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Concomitant monitoring of implant formation and drug release of in situ forming poly (lactide-co-glycolide acid) implants in a hydrogel matrix mimicking the subcutis using UV-vis imaging.
Sun, Y, Jensen, H, Petersen, NJ, Larsen, SW, Østergaard, J
Journal of pharmaceutical and biomedical analysis. 2018;:95-106
Abstract
For poly (lactide-co-glycolide acid) (PLGA)-based in situ forming implants, the rate of implant formation plays an important role in determining the overall drug release kinetics. Currently, in vitro techniques capable of characterizing the processes of drug release and implant formation at the same time are not available. A hydrogel-based in vitro experimental setup was recently developed requiring only microliter of formulation and forming a closed system potentially suitable for interfacing with various spectroscopic techniques. The aim of the present proof-of-concept study was to investigate the feasibility of concomitant UV imaging, Vis imaging and light microscopy for detailed characterization of the behavior of in situ forming PLGA implants in the hydrogel matrix mimicking the subcutis. The model compounds, piroxicam and α-lactalbumin were added to PLGA-1-methyl-2-pyrrolidinone and PLGA-triacetin solutions. Upon bringing the PLGA-solvent-compound pre-formulation in contact with the hydrogel, Vis imaging and light microscopy were applied to visualize the depot formation and UV imaging was used to quantify drug transport in the hydrogel. As compared to piroxicam, the α-lactalbumin invoked an acceleration of phase separation and an increase of implant size. α-Lactalbumin was released faster from the PLGA-1-methyl-2-pyrrolidinone system than the PLGA-triacetin system opposite to the piroxicam release pattern. A linear relationship between the rate of implant formation and initial compound release within the first 4h was established for the PLGA-NMP systems. This implies that phase separation may be one of the controlling factors in drug release. The rate of implant formation may be an important parameter for predicting and tailoring drug release. The approach combining UV imaging, Vis imaging and light microscopy may facilitate understanding of release processes and holds potential for becoming a useful tool in formulation development of in situ forming implants.
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Post-exercise recovery of biological, clinical and metabolic variables after different temperatures and durations of cold water immersion: a randomized clinical trial.
Vanderlei, FM, de Albuquerque, MC, de Almeida, AC, Machado, AF, Netto, J, Pastre, CM
The Journal of sports medicine and physical fitness. 2017;(10):1267-1275
Abstract
BACKGROUND Cold water immersion (CWI) is a commonly used recuperative strategy. However there is a lack of standardization of protocols considering the duration and temperature of application of the technique and the stress model. Therefore it is important to study the issue of dose response in a specific stress model. Thus the objective was to analyze and compare the effects of CWI during intense post-exercise recovery using different durations and temperatures of immersion. METHODS One hundred and five male individuals were divided into five groups: one control group (CG) and four recovery groups (G1: 5' at 9±1 °C; G2: 5' at 14±1 °C; G3: 15' at 9±1 °C; G4: 15' at 14±1 °C). The volunteers were submitted to an exhaustion protocol that consisted of a jump program and the Wingate Test. Immediately after the exhaustion protocol, the volunteers were directed to a tank with water and ice, where they were immersed for the recovery procedure, during which blood samples were collected for later lactate and creatine kinase (CK) analysis. Variables were collected prior to the exercise and 24, 48, 72, and 96 hours after its completion. RESULTS For the CK concentration, 15 minutes at 14 °C was the best intervention option, considering the values at 72 hours after exercise, while for the moment of peak lactate an advantage was observed for immersion for 5 minutes at 14 °C. Regarding the perception of recovery, CWI for 5 minutes at 14 °C performed better long-term, from the time of the intervention to 96 hours post-exercise. For pain, no form of immersion responded better than the CG at the immediately post-intervention moment. CONCLUSIONS There were no differences in behavior between the CWI intervention groups for the outcomes studied.
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Comparison of cellular effects of starch-coated SPIONs and poly(lactic-co-glycolic acid) matrix nanoparticles on human monocytes.
