Interview Feature: Interview with Frank N. Kelley, Dean, College of Polymer Science and Polymer Engineering, and Professor of Polymer Science, June 1996

Author Institution: Department of Educational Foundations and Leadership, The University of Akro

Elastin metabolism and chemistry: potential roles in lung development and structure.

Elastic fibers are important for elasticity and extensibility of lung tissue. In the developing lung, elastic fibers appear in greatest numbers during the process or period of alveolarization . A variety of mesenchymal cells in lung appear responsible for elastin synthesis. Elastin is a novel protein both from the standpoint of its processing into elastic fibers and chemical properties. For example, elastin undergoes posttranslational modification before its assembly into fibers. These steps include limited proteolysis, hydroxylation of prolyl residues and the oxidative deamination of lysyl residues prior to their incorporation into the crosslinks that covalently bond together polypeptide chains of elastin. The crosslinking amino acids include lysinonorleucine , merodesmosine and desmosine isomers. A key enzyme that controls this process is lysyl oxidase. Lysyl oxidase is a copper metalloprotein whose activity is responsive to and modulated by environmental insults, nutrition deficiencies and the administration of various pharmacological agents. Regarding chemical properties, elastin is one of the most apolar proteins secreted by mammalian cells. Moreover, elastin is one of the most long-lived proteins secreted into the extracellular matrix. In relationship to its processing into elastic fibers and chemical properties, details related to major aspects of elastin metabolism as well as speculation on its potential as a factor in lung development and disease are discussed

Influence of asymptomatic pneumonia on the response to hemorrhage and resuscitation in swine

INTRODUCTION: Investigation of resuscitation fluids in our swine hemorrhage model revealed moderate to severe chronic pneumonia in five swine at necropsy. Our veterinary staff suggested that we perform a retrospective analysis of prospectively collected data from these animals. We compared the data to that of ten healthy swine to determine the physiologic consequences of the added stress on our hemorrhage/resuscitation model. METHODS: Anesthetized, immature female swine (40 ± 5 kg) were instrumented for determining arterial and venous pressures, cardiac output and urine production. A controlled hemorrhage of 20 ml/kg over 4 min 40 sec was followed at 30 min by a second hemorrhage of 8 ml/kg and resuscitation with 1.5 ml/kg/min of LR solutions to achieve and maintain systolic blood pressure at 80 ± 5 mmHg for 3.5 hrs. Chemistries and arterial and venous blood gasses were determined from periodic blood samples along with hemodynamic variables. RESULTS: There were significant decreases in survival, urine output, cardiac output and oxygen delivery at 60 min and O2 consumption at 120 min in the pneumonia group compared to the non-pneumonia group. There were no differences in other metabolic or hemodynamic data between the groups. CONCLUSION: Although pneumonia had little influence on pulmonary gas exchange, it influenced cardiac output, urine output and survival compared to healthy swine, suggesting a decrease in the physiologic reserve. These data may be relevant to patients with subclinical infection who are stressed by hemorrhage and may explain in part why some similarly injured patients require more resuscitation efforts than others

Comparisons of normal saline and lactated Ringer’s resuscitation on hemodynamics, metabolic responses, and coagulation in pigs after severe hemorrhagic shock

BACKGROUND: Ongoing improvements in trauma care now recommend earlier use of blood products as part of damage control resuscitation, but generally these products are not available at far forward battlefield locations. For the military, questions continue to arise regarding efficacy of normal saline (NS) vs. lactated Ringer’s (LR). Thus, this study compared the effects of LR and NS after severe hemorrhage in pigs. METHODS: 20 anesthetized pigs were randomized into control (n = 6), LR (n = 7), and NS (n = 7) groups. Hemorrhage of 60% estimated total blood volume was induced in LR and NS groups by removing blood from the left femoral artery using a computer-controlled pump. Afterwards, the pigs were resuscitated with either LR at 3 times the bled volume or the volume of NS to reach the same mean arterial pressure (MAP) as in LR group. Hemodynamics were measured hourly and blood samples were taken at baseline (BL), 15 min, 3 h and 6 h after resuscitation to measure changes in coagulation using thrombelastograph®. RESULTS: MAP was decreased by hemorrhage but returned to BL within 1 h after resuscitation with LR (119 ± 7 ml/kg) or NS (183 ± 9 ml/kg, p < 0.05). Base excess (BE) was decreased by hemorrhage; resuscitation with LR recovered BE but not with NS. Total peripheral resistance was decreased with NS and LR, with a larger drop shown in NS. Serum potassium was increased with NS, but not affected with LR. Coagulation changes were similar between LR and NS. CONCLUSIONS: NS may be inferior to LR in resuscitation due to its vasodilator effects and the risks of metabolic acidosis and hyperkalemia

