Macrophage modulation by polymerized hemoglobins: Potential as a wound-healing therapy.

Chronic skin wounds are hypoxic and are stalled in a pro-inflammatory state. Hemoglobin (Hb)-based oxygen carriers have shown potential in increasing oxygen delivery to aid wound healing. Macrophages also take up Hb, thus altering their phenotype and the regulation of inflammation. Herein, we compared the effect of Hb and polymerized Hbs (PolyHbs) on the phenotype of human macrophages. Macrophages were incubated with Hb or different forms of PolyHbs, and the inflammatory secretion profile was analyzed. PolyHbs were produced by polymerizing Hb in the relaxed (R) or tense (T) quaternary state and by varying the molar ratio of the glutaraldehyde crosslinking agent to Hb. Hb decreased the secretion of most measured factors. PolyHb treatment led to generally similar secretion profiles; however, Hb had more similar trends to R-state PolyHb. Ingenuity pathway analysis predicted positive outcomes in wound healing and angiogenesis for T-state PolyHb prepared with a 30:1 (glutaraldehyde:Hb) polymerization ratio. When tested in diabetic mouse wounds, T-state PolyHb resulted in the greatest epidermal thickness and vascular endothelial CD31 staining. Thus, the effects of PolyHb on macrophages are affected by the polymerization ratio and the quaternary state, and T-state PolyHb yields secretion profiles that are most beneficial in wound healing.

Trauma Dictations in the Emergency Department: A Quality Improvement/Patient Safety Project.

CONTEXT: Trauma patients frequently represent a unique and challenging patient population in emergency medicine care settings. The policy of the McLaren Oakland Emergency Department (ED) is to have the treatment of all Level 1 and Level 2 trauma activations dictated by the ED resident. This policy is intended to facilitate both patient safety through clear communication between multiple medical services and quality improvement through reporting trauma specific quality metrics to third party agencies. Despite this requirement, trauma dictations in this setting were often found to not be completed. The purpose of this quality improvement/patient safety project was to implement a trauma dictation template to increase the rate of completed ED trauma dictations to above 75% of all Level 1 and Level 2 trauma activations. METHODS: A trauma dictation template was created to aid ED residents while completing trauma dictations. It was thought by the authors that the implementation of a standardized dictation template would help residents specify the necessary components needed to improve both patient safety and quality reporting. The development of the template was a collaborative effort between the emergency medicine residents and faculty, the trauma coordinator and trauma surgeons. The project was evaluated using two separate measures. A "process measure" was first used to determine if the addition of the trauma template made dictating less burdensome for ED residents, and an "outcomes measure" helped the authors examine whether template implementation actually led to an increased rate in completed trauma dictation. RESULTS: Data were collected during a three-month period prior to template implementation and three months after implementation. From November, 2015 through April, 2016, a total of 132 Trauma Activations were reviewed. The rate of completed dictations on Level 1 trauma activations increased from 45.16% to 53.33%. However, the rate of dictations on Level 2 trauma activations decreased from 50% to 30.4%, suggesting that Level 1 trauma patient care may have derived greater improvements from the new dictation template. CONCLUSIONS: The results of the ED residents' evaluative survey responses were generally positive, indicating that the trauma template was perceived by most residents as a useful tool to complete dictations. Even though the outcome goal was not achieved, the project successfully achieved the goal of creating and implementing a usable trauma dictation template. Following the Plan-Do-Study-Act model for quality improvement/patient safety projects, the next project will examine additional barriers preventing users from utilizing this initial well-received tool.

Mixtures of tense and relaxed state polymerized human hemoglobin regulate oxygen affinity and tissue construct oxygenation.

Pure tense (T) and relaxed (R) quaternary state polymerized human hemoglobins (PolyhHbs) were synthesized and their biophysical properties characterized, along with mixtures of T- and R-state PolyhHbs. It was observed that the oxygen affinity of PolyhHb mixtures varied linearly with T-state mole fraction. Computational analysis of PolyhHb facilitated oxygenation of a single fiber in a hepatic hollow fiber (HF) bioreactor was performed to evaluate the oxygenation potential of T- and R-state PolyhHb mixtures. PolyhHb mixtures with T-state mole fractions greater than 50% resulted in hypoxic and hyperoxic zones occupying less than 5% of the total extra capillary space (ECS). Under these conditions, the ratio of the pericentral volume to the perivenous volume in the ECS doubled as the T-state mole fraction increased from 50 to 100%. These results show the effect of varying the T/R-state PolyhHb mole fraction on oxygenation of tissue-engineered constructs and their potential to oxygenate tissues.

Erythrocytes Are Oxygen-Sensing Regulators of the Cerebral Microcirculation.

Energy production in the brain depends almost exclusively on oxidative metabolism. Neurons have small energy reserves and require a continuous supply of oxygen (O2). It is therefore not surprising that one of the hallmarks of normal brain function is the tight coupling between cerebral blood flow and neuronal activity. Since capillaries are embedded in the O2-consuming neuropil, we have here examined whether activity-dependent dips in O2 tension drive capillary hyperemia. In vivo analyses showed that transient dips in tissue O2 tension elicit capillary hyperemia. Ex vivo experiments revealed that red blood cells (RBCs) themselves act as O2 sensors that autonomously regulate their own deformability and thereby flow velocity through capillaries in response to physiological decreases in O2 tension. This observation has broad implications for understanding how local changes in blood flow are coupled to synaptic transmission.

Physicochemical and antibacterial properties of surfactant mixtures with quaternized chitosan microgels.

Antibacterial surfactant mixtures attract widespread interest in the design of consumer product formulations, but often use toxic biocidal agents such as cationic surfactants, triclosan or bleach. To address this, we explored replacing these toxic ingredients with quaternized chitosan microgels, which combine high antibacterial activity with cytocompatibility with mammalian cells. Specifically, three essential properties of microgel mixtures with model anionic (sodium dodecyl sulfate, SDS) and nonionic (Triton X-100, TX-100) surfactants (and with SDS/TX-100 mixtures) were investigated: (1) colloidal stability, (2) antibacterial activity, and (3) hydrophobe solubilization. Additionally, the effect of surfactant on dispersion turbidity, which can be important in the formulation of aesthetically-appealing products, was explored. The microgels formed more-stable dispersions when mixed with nonionic TX-100, but quickly precipitated when mixed with the electrostatically-binding SDS and SDS/TX-100 surfactant systems at fairly-low (millimolar) surfactant concentrations. At higher SDS concentrations the microgels were redispersed and ultimately dissolved when mixed with only SDS, but remained precipitated in SDS/TX-100 mixtures. Furthermore, the electrostatic binding of SDS to quaternized chitosan diminished its antibacterial activity and (because the SDS-bearing mixtures with strong biocidal activity were limited to low surfactant concentrations) also resulted in limited hydrophobe solubilization. Conversely, microgels mixed with TX-100 maintained their biocidal activity even when the surfactant was in excess, and exhibited good solubilization properties. This suggests that surfactant-based products that use quaternized chitosan microgels as antibacterial agents should optimally be formulated using nonionic surfactants.