Sodium Chondroitin Sulfate Research Articles

STUDY OF THE POTENTIAL ANALGESIC PROPERTIES OF CARBON DIOXIDE FOR THE TREATMENT OF PAIN SYNDROME IN CASE OF OSTEOARTHRITIS

Pain syndrome is a serious global problem that causes and complicates a number of diseases, the main symptom of which is joint pain. One of them is osteoarthritis (OA). Traditional methods of treating OA often have limited efficacy and can cause side effects, so it is important to study new approaches, such as carboxytherapy (use of carbon dioxide). Objective. To investigate the analgesic effect of carbon dioxide (CO2) and its combined use with other agents. Methods. The efficacy of carbon dioxide injections used alone and in combination with other drugs was studied in a formalin model of inflammation in rats. Results. The latent periods of phases I and II increased significantly in the experimental groups, especially in groups V, VI and VII (p < 0.001), indicating a delay in pain reactions. The duration of pain phase I was significantly shorter in the groups receiving CO2 compared to the control group (p < 0.001). The shortest duration was observed in group V, where it decreased by 1.77 minutes. The duration of pain phase II was also significantly shorter in groups V, VI, and VII treated with CO2 compared to group II (p < 0.001). The difference ranged from 7.49 to 12.54 minutes. The number of pain reactions after phase I decreased by 13.25– 16.1 points in the groups receiving CO2 compared to the control group. The data obtained indicate that CO2 significantly increases the duration of latent periods of pain (by 55–65 %), reduces the duration of its phases (by 40–50 %) and reduces the intensity of pain reactions (by 40–50 %) in rats compared to control pathology. The most pronounced effect was observed with the combined use of CO2 with sodium diclofenac or chondroitin sulfate. Conclusions. The results of the study expand the understanding of the analgesic effect of CO2 on the formalin model of inflammation. The use of CO2 significantly reduced the duration of both phases of the pain reaction and reduced the number of painful manifestations, which confirms the prospects of its use as an additional, and in some cases the main means of reducing pain and inflammation.

Effectiveness of the use of bioactive concentrate of marine fish in patients with back pain

Background. The urgency of pain relief and patient improvement necessitates evaluating the most effective treatment approaches. This includes a comparative analysis of medications with different mechanisms of action, both taken individually and in combination while considering potential drug toxicity and individual patient intolerances. The study purposed to assess the efficacy of a bioactive concentrate derived from marine fish (BCMF), both alone and in combination with a non-steroidal anti-inflammatory drug (NSAID), for the treatment of back pain, in comparison to therapy involving solely oral sodium chondroitin sulfate (CS). Materials and methods. We examined four groups of patients, each comprising 30 male or female subjects with complaints of back pain. Each group was administered one of three medications: NSAIDs in a standard dosage, CS in a daily dose of 1 g (two capsules of 500 mg each), and BCMF in the form of intramuscular injections in a daily dose of 1 ml (0.2 ml per injection). The fourth group of patients received combined treatment, namely, 1 ml of BCMF and NSAIDs in a standard dosage daily. All parti­cipants underwent laboratory tests and instrumental examinations. ­Results. The administration of BCMF, both alone and in combination with NSAIDs resulted in an improved subjective assessment of patients’ psychoemotional well-being, marked by reduced back pain intensity, enhanced quality of life indices, and diminished le­vels of anxiety and depression. The combination of BCMF with NSAIDs demonstrated a more pronounced effect on redu­cing tumor necrosis factor α serum concentration than monothe­rapy with BCMF. The combination therapy positively impacted the condition of lower extremity vessels as indicated by Doppler ultrasonography. Conclusions. BCMF can be an effective addition to the standard therapy of back pain.

Auricular cartilage regeneration using chondroitin sulfate-based hydrogel with mesenchymal stem cells in rabbits.