The Cutaneous Microbiome and Wounds: New Molecular Targets to Promote Wound Healing

The ecological community of microorganisms in/on humans, termed the microbiome, is vital for sustaining homeostasis. While culture-independent techniques have revealed the role of the gut microbiome in human health and disease, the role of the cutaneous microbiome in wound healing is less defined. Skin commensals are essential in the maintenance of the epithelial barrier function, regulation of the host immune system, and protection from invading pathogenic microorganisms. In this review, we summarize the literature derived from pre-clinical and clinical studies on how changes in the microbiome of various acute and chronic skin wounds impact wound healing tissue regeneration. Furthermore, we review the mechanistic insights garnered from model wound healing systems. Finally, in the face of growing concern about antibiotic-resistance, we will discuss alternative strategies for the treatment of infected wounds to improve wound healing and outcomes. Taken together, it has become apparent that commensals, symbionts, and pathogens on human skin have an intimate role in the inflammatory response that highlights several potential strategies to treat infected, non-healing wounds. Despite these promising results, there are some contradictory and controversial findings from existing studies and more research is needed to define the role of the human skin microbiome in acute and chronic wound healing

Vitamin C acts indirectly to modulate isotype switching in mouse B cells

Vitamin C, one of essential micronutrients, has been reported to modulate the humoral immune responses in some mammals. We investigated whether vitamin C might modulate this response in mice by directly affecting B cells. Splenic B cells were isolated and activated by CD40- and B cell receptor-ligation in vitro. The cells were cultured with a pretreatment of vitamin C from 0 to 1 mM of concentrations. Vitamin C slightly increased apoptosis of B cells dose-dependently and behaved as an antioxidant. We found that in vivo administration of vitamin C by intraperitoneal injection affected isotype switching as previously reported: the titer of antigen-specific IgG1 antibody was decreased, while that of IgG2a was unaffected. Somewhat different from those observed in vivo, in vitro exposure to vitamin C slightly decreased isotype switching to IgG1 and increased isotype switching to IgG2a. Pretreatment with vitamin C in the safe range did not affect either proliferation of cultured B cells or the expression of CD80 and CD86 in those cells. Taken together, in vivo results suggest that vitamin C acts to modulate isotype switching in the mouse. However, because of our in vitro results, we suggest that the modulation exerted by vitamin C in vivo is by indirectly affecting B cells, perhaps by directly influencing other immune cells such as dendritic cells

Isolation and Characterization of Multipotent CD24+ Cells From the Renal Papilla of Swine

Over 100,000 patients in the United States are currently waiting for a kidney transplant. With just over 10,000 cadaveric kidneys transplanted annually, it is of the utmost importance to optimize kidney viability upon transplantation. One exciting avenue may be xenotransplantation, which has rejuvenated interest after advanced gene editing techniques have been successfully used in swine. Simultaneously, acute kidney injury (AKI) is associated with high morbidity and mortality and currently lacks effective treatment. Animal models have been used extensively to address both of these issues, with recent emphasis on renal progenitor cells (RPCs). Due to anatomical similarities to humans we aimed to examine progenitor cells from the renal papillae of swine kidneys. To do this, RPCs were dissected from the renal papillae of healthy swine. Cell surface marker expression, proliferation, and differentiation of the RPCs were tested in vitro. Additionally, a mixed lymphocyte reaction was performed to examine immunomodulatory properties. RPCs displayed spindle shaped morphology with limited self-renewing capacity. Isolated RPCs were positive for CD24 and CD133 at early passages, but lost expression with subsequent passaging. Similarly, RPCs displayed myogenic, osteogenic, and adipogenic differentiation capacities at passage 2, but largely lost this by passage 6. Lastly, direct contact of RPCs with human lymphocytes increased release of IL6 and IL8. Taken together, RPCs from the papilla of porcine kidneys display transient stem cell properties that are lost with passaging, and either represent multiple types of progenitor cells, or a multipotent progenitor population. In instances of ischemic insult, augmentation of/with RPCs may potentiate regenerative properties of the kidney. While the use of swine for transplantation and ischemia studies confers obvious advantages, the populations of different progenitor cell populations within pig kidneys warrants further investigation. Ultimately, while gene editing techniques enhance the potential for xenotransplantation of organs or cells, the ultimate success of this strategy may be determined by the (dis)similarities of RPCs from different species