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1.
Int J Obes (Lond) ; 46(2): 433-436, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34671107

RESUMO

Several studies show an increased risk of coronary heart disease (CHD) among people with obesity, but it is largely unknown whether this association also depends on a familial predisposition to obesity. This study examined if associations between Body Mass Index (BMI) or waist circumference (WC) and incident CHD differed among Danish female nurses with and without familial overweight and obesity. Analyses were based on data from the Danish Nurse Cohort (n = 20,701). Self-reported height, weight and self-measured WC were assessed in 1999, as was information on familial overweight/obesity, defined as having one or both parents with overweight/obesity. Information on the development of or death from CHD was collected from nationwide Danish registries in 2015. Analyses were based on Cox proportional hazard regression models adjusted for potential confounding factors. Both BMI and WC were directly associated with CHD risk, but we found no evidence of effect modification from familial predisposition to obesity. Hence a familial predisposition to obesity does not seem to influence the risk of CHD associated with general or central obesity.


Assuntos
Doença das Coronárias/etiologia , Enfermeiras e Enfermeiros/estatística & dados numéricos , Obesidade/complicações , Índice de Massa Corporal , Estudos de Coortes , Doença das Coronárias/epidemiologia , Dinamarca/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Modelos de Riscos Proporcionais , Fatores de Risco , Circunferência da Cintura/fisiologia
2.
Nucleic Acids Res ; 40(Database issue): D242-51, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22110040

RESUMO

Linear motifs are short, evolutionarily plastic components of regulatory proteins and provide low-affinity interaction interfaces. These compact modules play central roles in mediating every aspect of the regulatory functionality of the cell. They are particularly prominent in mediating cell signaling, controlling protein turnover and directing protein localization. Given their importance, our understanding of motifs is surprisingly limited, largely as a result of the difficulty of discovery, both experimentally and computationally. The Eukaryotic Linear Motif (ELM) resource at http://elm.eu.org provides the biological community with a comprehensive database of known experimentally validated motifs, and an exploratory tool to discover putative linear motifs in user-submitted protein sequences. The current update of the ELM database comprises 1800 annotated motif instances representing 170 distinct functional classes, including approximately 500 novel instances and 24 novel classes. Several older motif class entries have been also revisited, improving annotation and adding novel instances. Furthermore, addition of full-text search capabilities, an enhanced interface and simplified batch download has improved the overall accessibility of the ELM data. The motif discovery portion of the ELM resource has added conservation, and structural attributes have been incorporated to aid users to discriminate biologically relevant motifs from stochastically occurring non-functional instances.


Assuntos
Motivos de Aminoácidos , Bases de Dados de Proteínas , Gráficos por Computador , Doença/genética , Eucariotos , Análise de Sequência de Proteína , Interface Usuário-Computador , Proteínas Virais/química
3.
Biomech Model Mechanobiol ; 23(3): 757-780, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38244146

RESUMO

The aim of this study was to design physics-preserving and precise surrogate models of the nonlinear elastic behaviour of an intervertebral disc (IVD). Based on artificial force-displacement data sets from detailed finite element (FE) disc models, we used greedy kernel and polynomial approximations of second, third and fourth order to train surrogate models for the scalar force-torque -potential. Doing so, the resulting models of the elastic IVD responses ensured the conservation of mechanical energy through their structure. At the same time, they were capable of predicting disc forces in a physiological range of motion and for the coupling of all six degrees of freedom of an intervertebral joint. The performance of all surrogate models for a subject-specific L4 | 5 disc geometry was evaluated both on training and test data obtained from uncoupled (one-dimensional), weakly coupled (two-dimensional), and random movement trajectories in the entire six-dimensional (6d) physiological displacement range, as well as on synthetic kinematic data. We observed highest precisions for the kernel surrogate followed by the fourth-order polynomial model. Both clearly outperformed the second-order polynomial model which is equivalent to the commonly used stiffness matrix in neuro-musculoskeletal simulations. Hence, the proposed model architectures have the potential to improve the accuracy and, therewith, validity of load predictions in neuro-musculoskeletal spine models.


