[Standardization of spirometry: 2015 update. Published by German Atemwegsliga, German Respiratory Society and German Society of Occupational and Environmental Medicine]. / Leitlinie zur Spirometrie. Leitlinie der Deutschen Atemwegsliga, der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin und der Deutschen Gesellschaft für Arbeitsmedizin und Umweltmedizin zur Spirometrie.

Spirometry is a simple test and considered the gold standard in lung function. An obstructive ventilatory defect is a disproportionate reduction of maximal airflow from the lung in relation to the maximal volume that can be displaced from the lung. It implies airway narrowing and is defined by a reduced FEV1/FVC ratio below the 5th percentile of the predicted value (lower limit of normal, LLN). A restrictive disorder may be suspected when vital capacity (FVC) is reduced and FEV1/FVC is normal. It is definitely proven, however, only by a decrease in TLC below the 5th percentile of predicted value (LLN). The measurement of TLC by body plethysmography is necessary to confirm or exclude a restrictive defect or hyperinflation of the lung when FVC is below the LLN. 2012 a task force of the ERS published new reference values based on 74,187 records from healthy non-smoking males and females from 26 countries. The new reference equations for the 3-95 age range are now available that include appropriate age-dependent mean values and lower limits of normal (LLN). This presentation aims at providing the reader with recommendations dealing with standardization and interpretation of spirometry.

Assessment of airway hyperresponsiveness: comparison of spirometry and body plethysmography.

While methacholine (MCH) testing is commonly used in the clinical diagnosis of asthma, the detection of airway narrowing often relies on either spirometry or body plethysmography, however comparative studies are rare. In this study we performed MCH testing in 37 patients with variable shortness of breath at work and in 37 patients with no history of airway disease. The inclusion criteria were: no acute respiratory infection within 6 weeks, no severe diseases, normal baseline specific airway resistance (sR(aw)), normal baseline forced expiratory volume in 1 s (FEV(1)), Tiffeneau index >70%, no previous treatment with steroids within 14 days and no short acting bronchodilators within 24 h. Cumulative doses of 0.003, 0.014, 0.059, 0.239 and 0.959 mg MCH were inhaled by a dosimeter method. A FEV(1) decrease of ≥20% from baseline and a 100% increase of sR(aw) to ≥2.0 kPa/s was defined as end-of-test-criterion. Provocation doses were calculated by interpolation. Performance of lung function parameters was compared using receiver-operating-characteristic (ROC) analysis. ROC analysis resulted in an area under the ROC curve (AUC) of 0.74 for FEV(1) vs. 0.82 for sR(aw). The corresponding Youden Indices (J) were 0.46 for FEV(1) and 0.57 for sR(aw). The Youden Index of sR(aw) was higher and sensitivity and specificity (73%/84%) were rather well-balanced, in contrast to FEV(1) (54%/92%). In conclusion, in cumulative MCH challenges sR(aw) was found to be the overall most useful parameter for the detection of bronchial hyperresponsiveness. Body plethysmography yielded a balanced sensitivity-specificity ratio with higher sensitivity than spirometry, but comparable specificity.

Lung function at age 18-25 years: a comparison of different reference value systems.

The anthropometrical data of the Caucasian population have significantly changed within the last five decades. The European Community for Coal and Steel (ECCS) assumes a plateau phase and recommends the entry of 25 years old for calculation of reference values in this age range. The question arises if the commonly used reference recommendations for lung function of the ECCS can still be accepted. In the present study standardized spirometric lung function tests were performed by pneumotachography, recording lung volumes and flows (MasterScreen Pneumo, CareFusion, Höchberg) in asymptomatic nonsmoking subjects (202 females, 201 males), aged between 18 and 26, according to the ATS/ERS criteria. The results were compared with the reference recommendations of ECCS, SAPALDIA, LuftiBus, and Bochum (only males). All absolute lung function values showed a correlation (p< 0.05) with height. With respect to FVC and FEV(1), SAPALDIA and Bochum reference values were comparable and close to a 100 (range 97.6-101.4) %pred, whereas both ECCS and LuftiBus showed higher values (range 103.6-109.9%pred). The FEV(1)/FVC ratio was close to a 100 (range 97.6-101.7) %pred in all reference systems, whereas flows showed a wide variability between the reference systems (77.1-114.6%pred), single flows (e.g., 96.9-114.2%pred for MEF(50)) and males/females (males: 93.6-114.6%pred; females: 77.1-107.9%pred). We conclude that SAPALDIA reference values for FVC and FEV(1) should be used, as they better represent lung function in the age group. ECCS and LuftiBus reference values are appreciably (4-10%) lower. Differences between reference systems were less important for the FEV(1)/FVC ratio and lung flows.

