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C Gallina

Publications and source records attributed to C Gallina.

At least 37 records · Page 2Linked to original sources

Synthesis and inhibiting properties toward trypsin like proteases of N alpha-(N,N-dimethylcarbamoyl)-alpha-azaornitine and alpha-azalysine esters.

N alpha-(N,N-dimethylcarbamoyl)-alpha-azaornitine and N alpha-(N,N-dimethylcarbamoyl)-alpha-azalysine phenyl and p-nitrophenyl esters (7-10) were synthesized and tested as inhibitors of trypsin, chymotrypsin and thrombin. The N,N-dimethylcarbamoyl group was chosen to decrease the tendency of acylcarbazates to cyclization into 1,3,4-oxadiazol-2(3H)-ones. Only the p-nitrophenyl alpha-azaornithine derivative 8 was inactivated rapidly by intramolecular acylation of the terminal amino group, rather than by cyclization to oxadiazolone, in aqueous solution at pH 8. The corresponding alpha-azalysine derivative 10 is completely unaffected under the same conditions. Rapid inactivation of thrombin and trypsin only was observed for all alpha-azapeptide esters 7-10 at 0.5 mM inhibitor concentration. No proteolytic activity was restored after 24 h following 2,000 fold dilution of the inhibitor concentration suggesting formation of very stable acylenzymes.

Animals↗

Respiratory impedance to ambient pressure changes at low frequencies.

Respiratory impedance may be studied by measuring airway flow (Vaw) when pressure is varied at the mouth (input impedance) or around the chest (transfer impedance). A third possibility, which had not been investigated so far, is to apply pressure variations simultaneously at the two places, that is to vary ambient pressure (Pam). This provides respiratory impedance to ambient pressure changes (Zapc = Vaw/Pam). In that situation airway impedance (Zaw) and tissue impedance (Zt) are mechanically in parallel, and both are in series with alveolar gas impedance (Zg): Zapc = Zaw + Zg + Zaw.Zg/Zt. We assessed the frequency dependence of Zapc from 0.05 to 2 Hz in nine normal subjects submitted to sinusoidal Pam changes of 2-4 kPa peak to peak. The real part of Zapc (Rapc) was of 6.2 kPa.1(-1).s at 0.05 Hz and decreased to 1.9 kPa.1(-1).s at 2 Hz. Similarly the effective compliance (Capc), computed from the imaginary part of Zapc, decreased from 0.045 1.kPa-1 at 0.05 Hz to 0.027 1.kPa-1 at 2 Hz. Breathing against an added resistance of 0.46 kPa.1(-1).s exaggerated the negative frequency dependence of both Rapc and Capc. When values of airway resistance and inertance derived from transfer impedance data were introduced, Zapc was used to compute effective tissue resistance (Rt) and compliance (Ct). Rt was found to decrease from 0.32 to 0.15 kPa.1(-1).s and Ct from 1.11 to 0.64 1.kPa-1 between 0.25 and 2 Hz. Ct was slightly lower with the added resistance. These results are in good agreement with the data obtained by other approaches.

Adult↗

Stress adaptation and low-frequency impedance of rat lungs.