Cartilage is an avascular and alymphatic tissue that lacks the intrinsic ability to undergo spontaneous repair and regeneration in the event of significant injury. The efficacy of conventional therapies for invasive cartilage injuries is limited, thereby prompting the emergence of cartilage tissue engineering as a possible alternative. In this study, we fabricated three-dimensional hydrogel films utilizing sodium alginate (SA), gelatin (Gel), and chondroitin sulfate (CS). These films were included with Wharton's jelly mesenchymal stem cells (WJ-MSCs) and intended for cartilage tissue regeneration. The hydrogel film that were prepared underwent evaluation using various techniques including scanning electron microscope (SEM), Fourier transform infrared (FTIR) spectroscopy, assessment of the degree of swelling, degradation analysis, determination of water vapor transmission rate (WVTR), measurement of water contact angle (WCA), evaluation of mechanical strength, and assessment of biocompatibility. The rabbit ear cartilage regeneration by hydrogel films with and without of WJ-MSCs was studied by histopathological investigations during 15, 30, and 60 days. The hydrogel films containing CS exhibited superior metrics compared to other nanocomposites such as better mechanical strength (12.87 MPa in SA/Gel compared to 15.56 in SA/Gel/CS), stability, hydrophilicity, WVTR (3103.33 g/m2/day in SA/Gel compared to 2646.67 in nanocomposites containing CS), and swelling ratio (6.97 to 12.11% in SA/Gel composite compared to 5.03 to 10.90% in SA/Gel/CS). Histopathological studies showed the presence of chondrocyte cells in the lacunae on the 30th day and the complete restoration of the cartilage tissue on the 60th day following the injury in the group of SA/Gel/CS hydrogel containing WJ-MSCs. We successfully fabricated a scaffold composed of alginate, gelatin, and chondroitin sulfate. This scaffold was further enhanced by the incorporation of Wharton's jelly mesenchymal stem cells. Our findings demonstrate that this composite scaffold has remarkable biocompatibility and mechanical characteristics. The present study successfully demonstrated the therapeutic potential of the SA-Gel-CS hydrogel containing WJ-MSCs for cartilage regeneration in rabbits.

Zein/Polysaccharide Nanoscale Electrostatic Complexes: Preparation, Drug Encapsulation and Antibacterial Properties.

Characterization of zein aqueous solutions, as a function of the ethanol content and pH, was performed, giving information on the zein aggregation state for the construction of complexes. The aggregation state and surface charge of zein was found to depend on the mixed solvent composition and pH. Nonstoichiometric complex nanoparticles (NPECs) were prepared by electrostatically self-assembling zein, as the polycation, and sodium alginate or chondroitin sulfate, as the polyanions, at a pH of 4. A wide range of parameters were investigated: the alcohol-water content in the zein solutions, the charge molar ratios, the solution addition order and the addition rate. The resulting nanoparticles were characterized by dynamic and electrophoretic light scattering, circular dichroism and scanning electron microscopy. The smallest size for the NPECs (100 nm) was obtained when the polysaccharides acted as the titrate with an addition rate of 0.03 mL·min-1. The NPECs with the best characteristics were selected for loading with ciprofloxacin and then deposited on a cellulosic material in order to evaluate their antibacterial activity. Substantial drug encapsulation with desired drug release profiles were found together with notable antibacterial efficiency, showing the tunability of the properties for both the zein and its complexes with polysaccharides, together with their application potential in the biomedical field.

Formation of Polyion Complex Aggregate Formed from a Cationic Block Copolymer and Anionic Polysaccharide.

Block copolymers (PmMn; P20M101 and P100M98) comprising poly(2-(methacryloyloxy)ethylphosphorylcholine) (PMPC, P) containing biocompatible phosphorylcholin pendants and cationic poly((3-acryloylaminopropyl) trimethylammonium chloride) (PMAPTAC, M) were synthesized via a controlled radical polymerization method. The degrees of polymerization of the PMPC and PMAPTAC segments are denoted by subscripts (PmMn). The mixture of cationic PmMn and anionic sodium chondroitin sulfate C (CS) with the pendant anionic carboxylate and sulfonate groups formed polyion complex (PIC) aggregates in phosphate-buffered saline. A charge-neutralized mixture of P20M101 with CS formed P20M101/CS PIC vesicles with a hydrodynamic radius (Rh) of 97.2 nm, zeta potential of ca. 0 mV, and aggregation number (Nagg) of 23,044. PMPC shells covered the surface of the PIC vesicles. The mixture of P100M98 and CS formed PIC spherical micelles with the PIC core and hydrophilic PMPC shells. The Rh, zeta potential, and Nagg of the PIC micelles were 26.4 nm, ca. 0 mV, and 404, respectively. At pH < 4, the carboxylate anions in CS were protonated. Thus, the charge balance in the PIC micelles shifted to decrease the core density owing to the electrostatic repulsions of the excess cations in the core. The PIC micelles dissociated at a NaCl concentration ≥0.6 M owing to the charge screening effect. The positively charged PIC micelles with excess P100M98 can encapsulate anionic dyes owing to electrostatic interaction.

