Analysis of pectin biopolymer phase states using acoustic emissions.

Acoustic emissions are stress or elastic waves produced by a material under external load. Since acoustic emissions are generated from within and transmitted through the substance, the acoustic signature provides insights into the physical and mechanical properties of the material. In this report, we used a constant velocity probe with force and acoustic emission monitoring to investigate the properties of glass phase and gel phase pectin films. In the gel phase films, a constant velocity uniaxial load produced periodic premonitory acoustic emissions with coincident force variations (saw-tooth pattern). SEM images of the gel phase microarchitecture indicated the presence of slip planes. In contrast, the glass phase films demonstrated early acoustic emissions, but effectively no force or acoustic evidence of periodic or premonitory emissions. Microstructural imaging of the glass phase films indicated the presence of early microcracks as well as dense polymerization of the pectin (without evidence of slip planes). We conclude that the water content in the pectin films contributes to not only the physical properties of the films, but also the stick-slip motion observed with constant uniaxial load. Further, acoustic emissions provide a sensitive and practical measure of this mechanical behavior.

Synergistic effects of psychological and immune stressors on inflammatory cytokine and sickness responses in humans.

Activation of the innate immune system is commonly accompanied by a set of behavioural, psychological and physiological changes known as 'sickness behaviour'. In animals, infection-related sickness symptoms are significantly increased by exposure to psychosocial stress, suggesting that psychological and immune stressors may operate through similar pathways to induce sickness. We used a double-blind, randomised, placebo-controlled design to examine the effect of acute psychological stress on immune and subjective mood responses to typhoid vaccination in 59 men. Volunteers were assigned to one of four experimental conditions in which they were either injected with typhoid vaccine or saline placebo, and then either rested or completed two challenging behavioural tasks. Typhoid vaccine induced a significant rise in participants' serum levels of interleukin-6 (IL-6) and this response was significantly larger in the stress versus rest conditions. Negative mood increased immediately post-tasks, an effect also more pronounced in the vaccine/stress condition. In the vaccine/stress group, participants with larger IL-6 responses had heightened systolic blood pressure responses to tasks and elevated post-stress salivary levels of the noradrenaline metabolite 3-methoxy-phenyl glycol (MHPG) and cortisol. Our findings suggest that, as seen in animals, psychological and immune stressors may act synergistically to promote inflammation and sickness behaviour in humans.

Deep pulmonary lymphatics in immature lungs.

Recently, we found that the translocation of inhaled nanoparticles from the air space to secondary organs is age dependent and substantially greater in neonates than in adults (J Respir Crit Care Med 177: A48, 2008). One reason for this difference might be age-dependent differences in alveolar barrier integrity. Because the neonate lung is undergoing morphogenetic and fluid balance changes, we hypothesize that the alveolar barrier of developing lungs is more easily compromised and susceptible to foreign material influx than that of adult lungs. On the basis of these hypotheses, we predict that the postnatally developing lung is also more likely to allow the translocation of some materials from the air space to the lymphatic lumens. To test this idea, we intratracheally instilled methyl methacrylate into immature and adult lungs and compared lymphatic filling between these two age groups. Scanning electron microscopy of the resultant corrosion casts revealed peribronchial saccular and conduit lymphatic architecture. Deep pulmonary lymphatic casts were present on the majority (58.5%) of airways in immature lungs, but lymphatic casting in adult lungs, as anticipated, was much more infrequent (21.6%). Thus the neonate lung appears to be more susceptible than the adult lung to the passage of instilled methyl methacrylate from the air space into the lymphatics. We speculate that this could imply greater probability of translocation of other materials, such as nanoparticles, from the immature lung as well.

Structural heteropolysaccharides as air-tight sealants of the human pleura.

