New Applications of HBOC-201: A 25-Year Review of the Literature

If not cured promptly, tissue ischemia and hypoxia can cause serious consequences or even threaten the life of the patient. Hemoglobin-based oxygen carrier-201 (HBOC-201), bovine hemoglobin polymerized by glutaraldehyde and stored in a modified Ringer's lactic acid solution, has been investigated as a blood substitute for clinical use. HBOC-201 was approved in South Africa in 2001 to treat patients with low hemoglobin (Hb) levels when red blood cells (RBCs) are contraindicated, rejected, or unavailable. By promoting oxygen diffusion and convective oxygen delivery, HBOC-201 may act as a direct oxygen donor and increase oxygen transfer between RBCs and between RBCs and tissues. Therefore, HBOC-201 is gradually finding applications in treating various ischemic and hypoxic diseases including traumatic hemorrhagic shock, hemolysis, myocardial infarction, cardiopulmonary bypass, perioperative period, organ transplantation, etc. However, side effects such as vasoconstriction and elevated methemoglobin caused by HBOC-201 are major concerns in clinical applications because Hbs are not encapsulated by cell membranes. This study summarizes preclinical and clinical studies of HBOC-201 applied in various clinical scenarios, outlines the relevant mechanisms, highlights potential side effects and solutions, and discusses the application prospects. Randomized trials with large samples need to be further studied to better validate the efficacy, safety, and tolerability of HBOC-201 to the extent where patient-specific treatment strategies would be developed for various clinical scenarios to improve clinical outcomes.

An Overview on Pressure Ulcers: Prevention and Management

Pressure ulcers are significant and painful side effects that might indicate a lack of care. The formation of a pressure ulcer is a major complication of reduced mobility. And since over 65-year-olds are the fastest-growing sector of the population in many developed countries, it imposes the risk of increasing disease incidences. There are also higher rates of obesity, diabetes, and cardiovascular disease, which also increase the risk. There are many causes that can contribute to the formation of pressure ulcers; tissue ischemia is the most prevalent route to ulceration. Pressure ulcer prevention generally begins with an examination to determine who is most vulnerable to pressure ulcers, such as the elderly, the immobile, or individuals with a spinal cord injury. Wound dressings, debridement, physical therapy, antibiotics, and antimicrobials are all possible therapeutic options for pressure ulcers. Interventions such as mobilization, positioning, and repositioning, as well as support surfaces, are utilized in conjunction with other wound care methods. In this review we’ll be looking at prevention and management of pressure ulcers.

Multisystem inflammatory syndrome in children аssociated with COVID-19

Coronavirus disease is severe in the elderly and in people with chronic diseases such as diabetes mellitus, heart disease, chronic obstructive pulmonary disease, and cancers. It is generally accepted that in children, COVID-19 is much milder, and often is even asymptomatic. But there are some children who, against the background of the coronavirus infection, developed multisystem inflammatory syndrome (MIS-C). Its pathophysiology is not fully understood. There are several hypotheses about the mechanisms of MIS-C development. It is assumed that the syndrome develops due to an excessive immune response to the virus. Having some similar mechanisms with Kawasaki disease, macrophage activation syndrome, the development of MIS-C still has significant diffe-rences. Multiple organ damage occurs due to systemic inflammation, hypoxia, tissue ischemia. As a result, multiple organ dysfunction syndrome develops. Clinical manifestations are specific and reflect changes in all body systems. Laboratory studies revealed an increase in inflammatory markers, transaminases, creatinine, urea, coagulation disturbances. Treatment of multisystem inflammatory syndrome includes immunomodulatory and glucocorticoid therapies. Antibiotics, anticoagulants, antiplatelet agents are also administered, and in case of renal failure symptoms — dialysis replacement therapy. The article describes cases of successful treatment of children with multisystem inflammatory syndrome associated with COVID-19, which show that MIS-C can mask a large number of diseases. Attention should be paid to the need for hospitalization of such patients into a unit with the possibility of hemodialysis, to the different approaches to treatment, the importance of renal replacement therapy. If the above requirements are met, it is possible to achieve a complete recovery of patients.

