RESUMO
Trifluoroacetic acid (TFA) is a breakdown product of several hydrochlorofluorocarbons (HCFC), regulated under the Montreal Protocol (MP), and hydrofluorocarbons (HFC) used mainly as refrigerants. Trifluoroacetic acid is (1) produced naturally and synthetically, (2) used in the chemical industry, and (3) a potential environmental breakdown product of a large number (>1 million) chemicals, including pharmaceuticals, pesticides, and polymers. The contribution of these chemicals to global amounts of TFA is uncertain, in contrast to that from HCFC and HFC regulated under the MP. TFA salts are stable in the environment and accumulate in terminal sinks such as playas, salt lakes, and oceans, where the only process for loss of water is evaporation. Total contribution to existing amounts of TFA in the oceans as a result of the continued use of HCFCs, HFCs, and hydrofluoroolefines (HFOs) up to 2050 is estimated to be a small fraction (<7.5%) of the approximately 0.2 µg acid equivalents/L estimated to be present at the start of the millennium. As an acid or as a salt TFA is low to moderately toxic to a range of organisms. Based on current projections of future use of HCFCs and HFCs, the amount of TFA formed in the troposphere from substances regulated under the MP is too small to be a risk to the health of humans and environment. However, the formation of TFA derived from degradation of HCFC and HFC warrants continued attention, in part because of a long environmental lifetime and due many other potential but highly uncertain sources.
Assuntos
Exposição Ambiental , Poluentes Ambientais/análise , Ácido Trifluoracético/análise , Animais , Monitoramento Ambiental , Humanos , Sais/análiseRESUMO
The recommended treatment for post-exposure prophylaxis (PEP) following known/suspected exposure to Bacillus anthracis involves immunization with anthrax vaccine adsorbed (AVA, i.e., BioThrax® vaccine) and a course of antimicrobial therapy. A drug-vaccine interaction clinical trial was conducted to determine whether this combined treatment might modify antimicrobial exposure or vaccine immunogenicity. A Phase 2, randomized, open-label, multi-center trial involving 154 healthy adult participants was completed to evaluate the effect of AVA immunization (three doses administered subcutaneously (SC) at weeks 0, 2 and 4) on the pharmacokinetics (PK) of ciprofloxacin, as well as the effect of ciprofloxacin administration (500 mg po bid) on the immunogenicity of AVA. PK parameters were derived using noncompartmental analysis of ciprofloxacin serum concentrations. Immunogenicity was assessed using a toxin neutralizing antibody (TNA) assay resulting in 50 % neutralization factor (NF50) values. Safety was assessed via reports of adverse events (AEs), clinically significant changes in laboratory parameters and vital signs, and collection of solicited local and systemic reactogenicity reactions. Statistical analyses of the steady state (SS) and single dose PK parameters Cmax and AUC0--12h indicated that the AVA PEP regimen did not significantly modify ciprofloxacin exposure. Comparison of the geometric mean TNA NF50 values between participants receiving AVA + ciprofloxacin and those receiving AVA alone showed that the combined treatment was non-inferior to AVA alone. The trial met all prospectively defined success criteria for the primary PK endpoint and for the secondary PK and immunogenicity endpoints. There were no deaths, SAEs or AEs leading to drug discontinuation or study withdrawal during the trial. Overall, concomitant administration of ciprofloxacin and AVA produced no significant changes in the PK profile of ciprofloxacin nor in the immunogenicity of AVA. Furthermore, this trial demonstrated that the co-administration of ciprofloxacin and AVA was well tolerated in healthy adult participants.
RESUMO
The parties to the Montreal Protocol are informed by three panels of experts. One of these is the Environmental Effects Assessment Panel (EEAP), which deals with two focal issues. The first focus is the effects of increased UV radiation on human health, animals, plants, biogeochemistry, air quality, and materials. The second focus is on interactions between UV radiation and global climate change and how these may affect humans and the environment. When considering the effects of climate change, it has become clear that processes resulting in changes in stratospheric ozone are more complex than believed previously. As a result of this, human health and environmental problems will be longer-lasting and more regionally variable. Like the other panels, the EEAP produces a detailed report every four years; the most recent was published in 2010 (Photochem. Photobiol. Sci., 2011, 10, 173-300). In the years in between, the EEAP produces less detailed and shorter progress reports, which highlight and assess the significance of developments in key areas of importance to the parties. The next full quadrennial report will be published in 2014-2015.