Pulmonary "air leaks," typically the result of pleural injury caused by lung surgery or chest trauma, result in the accumulation of air in the pleural space (pneumothorax). Air leaks are a major source of morbidity and prolonged hospitalization after pulmonary surgery. Previous work has demonstrated structural heteropolysaccharide (pectin) binding to the mouse pleural glycocalyx. The similar lectin-binding characteristics and ultrastructural features of the human and mouse pleural glycocalyx suggested the potential application of these polymers in humans. To investigate the utility of pectin-based polymers, we developed a simulacrum using freshly obtained human pleura. Pressure-decay leak testing was performed with an inflation maneuver that involved a 3 s ramp to a 3 s plateau pressure; the inflation was completely abrogated after needle perforation of the pleura. Using nonbiologic materials, pressure-decay leak testing demonstrated an exponential decay with a plateau phase in materials with a Young's modulus less than 5. In human pleural testing, the simulacrum was used to test the sealant function of four mixtures of pectin-based polymers. A 50% high-methoxyl pectin and 50% carboxymethylcellulose mixture demonstrated no sealant failures at transpleural pressures of 60 cmH2 O. In contrast, pectin mixtures containing 50% low-methoxyl pectin, 50% amidated low-methoxyl pectins, or 100% carboxymethylcellulose demonstrated frequent sealant failures at transpleural pressures of 40-50 cmH2 O (p < 0.001). Inhibition of sealant adhesion with enzyme treatment, dessication and 4°C cooling suggested an adhesion mechanism dependent upon polysaccharide interpenetration. We conclude that pectin-based heteropolysaccharides are a promising air-tight sealant of human pleural injuries. © 2018 Wiley Periodicals, Inc. J. Biomed. Mater. Res. Part B, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 799-806, 2019.

ß-Eudesmol, an Oxygenized Sesquiterpene, Reduces the Increase in Saliva 3-Methoxy-4-Hydroxyphenylglycol After the "Trier Social Stress Test" in Healthy Humans: A Randomized, Double-Blind, Placebo-Controlled Cross-Over Study.

Hops, the immature inflorescences of the female hop plant (Humulus lupulus L.) are one of the main components of beer and provides flavor and bitterness. ß-Eudesmol, an oxygenated sesquiterpene, is reported to accumulate in a particular hop cultivar. Recently, we revealed that ß-Eudesmol ingestion affected autonomic nerve activity in an animal model. The effect on humans has not been elucidated, therefore, we investigated the effects of ß-Eudesmol on reducing objective and subjective markers related to sympathetic nerve activity after the application of mental stress in healthy participants. Fifty participants (male and female aged 20 to 50 years) were randomly assigned to two groups. Five minutes before taking the Trier Social Stress Test (TSST) as a mental stressor, participants in each group ingested a beverage containing ß-Eudesmol, the active beverage, or a placebo beverage that did not contain ß-Eudesmol. Saliva 3-methoxy-4-hydroxyphenylglycol (MHPG), a major product of noradrenaline breakdown and a representative marker of sympathetic nerve activity, was significantly lower just after the TSST in the active group compared with the placebo group. Saliva cortisol, a marker of the endocrine stress response system, was not significantly different between the two groups. No adverse events related to test beverage ingestion were observed. This is the first experimental evidence of ß-Eudesmol effect for mental stress in human.

Functional Mechanics of a Pectin-Based Pleural Sealant after Lung Injury.

Pleural injury and associated air leaks are a major influence on patient morbidity and healthcare costs after lung surgery. Pectin, a plant-derived heteropolysaccharide, has recently demonstrated potential as an adhesive binding to the glycocalyx of visceral mesothelium. Since bioadhesion is a process likely involving the interpenetration of the pectin-based polymer with the glycocalyx, we predicted that the pectin-based polymer may also be an effective sealant for pleural injury. To explore the potential role of an equal (weight%) mixture of high-methoxyl pectin and carboxymethylcellulose as a pleural sealant, we compared the yield strength of the pectin-based polymer to commonly available surgical products. The pectin-based polymer demonstrated significantly greater adhesion to the lung pleura than the comparison products (p < 0.001). In a 25 g needle-induced lung injury model, pleural injury resulted in an air leak and a loss of airway pressures. After application of the pectin-based polymer, there was a restoration of airway pressure and no measurable air leak. Despite the application of large sheets (50 mm2) of the pectin-based polymer, multifrequency lung impedance studies demonstrated no significant increase in tissue damping (G) or hysteresivity (η)(p > 0.05). In 7-day survival experiments, the application of the pectin-based polymer after pleural injury was associated with no observable toxicity, 100% survival (N = 5), and restored lung function. We conclude that this pectin-based polymer is a strong and nontoxic bioadhesive with the potential for clinical application in the treatment of pleural injuries.

Biological and optical properties of fluorescent nanoparticles developed for intravascular imaging.

Intravascular tracers in the blood circulation can provide a description of the flow field over time and space. To address the limitations of existing intravascular tracers, we have developed fluorescent nanoparticles capable of providing detailed information regarding the intravascular flow field. The nanoparticles were designed to maximize plasma half-life as well as minimize interactions with other blood components. The bioavailability of the particles in the blood circulation required nanoscale size and low surface charge density. Intravital imaging of nanoparticles in the microcirculation demonstrated that the fluorescence intensity of the nanoparticles was a major determinant of both temporal and spatial resolution of the flow field. We conclude that nanoparticles prepared with these physical and optical properties can provide an accurate description of the localized intravascular flow field.

