Arthroscopic Treatment of a Subchondral Bone Cyst via Stem Cells Application: A Case Study in Equine Model and Outcomes.

Subchondral bone cysts in horses represent one of the main causes of lameness that can occur in different anatomical locations. The study describes the treatment in regenerative therapy of the intracystic implantation of adipose tissue mesenchymal stromal cells (AMSCs) included in platelet-rich plasma (PRP). The ability of AMSCs to differentiate in osteogenic cells was tested in vitro and in vivo. Given the aim to investigate the application of AMSCs in bone defects and orthopedic pathologies in horses, a four-year-old male thoroughbred racing horse that had never raced before was treated for lameness of the left hind leg caused by a cyst of the medial femoral condyle. The horse underwent a new surgery performed with an arthroscopic approach in which the cystic cavity was filled with AMSCs contained in the PRP. Radiographs were taken 3, 5, and 10 months after the surgery to assess the development of newly regenerated bone tissue in the gap left by the cyst. Twelve months after the operation and after six months of regular daily training, the horse did not show any symptoms of lameness and started a racing career. According to the study, the use of AMSCs and PRP suggests promising benefits for treating subchondral bone cysts.

Innovative Nanostructured Fillers for Dental Resins: Nanoporous Alumina and Titania Nanotubes.

The possibility of improving dental restorative materials is investigated through the addition of two different types of fillers to a polymeric resin. These fillers, consisting of porous alumina and TiO2 nanotubes, are compared based on their common physicochemical properties on the nanometric scale. The aim was to characterize and compare the surface morphological properties of composite resins with different types of fillers using analytical techniques. Moreover, ways to optimize the mechanical, surface, and aesthetic properties of reinforced polymer composites are discussed for applications in dental treatments. Filler-reinforced polymer composites are the most widely used materials in curing dental pathologies, although it remains necessary to optimize properties such as mechanical resistance, surface characteristics, and biocompatibility. Anodized porous alumina nanoparticles prepared by electrochemical anodization offer a route to improve mechanical properties and biocompatibility as well as to allow for the controlled release of bioactive molecules that can promote tissue integration and regeneration. The inclusion of TiO2 nanotubes prepared by hydrothermal treatment in the resin matrix promotes the improvement of mechanical and physical properties such as strength, stiffness, and hardness, as well as aesthetic properties such as color stability and translucency. The surface morphological properties of composite resins with anodized porous alumina and TiO2 nanotube fillers were characterized by Atomic Force Microscopy (AFM), Scanning Electron Microscopy (SEM), and X-ray chemical analysis. In addition, the stress-strain behavior of the two composite resins is examined in comparison with enamel and dentin.

Articular Cartilage Regeneration by Hyaline Chondrocytes: A Case Study in Equine Model and Outcomes.

Cartilage injury defects in animals and humans result in the development of osteoarthritis and the progression of joint deterioration. Cell isolation from equine hyaline cartilage and evaluation of their ability to repair equine joint cartilage injuries establish a new experimental protocol for an alternative approach to osteochondral lesions treatment. Chondrocytes (CCs), isolated from the autologous cartilage of the trachea, grown in the laboratory, and subsequently arthroscopically implanted into the lesion site, were used to regenerate a chondral lesion of the carpal joint of a horse. Biopsies of the treated cartilage taken after 8 and 13 months of implantation for histological and immunohistochemical evaluation of the tissue demonstrate that the tissue was still immature 8 months after implantation, while at 13 months it was organized almost similarly to the original hyaline cartilage. Finally, a tissue perfectly comparable to native articular cartilage was detected 24 months after implantation. Histological investigations demonstrate the progressive maturation of the hyaline cartilage at the site of the lesion. The hyaline type of tracheal cartilage, used as a source of CCs, allows for the repair of joint cartilage injuries through the neosynthesis of hyaline cartilage that presents characteristics identical to the articular cartilage of the original tissue.

Nanotechnology meets atopic dermatitis: Current solutions, challenges and future prospects. Insights and implications from a systematic review of the literature.

