RESUMEN
BACKGROUND: Laboratory methods for measuring vaccine potency of nebulized aerosol are required to support clinical trials of measles aerosol vaccination. METHODS: Measles vaccine containing the Edmonston Zagreb virus strain was reconstituted in sodium fluoride as tracer and nebulized from three devices. Emitted aerosol was collected using an impinger. Aliquots were removed from the impinger chamber for vaccine virus plaque assay and for fluoride measurement to determine aerosol output. RESULTS: Vaccine potency retention results were adjusted to take into account the effect of aerosol output on estimates. Adjusted potency of nebulized vaccine ranged from 88% to 102%. CONCLUSIONS: New laboratory methods to measure aerosol vaccine potency retention were reliable and accurate. The results demonstrated that Edmonston Zagreb vaccine remains robust during aerosolisation and imply that this is a viable candidate for further evaluation in the measles aerosol project.
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Aerosoles/normas , Vacuna Antisarampión/normas , Virus del Sarampión/aislamiento & purificación , Viabilidad Microbiana , Nebulizadores y Vaporizadores , Ensayo de Placa Viral/métodos , Administración por Inhalación , Humanos , Sarampión/prevención & control , Reproducibilidad de los Resultados , Organización Mundial de la SaludRESUMEN
Concentrations of cadmium, lead, nickel and vanadium were determined in water, surficial sediments and the muscle of three demersal fish species (Epinephelus coioides, Psettodes erumei and Solea elongate) from 15 sampling sites in the northern part of Persian Gulf. Concentrations of the elements were determined using Inductively Coupled Plasma Mass Spectrometer. There were no significant differences among the sampling sites in Cd and Pb levels in the sediments. The highest concentrations of Ni and V in sediments were found near the southern coast of Qeshm Iland and Bandar Lengeh. Concentrations of Cd, Pb and Ni in the sediments were notably higher than global baseline values. Nearly in all cases the element concentrations in the sediments were considerably greater than RSA (ROPME Sea Area) and the ERL (Effects Range Low) guidelines. Significant differences among the sampling sites could be found for concentrations of all the four metals in water. The mean Ni, Pb and Cd levels in the water samples were relatively higher than those in some other regions of the Persian Gulf. Except few cases, the mean concentrations of the elements in muscle of the selected fish species were markedly below the international guidelines for human consumption.
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Peces/metabolismo , Sedimentos Geológicos/análisis , Metales Pesados/análisis , Contaminantes Químicos del Agua/análisis , Animales , Tamaño Corporal , Monitoreo del Ambiente , Músculos/química , Océanos y Mares , Tamaño de la Partícula , Factores Sexuales , Especificidad de la EspecieRESUMEN
This study investigates the distribution of three trace elements (Cd, Cu and Zn) in tissues (exoskeleton, abdominal muscle and hepatopancreas) of two shrimp species (Penaeus merguiensis and Penaeus semisulcatus). Special emphasis in this study was placed on evaluating the effects of storage conditions on redistribution of the elements and moreover the potential roles of metallothionein in tissue redistribution. The specimens were collected from the northern part of Persian Gulf during September 2001 and January 2002. The concentrations of metals in the tissues were measured using an Inductively Coupled Plasma-Atomic Emission Spectrophotometer (ICP-AES) and an ICP-Mass Spectrometer (ICP-MS). Metallothionein levels were determined using Differential pulse polarography. Results show a similar hierarchy for Cd and Cu concentrations among different tissues as follows: hepatopancreas>exoskeleton>muscle; and for Zn, the hepatopancreas again contained the highest levels, though there were not any significant differences in Zn concentrations between muscle and exoskeleton. Significant differences were found between the species in the case of Cd and Zn concentrations. Cd and Zn levels in P. semisulcatus were markedly higher than in P. merguiensis. In general, there were highly significant differences among the storage conditions from accumulation the selected