Preclinical In Vitro Safety Investigations of Submicron Sized Hemoglobin Based Oxygen Carrier HbMP‐700

Hemoglobin‐based oxygen carriers (HBOCs) are being developed as oxygen and plasma volume‐expanding therapeutics though their potential to promote oxidative tissue injury and nitric oxide (NO) scavenging combined with vasoconstriction has raised safety concerns. Therefore, we focused on these aspects during preclinical studies performed with the recently introduced hemoglobin microparticles (HbMP‐700). Besides oxidative stress, we investigated possible vasoconstrictory influence of HBOCs as well as genetic toxicity. The novel developed HbMP‐700 presented here provides a high oxygen affinity which prevents premature oxygen oversupply and avoids vasoconstriction of small blood vessels in vitro. The size of these particles is 700 nm (larger than 100 nm and smaller than 1000 nm) in order to prevent penetration through the blood vessel's endothelial gaps, NO‐scavenging, and to avoid phagocytosis of large particles. We expect that the HbMP‐700 meets the sophisticated requirements as a universal blood substitute.     

Implementation of the Swedish Fracture Register

Large financial resources are needed to treat fractures. Surprisingly little is, however, known about actual numbers, treatment methods or outcomes. A large population-based observational study can add valuable knowledge, especially if patient-reported results are included. There is no previous national fracture register with prospectively collected data on fractures of all types, treated surgically as well as non-surgically. With the implementation of the Swedish Fracture Register (SFR), we have shown that this is possible. More than 285,000 fractures have been registered. The database is increasing at a rate of 70,000 fractures a year, i.?e. one fracture every 7 min. The aim of this article is to describe the first seven years in the history of the SFR, with opportunities for the future as well as limitations.     

MagicTube: Neue Möglichkeiten zum komplett internen Knochensegmenttransport und optionaler Verlängerung

Segmental bone transport is an effective method of treatment for segmental defects but the previous need for external fixation constructs during the transport phase is a great disadvantage, especially in the femur. In order to avoid external fixation, a new cylindrical combitube segmental transport (CKTST, MagicTube) module for combination with a commercially available motorized lengthening nail was developed by the author. This MagicTube module enables completely internal segmental bone transport and also enables optional lengthening if needed. The concept and surgical technique of MagicTube are described, illustrated, discussed and exemplified by clinical cases involving the tibia and femur.     

Simulated Transcatheter Aortic Valve Flow: Implications of Elliptical Deployment and Under‐Expansion at the Aortic Annulus

Clinical use of transcatheter aortic valves (TAVs) has been associated with abnormal deployment, including oval deployment and under‐expansion when placed into calcified aortic annuli. In this study, we performed an integrated computational and experimental investigation to quantify the impact of abnormal deployment at the aortic annulus on TAV hemodynamics. A size 23 mm generic TAV computational model, developed and published previously, was subjected to elliptical deployment at the annulus with eccentricity levels up to 0.68 and to under‐expansion of the TAV at the annulus by up to 25%. The hemodynamic performance was quantified for each TAV deployment configuration. TAV opening geometries were fabricated using stereolithography and then subjected to steady forward flow testing in accordance with ISO‐5840. Centerline pressure profiles were compared to validate the computational model. Our findings show that slight ellipticity of the TAV may not lead to degeneration of hydrodynamic performance. However, under large ellipticity, increases in transvalvular pressure gradients were observed. Under‐expanded deployment has a much greater negative effect on the TAV hemodynamics compared with elliptical deployment. The maximum turbulent viscous shear stress (TVSS) values were found to be significantly larger in under‐expanded TAVs. Although the maximum value of TVSS was not large enough to cause hemolysis in all cases, it may cause platelets activation, especially for under‐expanded deployments.     