Atopic dermatitis is a chronic, relapsing, non-contiguous, exudative eczema/dermatitis, which represents a complex, multi-factorial disorder, due to an impairment of the stratum corneum barrier. Currently available drugs have a low skin bioavailability and may give rise to severe adverse events. Nanotechnologies, including nano-particles, liposomes, nano-gels, nano-mixtures, nano-emulsions and other nano-carriers, offer unprecedented solutions to these issues, enabling: i) the management of different clinical forms of atopic dermatitis, especially the recalcitrant ones, i) a better bio-availability and trans-dermal drug targeted delivery at the inflammation site, ii) dose control, iii) significant improvements both in clinical symptoms and immune responses, iv) with less adverse events being reported and a better safety profile. However, some nano-sized structures could amplify and even worsen symptoms in particularly susceptible individuals. Furthermore, most studies included in the present systematic review have been conducted in-vitro or in-vivo, with few randomized controlled clinical trials (RCTs). Future investigations should adopt this design in order to enable scholars achieving robust findings and evidence. Therefore, given the above-mentioned shortcomings, further research in the field is urgently warranted.

Oral administration of a lecithin-based delivery form of boswellic acids (Casperome®) for the prevention of symptoms of irritable bowel syndrome: a randomized clinical study.

BACKGROUND: The purpose of this study was to evaluate the long-term efficacy and the safety of a lecithin-based delivery form of boswellic acids from Boswellia serrata (Casperome®) for the prevention of symptoms in otherwise healthy subjects with mild irritable bowel syndrome (IBS). METHODS: The study included 69 otherwise healthy participants with a mild form of IBS who completed a 6-month follow-up period. In total, 34 subjects were assigned to the standard management (SM) group: diet and, if needed, hyoscine butylbromide (Buscopan®) or papaverine hydrochloride + 10 mg of Atropa belladonna extract; 35 subjects were assigned to supplementation with the Boswellia serrata lecithin-based delivery form (one tablet/day; Casperome®). IBS signs and symptoms were evaluated at inclusion (T0), after 3 (T1) and 6 months (T2). The numbers of patients who needed rescue medication were recorded. Adverse events were also evaluated. RESULTS: At baseline, the groups were comparable in terms of demographic and clinical characteristics. At follow-up, compared with the SM group, the Boswellia group showed lower mean score values for almost all self-assed IBS symptoms. A significantly lower need for rescue medications and consultations or medical evaluation/admissions was found in the Boswellia group compared with the SM group. The incidence of minimal adverse events - mainly stipsis - was significantly higher in the SM group. Oxidative stress at T2 was significantly decreased in Boswellia-supplemented subjects. CONCLUSIONS: Boswellia serrata lecithin-based delivery form (Casperome®) appears to be effective and safe in improving signs and symptoms in IBS subjects who are otherwise healthy, particularly in comparison with symptomatic drug treatment that may cause side effects and stiptis.

Interaction study between antiplatelet agents, anticoagulants, diabetic therapy and a novel delivery form of quercetin.

BACKGROUND: In this pilot non-interference clinical study we evaluated possible interactions between Quercetin Phytosome® (Quercefit™), an innovative delivery form of quercetin, and antiplatelet agents, anticoagulants, and anti-diabetic therapy in otherwise healthy subjects. METHODS: Interaction with antiplatelet therapy was assessed through the bleeding time (BT) test in 30 patients treated with acetylsalicylic acid, ticlopidine or clopidogrel before and after 10 days of supplementation with Quercetin Phytosome®. Interaction with anticoagulants was evaluated by measuring the International Normalized Ratio (INR) in 20 patients using warfarin or dabigatran before and after 20 days of supplementation with Quercetin Phytosome®. Lastly, glycaemia and glycated hemoglobin were measured in 12 diabetic patients treated with metformin and restricted diet before and after 20 days of supplementation with Quercetin Phytosome®. RESULTS: After 10 days of supplementation no significant difference was observed in mean BT in patients treated with acetylsalicylic acid, ticlopidine or clopidogrel at standard dosages. Similarly, after 20 days of supplementation, the INR level among patients assuming warfarin or dabigatran was not statistically different from baseline. Lastly, no statistically significant difference in mean levels of glycaemia and glycated hemoglobin was reported before and after 20 days of complementary administration of Quercetin Phytosome® in diabetic patients treated with metformin and restricted diet. CONCLUSIONS: Quercetin Phytosome® does not alter the antiplatelet activity of the most common antiplatelet agents, has no impact on the INR values in stable patients treated with warfarin or dabigatran, and does not influence the metabolic control of diabetic patient treated with metformin.

Immunogenicity, safety and tolerability of anti-pneumococcal vaccination in systemic lupus erythematosus patients: An evidence-informed and PRISMA compliant systematic review and meta-analysis.

