RESUMO
AIM: To define practical limitations of diagnostic image quality for recently introduced turbo high-pitch scan mode (THP) in third-generation dual-source computed tomography (CT). MATERIALS AND METHODS: Two hundred and twenty-nine consecutive patients undergoing CT coronary angiography were included in this retrospective single-centre analysis. A contrast-enhanced volume dataset was acquired in THP. Image quality of coronary segments was classified as diagnostic or non-diagnostic by three blinded readers. Segments were stated as non-diagnostic if at least one of three readers could neither exclude nor confirm significant stenoses. Multivariable logistic regression was used to assess relationships between number of non-diagnostic segments and common influencing factors. RESULTS: Median effective radiation dose was 0.6 (interquartile range [IQR], 0.4-0.8) mSv overall and 0.3 (IQR, 0.3-0.4) mSv in the 70 kV subgroup of this middle aged, predominantly pre-obese cohort (age: 61 [IQR, 52-67] years; body mass index [BMI]: 26 [IQR, 23-29] kg/m2) with a low-moderate median Agatston score (AS) 0 (IQR, 0-70). Diagnostic image quality was found in 98.1% of 3,678 coronary segments. AS was independently associated with diagnostic image quality (B=0.34; p=0.02), whereas heart rate, BMI, and presence of arrhythmia were not. The portion of diagnostic coronary segments decreased slightly in obese patients with heart rates >65 beats/min and dropped significantly in patients with an AS >600 (p=0.003). CONCLUSION: THP enables CT coronary angiography with minimal radiation exposure and is most appropriate in non-obese patients with stable sinus rhythm ≤65 beats/min and a calcium score ≤600.
Assuntos
Angiografia por Tomografia Computadorizada/métodos , Estenose Coronária/diagnóstico por imagem , Idoso , Técnicas de Imagem de Sincronização Cardíaca , Meios de Contraste , Angiografia Coronária/métodos , Feminino , Humanos , Iopamidol/análogos & derivados , Masculino , Pessoa de Meia-Idade , Exposição à Radiação , Interpretação de Imagem Radiográfica Assistida por Computador , Estudos RetrospectivosRESUMO
The upper esophageal sphincter (UES) forms a barrier between the pharynx and the esophagus. When closed, the barrier function serves to prevent reflux and aerophagia; when open, swallowing, belching and vomiting are possible. The closing muscles include caudal parts of the inferior pharyngeal sphincter and cranial parts of the upper esophagus musculature. Sphincter opening is achieved by muscles that insert from the outside to connect to the larynx and pharynx in the sphincter region. The closing muscles are innervated by branches of the glossopharyngeal and vagal nerves, and central control is probably mediated by several reflexes. This article presents an overview of the current understanding of the complex UES anatomy.
Assuntos
Esfíncter Esofágico Superior/anatomia & histologia , Modelos Anatômicos , HumanosRESUMO
The upper esophageal sphincter (UES) forms a barrier between the pharynx and the esophagus. When opened, the UES allows the food bolus to pass into the esophagus, as well as permitting emesis and eructation. The basal sphincter tone constitutes a barrier function which serves to prevent reflux and passive aerophagia in the case of deep breathing. Basal sphincter tone is dependent on several influencing factors; during swallowing, sphincter opening and closure follow a complex multiphase pattern. This article presents an overview of the current understanding of UES physiology.