Assuntos
Mudança Climática , Ozônio/análise , Animais , Humanos , Raios UltravioletaRESUMO
The parties to the Montreal Protocol are informed by three panels of experts. One of these is the Environmental Effects Assessment Panel (EEAP), which deals with UV radiation and its effects on human health, animals, plants, biogeochemistry, air quality and materials. Since 2000, the analyses and interpretation of these effects have included interactions between UV radiation and global climate change. When considering the effects of climate change, it has become clear that processes resulting in changes in stratospheric ozone are more complex than believed previously. As a result of this, human health and environmental problems will likely be longer-lasting and more regionally variable. Like the other panels, the EEAP produces a detailed report every four years; the most recent was that for 2006 (Photochem. Photobiol. Sci., 2007, 6, 201-332). In the years in between, the EEAP produces a less detailed and shorter progress report, as is the case for this present one for 2009. A full quadrennial report will follow for 2010.
Assuntos
Mudança Climática , Meio Ambiente , Ozônio/análise , Desenvolvimento de Programas , Ar/análise , Animais , Ecossistema , Humanos , Raios Ultravioleta/efeitos adversosRESUMO
INTRODUCTION: The availability of a licensed anthrax vaccine that is safe, effective, and easy to administer for both pre- and post-exposure prophylaxis is critical to successfully manage and prevent potential anthrax attacks. BioThrax® (Anthrax Vaccine Adsorbed; AVA) is the only licensed anthrax vaccine in the US. Areas covered: Recent licensed improvements to BioThrax vaccine for pre-exposure prophylaxis (PrEP) have included an intramuscular (IM) five-dose schedule (in 2008) and a three-dose IM primary series at 0, 1 and 6 months (in 2012). Post-exposure prophylaxis (PEP) - three doses given subcutaneously (SC) at 0, 2, and 4 weeks - was licensed in 2015. We review the anthrax disease and vaccine literature that supported these licensure efforts. Expert commentary: This PEP licensure is the first time the FDA's Animal Rule has been used to license a vaccine. Additional improvements such as fewer vaccine doses and reduced time to protection are desirable for a PEP vaccine and are being pursued with next generation vaccine candidates.
Assuntos
Vacinas contra Antraz/administração & dosagem , Vacinas contra Antraz/imunologia , Antraz/prevenção & controle , Aprovação de Drogas , Profilaxia Pós-Exposição/métodos , Animais , Humanos , Esquemas de Imunização , Injeções Intramusculares , Injeções Subcutâneas , Estados Unidos , United States Food and Drug AdministrationRESUMO
Exposure to ultraviolet radiation results in increased levels of intradermal cis-urocanic acid (cUCA) and alters cutaneous immunity by interfering with processing and presentation of antigen by Langerhans cells. Reports on effects of systemic immunotoxicity with 30 day cUCA exposure in laboratory rodents include thymic atrophy, thymic hypocellularity and decreased T-cell-mediated immunity; however, immune effects of single exposure or 5 day cUCA administration, which may better mimic human exposures, are poorly defined. The present study initially evaluated immune effects of single, 5 day, and 4 week cUCA exposure in C57BL/6N mice. Single administration of intradermal cUCA resulted in decreased splenocyte phagocytosis that persisted for 30 days after cUCA exposure. Five day consecutive cUCA exposure decreased numbers of phenotypically mature CD4(+)CD8(-) and CD4(-)CD8(+) (single positive) thymocytes, increased CD4(+)CD8(+) (double positive) immature thymocytes and increased splenocyte proliferation. Prolonged cUCA exposure (4 weeks) caused profound thymic hypocellularity and splenic hypercellularity and increased splenic macrophage chemiluminescence. Because of this apparent sensitivity of C57BL/6N mice to cUCA, thymic hypocellularity was compared between C57BL/6N and C3H/HeN mice dosed with cUCA, and was found to be more pronounced in the C57BL/6N strain. These results are an extension of previous conclusions on immune modulation caused by cUCA in the spleen and thymus. Further, the observed variation in sensitivity between the mouse strains is consistent with known genetic susceptibility of these strains to the immunomodulatory effects of exposure to sunlight.
