RESUMO
INTRODUCTION: A hospital environment can be a significant burden and a health risk especially for dementia patients. Mobile x-ray equipment (ME) is used to enable imaging of these patients at home. The aim was to compare image quality (IQ) of chest, hip and pelvis images from ME to the stationary equipment (SE) used in a hospital department. METHODS: We analysed examinations of the chest (n = 20), hip (n = 64) and pelvis (n = 32). Images were equally obtained from each setting of ME and SE. All images were graded using Visual Grading Analysis (VGA) by three radiographers (hip and pelvis) and three radiologists (chest). Technical IQ assessment was done by 80 additional images of a Contrast-Detail Radiography phantom (CDRAD). RESULTS: All chest images were approved for diagnostic use, as well as the hip AP and pelvis images from SE. 'Approved proportion of ME images was for HIP antero-posterior (AP) and pelvis, 78% [95% CI: 52-94%] and 81% [95% CI: 54-96%] respectively. Hip axial had an overall low, but not significant different approval rate. Ordered logistic regression indicated higher IQ of HIP AP and pelvic images from SE. This contrasts that the CDRAD substudy indicated better IQ, expressed as IQFinv, from ME. CONCLUSION: The VGA showed higher IQ for the SE system, while the CDRAD showed higher IQ for the ME system. IMPLICATIONS FOR PRACTICE: Dementia patients can be examined at their home if the acquisition is optimised according to image quality in conjunct to radiation dose. Performing imaging out of the hospital and coordinating the patients' further treatment are new work areas for radiographers and requires excellent communication skills.
Assuntos
Demência , Quadril/diagnóstico por imagem , Hospitais , Casas de Saúde , Pelve/diagnóstico por imagem , Radiografia/instrumentação , Tórax/diagnóstico por imagem , Humanos , Imagens de Fantasmas , Sistemas Automatizados de Assistência Junto ao Leito , Qualidade da Assistência à Saúde , Radiografia/normasRESUMO
During the oxidation of LDL, a central pathophysiological component of atherogenesis, a wide variety of chemical and physical changes occur leading to the generation of oxidation-specific neoepitopes. These epitopes are not only immunogenic, leading to adaptive humoral responses, but are also a prominent target of multiple arcs of innate immunity. The pattern recognition receptors (PRRs) of innate immunity are germ line encoded, conserved by natural selection, and bind to pathogen-associated molecular patterns (PAMPs) common on multiple structures. However, it is not intuitive as to why they should recognize oxidation-specific neoepitopes. Yet it is clear that multiple macrophage scavenger receptors, which are classic PRRs, recognize oxidation-specific epitopes, such as those found on oxidized LDL (OxLDL). Other innate proteins, such as C-reactive protein, also bind to OxLDL. Natural antibodies (NAbs), the humoral arc of innate immunity, provide a nonredundant role in the first line of defence against pathogens, but are also believed to provide important homeostatic house-keeping functions against self-antigens. Our work demonstrates that oxidation-specific epitopes, as found on OxLDL, are a major target of NAbs. In this review, we will discuss the specific example of the prototypic NAb T15/E06, which is increased in atherosclerotic mice and mediates atheroprotection, and discuss the potential role of NAbs in atherogenesis, and in inflammation in general. We also review data that oxidation-specific epitopes are generated whenever cells undergo programmed cell death, forming a common set of PAMPs recognized by oxidation-specific PRRs on macrophages, NAbs and innate proteins. We present the hypothesis that oxidation-specific epitopes on apoptotic cells exerted evolutionary pressure for the conservation of these PRRs and also serve to maintain the expansion of a substantial proportion of NAbs directed to these stress-induced self-antigens.