trace elements and metallothionein in both species point of view, but in most cases, no significant differences could be observed among the fresh, refrigerated and frozen specimens of P. semisulcatus. In regards to Zn and Cu accumulation in edible (muscle) tissues of P. merguiensis, optimum conditions for frozen storage is -30 degrees C as ice-frozen, and in terms of short-term storage, 1-day refrigeration is recommended. The redistribution of Zn and Cu during the storage period can be attributed to the role of metallothionein in their transport from organ(s) to muscle during storage. The variations in pH values measured in the muscle of P. merguiensis in different storage conditions showed a similar trend with metallothionein, Zn and Cu. In contrast, it appears that cadmium is transported from muscle to the other tissues. Exoskeleton is probably one of the recipient tissues of cadmium. The inter-elemental relationships were assessed for each species, separately. A significant positive relationship was observed between the concentrations of Zn and metallothionein in P. semisulcatus, whereas in P. merguiensis, Cd concentrations decreased significantly with increasing metallothionein. Highly significant differences between the sexes in Cu and Zn contents could be detected. The differences between the sexes in the levels of Zn and Cu were significantly greater in P. semisulcatus. Highly significant size-related differences were found in the levels of Cd, Cu and metallothionein in the selected tissues of the shrimp species. Comparison between the mean concentrations of the elements in muscle tissue and existing guidelines indicate that in nearly all cases, the concentrations were well below permissible levels for human consumption. The only exception was observed regarding mean values of Cd, which was somewhat greater than some of the recommended levels.
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Cadmio/farmacocinética , Cobre/farmacocinética , Metalotioneína/farmacología , Penaeidae/química , Contaminantes del Agua/farmacocinética , Zinc/farmacocinética , Animales , Cadmio/análisis , Cobre/análisis , Monitoreo del Ambiente , Femenino , Océano Índico , Masculino , Factores Sexuales , Distribución Tisular , Contaminantes del Agua/análisis , Zinc/análisisRESUMEN
The study was conducted between January and December 2002. The main objective of this study was evaluation of effects of refrigerated storage duration on redistribution of three trace elements (Cd, Cu and Zn) in tissues (exoskeleton, abdominal muscle and hepatopancreas) of a shrimp species (Penaeus semisulcatus). Moreover, the possible roles of metallothionein (a kind of metalloprotein) in redistribution of the elements in tissues of the selected species were assessed. The specimens were sampled from northwestern part of the Persian Gulf. The concentrations of metals in the tissues were measured using Inductively Coupled Plasma-Optical Emission Spectrophotometer (ICP-OES). Metallothionein levels were determined by Differential Pulse Polarography (DPP) method. pH of the muscle samples was also measured in different stages. Different statistical methods were used for interpretation of the results. There were no size-dependent differences in metal contents of the species. The results were compared with specimens from other areas of the world and existing guidelines and limits. Concentrations of the metals in the muscle (0.103, 3.418 and 8.977 microg g(-1) wet weight in the case of Cd, Cu and Zn, respectively) samples were below the most guidelines for human consumption. The results were in general agreement with those obtained by some other researchers. There were highly significant differences between sexes in Zn and Cu contents. Levels of Zn in females were significantly higher than males. The reverse case observed for Cu. The highest mean Cu and Zn concentrations (15.939 and 43.394 microg g(-1) wet weight, respectively) were found in hepatopancreas samples, but the highest level of Cd (0.790 microg g(-1) wet weight) was observed in exoskeleton. There were significant differences between the fresh and refrigerated samples from accumulation of Cd and Zn in tissues point of view, which can be attributed to the metal binding properties of metallothioneins as well as their degradation during the storage.
