Hyaluronate Group Research Articles

Arthroscopic debridement combined with platelet-rich plasma injection for the treatment of Kellgren-Lawrence gradeⅠ-Ⅲ knee osteoarthritis

To explore clinical effect of arthroscopic debridement combined with platelet-rich plasma (PRP) injection for Kellgren-Lawrence(K-L) gradeⅠ-Ⅲ knee osteoarthritis (KOA) . Totally 117 patients with KOA who underwent arthroscopic debridement combined with injection from November 2015 to January 2019 were retrospectively analyzed. According to different injection drugs, the patients were divided into sodium hyaluronate group(group A) and PRP group(group B). In group A, there were 60 patients, including 27 males and 33 females, aged from 49 to 67 years old with an average age of (54.1±4.8) years old;12 patients with gradeⅠ, 23 patients with gradeⅡand 25 patients with grade Ⅲ according to K-L clssification, 2 ml(20 g) sodium hyaluronate was injected into knee joint after intraoperative, 1, 2, 3 weeks after operation for 4 times. In group B, there were 57 patients, including 25 males and 32 females, aged from 47 to 70 years old with an average of (55.8±5.0) years old, 10 patients with gradeⅠ, 20 patients with gradeⅡand 27 patients with grade Ⅲ according to K-L classification, injected 5 ml PRP at the same time. Postoperative complications was recorded between two groups. Postoperative visual analogue scale(VAS) and Lysholm score at 3, 6, 12 months were used to evaluate improvement of knee pain and joint function. All patients were followed up for 12 to 19 months with an average of (14.1±1.6) months. There was no significant difference in postopertaive complications between group A and group B (P>0.05). Postoperative VAS score in group A at 3, 6, 12 months were 3.0±0.8, 2.0±0.8, 2.6±0.9 respectively, and 2.9±0.8, 1.9±0.7, 2.2±0.8 in group B respectively; and no differnece at 3 and 6 months after operation between two groups (P<0.05), while VAS score in group B was higher than group A at 12 months after operation(P<0.05). Postoperative Lysholm score in group A at 1, 6, 12 months (86.6±1.8, 93.1±2.0, 86.7±1.7) were lower than group B(88.9±1.9, 95.0±2.0, 89.0±1.9)(P<0.05). Arthroscopic debridement combined with sodium hyaluronate or PRP injection for K-L gradeⅠ-Ⅲ KOA could effectively relieve pain and improve joint function with higher safety in short term, but the medium-long-term effect of PRP injection is stable.

Impact of Diquafosol Ophthalmic Solution on Tear Film and Dry Eye Symptom in Type 2 Diabetic Dry Eye: A Pilot Study

Purpose: Diquafosol ophthalmic solution (DQS) stimulates P2Y2 receptors on the ocular surface, which enhances mucin secretion from goblet cells. Therefore, tear film stability and hydration of the ocular surface can be achieved independent from lacrimal gland function. Methods: This prospective, open-label pilot study included 60 eyes of 30 diabetic patients diagnosed with dry eye disease (DED) and were randomly assigned to either DQS (n = 30 eyes) or hyaluronate (HA) group (n = 30 eyes). Participants in the DQS group received 3% diquafosol ophthalmic solution, whereas HA group received 0.1% sodium HA preservative-free artificial tears. The dosage for both drugs was 1 drop, 6 times per day for 4 weeks. Tear film lipid layer (TFLL), noninvasive breakup time (NITBUT), corneoconjunctival staining (CS) score, meibomian gland (MG), conjunctival hyperemia [redness score (RS)], ocular surface disease index (OSDI) was assessed and compared at baseline, day 14, and day 28. Results: Comparing baseline and day 28 measurements revealed that both groups found significant improvements in NITBUT, CS, MG quality, MG expressibility, and OSDI scores significantly (P < 0.05), in addition TFLL improvements were only found in the DQS group. At day 28, the magnitude of change in mean NITBUT was 1.74 (DQS) versus 0.31 (HA), 1.16 (DQS) versus 0.37 (HA) point grade reduction in corneoconjunctival staining score and 9.80 (DQS) versus 4.80 (HA) point grade in mean OSDI score. Conclusion: Three percent diquafosol ophthalmic solution treatment demonstrated the ability to improve the tear film dry eye parameters and clinically reduced sign and symptoms of DED in diabetic dry eye patients. Clinical Trials.gov ID: NCT04980144.

