Function and contribution of two putative Enterococcus faecalis glycosaminoglycan degrading enzymes to bacteremia and catheter-associated urinary tract infection.

Enterococcus faecalis is a common cause of healthcare-acquired bloodstream infections and catheter-associated urinary tract infections (CAUTIs) in both adults and children. Treatment of E. faecalis infection is frequently complicated by multi-drug resistance. Based on protein homology, E. faecalis encodes two putative hyaluronidases, EF3023 (HylA) and EF0818 (HylB). In other Gram-positive pathogens, hyaluronidases have been shown to contribute to tissue damage and immune evasion, but the function in E. faecalis has yet to be explored. Here, we show that both hylA and hylB contribute to E. faecalis pathogenesis. In a CAUTI model, ΔhylA exhibited defects in bladder colonization and dissemination to the bloodstream, and ΔhylB exhibited a defect in kidney colonization. Furthermore, a ΔhylAΔhylB double mutant exhibited a severe colonization defect in a model of bacteremia while the single mutants colonized to a similar level as the wild-type strain, suggesting potential functional redundancy within the bloodstream. We next examined enzymatic activity, and demonstrate that HylB is capable of digesting both hyaluronic acid (HA) and chondroitin sulfate in vitro, while HylA exhibits only a very modest activity against heparin. Importantly, HA degradation by HylB provided a modest increase in cell density during the stationary phase and also contributed to dampening of lipopolysaccharide-mediated NF-κB activation. Overall, these data demonstrate that glycosaminoglycan degradation is important for E. faecalis pathogenesis in the urinary tract and during bloodstream infection.

Cloning and characterization of a hyaluronate lyase EsHyl8 from Escherichia sp. A99.

Hyaluronidase, an enzyme that degrades hyaluronic acid (HA), is utilized in clinical settings to facilitate drug diffusion, manage extravasation, and address injection-related complications linked to HA-based fillers. In this study, a novel hyaluronate lyase EsHyl8 was cloned, expressed, and characterized from Escherichia sp. A99 of human intestinal origin. This lyase belongs to polysaccharide lyase (PL) family 8, and showed specific activity towards HA. EsHyl8 exhibited optimal degradation at 40 °C and pH 6.0. EsHyl8 exhibited a high activity of 376.32 U/mg among hyaluronidases of human gut microorganisms. EsHyl8 was stable at 37 °C and remained about 70 % of activity after incubation at 37 °C for 24 h, demonstrating excellent thermostability. The activity of EsHyl8 was inhibited by Zn2+, Cu2+, Fe3+, and SDS. EsHyl8 was an endo-type enzyme whose end-product was unsaturated disaccharide. This study enhances our understanding of hyaluronidases from human gut microorganisms.

Experimental Study of Autologous Platelet-rich Plasma Combined With Sodium Hyaluronate on Tendon-bone Healing After Rotator Cuff Injury Repair in Rabbits.

OBJECTIVE: To investigate the therapeutic effects of autologous platelet-rich plasma (PRP) combined with sodium hyaluronate on tendon healing following rotator cuff injury repair in rabbits. METHODS: New Zealand white rabbits were randomly assigned to five groups: sham operation group, control group, PRP group, sodium hyaluronate group, and combined group, each comprising 12 rabbits. A rotator cuff injury model was established in all groups except the sham operation group. At 8 weeks post-surgery, 12 lateral rotator cuff specimens were taken from each group. Four specimens were randomly selected from each group for biomechanical testing, and analyses were conducted on the expression of vascular endothelial growth factor (VEGF), the fiber area ratio of COL-I and COL-III, and tissue morphology. RESULTS: The combined group exhibited the highest biomechanical strength in the cuff tissue of white rabbits (P < 0.05). There was no significant difference in VEGF levels among the five groups (F = 0.814, P = 0.523). However, a significant difference was observed in the ratio of fiber area between COL-I and COL-III groups (F = 11.600, P < 0.001), with the combined group scoring the highest (3.82 ± 0.47 minutes). The inflammatory infiltration in tendon-bone tissue was minimal, and histological morphology was optimal. CONCLUSION: The combination of PRP and sodium hyaluronate effectively promotes the repair of rotator cuff injuries and accelerates tendon-bone healing.