Assuntos
Aterosclerose/imunologia , Epitopos/imunologia , Imunidade Inata/imunologia , Animais , Apoptose/fisiologia , Aterosclerose/fisiopatologia , Linfócitos B/imunologia , Epitopos/biossíntese , Imunoglobulina M/imunologia , Lipoproteínas LDL , Camundongos , Coelhos , Receptores de Reconhecimento de PadrãoRESUMO
The pathogenesis of atherosclerosis is mediated by genetic susceptibility along with a variety of cardiovascular risk factors and environment influences. As atherosclerotic lesions progress, they manifest several features typical of chronic inflammation, such as the presence of monocyte/macrophages, T-cells and inflammatory cytokines. This inflammatory response is fueled and enhanced by oxidative stress, which may be the link between lipid disorders and inflammation. Oxidation of lipoproteins is intimately involved in all stages of atherosclerosis and oxidative byproducts co-localize with inflammatory cells. When low density lipoprotein enters the subintimal space, it is oxidized by several mechanisms, including both enzymatic and non-enzymatic pathways and becomes a ligand for scavenger receptors on macrophages leading to generation of foam cells. Oxidized LDL is not only pro-inflammatory and pro-atherogenic, but several of the neoepitopes generated during oxidation are highly immunogenic and result in the generation of autoantibodies. Autoantibodies to OxLDL are found within atherosclerotic lesions and in apparently healthy subjects, as well as patients with various manifestations of cardiovascular disease. In this article, the role of circulating autoantibodies to OxLDL in cardiovascular disease will be reviewed. Although controversy still exists, the overall evidence supports the notion that IgG autoantibodies to OxLDL are associated with pro-atherogenic properties and IgM autoantibodies to OxLDL with atheroprotective properties. Whether such antibodies have a modulating role or are merely reflectors of atherogenesis has not been fully determined. Data is also emerging on the role of natural antibodies, which are primarily of the IgM class, that recognize oxidation-specific epitopes. Among other properties, these antibodies may be involved in housekeeping functions in binding and clearing pro-inflammatory oxidized lipids and therefore may be atheroprotective. Several studies have also recently evaluated the potential therapeutic role of antibodies to OxLDL either through active immunization using OxLDL or model oxidation-specific epitopes as immunogens or through passive immunization with human antibodies directed to oxidation-specific epitopes. Although these investigation are at an early stage, they show promise that immune modulation may lead to novel approaches to treat atherosclerosis and cardiovascular disease.
Assuntos
Anticorpos/imunologia , Autoanticorpos/imunologia , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/terapia , Lipoproteínas LDL/imunologia , Adulto , Idoso , Animais , Formação de Anticorpos , Aterosclerose/imunologia , Aterosclerose/terapia , Modelos Animais de Doenças , Progressão da Doença , Epitopos , Feminino , Humanos , Hipolipemiantes/uso terapêutico , Masculino , Camundongos , Pessoa de Meia-Idade , Razão de Chances , Oxirredução , Estresse Oxidativo , Coelhos , Fatores de Risco , VacinaçãoRESUMO
Sensory irritation due to inhalation of n-pentanol, n-heptanol, sec-butanol and tert-pentanol was determined from the reflexively induced decrease in respiratory rate in CF-1 mice. The concentration-effect relations followed Michaelis-Menten equations, complying with receptor mediated processes. The relations were transformed into nearly rectilinear relationships in log concentration-effect plots, and the extrapolated threshold concentrations (RD-0) from the lines were 120, 28, 640 and 1210 ppm, respectively, obtained from the first 2 min of the exposure period. These values were comparable to those found in Swiss-Webster mice and to those obtained by electrophysiological experiments in Sprague-Dawley rats. The hydrophobic properties of the receptor biophase were found to approach that of the internal part of the bilayer membrane. Estimates on threshold limit values (TLV) were obtained and were found in reasonable agreement with the established values. The nose has a scrubbing effect, which reduces the concentration in the lungs in normal mice. n-Pentanol, sec-butanol and tert-pentanol decreased tidal volume in normal mice, explained either by an activation of receptors in the upper airways or by a sensitization of the stretch receptors. Two types of pulmonary responses were seen in tracheal-cannulated mice, which could be explained by an effect on stretch receptors and another type of lung receptors.