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Monitoreo del Ambiente , Metalotioneína/metabolismo , Metales Pesados/metabolismo , Penaeidae/metabolismo , Contaminantes Químicos del Agua/metabolismo , Animales , Sitios de Unión , Biodegradación Ambiental , Manipulación de Alimentos , Humanos , Océano Índico , Metalotioneína/análisis , Metales Pesados/análisis , Especificidad de la Especie , Distribución Tisular , Contaminantes Químicos del Agua/análisisRESUMEN
This study is focused on twenty trace elements (Ag, Ba, Bi, Cd, Co, Cr, Cs, Cu, Ga, In, Mn, Mo, Pb, Rb, Sb, Sn, Sr, Ti, V, Zn) accumulation in muscles of five sturgeon species (Acipenser guldenstaedti, A. persicus, A. nudiventris, A. stellatus and Huso huso) from the southern part of the Caspian Sea. Moreover the relationships between some biological characteristics and the levels of the selected elements as well as inter-elemental relationships were assessed. The samples (10 specimens for each the five species) were collected from two important sturgeon fishery zones located in the Iranian part of the Sea in 2002. Concentrations of the elements were determined using ICP-MS. Only in the case of Cs could significant differences between two selected sampling areas be detected. There were significant differences in levels of Co, Ga, Rb, Sn, Ti, Pb and Bi in muscles of the species. Only in the case of Cd weight related differences among the species were found. The significant length dependent relationships were observed for Ga and Ba. Patterns of elements accumulation were assessed by statistical methods and compared to the other researches. In all the cases, the amounts of toxic trace elements (Cd, Cu, Pb and Zn) were markedly below the international guidelines for human consumption.
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Monitoreo del Ambiente , Músculos/química , Oligoelementos/análisis , Contaminación Química del Agua/análisis , Animales , Peces , Inspección de Alimentos , Geografía , Humanos , Cooperación Internacional , Océanos y Mares , Guías de Práctica Clínica como Asunto/normas , Especificidad de la Especie , Estadística como AsuntoRESUMEN
This review is focused on distribution and redistribution of trace elements in various tissues of different shrimp species, especially genus Penaeus. The possible roles of metallothionein in this regard are emphasized. Factors affecting heavy metals uptake and distribution have also been reviewed separately. Moreover, patterns of metals bioaccumulation and their order of occurrence have been evaluated. Another part of this paper deals with comparison of the related data from different aquatic environments as well as existing guidelines and limits for human consumption. Generally, the number of conducted studies in some related context, especially in the case of possible roles of metallothionein during storage of organisms is very limited.
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Contaminantes Ambientales/metabolismo , Metalotioneína/metabolismo , Penaeidae/metabolismo , Animales , Contaminantes Ambientales/análisis , Humanos , Metalotioneína/análisis , Metales Pesados/metabolismo , Especificidad de la Especie , Distribución Tisular , Oligoelementos/análisis , Oligoelementos/metabolismoRESUMEN
The choice of a nebulized system for a patient usually depends on the equipment available. To date, there is limited guidance on the selection and use of a nebulizer. We have conducted in vitro tests described within the draft European Standard for Nebulisers (BSEN13544-1; CEN) and correlated these to in vivo pharmacokinetic performance of relative lung and systemic deposition in healthy volunteers. Eight nebulizer systems have been tested. The in vitro analysis used the recommended CEN methods to quantify the total dose available for inhalation as well as the size distribution from which the respirable dose was determined. The draft European Standard methods were slightly modified to use salbutamol rather than a fluoride tracer. For the in vivo study, nine volunteers provided urine samples after 30 min and then pooled for 24 h after the start of each nebulized dose (2.5 mg of salbutamol). Amounts of salbutamol and its metabolite excreted in the urine samples were determined. There was a significant (p = 0.02) correlation between the in vitro respirable dose and the amount of salbutamol excreted in the urine 30 min after the start of nebulization (relative bioavailability of salbutamol to the lung). Also, there was a significant (p < 0.001) correlation between the in vitro dose available for inhalation and the total amount of salbutamol and its metabolites excreted over the 24 h after the start of nebulization (relative bioavailability of salbutamol to the body). The results demonstrate that in vivo/in vitro correlations exist and warrant further investigations. The in vitro methods require further validation with in vivo correlations using patients with different severities of airway obstruction.