Radioactivity concentration measurements in fish and shellfish samples from the west coast of Canada after the Fukushima nuclear accident (2011-2018).

Radioactive contamination of the Pacific Ocean following the Fukushima nuclear accident has raised public concern about seafood safety, particularly in coastal Indigenous communities. To address this, Health Canada and partners have collected and analyzed a total of 621 samples of commonly consumed salmon, ground fish, and shellfish from the Canadian west coast from 2011 to 2018. While the vast majority of the 137Cs and 134Cs levels were below the Minimum Detectable Concentration (MDC, typically 0.7-1.0 Bq kg-1 fw for a 6 h counting), further examination of 19 fish samples revealed 137Cs concentrations of 0.17-0.53 Bq kg-1 fw with an average value and uncertainty (k = 1) of 0.29 ± 0.02 Bq kg-1 fw. Of these, only two samples were found to have trace levels of 134Cs likely derived from the Fukushima accident. The global fallout contribution from atmospheric nuclear weapons testing to the observed 137Cs in these two samples was determined to be 0.26 ± 0.08 Bq kg-1 fw (49 ± 14%) and 0.12 ± 0.02 Bq kg-1 fw (24 ± 4%) for collection years 2015 and 2016, respectively. The annual average level of 137Cs in fish and shellfish was also determined by spectral summation for collection years 2014-2018. In fish, 137Cs levels determined through spectral summation were relatively constant (0.18-0.25 Bq kg-1 fw) with an average value and uncertainty of 0.21 ± 0.02 Bq kg-1 fw. By contrast, 38 shellfish samples (bivalves) were measured and revealed no radiocesium or other anomalies in either tissue or shell. In all, measurements over eight years showed that the radioactivity in fish and shellfish was dominated by natural radionuclides and that the level of anthropogenic radionuclides, as indicated by the radioactive cesium content, remained small. An upper bound for ingested dose from 137Cs was determined to be approximately 0.26 µSv per year, far below the worldwide average annual effective dose of 2400 µSv from exposure to natural background radiation. We can therefore conclude that fish, such as salmon, ground fish, and shellfish from the Canadian west coast are of no radiological health concern despite the Fukushima Dai-ichi nuclear accident of 2011.

Neoadjuvant chemotherapy in breast cancer-response evaluation and prediction of response to treatment using dynamic contrast-enhanced and diffusion-weighted MR imaging.

OBJECTIVE: To explore the predictive value of MRI parameters and tumour characteristics before neoadjuvant chemotherapy (NAC) and to compare changes in tumour size and tumour apparent diffusion coefficient (ADC) during treatment, between patients who achieved pathological complete response (pCR) and those who did not. METHODS: Approval by the Regional Ethics Committee and written informed consent were obtained. Thirty-one patients with invasive breast carcinoma scheduled for NAC were enrolled (mean age, 50.7; range, 37-72). Study design included MRI before treatment (Tp0), after four cycles of NAC (Tp1) and before surgery (Tp2). Data in pCR versus non-pCR groups were compared and cut-off values for pCR prediction were evaluated. RESULTS: Before NAC, HER2 overexpression was the single significant predictor of pCR (p = 0.006). At Tp1 ADC, tumour size and changes in tumour size were all significantly different in the pCR and non-pCR groups. Using 1.42 × 10(-3) mm(2)/s as the cut-off value for ADC, pCR was predicted with sensitivity and specificity of 88% and 80%, respectively. Using a cut-off value of 83% for tumour volume reduction, sensitivity and specificity for pCR were 91% and 80%. CONCLUSION: ADC, tumour size and tumour size reduction at Tp1 were strong independent predictors of pCR.

Lung function in our aging population.