Efficacy of topical 0.05% cyclosporine A and 0.1% sodium hyaluronate in post-refractive surgery chronic dry eye patients with ocular pain.

BACKGROUND: The management of post-refractive surgery dry eye disease (DED) can be challenging in clinical practice, and patients usually show an incomplete response to traditional artificial tears, especially when it is complicated with ocular pain. Therefore, we aim to investigate the efficacy of combined topical 0.05% cyclosporine A and 0.1% sodium hyaluronate treatment in post-refractive surgery DED patients with ocular pain unresponsive to traditional artificial tears. METHODS: We enrolled 30 patients with post-refractive surgery DED with ocular pain who were unresponsive to traditional artificial tears. Topical 0.05% cyclosporine A and 0.1% sodium hyaluronate were used for 3 months. They were evaluated at baseline and 1 and 3 months for dry eye and ocular pain symptoms and objective parameters, including Numerical Rating Scale (NRS), Neuropathic Pain Symptom Inventory modified for the Eye (NPSI-Eye), tear break-up time (TBUT), Schirmer I test (SIt), corneal fluorescein staining (CFS), corneal sensitivity, and corneal nerve morphology. In addition, tear levels of inflammatory cytokines and neuropeptides were measured using the Luminex assay. RESULTS: After 3 months of treatment, patients showed a statistically significant improvement in the ocular surface disease index (OSDI), TBUT, SIt, CFS, and corneal sensitivity (all P < 0.01) using linear mixed models. As for ocular pain parameters, the NRS and NPSI-Eye scores were significantly reduced (both P < 0.05) and positively correlated with the OSDI and CFS scores. Additionally, tear IL-1ß, IL-6, and TNF-α levels were improved better than pre-treatment (P = 0.01, 0.03, 0.02, respectively). CONCLUSION: In patients with post-refractive surgery DED with ocular pain, combined topical 0.05% cyclosporine A and 0.1% sodium hyaluronate treatment improved tear film stability, dry eye discomfort, and ocular pain, effectively controlling ocular inflammation. TRIAL REGISTRATION: Registration number: NCT06043908.

Sodium hyaluronate and pranoprofen improve visual function and reduce inflammation in patients with dry eye.

OBJECTIVE: The aim of this study was to investigate the clinical use of sodium hyaluronate (SH) combined with pranoprofen in treating patients with dry eye. METHODS: A total of 117 patients with dry eye who were treated in the Traditional Chinese Medicine Hospital of Kunshan from March 2020 and May 2022 were included. According to the therapy approaches, they were treated with SH (SH group), pranoprofen (pranoprofen group), and SH combined with pranoprofen (joint group) (n = 39). RESULTS: The effective rates of dry eye were 79.49%, 74.36% and 94.87% in the SH group, the pranoprofen group and the joint group, respectively (p < 0.05). After treatment, the tear BUT and SIT in the joint group were all prominently increased than those in the other two groups (p < 0.05). The corneal fluorescein staining and dry eye symptom scores in the joint group after treatment were dramatically lower than those in the other two groups (p < 0.001). After treatment, the visual contrast sensitivity (12 c/d, 18 c/d and 24 c/d) in the joint group was markedly higher than those in the other two groups (p < 0.001). The CPR, TNF-α, IFN-γ and IL-1ß levels in the joint group were notably decreased than those in other two groups (p < 0.001). After treatment, the VRQOL quality-of-life scores in the joint group were significantly higher than those in the other two groups (p < 0.05). CONCLUSION: SH combined with pranoprofen showed clear therapeutic benefit in treating dry eye, and the curative effect was more favorable than with either medication alone.