The Inhibitory Effects of Naringin in a Rat Model of Postoperative Intraperitoneal Adhesion Formation.

Background Many attempts have been made to inhibit the formation of postoperative intraperitoneal adhesions, but the results have been discouraging. Therefore, the identification of effective preventative measures or treatments is of great importance. In this study, the substantial potential of naringin (NG) to reduce peritoneal adhesions was validated in a rat model. Materials and Methods A rat peritoneal adhesion model was established by abrasion of the cecum and its opposite intraperitoneal region under aseptic surgical conditions. After the operation, three groups of NG-treated rats were given 2 mL of NG by gavage at different concentrations (40, 60, or 80 mg/kg/d). The sham, control, and hyaluronan (HA) groups were given equal volumes of normal saline daily. On the 8th day, all rats were sacrificed 30 min after the administration of an activated carbon solution (10 mL/kg) by oral gavage. Intraperitoneal adhesion formation was adequately evaluated by necropsy, hematoxylin and eosin (HE) staining, Sirius red staining, immunofluorescence staining, enzyme-linked immunosorbent assays, and reactive oxygen species (ROS) probes. The gastrointestinal dynamics of the rats were assessed on the basis of a small intestinal charcoal powder propulsion test and the detection of motilin and gastrin levels in serum. Results Intraperitoneal adhesions were markedly reduced in the group of rats receiving high-dose NG. Compared with the control group, the high-dose NG group showed clear reductions in inflammatory reactions, oxidative stress, collagen deposition, and fibroblast formation in the adhesion tissue and enhanced gastrointestinal dynamics (P < 0.05). Conclusion NG alleviated the severity of intraperitoneal adhesions in a rat model by reducing inflammation, oxidative stress, collagen deposition, and fibroblast formation, highlighting the potential of NG as a drug candidate to prevent postoperative peritoneal adhesion formation.

An animal study on the effect of topically administered ambroxol for dry eye.

To evaluate the effect of 0.2% ambroxol eye drop on tear secretion and corneal healing on a rabbit dry eye model, and to delineate potential underlying mechanisms. A mixed mechanism dry eye model was created using 12 healthy New Zealand rabbits by excision of the main lacrimal glands, Harderian gland and nictitating membrane. Establishment of the model was confirmed by the decrease of Schirmer I and increase of corneal fluorescein staining scores. Two weeks after model creation, the rabbits were randomly and evenly divided into NaCl, 0.1% sodium hyaluronate and 0.2% ambroxol groups. Each group was administered the respective eye drops 4 times a day for four weeks. The Schirmer I test and corneal fluorescein staining were performed at two and four weeks. After four weeks of treatment, the animals were sacrificed and the conjunctiva and eyelid specimens collected. Inflammatory factors IL-8, TNF-α, and goblet cell specific mucin MUC5AC were measured by ELISA while the lid meibomian gland was evaluated by oil red O staining. Compared with the baseline, 2 weeks after the surgery, Schirmer I test value decreased significantly (20.35 ± 5.18 mm/5 min vs 13.95 ± 4.64 mm/5 min, p < 0.01), and the fluorescein staining score increased significantly (0.5 ± 0.6 vs 5.5 ± 1.4, p < 0.01). After four weeks of treatment, compared with the NaCl and sodium hyaluronate groups, tear secretion in ambroxol group increased significantly (p < 0.01), while the corneal fluorescence staining score decreased significantly (p < 0.01). In the conjunctival tissue, significant decrease was seen in TNF-α (p < 0.01) and IL-8 [p (unilateral) < 0.05] concentrations in ambroxol group, and significant increase in MUC5AC concentration (p < 0.01) in ambroxol group as well. The lipid content in the lid meibomian glands appeared increased after the administration of ambroxol. The present rabbit dry eye model study demonstrated potentials of topically administered 0.2% ambroxol in stimulating tear and mucin secretion, inhibiting ocular surface inflammation, promoting corneal healing, and possibly augmenting meibomian gland lipid production.

