Safety of the injectable expanding biopolymer foam for non-compressible truncal bleeding in swine.

BACKGROUND: A novel hydrophobically modified chitosan (hm-chitosan) polymer has been previously shown to improve survival in a non-compressible intra-abdominal bleeding model in swine. We performed a 28-day survival study to evaluate the safety of the hm-chitosan polymer in swine. METHODS: Female Yorkshire swine (40-50 kg) were used. A mild, non-compressible, closed-cavity bleeding model was created with splenic transection. The hm-chitosan polymer was applied intra-abdominally through an umbilical nozzle in the same composition and dose previously shown to improve survival. Animals were monitored intraoperatively and followed 28 days postoperatively for survival, signs of pain, and end-organ function. Gross pathological and microscopic evaluations were performed at the conclusion of the experiment. RESULTS: A total of 10 animals were included (hm-chitosan = 8; control = 2). The 2 control animals survived through 28 days, and 7 of the 8 animals from the hm-chitosan group survived without any adverse events. One animal from the hm-chitosan group required early termination of the study for signs of pain, and superficial colonic ulcers were found on autopsy. Laboratory tests showed no signs of end-organ dysfunction after exposure to hm-chitosan after 28 days. On gross pathological examination, small (<0.5 cm) peritoneal nodules were noticed in the hm-chitosan group, which were consistent with giant-cell foreign body reaction in microscopy, presumably related to polymer remnants. Microscopically, no signs of systemic polymer embolization or thrombosis were noticed. CONCLUSION: Prolonged intraperitoneal exposure to the hm-chitosan polymer was tolerated without any adverse event in the majority of animals. In the single animal that required early termination, the material did not appear to be associated with end-organ dysfunction in swine. Superficial colonic ulcers that would require surgical repair were identified in 1 out of 8 animals exposed to hm-chitosan.

Impact of pH on Gas-Particle Partitioning of Semi-Volatile Organics in Multicomponent Aerosol.

The partitioning of semivolatile organic compounds (SVOCs) between the condensed and gas phases can have significant implications for the properties of aerosol particles. In addition to affecting size and composition, this partitioning can alter radiative properties and impact cloud activation processes. We present measurements and model predictions on how activity and pH influence the evaporation of SVOCs from particles to the gas phase, specifically investigating aqueous inorganic particles containing dicarboxylic acids (DCAs). The aerosols are studied at the single-particle level by using optical trapping and cavity-enhanced Raman spectroscopy. Optical resonances in the spectra enable precise size tracking, while vibrational bands allow real-time monitoring of pH. Results are compared to a Maxwell-type model that accounts for volatile and nonvolatile solutes in aqueous droplets that are held at a constant relative humidity. The aerosol inorganic-organic mixture functional group activity coefficients thermodynamic model and Debye-Hückel theory are both used to calculate the activities of the species present in the droplet. For DCAs, we find that the evaporation rate is highly sensitive to the particle pH. For acidity changes of approximately 1.5 pH units, we observe a shift from a volatile system to one that is completely nonvolatile. We also observe that the pH itself is not constant during evaporation; it increases as DCAs evaporate, slowing the rate of evaporation until it eventually ceases. Whether a DCA evaporates or remains a stable component of the droplet is determined by the difference between the lowest pKa of the DCA and the pH of the droplet.

Chitosan-based lifefoam improves survival in lethal noncompressible abdominal bleeding in swine.