UNLABELLED: AIMS OF INVESTIGATION: The chronological age of the Caucasian population and their anthropometrical data have significantly changed within the last five decades. Therefore the question arises whether or not the commonly used reference values of the European Community (ECCS) for lung function may still be accepted today. Since these values were obtained in the 1960s from subjects in a limited age range. For the elderly, the measured values are deduced by extrapolation beyond the range of reference equations which had been obtained in a different population. Therefore decisions concerning elderly and smaller subjects concerning remuneration due to impaired lung function after industrial exposure on the basis of EGKS values are questionable. METHODS: Lung function tests were performed by pneumotachography, recording static lung volumes and flow-volume-curves in 262 asymptomatic non smoking males, aged 20 to 90 years. Measurements were performed with the MasterLab, or PneumoScreen systems (CareFusion, Höchberg). RESULTS were compared to the reference values of ECCS, SAPALDIA and LuftiBus. - RESULTS: For simplicity analysis of age and height dependence of investigated respiratory parameters (VC, FVC, FEV⊂1, FEV⊂1%FVC, PEF, MEF⊂75,50,25) can be described by linear functions (y = a * height ? b * age + c). The forced expiratory vital capacity, FVC, was calculated by FVC = 0.0615*H - 0.0308*A - 4.673; r = 0.78. Mean FVC for younger subjects was found to be 104.7 ± 10.7% of the ECCS reference values and 96.5 ± 11.8 % in older subjects. For most parameters investigated linear regressions on age were steeper than described by the ECCS reference values. The regression of lung function to height largely follows the ECCS prescriptions. SUMMARY: Bochum lung function values of younger healthy subjects were higher compared to the reference values of the ECCS and showed a steeper age descent. The alternatively discussed reference values of the SAPALDIA-, or LuftiBus-Study are higher, but do not cover all necessary parameters and/or the age range. A multi centre study for contemporary reference values is recommended.

Gynecologic oncology patients are ready for telemedicine in routine care: Results from a pre-COVID survey.

OBJECTIVES: To assess telemedicine readiness of gynecologic oncology patients, particularly those at risk for care access disparities (increased distance to care, rural populations.). METHODS: Patients at all disease/treatment stages completed an anonymous survey during in-person outpatient appointments at an academic comprehensive cancer center from 1/6/2020 to 2/28/2020, conducted prior to the COVID-19 pandemic, before the introduction of telemedicine in this practice. RESULTS: Of 180 patients approached, 170 completed the survey (94.4%). Mean age was 59.6 years; 73.4% identified as White, 23.7% Black, and 2.9% other race. Ovarian cancer was most common (41.2%), followed by endometrial (27.1%), cervical (20.6%), and vaginal/vulvar (7.1%). Most patients traveled > 50 miles for appointments (63.8%); they were more likely from rural counties with significantly higher travel costs/visit ($60.77 vs $37.98, p = 0.026.) The majority expressed interest in using telemedicine (75.7%) or a smartphone app (87.5%) in their care. The majority of patients with difficulty attending appointments (88.9 vs 70.2%, p = 0.02) or from rural counties (88.7% vs 69.6%, p = 0.03) were interested in telemedicine; those with both characteristics reported 100% interest. The majority in both urban and rural counties had home internet access, and reported similarly high rates of daily use (79% vs 75%). Race and age were not associated with differences in internet access or use or telemedicine interest. CONCLUSIONS: Telemedicine is attractive to the majority of patients and may offer financial/logistical advantages. Patients have high internet use rates and comfort with using technology for healthcare. Telemedicine should be incorporated into standard practice beyond the COVID-19 pandemic to reduce healthcare access disparities.

Craniofacial growth disturbance is related to temporomandibular joint abnormality in patients with juvenile idiopathic arthritis, but normal facial profile was also found at the 27-year follow-up.

OBJECTIVES: To assess the long-term outcome of craniofacial morphology related to disease variables and temporomandibular joint (TMJ) involvement as demonstrated with computed tomography (CT) and magnetic resonance imaging (MRI) in adult patients with juvenile idiopathic arthritis (JIA). METHODS: Sixty of 103 patients participated in a re-examination on average 27 years after baseline. Craniofacial morphology, with emphasis on size and position of the mandible, was assessed in lateral cephalographic images and related to disease variables and TMJ involvement by CT and MRI. Definitions of craniofacial growth disturbances were based on measurements outside 2 SD from the mean of healthy adult controls. RESULTS: Sagittal craniofacial growth disturbances were found in 57% and micrognathia in 27% of the 60 patients. Of those with JIA TMJ involvement, 70% had some form of growth disturbance. Micrognathia occurred only in patients with bilateral TMJ involvement. The bilateral TMJ group had significantly different craniofacial morphology than healthy controls and patients without TMJ involvement. Growth disturbances and TMJ involvement were present in all subtypes of JIA, except for one subtype comprising one patient. Patients with growth disturbances had more severe disease than patients with normal craniofacial growth, regarding both present and previous disease activity. Unexpectedly, half of the patients without craniofacial growth disturbances also had TMJ involvement, many from before the age of 12. CONCLUSIONS: Craniofacial growth disturbances were found to be frequent in adult JIA patients, especially in those with bilateral TMJ involvement. However, growth disturbances did not always follow TMJ involvement, not even when affected early.

