Collagen and elastin are thought to dominate the elasticity of the connective tissue including lung parenchyma. The glycosaminoglycans on the proteoglycans may also play a role because osmolarity of interstitial fluid can alter the repulsive forces on the negatively charged glycosaminoglycans, allowing them to collapse or inflate, which can affect the stretching and folding pattern of the fibers. Hence, we hypothesized that the elasticity of lung tissue arises primarily from 1) the topology of the collagen-elastin network and 2) the mechanical interaction between proteoglycans and fibers. We measured the quasi-static, uniaxial stress-strain curves of lung tissue sheets in hypotonic, normal, and hypertonic solutions. We found that the stress-strain curve was sensitive to osmolarity, but this sensitivity decreased after proteoglycan digestion. Images of immunofluorescently labeled collagen networks showed that the fibers follow the alveolar walls that form a hexagonal-like structure. Despite the large heterogeneity, the aspect ratio of the hexagons at 30% uniaxial strain increased linearly with osmolarity. We developed a two-dimensional hexagonal network model of the alveolar structure incorporating the mechanical properties of the collagen-elastin fibers and their interaction with proteoglycans. The model accounted for the stress-strain curves observed under all experimental conditions. The model also predicted how aspect ratio changed with osmolarity and strain, which allowed us to estimate the Young's modulus of a single alveolar wall and a collagen fiber. We therefore identify a novel and important role for the proteoglycans: they stabilize the collagen-elastin network of connective tissues and contribute to lung elasticity and alveolar stability at low to medium lung volumes.
Emphysema causes a permanent destruction of alveolar walls leading to airspace enlargement, loss of elastic recoil, decrease in surface area for gas exchange, lung hyperexpansion, and increased work of breathing. The most accepted hypothesis of how emphysema develops is based on an imbalance of protease and antiprotease activity leading to the degradation of elastin within the fiber network of the extracellular matrix. Here we report novel roles for mechanical forces and collagen during the remodeling of lung tissue in a rat model of elastase-induced emphysema. We have developed a technique to measure the stress-strain properties of tissue sections while simultaneously visualizing the deformation of the immunofluorescently labeled elastin-collagen network. We found that in the elastase treated tissue significant remodeling leads to thickened elastin and collagen fibers and during stretching, the newly deposited elastin and collagen fibers undergo substantially larger distortions than in normal tissue. We also found that the threshold for mechanical failure of collagen, which provides mechanical stability to the normal lung, is reduced. Our results indicate that mechanical forces during breathing are capable of causing failure of the remodeled extracellular matrix at loci of stress concentrations and so contribute to the progression of emphysema.
The dynamic stiffness (H), damping coefficient (G), and harmonic distortion (k(d)) characterizing tissue nonlinearity of lung parenchymal strips from guinea pigs were assessed before and after treatment with elastase or collagenase between 0.1 and 3.74 Hz. After digestion, data were obtained both at the same mean length and at the same mean force of the strip as before digestion. At the same mean length, G and H decreased by approximately 33% after elastase and by approximately 47% after collagenase treatment. At the same mean force, G and H increased by approximately 7% after elastase and by approximately 25% after collagenase treatment. The k(d) increased more after collagenase (40%) than after elastase (20%) treatment. These findings suggest that, after digestion, the fraction of intact fibers decreases, which, at the same mean length, leads to a decrease in moduli. At the same mean force, collagen fibers operate at a higher portion of their stress-strain curve, which results in an increase in moduli. Also, G and H were coupled so that hysteresivity (G/H) did not change after treatments. However, k(d) was decoupled from elasticity and was sensitive to stretching of collagen, which may be of value in detecting structural alterations in the connective tissue of the lung.
We measured lung impedance in rats in closed chest (CC), open chest (OC), and isolated lungs (IL) at four transpulmonary pressures with a optimal ventilator waveform. Data were analyzed with an homogeneous linear or an inhomogeneous linear model. Both models include tissue damping and elastance and airway inertance. The homogeneous linear model includes airway resistance (Raw), whereas the inhomogeneous linear model has a continuous distribution of Raw characterized by the mean Raw and the standard deviation of Raw (SDR). Lung mechanics were compared with tissue strip mechanics at frequencies and operating stresses comparable to those during lung impedance measurements. The hysteresivity (eta) was calculated as tissue damping/elastance. We found that 1) airway and tissue parameters were different in the IL than in the CC and OC conditions; 2) SDR was lowest in the IL; and 3) eta in IL at low transpulmonary pressure was similar to eta in the tissue strip. We conclude that eta is primarily determined by lung connective tissue, and its elevated estimates from impedance data in the CC and OC conditions are a consequence of compartment-like heterogeneity being greater in CC and OC conditions than in the IL.