BACKGROUND: In military combat settings, noncompressible closed cavity exsanguination is the leading cause of potentially survivable deaths, with no effective treatment available at point of injury. The aim of this study was to assess whether an expanding foam based on hydrophobically modified chitosan (hm-chitosan) may be used as a locally injectable hemostatic agent for the treatment of noncompressible bleeding in a swine model. METHODS: A closed-cavity, grade V hepato-portal injury was created in all animals resulting in massive noncoagulopathic, noncompressible bleeding. Animals received either fluid resuscitation alone (control, n = 8) or fluid resuscitation plus intraperitoneal hm-chitosan agent through an umbilical port (experimental, n = 18). The experiment was terminated at 180 minutes or death (defined as end-tidal CO2 <8mmHg or mean arterial pressure [MAP] <15mmHg), whichever came first. RESULTS: All animals had profound hypotension and experienced a near-arrest from hypovolemic shock (mean MAP = 24 mmHg at 10 minutes). Mean survival time was higher than 150 minutes in the experimental arm versus 27 minutes in the control arm (P < .001). Three-hour survival was 72% in the experimental group and 0% in the control group (P = .002). Hm-chitosan stabilized rising lactate, preventing acute lethal acidosis. MAP improved drastically after deployment of the hm-chitosan and was preserved at 60 mmHg throughout the 3 hours. Postmortem examination was performed in all animals and the hepatoportal injuries were anatomically similar. CONCLUSION: Intraperitoneal administration of hm-chitosan-based foam for massive, noncompressible abdominal bleeding improves survival in a lethal, closed-cavity swine model. Chronic safety and toxicity studies are required.

Simultaneous Retrieval of the Size and Refractive Index of Suspended Droplets in a Linear Quadrupole Electrodynamic Balance.

Single-particle trapping is an effective strategy to explore the physical and optical properties of aerosol with high precision. Laser-based methods are commonly used to probe the size, optical properties, and composition of nonlight-absorbing droplets in optical and electrodynamic traps. However, these methods cannot be applied to droplets containing photoactive chromophores, and thus, single-particle methods have been restricted to only a subset of atmospherically relevant particle compositions. In this work, we explore the application of a broadband light scattering approach, Mie resonance spectroscopy, to simultaneously probe the size and the refractive index (RI) of droplets in a linear quadrupole electrodynamic balance. We examine the evaporation of poly(ethylene glycol)s and compare the calculated vapor pressures with literature values to benchmark the size accuracy without prior constraint on the RI. We then explore the hygroscopic growth and deliquescence of sodium chloride droplets, measuring RI at the deliquescence relative humidity and demonstrating agreement to literature values. These data allow the wavelength dependence of the RI of aqueous NaCl to be determined using a first-order Cauchy equation, and we effectively reproduce literature data from multiple techniques. We finally discuss measurements from a light-absorbing aqueous droplet containing humic acid and interpret the spectra via the imaginary component of the RI. The approach described here allows the radius of nonabsorbing droplets to be determined within 0.1%, the refractive index within 0.2%, and the first-order term in the Cauchy dispersion equation within ∼5%.

Water Uptake and Loss in Viscous Aerosol Particles with Concentration-Dependent Diffusivities.

An accurate understanding of the equilibration timescale of organic aerosol particles with surrounding water vapor is difficult because of the strong concentration-dependent diffusivities that are present in these systems. We examine this problem along with the closely related problem of the time-dependent radius of a binary aerosol particle during the uptake or loss of water. The governing equations and boundary conditions are discussed and a boundary value problem is formulated and solved. The resulting expressions are applied to water uptake and loss in two systems of atmospheric importance: aqueous-inorganic particles and high-viscosity organic particles. Accuracy is evaluated through a comparison with numerical solutions. For particles whose diffusivity has a strong dependence on water concentration and whose viscosity remains above 1 Pa·s during water uptake or loss, the expression for the characteristic equilibration time is found to be in excellent agreement with numerical results. Moreover, it provides physical insights into mass transport processes.

Synthesis of Oligo(1,8-pyrenylene)s: A Series of Functional Molecular Liquids.

A monomer-through-pentamer series of oligo(1,8-pyrenylene)s was synthesized using a two-step iterative synthetic strategy. The trimer, tetramer, and pentamer are mixtures of atropisomers that interconvert slowly at room temperature (as shown by variable-temperature NMR analysis). They are liquids well below room temperature, as indicated by POM, DSC and SWAXS analysis. These oligomers are highly fluorescent both in the liquid state and in dilute solution (λF,max = 444-457 nm, φF = 0.80) and an investigation of their photophysical properties demonstrated that delocalization plays a larger role in their excited states than it does in related pyrene-based oligomers.