At transpulmonary pressures (Ptp) of 7-12 cmH2O, pressure-volume hysteresis of isolated cat lungs has been found to be 20-50% larger than predicted from their amount of stress adaptation (J. Hildebrandt, J. Appl. Physiol. 28: 365-372, 1970). This behavior is inconsistent with linear viscoelasticity and has been interpreted in terms of plastoelasticity. We have reinvestigated this phenomenon in isolated lungs from 12 Wistar rats by measuring 1) the changes in Ptp after 0.5-ml step volume changes (initial Ptp of 5 cmH2O) and 2) their response to sinusoidal pressure forcing from 0.01 to 0.67 Hz (2 cmH2O peak to peak, mean Ptp of 6 cmH2O). Stress adaptation curves were found to fit approximately Hildebrandt's logarithmic model [delta Ptp/delta V = A - B.log(t)] from 0.2 to 100 s, where delta V is the step volume change, A and B are coefficients, and t is time. A and B averaged 1.06 +/- 0.11 and 0.173 +/- 0.019 cmH2O/ml, respectively, with minor differences between stress relaxation and stress recovery curves. The response to sinusoidal forcing was characterized by the effective resistance (Re) and elastance (EL). Re decreased from 2.48 +/- 0.41 cmH2O.ml-1.s at 0.01 Hz to 0.18 +/- 0.03 cmH2O.ml-1.s at 0.5 Hz, and EL increased from 0.99 +/- 0.10 to 1.26 +/- 0.20 cmH2O/ml on the same frequency range. These data were analyzed with the frequency-domain version of the same model, complemented by a Newtonian resistance (R) to account for airway resistance: Re = R + B/ (9.2f) and EL = A + 0.25B + B . log 2 pi f, where f is the frequency.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

Respiratory input and transfer mechanical impedances in patients with chronic obstructive pulmonary disease.

Total respiratory input (Zin) and transfer (Ztr) mechanical impedances were measured from 4-30 Hz in 9 patients with severe chronic obstructive pulmonary disease (COPD) and in 12 healthy subjects. Zin was obtained by applying a pressure input around the head to minimize transmural pressure across extrathoracic airway walls, and Ztr was obtained with a pressure input at the chest. In agreement with previous studies total respiratory compliance and inertance were decreased in patients, while effective input resistance was increased and exhibited a negative frequency dependence. Effective transfer resistance (Re(Ztr)) was also increased at all frequencies, and, in some patients, the Re(Ztr)-frequency curve was sigmoid in shape, which was never seen in normals. When Ztr was analysed with a six-coefficient monoalveolar model featuring tissue properties, alveolar gas compliance, and airways properties, the model fitted the data less closely in patients than in normals and, in the former, provided unrealistic coefficients. Such was also the case with a bialveolar model. A better fit with more realistic values for the coefficients was obtained in selected patients with a model where central and peripheral (Rp) airway resistance were separated by a shunt representing airway wall compliance (Cb): Cb was found to range from 0.029-0.062 l.kPa-1 and Rp represented 44-81% of total airway resistance.

Adult↗

Measurement of ventilatory mechanical impedance in infants using a head pressure generator.

Two methods of measuring ventilatory mechanical impedance (Z) by forced oscillations between 6 and 20 Hz were compared in 24 infants aged 2 to 49 months: 1) the application of pressure oscillations at the airway opening (Z1); and 2) the application of pressure oscillations around the head (Z2). The latter has been recently proposed to minimize the influence of compliant upper airway walls (Peslin et al., J Appl Physiol. 1985, 59:1790-1795). Ventilatory resistance and compliance (Rsb, Csb) were also obtained with the single breath method. The real part of Z1 (R1) was markedly lower than that of the corresponding Z2 (R2), at any frequency. R1 exhibited a systematic negative frequency dependence, in contrast with R2. At any frequency, the slope of the regression equation on Rsb was closer to unity for R2 than for R1. The imaginary part of Z1 (X1) was negative over the whole frequency interval, and negative values of inertance were derived from X1. X2 was negative at low and positive at high frequencies. Resonant frequency (mean +/- SD = 10.5 +/- 3.5 Hz) was always reached with Z2 and correlated negatively with body weight (r = -0.61). Inertance estimated from X2 was positive and correlated negatively with body height (r = -0.66). The compliance derived from Z1 (C1 = 3.35 +/- 2.32 10(-3) L.cm H2O-1) was not significantly different from that derived from Z2 (C2 = 2.99 +/- 2.02 10(-3) L.cm H2O-1). The marked difference observed between Z1 and Z2 is related to the importance of the upper airway shunt and may be explained by inaccuracies of both methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Analysis of the dynamic characteristics of pressure transducers for studying respiratory mechanics at high frequencies.