Assuntos
Deglutição/fisiologia , Esfíncter Esofágico Inferior/fisiologia , Esôfago/fisiologia , Laringe/fisiologia , Modelos Biológicos , Contração Muscular/fisiologia , Faringe/fisiologia , HumanosRESUMO
The acquisition of specific antibodies is paramount to protect children against pneumococcal diseases, and a better understanding of how age, ethnicity and/or Streptococcus pneumoniae (Spn) nasopharyngeal carriage influence the acquisition of antibodies to pneumococcal surface proteins (PSP) is important for the development of novel serodiagnostic and immunisation strategies. IgG antibody titres against three conserved PSP (PhtD, PcpA and PrtA) in the sera of 451 healthy children aged 1 to 24 months from Israel [Jewish (50.1 %) and Bedouin (49.9 %)] were measured by enzyme-linked immunosorbent assay (ELISA), while nasopharyngeal swabs from these children were assessed for the presence of Spn. Globally, anti-PhtD and anti-PrtA geometric mean concentrations (GMC; EU/ml) were high at <2.5 months of age [PhtD: 35.3, 95 % confidence interval (CI) 30.6-40.6; PrtA: 71.2, 95 % CI 60-84.5], was lower at 5-7 months of age (PhtD: 10, 95 % CI 8-12.4; PrtA: 17.9, 95 % CI 14.4-22.1) and only increased after 11 months of age. In contrast, an increase in anti-PcpA was observed at 5-7 months of age. Anti-PcpA and anti-PrtA, but not anti-PhtD, were significantly higher in Bedouin children (PcpA: 361.6 vs. 226.3, p = 0.02; PrtA: 67.2 vs. 29.5, p < 0.001) in whom Spn nasopharyngeal carriage was identified earlier (60 % vs. 38 % of carriers <6 months of age, p = 0.002). Spn carriage was associated with significantly higher anti-PSP concentrations in carriers than in non-carriers (p < 0.001 for each PSP). Thus, age, ethnicity and, essentially, nasopharyngeal carriage exert distinct cumulative influences on infant responses to PSP. These specific characteristics are worthwhile to include in the evaluation of pneumococcal seroresponses and the development of new PSP-based vaccines.
Assuntos
Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Proteínas de Transporte/imunologia , Portador Sadio/epidemiologia , Proteínas de Membrana/imunologia , Infecções Pneumocócicas/epidemiologia , Streptococcus pneumoniae/imunologia , Fatores Etários , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Etnicidade , Humanos , Imunoglobulina G/sangue , Lactente , Peptídeos e Proteínas de Sinalização Intracelular , Israel/epidemiologia , Masculino , Nasofaringe/microbiologia , Rede SocialRESUMO
Complex association analysis of copaxone (glatiramer acetate) immunotherapy efficacy with allelic polymorphism in the number of immune response genes, which encode interferone beta (IFNB1), transforming growth factor beta1 (TGFB1), interferone gamma (IFNG), tumor necrosis factor (TNF), interferon alpha/beta receptor 1 (IFNAR1), CC chemokine receptor 5 (CCR5), interleukin 7 receptor alpha subunit (IL7RA), cytotoxic T-lymphocyte antigen 4 (CTLA4) and HLA class II histocompatibility antigen beta chain (DRB1) was performed with APSampler algorithm for 285 multiple sclerosis patients of Russian ethnicity. The results show evidence for the contribution of polymorphic variants in CCRS, DRB1, IFNG, TGFB1, IFNAR1, IL7RA and, probably, TNF and CTLA4 genes to copaxone treatment response. Single alleles of CCR5 and DRB1 genes are reliably associated with treatment efficacy. Carriage of allelic variants of other above mentioned genes contribute with reliable effect to copaxone treatment response as part of bi- and three-allelic combinations only. Present investigation may support basis toward the future possibility of prognostic test realization, which can provide a personal choice of immunomodulatory treatment for a patient with multiple sclerosis.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/genética , Peptídeos/uso terapêutico , Adjuvantes Imunológicos/farmacocinética , Biomarcadores Farmacológicos , Antígeno CTLA-4/genética , Frequência do Gene , Estudos de Associação Genética , Acetato de Glatiramer , Cadeias HLA-DRB1/genética , Humanos , Interferon beta/genética , Interferon gama/genética , Subunidade alfa de Receptor de Interleucina-7/genética , Peptídeos/farmacocinética , Polimorfismo de Nucleotídeo Único , Receptores CCR5/genética , Fator de Crescimento Transformador beta1/genética , Fator de Necrose Tumoral alfa/genéticaRESUMO
Cardiovascular magnetic resonance imaging is one of the most important diagnostic modalities in the evaluation of cardiomyopathies. However, significant limitations are the complex and time-consuming workflows and the need of contrast agents. The aim of this multi-center retrospective study was to assess workflows and diagnostic value of a short, contrast agent-free cardiac magnetic resonance protocol. 160 patients from Heidelberg, Germany and 119 patients from Montreal, Canada with suspected cardiomyopathy and 20 healthy volunteers have been enrolled. Scans were performed at a 1.5Tesla or 3Tesla scanner in Heidelberg and at a 3Tesla scanner in Montreal. We used single-slice T1 map only. A stepwise analysis of images has been performed. The possible differential diagnosis after each step has been defined. T1-values and color-encoded T1 maps significantly contributed to the differential diagnosis in 54% of the cases (161/299); the final diagnosis has been done without late gadolinium enhancement images in 83% of healthy individuals, in 99% of patients with dilated cardiomyopathy, in 93% of amyloidosis patients, in 94% of patients with hypertrophic cardiomyopathy and in 85% of patients with hypertensive heart disease, respectively. Comparing the scan time with (48 ± 7 min) vs. without contrast agent (23 ± 5 min), significant time saving could be reached by the short protocol. Subgroup analysis showed the most additional diagnostic value of T1 maps in amyloidosis and hypertrophic cardiomyopathy or in confirmation of normal findings. In patients with unclear left ventricular hypertrophy, a short, non-contrast protocol can be used for diagnostic decision-making, if the quality of the T1 map is diagnostic, even if only one slice is available.