Assuntos
Análise de Elementos Finitos , Disco Intervertebral , Modelos Biológicos , Dinâmica não Linear , Disco Intervertebral/fisiologia , Humanos , Fenômenos Biomecânicos , Elasticidade , Simulação por Computador , Amplitude de Movimento Articular/fisiologia
4.
Toxicol Appl Pharmacol ; 268(3): 294-9, 2013 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-23462310

RESUMO

We investigated the role of air humidity and allergic sensitization on the acute airway response to inhaled formaldehyde (FA) vapor. Mice were sensitized to the immunogen ovalbumin (OVA) by three intraperitoneal injections followed by two aerosol challenges, giving rise to allergic airway inflammation. Control mice were sham sensitized by saline injections and challenged by saline aerosols. Once sensitized, the mice were housed at high (85-89%) or low (<10%) relative humidity, respectively for 48h prior to a 60-min exposure to either 0.4, 1.8 or about 5ppm FA. Before, during and after exposure, breathing parameters were monitored. These included the specific markers of nose and lung irritations as well as the expiratory flow rate, the latter being a marker of airflow limitation. The sensory irritation response in the upper airways was not affected by allergic inflammation or changes in humidity. At high relative humidity, the OVA-sensitized mice had a decreased expiratory airflow rate compared to the saline control mice after exposure to approximately 5ppm FA. This is in accordance with the observations that asthmatics are more sensitive than non-asthmatics to higher concentrations of airway irritants including FA. In the dry environment, the opposite trend was seen; here, the saline control mice had a significantly decreased expiratory airflow rate compared to OVA-sensitized mice when exposed to 1.8 and 4ppm FA. We speculate that increased mucus production in the OVA-sensitized mice has increased the "scrubber effect" in the nose, consequently protecting the conducting and lower airways.


Assuntos
Poluentes Atmosféricos/toxicidade , Bronquite/induzido quimicamente , Exposição Ambiental/efeitos adversos , Formaldeído/administração & dosagem , Formaldeído/toxicidade , Umidade , Animais , Bronquite/imunologia , Bronquite/fisiopatologia , Galinhas , Exposição por Inalação/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/toxicidade , Ventilação Pulmonar/efeitos dos fármacos , Ventilação Pulmonar/fisiologia
5.
Front Physiol ; 14: 1135531, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37324394

RESUMO

Purpose: Inverse-dynamics (ID) analysis is an approach widely used for studying spine biomechanics and the estimation of muscle forces. Despite the increasing structural complexity of spine models, ID analysis results substantially rely on accurate kinematic data that most of the current technologies are not capable to provide. For this reason, the model complexity is drastically reduced by assuming three degrees of freedom spherical joints and generic kinematic coupling constraints. Moreover, the majority of current ID spine models neglect the contribution of passive structures. The aim of this ID analysis study was to determine the impact of modelled passive structures (i.e., ligaments and intervertebral discs) on remaining joint forces and torques that muscles must balance in the functional spinal unit. Methods: For this purpose, an existing generic spine model developed for the use in the demoa software environment was transferred into the musculoskeletal modelling platform OpenSim. The thoracolumbar spine model previously used in forward-dynamics (FD) simulations provided a full kinematic description of a flexion-extension movement. By using the obtained in silico kinematics, ID analysis was performed. The individual contribution of passive elements to the generalised net joint forces and torques was evaluated in a step-wise approach increasing the model complexity by adding individual biological structures of the spine. Results: The implementation of intervertebral discs and ligaments has significantly reduced compressive loading and anterior torque that is attributed to the acting net muscle forces by -200% and -75%, respectively. The ID model kinematics and kinetics were cross-validated against the FD simulation results. Conclusion: This study clearly shows the importance of incorporating passive spinal structures on the accurate computation of remaining joint loads. Furthermore, for the first time, a generic spine model was used and cross-validated in two different musculoskeletal modelling platforms, i.e., demoa and OpenSim, respectively. In future, a comparison of neuromuscular control strategies for spinal movement can be investigated using both approaches.

6.
Biomech Model Mechanobiol ; 22(2): 669-694, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36602716

RESUMO

In spine research, two possibilities to generate models exist: generic (population-based) models representing the average human and subject-specific representations of individuals. Despite the increasing interest in subject specificity, individualisation of spine models remains challenging. Neuro-musculoskeletal (NMS) models enable the analysis and prediction of dynamic motions by incorporating active muscles attaching to bones that are connected using articulating joints under the assumption of rigid body dynamics. In this study, we used forward-dynamic simulations to compare a generic NMS multibody model of the thoracolumbar spine including fully articulated vertebrae, detailed musculature, passive ligaments and linear intervertebral disc (IVD) models with an individualised model to assess the contribution of individual biological structures. Individualisation was achieved by integrating skeletal geometry from computed tomography and custom-selected muscle and ligament paths. Both models underwent a gravitational settling process and a forward flexion-to-extension movement. The model-specific load distribution in an equilibrated upright position and local stiffness in the L4/5 functional spinal unit (FSU) is compared. Load sharing between occurring internal forces generated by individual biological structures and their contribution to the FSU stiffness was computed. The main finding of our simulations is an apparent shift in load sharing with individualisation from an equally distributed element contribution of IVD, ligaments and muscles in the generic spine model to a predominant muscle contribution in the individualised model depending on the analysed spine level.