Physical Characteristics, Clinical Application, and Side Effects of Viscoelastics in Ophthalmology.

To explain the physical properties of ophthalmic viscoelastic devices (OVDs), covering their structural units, optimal features, existing viscoelastic materials, clinical applications, and potential side effects. This is a narrative review on the OVDs. A literature review was conducted in PubMed, Google Scholar, and Scopus databases. Studies that investigated physical characteristics, clinical applications, OVD commercial products, and their complications were included. We included 42 articles from 2010 and discussed physical characteristics, properties of a desirable OVD, structural units of common OVDs, OVD commercial products, clinical applications, and also complications of OVDs. Today, viscoelastics hold a distinct and crucial role in intraocular surgery due to their remarkable properties. These materials safeguard the endothelium and epithelium, uphold anterior chamber depth, manage intraocular bleeding, ease tissue handling, and aid intraocular lens placement. Currently, the American market features 12 prevalent viscoelastic types, including 7 sodium hyaluronate derivatives (Healon, Healon-Greater Viscosity, Healon-5, Amvisc, Amvisc Plus, Advanced Medical Optics Vitrax, and Provisc), 2 hydroxypropyl methylcellulose 2% derivatives (OcuCoat and Cellugel), and 3 combinations of sodium hyaluronate and chondroitin sulfate (Viscoat, DisCoVisc, and DuoVisc). Despite the introduction of new viscoelastic materials annually, no single material encompasses all desired properties. Surgeons must select and employ suitable viscoelastics based on surgical conditions and patient requirements. Advancements in material development and understanding of physical properties and clinical applications continue to refine viscoelastic selection.

Suprachoroidal triamcinolone versus posterior subtenon triamcinolone either alone or formulated in the management of diabetic macular edema

PurposeThis study aims to compare posterior subtenon triamcinolone acetonide injection either formulated or alone versus suprachoroidal triamcinolone in the management of diabetic macular edema.MethodsThis study is a prospective interventional study that included 75 patients, divided into three groups, each group with 25 patients. Group I received a combination of triamcinolone acetonide (TA) (40 mg) and VISCOAT, which is a combination of sodium chondroitin sulfate (20 mg) and sodium hyaluronate (15 mg). The injection was done in the posterior subtenon space using the NAGATA cannula. Group II received TA (40 mg) in the posterior subtenon space. Group III underwent an injection of 4 mg/100µl of TA in the supra choroidal space.ResultsWe found a statistically significant difference between the three studied groups regarding BCVA (P = 0.001) and CMT at six months postoperative (P = 0.001) with the highest median BCVA and lowest median CMT observed in the formulated TA group.ConclusionWe concluded that early treatment of DME by formulated TA is better than TA alone, and suprachoroidal TA in the form of increasing the BCVA and decreasing the CMT without any elevation of IOP.Trial registration number NCT05464953.Date of registration 17/7/2022 (retrospectively registered).