Efficacy of an experimental toothpaste containing sodium bicarbonate, sodium hyaluronate and sodium fluoride on gingivitis.

BACKGROUND: Gingivitis is driven by plaque accumulation and, if left untreated, can progress to irreversible periodontitis. For many, the mechanical action of toothbrushing does not achieve adequate plaque control. The aim of this study was to investigate whether twice-daily use of a toothpaste containing 0.2% high molecular weight (HMW) sodium hyaluronate with 67% sodium bicarbonate and 0.221% sodium fluoride (experimental toothpaste) could improve gingival health compared with a regular fluoride toothpaste (negative control). The study also assessed whether the experimental toothpaste could provide additive gingival health benefit over a toothpaste containing only 67% sodium bicarbonate and 0.221% sodium fluoride (positive control). METHODS: This was a single-center, examiner-blinded, randomized, clinical study in healthy adults with mild-to-moderate gingivitis. At baseline, after abstaining from toothbrushing for 12 h, prospective participants underwent oral soft tissue (OST) and oral hard tissue examination followed by assessments for gingival inflammation (Modified Gingival Index [MGI]), gingival bleeding (Bleeding Index [BI]), and supra-gingival plaque (Turesky Plaque Index [TPI]). Eligible participants were stratified by gender and baseline number of bleeding sites (low: <45; high: ≥45 bleeding sites). Following randomization, participants underwent prophylactic dental treatment. Participants received a full OST examination, MGI, BI and TPI assessments after 3 days, 1, 2 and 6 weeks of product use. RESULTS: In total, 110 participants were screened for study entry and all were randomized to receive one of three toothpastes (experimental: sodium hyaluronate, sodium bicarbonate, sodium fluoride; positive control: sodium bicarbonate, sodium fluoride; negative control: regular fluoride toothpaste). For all measures, significant improvements were observed in participants receiving either sodium bicarbonate-containing toothpaste (experimental or positive control) compared with the regular fluoride toothpaste (negative control) at week 6. No significant difference was observed in any assessment or visit comparing the experimental toothpaste with the positive control. CONCLUSIONS: Both the experimental and the positive control toothpastes demonstrated clinically relevant improvements in gingival health compared with a regular fluoride toothpaste (negative control). However, no additional gingival health improvement was observed for the experimental toothpaste compared with the positive control, therefore, no additional gingival health benefit can be attributed to the inclusion of sodium hyaluronate in this formulation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04737538 (04/02/2021).

A randomized controlled clinical trial of concentrated growth factor combined with sodium hyaluronate in the treatment of temporomandibular joint osteoarthritis.

OBJECTIVE: To investigate the effect of concentrated growth factor (CGF) combined with sodium hyaluronate (SH) on temporomandibular joint osteoarthritis (TMJOA). METHODS: Sixty patients with TMJOA who were diagnosed by cone-beam computed tomography (CBCT) between March 2020 and March 2023 at the Stomatological Hospital of Xi'an Jiaotong University were randomly divided into a control group (n = 30) and an experimental group (n = 30). The patients in the experimental group were treated with CGF + SH, and those in the control group were treated with SH only. The visual analogue scale (VAS) score indicating pain in the temporomandibular joint (TMJ) area; the Helkimo Clinical Dysfunction Index (Di); and changes in condylar CBCT at the first visit and 2 weeks, 3 months and 6 months after treatment were recorded. The CBCT data of the patients in the experimental and control groups were collected, and the three-dimensional CBCT image sequences were imported into Mimics Medical 19.0 software in DICOM format for condylar reconstruction. RESULTS: The VAS scores at 2 weeks, 3 months and 6 months after treatment were significantly lower in the experimental group than in the control group (P < 0.05), and the pain in the experimental group was significantly relieved. The Di was significantly lower in the experimental group than in the control group (P < 0.05), and the clinical function of the TMJ improved. After treatment, the CBCT score was significantly lower in the experimental group than in the control group (P < 0.05), and the condylar bone cortex was obviously repaired. Observation of the condylar bone cortex by three-dimensional reconstruction showed the same results as those obtained by CBCT. CONCLUSION: CGF combined with SH is effective in the treatment of TMJOA and can improve muscle pain, TMJ pain, Impaired TMJ function, Impaired range of movement, Pain on movement of the mandible and promote bone repair. THE REGISTRATION NUMBER (TRN): ChiCTR2400082712. THE DATE OF REGISTRATION: April 5, 2024.