[Geometry and function of the dog nose: how does function change when form of the nose is changed?]. / Geometrie und Funktion der Hundenase: Wie ändert sich die Funktion, wenn die Form verändert wird?

Nasal airflow resistance in brachycephalic dogs is significantly elevated compared to normal dogs. LaserAssisted TurbinEctomy (LATE)-surgery as well as xylometazolin were shown to reduce pathologically increased intranasal airway resistance in brachycephalic dogs by approximately 50 %. Impulse oscillometry provides a reliable and sensitive method to examine intranasal stenoses in the canine nose. Acoustic rhinometry allows assessment of changes in cross sectional area and volume of the canine nasal cavity.

Modification and validation of the Lysholm Knee Scale to assess articular cartilage damage.

OBJECTIVE: The Lysholm Knee Scale is an 8-item questionnaire originally designed as an outcome measure for ligament reconstruction but is commonly used as a measure for knee chondral damage. This study tests the scale's internal construct validity using the Rasch model, a measurement model which sets strict standards for the quality of measurement derived from the scale. The study also investigates the level of agreement between scores from patients and physiotherapists; and reviews the present weighting system. DESIGN: One hundred and fifty-seven patients with knee chondral damage awaiting surgery completed the Lysholm as part of a multicentre clinical trial based in 16 UK and two Norwegian hospitals. The patients were assessed by a physiotherapist who independently completed the Lysholm on the same day. RESULTS: Fit to the Rasch model was achieved [mean item fit -0.26, standard deviation (SD) 1.01] after removal of one item (Swelling). With no differential item functioning (DIF) by rater, the intraclass correlation coefficient was 0.9 [95% confidence interval (CI): 0.86-0.93] and a Bland-Altman plot showed no consistent difference in rating. CONCLUSIONS: The Lysholm Knee Scale satisfies Rasch model expectations after removal of the swelling item. Generally there is a high degree of agreement between the patient and professional ratings. By removing the swelling item and using unweighted scores, a modified version of the Lysholm Knee Scale is recommended as an outcome measure for knee chondral damage.

Assessment of airway hyperreactivity: comparison of forced spirometry and body plethysmography for methacholine challenge tests.

INTRODUCTION: Bronchial challenge tests by inhalation of aerosolized methacholine (MCH) are commonly used in the clinical diagnosis of airway hyperresponsiveness (AHR). While the detection of airway narrowing relies on the patient's cooperation performing forced spirometry, body plethysmographic measurements of airway resistance are less depending on the patient's cooperation and do not alter the respiratory tract by maximal maneuvers. Hence we compared both methods concerning their clinical value and correlation during MCH challenges in patients with asthma. MATERIAL AND METHODS: Cumulative MCH challenges test, consisting of up to 5 steps, evaluated with body plethysmography on each step were performed in 155 patients with bronchial asthma. Airway responses were recorded at each step of MCH application (MasterScreen Body, Cardinal Health, Höchberg). At the baseline test and after crossing the provocation dose (PD) threshold in body plethysmography (PD+100 sReff), forced expirations were performed and FEV(1), FVC, and FEV(1) %FVC were measured. Using regression analysis of the airway parameters and taking the MCH dose as the covariate, we could extrapolate to missing spirometric values and interpolate the estimated MCH dose when crossing the PD threshold (PD-20 FEV(1)) between two consecutive measurements. The administered PD+100 MCH doses for specific airway resistance, sRtot, and sReff were compared with resistance parameters Rtot and Reff, and to PD-20 of FEV(1) and FEV(1) %FVC. RESULTS: Regarding sReff we found a mild, moderate, or severe AHR in 114 patients (75%), but only 50 (32%) according to FEV1. A statistical analysis showed strongly linear correlated parameters of airway resistance, but no significant correlation between the results of body plethysmography and forced spirometry. CONCLUSIONS: Using MCH challenges, we found specific airway resistance to be the most sensitive parameter to detect AHR. Raw is largely independent of height and gender facilitating the interpretation of measurements carried out longitudinally.