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Albuterol/administración & dosificación , Broncodilatadores/administración & dosificación , Nebulizadores y Vaporizadores , Aerosoles , Albuterol/farmacocinética , Disponibilidad Biológica , Broncodilatadores/farmacocinética , Humanos , Tamaño de la PartículaRESUMEN
This paper evaluates the suitability of various compressors available in Europe to generate and deliver tobramycin nebulizer solution to cystic fibrosis patients from the PARI LC PLUS jet nebulizer. This evaluation has been undertaken (i) by establishing an in vitro equivalence to the DeVilbiss PulmoAide compressor (operating at 4.6 l/min) proven effective in US clinical trials, and (ii) by determining equivalent in vitro performance of the LC PLUS nebulizer driven by alternative airflows. Equivalent performance is judged as having both an aerosol output and aerosol size within +/-10% of that obtained with the LC PLUS/PulmoAide combination. The two different in vitro methodologies applied to this investigation were based on the British Standard and a European Standard to assess nebulizer output. The results demonstrate that a wide range of compressed airflow rates generate aerosol output from the PARI LC PLUS equivalent to that obtained from the PulmoAide compressor. This range of airflows encompasses many compressors commonly available in Europe.
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Antibacterianos/administración & dosificación , Fibrosis Quística/tratamiento farmacológico , Nebulizadores y Vaporizadores , Tobramicina/administración & dosificación , Administración por Inhalación , Europa (Continente) , Humanos , Modelos TeóricosRESUMEN
The Brn-3b POU domain containing transcription factor is expressed in the developing sensory nervous system as well as in epithelial cells of the breast, cervix, and testes. Brn-3b functionally interacts with the estrogen receptor (ER) and in association with the ER, regulates transcription from estrogen responsive genes. In addition, Brn-3b expression is elevated in breast tumours compared to levels in normal mammary cells. To explore the role of Brn-3b in breast cancer, we established stable cell lines derived from the MCF7 human breast cancer cell line which had been transfected with Brn-3b sense or anti-sense constructs. The Brn-3b over-expressing cell lines exhibited increased growth rate, reached confluence at a higher saturation density, had higher proliferative activity, and an enhanced ability to form colonies in soft agar when compared to the control empty vector transfected cells. Likewise, the Brn-3b anti-sense cell lines showed reduced cellular growth and proliferation, reached confluence at a lower density, and exhibited a decreased ability to form colonies in soft agar when compared to the vector controls. Five to ten per cent of the Brn-3b over-expressing cells exhibited a severely altered morphology characterized by reduced adherence to tissue culture plastic, increased cell size, and a vacuolar cell shape. These results thus further indicate a role for the Brn-3b transcription factor in regulating mammary cell growth and suggest that its elevation in breast cancer is of functional significance.
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Adenocarcinoma/patología , Neoplasias de la Mama/patología , Proteínas de Unión al ADN/fisiología , Factores de Transcripción/fisiología , Adenocarcinoma/metabolismo , Neoplasias de la Mama/metabolismo , División Celular , Línea Celular Transformada , Proteínas de Unión al ADN/genética , Estradiol/farmacología , Antagonistas de Estrógenos/farmacología , Femenino , Humanos , Moduladores Selectivos de los Receptores de Estrógeno/farmacología , Tamoxifeno/farmacología , Timidina/metabolismo , Factor de Transcripción Brn-3 , Factor de Transcripción Brn-3B , Factores de Transcripción/genética , Transfección , Células Tumorales CultivadasRESUMEN
The objective was to investigate the reliability and effects of age and noise on high-frequency hearing thresholds. A cross-sectional study was used involving 187 exposed and 52 non-industrial noise-exposed subjects selected randomly from noise-exposed and non-industrial noise-exposed subjects, respectively. Each subject was tested with both conventional-frequency (0.25-8 kHz) and high-frequency (10-18 kHz) audiometry. Test-retest results showed that high-frequency audiometry (HFA) was as reliable as the conventional procedure. Although the inter-subject variation was large, the intra-subject variation was small, indicating that HFA can be used more reliably than the conventional procedure to monitor individual cases over time. Both the hearing threshold at high frequencies and the upper frequency limit deteriorated as a function of age and frequency. The exposed subjects had significantly higher hearing thresholds than the non-exposed subjects at all the high frequencies tested, the difference between the two groups being greatest at 14 kHz. Multivariate analysis indicated that age was the primary predictor and noise exposure the secondary predictor of hearing thresholds in a high frequency range (10-18 kHz). In contrast, multivariate analysis indicated the reverse order-noise exposure as the primary predictor, then age-for a conventional frequency range (0.25-8 kHz). The results of this study suggest that HFA might be used as an early indicator for noise-induced hearing loss and acoustic trauma rather than audiometry at a conventional frequency (4 kHz), particularly for younger groups.