Assuntos
Disco Intervertebral , Vértebras Lombares , Humanos , Vértebras Lombares/fisiologia , Suporte de Carga/fisiologia , Fenômenos Biomecânicos , Ligamentos/fisiologia , Disco Intervertebral/fisiologia , Músculos/fisiologia , Rotação , Modelos Biológicos , Análise de Elementos Finitos
7.
Artigo em Inglês | MEDLINE | ID: mdl-38126259

RESUMO

The muscle spindle is an essential proprioceptor, significantly involved in sensing limb position and movement. Although biological spindle models exist for years, the gold-standard for motor control in biomechanics are still sensors built of homogenized spindle output models due to their simpler combination with neuro-musculoskeletal models. Aiming to improve biomechanical simulations, this work establishes a more physiological model of the muscle spindle, aligned to the advantage of easy integration into large-scale musculoskeletal models. We implemented four variations of a spindle model in Matlab/Simulink®: the Mileusnic et al. (2006) model, Mileusnic model without mass, our enhanced Hill-type model, and our enhanced Hill-type model with parallel damping element (PDE). Different stretches in the intrafusal fibers were simulated in all model variations following the spindle afferent recorded in previous experiments in feline soleus muscle. Additionally, the enhanced Hill-type models had their parameters extensively optimized to match the experimental conditions, and the resulting model was validated against data from rats' triceps surae muscle. As result, the Mileusnic models present a better overall performance generating the afferent firings compared to the common data evaluated. However, the enhanced Hill-type model with PDE exhibits a more stable performance than the original Mileusnic model, at the same time that presents a well-tuned Hill-type model as muscle spindle fibers, and also accounts for real sarcomere force-length and force-velocity aspects. Finally, our activation dynamics is similar to the one applied to Hill-type model for extrafusal fibers, making our proposed model more easily integrated in multi-body simulations.

8.
Nanomaterials (Basel) ; 12(19)2022 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-36234596

RESUMO

Aliovalent-doped metal oxide nanocrystals exhibiting localized surface plasmons (LSPRs) are applied in systems that require reflection/scattering/absorption in infrared and optical transparency in visible. Indium tin oxide (ITO) is currently leading the field, but indium resources are known to be very restricted. Antimony-doped tin oxide (ATO) is a cheap candidate to substitute the ITO, but it exhibits less advantageous electronic properties and limited control of the LSPRs. To date, LSPR tuning in ATO NCs has been achieved electrochemically and by aliovalent doping, with a significant decrease in doping efficiency with an increasing doping level. Here, we synthesize plasmonic ATO nanocrystals (NCs) via a solvothermal route and demonstrate ligand exchange to tune the LSPR energies. Attachment of ligands acting as Lewis acids and bases results in LSPR peak shifts with a doping efficiency overcoming those by aliovalent doping. Thus, this strategy is of potential interest for plasmon implementations, which are of potential interest for infrared upconversion, smart glazing, heat absorbers, or thermal barriers.

9.
ScientificWorldJournal ; 11: 801-25, 2011 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-21479351

RESUMO

This study investigated the acute and subchronic inflammatory effects of micrometer-size (micro-size) and nanometer-size (nano-size) particles after intratracheal (i.t.) installation in mice. The role of the type of compound, polymorphism, and size of the particles was investigated. Studied compounds were the two micro-size reference quartzes, SRM1878a and DQ12, a micro- and nano-size rutile titanium dioxide (TiO2), a nano-size anatase, and an amorphous TiO2. Particles were administered by a single i.t. instillation in mice at a fixed dose of 5, 50, and 500 micrograms, respectively. Inflammation was evaluated from the bronchoalveolar lavage fluid (BALF) content of inflammatory cells, the cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6), as well as from lung histology. Evaluations were at 24 h (acute effects) and 3 months (subchronic effects) after instillations. Both types of quartz induced a dose-dependent acute increase of neutrophils, IL-6, and total protein in BALF. Limited subchronic inflammation was observed. All types of TiO2 induced a dose-dependent acute increase of neutrophils in BALF. In the acute phase, micro- and nano-size rutile and nano-size amorphous TiO2 induced elevated levels of IL-6 and total protein in BALF at the highest dose. At the nano-size rutile and amorphous TiO2, subchronic lung inflammation was apparent from a dose-dependent increase in BALF macrophages. Histology showed little inflammation overall. The two types of quartz showed virtually similar inflammatory effects. Nearly similar effects were observed for two sizes of rutile TiO2. Differences were seen between the different polymorphs of nano-size TiO2, with rutile being the most inflammogenic and amorphous being the most potent in regard to acute tissue damage.