Differential pressure transducers are commonly used to study respiratory mechanics at physiological frequencies as well as during external forcing at high frequencies. In the latter condition, measuring errors could occur if the input impedance of the pressure transducers is not sufficiently large with respect to that of the respiratory system. In this work we analysed the input impedance Z and the transfer function H of two common pressure transducers (Validyne MP-45 and Celesco LCVR) equipped with membranes of different sensitivities and with connecting tubes of different lengths. Z was measured by the tube method and H was measured by comparison with a flat-response pressure transducer. In agreement with the predictions based on a simple lumped-parameters model, we found that Z reached very low values, especially at the frequencies where H had a resonance peak. For instance, for the widespread Validyne MP-45 transducer (200 Pa) with connecting tubes of 16 cm length and 3.8 mm internal diameter a minimum of Z of 8300 Pa s litre-1 at 96 Hz was measured; at that frequency the amplitude of H attained a value of 3.1. Using the above transducer model we simulated the measurement of a rat input impedance up to 128 Hz using Validyne and Celesco transducers. With the Validyne MP-45 (200 Pa), equipped with the same connecting tubes as above, the computed error reached up to 50 per cent for the real part and 140 per cent for the imaginary part.

Animals↗

Flow and volume dependence of respiratory mechanical properties studied by forced oscillation.

The influence of inspiratory and expiratory flow magnitude, lung volume, and lung volume history on respiratory system properties was studied by measuring transfer impedances (4-30 Hz) in seven normal subjects during various constant flow maneuvers. The measured impedances were analyzed with a six-coefficient model including airway resistance (Raw) and inertance (Iaw), tissue resistance (Rti), inertance (Iti), and compliance (Cti), and alveolar gas compressibility. Increasing respiratory flow from 0.1 to 0.4 1/s was found to increase inspiratory and expiratory Raw by 63% and 32%, respectively, and to decrease Iaw, but did not change tissue properties. Raw, Iti, and Cti were larger and Rti was lower during expiration than during inspiration. Decreasing lung volume from 70 to 30% of vital capacity increased Raw by 80%. Cti was larger at functional residual capacity than at the volume extremes. Preceding the measurement by a full expiration rather than by a full inspiration increased Iaw by 15%. The data suggest that the determinants of Raw and Iaw are not identical, that airway hysteresis is larger than lung hysteresis, and that respiratory muscle activity influences tissue properties.

Adult↗

Functional residues at the active site of horse liver phosphopantothenoylcysteine decarboxylase.

Horse liver phosphopantothenoylcysteine decarboxylase (EC 4.1.1.36) is rapidly inactivated by N-acetoacetylation with diketene following a pseudo-first-order kinetics: the presence of substrate quantitatively protects against this inactivation. Histidine photo-oxidation with methylene blue or rose bengal brings about the total loss of activity. These results indicate the presence of functional lysyl and histidyl groups at the active site of the enzyme. The substrate sulphydryl group is essential for enzyme activity. Enzymatic decarboxylation is proposed to result from a combined action of the keto group of the enzyme-bound pyruvate protonated by an essential histidine and a protonated amino group of a lysine.

Animals↗

Mechanics of the ventilatory system in sedated infants: forced oscillations versus single-breath method.

The real--Re(Z)--and imaginary--Im(Z)--parts of the ventilatory system impedance were measured between 6 and 30 Hz in 18 normal infants and in 19 with airway obstruction. The intercept (R0) and slope (S) of the Re(Z)-frequency function, as well as inertance (I) and compliance (C) estimated from Im(Z), were compared with ventilatory system resistance (Rrs) and compliance (Crs) (single-breath method). R0 correlated significantly with Rrs (r = 0.86), although the slope of the regression equation was significantly lower than 1 (P less than 0.01). Negative frequency dependence of Re(Z) was observed in all subjects and a significant correlation was found between S and Rrs (r = -0.80). "Inertance" was negative in 20 subjects and correlated negatively with Rrs (r = -0.61). C correlated with Crs (r = 0.64) and with 1/Rrs (r = 0.85). The ratio of C to Crs (mean +/- SD = 0.168 +/- 0.082) also correlated with 1/Rrs (r = 0.51). The main characteristics of the total impedance/frequency function could be simulated with a model featuring the upper airway wall (Zuaw) in parallel with the ventilatory system (Zrs). It is suggested that the differential change in Zuaw and Zrs with growth accounts for the marked frequency dependence of Re(Z) as well as the inaccurate estimation of both I and C in this population.