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Umbral Auditivo/fisiología , Pérdida Auditiva Provocada por Ruido/diagnóstico , Ruido en el Ambiente de Trabajo/efectos adversos , Exposición Profesional/efectos adversos , Adolescente , Adulto , Factores de Edad , Análisis de Varianza , Audiometría/métodos , Audición/fisiología , Humanos , Modelos Lineales , Masculino , Exposición Profesional/estadística & datos numéricos , Valor Predictivo de las PruebasRESUMEN
OBJECTIVE: To determine the prevalence of hearing loss associated with occupational noise exposure and other risk factors. DESIGN: A cross-sectional study involving 269 exposed and 99 non-exposed subjects (non-industrial noise exposed subjects) randomly selected. Current noise exposure was estimated using both sound level meter and noise-dosimeter. Past noise exposure was estimated by interview questionnaire. Otoscopic examination and conventional frequency (0.25-8 kHz) audiometry were used to assess the hearing loss in each subject. RESULTS: 75% (202 subjects) from the exposed group were exposed to a daily Leq above the permissible level of 85 dB(A) and most (61%) of these did not and had never used any form of hearing protection. Hearing loss was found to be bilateral and symmetrical in both groups. Bivariate analysis showed a significant hearing loss in the exposed vs non-exposed subjects with a characteristic dip at 4 kHz. Thirty eight percent of exposed subjects had hearing impairment, which was an 8-fold higher rate than that found for non-exposed subjects. Multivariate analysis indicated exposure to noise was the primary, and age the secondary predictor of hearing loss. Odds of hearing impairment were lower for a small sub-group of exposed workers using hearing protection (N=19) in which logistic regression analysis showed the probability of workers adopting hearing protective devices increased with noise exposure, education, and awareness of noise control. Hearing loss was also greater amongst those who used headphones to listen to recorded cassettes. CONCLUSION: Gross occupational exposure to noise has been demonstrated to cause hearing loss and the authors believe that occupational hearing loss in Saudi Arabia is a widespread problem. Strategies of noise assessment and control are introduced which may help improve the work environment.
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Pérdida Auditiva Provocada por Ruido/epidemiología , Ruido en el Ambiente de Trabajo , Adulto , Estudios Transversales , Humanos , Masculino , Análisis Multivariante , Prevalencia , Análisis de Regresión , Medición de Riesgo , Factores de Riesgo , Arabia Saudita/epidemiologíaRESUMEN
Inhalation provocation tests were used to assess whether the volatile products of an activated resin had caused occupational asthma in a non-random sample of six asthmatic coal miners. The resin system uses the polymerization of polyester and styrene under the influence of the cross-linking agent dibenzoyl peroxide to secure roof, wall and floor bolts in mine tunnels. The tests were conducted sequentially in a double-blind fashion over a 'dose' range which extended just beyond the maximum likely to have been experienced occupationally during a single day's work. The tests were monitored by symptoms, changes in the forced expiratory volume in 1 s (FEV1) and changes in airway responsiveness. All subjects completed the series of tests without any significant decrements in FEV1 or significant increases in airway responsiveness. We conclude that the use of this resin system is not likely to have been the cause of the asthma in the test subjects, nor in the larger group of miners of which they were a sample, but neither possibility is fully excluded and the participants may not have been adequately representative of other asthmatic coal miners.