Index Evaluation of Clinical Efficacy of Immunomodulatory and Osteotropic Therapy for Chronic Generalized Periodontitis of Varying Severity: A Prospective Cohort Study

Background. The significant prevalence of chronic generalized periodontitis, the severity of its course, the increase in the number of complicated forms and short-term remissions cause a constant search for new methods and means of its treatment. When choosing the most effective methods of therapy, specialists mostly prefer a complex effect on the main pathogenetic links of the disease, while often losing sight of the body's own defenses, especially in terms of pharmacotherapeutic support and immunity strengthening. This study presents the results of a study of the clinical efficacy of the treatment of chronic generalized periodontitis by means of the developed therapy complex, including the use of immunomodulatory and osteotropic drugs.Objective — to study clinical efficacy of the developed complex immunomodulatory and osteotropic treatment for chronic generalized periodontitis.Methods. A prospective cohort study was conducted in 154 patients aged 20 to 75 with periodontitis of varying severity. Conventional examination of patients was carried out in specialized dental clinics DentoProma (Krasnodar) and Dentalife (Stavropol) based at the Dentistry Department, Stavropol State Medical University (Russia). The study period was 24 months. The patients were divided into a main group of 118 participants and a control group of 36 participants. The comprehensive treatment plan, prescribed to all patients, included proper oral hygiene education, individual and professional dental hygiene, topical anti-inflammatory agents, Vector therapy, open flap debridement, flap surgery, relevant splinting prosthetics (if necessary). The authors developed a comprehensive therapy, which included administration of the immunomodulatory agent Hepon (Immapharma Company, Russia), glucosamine hydrochloride and chondroitin sulfate sodium. All patients of the main and control groups were additionally ranked into subgroups depending on the severity of diagnosed periodontitis: slight (subgroup 1), moderate (subgroup 2) and severe (subgroup 3). The major focus of the study was to establish efficacy of the developed therapy which was defined by the degree of resolution of the inflammatory process and increase in the period of remission. Reflecting the presence and degree of inflammation, dental plaque index and oral hygiene status were considered to be the target indicators. Analysis and statistical processing of the obtained data were carried out using Microsoft Excel (Microsoft, USA).Results. The analysis of the data revealed that the immediate clinical results of the developed complex therapy both in the main group and in the control group were approximately identical. According to the follow-up data obtained one month after the treatment, additional prescription of complex osteotropic treatment to the patients with chronic generalized periodontitis contributed to rapid resolution of infection in the gingival tissues and provided stable treatment results.Conclusion. Introduction of the complex clinical and hygienic treatment promoted resolution of the inflammatory process in the gingival tissues of all patients who received immunomodulatory and osteotropic therapy.

Review on Quality Safety Standards and Critical Control Points of Chondroitin Sulfate Sodium

Review on Quality Safety Standards and Critical Control Points of Chondroitin Sulfate Sodium

Fabrication and Characterization of Chicken- and Bovine-Derived Chondroitin Sulfate/Sodium Alginate Hybrid Hydrogels.

The physicochemical properties and microstructure of hybrid hydrogels prepared using sodium alginate (SA) and chondroitin sulfate (CS) extracted from two animal sources were investigated. SA-based hybrid hydrogels were prepared by mixing chicken- and bovine-derived CS (CCS and BCS, respectively) with SA at 1/3 and 2/3 (w/w) ratios. The results indicated that the evaporation water loss rate of the hybrid hydrogels increased significantly upon the addition of CS, whereas CCS/SA (2/3) easily absorbed moisture from the environment. The thermal stability of the BCS/SA (1/3) hybrid hydrogel was higher than that of CCS/SA (1/3) hybrid hydrogel, whereas the hardness and adhesiveness of the CCS/SA (1/3) hybrid hydrogel were lower and higher, respectively, than those of the BCS/SA (1/3) hybrid hydrogel. Low-field nuclear magnetic resonance experiments demonstrated that the immobilized water content of the CCS/SA (1/3) hybrid hydrogel was higher than that of the BCS/SA (1/3) hybrid hydrogel. FTIR showed that S=O characteristic absorption peak intensity of BCS/SA (2/3) was obviously higher, suggesting that BCS possessed more sulfuric acid groups than CCS. SEM showed that the hybrid hydrogels containing CCS have more compact porous microstructure and better interfacial compatibility compared to BCS.