Assuntos
Ácido Urocânico/toxicidade , Animais , Feminino , Células de Langerhans/citologia , Células de Langerhans/efeitos dos fármacos , Células de Langerhans/imunologia , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos , Baço/efeitos dos fármacos , Timo/efeitos dos fármacosRESUMO
Actinobacillus pleuropneumoniae is the etiologic agent of swine pleuropneumonia. Live, non-encapsulated vaccine strains have been shown to be efficacious in preventing acute disease in pigs. Recombinant DNA technology has the advantage of generating defined mutants that are safe, but maintain critical immunoprotective components. However, some recombinant strains have the disadvantage of containing antibiotic resistance genes that could be transferred to the animal's normal bacterial flora. Using DNA allelic exchange we have constructed attenuated, capsule-deficient mutants of A. pleuropneumoniae that contain a kanamycin resistance (Kn(R)) gene within the capsule locus of the genome. Following intranasal or intratracheal challenge of pigs the encapsulated parent strains colonized the challenge pigs, and were transmitted to contact pigs. In contrast, the capsule-deficient mutants were recovered only from the challenged pigs and not from contact pigs. Each kanamycin-resistant colony type recovered from the respiratory or gastrointestinal tracts of pigs challenged with the recombinant strain was screened with a probe specific for the Kn(R) gene. All probe-positive colonies were assayed for the specific Kn(R) gene by amplification of a 0.9 kb fragment of the antibiotic resistance gene by PCR. The 0.9 kb fragment was amplified from the recombinant A. pleuropneumoniae colonies, but not from any of the heterologous bacteria, indicating there was no evidence of transmission of the Kn(R) gene to resident bacteria. Following aerosol exposure of 276 pigs with recombinant, non-encapsulated A. pleuropneumoniae the recombinant bacteria were not recovered from any nasal swabs of 75 pigs tested or environmental samples 18 h after challenge. Statistical risk analysis, based on the number of kanamycin-resistant colonies screened, indicated that undetected transmission of the Kn(R) gene could still have occurred in at most 1.36% of kanamycin-resistant bacteria in contact with recombinant A. pleuropneumoniae. However, the overall risk of transmission to any resident bacteria was far lower. Our results indicate there was little risk of transmission of capsule-deficient, recombinant A. pleuropneumoniae or its Kn(R) gene to contact pigs or to the resident microflora.
Assuntos
Infecções por Actinobacillus/veterinária , Actinobacillus pleuropneumoniae/patogenicidade , Pleuropneumonia/veterinária , Doenças dos Suínos/microbiologia , Infecções por Actinobacillus/imunologia , Infecções por Actinobacillus/microbiologia , Infecções por Actinobacillus/transmissão , Actinobacillus pleuropneumoniae/genética , Actinobacillus pleuropneumoniae/imunologia , Animais , Vacinas Bacterianas/imunologia , DNA Bacteriano/química , DNA Bacteriano/genética , Resistência a Canamicina/genética , Mutagênese Insercional , Mucosa Nasal/microbiologia , Hibridização de Ácido Nucleico , Pleuropneumonia/imunologia , Pleuropneumonia/microbiologia , Reação em Cadeia da Polimerase/veterinária , Proteínas Recombinantes/genética , Suínos , Doenças dos Suínos/imunologia , Doenças dos Suínos/transmissão , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/normasRESUMO
After the enthusiastic celebration of the 20th Anniversary of the Montreal Protocol on Substances that Deplete the Ozone Layer in 2007, the work for the protection of the ozone layer continues. The Environmental Effects Assessment Panel is one of the three expert panels within the Montreal Protocol. This EEAP deals with the increase of the UV irradiance on the Earth's surface and its effects on human health, animals, plants, biogeochemistry, air quality and materials. For the past few years, interactions of ozone depletion with climate change have also been considered. It has become clear that the environmental problems will be long-lasting. In spite of the fact that the worldwide production of ozone depleting chemicals has already been reduced by 95%, the environmental disturbances are expected to persist for about the next half a century, even if the protective work is actively continued, and completed. The latest full report was published in Photochem. Photobiol. Sci., 2007, 6, 201-332, and the last progress report in Photochem. Photobiol. Sci., 2008, 7, 15-27. The next full report on environmental effects is scheduled for the year 2010. The present progress report 2008 is one of the short interim reports, appearing annually.