Assuntos
Álcoois/toxicidade , Neurônios Aferentes/efeitos dos fármacos , Sistema Respiratório/efeitos dos fármacos , Administração por Inalação , Álcoois/administração & dosagem , Animais , Butanóis/toxicidade , Relação Dose-Resposta a Droga , Heptanol , Masculino , Camundongos , Camundongos Endogâmicos , Pentanóis/toxicidade , Relação Estrutura-Atividade , Fatores de TempoRESUMO
Intranasal irrigation with ZnSO4 solutions is used for experimental induction of anosmia. It is, however, unknown whether the trigeminal nerve is affected by the treatment. One day after irrigation (concentrations investigated were between 0.05-1%) the ability of food finding, an olfactory cue, was decreased in a concentration-dependent manner. The trigeminal effect was investigated from a reflexively induced decrease in respiratory rate due to n-propanol exposure. No impairment occurred at 1% ZnSO4. Anosmia was also seen 2-3 h after an irrigation with solutions of 0.05-1% ZnSO4. At the same time, 0.2 and 1% solutions in themselves decreased the respiratory rate due to reflexes from the upper and lower respiratory tract. A conspicuous systemic effect can be ruled out as the Zn++ antidote, CaNa2EDTA, had no effect on the decrease. A direct activation of the trigeminal nerve due to a reaction with a thiol group may explain the effect from the upper airways.
Assuntos
Mucosa Olfatória/inervação , Nervo Olfatório/efeitos dos fármacos , Olfato/efeitos dos fármacos , Sulfatos/farmacologia , Nervo Trigêmeo/efeitos dos fármacos , Compostos de Zinco/farmacologia , 1-Propanol/farmacologia , Animais , Comportamento Apetitivo/efeitos dos fármacos , Comportamento Apetitivo/fisiologia , Sinais (Psicologia) , Relação Dose-Resposta a Droga , Masculino , Camundongos , Nervo Olfatório/fisiologia , Ventilação Pulmonar/efeitos dos fármacos , Ventilação Pulmonar/fisiologia , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , Olfato/fisiologia , Irrigação Terapêutica , Nervo Trigêmeo/fisiologia , Sulfato de ZincoRESUMO
Protection against lipid oxidation and formation of unpleasant fishy and rancid off-flavors in oil-in-water food emulsions, such as fish oil enriched mayonnaise, is difficult to achieve. Volatile profiles from stored mayonnaises with different oil phase compositions were collected using a developed dynamic headspace sampling technique, in which interfering acetic acid was removed in situ with potassium hydroxide, and subsequently 148 volatiles were characterized and monitored by gas chromatography/mass spectrometry. Multivariate statistics showed correlation between the concentration of 62 volatiles and the fish oil and storage parameters, indicating the formation of lipid oxidation products, which impose fishy off-flavors. Further verification was obtained by gas chromatography/olfactometry, by which, among 78 odors, cis-4-heptenal and trans,cis-2,4-heptadienal were detected as distinct fishy notes. In total, 27 volatiles, including 1-penten-3-one, cis-2-penten-1-ol, cis-3-hexenal, cis-4-heptenal, 1-octen-3-one, 1,cis-5-octadien-3-one, 1-octen-3-ol, trans,cis-2, 4-heptadienal, and trans,cis-2,6-nonadienal, were suggested to contribute to the developed unpleasant fishy and rancid off-flavors.