Effect of Vibration on Alleviating Foot Pressure-Induced Ischemia under Occlusive Compression

Objectives. Foot ulcers often occur in people with diabetes because of pressure-induced tissue ischemia. Vibration has been reported to be helpful in alleviating mechanical damage and promoting wound healing. The objective of this study is to explore whether vibration can relieve reactive hyperemia in foot tissue under occlusive compression. Methods. Thirteen healthy adults participated in the study. Each foot was placed under occlusive compression without or with vibration intervention, which was randomly assigned every other day. The dorsal foot skin blood flow (SBF) was measured pre- and postintervention for each subject in each test. Temporal variations and spectral features of SBF were recorded for comparison. Results. The results showed that subjects displayed an obvious reactive hyperemia in the foot tissue after pressure occlusion, whereas they displayed a more regular SBF when vibration was applied along with occlusive compression. Moreover, the amplitude of metabolic, neurogenic, and myogenic pathways for SBF was significantly reduced during the hyperemia process when vibration was applied. Conclusions. This study demonstrated that vibration can effectively reduce the level of hyperemia in foot tissue under occlusive compression and also induce less protective physiological regulatory activities. This is helpful for protecting foot tissue from pressure-induced ischemic injury and foot ulcers.

Angiogenic Effects and Crosstalk of Adipose-Derived Mesenchymal Stem/Stromal Cells and Their Extracellular Vesicles with Endothelial Cells

Adipose-derived mesenchymal stem/stromal cells (ASCs) are an adult stem cell population able to self-renew and differentiate into numerous cell lineages. ASCs provide a promising future for therapeutic angiogenesis due to their ability to promote blood vessel formation. Specifically, their ability to differentiate into endothelial cells (ECs) and pericyte-like cells and to secrete angiogenesis-promoting growth factors and extracellular vesicles (EVs) makes them an ideal option in cell therapy and in regenerative medicine in conditions including tissue ischemia. In recent angiogenesis research, ASCs have often been co-cultured with an endothelial cell (EC) type in order to form mature vessel-like networks in specific culture conditions. In this review, we introduce co-culture systems and co-transplantation studies between ASCs and ECs. In co-cultures, the cells communicate via direct cell–cell contact or via paracrine signaling. Most often, ASCs are found in the perivascular niche lining the vessels, where they stabilize the vascular structures and express common pericyte surface proteins. In co-cultures, ASCs modulate endothelial cells and induce angiogenesis by promoting tube formation, partly via secretion of EVs. In vivo co-transplantation of ASCs and ECs showed improved formation of functional vessels over a single cell type transplantation. Adipose tissue as a cell source for both mesenchymal stem cells and ECs for co-transplantation serves as a prominent option for therapeutic angiogenesis and blood perfusion in vivo.

Inhibition of Prolyl Oligopeptidase Prevents Consequences of Reperfusion following Intestinal Ischemia

Background: Intestinal ischemia/reperfusion injury (IRI) remains a clinical event that contributes to high morbidity and mortality rates. Intestinal epithelium is exposed to histological and vascular changes following tissue ischemia. Prolyl endopeptidase (PREP), involved in inflammatory responses, could be targeted for recovery from the permanent consequences following intestinal ischemia. Our aim was to investigate the role of PREP inhibitor KYP-2047 in tissue damage, angiogenesis, and endothelial barrier permeability after intestinal IRI in mice. Methods: KYP-2047 treatments were performed 5 min prior to intestinal damage. Intestinal IRI was induced in mice by clamping the superior mesenteric artery and the celiac trunk for 30 min, followed by 1 h of reperfusion. Results: PREP inhibition by KYP-2047 treatment reduced intestinal IR-induced histological damage and neutrophil accumulation, limiting inflammation through decrease of NF-ĸB nuclear translocation and fibrotic processes. KYP-2047 treatment restored barrier permeability and structural alteration following intestinal IRI, attenuating neovascular processes compromised by ischemia/reperfusion. Additionally, loss of epithelial cells during intestinal ischemia occurring by apoptosis was limited by KYP-2047 treatment, which showed strong effects counteracting apoptosis and DNA damage. Conclusions: These findings provide the first evidence that PREP inhibition through KYP-2047 inhibitor use could be a validate strategy for resolving alterations of intestinal epithelium the pathophysiology of intestinal disease.

Experimental Study of the Quantification of Indocyanine Green Fluorescence in Ischemic and Non-Ischemic Anastomoses, Using the Sergreen Software Program

Background: Tissue ischemia is a key risk factor for anastomotic leakage (AL). Indocyanine green (ICG) is widely used in colorectal surgery to define the segments with the best vascularization. In an experimental model, we present a new system for quantifying ICG saturation, SERGREEN software.Methods: This was a controlled experimental study with eight pigs. In the initial control stage, ICG saturation was analyzed at the level of two anastomoses in the right and left colon. Control images of the two segments were taken after ICG administration. The images were processed with the SERGREEN program. Then, in the experimental ischemia stage, the inferior mesenteric artery was sectioned at the level of the anastomosis of the left colon. Fifteen minutes after the section, sequential images of the two anastomoses were taken every 30’ for the following 2 h.Results: At the control stage, the mean scores were 134.2 (95% CI: 116.3-152.2) for the right colon and 147 (95% CI: 134.7-159.3) for the left colon (p = 0.174). The right colon remained stable throughout the experiment. In the left colon, saturation fell by 47.9 points with respect to the preischemia value (p <0.01). After the first postischemia determination, the values of the ischemic left colon remained stable throughout the experiment. The relative decrease in ICG saturation of the ischemic left colon was 32.6%.Conclusions: The SERGREEN program quantifies ICG saturation in normal and ischemic situations and detects differences between them. A reduction in ICG saturation of 32.6% or more was correlated with complete tissue ischemia.