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Asma/inducido químicamente , Peróxido de Benzoílo/efectos adversos , Pruebas de Provocación Bronquial/métodos , Enfermedades Profesionales/inducido químicamente , Resinas Sintéticas/efectos adversos , Estireno/efectos adversos , Minas de Carbón , Método Doble Ciego , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Exposición Profesional/efectos adversosRESUMEN
Prediction of fume formation rate during metal arc welding and the composition of the fume are of interest to occupational hygienists concerned with risk assessment and to manufacturers of welding consumables. A model for GMAW (DC electrode positive) is described based on the welder determined process parameters (current, wire feed rate and wire composition), on the surface area of molten metal in the arc and on the partial vapour pressures of the component metals of the alloy wire. The model is applicable to globular and spray welding transfer modes but not to dip mode. Metal evaporation from a droplet is evaluated for short time increments and total evaporation obtained by summation over the life of the droplet. The contribution of fume derived from the weld pool and spatter (particles of metal ejected from the arc) is discussed, as are limitations of the model. Calculated droplet temperatures are similar to values determined by other workers. A degree of relationship between predicted and measured fume formation rates is demonstrated but the model does not at this stage provide a reliable predictive tool.
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Contaminantes Ocupacionales del Aire/análisis , Monitoreo del Ambiente/estadística & datos numéricos , Soldadura , Humanos , Modelos Teóricos , Medición de Riesgo , Soldadura/métodosRESUMEN
A 2-day conference on Advances in Inhalation Therapy drew together 16 speakers, experts in their respective fields, to summarize recent developments in delivery device design, drug formulation, in vitro and in vivo assessment, and to provide a clinical overview of the future of drug aerosol therapy. Concurrent advances are being made in the design of aerosol delivery devices in all areas. Reformulation of non-CFC pressurized metered dose inhalers (pMDIs) is overcoming technical, legal and engineering obstacles, although whether the new hydrofluorocarbon (HFA) products will already be limited and dated is a distinct possibility. New 'soft mist inhalers' offer a viable alternative for drug aerosol delivery that has potential advantages in efficiency in design and aerosol delivery compared to conventional pMDIs and DPIs. The reproducible generation and delivery of micronized macromolecules to the peripheral lung offers an efficient and novel means for the effective and safe delivery of peptides and proteins, with notable successes in delivery of analgesics and insulin. Novel means of designing 'smart drugs' through supercritical fluid engineering promises to further enhance the advantages of inhalation for routine drug administration.
RESUMEN
The standardization of in vitro bench-top assessment of nebulizer performance could prove to be extremely beneficial in the advancement of aerosol delivered by nebulizers. At the present time, there is considerable confusion as to how different nebulizer systems perform. Clinical in vivo tests are often compromised, as high patient variability requires large study numbers before differences become significant. In vitro tests should offer less variability and much lower costs, but the test criteria must be standardized and be clinically representative. Standard methods to assess nebulizer performance should therefore be designed to reflect the clinical situation as far as practicable. This would incorporate test methods involving: 1. simulated breathing patterns to estimate the amount of aerosol released and inhaled 2. use of solute tracers to measure aerosol release of salts or drugs themselves 3. use of aerosol sizing instruments such as low-flow cascade impactors that would reflect in vivo deposition. Standards must be written to accommodate the variety of existing devices currently on the market. Because standards take a significant time (typically 1-3 years) to prepare and are intended to operate for a further 10 or more years, they should also aim to accommodate possible advancements in device technology. The potential for such developments should not be overlooked in preparing a standard for in vitro testing of nebulization devices.