RESUMO
We present an unbiased estimator of the total number of alveolar structures distal to the transition from a bronchiole to an alveolar duct system ('ventilatory units', VUs). In species without respiratory bronchioles, including mice, the number of VUs is equivalent to the number of acini. The acinus is a functional unit of gas exchange, defined as a parenchymal unit distal to a terminal bronchiole in which all airways contain alveoli and thus participate in gas exchange. The estimator combines two different estimators of the number of VUs: (1) an estimator derived from the Euler number of all the openings of the bronchial tree and (2) an estimator derived from direct counts of topological changes occurring at bronchiole-alveolar duct junctions. Combining the two estimators eliminates the requirement to be able to identify even vanishingly small pieces of bronchial tissue in physical disectors. We implemented the fractionator estimator in five adult mice lungs using physical fractionators with varying but known sampling fractions (Horvitz-Thompson estimator). We obtained total values of about 4200 VUs (CV = 0.05) in 21-day-old and 4480 (CV = 0.06) in 69-day-old animals. Being fractionator estimates, these total numbers are independent of shrinkage. The densities of VUs per unit volume of tissue (values corrected for tissue shrinkage) were similar in left and right lungs.
Assuntos
Biometria/métodos , Pulmão/anatomia & histologia , Pulmão/fisiologia , Alvéolos Pulmonares/anatomia & histologia , Alvéolos Pulmonares/fisiologia , Ventilação Pulmonar , Animais , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Modelos BiológicosRESUMO
Carriage frequencies of alleles and genotypes of functionally important polymorphous loci of some inflammation genes: proinflammatory cytokines genes IL-6, LTA and TNF, anti-inflammatory cytokine gene TGFB1 and CC chemokine receptor 5 gene CCR5 were analyzed in the patients with myocardial infarction (MI) of Russian ethnic descent (199 cases) and in the control group of the same ethnic descent (142 controls). Complex analysis using APSampler algorithm revealed MI association with carriage of all polymorphous variants studied, as individual risk factors (insertion/deletion polymorphism of CCR5 and SNP G252A LTA) or only in combination with other alleles/genotypes. Carriage of bi- or triallelic combinations was associated with MI more significantly than carriage of any their subsets: single alleles or allele pairs. Protective triallelic combination d*CCR5 + 252G*LTA(+) -174C*Ll-6 was found to be most significant (p = 0.0006, OR = 0.23, CI = 0.090-0.56). Separate analysis of genetic susceptibility to MI for men and women displayed sexual dimorphism for CCR5 gene.