The immunological perturbations associated with systemic lupus erythematosus (SLE) put many patients at a higher risk of infections, including pneumococcal pneumonia. However, the uptake and utility of anti-pneumococcal vaccines in SLE patient is both controversial and not completely agreed upon. Indeed, several epidemiological studies of anti-pneumococcal vaccine safety and efficacy in SLE have reported short-term immunogenicity with elevated anti-pneumococcal antibody titres but inconsistent long-term findings, with some studies finding poor responses, mainly for long-term immune protection. Moreover, the safety and efficacy of the pneumococcal vaccine in SLE patients remains controversial due to the different types of anti-pneumococcal vaccines, and the heterogeneity of SLE patients. Several reviews addressing anti-pneumococcal vaccination in SLE patients exist, however, to the best of our knowledge, the present is the first systematic review and meta-analysis. To better understand the efficacy and safety of pneumococcal vaccination in SLE, a comprehensive literature search was performed identifying 18 studies, which have been included in the present systematic review and meta-analysis. All studies were designed as longitudinal investigations, 2, in particular, were of high quality, being randomized, double-blind trials (RCTs). Four studies had control groups. Total sample size included 601 participants. Vaccine immunogenicity in terms of subjects with protective antibody titers ranged from 36% to 97.6%. According to our systematic review and metanalysis, high erythrocyte sedimentation rate (ESR), older age, earlier SLE onset, high disease activity, and immunosuppressive therapy were predictors of poor immunogenicity, although belimumab was found to have no significant impact. With regard to safety, no serious adverse events were found, with up to one third of cases reporting mild/low-grade complaints. In conclusion, due to the high risk of pneumococcal infection in SLE patients and given the safety and, at least partial, effectiveness, according to our systematic review and meta-analysis, in such patients, preventive strategies mainly by immunization, are required in all age groups and, in those needing immunosuppressive therapy, immunization should be given prior the initiation of the treatment. PROSPERO registration code CRD42018103605.

Quercetin phytosome® in triathlon athletes: a pilot registry study.

BACKGROUND: Oxidative stress is associated with delayed recovery and higher risk of post-training pain in triathlon athletes. Therefore, supplementation with antioxidant compounds may have a role in enhancing recovery. Quercetin presents marked antioxidant activity. In this pilot registry study, we evaluated the effects of the supplementation with a novel proprietary delivery form (phytosome®) of quercetin in amateur triathlon athletes. METHODS: We employed a specific study model of triathlon according to the "Sprint" distance. The individual triathlon training included repetition of the run 8 times in 14 days. A group of athletes used quercetin phytosome® supplementation (one tablet of 250 mg quercetin phytosome® twice daily). A control group did not use supplementation. All subjects attended a baseline measurement run and a second final measurement run at day 14. At the end of the study, subjective performance, post-training pain, cramps, time to full recovery and oxidative stress were measured. RESULTS: In total, 23 subjects used the supplement and 25 did not. No side effects were reported. The improvement of time to complete the run was greater in subjects on quercetin supplementation compared with the control group (-11.3% vs. -3.9%; P<0.05). Training was considered more valuable in the quercetin group compared with controls (P<0.05). Similarly, post-run muscular pain, cramps, localized pain and the post-exercise recovery time were all considered better with the supplementation (P<0.05). Oxidative stress was also reduced (P<0.05). CONCLUSIONS: This pilot study suggests that the oral supplementation with quercetin phytosome® may result in improved training and performance in amateur triathlon athletes.

In vivo validation of the multicomponent powder (Vitachelox®) against the deposition of polluting ions.

PURPOSE: The purpose of this in vivo study is to evaluate the acute clinical application of a multicomponent powder (Vitachelox®), including three naturally occurring standardized extracts rich in polyphenols (grape seed extract, green tea extract, oak wood/bark extract), on healthy volunteers by measuring prevention of any metal deposition within the stratum corneum (SC) following a 6-h exposure period in a polluted environment. PATIENTS AND METHODS: In this in vivo study, we evaluated the skin protective activity of the multicomponent powder formulated in a base emulsion compared to a relevant placebo cream. Using the tape stripping method, SC samples of face skin obtained from 30 healthy volunteers were compared following a 6-h exposure in a polluted area. RESULTS: No statistically significant variations on the amount of heavy metals were found in the samples of SC cells obtained from the hemi-faces treated with the multicomponent powder, with respect to baseline. On the contrary, a significantly higher concentration of heavy metals was found in the cells samples obtained from the hemi-faces treated with the placebo cream. In particular, an increased concentration of heavy metals superior to 100% were found for iron and zinc (+130.2% and +142.6%, respectively; p<0.001). CONCLUSION: This in vivo study validates and extends previous in vitro findings, indicating that the multicomponent powder allows the prevention of any metal deposition within the SC following exposure in a polluted environment. Our results suggest that the test product could play an effective role in counteracting skin damages induced by air pollution.