Airway Resistance↗

Measurement of ventilatory system resistance in infants and young children.

The mechanics of the ventilatory system were studied in 29 sleeping infants and young children by the analysis of a passive expiration following an end-inspiratory airway occlusion ('single breath' method). The ventilatory system time constant (tau rs) to compliance ratio yielded the value of ventilatory system resistance (Rrs). The calculated ventilatory system compliance correlated well with the slope of the quasi static pressure-volume curve (r = 0.97). The allometric relationship between Rrs and height (Rrs = 81.9.10(3).Ht (cm)-1.76, r = -0.82) is in agreement with forced oscillation measurements during the first year of life (Wohl et al., 1969). tau rs was found to increase significantly over the first months of life (P less than 0.01).

Airway Resistance↗

Density dependence of respiratory input and transfer impedances in humans.

Total respiratory input (Zin) and transfer (Ztr) impedances were obtained from 4 to 30 Hz in 10 healthy subjects breathing air and He-O2. Zin was measured by applying pressure oscillations around the head to minimize the upper airway shunt and Ztr by applying pressure oscillations around the chest. Ztr was analyzed with a six-coefficient model featuring airways resistance (Raw) and inertance (Iaw), alveolar gas compressibility, and tissue resistance, inertance, and compliance. Breathing He-O2 significantly decreased Raw (1.35 +/- 0.32 vs. 1.74 +/- 0.49 cmH2O.l-1.s in air, P less than 0.01) and Iaw (0.59 +/- 0.33 vs. 1.90 +/- 0.44 x 10(-2) cmH2O.l-1.s2), but, as expected, it did not change the tissue coefficients significantly. Airways impedance was also separately computed by combining Zin and Ztr data. This approach demonstrated similar variations in Raw and Iaw with the lighter gas mixture. With both analyses, however, the changes in Iaw were more than what was expected from the change in density. This indicates that factors other than gas inertance are included in Iaw and reveals the short-comings of the six-coefficient model to interpret impedance data.

Airway Resistance↗

Measurement of alveolar gas volume by ambient pressure changes in isolated lungs.

Alveolar gas volume (AGV) may be measured in humans (Peslin et al., J. Appl. Physiol. 62: 359-363, 1987) by applying very slow sinusoidal variations of ambient pressure (delta Pam) around the body and studying the relationship between delta Pam and the resulting gas displacement at the mouth (delta Vaw): AGVapc = (PB.delta Vaw)/(delta Pam.cos phi), where AGVapc is AGV measured by ambient pressure changes, PB is barometric minus alveolar water vapor pressure, and phi is the phase angle between Pam and Vaw. The applicability of this method to excised lungs at various transpulmonary pressures was assessed in six rabbit lungs and three dog lobes by reference to AGV measurements by He dilution (AGVdil) and by a volumetric method (AGVvol). Except in one instance, AGVapc did not change significantly when the frequency of delta Pam was varied from 0.02 to 0.2 Hz. AGVapc was highly correlated (P less than 0.001) to both AGVdil and AGVvol. It did not differ significantly from AGVdil (81.4 +/- 50.6 vs. 80.2 +/- 44.2 ml) and was only marginally higher than AGVvol (64.6 +/- 26.9 vs. 62.4 +/- 24.4 ml, P less than 0.05). We conclude that the method usually provides accurate results in excised lung preparations. Its main advantages are that it does not require manipulating the lung or changing its volume and that the measurement takes less than 1 min.