Assuntos
Citocinas/genética , Predisposição Genética para Doença , Mutação INDEL , Mediadores da Inflamação , Infarto do Miocárdio/imunologia , Polimorfismo de Nucleotídeo Único , Caracteres Sexuais , Adulto , Idoso , Alelos , Feminino , Humanos , Inflamação/etnologia , Inflamação/genética , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etnologia , Receptores CCR5 , Federação RussaRESUMO
The optimal timing of exogenous surfactant application to reduce pulmonary injury and dysfunction was investigated in a rat lung ischaemia and reperfusion injury model. Lungs were subjected to flush perfusion, surfactant instillation, cold ischaemia (4 degrees C, 4 h) and reperfusion (60 min). Animals received surfactant before (group 1) or at the end (2) of ischaemia, or during reperfusion (3) or not at all (4). Control groups included "worst case" without Perfadex and surfactant (5), "no injury" without (6) or with surfactant (7), and ischaemia with pre-ischaemic surfactant (8). Intra-alveolar oedema and blood-air barrier injury were estimated by light and electron microscopic stereology. Perfusate oxygenation and pulmonary arterial pressure (P(pa)) were determined during reperfusion in groups 1 to 4. Intra-alveolar oedema was almost absent in groups 1, 6, 7 and 8, pronounced in 2, 3 and 4, and severe in 5. Blood-air barrier injury was moderate in groups 1 and 8, slightly pronounced in 2, 3 and 4, extensive in 5 and almost absent in 6 and 7. Perfusate oxygenation was significantly higher in group 1 compared with groups 2 to 4. P(pa) did not differ between the groups. In conclusion, exogenous surfactant attenuates intra-alveolar oedema formation and blood-air barrier damage and improves perfusate oxygenation in the rat lung, especially when applied before ischaemic storage.
Assuntos
Surfactantes Pulmonares/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Animais , Citratos/farmacologia , Edema/patologia , Humanos , Isquemia/patologia , Pulmão/patologia , Lesão Pulmonar/tratamento farmacológico , Masculino , Microscopia Eletrônica/métodos , Microscopia Eletrônica de Transmissão/métodos , Perfusão , Ratos , Ratos Sprague-DawleyRESUMO
Carriage frequencies of alleles and genotypes of 10 functionally important single nucleotide polymorphisms that are located in genes FGA, FGB, APOE, LPL, ACE and CMA1 were analyzed in the ischemic stroke (IS) patients of Russian ethnic descent and in the control group of the same ethnic descent and of similar gender and age. Comparison between patients and control group revealed no significant differences in frequencies of individual alleles and genotypes for all the polymorphic loci studied. However, complex analysis of genetic predisposition using APSampler algorithm revealed carriage of allele (-491A) APOE as a predisposing factor for IS (p = 0.044, OR 3.8, 95% CI 1.0-15.1). Accordingly, carriage of genotype (-491T/T) APOE was associated with resistance to IS (p = 0.044, OR 0.26, 95% CI 0.07-1.0). The allele -249C FGB carriage addition to this genotype enhances its protective properties, p-value of the combination is 2-fold lower than that of the genotype (-491T/T) APOE (OR 0.17, 95% CI 0.04-0.8). Two more protective combinations were identified: biallelic (-427C) APOE + (1595G) LPL and triallelic (-491C) APOE + (1595G) LPL + (-1903G) CMAI (in both cases p = 0.0052, OR 0.18, 95% CI 0.05-0.66). Overall, involvement in formation of the risk of IS development in Russians was evidenced for alleles of four genes: APOE, FGB, LPL and CMA1, where APOE gene involvement was evidenced for alleles of two polymorphic loci, -491T and -427C. Linkage analysis suggested that involvement of these loci in insusceptibility to IS is mutually independent.
Assuntos
Alelos , Isquemia Encefálica/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/genética , Isquemia Encefálica/etnologia , Feminino , Genótipo , Humanos , Masculino , Federação Russa , Acidente Vascular Cerebral/etnologiaRESUMO
The mouse Foxq1 gene, also known as Hfh1, encodes a winged helix/forkhead transcription factor. In adult mice, Foxq1 is highly expressed in kidney and stomach. Here, we report that Foxq1 is expressed during prenatal and postnatal stomach development and the transcripts are restricted to acid secreting parietal cells. Mice homozygous for a deletion of the Foxq1 locus on a 129/Sv x C57BL/6J hybrid genetic background display variable phenotypes consistent with requirement of the gene during embryogenesis. Approximately 50% of Foxq1-/- embryos die in utero. Surviving homozygous mutants are normal and fertile, and have a silky shiny coat. Although the parietal cell development is not affected in the absence of Foxq1, there is a lack of gastric acid secretion in response to various secretagogue stimuli. Ultrastructural analysis suggests that the gastric acid secretion defect in Foxq1-deficient mice might be due to impairment in the fusion of cytoplasmic tubulovesicles to the apical membrane of secretory canaliculi.