Time for new reference values for ventilatory lung function.

OBJECTIVE: The anthropometrical data of our aging population has significantly changed within the last five decades. Therefore the question arises whether or not the commonly used reference values of the European Community (ECCS) for lung function, may still be accepted today. Measured values for elderly are classified by extrapolation beyond the range of reference equations. MATERIAL AND METHODS: Lung function was examined by pneumotachography for recording static lung volumes and flow-volume-curves in 257 asymptomatic non smoking males, aged 20-90 years. Results were compared to the reference values of ECCS, SAPALDIA, LuftiBus, and NHANES. RESULTS: For analysis age and height dependence of investigated respiratory parameters (VC, FVC, FEV(1), FEV(1) %FVC, PEF, MEF(75,50,25)) can for simplicity be described by linear functions (y = a . height(H)-b . age (A)+c). The forced expiratory volume in one second, FEV(1), was calculated by FEV(1) = 0.0432 . H-0.0347 . A -2.114; where H - height, A - age; r = 0.78. Mean FEV(1) for younger subjects was found to be 106.1 +/- 11.2% of the ECCS reference values and 97.8 +/- 11.7% in older subjects. For all parameters investigated linear regressions on age were steeper than described by the ECCS reference values. The regression of lung function to height largely follows the ECCS prescriptions. SUMMARY: Bochum lung function values of healthy subjects showed a steeper age descent compared to the reference values of the ECCS. The alternatively discussed reference values of the SAPALDIA-, NHANES- or LuftiBus-Study are higher, but do not cover all necessary parameters and/or the age range. A multi centre study for contemporary reference values is recommended.

[Lung function in the elderly: do we need new reference values?]. / Lungenfunktion im Alter: Brauchen wir neue Referenzwerte?

INTRODUCTION: The structure of our aging population has significantly changed in the last three decades as have also the anthropometric data. Therefore, the question arises as to whether or not the largely accepted reference values for ventilatory lung function, which were suggested by the European Community for Coal and Steel (EGKS), may still be used today, since these values were obtained in the 1960s from subjects in a limited age range. For the elderly, the measured values are deduced by extrapolation beyond the range of reference equations which had been obtained in a different population. Therefore decisions concerning elderly and smaller subjects concerning remuneration due to impaired lung function after industrial exposure on the basis of EGKS values are questionable. METHODS: We have examined lung function using pneumotachography for recording static lung volumes and flow-volume curves in 176 asymptomatic non-smoking males, aged 20 to 90 years, and correlated the results to the reference values of the EGKS, SAPALDIA and LuftiBus. RESULTS: The age dependence of respiratory parameters (VC, FVC, FEV (1), FEV (1) %FVC, PEF, MEF (75,50,25)) for the healthy subjects can be described with a linear function (y = - m x age + n). The forced expiratory volume in one second, FEV (1), is calculated by FEV (1) = - 0.046 x age + 6.11; r = 0.88. Mean FEV1 for younger subjects was found to be 108 +/- 9.9 % of the EGKS reference values, 105 +/- 13.7 % in the middle-aged group and 97.3 +/- 12.4 % in the older subjects. All measured parameters concerning lung function can be described as linear functions of age which are steeper than those described by the EGKS reference values. The steeper slope in age dependency was also seen in other investigated parameters. The correlation of lung function parameters to height largely follows the EGKS predictions. CONCLUSIONS: Measured lung function values of healthy younger and elderly subjects showed a close correlation to the extrapolated reference values of the EGKS. Our results relating to normal lung function justify an extrapolation of the reference equations beyond the common ranges of age while applying the same limitations as described for subjects in the middle-age range. Our results permit an extrapolation of EGKS values beyond the range of the reference values and can be used for the classification of impaired lung function in older subjects. The alternatively discussed reference equations of the SALPADIA Study, of NHANES and partially of the LuftiBus Study are higher, but do not cover all the necessary parameters and/or age ranges. A multicentric study for contemporary reference values should be performed in order to solve the problems concerning valid reference values.

Dynamic processing of DOM: Insight from Exometabolomics, Fluorescence Spectroscopy, and Mass Spectrometry.