Meta-analysis of minimally invasive arthroscopy with sodium hyaluronate for wound healing of knee osteoarthritis treatment in the elderly.

Knee osteoarthritis (KOA) is not merely a medical condition-it is a prevalent and incapacitating ailment that significantly affects the quality of life for millions worldwide, especially as they age. The incidence of KOA increases year by year with increasing age. This study evaluated the therapeutic efficacy of combining arthroscopy with sodium hyaluronate (SH) in the treatment of wound healing of knee osteoarthritis (KOA) in elderly patients, with a focus on wound healing and overall joint function restoration. Randomized controlled trials (RCTs) evaluating the combination of arthroscopy and SH in geriatric KOA patients were identified through a systematic search of the scientific literature utilizing multiple databases and predefined search criteria. Ultimately, twelve investigations were included in the meta-analysis. Using Stata 15.1 software, data extraction and analysis were conducted using both fixed- and random-effects models, and a sensitivity analysis was conducted to assure the validity of the findings. Compared with arthroscopy alone, the combination of arthroscopy and SH significantly improved the efficiency rate, pain management (as measured by the Visual Analogue Scale), knee function (as measured by the Lysholm Knee Scoring Scale) and decreased levels of the pro-inflammatory cytokines IL-1 and IL-6. The meta-analysis revealed minimal heterogeneity between studies, and the sensitivity analysis validated the results' reliability. The incorporation of SH into arthroscopic procedures for elderly patients with KOA provides significant therapeutic benefits, including improved wound healing, reduced inflammation and enhanced joint function overall. These results support the use of this combined approach in the management of KOA in the elderly population and emphasize the need for additional research to optimize treatment protocols and comprehend long-term outcomes.

The effect of sodium hyaluronate on dry eye and corneal epithelial thickness following cataract surgery.

PURPOSE: To evaluate the effects of sodium hyaluronate drops on dry eye parameters and corneal epithelial thickness following cataract surgery. METHODS: The study included 84 patients who underwent uncomplicated phacoemulsification. In Group A, 0.15% sodium hyaluronate drops were added to the postoperative antibiotic/anti-inflammatory treatment. In Group B, only antibiotic/anti-inflammatory treatment was applied. Preoperatively and at 1 week and 1 month postoperatively, all the patients were evaluated in respect of tear break-up time (TBUT), the Schirmer test under anesthesia, the corneal fluorescein staining (CFS) score, mean central corneal thickness (CCT) and mean central corneal epithelial thickness (CCET), and the two groups were compared. RESULTS: A statistically significant difference was determined between the two groups at postoperative 1 month in respect of TBUT, Schirmer test, CFS score, and CCET (p < 0.01). In Group A, a statistically significant increase was determined in the TBUT and Schirmer values at 1 month postoperatively (p < 0.01, p = 0.01, respectively) and in Group B, these values were decreased compared to preoperatively (p < 0.01). The CCET was determined to be significantly thinner in Group B 1 month postoperatively (p < 0.01). A significant increase in CCT was observed in both groups at postoperative 1 week (p < 0.01) and preoperative values were reached at 1 month postoperatively. CONCLUSION: In the patient group using sodium hyaluronate, significant differences were determined in all dry eye parameters and CCET. The use of hyaluronate sodium drops after cataract surgery was seen to improve dry eye parameters and contribute to a healthy ocular surface by ensuring continuity of the corneal epithelium.