The effect of 3-D printed polylactic acid scaffold with and without hyaluronic acid on bone regeneration.

Three- dimensional (3D) technology has been suggested to overcome several limitations in guided bone regeneration (GBR) procedures because 3D-printed scaffolds can be easily molded to patient-specific bone defect site. This study aimed to investigate the effect of 3-D printed polylactic acid (PLA) scaffolds with or without hyaluronic acid (HA) in a rabbit calvaria model. A calvaria defect with a diameter of 15mm was created in 30 New Zealand white rabbits. The rabbits were randomly allocated into three groups including no graft group (control, n=10), 3D printed PLA graft group (3D-PLA, n=10), and 3D printed PLA with hyaluronic acid graft group (3D-PLA/HA, n=10). Five animals in each group were sacrificed at 4 and 12weeks after surgery. Microcomputed tomography and histologic and histomorphometric analyses were performed. Over the whole examination period, no significant adverse reactions were observed. There were no statistically significant differences in bone volume (BV) /tissue volume (TV) among the three groups at 4weeks. However, the highest BV/TV was observed in the 3D-PLA/HA group at 12weeks. The new bone area for control, 3D-PLA, and 3D-PLA/HA showed no statistical differences at 4weeks. However, the value was significantly higher in the 3D-PLA and 3D-PLA/HA groups compared to the control group at 12weeks. The 3D printed PLA scaffolds was biocompatible and integrated well with bone defect margin. They were also provided the proper space for new bone formation. Therefore, 3D printed PLA/HA might be a potential tool to enhance bone augmentation.

Effect of holistic stratification acupotomy on lower limb function, MMP1 and MMP13 in bursal fluid of patients with knee osteoarthritis整体分层针刀疗法对KOA患者下肢功能及滑囊液

ObjectiveTo observe the differences in clinical effect on knee osteoarthritis (KOA) between the holistic stratification acupotomy and the joint injection with sodium hyaluronate so as to provide a safe and effective treatment for KOA. MethodsA total of 100 KOA patients were randomly divided into an acupotomy group and a sodium hyaluronate group, 50 patients in each one. In the acupotomy group, the holistic stratification acupotomy was adopted. In the sodium hyaluronate group, sodium hyaluronate injection was applied in the joints. The index of Western Ontario and McMaster University (WOMAC) and the expressions of MMP1 and MMP13 in bursal fluid of the patients were compared before and after treatment in the patients between two groups before and after treatment, and the clinical therapeutic effect was observed. ResultsAfter treatment, WOMAC score of each dimension and the concentrations of MMP1 and MMP13 in bursal fluid of the patients of either group were all lower than those before treatment (all P < 0.05). After treatment, WOMAC score of each dimension and the concentrations of MMP1 and MMP13 in bursal fluid in the acupotomy group were lower than the sodium hyaluronate group (all P < 0.05). The total effective rate in the acupotomy group was higher than that of the sodium hyaluronate group (P < 0.05). ConclusionBoth the holistic stratification acupotomy and the joint injection with sodium hyaluronate are effective on KOA in this trial. However, the therapeutic effect of holistic stratification acupotomy is remarkable, which is probably related to the improvements in inflammatory response.

Subacromial Injections of Low- or High-Molecular-Weight Hyaluronate Versus Physical Therapy for Shoulder Tendinopathy: A Randomized Triple-Blind Controlled Trial.