Assuntos
Quartzo/efeitos adversos , Titânio/efeitos adversos , Traqueíte/induzido quimicamente , Doença Aguda , Animais , Líquido da Lavagem Broncoalveolar , Doença Crônica , Relação Dose-Resposta a Droga , Interleucina-6/metabolismo , Camundongos , Nanopartículas , Quartzo/administração & dosagem , Titânio/administração & dosagem , Fator de Necrose Tumoral alfa/metabolismo
10.
Comput Biol Med ; 135: 104528, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34166878

RESUMO

A variety of medical imaging procedures, cadaver experiments, and computer models have been utilized to capture, depict, and understand the motion of the human lumbar spine. Particular interest lies in assessing the relative movement between two adjacent vertebrae, which can be represented by a temporal evolution of finite helical axes (FHA). Mathematically, this FHA evolution constitutes a seven-dimensional quantity: one dimension for the time, two for the (normalized) direction vector, another two for the (unique) position vector, as well as one for each the angle of rotation around and the amount of translation along the axis. Predominantly in the literature, however, movements are assumed to take place in certain physiological planes on which FHA are projected. The resulting three-dimensional quantity - the so-called centrode - is easily presentable but leaves out substantial pieces of available data. Here, we investigate and assess several possibilities to visualize subsets of FHA data of increasing dimensionality. Finally, we utilize an agglomerative hierarchical clustering algorithm and propose a novel visualization technique, namely the quiver principal axis plot (QPAP), to depict the entirety of information inherent to hundreds or thousands of FHA. The QPAP method is applied to flexion-extension, lateral bending, and axial rotation movements of a lumbar spine within both a reduced model as well as a complex upper body system.


Assuntos
Vértebras Lombares , Fenômenos Biomecânicos , Análise por Conglomerados , Humanos , Vértebras Lombares/diagnóstico por imagem , Amplitude de Movimento Articular , Rotação
11.
BMC Microbiol ; 10: 233, 2010 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-20815884

RESUMO

BACKGROUND: The aim of the present study was to assess possible health effects of airway exposures to Bacillus thuringiensis (Bt) based biopesticides in mice. Endpoints were lung inflammation evaluated by presence of inflammatory cells in bronchoalveolar lavage fluid (BALF), clearance of bacteria from the lung lumen and histological alterations of the lungs. Hazard identifications of the biopesticides were carried out using intratracheal (i.t.) instillation, followed by an inhalation study. The two commercial biopesticides used were based on the Bt. subspecies kurstaki and israelensis, respectively. Groups of BALB/c mice were i.t instilled with one bolus (3.5 × 105 or 3.4 × 106 colony forming units (CFU) per mouse) of either biopesticide. Control mice were instilled with sterile water. BALFs were collected and the inflammatory cells were counted and differentiated. The BALFs were also subjected to CFU counts. RESULTS: BALF cytology showed an acute inflammatory response dominated by neutrophils 24 hours after instillation of biopesticide. Four days after instillation, the neutrophil number was normalised and inflammation was dominated by lymphocytes and eosinophils, whereas 70 days after instillation, the inflammation was interstitially located with few inflammatory cells present in the lung lumen.Half of the instilled mice had remaining CFU recovered from BALF 70 days after exposure. To gain further knowledge with relevance for risk assessment, mice were exposed to aerosols of biopesticide one hour per day for 2 × 5 days. Each mouse received 1.9 × 104 CFU Bt israelensis or 2.3 × 103 CFU Bt kurstaki per exposure. Seventy days after end of the aerosol exposures, 3 out of 17 mice had interstitial lung inflammation. CFU could be recovered from 1 out of 10 mice 70 days after exposure to aerosolised Bt kurstaki. Plethysmography showed that inhalation of Bt aerosol did not induce airway irritation. CONCLUSIONS: Repeated low dose aerosol exposures to commercial Bt based biopesticides can induce sub-chronic lung inflammation in mice, which may be the first step in the development of chronic lung diseases. Inhalation of Bt aerosols does not induce airway irritation, which could explain why workers may be less inclined to use a filter mask during the application process, and are thereby less protected from exposure to Bt spores.