Assuntos
Perda do Embrião/genética , Perda do Embrião/fisiopatologia , Fatores de Transcrição Forkhead/deficiência , Fatores de Transcrição Forkhead/genética , Ácido Gástrico/metabolismo , Animais , Sequência de Bases , Northern Blotting , Citogenética , Primers do DNA/genética , Feminino , Fatores de Transcrição Forkhead/fisiologia , Mucosa Gástrica/embriologia , Mucosa Gástrica/metabolismo , Mucosa Gástrica/ultraestrutura , Regulação da Expressão Gênica no Desenvolvimento , Marcação de Genes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia Eletrônica de Transmissão , Células Parietais Gástricas/metabolismo , Células Parietais Gástricas/ultraestrutura , Gravidez , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND: Optimal allograft protection is essential in lung transplantation to reduce postoperative organ dysfunction. Although intravenous prostanoids are routinely used to ameliorate reperfusion injury, the latest evidence suggests a similar efficacy of inhaled prostacyclin. Therefore, we compared donor lung-pretreatment using inhaled lioprost (Ventavis) with the commonly used intravenous technique. METHODS: Five pig lungs were each preserved with Perfadex and stored for 27 hours without (group 1) or with (group-2, 100 prior aerosolized of iloprost were (group 3) or iloprost (IV). Following left lung transplantation, hemodynamics, Po(2)/F(i)o(2), compliance, and wet-to-dry ratio were monitored for 6 hours and compared to sham controls using ANOVA analysis with repeated measures. RESULTS: The mortality was 100% in group 3. All other animals survived (P < .001). Dynamic compliance and PVR were superior in the endobronchially pretreated iloprost group as compared with untreated organs (P < .05), whereas oxygenation was comparable overall W/D-ratio revealed significantly lower lung water in group 2 (P = .027) compared with group 3. CONCLUSION: Preischemic alveolar deposition of iloprost is superior to IV pretreatment as reflected by significantly improved allograft function. This strategy offers technique to optimize pulmonary preservation.
Assuntos
Sobrevivência de Enxerto/efeitos dos fármacos , Iloprosta/uso terapêutico , Transplante de Pulmão/fisiologia , Traumatismo por Reperfusão/prevenção & controle , Administração por Inalação , Animais , Iloprosta/administração & dosagem , Injeções Intravenosas , Transplante de Pulmão/efeitos adversos , Modelos Animais , Inibidores da Agregação Plaquetária/uso terapêutico , SuínosRESUMO
To provide reliable K(d) data for Cs required for the performance assessment of cement-based radioactive waste repositories, two complementary approaches were followed. First, Cs sorption was determined on a range of hydrated cement paste (HCP) and mortar samples of CEM I and CEM V for different degradation states and solution compositions, as well as on some single mineral phases. Second, a surface complexation-diffuse layer model previously developed by Pointeau et al. [Pointeau, I., Marmier, N., Fromage, F., Fedoroff, M., Giffaut, E., 2001. Cs and Pb uptake by CSH phases of hydrated cement. Material Research Society Symposium Proceedings, 663, 105-113] for Cs sorption on synthetic CSH phases was simplified to facilitate its application to whole HCP and mortars or concrete, following re-assessment of the model parameters. All measurements were compared with model predictions. The sorption data obtained on the different solid phases as a function of conditions corroborate that CSH minerals are the main sorbing phase for Cs in HCP. The data also clearly show the important influence of pH and the dissolved concentration of Na, K and Ca on K(d). It is further suggested that a decrease of pH is concomitant with a decrease of the Ca/Si ratio and a corresponding increase in surface sites with high affinity for Cs and, thus, K(d). Elevated concentrations of cations able to compete with Cs for these sites lead to a decrease of K(d), on the other hand. The simplified model was applied to the sorption measurements performed within this study as well as to a variety of literature data, mainly K(d) values for a variety of fresh HCP and mortar or concrete samples based on different samples of Ordinary Portland Cement as well as blended cements. The results show that the model can be applied reasonably well to a very large variety of conditions in terms of solid and solution compositions that cover a range of K(d) values from 10(-4) to ca. 3.2m(3)/kg. The large scatter typically observed for Cs sorption, especially on fresh HCP samples prepared from different formulations, can be explained quantitatively by the variable concentrations of Na and K in the respective solutions, which compete with Cs for fixation sites. On the other hand, the comparatively uniform conditions in degraded HCP typically render the prediction of K(d) values less uncertain than in case of fresh HCP.