Shoulder tendinopathy is a prevalent and debilitating problem. We compared the effects of subacromial high- or low-molecular-weight hyaluronate injection with physical therapy (PT) in shoulder tendinopathy. A triple-blinded randomized controlled trial. We conducted the trial in an outpatient clinic at a teaching hospital. In total, 79 patients with shoulder tendinopathy were randomly allocated to high- (n = 27) or low-molecular-weight (n = 28) hyaluronate or PT (n = 24) groups. We administered a 20-mg injection of high- or low-molecular-weight hyaluronate. For PT, we prescribed 10 sessions of physiotherapy and exercise. The primary outcome was shoulder pain and the secondary outcomes included Disability of the Arm Shoulder and Hand score, shoulder range of movement and QoL. We measured the outcomes at baseline, 1, and 3 months of treatment, and assessed shoulder pain at the sixth month postintervention. The interventions were all clinically beneficial in the management of tendinopathy for high- (n = 25) and low-molecular-weight (n = 24) hyaluronate and PT (n = 19) groups (all P < 0.05). However, between-group analyses indicated that hyaluronate preparations were more effective in controlling pain, decreasing disability, increasing range of motion, and improving the quality of life (all P < 0.05). The pain and subjective feeling of rigidity at the injection area ( P = 0.012) were less prominent for low-molecular-weight hyaluronate. High- or low-molecular-weight hyaluronate is more effective than PT in the treatment of shoulder tendinopathy. The clinical benefits of hyaluronate last for at least 3 months, and the pain alleviation sustains partially for 6 months. Shoulder injection of low-molecular-weight hyaluronate is more tolerable to the patient than high-molecular-weight hyaluronate.

Liquid combination of hyaluronan, glucosamine, and chondroitin as a dietary supplement for knee osteoarthritis patients with moderate knee pain: A randomized controlled study.

Background:Hyaluronan (HA), glucosamine, and chondroitin sulfate are widely consumed as dietary supplements for the treatment of knee osteoarthritis (OA). This study aimed to explore the efficacy and safety of a dietary liquid supplement mixture containing HA, glucosamine, and chondroitin in patients with knee OA who had moderate knee pain (visual analogue scale of 4–6 points).Methods:This was a short-term, randomized, double-blind, placebo-controlled study. Subjects were allocated to administer either a bottle of 20 mL supplement mixture (50 mg HA plus 750 mg glucosamine plus 250 mg chondroitin, namely A + HA) or placebo once daily for 8 weeks. Outcome measures included the Knee Injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Osteoarthritis Index, 36-item Short Form Survey (SF-36), Chinese version of Pittsburgh Sleep Quality Index, and incidence of adverse event were evaluated at the end of week 8. Efficacy analyses were conducted in the modified intent-to-treat population.Results:Of the 80 subjects in the modified intent-to-treat population, 39 received A + HA while 41 received placebo. After 8 weeks of treatment, the A + HA group failed to demonstrate a significant symptomatic efficacy and quality of life improvement in terms of Knee Injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Osteoarthritis Index, SF-36, and Chinese version of Pittsburgh Sleep Quality Index as compared to the placebo group. However, the mean changes in most of the SF-36 scale scores were numerically higher in the A + HA group than in the placebo group. No treatment-related adverse event was reported in both groups.Conclusions:This present study found that the combination of liquid low molecular weight HA, glucosamine, and chondroitin oral supplement did not effectively improve knee OA pain and symptoms after short-term use in knee OA patients with moderate knee pain. However, these results should be interpreted with caution due to the intrinsic limitation of the study design.