INTRA-ARTICULAR PHARMACOLOGICAL INJECTIONS FOR TEMPOROMANDIBULAR JOINT OSTEOARTHRITIS ARE COMPARABLE TO PLACEBO.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Effectiveness of intra-articular injections of sodium hyaluronate, corticosteroids, platelet-rich plasma on temporomandibular joint osteoarthritis: a systematic review and network meta-analysis of randomized controlled trials. Xie Y, Zhao K, Ye G, Yao X, Yu M, Ouyang H. J Evid Based Dent Pract. 2022 Sep;22(3):101720. doi:10.1016/j.jebdp.2022.101720. SOURCE OF FUNDING: National Natural Science Foundation of China (nos. T2121004, 81630065). TYPE OF STUDY/DESIGN: Systematic review with network meta-analysis of data.

Comparison of Polynucleotide, Sodium Hyaluronate, and Crosslinked Sodium Hyaluronate for the Management of Painful Knee Osteoarthritis: A Multi-Center, Randomized, Double-Blind, Parallel-Group Study.

OBJECTIVE: To compare the clinical effectiveness of sodium polynucleotide, classic hyaluronic acid, and crosslinked hyaluronic acid for the management of painful knee osteoarthritis. DESIGN: Randomized, double-blind, parallel-group clinical trial. SETTING: Multicenter study. SUBJECTS: Patients with chronic painful knee osteoarthritis. METHODS: Ninety patients were selected and randomized into polynucleotide, classic hyaluronic acid, and crosslinked hyaluronic acid groups (30 per group). Intra-articular injections of the viscosupplement for each group were administered to the patients three times at one-week intervals. The primary outcome was differences in changes of weight-bearing pain scores at 16 weeks between the groups. The secondary outcomes were changes in the intensity of knee pain during weight-bearing, walking, and rest, and functional disability, quality of life, and adverse events during the 16-week follow-up period. RESULTS: At 16 weeks, the polynucleotide group showed a higher reduction in pain score using a Visual Analog Scale score (0-100) than the classic hyaluronic acid (-17.6 [95% CI = -35.1 to -0.1]; P = .048) and crosslinked hyaluronic acid (-22.4 [95% CI = -41.5 to -3.3]; P = .016) groups. The polynucleotide and crosslinked hyaluronic acid groups showed an early-onset reduction in knee pain during weight-bearing, walking, and rest. All three groups showed reductions in functional disability and improved quality of life at 16 weeks without inter-group differences. No severe adverse events were reported throughout the study period. CONCLUSION: Polynucleotide significantly relieves pain more and relieves pain faster in patients with knee osteoarthritis than classic and crosslinked hyaluronic acid, with improved health-related quality of life.

A heterodimeric hyaluronate lyase secreted by the activated sludge bacterium Haliscomenobacter hydrossis.

Haliscomenobacter hydrossis is a filamentous bacterium common in activated sludge. The bacterium was found to utilize hyaluronic acid, and hyaluronate lyase activity was detected in its culture. However, no hyaluronate lyase gene was found in the genome, suggesting the bacterium secretes a novel hyaluronate lyase. The purified enzyme exhibited two bands on SDS-PAGE and a single peak on gel filtration chromatography, suggesting a heterodimeric composition. N-terminal amino acid sequence and mass spectrometric analyses suggested that the subunits are molybdopterin-binding and [2Fe-2S]-binding subunits of a xanthine oxidase family protein. The presence of the cofactors was confirmed using spectrometric analysis. Oxidase activity was not detected, revealing that the enzyme is not an oxidase but a hyaluronate lyase. Nuclear magnetic resonance analysis of the enzymatic digest revealed that the enzyme breaks hyaluronic acid to 3-(4-deoxy-ß-d-gluc-4-enuronosyl)-N-acetyl-d-glucosamine. As hyaluronate lyases (EC 4.2.2.1) are monomeric or trimeric, the enzyme is the first heterodimeric hyaluronate lyase.