The effects of depressive symptoms on cardiovascular and catecholamine responses to the induction of depressive mood.

We examined the effects of depressive symptoms on cardiovascular and catecholamine responses to the induction of different mood states. Fifty-five healthy men and women (mean age 23.4 +/- 3 years) were recruited. Depressive symptoms were evaluated using the Center for Epidemiological Studies Depression Scale (CES-D) and participants were classified into high depressive (CES-D*16) or low depressive symptoms (CES-D < 16) groups. Following a baseline period, participants were required to complete two separate speech tasks where they were asked to recall life events that made them feel angry or depressed. The tasks were separated by a 30-min recovery period and the order was randomised between participants using a counterbalanced design. Cardiovascular function was monitored continuously using a Finometer device and saliva was collected for the assessment of 3-methoxy-phenylglycol (MHPG, the major metabolite of norephinephrine). Blood pressure (BP), heart rate, and total peripheral resistance (TPR) were significantly increased in response to both tasks (p = .001). Averaged over conditions, higher diastolic BP and higher MHPG levels were observed in high depressive symptoms participants. MHPG levels did not change in response to mood induction in the low depressive symptoms group. However, the high depression symptoms group showed significantly higher levels of MHPG during recovery from the depressed mood induction task and increased levels immediately after the anger induction task. These findings suggest depressive symptoms are associated with heightened central adrenergic activation during negative mood induction, but that the time course of responses is dependent on the type of emotion elicited.

Salivary 3-methoxy-4-hydroxyphenylglycol increases after awakening in healthy young adults.

Levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) may reflect central noradrenergic activity. In this study, we investigated salivary MHPG changes after awakening, and explored their relationships with cortisol and peripheral autonomic activity. The participants were 25 college students. Saliva samples were collected on awakening and 30 min after awakening to determine MHPG and cortisol. Ambulatory electrocardiograms were obtained to assess heart rate, cardiac sympathetic index (CSI), and cardiac vagal index (CVI) before and after awakening. MHPG levels increased significantly during the first 30 min after awakening. Similarly, cortisol, heart rate, and CSI increased during the 30 min after awakening, but changes in MHPG did not correlate with changes in cortisol, heart rate, CSI, and CVI during that period. This study demonstrated that salivary MHPG levels increase after awakening, in common with cortisol, heart rate, and cardiac sympathetic activity.

Short sleeping time and psychobiological responses to acute stress.

The aim of this study was to examine the association between self-reported sleeping time and psychobiological stress responses [3-Methoxy-4-hydroxyphenylglycol (MHPG) and Secretory immunoglobulin A (IgA), perceived stress responses]. Thirty seven healthy men and women were recruited, and participants were divided according to the habitual number of hours of sleep as follows: adequate sleepers (AS) (6-8h sleep per night regularly) (N=22) and short sleepers (SS) (less than 5h sleep per night regularly) (N=15). Salivary MHPG, s-IgA and perceived stress were measured at baseline, immediately after task and recovery period. An increase in free-MHPG during the task period was observed in AS although free-MHPG increased only after the task period in SS. The level of s-IgA in both groups significantly increased during the task period, and quickly returned to a basal level during the recovery period. The results show that less than 5h of sleep was associated with different responsiveness to the Stroop color word conflict task compared to sufficient sleep, especially in the NA system.

Effect of intraluminal pillars on particle motion in bifurcated microchannels.

A central feature of intussusceptive angiogenesis is the development of an intravascular pillar that bridges the opposing sides of the microvessel lumen. In this report, we created polydimethyl siloxane (PDMS) microchannels with geometric proportions based on corrosion casts of the colon microcirculation. The structure of the PDMS microchannels was a bifurcated channel with an intraluminal pillar in the geometric center of the bifurcation. The effect of the intraluminal pillar on particle flow paths was investigated using an in vitro perfusion system. The microchannels were perfused with fluorescent particles, and the particle movements were recorded using fluorescence videomicroscopy. We found that the presence of an intravascular pillar significantly decreased particle velocity in the bifurcation system (p < 0.05). In addition, the pillar altered the trajectory of particles in the center line of the flow stream. The particle trajectory resulted in prolonged pillar contact as well as increased residence time within the bifurcation system (p < 0.001). Our results suggest that the intravascular pillar not only provides a mechanism of increasing resistance to blood flow but may also participate in spatial redistribution of cells within the flow stream.