Antimicrobial photodynamic therapy as a new approach for the treatment of vulvovaginal candidiasis: preliminary results

In this work, we present the efficacy of photodynamic therapy against yeast cells in an animal model. We tested two photosensitizers, methylene blue and protoporphyrin IX. Thirty-seven female BALB-c mice with a body mass of 20–25 g were used. To achieve persistent vaginitis, estrus was induced by subcutaneous injection of 0.1 mg/mL estradiol valerate applied weekly. Three days after pseudo-estrus, intravaginal inoculation with Candida albicans was performed. Mice were anesthetized with ketamine (80 mg/kg) and xylazine (10 mg/kg) by intraperitoneal injection before inoculation, and antimicrobial photodynamic therapy (aPDT) was performed 5 days after fungal inoculation. Two photosensitizers were tested, methylene blue (MB; 100 μM) and protoporphyrin IX (PpNetNI; 10 μM). Two custom-made LEDs emitting light at 660 and 630 nm at approximately 800 mW each were used for irradiation. The aPDT treatment reduced the fungal colony-forming units (CFUs) by one order of magnitude for the MB (p?=?0.020) and PpNetNI (p?=?0.018) photosensitizers. Seven days after the treatment, there were significantly fewer CFUs compared to the control group (p?=?0.041 and p?=?0.035 for MB and PpNetNI, respectively), but this was not increased compared to the initial number immediately after aPDT. Using aPDT as a therapeutic option to decrease fungal infection in a vaginal candidiasis model resulted in a significant reduction in the C. albicans population. Both photosensitizers were effective for preventing reinfection within 7 days. The aPDT also had no effect on the vaginal mucosa at the ultrastructural level. In addition to the fungicide effect, we observed reduced swelling and lack of the formation of abscesses, microabscesses coating the cornified epithelial layer, and the accumulation of neutrophils in the submucosa.     

Evaluation of scars in children after treatment with low-level laser

Burn scars are known for their tendency to worsen with hypertrophy and contracture, causing esthetic and functional problems. The objective is to analyze the effectiveness of low-level laser therapy on post-burn hypertrophic scar tissue in children. A randomized controlled study included 15 children, ranging from 2 to 10 years of age, presented with post-burn hypertrophic scars. They received He-Ne laser and topical treatment. Each scar was divided into two halves. One half was treated with laser therapy and topical treatment (study area), and the other half was treated with topical treatment only (control area). The children were evaluated before, and after 3 months of the study by Vancouver Scar Scale (VSS), ultrasonography, and laser Doppler perfusion imaging. Significant improvement was reported in the studied area, compared to the control area for patients with P values (P =?0.003) and (P =?0.005), for VSS and U/S scores, respectively. No differences were detected for blood perfusion of the scar between both areas (P?=?0.73). In addition, no adverse effects were reported. Photobiomodulation (PBM) is an efficient and safe therapeutic modality for post-burn hypertrophic scars in children, with no side effects, and should be considered a part of combination therapy for better results.     

Low-level laser therapy improves the VO<Subscript>2</Subscript> kinetics in competitive cyclists

Some evidence supports that low-level laser therapy (LLLT) reduces neuromuscular fatigue, so incrementing sports performance. A previous randomized controlled trial of our group showed increased exercise tolerance in male competitive cyclists treated with three different LLLT doses (3, 6, and 9 J/diode; or 135, 270, and 405 J/thigh) before time-to-exhaustion cycling tests. Now, the present study was designed to evaluate the effects of these LLLT doses on the VO₂ kinetics of athletes during cycling tests. Twenty male competitive cyclists (29 years) participated in a crossover, randomized, double-blind, and placebo-controlled trial. On the first day, the participants performed an incremental cycling test to exhaustion to determine maximal oxygen uptake (VO_2MAX) and maximal power output (PO_MAX), as well as a familiarization with the time-to-exhaustion test. In the following days (2 to 5), all participants performed time-to-exhaustion tests at PO_MAX. Before the exhaustion test, different doses of LLLT (3, 6, and 9 J/diode; or 135, 270, and 405 J/thigh, respectively) or placebo were applied bilaterally to the quadriceps muscle. All exhaustion tests were monitored online by an open-circuit spirometry system in order to analyze the VO₂ amplitude, VO₂ delay time, time constant (tau), and O₂ deficit. Tau and O₂ deficit were decreased with LLLT applications compared to the placebo condition (p < 0.05). No differences (p > 0.05) were found between the experimental conditions for VO₂ amplitude and VO₂ delay time. In conclusion, LLLT decreases tau and O₂ deficit during time-to-exhaustion tests in competitive cyclists, and these changes in VO₂ kinetics response can be one of the possible mechanisms to explain the ergogenic effect induced by LLLT.