Molecular engineering for construction of a novel ONOO−- activated multicolor fluorescent nanoprobe for early diagnosis and assessing treatment of arthritis in vivo

Early diagnosis and assessment of the therapeutic effect of arthritis requires a reliable bioanalytical method to quantitatively and selectively detect the biomarkers peroxynitrite (ONOO−) in inflammatory diseases. Compared with previously reported probes for the specific detection of ONOO−, molecular engineering based on ONOO−-activated multicolor fluorescence nanoprobes will have the advantages of providing multi-channel information and be more suitable for bioimaging in multicomponent complex environments. Herein, for the first time, a fluorescent nanoprobe (CSU-FT) based on fluorescence resonance energy transfer (FRET), which can be activated by ONOO−, was constructed for multicolor fluorescence imaging, diagnosis and treatment of arthritis in inflammatory mice. Specifically, an energy transfer scaffold was constructed by conjugation of a near-infrared (NIR) xanthane fluorophore with a rhodamine B fluorophore and multicolor by ONOO−-modulated, which was then grafted onto sodium chondroitin sulfate (CSNa) to form CSU-FT through self-assembly. This nanoprobe shows a fast response time (<20s), outstanding selectivity and excellent detection limits as low as 11.7 nM. Interestingly, CSU-FT has been successfully used for intracellular multichannel imaging of endogenous ONOO− production as well as for diagnosis and treatment in a mice model of arthritis with impressive results, revealing practical application in physiological and pathological connection between ONOO− and arthritis.

Comparative effectiveness and safety of cocktail therapy versus combined sodium hyaluronate and chondroitin sulphate (Ialuril): Intravesical instillation treatment of interstitial cystitis/bladder pain syndrome, which one to use?

Objective: To compare effectiveness and safety of intravesical therapy (sodium hyaluronate and chondroitin sulphate) Ialuril versus cocktail therapy for treatment of interstitial cystitis (IC). Materials and methods: Prospective study from March 2013 till August 2019 including all IC patients presented to our urology clinic. All IC patients underwent basic workup including urine test, urodynamic test and gynaecological/genital exam. Postoperatively, all patients received intravesical therapy. Patients were randomly allocated to either cocktail therapy (NaOH + heparin + lidocaine) or Ialuril (Sodium hyaluronate and chondroitin sulphate) therapy as intravesical seven cycles. The primary outcome was therapy effectiveness using Interstitial Cystitis Problem Index (ICPI) and Interstitial Cystitis Symptom Index (ICSI) improvement post therapy. Secondary outcome were for complications and compliance. Results: Total of 32 patients were included (6 males, 26 females) with mean age of 43 years (24–72 years), mean follow-up 36 months (15–72 months). Cocktail intravesical therapy was used in 21 patients while 11 patients received Ialuril. All patients showed improvement on their ICSI and ICPI scores post therapy from their baseline. Statistical analysis showed no significant difference between both groups regarding improvement in ICSI and ICPI index with p-value = 0.552 and p = 0.79, respectively. Infection and non-compliance is significantly high in the cocktail arm p = 0.004, p = 0.027 Conclusions: Intravesical cocktail therapy was equally effective as Ialuril in treating IC. Ialuril was preferred over cocktail therapy because of lower side effect; when considering ulcerative IC subgroup, we need large randomised controlled trials to compare therapy benefits.

A theranostic microneedle array patch for integrated glycemia sensing and self-regulated release of insulin.

Diabetes can cause various complications and affect the normal functioning of the human body. A theranostic and diagnostic platform for real-time glycemia sensing and simultaneous self-regulated release of insulin is desired to improve diabetic patients' life quality. Here, we describe a theranostic microneedle array patch, which enables the achievement of visualization quantification of glycemia and simultaneously self-regulated release of insulin. The microneedle patch (MNDF) was fabricated by crosslinking of 3-aminophenylboronic acid (ABA)-modified sodium alginate and chondroitin sulfate. The hierarchical structure consisted of a tip part containing mineralized insulin particles and glucose oxidase (GOD) for insulin release, and a base surface embodying 3,3',5,5'-tetramethylbenzidine (TMB) and (horseradish peroxidase) HRP for real-time glycemia sensing. In the presence of glucose, GOD converts glucose into H+ and H2O2, driving gradual dissolution of the calcium layer of insulin particles, resulting in long-acting release of insulin. By the bio-catalytic action of HRP, the generated H2O2 brings about a visible color change allowing the glucose level at the base surface to be read out. We believe that the theranostic microneedle array patch can act as a promising alternative for future clinical applications.

