Spirulina supplementation prevents exercise-induced lipid peroxidation, inflammation and skeletal muscle damage in elite rugby players.

BACKGROUND: The present study aimed to examine the effects of spirulina supplementation on pro/antioxidant status, inflammation and skeletal muscle damage markers immediately and 24 h after exhaustive exercise in elite rugby players. METHODS: Seventeen elite male Rugby Union players were randomly assigned to a spirulina (SPI: n = 9) or placebo (PLA: n = 8) group in a double-blind design. Subjects were supplemented with Spirulina platensis (5.7 g day-1 ) or placebo (isoproteic and caloric) for 7 weeks. At baseline and after 7 weeks of supplementation, blood samples were obtained before (T0), immediately after (T1) and 24 h after (T2) exhaustive exercise. The Yoyo Intermittent Recovery Test Level 2 was used as an exhaustive exercise to induce oxidative stress (OS), inflammation and skeletal muscle damage. The studied parameters included pro/antioxidant status markers (superoxide dismutase, glutathione peroxidase, reduced glutathione/glutathione disulphide ratio, oxidised low-density lipoprotein and F2α-isoprostanes [F2-Isop]), inflammation markers (myeloperoxidase and C-reactive protein [CRP]) and skeletal muscle damage markers (lactate dehydrogenase and creatine kinase [CK]). RESULTS: Our results showed that F2-Isop, CRP and CK levels significantly increased at T1 only in the PLA group (p < 0.05, p < 0.05 and p < 0.001, respectively) with no change in the SPI group, which reflects the effect of spirulina to prevent lipid peroxidation, inflammation and skeletal muscle damage induced by exhaustive exercise. Moreover, spirulina supplementation accelerated the return to baseline values given that F2-Isop, CRP and CK levels at T2 were significantly lower than at T0 in the SPI group (p < 0.05, p < 0.01 and p < 0.001, respectively). CONCLUSIONS: Based on the markers used in the present study, our results show that spirulina supplementation potentially prevents exercise-induced lipid peroxidation, inflammation and skeletal muscle damage, and may also accelerate the recovery of some of these markers. Based on our findings, we recommend spirulina supplementation especially for those athletes who do not achieve the recommended antioxidant dietary intake and who perform a high training load aiming to reduce the magnitude of OS, inflammation and skeletal muscle damage, which could help to reduce performance losses and accelerate recovery after training/competitions throughout the season.

The Yucatan minipig model: A new preclinical model of malnutrition in obese patients with acute or chronic diseases.

BACKGROUND & AIMS: Malnutrition can develop in patients with obesity suffering from acute or chronic illness or after obesity surgery, promoting sarcopenic obesity. A better understanding of this pathophysiology and the development of new therapeutics for chronic diseases, that are often complicated with malnutrition and obesity, justify the development of new animal experimental models close to the human physiology. This study aims to characterize the effects of obesity and underfeeding on Yucatan obese minipigs, assessing its validity as a preclinical model for obesity-related malnutrition. METHODS: Sixteen 30-month-old Yucatan minipigs were divided into two groups for 8 weeks: a standard diet group (ST, n = 5) and an obesogenic diet group (OB, n = 11). After 8 weeks, the OB group was further divided into two sub-groups: a standard diet group (OB-ST, n = 5) and a low-calorie/low-protein diet group (OB-LC/LP, n = 6) for 8 weeks. Body composition by CT-Scan and blood parameters were monitored, and trapezius muscle biopsies were collected to analyse signaling pathways involved in protein turnover and energy metabolism. RESULTS: At W8, OB-ST animals exhibited significantly higher body weight (+37.7%, p = 0.03), muscle mass (+24.9%, p = 0.02), and visceral fat (+192.0%, p = 0.03) compared to ST. Trapezius cross sectional area (CSA) normalized to body weight was lower in OB-ST animals (-15.02%, p = 0.017). At W16, no significant changes were observed in protein turnover markers, although REDD1 increased in OB-ST (96.4%, p = 0.02). After 8 weeks of low-caloric/low protein diet, OB-LC/LP showed decreased body weight (-9.8%, p = 0.03), muscle mass (-6.5%, p = 0.03), and visceral fat (-41.5%, p = 0.03) compared to OB-ST animals. Trapezius fiber CSA significantly decreased in OB-LC/LP (-36.1%, p < 0.0001) and normalized to body weight (-25.4%, p < 0.0001), combined to higher ubiquitinated protein content (+38.3%, p = 0.02). CONCLUSION: Our data support that the Yucatan minipig model mimics nutritional and skeletal muscle phenotypes observed in obese patients, with or without protein-energy malnutrition. It also reproduces muscle atrophy observed in chronic diseases or post-obesity surgery, making it a promising preclinical model for obesity-related malnutrition.