Assuntos
Bacillus thuringiensis/imunologia , Exposição por Inalação/efeitos adversos , Pulmão/imunologia , Praguicidas/efeitos adversos , Animais , Bacillus thuringiensis/fisiologia , Líquido da Lavagem Broncoalveolar/imunologia , Líquido da Lavagem Broncoalveolar/microbiologia , Feminino , Humanos , Pulmão/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Controle Biológico de Vetores , Praguicidas/imunologia , Sistema Respiratório/imunologia , Sistema Respiratório/microbiologia
12.
Biomech Model Mechanobiol ; 19(6): 2015-2047, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32314072

RESUMO

The load distribution among lumbar spinal structures-still an unanswered question-has been in the focus of this hybrid experimental and simulation study. First, the overall passive resistive torque-angle characteristics of healthy subjects' lumbar spines during flexion-extension cycles in the sagittal plane were determined experimentally by use of a custom-made trunk-bending machine. Second, a forward dynamic computer model of the human body that incorporates a detailed lumbar spine was used to (1) simulate the human-machine interaction in accordance with the experiments and (2) validate the modeled properties of the load-bearing structures. Third, the computer model was used to predict the load distribution in the experimental situation among the implemented lumbar spine structures: muscle-tendon units, ligaments, intervertebral discs, and facet joints. Nine female and 10 male volunteers were investigated. Lumbar kinematics were measured with a marker-based infrared device. The lumbar flexion resistance was measured by the trunk-bending machine through strain gauges on the axes of the machine's torque motors. Any lumbar muscle activity was excluded by simultaneous sEMG monitoring. A mathematical model was used to describe the nonlinear flexion characteristics. The subsequent extension branch of a flexion-extension torque-angle characteristic could be significantly distinguished from its flexion branch by the zero-torque lordosis angle shifted to lower values. A side finding was that the model values of ligament and passive muscle stiffnesses, extracted from well-established literature sources, had to be distinctly reduced in order to approach our measured overall lumbar stiffness values. Even after such parameter adjustment, the computer model still predicts too stiff lumbar spines in most cases in comparison with experimental data. A review of literature data reveals a deficient documentation of anatomical and mechanical parameters of spinal ligaments. For instance, rest lengths of ligaments-a very sensitive parameter for simulations-and cross-sectional areas turned out to be documented at best incompletely. Yet by now, our model well reproduces the literature data of measured pressure values within the lumbar disc at level L4/5. Stretch of the lumbar dorsal (passive) muscle and ligament structures as an inescapable response to flexion can fully explain the pressure values in the lumbar disc. Any further external forces like gravity, or any muscle activities, further increase the compressive load on a vertebral disc. The impact of daily or sportive movements on the loads of the spinal structures other than the disc cannot be predicted ad hoc, because, for example, the load distribution itself crucially determines the structures' current lever arms. In summary, compressive loads on the vertebral discs are not the major determinants, and very likely also not the key indicators, of the load scenario in the lumbar spine. All other structures should be considered at least equally relevant in the future. Likewise, load indicators other than disc compression are advisable to turn attention to. Further, lumbar flexion is a self-contained factor of lumbar load. It may be worthwhile, to take more consciously care of trunk flexion during daily activities, for instance, regarding long-term effects like lasting repetitive flexions or sedentary postures.


Assuntos
Disco Intervertebral/fisiologia , Vértebras Lombares/fisiologia , Adulto , Antropometria , Fenômenos Biomecânicos , Simulação por Computador , Eletromiografia , Desenho de Equipamento , Feminino , Humanos , Ligamentos/fisiologia , Lordose , Masculino , Movimento , Músculo Esquelético/fisiologia , Músculos/fisiologia , Postura/fisiologia , Amplitude de Movimento Articular/fisiologia , Pele , Software , Coluna Vertebral/fisiologia , Estresse Mecânico , Suporte de Carga/fisiologia , Adulto Jovem
13.
Inhal Toxicol ; 21(13): 1123-8, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19852554

RESUMO

Occupational exposures to the butter flavouring agent diacetyl (2,3-butanedione) have caused lung inflammation and severe airflow limitation due to bronchiolitis obliterans. Diacetyl is naturally present in butter, beer, white wine, etc., and its pleasant odour is easily recognized by consumers. However, this pleasant odour may induce a false sense of safety when higher airborne concentrations are encountered in industrial use. In this study, the acute warning properties, in terms of sensory irritation, that could be useful to prevent workers from exposures to a high concentration were first investigated in a mouse bioassay. Then at higher exposure concentrations, the possibility of airflow limitation and pulmonary irritation were studied with the same mouse bioassay. Diacetyl induces concentration-dependent irritation in all parts of the respiratory tract during a 2-h exposure period. The no-observed-effect levels for each effect in the mice were above 100 ppm and initiation of sensory irritation in humans was estimated to occur above 20 ppm. No acute warning signal from the airways is expected at diacetyl levels that have caused bronchiolitis obliterans and other toxic effects. The sensory irritation effect, which occurred rapidly upon initiation of exposure, faded rapidly. Furthermore, high-level diacetyl exposures decreased the sensory irritation warning signal in mice upon repeated exposure, which suggests that the compound is especially insidious.