The Absence of Extracellular Cold-Inducible RNA-Binding Protein (eCIRP) Promotes Pro-Angiogenic Microenvironmental Conditions and Angiogenesis in Muscle Tissue Ischemia

Extracellular Cold-inducible RNA-binding protein (eCIRP), a damage-associated molecular pattern, is released from cells upon hypoxia and cold-stress. The overall absence of extra- and intracellular CIRP is associated with increased angiogenesis, most likely induced through influencing leukocyte accumulation. The aim of the present study was to specifically characterize the role of eCIRP in ischemia-induced angiogenesis together with the associated leukocyte recruitment. For analyzing eCIRPs impact, we induced muscle ischemia via femoral artery ligation (FAL) in mice in the presence or absence of an anti-CIRP antibody and isolated the gastrocnemius muscle for immunohistological analyses. Upon eCIRP-depletion, mice showed increased capillary/muscle fiber ratio and numbers of proliferating endothelial cells (CD31+/CD45−/BrdU+). This was accompanied by a reduction of total leukocyte count (CD45+), neutrophils (MPO+), neutrophil extracellular traps (NETs) (MPO+CitH3+), apoptotic area (ascertained via TUNEL assay), and pro-inflammatory M1-like polarized macrophages (CD68+/MRC1−) in ischemic muscle tissue. Conversely, the number of regenerative M2-like polarized macrophages (CD68+/MRC1+) was elevated. Altogether, we observed that eCIRP depletion similarly affected angiogenesis and leukocyte recruitment as described for the overall absence of CIRP. Thus, we propose that eCIRP is mainly responsible for modulating angiogenesis via promoting pro-angiogenic microenvironmental conditions in muscle ischemia.

Fabrication and Use of a Customized Provisional Composite Abutment in Dental Practice

Introduction. Reducing the time of implant integration and the period of prosthetics is an important task of dentistry since this leads to improved quality of life and successful rehabilitation of the patient. Therefore, currently, there is an intensely increased interest in immediate or early loading of the implant, when certain parameters of primary implant stability in the bone tissue are achieved. Materials and Methods. The materials used to perform the procedure for placement of a customized provisional composite abutment were a provisional prefabricated abutment with a retention grip for the composite; aluminum oxide powder with a particle size of 27 μm for better adhesion of the composite, with which the retention grip of the provisional abutment is coated; 3M Single Bond Universal light-curing adhesive applied to the provisional abutment; and Filtek Bulk Fill 3M composite including a low-viscosity radiopaque nanocomponent and ytterbium trifluoride filler with a particle size of 0.01–3.5 nm. Methods used in this study were as follows: fabrication technique using the Cervico system for a customized provisional composite abutment; sandblasting of the provisional abutment using the apparatus RONDOFLEX (KERR); light polymerization of low-viscosity composite using Demi Ultra Kerr lamp (luminous flux power not less than 1100 mW/cm2); and radiographic control of the abutment fit in the implant. Results. The surgical and orthopedic treatment of 20 patients was performed using this technique. The control group consisted of 11 patients with similar pathology, in whose surgery the fabrication of a provisional prosthesis was used. As a result, it was possible to form a gingival profile, in comparison with the control group, to accelerate mucogingival and bone integration, as well as to quickly carry out orthopedic rehabilitation of the patient. The average value of the time required for the final formation of soft tissues for prosthetics in patients in the experimental group was significantly lower than those in the comparison group ( p = 0.007 and p = 0.028 , respectively). In most clinical cases, there is no need for surgery on soft tissues, which eliminates the possibility of additional traumas. Conclusions. The use of a promising technology for the fabrication of a crown on the implant and a customized provisional composite abutment significantly reduced the period of orthopedic rehabilitation of the patient. Immediate implantation with a customized provisional composite abutment completely forms the gingival profile, reduces the risk of microbial contamination in the area of bone formation, minimizes soft tissue ischemia, and accelerates the processes of mucogingival and bone integration around the implant.