Spirulina platensis Provides a Small Advantage in Vertical Jump and Sprint Performance But Does Not Improve Elite Rugby Players' Body Composition.

The present study aimed to examine the effects of Spirulina supplementation on anthropometrical measurements and physical performance in elite rugby players. Twenty-two elite male Rugby Union players (21-36 years old) volunteered to participate in this study. They were randomly assigned to a Spirulina group (SPI: n = 11), or a placebo group (PLA: n = 11) in a double-blind design. Subjects were supplemented with Spirulina platensis (5.7 g/d) or placebo (isoproteic and caloric) for 7 weeks. At baseline (W0) and after 7 weeks of supplementation (W7), the same anthropometric measurements and physical performance test battery were performed. These tests included isokinetic leg strength and power, vertical jump, speed, and aerobic fitness assessment. For anthropometric data, the fat mass percentage was significantly reduced in both groups without significant difference between groups. While both groups exhibited significant improvements for Squat Jump (SJ), Countermovement Jump (CMJ), and 10- and 30-m sprints between W0 and W7, higher percentage improvements with the SPI group did not reach significance. Neither training alone (PLA) nor training associated with Spirulina supplementation affected leg maximal strength and power or aerobic fitness. Seven weeks of Spirulina supplementation in elite rugby players did not improve body composition or substantially increase physical performance. We only observed a non-significant small advantage in vertical jump and sprint performance in the SPI group. Based on the data from this study, Spirulina supplementation has modest effects in elite rugby players during the competitive phase. Further studies are required to verify Spirulina supplementation effects among athletes of different sports, ages, genders, and athletic levels with longer durations and higher dosages.

Safety and efficacy of a carboxymethyl chitosan dermal injection device for the treatment of skin defects: a first-in-man, pilot, comparative, split-body study.

Injectable soft-tissue devices are increasingly used for improving skin defects and deficiencies related to ageing. To assess the safety and efficacy of KIO015, a new injectable soft-tissue device formulated with carboxymethyl chitosan for the intradermal treatment of skin defects associated with ageing. Twenty-two subjects (40-65 years) were randomized to receive injections in the neckline of KIO015 and a non-cross-linked HA-based device, and were followed for up to 10 months. Injection site reactions (ISRs) and adverse events (AEs) were documented. Skin improvement was assessed instrumentally and clinically. Skin biopsies at injection zones in the lower back were taken at Day 28 for histopathology and immunohistochemistry analyses, to further assess product performance. Histomorphometric analyses on rabbits and in vitro assessment of KIO015 antioxidant capacity were also conducted. KIO015 was very well tolerated. Only expected and transient ISRs were observed; mainly erythema and hematoma. No adverse local effects or foreign body granuloma were observed histologically. Both clinical and instrumental evaluations confirmed the performance of KIO015. The skin was firmer and more elastic. Skin hydration showed significant improvement three days after injection. KIO015 exhibited superior overall maintenance of skin hydration after 10 months as compared to HA. These clinical results were supported by in vitro trials and implantation tests in the rabbit. The results from this pilot study support the use of KIO015 as an innovative alternative to HA-based devices for intradermal treatment of skin disorders.

Non-clinical assessment of lubrication and free radical scavenging of an innovative non-animal carboxymethyl chitosan biomaterial for viscosupplementation: An in-vitro and ex-vivo study.

