , Propilaminas/farmacologia , Simpatolíticos/farmacologia , Ioimbina/farmacologiaRESUMO
Intrathecal chemotherapy has been determined to cause transient or permanent paraparesis due to myelopathy in patients with leukemia or other malignancies. To systematically evaluate the effect of methotrexate on spinal cord function, somatosensory evoked potentials (SEP) were measured in children with acute lymphoblastic leukemia (ALL). A prospective evaluation was performed in 38 consecutive children aged 1.4-15.3 years with newly diagnosed ALL during treatment. Intrathecal methotrexate therapy was included in the therapy schedule of all patients as central nervous system (CNS) therapy in addition to intravenous chemotherapy in 19 standard risk patients and intravenous chemotherapy with cranial irradiation in 19 intermediate or high-risk patients. The measured conduction times were compared with those of 38 control children matched for age, height, and sex. A significant increase in the conduction time of the tibial nerve SEP was found between the Th12 level and the cortex in children with ALL after receiving intrathecal methotrexate therapy during the induction and CNS therapy phases when compared with their controls. The difference of the mean latencies was 1.45 ms (95% CI 0.39-2.51; P < 0.01). There was no significant delay in the median nerve SEP from the brain stem to the cortex, indicating that the conduction delay was in the area of the spinal cord exposed to intrathecal methotrexate. Moreover, the cortical amplitudes of the median nerve SEPs were significantly reduced when measured immediately after intravenous and intrathecal methotrexate and compared to the amplitudes measured after induction therapy in standard risk patients (P = 0.001). Intrathecal methotrexate with systemic chemotherapy causes a deterioration in the somatosensory pathways within the CNS, suggesting also spinal cord dysfunction in children with ALL in addition to the cerebral dysfunction described earlier.
Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Potenciais Somatossensoriais Evocados/efeitos dos fármacos , Metotrexato/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Medula Espinal/efeitos dos fármacos , Adolescente , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Injeções Intravenosas , Injeções Espinhais , Masculino , Metotrexato/administração & dosagem , Condução Nervosa , Tempo de Reação , Indução de Remissão , Medula Espinal/fisiopatologiaRESUMO
Neurotoxic effects of industrial solvents have recently aroused great interest. Few studies have applied evoked potential methods to test acute or chronic neurotoxicity of solvents or alcohol. Eight young healthy male volunteers were exposed for 4 h to about 1200 or 700 mg/m3 of xylene alone or in combination with alcohol 0.8 g/kg. Single doses of 0.4 g/kg and 0.8 g/kg alcohol were also used as test substances, and the subjects stayed for 4 h in the exposure chamber also during 3 control days. Tests were conducted single-blind and the subjects acted as their own controls. Visual (VEPs) and somatosensory (SEPs) evoked potentials as well as electroretinograms (ERGs) were recorded in the mornings before the exposure and in the afternoons immediately after exposure stopped. A single dose of alcohol 4 h prior to recording increased the latencies of P50, N60, P115 and N155 of VEP dose-dependently. Alcohol alone did not change significantly the amplitude of VEP, but xylene 1200 mg/m3 in combination with alcohol 0.8 g/kg decreased significantly the amplitude of N60-P115. The lower concentration of xylene in combination with alcohol as well as xylene 1200 mg/m3 alone tended to have similar effects. Concerning the latency changes simultaneous xylene exposure tended to counteract the effect of alcohol. No significant effects on ERGs could be shown in any of situations. The effects of SEPs were minor or lacking, and the lower exposure levels were associated with more statistically significant changes than higher exposure levels.
Assuntos
Etanol/farmacologia , Potenciais Evocados/efeitos dos fármacos , Xilenos/farmacologia , Adulto , Eletrorretinografia , Humanos , Masculino , Sensação/efeitos dos fármacos , Percepção Visual/efeitos dos fármacosRESUMO
A potential role for cAMP in regulating the differentiation of myoblasts has led us to examine the components of the cAMP signaling system, including the type IV, cAMP-specific phosphodiesterases. The full coding sequence of the phosphodiesterase PDE4D1 was inserted in the bacterial expression vector pGEX-KG. N- and C-terminal truncations were also placed in the same vector, allowing the expression and purification of glutathione S-transferase (GST)-PDE fusion proteins using glutathione-Sepharose. The purified PDE was active [V(max) = 318 +/- 18 nmol min(-1)(mg of protein)(-1)] and inhibited by RO 20-1724, rolipram, and MIX (IC50 values of 2, 0.4, and 40 microM, respectively). The requirement of PDE4D1 for a divalent cation was also examined. It was able to use Mg2+, Co2+, and Mn2+, but not Zn2+, suggesting that it is not a zinc hydrolase as has been proposed for other PDE types. Deletion of both C- and N-terminal regions affected the apparent native size of the enzyme. The C-terminal region was involved in dimer formation, whereas an N-terminal region was responsible for larger aggregates. Removal of the last 35 amino acids of an N-terminal 80-residue highly conserved region (UCR2) resulted in a 6-fold increase in PDE activity, providing evidence that this part of the molecule acts as an intramolecular inhibitor. The availability of a highly purified, enzymatically active protein in substantial quantities has allowed us to directly examine PDE4D1 for the first time.