Assuntos
Césio/química , Materiais de Construção , Modelos Teóricos , Água/química , Concentração de Íons de HidrogênioRESUMO
To maintain normal blood flow, pressure overload in both arteries and veins requires a structural adaptation of the vessel wall (remodelling) that involves smooth muscle cell (SMC) hypertrophy and/or hyperplasia. Due to its potent vasoconstrictor and growth-promoting effects, endothelin-1 (ET-1) is a likely candidate to initiate and/or promote remodelling in blood vessels exposed to a chronic increase in blood pressure. To test this hypothesis, isolated segments of the rabbit carotid artery and jugular vein were perfused at different levels of intraluminal pressure. In both types of segments, pressure overload (160 and 20 mmHg, respectively) resulted in an increase in endothelial prepro-ET-1 and SMC endothelin B receptor (ETB-R) expression. Moreover, in pressurised segments from the carotid artery an ETB-R antagonist-sensitive increase in SMC apoptosis in the media was observed, while in the vein medial SMC started to proliferate. Isolated SMC from these rabbit blood vessels as well as from the aorta and vena cava of the rat, when cultured on a collagen or laminin matrix, uniformly revealed an ETB-R-mediated increase in apoptosis upon exposure to mechanical deformation plus exogenous ET-1 (10 nmol/L). However, when grown on a fibronectin matrix, the cultured SMC did not respond with an increase in apoptosis under otherwise identical experimental conditions. These findings suggest that deformation-induced activation of the endothelin system in the vessel wall not only plays a crucial role in remodelling, but that the structural components of the vessel wall, in particular the cell-matrix interaction, determine how SMC respond phenotypically to these changes in gene expression.
Assuntos
Apoptose , Proteínas da Matriz Extracelular/fisiologia , Músculo Liso Vascular/ultraestrutura , Receptores de Endotelina/fisiologia , Animais , Artérias Carótidas/metabolismo , Artérias Carótidas/ultraestrutura , Caspase 3 , Caspases/metabolismo , Diferenciação Celular , Divisão Celular , Cromatina/ultraestrutura , Técnicas de Cultura , Antagonistas dos Receptores de Endotelina , Endotelina-1/genética , Endotelina-1/metabolismo , Masculino , Músculo Liso Vascular/metabolismo , Oligopeptídeos/farmacologia , Peptídeos Cíclicos/farmacologia , Piperidinas/farmacologia , Pressão , RNA Mensageiro/biossíntese , Coelhos , Ratos , Ratos Wistar , Receptor de Endotelina B , Receptores de Endotelina/genética , Estresse Mecânico , Veias/ultraestruturaRESUMO
Normal human serum contains a 230,000 Mr protein that inhibits fibroblast chemotactic and random migration. This serum inhibitor of fibroblast migration (SIFM) is a heat-stable, trypsin-sensitive protein with a pI of 4.8 that reversibly inhibits the random and chemotactic migration of fibroblasts in vitro. Although SIFM effectively inhibits the chemotaxis of fibroblasts to interstitial collagens, fibronectin, lymphocyte-derived chemotactic factor for fibroblasts, and serum-derived chemotactic factor, it does not alter the chemotactic migration of human peripheral blood neutrophils or monocytes, and does not act as a cytotoxin to human dermal fibroblasts. The SIFM appears to act through a cell-directed mechanism to alter the fibroblast's ability to migrate. Serum inhibitor of fibroblast migration may function in vivo to modulate fibroblast migration under physiologic and pathologic conditions.