OBJECTIVE: Lubrication and free radical scavenging are key features of biomaterials used for viscosupplementation (VS) of joints affected by osteoarthritis (OA). The objective of this study was to describe the non-clinical performance characterization of KiOmedine® CM-Chitosan, a non-animal carboxymethyl chitosan, in order to assess its intended action in VS and to compare it to existing viscosupplements based on crosslinked hyaluronan (HA) formulations. METHOD: The lubrication capacity of the tested viscosupplements (VS) was evaluated in-vitro and ex-vivo. In-vitro, the coefficient of friction (COF) was measured using a novel tribological system. Meanwhile, an ex-vivo biomechanical model in ovine hindlimbs was developed to assess the recovery of join mobility after an intra-articular (IA) injection. Free radical scavenging capacity of HA and KiOmedine® CM-Chitosan formulations was evaluated using the Trolox Equivalent Antioxidant Capacity (TEAC) assay. RESULTS: In the in-vitro tribological model, KiOmedine® CM-Chitosan showed high lubrication capacity with a significant COF reduction than crosslinked HA formulations. In the ex-vivo model, the lubrication effect of KiOmedine® CM-Chitosan following an IA injection in the injured knee was proven again by a COF reduction. The recovery of joint motion was optimal with an IA injection of 3 ml of KiOmedine® CM-Chitosan, which was significantly better than the crosslinked HA formulation at the same volume. In the in-vitro TEAC assay, KiOmedine® CM-Chitosan showed a significantly higher free radical scavenging capacity than HA formulations. CONCLUSION: Overall, the results provide a first insight into the mechanism of action in terms of lubrication and free radical scavenging for the use of KiOmedine® CM-Chitosan as a VS treatment of OA. KiOmedine® CM-Chitosan demonstrated a higher capacity to scavenge free radicals, and it showed a higher recovery of mobility after a knee lesion than crosslinked HA formulations. This difference could be explained by the difference in chemical structure between KiOmedine® CM-Chitosan and HA and their formulations.

Surface modification of metallic cardiovascular stents by strongly adhering aliphatic polyester coatings.

This article reports on a novel two-step strategy for the coating of cardiovascular stents by strongly adhering biocompatible and biodegradable aliphatic polyesters. First, a precoating of poly(ethylacrylate) (PEA) was electrografted onto the metallic substrate by cathodic reduction of the parent monomer in dimethylformamide (DMF). The electrodeposition of PEA, in a good solvent of it, was confirmed by both Infra-red and Raman spectroscopies. The pendant ester groups of PEA were then chemically reduced into aluminum alkoxides, able to initiate the ring-opening polymerization (ROP) of either D,L-lactide (LA) or epsilon-caprolactone (CL). Growth of biodegradable PLA or PCL coatings from the adhering precoating was confirmed by both Infra-red and Raman spectroscopies, and directly observed by scanning electron microscopy (SEM). This type of coating can act as an anchoring layer for the subsequent casting of drug-loaded polyester films allowing the controlled release of antiproliferative agents for the treatment of in-stent restenosis.

Ocular drug delivery targeting the retina and retinal pigment epithelium using polylactide nanoparticles.

PURPOSE: To study the kinetics of polylactide (PLA) nanoparticle (NP) localization within the intraocular tissues and to evaluate their potential to release encapsulated material. METHODS: A single intravitreous injection (5 micro L) of an NP suspension (2.2 mg/mL) encapsulating either Rh-6G (Rh) or Nile red (Nr) was performed. Animals were killed at various times, and the NPs localization within the intraocular tissues was studied by environmental scanning electron microscopy (ESEM), confocal microscopy, light microscopy histology, fluorescence microscopy, and immunohistochemistry. Eyes injected with blank NPs, free Rh, or PBS solution were used as the control. RESULTS: ESEM showed the flow of the NPs from the site of injection into the vitreous cavity and their rapid settling on the internal limiting membrane. Histology demonstrated the anatomic integrity of the injected eyes and showed no toxic effects. A mild inflammatory cell infiltrate was observed in the ciliary body 6 hours after the injection and in the posterior vitreous and retina at 18 to 24 hours. The intensity of inflammation decreased markedly by 48 hours. Confocal and fluorescence microscopy and immunohistochemistry showed that a transretinal movement of the NPs was gradually taking place with a later localization in the RPE cells. Rh encapsulated within the injected NPs diffused and stained the retina and RPE cells. PLA NPs were still present within the RPE cells 4 months after a single intravitreous injection. CONCLUSIONS: Intravitreous injection of PLA NPs appears to result in transretinal movement, with a preferential localization in the RPE cells. Encapsulated Rh diffuses from the NPs and stains the neuroretina and the RPE cells. The findings support the idea that specific targeting of these tissues is feasible. Furthermore, the presence of the NPs within the RPE cells 4 months after a single injection shows that a steady and continuous delivery of drugs can be achieved.

Freeze-dried poly(D,L-lactic acid) macroporous guidance scaffolds impregnated with brain-derived neurotrophic factor in the transected adult rat thoracic spinal cord.