Assuntos
Óleos de Peixe/análise , Análise de Alimentos , Conservação de Alimentos , Cromatografia Gasosa-Espectrometria de Massas , Odorantes/análiseRESUMO
A fast (12 min) high-performance size exclusion chromatography (HPSEC) method for the separation of neutral lipid class hydroperoxides in the oil phases from fish oil enriched mayonnaises was developed. Detection and quantification were performed using the postcolumn fluorometric (FL) diphenyl-1-pyrenylphosphine oxidation principle. The reproducibilities judged by intra- and inter-assay variations were 0.64 and 7.2%, respectively. The HPSEC-FL method was applied to assess the effect of supplementations with emulsifier, gallic acid, and EDTA on the oxidative processes in the mayonnaises during storage. Substantial amounts of hydroperoxy triacylglycerols (TAGOOH) and cholesterol esters (CEOOH), together with traces of TAGOOH-dimers, were detected. All supplementations significantly decreased the levels of TAGOOH and to a lesser degree CEOOH. Supplementations with EDTA and gallic acid resulted in constant and slightly increasing levels of TAGOOH, respectively, thus affecting the oxidation mechanisms seen in reference mayonnaise. The emulsifier Panodan TR DATEM reduced the levels of TAGOOH as compared to the appropriate controls.
Assuntos
Óleos de Peixe/química , Conservação de Alimentos , Peróxidos Lipídicos/análise , Cromatografia Líquida de Alta Pressão , Emulsões , Fluorometria , Peróxidos Lipídicos/metabolismo , Oxirredução , Tamanho da Partícula , Reprodutibilidade dos TestesRESUMO
The antioxidative effects of gallic acid, EDTA, and extra emulsifier Panodan DATEM TR in mayonnaise enriched with 16% fish oil were investigated. EDTA reduced the formation of free radicals, lipid hydroperoxides, volatiles, and fishy and rancid off-flavors. The antioxidative effect of EDTA was attributed to its ability to chelate free metal ions and iron from egg yolk located at the oil-water interface. Gallic acid reduced the levels of both free radicals and lipid hydroperoxides but promoted slightly the oxidative flavor deterioration in mayonnaise and influenced the profile of volatiles. Gallic acid may therefore promote the decomposition of lipid hydroperoxides to volatile oxidation products. Addition of extra emulsifier reduced the lipid hydroperoxide levels but did not influence the level of free radicals or the oxidative flavor deterioration in mayonnaisse; however, it appeared to alter the profile of volatiles. The effect of the emulsifier on the physical structure and rheological properties depended on the presence of antioxidants.
Assuntos
Antioxidantes/farmacologia , Ácido Edético/farmacologia , Óleos de Peixe/química , Aditivos Alimentares , Manipulação de Alimentos , Ácido Gálico/farmacologia , Ovos , Excipientes/farmacologia , Ácidos Graxos Monoinsaturados , Alimentos , Peróxidos Lipídicos/análise , Odorantes/análise , Óleos de Plantas , Óleo de Brassica napusAssuntos
Acetaminofen/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas , Fígado/efeitos dos fármacos , Adulto , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Feminino , Encefalopatia Hepática/induzido quimicamente , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
We report on a child with blue rubber bleb nevus syndrome (BRBNS) presenting during the first days of life with severe bleeding from the upper gastrointestinal tract. Medical treatment with methylprednisolone, cyklokapron, interferon 1 alpha and numerous blood transfusions were given to control bleeding during the first 3 years of life. Afterwards repeated endoscopic electrocoagulation were performed over a period of one year resulting in a termination of bleeding episodes. At ten years of age the patient developed spastic diplegia with slight walking disabilities, coordination and fine motor problems. The case is unique because 1) it is the first neonatal case with BRBNS and severe gastrointestinal bleeding; 2) the patient was successfully treated by endoscopic electrocoagulation; and 3) the long-term follow-up. The use of electrocoagulation appears to have been effective and ablation of the stomach could be avoided until now.
