Avaliação do tratamento com um inibidor para serinoprotease em modelo experimental de enfisema induzido por exposição à fumaça de cigarro

Introdução: Demonstramos previamente que em modelo experimental de enfisema pulmonar induzido por instilação de elastase, o inibidor de serinoprotease rBmTI-A promoveu a melhora da destruição tecidual em camundongos. Considerando que o tabagismo é o principal fator de risco para o desenvolvimento da Doença Pulmonar Obstrutiva Crônica (DPOC) e que o modelo de exposição à fumaça de cigarro é considerado o que melhor mimetiza esta doença em humanos, este estudo teve por objetivo verificar a ação do inibidor para serinoproteases rBmTI-A sobre os processos fisiopatológicos envolvidos no desenvolvimento do enfisema pulmonar, em modelo de exposição ao tabaco. Métodos: Para a indução do enfisema pulmonar, os animais foram expostos à fumaça de cigarro (duas vezes ao dia/ 30 minutos/ 5 dias por semana/ durante 12 semanas), e os animais controle permaneceram expostos ao ar ambiente. Dois protocolos de tratamento com o inibidor rBmTI-A foram realizados. No primeiro, os animais receberam duas administrações do inibidor rBmTI-A ou de seu veículo (Solução Salina 0,9%) por via intranasal, sendo a primeira após 24h do término das exposições ao cigarro e outra, 7 dias após à primeira instilação do inibidor. No segundo protocolo, os animais receberam 3 administrações do inibidor rBmTI-A, durante o tempo de exposição (1ª dose: 24h antes do início da exposição à fumaça de cigarro; 2ª dose: um mês após o início da exposição; 3ª dose: dois meses após o início). Após o término dos protocolos de exposição e tratamento, os animais foram submetidos aos procedimentos para coleta dos dados de mecânica respiratória e avaliação do Intercepto Linear Médio (Lm). Para o segundo protocolo, realizamos também as medidas para quantificação de fibras de colágeno e elástica, da densidade de células positivas para MAC-2, MMP-12 e 9, TIMP-1, Gp91phox e TNFalfa; no parênquima através de imunohistoquímica, contagem de células polimorfonucleares além da expressão gênica de MMP-12 e 9 no pulmão através de RT-qPCR. Resultados e Discussão: O tratamento com o inibidor para serinoprotease rBmTI-A atenuou o desenvolvimento do enfisema pulmonar apenas no segundo protocolo, quando foi administrado durante a exposição à fumaça de cigarro. Embora os grupos Fumo-rBmTIA e Fumo-VE apresentem aumento de Lm comparados aos grupos controles, houve uma redução deste índice no grupo Fumo-rBmTIA comparado ao grupo Fumo-VE. O mesmo comportamento foi observado para as análises de proporção em volume de fibras de elástica e colágeno no parênquima. Além disto, observamos aumento de macrófagos, MMP-12, MMP-9 e TNFalfa; nos grupos expostos à fumaça de cigarro, mas o tratamento com o inibidor rBmTI-A diminuiu apenas a quantidade de células positivas para MMP-12. Na avaliação da expressão gênica para MMP-12 e 9, não observamos diferença entre os grupos experimentais e o mesmo comportamento foi observado para a quantidade de células polimorfonucleares no parênquima. Além disso, observamos aumento de GP91phox e TIMP-1 nos grupos tratados com rBmTIA. Conclusões: Tais resultados sugerem que o inibidor rBmTI-A não foi efetivo como tratamento da lesão após a doença instalada. Entretanto, atenuou o desenvolvimento da doença quando administrado durante a indução do enfisema, possivelmente através do aumento de GP91phox e TIMP-1, acompanhados pela diminuição de MMP-12.

Small car driver inflatable restraint system evaluation. Volume III: investigation of potential crash survivability of a current production subcompact vehicle equipped with an advanced driver restraint system. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Small car driver inflatable restraint system evaluation. Volume IV - evolving a low mount passenger air cushion restraint system (ACRS) for the Vega subcompact vehicle. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Subcompact vehicle energy absorbing column evaluation and improvement. Volume II: analysis of accident data, statistician/analyst's point of view. Interim report.

National Highway Traffic Safety Administration, Washington, D.C.

Subcompact vehicle energy absorbing column evaluation and improvement. Volume I: analysis of accident data, engineer's point of view. Interim report.

National Highway Traffic Safety Administration, Washington, D.C.

Small car driver inflatable restraint system evaluation, volume II - driver air cushion (ACRS) development for 1976 Vega, Valiant, and Chevette subcompact vehicles. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Subcompact vehicle energy absorbing column evaluation and improvement. Volume III: appendices. Interim report.

National Highway Traffic Safety Administration, Washington, D.C.

Diagnostic motor vehicle inspection demonstration projects, program engineering support. Volume 9 - appendix H: vehicle designs that facilitate or hinder inspection and repair and interchangeability and interface capability of test equipment and vehicles. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

The management and logistics of blood banking : conference proceedings, volume III, June 1-2, 1978, Washington, D. C. /

Volume I, with the title, The logistics of blood transfusion therapy, is the proceedings of the first two symposia presented in 1974-75; volume II is the proceedings of the 1977 conference.