Assuntos
3',5'-AMP Cíclico Fosfodiesterases/química , 3',5'-AMP Cíclico Fosfodiesterases/metabolismo , 3',5'-AMP Cíclico Fosfodiesterases/genética , Animais , Cátions Bivalentes/farmacologia , Linhagem Celular , Cromatografia em Gel , Clonagem Molecular , Primers do DNA , Eletroforese em Gel de Poliacrilamida , Escherichia coli/genética , Expressão Gênica , Cinética , Fibras Musculares Esqueléticas/enzimologia , Mutação , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/isolamento & purificação , Proteínas Recombinantes de Fusão/metabolismo , Deleção de Sequência , Relação Estrutura-AtividadeRESUMO
We have been studying cAMP signaling in L6 myoblasts because of its potential role in regulating the differentiation of these cells into multinucleate myotubes. Previous studies have shown that treatment of L6 myoblasts with cAMP analogs causes an increase in cAMP phosphodiesterase activity. To assess the role of protein kinase A in this cAMP-mediated increase in cAMP phosphodiesterase activity, L6 myoblasts were transfected with a plasmid containing the cDNA for a mutant regulatory subunit of protein kinase A, which functions as a dominant negative inhibitor of this enzyme. The cDNA was under control of the metallothionein promoter in the construct. Induction of the mutant regulatory subunit with Zn2+ decreased cAMP-dependent protein kinase activity by 90%. Zn2+ treatment was also able to completely block the cAMP-mediated increase in phosphodiesterase activity, showing that this effect is mediated by protein kinase A. The activity of the cAMP-induced phosphodiesterase was inhibited by low concentrations of RO 20-1724, showing that it was a member of the type IV low Km cAMP phosphodiesterase family of enzymes. We used the polymerase chain reaction and consensus primers designed to amplify phosphodiesterase sequences to show that L6 myoblasts also contain mRNA for a type IV low Km cAMP phosphodiesterase designated PDE3.1. The levels of this mRNA were increased greatly by treatment with dibutyryl cAMP or forskolin in L6 myoblasts and also in differentiated L6 myotubes. Run-off transcription assays showed that this increase in PDE mRNA was regulated, at least in part, by an increase in the rate of transcription of the PDE3 gene. The induction of PDE3 message by cAMP was blocked when the L6 transfectants were treated with Zn2+ to induce protein kinase A inhibition. Therefore, some of the cAMP-mediated increase in phosphodiesterase activity seen in L6 myoblasts is due to a protein kinase A-mediated increase in PDE3 mRNA. This pathway may serve as a feedback mechanism to modulate the inhibitory effects of cAMP on myogenesis.
Assuntos
3',5'-AMP Cíclico Fosfodiesterases/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Músculos/enzimologia , 1-Metil-3-Isobutilxantina/farmacologia , 3',5'-AMP Cíclico Fosfodiesterases/genética , Animais , Sequência de Bases , Bucladesina/farmacologia , Diferenciação Celular , Linhagem Celular , Colforsina/farmacologia , Primers do DNA/química , Expressão Gênica , Dados de Sequência Molecular , Músculos/citologia , RNA Mensageiro/genética , RatosRESUMO
OBJECTIVES: Assessment of neurophysiological functions in workers with low level exposure to lead and evaluation of the efficacy of bone lead measurements in the prediction of effects of lead. METHODS: Exposure to lead of 60 workers from a lead battery battery factory was estimated from historical blood lead measurements and analysis of lead in the tibial and calcaneal bones with x ray fluorescence. Peripheral and central nervous system functions were assessed by measuring conduction velocities, sensory distal latencies, sensory amplitudes, and vibration thresholds as well as by quantitative measurement of the absolute and relative powers and mean frequencies of different electroencephalograph (EEG) channels. RESULTS: Sensory amplitudes, and to a smaller degree sensory or motor conduction velocities, showed a negative correlation with long term exposure to lead, most clearly with integrated blood lead concentration and exposure time. Vibration thresholds measured in the arm were related to recent exposure to lead, those measured in the leg to long term exposure. The alpha and beta activities of the EEG were more abundant in subjects with higher long term exposure to lead. Calcaneal lead content reflected short term exposure, tibial lead content reflected long term exposure. Blood lead history showed a closer relation with effects of lead than the tibial or calcaneal lead concentrations. CONCLUSIONS: Vibratory thresholds, quantitative EEG, and to a smaller extent the sensory amplitude, provide sensitive measures of effects of lead in occupationally exposed adults. Most accurate estimates of health risks induced by lead can be obtained from a good history of blood lead measurements. If such a history of blood lead concentrations is not available, analysis of bone lead may be used for the assessment of health risks.