Assuntos
Malformações Arteriovenosas/cirurgia , Eletrocoagulação/métodos , Hemorragia Gastrointestinal/cirurgia , Gastroscopia , Nevo Azul , Neoplasias Cutâneas/cirurgia , Neoplasias Gástricas/cirurgia , Antifibrinolíticos/uso terapêutico , Malformações Arteriovenosas/complicações , Malformações Arteriovenosas/tratamento farmacológico , Quimioterapia Combinada , Hemorragia Gastrointestinal/tratamento farmacológico , Hemorragia Gastrointestinal/etiologia , Glucocorticoides/uso terapêutico , Hemangioma/cirurgia , Humanos , Fatores Imunológicos/uso terapêutico , Recém-Nascido , Interferon-alfa/uso terapêutico , Masculino , Metilprednisolona/uso terapêutico , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/tratamento farmacológico , Síndrome , Ácido Tranexâmico/uso terapêutico , Resultado do TratamentoRESUMO
Irritation of upper respiratory tract (sensory irritation) due to two model solvents, ethylbenzene and propanol, were investigated from their reflex-induced decrease in respiratory rate in mice. Intranasal application of capsaicin decreased the sensory irritation response of both solvents, indicating that at least part of the sensory irritation effect must occur as a result of activation of capsaicin sensitive afferent nerves. The vehicle used for the application of capsaicin in itself decreased the respiratory rate strongly, either caused by effects on the upper respiratory tract or on the lungs. This demonstrates the need for a formulation of a pharmacologically inactive vehicle for nasal application of lipophilic substances. Pretreatment with indomethacin had no influence on sensory irritation of any of the solvents. This suggests that sensory irritation is caused by a direct interaction between receptors on the trigeminal nerves and the vapours rather than being an indirect effect of tissue damage giving rise to metabolites from the cyclooxygenase pathway.
Assuntos
1-Propanol/toxicidade , Derivados de Benzeno/toxicidade , Capsaicina/farmacologia , Indometacina/farmacologia , Respiração/efeitos dos fármacos , Sistema Respiratório/inervação , Células Receptoras Sensoriais/efeitos dos fármacos , Animais , Irritantes , Masculino , Camundongos , Mucosa Nasal/efeitos dos fármacos , Neurônios Aferentes/efeitos dos fármacos , Neurônios Aferentes/fisiologia , Respiração/fisiologia , Nervo Trigêmeo/fisiologiaRESUMO
Activation of the trigeminal nerve endings in eyes and nose, termed sensory irritation, was determined from the reflexively induced decrease in respiratory rate in mice for methyl propyl ketone, methyl butyl ketone, methyl amyl ketone and methyl hexyl ketone. The relationship between exposure concentration and the decrease in respiratory rate followed Michaelis-Menten equations. Two estimates of each agonist-receptor dissociation constant were obtained, one from the Michaelis-Menten equation and one from the threshold (RD-0) of the log concentration-effect curve. The values were equal and thus one receptor type could account for the activation process. The hydrophobic properties of the receptor biophase were found to approach that of the internal part of the bilayer membrane. It therefore follows that the receptor-air partition coefficients increase with the size of the ketones, thus accounting for the observed increase in potency. Estimates of Threshold Limit Values (TLV) were obtained and compared with established values. Close agreements were found for methyl propyl ketone and methyl amyl ketone, but not for methyl butyl ketone, where the neurotoxic effect constituted a more sensitive endpoint than sensory irritation.