Assessment of volume depletion in children with malaria

Background The degree of volume depletion in severe malaria is currently unknown, although knowledge of fluid compartment volumes can guide therapy. To assist management of severely ill children, and to test the hypothesis that volume changes in fluid compartments reflect disease severity, we measured body compartment volumes in Gabonese children with malaria. Methods and Findings Total body water volume (TBW) and extracellular water volume (ECW) were estimated in children with severe or moderate malaria and in convalescence by tracer dilution with heavy water and bromide, respectively. Intracellular water volume (ICW) was derived from these parameters. Bioelectrical impedance analysis estimates of TBW and ECW were calibrated and bioelectrical impedance analysis measurements were taken daily against dilution methods, until discharge. Sixteen children had severe and 19 moderate malaria. Severe childhood malaria was associated with depletion of TBW (mean [SD] of 37 [33] ml/kg, or 6.7% [6.0%]) relative to measurement at discharge. This is defined as mild dehydration in other conditions. ECW measurements were normal on admission in children with severe malaria and did not rise in the first few days of admission. Volumes in different compartments (TBW, ECW, and ICW) were not related to hyperlactataemia or other clinical and laboratory markers of disease severity. Moderate malaria was not associated with a depletion of TBW. Conclusions Significant hypovolaemia does not exacerbate complications of severe or moderate malaria. As rapid rehydration of children with malaria may have risks, we suggest that fluid replacement regimens should aim to correct fluid losses over 12-24 h.

Inflammatory markers are associated with ventilatory limitation and muscle dysfunction in obstructive lung disease in well functioning elderly subjects

Background: Inflammatory markers are increased in chronic obstructive pulmonary disease ( COPD) and are hypothesised to play an important part in muscle dysfunction and exercise intolerance. Methods: The Health Aging and Body Composition ( Health ABC) study is a prospective observational cohort of well functioning individuals aged 70 - 79 years. A cross sectional analysis of the baseline data was conducted to examine the association between inflammatory markers and ventilatory limitation, muscle strength, and exercise capacity. These associations were compared in participants with and without obstructive lung disease ( OLD). Results: Of the 3075 participants enrolled in the Health ABC cohort, OLD was identified by spirometric testing in 268 participants and 2005 participants had normal spirometric results. Of the participants with OLD, 35%, 38%, and 27% participants had mild, moderate, and severe OLD, respectively. Participants with OLD had lower quadriceps strength (102.5 Nm v 108.9 Nm, p = 0.02), lower maximum inspiratory pressure (64.7 cm H2O v 74.2 cm H2O, p< 0.0001), higher systemic interleukin (IL)-6 levels (2.6 pg/ml v 2.2 pg/ml, p< 0.0001), and higher C-reactive protein (CRP) levels (3.5 mg/l v 2.5 mg/l, p< 0.0001) than those with normal spirometry. In participants with OLD and those with normal spirometry, forced expiratory volume in 1 second (FEV1) was associated with IL-6 ( adjusted regression coefficients (beta) = -5.3 (95% CI -9.1 to -1.5) and -3.1 (95% CI -4.3 to -1.9), respectively). IL-6 and TNF were also associated with quadriceps strength among participants with OLD and those with normal spirometry (beta = -6.4 (95% CI -12.8 to -0.03) and -3.4 (95% CI -5.4 to -1.3), respectively, for IL-6 and beta = -10.1 (95% CI -18.7 to -1.5) and -3.8 (95% CI -7 to -0.6), respectively, for TNF). IL-6, quadriceps strength, and maximum inspiratory pressures were independent predictors of reduced exercise capacity in both groups. Conclusions: In well functioning elderly subjects with or without OLD, IL-6 is associated with reduced FEV1, quadriceps strength, and exercise capacity.

Reliability and validity of arm volume measurements for assessment of lymphedema

Background and Purpose. Arm lymphedema following breast cancer In this study, we assessed the surgery is a continuing problem. reliability and validity of circumferential measurements and water displacement for measuring upper-limb volume. Subjects. Participants included subjects who had had breast cancer surgery, including axillary dissection-19 with and 22 without a diagnosis of arm lymphedema-and 25 control subjects. Methods. Two raters measured each subject by using circumferential tape measurements at specified distances from the fingertips and in relation to anatornic landmarks and by using water displacement. Interrater reliability was calculated by analysis of variance and multilevel modeling. Volumes from circumferential measurements were compared with those from water displacement by use of means and correlation coefficients, respectively. The standard error of measurement, minimum detectable change (MDC), and limits of agreement (LOA) for volumes also were calculated. Results. Arm volumes obtained with these methods had high reliability. Compared with volumes from water displacement, volumes from circumferential measurements had high validity, although these volumes were slightly larger. Expected differences between subjects with and without clinical lymphedema following breast cancer were found. The MDC of volumes or the error associated with a single measure for data based oil anatomic landmarks was lower than that based oil distance from fingertips. The mean LOA with water displacement were lower for data based on anatomic landmarks than for data based on distance from fingertips. Discussion and Conclusion. Volumes calculated from anatomic landmarks are reliable, valid, and more accurate than those obtained from circumferential measurements based on distance from fingertips.

Electrical impedance tomography in extremely prematurely born infants and during high frequency oscillatory ventilation analyzed in the frequency domain

Functional electrical impedance tomography (EIT) measures relative impedance change that occurs in the chest during a distinct observation period and an EIT image describing regional relative impedance change is generated. Analysis of such an EIT image may be erroneous because it is based on an impedance signal that has several components. Most of the change in relative impedance in the chest is caused by air movement but other physiological events such as cardiac activity change in end expiratory level or pressure swings originating from a ventilator circuit can influence the impedance signal. We obtained EIT images and signals in spontaneously breathing healthy adults, in extremely prematurely born infants on continuous positive airway pressure and in ventilated sheep on conventional mechanical or high frequency oscillatory ventilation (HFOV). Data were analyzed in the frequency domain and results presented after band pass filtering within the frequency range of the physiological event of interest. Band pass filtering of EIT data is necessary in premature infants and on HFOV to differentiate and eliminate relative impedance changes caused by physiological events other than the one of interest.