Phytoproflex®: supplementary management of osteoarthrosis: a supplement registry.

BACKGROUND: Curcumin is a powerful anti-oxidant that can be used to treat inflammation and pain in chronic conditions such as osteoarthrosis (OA). Phytoproflex® is characterized by an innovative delivery system that improves bioavailability of curcuminoids and could be useful in the management of OA. METHODS: This 4-week registry included 56 patients with knee OA treated according to the best standard management for symptomatic OA. On top of that, 24 patients used Phytoproflex® supplement preparation (an extract containing boswellic acid 90%, curcumin 20% and valeric acid 0.8%). Patients' control of symptoms and functional capacity were evaluated through the Karnofsky Scale and standardized treadmill test, together with measurement of oxidative stress levels and use of rescue medication. RESULTS: No problems of tolerability or safety were reported among subjects using the supplement. After 4 weeks, patients treated with the supplement reported a significant decrease in pain (P<0.05), and a significant improvement in the fitness scale (P<0.05), indicating that subjects were able to perform normal daily tasks. Less subjects in the supplement group had to use rescue medication (P<0.05), while oxidative stress levels, which were high at inclusion, significantly decreased in both groups (P<0.05). Moreover, the variation in pain-free walking distance and the Karnofsky Scale were significantly more improved (P<0.05) in patients taking the supplement compared to controls. CONCLUSIONS: This preliminary registry study indicates that Phytoproflex® can be safely used as an effective, supplementary management in most OA patients.

Combined characterization of bovine polyhemoglobin microcapsules by UV-Vis absorption spectroscopy and cyclic voltammetry.

Polyhemoglobin produced from pure bovine hemoglobin by reaction with PEG bis(N-succynimidil succinate) as a cross-linking agent was encapsulated in gelatin and dehydrated by freeze-drying. Free carboxyhemoglobin and polyhemoglobin microcapsules were characterized by UV-Vis spectroscopy in the absorption range 450-650 nm and cyclic voltammetry in the voltage range from -0.8 to 0.6 mV to evaluate the ability to break the bond with carbon monoxide and to study the carrier's affinity for oxygen, respectively. SEM used to observe the shape of cross-linked gelatin-polyhemoglobin microparticles showed a regular distribution of globular shapes, with mean size of ~750 nm, which was ascribed to gelatin. Atomic absorption spectroscopy was also performed to detect iron presence in microparticles. Cyclic voltammetry using an Ag-AgCl electrode highlighted characteristic peaks at around -0.6 mV that were attributed to reversible oxygen bonding with iron in oxy-polyhemoglobin structure. These results suggest this technique as a powerful, direct and alternative method to evaluate the extent of hemoglobin oxygenation.

Direct electrical control of IgG conformation and functional activity at surfaces.

We have devised a supramolecular edifice involving His-tagged protein A and antibodies to yield surface immobilized, uniformly oriented, IgG-type, antibody layers with Fab fragments exposed off an electrode surface. We demonstrate here that we can affect the conformation of IgGs, likely pushing/pulling electrostatically Fab fragments towards/from the electrode surface. A potential difference between electrode and solution acts on IgGs' charged aminoacids modulating the accessibility of the specific recognition regions of Fab fragments by antigens in solution. Consequently, antibody-antigen affinity is affected by the sign of the applied potential: a positive potential enables an effective capture of antigens; a negative one pulls the fragments towards the electrode, where steric hindrance caused by neighboring molecules largely hampers the capture of antigens. Different experimental techniques (electrochemical quartz crystal microbalance, electrochemical impedance spectroscopy, fluorescence confocal microscopy and electrochemical atomic force spectroscopy) were used to evaluate binding kinetics, surface coverage, effect of the applied electric field on IgGs, and role of charged residues on the phenomenon described. These findings expand the concept of electrical control of biological reactions and can be used to gate electrically specific recognition reactions with impact in biosensors, bioactuators, smart biodevices, nanomedicine, and fundamental studies related to chemical reaction kinetics.