Assuntos
Irritantes/toxicidade , Cetonas/toxicidade , Pneumopatias/induzido quimicamente , Receptores de Droga/efeitos dos fármacos , Limiar Sensorial/efeitos dos fármacos , Administração por Inalação , Anestesia , Animais , Fenômenos Químicos , Físico-Química , Oftalmopatias/induzido quimicamente , Irritantes/administração & dosagem , Cetonas/administração & dosagem , Cetonas/química , Masculino , Camundongos , Mucosa Nasal/efeitos dos fármacos , Terminações Nervosas/efeitos dos fármacos , Pletismografia TotalRESUMO
The burning and painful effect in nose and eyes, termed sensory irritation, of methyl ethyl ketone vapours was investigated in a mouse bioassay. Sensory irritation is mediated via the trigeminal nerves and results in a reflexively induced decrease in respiratory rate in mice. Methyl ethyl ketone was used as a model substance for ketones. At the lower exposure concentrations a partial fading (desensitization) of the response was seen. Little desensitization was seen at higher concentrations. n-Propanol, a model substance for alcohols, desensitized the receptor at all exposure levels. Preexposure to propanol did not influence the response at high methylethyl ketone concentrations. This suggests that the two substances bind to different receptive sites with different properties, if the ketone response is due to a high exposure concentration. A decrease in tidal volume was also mediated from the upper respiratory tract. The tidal volume effect is mediated by nerves different from those mediating the frequency response, as the time-response relationship, the desensitization pattern, the maximum response and the apparent dissociation constants were different for the two types of effect. Neither the location nor the perceived response related to the volume response is known.
Assuntos
Butanonas/toxicidade , Irritantes/toxicidade , Respiração/efeitos dos fármacos , Células Receptoras Sensoriais/efeitos dos fármacos , 1-Propanol/toxicidade , Animais , Bioensaio , Relação Dose-Resposta a Droga , Olho/efeitos dos fármacos , Masculino , Camundongos , Nariz/efeitos dos fármacosRESUMO
One- and two-dimensional 1H NMR spectroscopy were used to characterize the binding of a homodimeric thiazole orange dye, 1,1'-(4,4,8,8-tetramethyl-4,8-diazaundecamethylene)-bis-4-(3 -methyl-2,3-dihydro-(benzo- 1,3-thiazole)-2-methylidene)-quinolinium tetraiodide (TOTO), to various double-stranded DNA oligonucleotides containing symmetric (5'-pyr-pyr-pu-pu-3')2 or (5'-pu-pu-pyr-pyr-3')2 sequences. It was found that TOTO binds preferentially to oligonucleotides containing a (5'-CTAG-3')2 or a (5'-CCGG-3')2 sequence. Binding to the (5'-CCGG-3')2 sequence is less favored than to the (5'-CTAG-3')2 sequence. The complexes of TOTO with d(CGCTAGCGCTAGCG)2 (10) and d(CGCTAGCCGGCG):d(CGCCGGCTAGCG) (11) oligonucleotides, each containing two preferential binding sites, was also examined. In both cases TOTO forms mixtures of 1:1 and 1:2 dsDNA-TOTO complexes in ratios dependent on the relative amount of TOTO and the oligonucleotides in the sample. Binding of TOTO to the two oligonucleotides is sequence selective at the (5'-CTAG-3')2 and (5'-CCGG-3')2 sites. The 1H NMR spectra of both the 1:2 complexes and the three different 1:1 complexes have been assigned. A slight negative cooperativity is observed in formation of the 1:2 complexes. The ratio between the two different 1:1 complexes formed with oligonucleotide 11 is 2.4 in favor of binding to the (5'-CTAG-3')2 site. This is very similar to results obtained when the two sites are in different oligonucleotides. Thus the distribution of TOTO among the (5'-CTAG-3')2 and (5'-CCGG-3')2 sites is independent of whether the two sites are in the same or two different oligonucleotides.