The effect of sodium hyaluronate on tear film stability in patients with dry eye syndrome after cataract surgery.

BACKGROUND: This study aimed to observe the changes in the ocular surface after phacoemulsification in patients with age-related cataracts with respect to the addition of varying concentrations of hyaluronate. METHODS: Patients with dry eye syndrome were treated with 0.3% and 0.1% sodium hyaluronate eye drops to evaluate the clinical improvement in each treatment group. A total of 73 patients (91 eyes) with age-related cataracts suffering from dry eye syndrome after phacoemulsification were divided into treatment group A (30 eyes), undergoing conventional therapy and treatment with 0.3% sodium hyaluronate; treatment group B (31 eyes), undergoing conventional therapy and treatment with 0.1% sodium hyaluronate; and the control group (group C; 30 eyes), undergoing conventional therapy only. Two groups were given different concentrations of sodium hyaluronate eye drops four times a day (should be completed between 8 AM and 8 PM), one drop at a time. RESULTS: Seven days, 2 weeks, 1 month, and 2 months postoperatively, there were significant differences in the Schirmer I test (SIt), first noninvasive tear film break-up time (NIBUTf), average noninvasive tear film break-up time (NIBUTav), tear meniscus height (TMH), and irregularity (when the refractive force of different parts of different meridians on the same meridian is different. The main manifestation is that the two meridians on the anterior surface of the cornea do not show a 90-degree vertical distribution, which cannot be corrected by conventional astigmatism lenses) between the three groups (p < 0.05). When compared with group C, there were significant differences in the SIt, NIBUTf, NIBUTav, TMH, and irregularity of group A and group B (p < 0.05). When compared with group B, there were significant improvements in the SIt, NIBUTf, NIBUTav, and TMH in group A (p < 0.05). CONCLUSIONS: In the early stage after phacoemulsification, the stability of the tear film is reduced. Adding sodium hyaluronate eye drops can restore tear film structure and improve corneal surface regularity, and a 0.3% solution of sodium hyaluronate eye drops is more effective than a 0.1% solution.

Fundamental Aspects and Relevance of Components in Antihistamine Eye Drops.

Ocular allergy covers a series of immune-allergic inflammatory diseases of the ocular surface, with different degrees of involvement and severity. These pathologies are caused by a variety of IgE- and non-IgE-mediated immune mechanisms and may involve all parts of the external eye, including the conjunctiva, cornea, eyelids, tear film, and commensal flora. The most frequent is allergic conjunctivitis, a condition with different clinical forms that are classified according to the degree of involvement and the presence or absence of proliferative changes in the palpebral conjunctiva, associated atopic dermatitis, and mechanical stimuli by foreign bodies, including contact lenses. Treatment guidelines for allergic conjunctivitis propose a stepwise approach that includes medications for both ophthalmic and oral administration depending on symptom severity, allergic comorbidities, and degree of control. In the case of antihistamines, eye drops are the most prescribed ophthalmic formulations. To avoid disrupting the delicate balance of the ocular surface, topical ophthalmic medications must be well tolerated. The primary aim of this article is to review the physicochemical characteristics and other features of excipients (preservative agents, buffers, pH adjusters, viscosity enhancers, wetting agents or cosolvents, antioxidants, tonicity adjusters, and osmo-protectants) and active compounds (ocular antihistamines) that must be considered when developing formulations for ophthalmic administration of antihistamines. We also provide a brief overview of antihistamine eye drops that could be of interest to professionals treating ocular allergy and encourage the use of preservative-free formulations when possible.

The value of injectable viscoelastic supplements for joints.