Assuntos
Diacetil/administração & dosagem , Diacetil/toxicidade , Exposição por Inalação , Sistema Respiratório/efeitos dos fármacos , Animais , Bronquiolite Obliterante/induzido quimicamente , Bronquiolite Obliterante/patologia , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Sistema Respiratório/patologia , Fatores de Tempo
14.
Toxicol Lett ; 181(3): 171-6, 2008 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-18723085

RESUMO

There are concerns about ozone-initiated chemistry, because the formation of gaseous oxidation products and ultrafine particles may increase complaints, morbidity and mortality. Here we address the question whether the gaseous products or the ultrafine particles from the ozone-initiated chemistry of limonene, a common and abundant indoor pollutant, cause acute airway effects. The effects on the airways by d-limonene, a ca. 16s old ozone/d-limonene mixture, and clean air were evaluated by a mice bioassay, from which sensory irritation of the upper airways, airflow limitation, and pulmonary irritation can be obtained. A denuder was inserted to separate the ultrafine particles from the gaseous products prior to the exposure chamber. Reduction of mean respiratory frequency (>30%) and 230% increase of time of brake were observed without denuder, during 30min exposure, to the ozonolyzed d-limonene mixture, which are indicative of prominent sensory effects. The initial concentrations (ppm) were 40 d-limonene and 4 ozone. The exposure concentrations (ppm) were about 35 d-limonene and 0.05 ozone. Formaldehyde and residual d-limonene, the salient sensory irritants, accounted for up to three-fourth of the sensory irritation. The upper airway effects reversed to baseline upon cessation of exposure. An effect on the conducting airways was also significant, which did not reverse completely upon cessation. Airway effects were absent with the denuder inserted, which did not alter the size distribution of ultrafine particles ( approximately 10mg/m(3)), significantly. The result was statistically indistinguishable from clean dry air. It is concluded that ultrafine particles that are generated from ozone-initiated d-limonene chemistry and denuded are not causative of sensory effects in the airways.


Assuntos
Poluentes Atmosféricos , Cicloexenos , Ozônio , Sistema Respiratório/efeitos dos fármacos , Terpenos , Testes de Toxicidade Aguda , Poluentes Atmosféricos/química , Poluentes Atmosféricos/toxicidade , Animais , Cicloexenos/química , Cicloexenos/toxicidade , Limoneno , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Oxirredução , Ozônio/química , Ozônio/toxicidade , Material Particulado/química , Material Particulado/toxicidade , Testes de Função Respiratória , Terpenos/química , Terpenos/toxicidade , Fatores de Tempo , Testes de Toxicidade Aguda/instrumentação , Testes de Toxicidade Aguda/métodos
15.
Basic Clin Pharmacol Toxicol ; 96(6): 420-8, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15910405

RESUMO

The effects of (+)-alpha-pinene and (-)-alpha-pinene vapours were studied for respiratory effects in BALB/c mice. The (+) enantiomer showed persistent sensory irritation effect on the upper respiratory tract during exposures in the range of 100 to 3691 ppm. The threshold concentration for this effect was calculated to be about 70 ppm, which is close to the no-effect level of about 40 ppm in humans. A significant airflow limitation occurred from exposure concentrations of 200 ppm and higher. No irritating effect was observed at the alveolar level and no central nervous system effect was obvious. In the exposure range from 218 to 5213 ppm, the (-) enantiomer produced only a short-lasting sensory irritation effect during the first 10 min. of exposure and only at concentrations above 2900 ppm. The tidal volume decreased significantly from approximately 400 ppm, but it was first conspicuous above 1000 ppm. Airflow limitation appeared consistently from approximately 2000 ppm. The (-) enantiomer also induced anesthesia/and or pulmonary irritation as well as sudden death at concentrations above 2600 ppm. Overall, the enantiomers showed different time-dependent and stereoselective effects. The lower sensory irritation effect of the (-) enantiomer probably being due to less of the molecule being adsorbed to a sensory irritant receptor.