Assuntos
DNA/química , Oligonucleotídeos/química , Tiazóis/química , Sequência de Bases , Benzotiazóis , Corantes Fluorescentes/química , Dados de Sequência Molecular , Purinas , Pirimidinas , QuinolinasRESUMO
We have used one and two dimensional 1H NMR spectroscopy to characterize the binding of a homodimeric thiazole orange dye, 1,1'-(4,4,8,8-tetramethyl-4,8-diaza-undecamethylene)-bis-4- (3-methyl-2,3-dihydro-(benzo-1,3-thiazole)-2-methylidene)-quinolin ium tetraiodide (TOTO), to various double stranded DNA oligonucleotides. TOTO binds strongly to all the oligonucleotides used, but usually more than one complex is observed and exchange between different binding sites broadens the lines in the NMR spectra. Complete precipitation occurs when TOTO is bound to small oligonucleotides. Binding to larger oligonucleotides occurs by bis-intercalation. The 1:1 complex of TOTO with the oligonucleotide d(CCGACTGATGC):d (GCATCAGTCGG) gave only one complex that was shown to be a bis-intercalation in the CTGA:TCAG binding site. The binding to this site was also characterized by studying the TOTO complex with the d(CCGCTGAGC):d(GCTCAGCGG) oligonucleotide. NOE connectivities and molecular modelling were used to characterize the complex. The 1:1 complex of TOTO with the oligonucleotide d(CCGCTAGCG):d(CGCTAGCGG) containing a CTAG:CTAG binding site was similarly characterized by NMR. It was concluded that the binding of TOTO to larger oligonucleotides is site selective with CTAG:CTAG as the preferred binding site.
Assuntos
DNA/química , Corantes Fluorescentes/química , Substâncias Intercalantes/química , Tiazóis/química , Sequência de Bases , Benzotiazóis , Espectroscopia de Ressonância Magnética , Dados de Sequência Molecular , Oligodesoxirribonucleotídeos/química , QuinolinasRESUMO
Respiratory rate (f), tidal volume (VT) and carbon dioxide production (VECO2) were measured in restrained, conscious CF-1 mice. Mean f +/- S.D. and mean VT +/- S.D. were 270 +/- 8 breaths/min. and 0.123 +/- 0.024 ml (STPD) for male, and 274 +/- 15 breaths/min. and 0.115 +/- 0.023 ml (STPD) for female mice, respectively. VECO2 was obtained from a rebreathing (closed loop) system. The maximum VECO2 (STPD) amounted to 95.5 +/- 15.4 ml/(kg min.) in males and to 72.7 +/- 4.2 ml/(kg min.) in females. The CO2 concentration in the closed loop system increased slowly during a 30 min. rebreathing period and reached a concentration of about 2.7%. No effect was seen on f and on VT. Dynamic (abrupt) exposure up to 10.3% CO2 had no effect on f in male mice, whereas VT increased from 112% (2.3% CO2) to 181% (10.3% CO2). The estimated O2 concentrations decreased from 20.5% to 18.7% with increasing CO2 exposure. The equivalent CO2 experiments with O2 kept at 16% by N2 administration showed that the lower O2 concentration added an additional drive on the respiratory centre.
Assuntos
Dióxido de Carbono/metabolismo , Respiração/fisiologia , Animais , Dióxido de Carbono/farmacologia , Estado de Consciência , Feminino , Pulmão/fisiologia , Masculino , Camundongos , Volume de Ventilação Pulmonar/fisiologiaRESUMO
Quantitative structure-activity relationships (QSAR) have suggested the importance of hydrogen bonding in relation to activation of the sensory irritant receptor by nonreactive volatile organic chemicals. To investigate this possibility further, three model compounds with different hydrogen bond acidity, trifluoroethanol, hexafluoroisopropanol and methyl hexafluoroisopropyl ether, were selected for study. The potency of each chemical is obtained from the concentration necessary to reduce respiratory rate in mice by 50% (RD50). The RD50 values obtained were: methyl hexafluoroisopropyl ether (> or = 160,000 ppm), trifluoroethanol (11,400-23,300 ppm), and hexafluoroisopropanol (165 ppm). QSAR showed that trifluoroethanol and methyl hexafluoroisopropyl ether behaved as predicted as nonreactive sensory irritants, whereas hexafluoroisopropanol was much more potent than predicted. The higher than predicted potency of hexafluoroisopropanol could be due to a coupled reaction, involving both strong hydrogen bonding and weak Brönsted acidity. A concerted reaction could thus be more efficient in activation of the receptor. Hydrogen bonding properties and concerted reactions may be important in the activation of the sensory irritant receptor by nonreactive volatile organic chemicals.