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Nebulizadores y Vaporizadores/normas , Aerosoles/administración & dosificación , Humanos , Ensayo de Materiales/normas , Tamaño de la PartículaRESUMEN
This paper describes the relationships between ultra-violet emission, ozone generation and CrVI production in MIG welding which were measured as a function of shield gas flow rate, welding voltage, electrode stick-out and shield gas composition using an automatic welding rig that permitted MIG welding under reproducible conditions. The experimental results are interpreted in terms of the physico-chemical processes occurring in the micro- and macro-environments of the arc as part of research into process modification to reduce occupational exposure to ozone and CrVI production rates in MIG welding. We believe the techniques described here, and in particular the use of what we have termed u.v.-ozone measurements, will prove useful in further study of ozone generation and CrVI formation and may be applied in the investigation of engineering control of occupational exposure in MIG and other welding process such as Manual Metal Arc (MMA) and Tungsten Inert Gas (TIG).
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Contaminantes Ocupacionales del Aire/análisis , Cromo/análisis , Exposición Profesional , Ozono/análisis , Rayos Ultravioleta , Soldadura , Argón/química , Dióxido de Carbono/química , Clorofluorocarburos de Metano/química , Cromo/química , Electricidad , Etilenos/química , Helio/química , Humanos , Óxido Nítrico/química , Exposición Profesional/prevención & control , Oxidación-Reducción , Ozono/químicaRESUMEN
By selective attachment of a DNA cleavage agent to specific residues in the yeast TATA box binding protein (yTBP), we demonstrate that, in solution, yTBP binds to the TATA boxes of both the adenovirus major late promoter and the yeast CYC1 promoter with only a modest preference in orientation and binds well to several overlapping binding sites. The general factors TFIIA and TFIIB each increase the rotational and translational selectivity of yTBP but are not sufficient, at least individually, to confer a unique polarity to the preinitiation complex. We conclude that TBP alone cannot define the productive orientation of general factor assembly on a promoter.
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Proteínas de Unión al ADN/metabolismo , TATA Box , Factores de Transcripción/metabolismo , Adenoviridae/genética , Alquilación , Secuencia de Bases , Sitios de Unión/genética , ADN de Hongos/química , ADN de Hongos/genética , ADN de Hongos/metabolismo , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/genética , Modelos Moleculares , Datos de Secuencia Molecular , Conformación de Ácido Nucleico , Regiones Promotoras Genéticas , Unión Proteica , Conformación Proteica , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteína de Unión a TATA-Box , Factores de Transcripción/química , Factores de Transcripción/genéticaRESUMEN
To clarify whether asthma may be caused by fume from welding mild steel and to evaluate the possible strength of such an effect, we quantified airway responsiveness among young shipyard workers with different levels of fume exposure. Clinical investigation comprised a cross-sectional survey of 19- to 27-yr-old workers who were completing 3 to 9 yr of employment in various trades, and a control group of 15- to 17-yr-old school leavers who were applying for apprenticeships within the same trades. Both groups were subdivided into negligible-, ambient-, or high-exposure subgroups according to expected levels of fume exposure. Actual exposures were assessed in a parallel environmental survey. Participants were investigated by questionnaire, skin prick tests, spirometry, and methacholine tests. Complete data sets were obtained from 1,024 of the 1,070 eligible subjects (96%). Among the workers but not the school leaver controls, there was an increasing prevalence of positive methacholine tests across the exposure subgroups-negligible 37%, ambient 44%, high 49% (p < 0.05). Regression analyses showed that in males after allowing for the effects of atopy, current smoking, and age, the estimated geometric mean level of airway responsiveness of regular welders was twice that of workers with negligible exposure after 5 yr of work. This implies that fume exposure may have been critical in causing asthma in about 1% of the welders. A lesser effect (though not significantly so) was noted among the workers with ambient exposure.