Pharmacologic treatment of GERD in adolescents: Is esophageal mucosal protection an option?

Background:Gastroesophageal reflux disease (GERD) is still a challenging and difficult to treat condition in children. Although acid suppression represents the mainstay of treatment in adolescents, it is not devoid of adverse events, especially in the long-term.Objectives:In this investigation we explored a new therapeutic avenue in GERD, that is esophageal mucosal protection.Design:To this end, we performed an investigator-initiated, retrospective study to evaluate the efficacy and safety of a short-term treatment with Esoxx™ medical device in 25 adolescents with GERD-related symptoms. This mucoadhesive formulation contains two natural mucopolysaccharides (sodium hyaluronate and chondroitin sulphate) and adheres to the esophageal mucosa, exerting a protective effect against refluxed gastric contents and allowing mucosal healing.Methods:Heartburn, epigastric burning and post-prandial regurgitation were scored with a pain VAS scale and re-evaluated after 3-week treatment with Esoxx (one stick post-prandially, three times daily).Results:All patients completed the treatment without adverse effects and with good tolerability and compliance. All the three major symptoms significantly (p<0.001) improved after treatment. No patient required additional investigation (i.e. upper Gastrointestinal endoscopy) or medication (i.e. antisecretory drugs).Conclusion:The results of this pilot study suggest that esophageal mucosal protection is a promising therapeutic avenue for GERD also in children. Provided, these data be confirmed by a large, randomized clinical trial, this medical device can enter our therapeutic armamentarium against this challenging disease.

Effects of an articular cartilage lubrication with a viscosupplement in vitro and in vivo following osteochondral fractures in horses.

To assess whether the combination of hyaluronan, sodium chondroitin sulfate, and N-acetyl-d-glucosamine (HCSG) lubricates articular cartilage in vitro and modulates joint lubrication in vivo. 16 healthy adult horses. The effects of HCSG injections on SF lubricant properties and joint health, immediately after injury and 2 weeks later, were analyzed by use an equine osteochondral fracture model of post-traumatic osteoarthritis (OA). Middle carpal joints of adult horses were randomly assigned to 1 of 4 surgical treatment groups as follows: normal nonsurgical group (n = 8), normal sham-surgical group (8), OA-induced surgical group with HCSG injection (8), or OA-induced surgical group with saline (0.9% NaCl) solution injection (8). Synovial fluid was aspirated periodically and analyzed for boundary lubrication function and lubricant molecules. At 17 days, joints were screened for gross pathological changes. Induction of OA led to an impairment of SF lubrication function and diminished hyaluronan concentration in a time-dependent manner following surgery, with HCSG injection lessening these effects. Certain friction coefficients approached those of unaffected normal equine SF. Induction of OA also caused synovial hemorrhage at 17 days, which was lower in joints treated with HCSG. After induction of OA, equine SF lubricant function was impaired. Hyaluronan-sodium chondroitin sulfate-N-acetyl-d-glucosamine injection restored lubricant properties at certain time points and reduced pathological joint changes.

A primer on ocular viscosurgical devices.

To provide pharmacists with an overview of ocular viscosurgical devices (OVDs) and a comprehensive resource describing characteristics of commercially available agents. OVDs are substances that are injected into the eye during ophthalmic procedures, such as cataract surgery, to reduce injury to the endothelium that may result from surgical manipulation. Currently available OVDs are composed of one or more of the following active ingredients: sodium hyaluronate, sodium chondroitin sulfate, and hydroxypropylmethylcellulose. Rheologic properties of OVDs, such as viscosity, elasticity, pseudoplasticity, and cohesion, affect the products' function and performance. Based on rheologic properties, OVDs can be generally classified as cohesive or dispersive. Given each products' unique characteristics, OVDs are not interchangeable. An understanding of OVD characteristics and role in practice allows for improved product selection, which varies based on patient characteristics and procedure. Availability of OVD information and literature is generally lacking since OVDs are regulated by the US Food and Drug Administration (FDA) as medical devices. This primer includes an overview of relevant ophthalmic surgical practices and the landscape of comparative efficacy and safety literature to assist in formulary decision-making. This review also provides a comprehensive guide to commercially available OVDs and a discussion on practical considerations for the pharmacist. Pharmacists may be tasked with handling OVDs in institutional settings. Knowledge about OVD rheologic properties, product characteristics, role in practice, and available literature is necessary for managing formularies and ensuring optimal product selection.