Glutathione in the treatment of liver diseases: insights from clinical practice.

Liver diseases markedly contribute to the global burden of mortality and morbidity. The pathogenesis of alcohol- and non-alcohol-induced liver diseases is complex, and many factors have been described to contribute to the progressive loss of liver functions, including the over-generation of reactive oxygen species. Glutathione (GSH) is the most important low-molecular-weight antioxidant synthesized in cells, as it is a reducing molecule which can react to oxygen species by neutralizing the unpaired electrons that make them highly reactive and dangerous. ROS over-production impairs the intracellular GSH homeostasis, leading to GSH deficiency, a pathophysiological hallmark in alcoholic and non-alcoholic liver diseases.Judging on the basis of the evidence obtained from experimental research and previous clinical studies, GSH administration seems to be a promising strategy to recover oxidative stress-induced liver damages in alcoholic and non-alcoholic liver diseases.

Transarterial radioembolization for hepatocellular carcinoma: a review.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is the second cause of death due to malignancy in the world. The treatment of HCC is complex and includes potentially curative and palliative approaches. However, both curative and palliative treatments for HCC are often associated with a not-completely favorable safety/efficacy ratio. Therefore, other treatment options appear necessary in clinical practice. Transarterial radioembolization has shown a promising efficacy in terms of disease control and is associated with a good safety profile. This review discusses the use of transarterial radioembolization in HCC, with a focus on the clinical aspects of this therapeutic strategy.

Soothing and anti-itch effect of quercetin phytosome in human subjects: a single-blind study.

BACKGROUND: We evaluated the ability of quercetin, a natural antioxidant formulated in a specific delivery system, to reduce skin inflammation induced by a variety of stimuli, including UV radiation, stimulation with a histamine solution, or contact with chemical irritants. In particular, we tested the soothing and anti-itch effect of Quercevita(®), 1% cream for external use, a formulation characterized by a phospholipids-based delivery system. PATIENTS AND METHODS: The study was a monocentric, single blind trial that enrolled a group of 30 healthy volunteers. The back of each subject was examined to identify four quadrants with no previous skin damage or naevi that were treated in order to induce a controlled and reversible form of skin stress. The areas were treated as follows: no product; Quercevita(®) 1% cream, 2 mg/cm(2); placebo; positive control (a commercially available topical formulation containing 1% dexchlorpheniramine). RESULTS: Only quercetin phospholipids 1% and dexchlorpheniramine 1% achieved a significant reduction in erythema with comparable results: (-10.05% [P=0.00329] for quercetin phospholipids 1% vs -14.05% [P=0.00046] for the positive control). Moreover, quercetin phospholipids 1% and dexchlorpheniramine 1% were both associated with a significant decrease in mean wheal diameter: (-13.25% and -12.23% for dexchlorpheniramine 1%, respectively). Similar findings were reported for the other tested parameters. CONCLUSION: Quercetin has a skin protective effect against damage caused by a variety of insults, including UV radiation, histamine, or contact with toxic chemical compounds. Indeed, quercetin is able to reduce redness, itching, and inflammation of damaged skin; it may also help restore skin barrier function, increasing hydration, and reducing water loss.

Curative therapies for hepatocellular carcinoma: an update and perspectives.

Curative treatments, including liver transplantation, surgical resection and percutaneous treatments, are the recommended therapies in BCLC-0 (Barcelona Clinic of Liver Cancer) or BCLC-A hepatocellular carcinoma (HCC). This review provides an overview of some issues of clinical importance concerning curative treatments in HCC.

Surface Morphology and Tooth Adhesion of a Novel Nanostructured Dental Restorative Composite.

Recently, a novel dental restorative composite based on nanostructured micro-fillers of anodic porous alumina has been proposed. While its bulk properties are promising thanks to decreased aging and drug delivery capabilities, its surface properties are still unknown. Here we investigated the surface morphology and the adhesion to tooth dentin of this composite as prepared. For comparison, we used two commercial composites: Tetric EVO Flow (Ivoclar) and Enamel HRi Plus (Micerium). The surface morphology was characterized by atomic force microscopy and the adhesion strength by tensile tests. The experimental composite is rougher than the commercial composites, with root mean square roughness of ~549 nm against 170-511 nm, and presents an adhesion strength of ~15 MPa against 19-21 MPa. These results show at the same time some proximity to the commercial composites, but also the need for optimization of the experimental material formulation.