Gonnissen, D, Qu, Y, Langer, K, Öztürk, C, Zhao, Y, Chen, C, Seebohm, G, Düfer, M, Fuchs, H, Galla, HJ, et al
International journal of nanomedicine. 2016;:5221-5236
Abstract
Within the last years, progress has been made in the knowledge of the properties of medically used nanoparticles and their toxic effects, but still, little is known about their influence on cellular processes of immune cells. The aim of our comparative study was to present the influence of two different nanoparticle types on subcellular processes of primary monocytes and the leukemic monocyte cell line MM6. We used core-shell starch-coated superparamagnetic iron oxide nanoparticles (SPIONs) and matrix poly(lactic-co-glycolic acid) (PLGA) nanoparticles for our experiments. In addition to typical biocompatibility testing like the detection of necrosis or secretion of interleukins (ILs), we investigated the impact of these nanoparticles on the actin cytoskeleton and the two voltage-gated potassium channels Kv1.3 and Kv7.1. Induction of necrosis was not seen for PLGA nanoparticles and SPIONs in primary monocytes and MM6 cells. Likewise, no alteration in secretion of IL-1β and IL-10 was detected under the same experimental conditions. In contrast, IL-6 secretion was exclusively downregulated in primary monocytes after contact with both nanoparticles. Two-electrode voltage clamp experiments revealed that both nanoparticles reduce currents of the aforementioned potassium channels. The two nanoparticles differed significantly in their impact on the actin cytoskeleton, demonstrated via atomic force microscopy elasticity measurement and phalloidin staining. While SPIONs led to the disruption of the respective cytoskeleton, PLGA did not show any influence in both experimental setups. The difference in the effects on ion channels and the actin cytoskeleton suggests that nanoparticles affect these subcellular components via different pathways. Our data indicate that the alteration of the cytoskeleton and the effect on ion channels are new parameters that describe the influence of nanoparticles on cells. The results are highly relevant for medical application and further evaluation of nanomaterial biosafety.
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Comparison of denitrification performances using PLA/starch with different mass ratios as carbon source.
Wu, C, Tang, D, Wang, Q, Wang, J, Liu, J, Guo, Y, Liu, S
Water science and technology : a journal of the International Association on Water Pollution Research. 2015;(7):1019-25
Abstract
A suitable carbon source is significant for biological nitrate removal from groundwater. In this study, slow-release carbon sources containing polylactic acid (PLA) and starch at 8:2, 7:3, 6:4, 5:5, 4:6, and 3:7 ratios were prepared using a blending and fusing technique. The PLA/starch blend was then used as a solid carbon source for biological nitrate removal. The carbon release rate of PLA/starch was found to increase with increased starch content in leaching experiments. PLA/starch at 5:5 mass ratio was found to have the highest denitrification performance and organic carbon consumption efficiency in semi-continuous denitrification experiments, and was also revealed to support complete denitrification at 50 mg-N/L influent nitrate concentration in continuous experiments. The effluent nitrate concentration was <2 mg NO(3)(-)-N/L, which met the national standard (GB 14848-93) for groundwater. Scanning electron microscopy results further showed that the surface roughness of PLA/starch increased with prolonged experimental time, which may be conducive to microorganism attachment. Therefore, PLA/starch was a suitable carbon source and biofilm carrier for groundwater remediation.
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Effect of sprint training: training once daily versus twice every second day.
Ijichi, T, Hasegawa, Y, Morishima, T, Kurihara, T, Hamaoka, T, Goto, K
European journal of sport science. 2015;(2):143-50
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Abstract
This study compared training adaptations between once daily (SINGLE) and twice every second day (REPEATED) sprint training, with same number of training sessions. Twenty physically active males (20.9 ± 1.3 yr) were assigned randomly to the SINGLE (n = 10) or REPEATED (n = 10) group. The SINGLE group trained once per day (5 days per week) for 4 weeks (20 sessions in total). The REPEATED group conducted two consecutive training sessions on the same day, separated by a rest period of 1 h (2-3 days per week) for 4 weeks (20 sessions in total). Each training session consisted of three consecutive 30-s maximal pedalling sets with a 10-min rest between sets. Before and after the training period, the power output during two bouts of 30-s maximal pedalling, exercise duration during submaximal pedalling and resting muscle phosphocreatine (PCr) levels were evaluated. Both groups showed significant increases in peak and mean power output during the two 30-s bouts of maximal pedalling after the training period (P < 0.05). The groups showed similar increases in VO2max after the training period (P < 0.05). The REPEATED group showed a significant increase in the onset of blood lactate accumulation (OBLA) after the training period (P < 0.05), whereas no change was observed in the SINGLE group. The time to exhaustion at 90% of VO2max and muscle PCr concentration at baseline did not change significantly in either group. Sprint training twice every second day improved OBLA during endurance exercise more than the same training once daily.
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The effects of high-intensity intermittent exercise compared with continuous exercise on voluntary water ingestion.