Ophthalmic Solution Safety Profile: Active Surveillance of a Sodium Hyaluronate/Chondroitin Sulfate Combination in Peruvian Population.

BackgroundSodium hyaluronate/chondroitin sulfate fixed combination plays an essential role in the treatment of keratoconjunctivitis sicca, a multifactorial disease accompanied by ocular symptoms like alteration of the tear film. Despite low or no absorption of such drugs, these can cause secondary effects. An essential tool in the study of medication behavior is active pharmacovigilance. Unlike spontaneous reporting pharmacovigilance, this tool allows an appraisal of adverse drug reactions (ADRs)’ real incidence, a higher capacity to identify safety signals, the relationship with concomitant drugs and pathologies prevalent in the study population. This study aimed to evaluate the safety profile and identify and/or assess adverse reactions in an uncontrolled population.MethodsActive pharmacovigilance by Drug Event Monitoring was performed. A total of 3 follow-up calls were made for 30 days for the identification of the ADRs, tolerability (ADR severity, seriousness, long term sequelae, and duration) and the possible risks (safety signals, medical interactions) of sodium hyaluronate and chondroitin sulfate (HUM).ResultsThirty-five ADRs were identified in the 212 patients included in the study (0.17 ADR/patient). The 35 ADRs were classified into 3 System Organ Class (SOC) groups: general disorders and administration site conditions (74.2%), eye disorders (22.9%), and nervous system disorders (2.9%); and 4 Preferred Term (PT) groups: burning sensation (74.2%), followed by blurred vision (20%), ocular pain (2.9%) and headache (2.9%). All the ADRs were categorized as mild and not serious. No statistically significant differences were found in concomitantly medications, posology and age groups.ConclusionGood tolerability to the solution was identified, with a low incidence of ADRs. Just the same, all the associated ADRs were consistent with the information found in HUM’s physicochemical profile and the physiopathology of DED. No unknown risks were identified, reinforcing HUM’s safety profile.

Rheological Behavior of a New Mucoadhesive Oral Formulation Based on Sodium Chondroitin Sulfate, Xyloglucan and Glycerol.

Background: The study aimed at assessing the mucoadhesive properties and the barrier effect of a formulation, labelled as AL2106, containing sodium chondroitin sulfate (ChS), xyloglucan from tamarind seed extract, and glycerol, by evaluating the capacity to adhere to a layer of mucin, the rheological synergism and the barrier effect in comparison to the marketed Esoxx One medical device. AL2106 is a medical device distributed by Alfasigma SpA, Italy with REF FTP57 (Manufacturer: Labomar SpA); it is analogous to Esoxx One medical device: the two products are drinkable solutions that, after swallowing, adhere to the esophageal mucosa, protecting it from the corrosive effect of the gastric acid reflux. AL2106 has been conceived to be better performing in terms of duration of the barrier effect compared to Esoxx One. Methods: The mucoadhesive properties, rheological behavior, buffering capacity against acidity, and film-forming ability with the resultant protecting effect on esophagus mucosa (caffeine permeation test) was compared between the two products. Results: The mucoadhesivity of the formulations was shown in vitro: both remained adherent to a mucin layer, also when the support was rotated by 90°, and when the film layer was washed with water, intended to simulate the washout due to swallowing. AL2106 showed a good buffering efficacy, being able to absorb at least 50% of its weight of 0.03 M HCl while maintaining the pH above 4. The film-forming effect and barrier properties of AL2106 and Esoxx One were confirmed by an in vitro study on reconstructed human esophageal epithelium. A greater film-forming efficacy of AL2106, lasting for at least 5 h, than Esoxx One was observed. Noteworthy, the barrier function of esophageal tissues was shown to be preserved after the application of both formulations. Conclusions: The combination of ChS with the mucoadhesive glycerol−xyloglucan complex and other excipients, which contribute to the barrier effect and to mucoadhesion, contained in AL2106, allowed a longer-lasting protective effect than Esoxx One, proving its effectivity and safety for oral use.