A Double-Blinded Positive Control Study Comparing the Relative Efficacy of 2.5% Polyacrylamide Hydrogel (PAAG) Against Triamcinolone Acetonide (TA) And Sodium Hyaluronate (HA) in the Management of Middle Carpal Joint Lameness in Racing Thoroughbreds

The purpose of this prospective double-blinded positive control study was to compare the efficacy of 2.5% polyacrylamide hydrogel (2.5% PAAG) in the management of middle carpal joint lameness in Thoroughbreds against treatments of triamcinolone acetonide (TA) or sodium hyaluronate (HA). A total of 31 flat-racing Thoroughbreds with lameness (grade 1-3/5) localized to the carpus by intra-articular analgesia were selected. Following a radiological assessment of the carpi confirming the absence of fragment/fracture, the horses were randomly assigned for intra-articular treatment with either 2 ml of 2.5% PAAG, 12 mg TA or 20 mg HA (followed by two further intravenous treatments of 40 mg, at weekly intervals in the HA group only), by a treating veterinarian. All horses were rested for 48 hours post-treatment and then re-entered an unaltered training regimen. Subsequent examinations at 2, 4, and 6 weeks were performed by a blinded examining veterinarian for all groups, while horses treated with 2.5% PAAG were monitored for 12 weeks for recurrence of lameness. Significantly more joints treated with 2.5% PAAG were lame free (83%) at 6 weeks compared to TA (27%; P = .007) and to HA (40%; P = .04). There was no significant difference between TA and HA groups at any time. All the joints treated within 2.5% PAAG that were lame free at 6 weeks (10/12) were still lame-free at 12 weeks. In conclusion, treatment with 2.5% PAAG led to statistically superior results compared to TA and HA in the management of selected middle carpal joint lameness in flat-racing Thoroughbreds, with therapeutic effects persisting up to 12 weeks.

Microcomputed tomographic analysis of bone microarchitecture after sinus augmentation with hyaluronic matrix: a case-control study.

The aim of this study was to analyze trabecular microarchitecture of augmented sinuses with hyaluronic matrix and xenograft by microcomputed tomography, and to investigate whether hyaluronic matrix has an effect on the newly formed bone quality. Thirteen patients undergoing maxillary sinus augmentation were included in this split-mouth study. Right and left sinus sites were randomly assigned to test and control group. In test group, the sinus was grafted with hyaluronic matrix and xenograft; in control group, only with xenograft. Four months after augmentation, bone samples were harvested during implant placement and analyzed for the following trabecular microarchitecture parameters using microcomputed tomography: bone volume (BV), total volume (TV), bone volume fraction (BV/TV), bone surface (BS), specific bone surface (BS/BV), bone surface density (BS/TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), trabecular pattern factor (Tb.Pf), and fractal dimension (FD). There was statistically significant difference only for BS/TV parameter between two groups. BS/TV was higher in hyaluronic matrix group compared with control group. Addition of hyaluronic matrix to xenograft may enhance bone quality in terms of bone surface density. However, more research investigating the microstructural variation of augmented sinuses is needed with a greater sample.

Evaluation of Intra-articular Injection of Simvastatin versus Hyaluronic Acid in Treatment of Internal Derangement of Temporomandibular Joint

ABSTRACTIntroduction: TMJ Internal Derangement is a common form of temporomandibularjoint disorder. Almost 80% of adult symptomatic patients with TMD have some form ofID. Temporomandibular joint arthrocentesis consists of lavage of upper joint space ofTMJ done with no direct vision, aiming primarily to remove necrotic tissue, bloodand pain mediators from the joint. One of these therapeutic substances is hyaluronicacid; which is a polysaccharide of the family of glycosaminoglycans, which can befound in many extracellular tissues, including synovial fluid and cartilage. Simvastatinsare group of drugs which have good results in regeneration of degenerated TMJ.Aim: This study aimed to evaluate the intra-articular injection of simvastatin versussodium hyaluronate following arthrocentesis for management of internal derangement(ID) of the temporomandibular joint(TMJ). Patients and methods: Thirty patients withinternal TMJ derangement were included in this study. All patients were subjected topreoperative clinical examination and preoperative magnetic resonance imaging (MRI)for the affected joints. Arthrocentesis was performed firstly for the affected joints inall patients followed by intra-articular injection of 1ml. simvastatin twice a month (ingroup I) and sodium hyaluronate twice a month ( in group II).Clinical follow up weredone at 24 hours post-operatively, one week, one month,and six months. Then, after sixmonths MRI was repeated to compare with preoperative images. Results: Better resultswere recorded with simvastatin group in comparison to sodium hyaluronate group; at 1week, 1 month,and six months intervals; which was superior to arthrocentesis followedby sodium hyaluronate intra-articular injection. Patients in group I showed better MRIfindings in comparison to group II where the position of the disc was almost returnedto its normal anatomical position. Conclusion: Arthrocentesis followed by simvastatinintra-articular injection was superior to the combination of arthrocentesis and sodiumhyaluronate intra-articular injection for management of TMJ internal derangementssymptoms.