Animals↗

Thoracic gas volume measurements in chronic obstructive pulmonary disease by low frequency ambient pressure changes.

The validity of a new method for measuring thoracic gas volume (Vtg) was studied in 18 bronchitic patients with mild to severe airway obstruction. The method entailed submitting the subject to very slow sinusoidal variations of ambient pressure (delta Pam) and studying the relationship between delta Pam and the resulting gas displacement at the mouth (delta Vaw): Vtgapc = PB.delta Vaw/delta Pam.cos phi, where PB is barometric minus alveolar water vapor pressure, and phi is the phase angle between Pam and Vaw. delta Pam of 40 cm H2O at 0.05 Hz were achieved by placing the subject in a 410-I body chamber connected to a large stroke volume reciprocating pump. Pam and Vaw were processed digitally by Fourier transform to obtain their amplitude ratio and phase angle at the frequency of interest. Vtg was also measured by body plethysmography (Vtgplet) during slow panting maneuvers (0.79 +/- 0.19 Hz) and also in order to detect any artifactual frequency dependence at a higher panting frequency (1.71 +/- 0.27 Hz); the agreement between the 2 estimates in all subjects (r = 0.975) suggested that Vtgplet could be taken as a valid reference. Functional residual capacities derived from Vtgapc and Vtgplet were not significantly different (5.113 +/- 1.198 versus 5.260 +/- 1.328 L) and were highly correlated (r = 0.915). Intermethod differences averaged 1.7 +/- 10.5% and were not significantly correlated to functional indices. We conclude that the new method provides accurate Vtg values in patients with chronic airway obstruction.

Adult↗

An incremental method to assess the linearity of gas flowmeters: application to Fleisch pneumotachographs.

A new method of studying the linearity of gas flowmeters was tested on different models of Fleisch pneumotachographs. The method applies a steady flow to the test flowmeter, which is increased in a stepwise manner by adding a constant flow-increment. This is achieved using two flow sources in parallel. The method does not require any reference flow channel and may be implemented with standard laboratory equipment. Using this method, the gain of Fleisch pneumotachographs, whatever their size, decreased by about 2-3% from low flows to about 40% of their nominal full scale (FS), and then increased almost linearly with increasing flow. The error was 8-13% at 200% FS. The following equation was devised to correct the data at high flow: Vc = Vt (1-K (Vt-S] where Vc and Vt are the corrected and measured flow respectively, K a gain correction factor and S a flow threshold below which no correction is needed. Applying this correction with suitable coefficients, the maximal error was below 3% from 0-200% FS.

Humans↗

Density dependence of respiratory input impedance re-evaluated with a head generator minimizing upper airway shunt.

Total respiratory impedance was assessed from 4 to 30 Hz in ten normal subjects breathing air and a helium-oxygen gas mixture using two methods of applying pressure oscillations at the airway opening: 1) the conventional method where pressure is varied at the mouth: 2) the method recently developed by Peslin et al. (J Appl Physiol, 1985, 59, 1790-1795) in which pressure is varied both at the mouth and around the head to minimize transmural pressure across upper airway walls, and the corresponding artefact. When breathing air slightly lower resistances (p less than 0.05) and considerably higher inertances (p less than 0.001) were found using the head generator. Breathing helium-oxygen reduced respiratory resistance and its frequency dependence, as well as respiratory inertance very significantly (p less than 0.001), with minor differences between the changes seen with the two methods. In contrast, the changes in respiratory compliance were small, and not in the same direction, when pressure was varied at the mouth and around the head. It is concluded that the accuracy of the conventional method may be sufficient for diagnostic purposes in subjects without gross mechanical abnormalities, i.e. for early detection of mechanical abnormalities.

Airway Resistance↗

Assessment of thoracic gas volume by low-frequency ambient pressure changes in children.