Intra-articular viscoelastic supplements are commonly administered by musculoskeletal radiologists for the treatment of symptomatic osteoarthritis (OA). This article provides an overview of the putative mechanism of action of the agents, a brief review of the evidence base underlying the practice, a commentary on some of the major society guidelines regarding the treatment, and a description of the adverse events that are associated with intra-articular hyaluronic acid administration.

Types and doses of anti-adhesive agents injected into subacromial space do not have an effect on the clinical and anatomical outcomes after arthroscopic rotator cuff repair.

PURPOSE: Joint stiffness after arthroscopic rotator cuff repair is a major concern for orthopaedic surgeons. Various antiadhesive agents are commonly administered after rotator cuff repair for its prevention. This study aimed to compare the outcomes among patients injected with different types and amounts of anti-adhesive agents after rotator cuff repair. It was hypothesized that the outcomes might differ depending on the use of the anti-adhesive agent and its type and dose. METHODS: A total of 267 patients who underwent arthroscopic rotator cuff repair with or without subacromial injection of anti-adhesive agents were enrolled. The first group (group A; 51 patients) were injected with 3 mL of poloxamer/sodium alginate-based anti-adhesive agent. The second group (group B; 93 patients) were injected with 3 mL of sodium hyaluronate-based anti-adhesive agent. The third group (group C; 82 patients) were injected with 1.5 mL of sodium hyaluronate-based anti-adhesive agent. Finally, the last group (group D; 41 patients) who did not use anti-adhesive agents served as the control. The range of motion (ROM) and pain VAS scores were measured preoperatively and at 5 weeks, 3 months, 6 months, and 1 year postoperatively. Functional outcomes were evaluated using American Shoulder and Elbow Surgeons and Constant scores, whereas cuff integrity was assessed via MRI or ultrasonography at least 6 months postoperatively. RESULTS: All ROM measurements, pain VAS scores, and functional scores were significantly improved regardless of the use, type, and dose of the anti-adhesive agents. In addition shoulder ROM and rotator cuff healing did not significantly differ among the groups (all n.s.). CONCLUSIONS: No significant differences were found in the clinical and anatomical outcomes according to the type and dose of the anti-adhesive agents subacromially injected after rotator cuff repair. LEVEL OF EVIDENCE: III.

Hyaluronic acid injections for pain relief and functional improvement in patients with temporomandibular disorders: An umbrella review of systematic reviews.

BACKGROUND: Temporomandibular disorders (TMD) are the main cause of chronic facial pain, and intra-articular (IA) injections of hyaluronic acid (HA) are commonly performed. OBJECTIVES: This umbrella review of systematic reviews aimed at analysing the effectiveness of HA injections on pain and functional outcomes in patients affected by TMD. METHODS: PubMed, Cochrane Library and PEDro were systematically searched from inception until 17 January 2023 to identify systematic reviews evaluating the effects on pain and functional outcomes of HA IA injections. PROSPERO registration number: CRD42022382586. RESULTS: Out of 316 papers suitable for title/abstract screening, 18 articles were included in the umbrella review. Thirteen studies included only randomized controlled clinical trials (RCTs). The included systematic reviews reported no statistically significant differences between HA and corticosteroids, whereas platelet derivates seem to have good results in pain relief. The literature did not show severe adverse events, except for mild pain in the site of injection. Concerning the quality assessment of the 18 systematic reviews, 2 (11.11%) had a high quality, 3 (16.67%) a moderate quality, 7 (38.89%) a low quality and 6 (33.33%) a critically low quality. CONCLUSIONS: Taken together, findings of this umbrella review showed intriguing effects of IA HA injections in terms of reduction of pain intensity and improvement of functioning in patients affected by TMD. Furthermore, there is no agreement on the effectiveness of a combination of arthrocentesis or arthroscopy with IA HA injections. Although the literature showed these positive results after IA HA injections, the overlapping of primary studies in the systematic reviews included might have affect our results, such as the very low quality of the papers. Thus, further RCTs are needed to confirm the efficacy of IA injections of HA on pain relief in patients with TMD.