1. The effects of the essential oil of Croton nepetaefolius (EOCN) and its major constituent, 1,8-cineole, on the compound action potential (CAP) of nerve were investigated. 2. Experiments were performed in sciatic nerves dissected from Wistar rats, mounted in a moist chamber and stimulated at a frequency of 0.2 Hz, with electric pulses of 100 micros duration at 20-40 V. Evoked CAP were displayed on an oscilloscope and recorded on a computer. The CAP control parameters were as follows: peak-to-peak amplitude 8.1 +/- 0.6 mV (n = 15); conduction velocity 83.3 +/- 4.2 m/s (n = 15); chronaxie 58.0 +/- 6.8 msec (n = 6); and rheobase 2.8 +/- 0.1 V (n = 6). 3. Lower concentrations of EOCN (100 and 300 microg/mL) and 1,8-cineole (153 and 307 microg/mL; i.e. 1 and 2 mmol/L, respectively) had no significant effects on CAP control parameters throughout the entire recording period. However, at the end of 180 min exposure of the nerve to the drug, peak-to-peak amplitude was significantly (P < 0.05) reduced to 27.4 +/- 6.7 and 1.7 +/- 0.8% of control values by 500 and 1000 microg/mL EOCN, respectively (n = 6), and to 76.5 +/- 4.4, 70.0 +/- 3.9 and 14.8 +/- 4.1% of control values by 614, 920 and 1227 microg/mL (i.e. 4, 6 and 8 mmol/L) 1,8-cineole, respectively (n = 6). Regarding conduction velocity, at the end of the 180 min exposure period, this parameter was significantly reduced to 85.8 +/- 7.3 and 48.7 +/- 12.3% (n = 6) of control values by 500 and 1000 microg/mL EOCN, respectively, and to 86.4 +/- 4.5 and 76.1 +/- 5.2% (n = 6) by 920 and 1227 microg/mL 1,8-cineole, respectively. Chronaxie and rheobase were significantly increased by the higher concentrations of both EOCN and 1,8-cineole. 4. It is concluded that EOCN and its main constituent 1,8-cineole block nerve excitability in a concentration-dependent manner, an effect that was totally reversible with 1,8-cineole but not with EOCN. This suggests that other constituents of EOCN, in addition to 1,8-cineole, may contribute to the mediation of this effect of EOCN.
The market for industrial enzymes has witnessed constant growth, which is currently around 7% a year, projected to reach $10.5 billion in 2024. Lipases are hydrolase enzymes naturally responsible for triglyceride hydrolysis. They are the most expansively used industrial biocatalysts, with wide application in a broad range of industries. However, these biocatalytic processes are usually limited by the low stability of the enzyme, the half-life time, and the processes required to solve these problems are complex and lack application feasibility at the industrial scale. Emerging technologies create new materials for enzyme carriers and sophisticate the well-known immobilization principles to produce more robust, eco-friendlier, and cheaper biocatalysts. Therefore, this review discusses the trending studies and industrial applications of the materials and protocols for lipase immobilization, analyzing their advantages and disadvantages. Finally, it summarizes the current challenges and potential alternatives for lipases at the industrial level.
1. 1,8-Cineole is a non-toxic small terpenoid oxide believed to have medicinal properties in folk medicine. It has been shown to have various pharmacological effects, including blockade of the compound action potential (AP). In the present study, using intracellular recording techniques, we investigated the effects of 1,8-cineole on the electrophysiological parameters of neurons of the superior cervical ganglion (SCG) in rats. 2. 1,8-Cineole (0.1-6 mmol/L) showed reversible and concentration-dependent effects on various electrophysiological parameters. At 3 and 6 mmol/L, but not at 0.1 and 1 mmol/L, 1,8-cineole significantly diminished the input resistance (R(i)) and altered the resting potential (E(m)) to more positive values. At 6 mmol/L, 1,8-cineole completely blocked all APs within 2.7 +/- 0.6 min (n = 12). In neurons exposed to 3 and 1 mmol/L 1,8-cineole, the effects regarding excitability varied from complete AP blockade to minor inhibition of AP parameters. The depolarization of E(m) and the decrease in R(i) induced by 6 mmol/L 1,8-cineole were unaltered by 200 micromol/L niflumic acid, a well known blocker of Ca(2+)-activated Cl(-) currents. 3. Significant correlations (Pearson correlation test) were found between changes in E(m) and decreases in AP amplitude (r = -0.893; P < 0.00282) and maximum ascendant inclination (r = -0.799; P < 0.0173), but not for maximum descendant inclination (r = 0.598; P < 0.117). Application of current to restore the transmembrane potential equal to control E(m) values in the presence of 6 mmol/L 1,8-cineole resulted in the partial recovery of AP. 4. The present study shows that 1,8-cineole effectively blocks the excitability of SCG neurons, probably through various mechanisms, one of which acts indirectly via depolarization of the neuronal cytoplasmatic membrane.
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