Assuntos
Irritantes/toxicidade , Monoterpenos/toxicidade , Ventilação Pulmonar/efeitos dos fármacos , Respiração/efeitos dos fármacos , Administração por Inalação , Animais , Monoterpenos Bicíclicos , Sistema Nervoso Central/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nível de Efeito Adverso não Observado , Estereoisomerismo , Volume de Ventilação Pulmonar/efeitos dos fármacos
16.
Toxicol Lett ; 143(2): 109-14, 2003 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-12749814

RESUMO

Recently, we reported the formation of unidentified strong upper airway irritants in reaction mixtures of terpenes and ozone. The identified products included aldehydes, ketones and carboxylic acids. Here we report the effects of variation of reaction time, relative humidity and initial ozone concentration on irritant formation in a flow reaction system using R-(+)-limonene and isoprene. Upper airway irritation was measured in mice as reduction of the respiratory rate. For both substances maximum irritation was observed for low humidity (<2% RH)/short time (16-30 s) reaction mixtures, and both moderate humidity ( approximately 32% RH) and longer reaction times (60-90 s) resulted in significantly less irritation. These results suggest that some unidentified intermediates react with water vapor to give less irritating products. Irritation measured at four ozone concentrations (0.5, 1, 2 and 3.5 ppm) using low humidity/short time reaction conditions for limonene (50 ppm) and isoprene (500 ppm) revealed that at 0.5 ppm, irritation was at the same level as that for the pure terpenes, indicating that at 0.5 ppm ozone the combined irritant effect was near the no effect level for the product mixture.


Assuntos
Butadienos/química , Butadienos/toxicidade , Hemiterpenos , Ozônio/química , Ozônio/toxicidade , Pentanos , Sistema Respiratório/efeitos dos fármacos , Terpenos/química , Terpenos/toxicidade , Animais , Cicloexenos , Umidade , Limoneno , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Oxirredução , Respiração/efeitos dos fármacos
17.
Toxicol Lett ; 151(2): 389-98, 2004 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-15183463

RESUMO

It has been suggested that occupational exposure to quaternary ammonium compounds (QACs) may promote the development of allergic airway diseases. In this study, hazard identifications of the adjuvant effect of cetylpyridinium chloride (CPC), dimethyldioctadecylammonium bromide (DDA), hexadecyltrimethylammonium bromide (HTA), and tetraethylammonium chloride (TEA) were performed in a screening bioassay. Female BALB/c mice were injected subcutaneously with the model allergen ovalbumin (OVA) alone or together with different quantities of one of the QAC test compounds. After one or two boosters, levels of OVA-specific IgE, IgG1 and IgG2a antibodies were measured in sera. CPC and DDA increased IgE and IgG1 antibody production, respectively, compared to the OVA control group, whereas HTA and TEA showed no adjuvant effect. Nevertheless, when TEA was given in combination with DDA, the adjuvant effect was up to six-fold higher than the adjuvant effect of DDA alone. Only DDA had a statistically significant adjuvant effect on IgG2a antibody levels.


Assuntos
Adjuvantes Imunológicos/toxicidade , Compostos de Amônio Quaternário/toxicidade , Animais , Bioensaio , Peso Corporal/efeitos dos fármacos , Cetrimônio , Compostos de Cetrimônio/toxicidade , Cetilpiridínio/imunologia , Cetilpiridínio/toxicidade , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Feminino , Imunoglobulinas/análise , Imunoglobulinas/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Compostos de Amônio Quaternário/imunologia , Relação Estrutura-Atividade , Tetraetilamônio/imunologia , Tetraetilamônio/toxicidade
18.
Toxicol Lett ; 216(1): 54-64, 2013 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-23164675

RESUMO

Ozone-initiated monoterpene reaction products have been hypothesized to cause eye and airway complaints in office environments and some have been proposed to cause skin irritation and sensitization. The respiratory effects of 60 min exposures to five common oxidation products from abundant terpenoids (e.g. limonene), used as solvent and fragrance in common household products or present in skin lipids (e.g. squalene), were studied in a head out mouse bioassay. This allowed determination of acute upper airway (sensory) irritation, airflow limitation in the conducting airways, and pulmonary irritation in the alveolar region. Derived human reference values (RFs) for sensory irritation were 1.3, 0.16 and 0.3 ppm, respectively, for 4-acetyl-1-methylcyclohexene ( 0.2 ppm) [corrected], 3-isopropenyl-6-oxo-heptanal (IPOH), and 6-methyl-5-heptene-2-one (6-MHO). Derived RFs for airflow limitation were 0.8, 0.45, 0.03, and 0.5 ppm, respectively, for dihydrocarvone (DHC), 0.2 ppm [corrected], 4-oxo-pentanal (0.3 ppm) [corrected], and 6-MHO. Pulmonary irritation was unobserved as a critical effect. The RFs indicate that the oxidation products would not contribute substantially to sensory irritation in eyes and upper airways in office environments. Reported concentrations in offices of 6-MHO and 0.3 ppm [corrected]would not result in airflow limitation. However, based upon the RFs for IPOH and 0.3 ppm [corrected], precautionary actions should be considered that disfavor their formation in excess.