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Clima , Conservação dos Recursos Naturais , Ozônio/química , Aerossóis , Animais , Humanos , Luz SolarRESUMO
The authors modeled the possible consequences for US cataract incidence of increases in ultraviolet B radiation due to ozone depletion. Data on the dose-response relation between ocular exposure to ultraviolet B radiation and cortical cataract were derived from a population-based study (the Salisbury Eye Evaluation Project, Salisbury, Maryland) in which extensive data on cataract and ultraviolet radiation were collected in persons aged 65-84 years. Exposure estimates for the US population were derived using estimated ultraviolet radiation fluxes as a function of wavelength. US Census data were used to obtain the age, ethnicity, and sex distribution of the population. Predicted probabilities of cataract were derived from the age-, sex-, and ethnicity-specific ocular ultraviolet exposure data and were modeled under conditions of 5-20% ozone depletion. The analysis indicated that by 2050, the prevalence of cortical cataract will increase above expected levels by 1.3-6.9%. The authors estimate that with 5-20% ozone depletion, there will be 167,000-830,000 additional cases of cortical cataract by 2050. Because of the high prevalence of cataract in older persons, at a 2003 cost of 3,370 dollars per cataract operation, this increase could represent an excess cost of 563 million dollars to 2.8 billion dollars.
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Atmosfera , Catarata/epidemiologia , Exposição Ambiental/estatística & dados numéricos , Modelos Estatísticos , Ozônio , Lesões por Radiação/epidemiologia , Raios Ultravioleta , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Relação Dose-Resposta à Radiação , Etnicidade/estatística & dados numéricos , Feminino , Humanos , Masculino , Prevalência , Medição de Risco/métodos , Fatores de Risco , Distribuição por Sexo , Estados Unidos/epidemiologiaRESUMO
The complexity of the linkages between ozone depletion, UV-B radiation and climate change has become more apparent.
Assuntos
Atmosfera/química , Ozônio , Raios Ultravioleta/efeitos adversos , Ecossistema , Meio Ambiente , Humanos , Ozônio/análise , Lesões por Radiação/epidemiologiaRESUMO
The potential health effects of elevated levels of ambient UV-B radiation are diverse, and it is difficult to quantify the risks, especially as they are likely to be considerably modified by human behaviour. Nevertheless epidemiological and experimental studies have confirmed that UV radiation is a definite risk factor for certain types of cataract, with peak efficacy in the UV-B waveband. The causal link between squamous cell carcinoma and cumulative solar UV exposure has been well established. New findings regarding the genetic basis of skin cancer, including studies on genetically modified mice, have confirmed the epidemiological evidence that UV radiation contributes to the formation of basal cell carcinomas and cutaneous melanomas, For the latter, animal models have demonstrated that UV exposure at a very young age is more detrimental than exposure in adulthood. Although suppression of certain immune responses has been recognised following UV exposure, the impact of this suppression on the control of infectious and autoimmune diseases is largely unknown. However, studies on several microbial infections have indicated significant consequences in terms of symptoms or reactivation of disease. The possibility that the immune response to vaccination could be depressed by UV-B exposure is of considerable concern. Newly emerging possibilities regarding interactions between ozone depletion and global climate change further complicate the risk assessments for human health but might result in an increased incidence of cataracts and skin cancer, plus alterations in the patterns of certain categories of infectious and other diseases.