Assuntos
Proteínas Sanguíneas/isolamento & purificação , Quimiotaxia/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Proteínas Sanguíneas/farmacologia , Células Cultivadas , Fatores Quimiotáticos/farmacologia , Depressão Química , Fibroblastos/fisiologia , Humanos , Recém-Nascido , Masculino , Monócitos/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , PênisRESUMO
We used electron spectroscopic imaging (ESI) and electron energy loss spectroscopy (EELS) to compare multilamellar bodies (MLB) of Type II alveolar epithelial cells with MLB-like structures that are present in various alveolar septal cells after fixation with tannic acid. Despite their structural similarity in conventional transmission electron microscopy, the phosphorus signal recorded by both ESI and EELS was considerably higher in multilamellar bodies than in MLB-like structures. This indicates that they are different in chemical composition.
Assuntos
Taninos Hidrolisáveis/toxicidade , Organelas/ultraestrutura , Alvéolos Pulmonares/ultraestrutura , Animais , Microscopia Eletrônica/métodos , Organelas/efeitos dos fármacos , Alvéolos Pulmonares/efeitos dos fármacos , SuínosRESUMO
BACKGROUND: The poor tolerance of the lung to ischemia and reperfusion (IR) still represents one of the limitations in clinically successful lung transplantation. Modified Euro-Collins (EC) is routinely used in lung preservation, but alternative solutions have been developed for improvement of pulmonary preservation. Celsior is an extracellular solution that has significantly reduced the IR-induced pulmonary damage in animal studies. So far, no extensive experimental studies exist concerning the influence of Celsior on pulmonary gas exchange following IR. METHODS: In an extracorporeal rat lung model 10 lungs, each, were preserved with Celsior (CE) and Celsior/prostacyclin (CEPC, 6 microg/100 ml) at 4 degrees and 15 degrees C, each, and compared to low-potassium Euro-Collins (EC-40, 40 mmol/liter potassium). After 2 hours of ischemia lungs were reventilated and reperfused using a roller pump. Oxygenation in terms of oxygen partial tension in the left atrial effluent, pulmonary vascular resistance (PVR), peak inspiratory pressure, and wet/dry ratio were monitored for 50 minutes. Furthermore, edema formation was evaluated by light microscopy. Statistical analysis was performed using ANOVA models. RESULTS: Compared to the EC-40 group, oxygenation was increased and amount of edema was reduced in most Celsior-preserved organs (p<0.032) with exception of the CEPC group at 4 degrees C (p = 0.06). Additional application of prostacyclin did not have any significant effect on oxygenation in the Celsior group. However, after temperature elevation of the CEPC perfusate to 15 degrees C, a superior partial tension of oxygen was observed (p<0.023) in contrast to the 4 degrees C groups CE and CEPC. The lowest PVR was found in the CE 4 degrees C group (p<0.02). CONCLUSIONS: Celsior provides better lung preservation than EC-40 solution. Application of prostacyclin at higher perfusate temperatures results in additional functional improvement. In vivo experiments and ultrastructural analysis are warranted for further evaluation of Celsior in lung preservation.
Assuntos
Epoprostenol/farmacologia , Pulmão/efeitos dos fármacos , Soluções para Preservação de Órgãos/farmacologia , Preservação de Órgãos/métodos , Animais , Dissacarídeos/farmacologia , Eletrólitos/farmacologia , Glutamatos/farmacologia , Glutationa/farmacologia , Histidina/farmacologia , Soluções Hipertônicas/farmacologia , Pulmão/anatomia & histologia , Pulmão/fisiologia , Masculino , Manitol/farmacologia , Preservação de Órgãos/estatística & dados numéricos , Oxigênio/fisiologia , Pressão Parcial , Perfusão/métodos , Perfusão/estatística & dados numéricos , Ratos , Ratos Sprague-Dawley , TemperaturaRESUMO
In ten cases of clinical human single-lung transplantation, the nontransplanted Euro-Collins-preserved contralateral lungs were examined using electron microscopy to determine the effects of ischaemia on the bronchiolar epithelium. Existing structural damage at the time of transplantation was characterized using this approach, and nine nonpreserved canine single lungs were also investigated to identify the impact of ischaemia. The study revealed a significant correlation between the duration of ischaemia and the mitochondrial surface-to-volume ratio, which can serve as a morphometric criterion for mitochondrial damage, in canine lungs. However, this correlation was not found in the human donor lungs. Further examination of human donor lungs showed slight to moderate damage to the endoplasmic reticulum and nuclear chromatin. In addition, various degrees of damage to mitochondrial structure, ranging from inconspicuous to severe, were found. The mitochondrial surface-to-volume ratio can be considered to be a suitable criterion for the quantification of ischaemic damage of the bronchiolar epithelium under experimental conditions. Ultrastructural analysis of human donor lungs revealed intact bronchiolar epithelial cell structures at the time of transplantation, reflecting adequate organ preservation with Euro-Collins solution.