Oral Hyaluronan Relieves Wrinkles and Improves Dry Skin: A 12-Week Double-Blinded, Placebo-Controlled Study.

Hyaluronan (HA) is present in all connective tissues and organs, including the skin and joint fluid. However, few clinical trials have comprehensively evaluated the impacts of oral HA on skin conditions, including wrinkles and moisturization. In this study, we conducted a placebo-controlled, randomized, double-blind trial of daily HA (120 mg) intake for 12 weeks in 40 healthy Asian men and women (aged 35–64 years). Skin condition was determined by the evaluation of wrinkles, stratum corneum water content, the amount of transepidermal water loss, elasticity, and through image analysis. After 12 weeks, skin condition was significantly improved in terms of wrinkle assessment, stratum corneum water content, transepidermal water loss, and elasticity in the HA group compared to the placebo group. Regarding the percentage change from baseline, wrinkle assessment, stratum corneum water content, and skin elasticity were significantly improved in the HA group versus the placebo group after 8 and 12 weeks of ingestion. The present findings indicate that oral ingestion of HA may suppress wrinkles and improve skin condition.

A Single-Blinded Randomized Controlled Trial of Mesenchymal Stem Cell Therapy for the Treatment of Osteoarthritis of the Knee with Active Control.

Background: Osteoarthritis is most prevalent in the knee and drives the growing incidence of total knee arthroplasty. There is a need to explore non-surgical treatment options to increase the portfolio of alternatives available. The study aimed to determine the clinical response to an autologous bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP) intra-articular injection compared to an active comparator. Methods: The study was a prospective, single-blinded, randomized controlled pilot study. Participants with diagnosed knee osteoarthritis were allocated to one of two treatment groups to receive a BMAC injection immediately followed by a PRP injection or a single injection of Gel-One® crosslinked hyaluronate (HA). Outcomes were assessed at 3, 6, and 12 months post-treatment. Results: Significant improvements were observed in both treatment groups for all Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales with the exception of the symptoms assessment at 12 months in the HA group. BMAC KOOS scores peaked at 12 months, while HA KOOS scores generally peaked at 6 months. The gap in mean scores at 12 months in favor of the BMAC group did not reach statistical significance. Secondary outcomes included a greater reduction in pain at 12 months in the BMAC group (-3.13 points; 95% CI: -3.96, -3.29) compared to the HA group (-1.56 points; 95% CI: -2.59, -0.53; p= 0.02) via the numeric pain rating scale. Conclusions: Results demonstrate that both treatment groups experienced clinically and statistically significant improvement across the KOOS subscales. While BMAC has shown promise in the treatment of knee OA, there is a need for multi-center investigations with larger sample sizes, an extended follow-up, and placebo-based control. ClinicalTrials.gov Identifier: NCT02958267.