Dissolved organic matter (DOM) in freshwater environments is an important source of organic carbon, supporting bacterial respiration. Frozen environments cover vast expanses of our planet, with glaciers and ice-sheets storing upwards of six petagrams of organic carbon. It is generally believed that DOM liberated from ice stimulates downstream environments. If true, glacial DOM is an important component of global carbon cycling. However, coupling the release of DOM to microbial activity is challenging due to the molecular complexity of DOM and the metabolic connectivity within microbial communities. Using a single environmentally relevant organism, we demonstrate that processing of compositionally diverse DOM occurs, but, even though glacially derived DOM is chemically labile, it is unable to support sustained respiration. In view of projected changes in glacier DOM export, these findings imply that biogeochemical impacts on downstream environments will depend on the reactivity and heterogeneity of liberated DOM, as well as the timescale.

Relationship between dissolved organic matter quality and microbial community composition across polar glacial environments.

Vast expanses of Earth's surface are covered by ice, with microorganisms in these systems affecting local and global biogeochemical cycles. We examined microbial assemblages from habitats fed by glacial meltwater within the McMurdo Dry Valleys, Antarctica and on the west Greenland Ice Sheet (GrIS), evaluating potential physicochemical factors explaining trends in community structure. Microbial assemblages present in the different Antarctic dry valley habitats were dominated by Sphingobacteria andFlavobacteria, while Gammaproteobacteria and Sphingobacteria prevailed in west GrIS supraglacial environments. Microbial assemblages clustered by location (Canada Glacier, Cotton Glacier and west GrIS) and were separated by habitat type (i.e. ice, cryoconite holes, supraglacial lakes, sediment and stream water). Community dissimilarities were strongly correlated with dissolved organic matter (DOM) quality. Microbial meltwater assemblages were most closely associated with different protein-like components of the DOM pool. Microbes in environments with mineral particles (i.e. stream sediments and cryoconite holes) were linked to DOM containing more humic-like fluorescence. Our results demonstrate the establishment of distinct microbial communities within ephemeral glacial meltwater habitats, with DOM-microbe interactions playing an integral role in shaping communities on local and polar spatial scales.

Impact of hydrologic boundaries on microbial planktonic and biofilm communities in shallow terrestrial subsurface environments.

Subsurface environments contain a large proportion of planetary microbial biomass and harbor diverse communities responsible for mediating biogeochemical cycles important to groundwater used by human society for consumption, irrigation, agriculture and industry. Within the saturated zone, capillary fringe and vadose zones, microorganisms can reside in two distinct phases (planktonic or biofilm), and significant differences in community composition, structure and activity between free-living and attached communities are commonly accepted. However, largely due to sampling constraints and the challenges of working with solid substrata, the contribution of each phase to subsurface processes is largely unresolved. Here, we synthesize current information on the diversity and activity of shallow freshwater subsurface habitats, discuss the challenges associated with sampling planktonic and biofilm communities across spatial, temporal and geological gradients, and discuss how biofilms may be constrained within shallow terrestrial subsurface aquifers. We suggest that merging traditional activity measurements and sequencing/-omics technologies with hydrological parameters important to sediment biofilm assembly and stability will help delineate key system parameters. Ultimately, integration will enhance our understanding of shallow subsurface ecophysiology in terms of bulk-flow through porous media and distinguish the respective activities of sessile microbial communities from more transient planktonic communities to ecosystem service and maintenance.

The use of impulse oscillometry for separate analysis of inspiratory and expiratory impedance parameters in horses: effects of sedation with xylazine.

AIM: To improve the outcome of parameters measured by the impulse oscillometry system (IOS) in horses by separate assessment of inspiratory and expiratory impedance spectra in the frequency range between 1 and 10 Hz. As basis for further studies, the influence of sedation with xylazine on respiratory impedance was also investigated. METHODS: (i) The respiratory impedance of 11 horses was measured using IOS before and 6 min after sedation (xylazine; 0.6 mg/kg b.w.). (ii) The time course of impedance parameters in a period of 24 min after administration of xylazine was evaluated in 12 horses at regular intervals of 3 min. Resistance (R(rs)), reactance (X(rs)), and coherence (Co) were calculated as mean spectra (R(rs),X(rs),Co) of the entire measurement as well as separated into inspiration (Ri(rs),Xi(rs),Coi) and expiration (Re(rs),Xe(rs),Coe) at frequencies of 1, 5, and 10 Hz. RESULTS: (i) R(rs), X(rs) as well as Re(rs) and Xe(rs) revealed no significant influence of sedation. However, separate analysis of inspiration and expiration revealed a significant influence of sedation on all inspiratory impedance parameters. (ii) During the 24 min period after sedation, almost all inspiratory parameters were found significantly dependent on the time course of sedation whereas expiratory parameters Re10, Xe1, and Xe5 were not influenced. These results indicate that confounding factors due to sedation act mainly during inspiration. Muscle relaxation in upper airways due to xylazine is suspected to be the main cause of these phenomena.