Influence of HA on Release Process of Anionic and Cationic API Incorporated into Hydrophilic Gel.

The properties of sodium hyaluronate (HA), such as hygroscopicity, flexibility, the ability to form hydrogels, as well as biocompatibility and biodegradability, are beneficial for the applications in pharmaceutical technology, cosmetics industry, and aesthetic medicine. The aim of this study was to prepare HA-based hydrogels doped with active pharmaceutical ingredient (API): a cationic drug-lidocaine hydrochloride or anionic drug-sodium. The interaction between the carrier and the implemented active pharmaceutical substances was evaluated in prepared systems by applying viscometric measurements, performing release tests of the drug from the obtained formulations, and carrying out FTIR and DSC. The data from release studies were analyzed using the zero-, first-, and second-order kinetics and Higuchi, Korsmeyer-Peppas, and Hixon-Crowell models. The respective kinetic parameters: the release rate constants, the half-release time and, in the case of the Korsmeyer-Peppas equation, the n parameter were calculated. The variability between the obtained release profiles was studied by calculating the difference (f1) and the similarity factor (f2) as well as employing statistical methods. It was revealed that the incorporation of the drugs resulted in an increase in the viscosity of the hydrogels in comparison to the respective drug-free preparations. The dissolution study showed that not entire amount of the added drug was released from the formulation, suggesting an interaction between the carrier and the drug. The FTIR and DSC studies confirmed the bond formation between HA and both medicinal substances.

Interactions between Sodium Hyaluronate and ß-Cyclodextrin as Seen by Transport Properties.

Knowledge of mass transport parameters, diffusion, and viscosity of hyaluronic acid (HA) in the presence of cyclodextrins is of considerable importance for areas such as food packaging and drug delivery, among others. Despite a number of studies investigating the functionalization of HA or the corresponding sodium salt by cyclodextrins, only a few studies have reported the effect of cyclodextrins on the mass transport of HA in the presence of these oligosaccharides. Here, we report the tracer binary and ternary interdiffusion coefficients of sodium hyaluronate (NaHy) in water and aqueous ß-cyclodextrin solutions. The diffusion behavior of sodium hyaluronate was dependent on the reduced viscosity of NaHy, which, in turn, presented a concave dependence on concentration, with a minimum at approximately 2.5 g dm-3. The significant decrease in the limiting diffusion coefficient of NaHy (at most 45%) at NaHy concentrations below 1 g dm-3 in the presence of ß-cyclodextrin, taking water as the reference, allowed us to conclude that NaHy strongly interacted with the cyclodextrin.

Sodium hyaluronate dry powder inhalation in combination with sodium cromoglycate prepared using optimized spray drying conditions.

Sodium hyaluronate (SHA) is an anti-inflammatory and protective agent against bronchoconstriction, and sodium cromoglicate (SCG) prevents exercise-induced bronchoconstriction and inflammation. Based on the pharmacological properties of both substances, this study aimed to develop a dry powder inhaler (DPI) of SHA alone and in combination with SCG. The target of the study was to develop flowable formulations without any surfactants by using the spray drying method. To obtain respirable SHA and SCG:SHA particles, variables of the spray dryer, such as inlet temperature, atomized air flow, and feed solution, were changed. The particles 1-8 µm in size were produced with high yield by spray drying and increasing the ethanol percentage of the feed solution (60%), which is the most remarkable parameter. After that, physicochemical characterizations were performed. The aerosol performance of DPI formulations prepared using lactose was evaluated using Handihaler® DPI. The fine particle fraction (FPF) was 36% for the SHA formulation, whereas it was 52 and 53% for SCG and SHA, respectively, in the SCG:SHA formulation. Consequently, both particles were produced reproducibly by spray drying, and inhaled SHA and SCG:SHA dry powder formulations were developed due to their high FPF and flowability with lactose.