The effects of poly(D,L-lactic acid) macroporous guidance scaffolds (foams) with or without brain-derived neurotrophic factor (BDNF) on tissue sparing, neuronal survival, axonal regeneration, and behavioral improvements of the hindlimbs following implantation in the transected adult rat thoracic spinal cord were studied. The foams were embedded in fibrin glue containing acidic-fibroblast growth factor. One group of animals received fibrin glue with acidic-fibroblast growth factor only. The foams were prepared by a thermally induced polymer-solvent phase separation process and contained longitudinally oriented macropores connected to each other by a network of micropores. Both foams and fibrin only resulted in a similar gliotic and inflammatory response in the cord-implant interfaces. With BDNF foam, up to 20% more NeuN-positive cells in the spinal nervous tissue close to the rostral but not caudal spinal cord-implant interface survived than with control foam or fibrin only at 4 and 8 weeks after implantation. Semithin plastic sections and electron microcopy revealed that cells and axons more rapidly invaded BDNF foam than control foam. Also, BDNF foam contained almost twice as many blood vessels than control foam at 8 weeks after implantation. Tissue sparing was similar in all three implantation paradigms; approximately 42% of tissue was spared in the rostral cord and approximately 37% in the caudal cord at 8 weeks post grafting. The number of myelinated and unmyelinated axons was low and not different between the two types of foams. Many more axons were found in the fibrin only graft. Serotonergic axons were not found in any of the implants and none of the axons regenerated into the caudal spinal cord. The behavioral improvements in the hindlimbs were similar in all groups. These findings indicated that foam is well tolerated within the injured spinal cord and that the addition of BDNF promotes cell survival and angiogenesis. However, the overall axonal regeneration response is low. Future research should explore the use of poly(D,L-lactic acid) foams, with or without axonal growth-promoting factors, seeded with Schwann cells to enhance the axonal regeneration and myelination response.

Amphiphilic copolymers of epsilon-caprolactone and gamma-substituted epsilon-caprolactone. Synthesis and functionalization of poly(D,L-lactide) nanoparticles.

Fully biodegradable and surface-functionalized poly(D,L-lactide) (PLA) nanoparticles have been prepared by a co-precipitation technique. Novel amphiphilic random copolyesters P(CL-co-gammaXCL) were synthesized by controlled copolymerization of epsilon-caprolactone and epsilon-caprolactone substituted in the gamma-position by a hydrophilic X group, where X is either a cationic pyridinium (gammaPyCL) or a non-ionic hydroxyl (gammaOHCL). Nanoparticles were prepared by co-precipitation of PLA with the P(CL-co-gammaXCL) copolyester from a DMSO solution. Small amounts of cationic P(CL-co-gammaPyCL) copolymers are needed to quantitatively form stable nanoparticles (ca. 10 mg/ 100 mg PLA), although larger amounts of non-ionic P(CL-co-gammaOHCL) copolymers are needed (> or = 12.5 mg/ 100 mg PLA). Copolymers with a low degree of polymerization (ca. 40) are more efficient stabilizers, probably because of faster migration towards the nanoparticle-water interface. The nanoparticle diameter decreases with the polymer concentration in DMSO, e.g. from ca. 160 nm (16 mg/ml) to ca. 100 nm (2 mg/ml) for PLA/P(CL-co-gammaPyCL) nanoparticles. Migration of the P(CL-co-gammaXCL) copolyesters to the nanoparticle surface was confirmed by measurement of the zeta potential, i.e. ca. +65 mV for P(CL-co-gammaPCL) and -7 mV for P(CL-co-gammaOHCL). The polyamphiphilic copolyesters stabilize PLA nanoparticles by electrostatic or steric repulsions, depending on whether they are charged or not. They also impart functionality and reactivity to the surface, which opens up new opportunities for labelling and targeting purposes.

Glycol chitosan improves the efficacy of intranasally administrated replication defective human adenovirus type 5 expressing glycoprotein D of bovine herpesvirus 1.

The ability of two soluble formulations, namely chitosan and glycol chitosan, when used as an intranasal adjuvant, to improve the immunogenicity of an intranasal human adenovirus type 5 replication defective expressing bovine herpesvirus 1 (BoHV-1) glycoprotein D based vaccine, was investigated in cattle. Their adjuvant effects on immune response by increasing clinical and especially virological protection against an intranasal BoHV-1 challenge were then evaluated. The best virological protection was obtained in calves immunized with the vaccine vector adjuvanted with glycol chitosan which decreased the challenge BoHV-1 virus excretion titres by 0.5-1.5 log when compared to those obtained in calves immunized with the vaccine vector alone or adjuvanted with chitosan. A slight difference in clinical scores was observed in calves immunized with the adjuvanted vaccine vector compared to calves immunized with the vaccine vector alone. The obtained data suggest that the tested soluble formulation of glycol chitosan has promising potential use as an intranasal adjuvant for recombinant viral vector vaccines in cattle.