Effect of a cancer cachectic factor on protein synthesis/degradation in murine C2C12 myoblasts: modulation by eicosapentaenoic acid.

The effect of a proteolysis inducing factor (PIF) on protein synthesis and degradation and the modulation of this effect by the polyunsaturated fatty acid, eicosapentaenoic acid (EPA), have been examined using a surrogate model system, C2C12 myoblasts in vitro. After 90 min of incubation, PIF produced a significant inhibition of protein synthesis in a dose-dependent manner, with maximal inhibition at a concentration of 4 nM. The effect was attenuated both by treatment with a monoclonal antibody to PIF and by treatment with insulin at physiological concentrations (1 nM) and below (0.1 nM), but not by EPA (50 microM). The inhibitory effect on protein synthesis was transitory and was not seen after prolonged incubation with PIF. An increased rate of protein degradation was observed in C2C12 myoblasts after addition of PIF, which was also maximal at a concentration of PIF of 4 nM. Higher concentrations of PIF did not produce an increase in protein degradation. Unlike the effect on protein synthesis, the enhanced protein degradation was completely abolished by pretreatment with 50 microM EPA, suggesting that the two effects are mediated by different mechanisms. PIF produced an increased release of [3H]arachidonic acid from prelabeled myoblasts with a dose-response curve parallel to that of protein degradation and with a maximum at 4 nM PIF. Release of [3H] arachidonic acid was completely blocked in cells pretreated with 50 microM EPA, suggesting that the effect was related to protein degradation. The [3H]arachidonic acid was rapidly metabolized to prostaglandins E2 and F2alpha and to 5-, 12-, and 15-hydroxyeicosatetraenoic acids (HETEs). Production of all eicosanoids was attenuated in cells pretreated with EPA. Of all of the metabolites, only 15-HETE produced a significant increase in protein degradation in C2C12 myoblasts with a maximal effect at 30 nM and with a bell-shaped dose-response curve similar to that produced by PIF. These results suggest that PIF enhances protein degradation as a result of an increased production of 15-HETE.

Mechanism of attenuation of skeletal muscle protein catabolism in cancer cachexia by eicosapentaenoic acid.

Cancer cachexia is characterized by selective depletion of skeletal muscle protein reserves. Soleus muscles from mice bearing a cachexia-inducing tumor (MAC16) showed an increased protein degradation in vitro, as measured by tyrosine release, when compared with muscles from nontumor-bearing animals. After incubation under conditions that modify different proteolytic systems, lysosomal, calcium-dependent, and ATP-dependent proteolysis were found to contribute to the elevated protein catabolism. Treatment of mice bearing the MAC16 tumor with the polyunsaturated fatty acid, eicosapentaenoic acid (EPA), attenuated loss of body weight and significantly suppressed protein catabolism in soleus muscles through an inhibition of an ATP-dependent proteolytic pathway. The ATP-ubiquitin-dependent proteolytic pathway is considered to play a major role in muscle catabolism in cachexia, and functional proteasome activity, as determined by "chymotrypsin-like" enzyme activity, was significantly elevated in gastrocnemius muscle of mice bearing the MAC16 tumor as weight loss progressed. When animals bearing the MAC16 tumor were treated with EPA, functional proteasome activity was completely suppressed, together with attenuation of the expression of 20S proteasome alpha-subunits and the p42 regulator, whereas there was no effect on the expression of the ubiquitin-conjugating enzyme (E2(14k)). These results suggest that EPA induces an attenuation of the up-regulation of proteasome expression in cachectic mice, and this was correlated with an increase in myosin expression, confirming retention of contractile proteins. EPA also inhibited growth of the MAC16 tumor in a dose-dependent manner, and this correlated with suppression of the expression of the 20S proteasome alpha-subunits in tumor cells, suggesting that this may be the mechanism of tumor growth inhibition. Thus EPA antagonizes loss of skeletal muscle proteins in cancer cachexia by down-regulation of proteasome expression, and this may also be the mechanism for inhibition of tumor growth.