Mechanical resistance of hydroxyapatite-based bio components for use in bone grafting

The use of bone grafts in orthopedic and dental surgeries is increasing due to the evolution of surgical procedures and the larger life expectancy of the population. Due to this, a wide range of biomaterials for use as bone grafts was investigated in the last years, including autologous bone, homologous bone, xenografts, and synthetics, with similar mechanical properties to bone. In order to add moldability and flexibility properties to hydroxyapatite, some binders have also been studied. The present work evaluates the mechanical resistance of hydroxyapatite-based bio components regarding their application in bone grafting. The raw material used was lyophilized bovine bone converted to powder with the addition of different binders, respecting parameters of toxicity and properties of the thickeners. Each binder was mixed to the powdered bone in proportions of 25%, 35%, and 50% volume/volume, in order to generate the test specimens. Samples were tested in compression, flexion, and fatigue. Considering compressive strength, phosphoric acid (8.50 MPa), collagen (8.00 MPa), chondroitin sulfate (6.90 MPa), and chitosan (19.50 MPa) presented the best results. In flexion, polyvinyl acetate presented flexural strength of (35% and 50%) 54.18 MPa and 50.24 MPa. In the fatigue test, the binders that presented the best performance were sodium alginate, collagen, and chondroitin sulfate. The use of medium (35%) and high (50%) amount of binder demonstrated better results. An extensive study evaluating the mechanical strength of hydroxyapatite-based bio components for use as a bone graft with various percentages of binders and bone was tested. Considering compressive strength, phosphoric acid, collagen, chondroitin sulfate, and chitosan presented the best results, whereas in flexion, the best resistance was obtained with polyvinyl acetate. In the fatigue test, the best performances were achieved by sodium alginate, collagen, and chondroitin sulfate.

Comparison of Intravesical Hyaluronic Acid, Chondroitin Sulfate, and Combination of Hyaluronic Acid-Chondroitin Sulfate Therapies in Animal Model of Interstitial Cystitis.

PurposeThree intravesical treatment agents were compared in an interstitial cystitis rat model: chondroitin sulfate, hyaluronic acid, and combined hyaluronic acid-chondroitin sulfate.MethodsThirty-five female rats were divided into 5 groups: control (group I), isotonic (group II), chondroitin sulfate (group III), hyaluronic acid (group IV), and hyaluronic acid-chondroitin sulfate (group V). Chemical cystitis was induced in all experimental groups by intravesical instillation of 1 mL of hydrogen peroxide (H2O2) for 15 minutes via the transurethral route. The treatment was administered every other day for 3 sessions 2 days after inducing chemical cystitis. Groups II, III, IV, and V received 1 mL of 0.9% NaCl, 1 mL of 0.2% sodium chondroitin sulfate, 1 mL of low-molecular-weight hyaluronic acid, and 1 mL of 2% sodium chondroitin sulfate+1.6% sodium hyaluronic acid, respectively. On day 7, the animals were sacrificed and the bladders were removed for histopathological and immunohistochemical assessments.ResultsSignificant between-group differences were found in vascular congestion (P=0.006). The grade of submucosal edema in groups II and IV was significantly higher than in group I (P=0.006, P=0.006, respectively). In group I, the grade of granulation tissue was lower than the other 4 groups, but no significant difference was found between the remaining groups (P=0.016). Neutrophil cell infiltration was more intense in groups II and IV than in group I (P=0.006, P=0.006, respectively). Significant differences in the leukocyte and mast cell count were detected between groups II and IV (P<0.001, P<0.001, respectively). Abnormal zonula occludens-1 and uroplakin-III immunoreactivity in group II was higher than in groups I, III, or V (P=0.002, P=0.010, respectively). Interleukin-8 expression was lower in group V than in group II (P=0.001).ConclusionA single treatment of chondroitin sulfate and combined hyaluronic acid-chondroitin sulfate treatment demonstrated efficacy by suppressing inflammation and achieving improvements in the urothelium.