Mears, SA, Shirreffs, SM
International journal of sport nutrition and exercise metabolism. 2013;(5):488-97
Abstract
Water intake occurs following a period of high-intensity intermittent exercise (HIIE) due to sensations of thirst yet this does not always appear to be caused by body water losses. Thu.s, the aim was to assess voluntary water intake following HIIE. Ten healthy males (22 ± 2 y, 75.6 ± 6.9 kg, VO2(peak) 57.3 ± 11.4 m · kg(-1) · min(-1); mean ± SD) completed two trials (7-14 d apart). Subjects sat for 30 min then completed an exercise period involving 2 min of rest followed by 1 min at 100% VO2(peak repeated for 60 min (HIIE) or 60 min continuously at 33% VO2(peak) (LO). Subjects then sat for 60 min and were allowed ad libitum water intake. Body )mass was measured at start and end of trials. Serum osmolality, blood lactate, and sodium concentrations, sensations of thirst and mouth dryness were measured at baseline, postexercise and after 5, 15, 30, and 60 min of recovery. Vasopressin concentration was measured at baseline, postexercise, 5 min, and 30 min. Body mass loss over the whole trial was similar (HIIE: 0.77 ± 0.50; LO: 0.85 ± 0.55%; p = .124). Sweat lost during exercise (0.78 ± 0.22 vs. 0.66 ± 0.26 L) and voluntary water intake during recovery (0.416 ± 0.299 vs. 0.294 ± 0.295 L; p < .05) were greater in HIIE. Serum osmolality (297 ± 3 vs. 288 ± 4 mOsmol · kg(-1)), blood lactate (8.5 ± 2.7 vs. 0.7 ± 0.4 mmol · L(-1)), serum sodium (146 ± 1 vs. 143 ± 1 mmol · L(-1)) and vasopressin (9.91 ± 3.36 vs. 4.43 ± 0.86 pg · ml(-1)) concentrations were higher after HIIE (p < .05) and thirst (84 ± 7 vs. 60 ± 21) and mouth dryness (87 ± 7 vs. 64 ± 23) also tended to be higher (p = .060). Greater voluntary water intake after HIIE was mainly caused by increased sweat loss and the consequences of increased serum osmolality mainly resulting from higher blood lactate concentrations.
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Acid production in dental plaque after exposure to probiotic bacteria.
Keller, MK, Twetman, S
BMC oral health. 2012;:44
Abstract
BACKGROUND The increasing interest in probiotic lactobacilli in health maintenance has raised the question of potential risks. One possible side effect could be an increased acidogenicity in dental plaque. The aim of this study was to investigate the effect of probiotic lactobacilli on plaque lactic acid (LA) production in vitro and in vivo. METHODS In the first part (A), suspensions of two lactobacilli strains (L. reuteri DSM 17938, L. plantarum 299v) were added to suspensions of supragingival dental plaque collected from healthy young adults (n=25). LA production after fermentation with either xylitol or fructose was analyzed. In the second part (B), subjects (n=18) were given lozenges with probiotic lactobacilli (L. reuteri DSM 17938 and ATCC PTA 5289) or placebo for two weeks in a double-blinded, randomized cross-over trial. The concentration of LA in supragingival plaque samples was determined at baseline and after 2 weeks. Salivary counts of mutans streptococci (MS) and lactobacilli were estimated with chair-side methods. RESULTS Plaque suspensions with L. reuteri DSM 17938 produced significantly less LA compared with L. plantarum 299v or controls (p<0.05). Fructose gave higher LA concentrations than xylitol. In part B, there were no significant differences in LA production between baseline and follow up in any of the groups and no differences between test and placebo were displayed. The salivary MS counts were not significantly altered during the intervention but the lactobacilli counts increased significantly in the test group (p<0.05). CONCLUSION Lactic acid production in suspensions of plaque and probiotic lactobacilli was strain-dependant and the present study provides no evidence of an increase in plaque acidity by the supply of selected probiotic lactobacilli when challenged by fructose or xylitol. The study protocol was approved by The Danish National Committee on Biomedical Research Ethics (protocol no H-2-2010-112). TRIAL REGISTRATION NCT01700712.
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Intermittent exercise with and without hypoxia improves insulin sensitivity in individuals with type 2 diabetes.