Assuntos
Brônquios/irrigação sanguínea , Brônquios/ultraestrutura , Isquemia/patologia , Preservação de Órgãos , Adolescente , Adulto , Animais , Cães , Epitélio/irrigação sanguínea , Epitélio/ultraestrutura , Feminino , Humanos , Soluções Hipertônicas , Masculino , Microscopia Eletrônica , Microscopia Eletrônica de Varredura , Pessoa de Meia-Idade , Mitocôndrias/ultraestruturaRESUMO
Alveolar type II pneumocytes (PII) were studied in 12 human donor lungs perfused with modified Euro-Collins solution during single-lung transplantation (SLTx). While one lung was transplanted, the contralateral donor lung (cDL) was fixed at the time of SLTx for examination by electron microscopy, stereology, and microanalysis. Three groups were then formed: group A (n = 7), cDL without contusions, uneventful early postoperative course; group B (n = 3), cDL with conclusions, uneventful early postoperative course; group C (n = 2), cDL without contusions, early postoperative respiratory dysfunction. The major findings were that the presence of contusions had no effect on PII ultrastructure and that intracellular surfactant-storing lamellar bodies of cDL in group C were characterized by a higher volume-to-surface ratio (VsR) and larger area per cell profile than group A. Correlation analysis based on pooled data (groups A and C) showed that ischaemic time had little effect on PII ultrastructure and bore no relationship to postoperative clinical variables. The duration of preoperative donor intubation had a pronounced influence on ultrastructure and postoperative clinical variables. The stereologically estimated amount of intracellular surfactant and mitochondrial VsR were the only ultrastructural parameters that were significantly associated with early postoperative oxygenation. Lamellar bodies were the only ultrastructural components found to have a significant relationship to postoperative intubation time. The ultrastructural integrity of type II pneumocytes of human donor lungs is an important determinant of early respiratory function following clinical lung transplantation.
Assuntos
Transplante de Pulmão/patologia , Alvéolos Pulmonares/patologia , Alvéolos Pulmonares/ultraestrutura , Doadores de Tecidos , Adolescente , Adulto , Idoso , Células Epiteliais/patologia , Células Epiteliais/ultraestrutura , Feminino , Humanos , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Organelas/patologia , Organelas/ultraestrutura , Complicações Pós-Operatórias/patologia , Traumatismo por Reperfusão/patologiaRESUMO
We tested the hypothesis whether allergic airway inflammation in ovalbumin sensitized and challenged Brown Norway rats is associated with intrinsic surfactant alteration and dysfunction. The determination of intra-alveolar surfactant subtypes and alveolar edema within their original microenvironment is only possible using an ultrastructural stereological approach. Therefore both lungs of control and asthmatic rats were fixed by vascular perfusion. The volume fractions of surfactant subtypes and the epithelial surface fraction covered with alveolar edema were determined by point and intersection counting. Furthermore, lung resistance was measured by means of whole-body plethysmography. The surface activity of surfactant from bronchoalveolar lavage was determined as minimum surface tension at minimal bubble size with a pulsating bubble surfactometer. Compared with controls, in asthmatics (1) the fraction of inactive unilamellar forms was significantly increased from 56% to 66%, (2) the fraction of alveolar epithelium covered with alveolar edema visible by light microscopy was significantly increased from 0.7% to 5.0%, (3) the fraction of alveolar epithelium covered with fluid seen by electron microscopy expanded significantly from 5% to 21%, (4) lung resistance was significantly elevated from 14% to 86% and (5) surface tension was enhanced from 6 mN/m to 12 mN/m. Thus, the inflammatory process after allergen challenge of sensitized Brown Norway rats causes intra-alveolar surfactant alterations. These surfactant alterations might contribute to small airway dysfunction.