The validity of a new method for measuring thoracic gas volume (TGV) was studied in 69 children, 4-16 yrs old, including twelve normal children and 57 children with an obstructive (n = 38) or restrictive (n = 19) respiratory disease. The method consisted of applying very slow (0.05 Hz) sinusoidal variations of ambient pressure around the body (delta Pam = 40 cmH2O peak to peak) and studying the relationship between delta Pam and the resulting gas displacement at the mouth (Vaw): TGVapc = PB.delta Vaw/delta Pam.cos phi, where PB is barometric minus alveolar water vapour pressure and phi the phase angle between Pam and Vaw. Functional residual capacities derived from TGVapc (FRCapc) were compared to the values obtained by plethysmography (FRCplet) and by helium dilution (FRCdil). FRCapc did not differ significantly from FRCplet in either the entire group (1.75 +/- 0.62 l vs 1.79 +/- 0.45 l) or in the patient subgroups. However, with the new method a trend to slightly lower FRCs was seen in patients with the most obstruction (p less than 0.05). FRCdil was significantly lower than both FRCapc and FRCplet (p less than 0.001), particularly in children with obstruction. Significant correlations were found between the three methods (p less than 0.001). On the other hand, the method investigated requires that the subject breathe very regularly for a period of several minutes. This was rarely achieved, so that the reproducibility of the measurements was unacceptably low. At present, the method cannot be recommended for routine use in 4-16 yr old children.

Adolescent↗

Measurement of thoracic gas volume by low-frequency ambient pressure changes.

When the whole body is exposed to sinusoidal variations of ambient pressure (delta Pam) at very low frequencies (f), the resulting compression and expansion of alveolar gas is almost entirely achieved by gas flow through the airways (Vaw). As a consequence thoracic gas volume (TGV) may be computed from the imaginary part (Im) of the delta Pam/Vaw relationship: TGV = PB/[2 pi f X Im(delta Pam/Vaw)], where PB is barometric minus alveolar water vapor pressure. The method was tested in 35 normal subjects and compared with body plethysmography. The subjects sat in a chamber connected to a large-stroke-volume reciprocating pump that brought about pressure swings of 40 cmH2O at 0.05 Hz. delta Pam and Vaw were digitally processed by fast Fourier transform to extract the low-frequency component from the much larger respiratory flow. Total lung capacities (TLC) obtained by ambient pressure changes and by plethylsmography were highly correlated (r = 0.959, p less than 0.001) and not significantly different (6.96 +/- 1.38 l vs. 6.99 +/- 1.38). TLC obtained by ambient pressure changes were not influenced by lowering the frequency to 0.03 Hz, adding an external resistance at the mouth, or increasing abdominal gas volume. We conclude that the method is practical and in agreement with body plethysmography in normal subjects.

Adolescent↗

Respiratory transfer impedances with pressure input at the mouth and chest.

Two methods of measuring respiratory transfer impedance (Ztr) were compared in 14 normal subjects, from 4 to 30 Hz, 1) studying the relationship between transrespiratory pressure (Prs) and flow at the chest when varying pressure at the mouth (Ztrm) and 2) studying the relationship between Prs and flow at the mouth when varying pressure around the chest wall (Ztrw). The similarity of the two relationships was expected on the basis of a T-network model. Almost identical phase responses were obtained from the two methods. Pressure-flow ratios were slightly larger for Ztrw than for Ztrm, but differences did not exceed 2% on average in 11 of 14 subjects. When the data were analyzed with the six-coefficient model proposed by DuBois et al. (J. Appl. Physiol. 8: 587-594, 1956), similar values were found for tissue compliance and tissue inertance but slightly different values for gaseous inertance in the airways (1.97 +/- 0.35 X 10(-2) cmH2O X l-1 X s2 for Ztrw vs. 1.73 +/- 0.26 for Ztrm; P less than 0.01). Similar results were also found for total respiratory resistance but with a slightly larger contribution of airway resistance for Ztrw (64 +/- 14 vs. 57 +/- 10%; P less than 0.05). As a practical conclusion it is recommended to measure Ztrw, which is technically much easier.

Adult↗