Assuntos
Chumbo/efeitos adversos , Sistema Nervoso/efeitos dos fármacos , Exposição Ocupacional/efeitos adversos , Adulto , Carga Corporal (Radioterapia) , Osso e Ossos/química , Eletroencefalografia/efeitos dos fármacos , Feminino , Reflexo H/efeitos dos fármacos , Humanos , Chumbo/sangue , Masculino , Pessoa de Meia-Idade , Fenômenos Fisiológicos do Sistema Nervoso , Condução Nervosa/efeitos dos fármacos , Limiar Sensorial/efeitos dos fármacos , VibraçãoRESUMO
The study evaluated the off-line relationship of attention, memory and other cognitive performances with the auditory event-related potentials P3 (P300) and N2. The sample comprised 200 middle-aged construction workers. Verbal, visuomotor and memory tests were administered. Attentional domains were examined using CogniSpeed software. Slowed reaction times in the test of sustained attention (vigilance) were associated with delayed P3 latency (p < 0.001) and decreased P3 amplitude (p = 0.005), as well as with delayed N2 latency (p < 0.001). Visuomotor slowing in Digit Symbol was also related to delayed P3 latency (p = 0.030) and decreased P3 amplitude (p = 0.014). In contrast, mild cognitive impairment, short- and long-term memory, and concentrating or sharing attention with high working memory demands were not related to P3. The results suggest that P3 is linked to attentional performance with low working memory demands rather than to effortful working memory updating, retrieval from memory stores, or mild cognitive impairment.
Assuntos
Atenção/fisiologia , Cognição/fisiologia , Potenciais Evocados P300/fisiologia , Potenciais Evocados Auditivos/fisiologia , Memória/fisiologia , Adulto , Fatores Etários , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Neurológicos , Testes Neuropsicológicos , Desempenho Psicomotor/fisiologia , Tempo de Reação , Período Refratário Eletrofisiológico , Estudos de AmostragemRESUMO
OBJECTIVE: To evaluate the neuropsychological effects of current low level and previous higher levels of exposure to lead and evaluate the relation between effects of lead and bone lead. METHODS: A neuropsychological test battery was given to 54 storage battery workers with well documented long term exposure to lead. The effect was studied in two subgroups: those whose blood lead had never exceeded 2.4 mmol/l (the low BPbmax group, n = 26), and those with higher exposure about 10 years earlier (the high BPbmax group, n = 28). In both groups, the recent exposure had been low. Correlations between the test scores and the indices of both long term and recent exposure--including the content of lead in the tibial and calcaneal bone--and covariance analyses were used to assess the exposure-effect relation. Age, sex, and education were controlled in these analyses. RESULTS: Analyses within the low BPbmax group showed a decrement in visuospatial and visuomotor function (block design, memory for design, Santa Ana dexterity), attention (digit symbol, digit span), and verbal comprehension (similarities) associated with exposure to lead and also an increased reporting of subjective symptoms. The performance of the high BPbmax group was worse than that of the low BPbmax group for digit symbol, memory for design, and embedded figures, but there was no reporting of symptoms related to exposure, probably due to selection in this group. No relation was found between the output variables and the tibial lead concentration. The calcaneal lead concentrations were related to the symptoms in the low BPbmax group. CONCLUSIONS: Neuropsychological decrements found in subjects with high past and low present exposure indicate that blood lead concentrations rising to 2.5-4.9 mmol/l cause a risk of long lasting or even permanent impairment of central nervous system function. Milder and narrower effects are associated with lower exposures; their reversibility and time course remain to be investigated. History of blood lead gives a more accurate prediction of the neuropsychological effects of lead than do measurements of bone lead.