Mackenzie, R, Maxwell, N, Castle, P, Elliott, B, Brickley, G, Watt, P
The Journal of clinical endocrinology and metabolism. 2012;(4):E546-55
Abstract
CONTEXT Hypoxia and muscle contraction stimulate glucose transport activity in vitro. Exercise and hypoxia have additive effects on insulin sensitivity in type 2 diabetics (T2D). OBJECTIVE The objective of the study was to examine the effectiveness of intermittent exercise with and without hypoxia on acute- and moderate-term glucose kinetics and insulin sensitivity in T2D. SETTING The study was conducted at a university research center. DESIGN, PARTICIPANTS, AND INTERVENTIONS Eight male T2D patients completed the following: 1) 60 min of continuous exercise at 90% lactate threshold in hypoxia (HyEx60); 2) intermittent exercise at 120% lactate threshold, separated by periods of passive recovery (5:5 min) in hypoxia [Hy5:5; O₂ ∼ 14.7 (0.2)%]; and 3) intermittent exercise (5:5 min) at 120% lactate threshold in normoxia (O₂ ∼ 20.93%). MAIN OUTCOME MEASURES Glucose appearance and glucose disappearance, using an adapted non-steady-state one-compartment model were measured. Homeostasis models of insulin resistance (HOMA(IR)), fasting insulin resistance index (FIRI), and β-cell function were calculated 24 and 48 h after exercise conditions. RESULTS Glucose disappearance increased from baseline (1.85 mg/kg · min⁻¹) compared with 24 h (2.01 min/kg · min⁻¹) after HyEx60 (P = 0.031). No difference was noted for both Hy5:5 (P = 0.064) and normoxia (P = 0.385). Hy5:5 demonstrated improvements in HOMA(IR) from baseline [d 1, 6.20 (0.40)] when comparisons were made with d 2 [4.83 (0.41)] (P = 0.0013). HOMA(IR) and FIRI improved in the 24 h (HOMA(IR), P = 0.002; FIRI, P = 0.003), remaining reduced 48 h after HyEx60 (HOMA(IR), P = 0.028; and FIRI, P = 0.034). CONCLUSION HyEx60 offered the greatest improvements in acute and moderate-term glucose control in T2D. Intermittent exercise stimulated glucose disposal and improved post-exercise insulin resistance, which was enhanced when exercise was combined with hypoxia (Hy5:5). The data suggest a use of hypoxic exercise in treatment of T2D.
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Clinical evaluation of 35% urea in a water-lipid-based foam containing lactic acid for treatment of mild-to-moderate xerosis of the foot.
Grossman, AB
Journal of the American Podiatric Medical Association. 2011;(2):153-8
Abstract
BACKGROUND We evaluated 35% urea in a water-lipid-based foam delivery system containing lactic acid in participants with mild-to-moderate xerosis of the foot. METHODS This 4-week open-label study enrolled 12 participants with xerosis of the foot; six participants were diabetic and six were nondiabetic. Study medication was applied to the affected area twice daily. All adverse events were recorded. Disease severity was measured at baseline and at the end of treatment by Investigator's Global Assessment, and investigator's and participant's signs and symptoms scores. At 4 weeks, compliance and participant satisfaction were determined from participant diaries and a 16-item survey instrument, respectively. RESULTS Ten participants completed the study. No adverse reactions were noted with application of the foam. All of the participants who completed the study experienced an improvement in xerosis. The median Investigator's Global Assessment score decreased significantly from baseline to the end of treatment (P = .005). The investigator and participants observed significant improvement (P < .05) in redness, scaling, and cracking from baseline to the end of treatment. Compliance with the regimen was good, and participants expressed satisfaction with the product. CONCLUSIONS Thirty-five percent urea in a water-lipid-based foam delivery system containing lactic acid can be an appropriate treatment option for mild-to-moderate xerosis of the foot.
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ω-3 Fatty acids have no impact on serum lactate levels after major gastric cancer surgery.
Makay, O, Kaya, T, Firat, O, Sozbilen, M, Caliskan, C, Gezer, G, Uyar, M, Ersin, S
JPEN. Journal of parenteral and enteral nutrition. 2011;(4):488-92
Abstract
BACKGROUND Preoperative and intraoperative nutrition support in patients undergoing major surgery results in decreased incidence of morbidity and mortality. Studies investigating the role of ω-3 fatty acids in these patients are increasing. Some are focused on perfusion at the cellular level. This study was undertaken to address the effect of postoperative administration of ω-3 fatty acids on cellular hypoperfusion associated with major gastric surgery. METHODS Twenty-six patients undergoing gastric cancer surgery were randomly assigned to receive parenteral nutrition (PN) supplemented with a combination of ω-6 and ω-3 fatty acids (Omegaven, 0.2 g/kg/d; Lipovenoes 10%, 0.6 g/kg/d) or with ω-6 fatty acid (Lipovenoes 10%, 0.8 g/kg/d) for 5 days. Blood samples were taken preoperatively, postoperative day 1, and on the last day of PN therapy (day 5). RESULTS Patients receiving ω-3 and ω-6 fatty acids showed neither lower serum lactate levels nor lower rates of complications compared with patients receiving ω-6 only. There were no statistically significant differences between the groups in other biochemical parameters, complications, or length of hospital stay or mortality. CONCLUSION PN with ω-3 fatty acid supplementation does not have a significant impact on cellular hypoperfusion and lactate clearance after major gastric surgery.