Assuntos
Poluentes Atmosféricos/toxicidade , Poluição do Ar em Ambientes Fechados/efeitos adversos , Ozônio/química , Terpenos/toxicidade , Poluentes Atmosféricos/química , Poluição do Ar em Ambientes Fechados/análise , Animais , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Valores de Referência , Terpenos/química
19.
Toxicol Lett ; 209(2): 166-72, 2012 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-22212438

RESUMO

Repeated low-level indoor air exposure to volatile organic compounds (VOCs) may influence the reporting of sensory irritation in the eyes and airways. The ozone-initiated reaction products of limonene, an abundant VOC, were used as a model of indoor air mixtures to study upper airway (sensory) irritation, bronchoconstrictive and alveolar level effects after repeated exposures. Mice were exposed 1h/day for 10 consecutive days to: air, limonene (52 ppm/289 mg/m(3)); ozone (0.1 ppm/0.2mg/m(3)); a reaction mixture of limonene (52±8 ppm) and ozone (0.5, 2.5 and 3.9 ppm) resulting in ~0.05 ppm residual ozone. Neither the limonene nor the ozone exposures alone showed consistent effects on the respiratory parameters. In the limonene/ozone groups, the respiratory rate decreased concentration-dependently with an extrapolated no-effect-level of ~0.3 ppm admixed ozone. Both sensory irritation and airflow limitation were conspicuous effects of the mixtures; sensory irritation appeared rapidly and airflow limitation developed slowly during each exposure. The effects of these parameters did not change with increasing number of exposures. No firm conclusion could be drawn about alveolar level effects. Cells in bronchoalveolar lavage were unchanged irrespective of exposure to air, ozone, and limonene with and without ozone. In conclusion, the study indicated that repeated exposures to ozone-initiated limonene mixtures did not cause sensitization of sensory irritation and airflow limitation. Bronchoalveolar lavage after exposures to ozone, and limonene with and without ozone, respectively, did not show airway inflammation.


Assuntos
Poluição do Ar em Ambientes Fechados/efeitos adversos , Cicloexenos/toxicidade , Exposição por Inalação/efeitos adversos , Ozônio/toxicidade , Sistema Respiratório/efeitos dos fármacos , Terpenos/toxicidade , Animais , Líquido da Lavagem Broncoalveolar/citologia , Cicloexenos/química , Relação Dose-Resposta a Droga , Limoneno , Modelos Lineares , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ozônio/química , Pletismografia , Testes de Função Respiratória , Terpenos/química
20.
Toxicol Sci ; 116(1): 216-24, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20348230

RESUMO

Exposures to two commercial nanofilm spray products (NFPs), a floor sealant (NFP 1) and a coating product for tiles (NFP 2), were investigated for airway irritation, airway inflammation, and lung damage in a mouse inhalation model. The particle exposure was characterized by particle number, particle size distribution, and gravimetric analysis. BALB/cJ mice were exposed for 60 min to the aerosolized products at 3.3-60 mg/m(3) (10(5)-10(6) fine particles/cm(3)) measured in the breathing zone of the mice. Lung inflammation and lung damage were assessed by study of bronchoalveolar lavage fluid (BALF) cytology, protein in BALF, and histology. Mass spectral analysis showed that NFP 1 and NFP 2 contained hydrolysates and condensates of a perfluorosilane and alkylsilane, respectively. NFP 1 induced a concentration-dependent decrease of the tidal volume lasting for at least 1 day. Exposure concentrations above 16.1 mg/m(3) (2.1 x 10(6) fine particles/cm(3)) gave rise to significant increases of protein level in BALF and reduced body weight, and histological examination showed atelectasis, emphysema, and hemorrhages. A narrow interval between the no-effect level (16.1 mg/m(3)) and the lethal concentrations (18.4 mg/m(3)) was observed. The alkylsilane-based product (NFP 2) had no effect at the concentrations studied. Experiments with different types of perfluorinated silanes and alkylsiloxanes showed that the toxic effects did not arise solely from the perfluorination. The number of free hydroxyl groups in the silanes/alkylsiloxanes was also critical for the toxicity.


Assuntos
Fluorocarbonos/toxicidade , Radical Hidroxila , Pulmão/efeitos dos fármacos , Nanopartículas , Animais , Fluorocarbonos/administração & dosagem , Exposição por Inalação , Masculino , Camundongos , Camundongos Endogâmicos BALB C
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