A randomised, prospective study of the effects of 3% diquafosol on ocular surface following cataract surgery

There is still no established therapeutic solution for postoperative Dry Eye Syndrome (DES) after cataract surgery, in spite of progress in surgical techniques. Diquafosol tetrasodium (DQS), a recently developed ophthalmic solution, has been reported to be effective in DES, but no study evaluated post-cataract surgery lipid layer thickness (LLT) changes in healthy patients who used DQS postoperatively. We randomly divided participants into two groups; the DQS group was treated six times daily with DQS after cataract surgery, and the sodium hyaluronate (HA) group was treated with HA in the same way. Throughout study period, the DQS group showed significantly higher tear break up time (TBUT) and LLT than HA group. In multivariate analysis, better preoperative TBUT, Schirmer’s I test score, ocular surface disease index (OSDI) score, and LLT were significantly associated with improved postoperative outcomes in each parameter. Also, the postoperative use of DQS served as an independent parameter of better TBUT, OSDI score, and LLT in postoperative 15 weeks. Treatment with 3% DQS following cataract surgery showed more improvement in TBUT and LLT, compared with 0.1% HA. Improving TBUT and LLT preoperatively and using 3% DQS postoperatively, could be a reliable choice for managing DES after cataract surgery.Trial Registration: ISRCTN registry with ISRCTN 18755487.

Effect of ligustrazine nanoparticles on Th1/Th2 balance by TLR4/MyD88/NF-\u03baB pathway in rats with postoperative peritoneal adhesion

BackgroundPostoperative peritoneal adhesion (PPA) is regarded as fibrous bands connecting both injured abdominal wall and organs or adjacent tissues. It is associated with T helper (Th)1 and Th2 differentiation. However, the critical role of the immunopathogenesis of adhesion formation was precisely unknown. The aim of this study was to investigate the effect of a new agent polylactic acid (PLA) nanoparticles loaded with ligustrazine, that is, ligustrazine nanoparticles (LN) on PPA and identify the potential mechanism.MethodsTwenty-four Sprague–Dawley rats were randomly divided into the sham, model, LN, and sodium hyaluronate (SH) groups. The structure of LN, including entrapment efficiency (EE) and loading capacity (LC), and in vitro drug release were calculated. Adhesions were scored and the Masson's trichrome staining was used to determine the collagen deposition. The expressions of TLR4, MyD88, and NF-κB were measured by qRT-PCR, immunohistochemistry, and western blot assay. Moreover, Th1-related cytokines (IFN-γ, IL-12), Th2-related cytokines (IL-4, IL-6) in the cecum tissue and serum were conducted by ELISA.ResultsLN had good EE, LC, and control-release delivery characters with fairly uniform diameter and spherical morphology. It could effectively prevent adhesion formation after surgery. Besides, it could reduce collagen fibers accumulation, downregulate the expression levels of TLR4, MyD88, and NF-κB, and maintain Th1/Th2 balance.ConclusionsLigustrazine nanoparticles had effective effects on Th1/Th2 balance by regulating TLR4/MyD88/NF-κB pathway in PPA rats. It may be served as a promising therapy on postoperative adhesion formation.

A 28-day clinical trial of aerosolized hyaluronan in alpha-1 antiprotease deficiency COPD using desmosine as a surrogate marker for drug efficacy

IntroductionA previous 2-week clinical trial of aerosolized hyaluronan (HA) in COPD showed a rapid reduction in lung elastic fiber breakdown, as measured by sputum levels of the unique elastin crosslinks, desmosine and isodesmosine (DID). To further assess the therapeutic efficacy of HA and the utility of DID as surrogate markers for the development of pulmonary emphysema, we have conducted a 28-day randomized, double-blind, placebo-controlled, phase 2 trial of HA involving 27 subjects with alpha-1 antiprotease deficiency COPD. MethodsThe study drug consisted of a 3 ml inhalation solution containing 0.03% HA with an average molecular weight of 150 kDa that was self-administered twice daily. DID levels were measured in urine, sputum, and plasma using tandem mass spectrometry. ResultsFree urine DID in the HA group showed a significant negative correlation with time between days 14 and 35 (r = -1.0, p = 0.023) and was statistically significantly decreased from baseline at day 35 (15.4 vs 14.2 ng/mg creatinine, p = 0.035). A marked decrease in sputum DID was also seen in the HA group between days 1 and 28 (0.96 vs 0.18 ng/mg protein), but the difference was not significant, possibly due to the small number of adequate specimens. Plasma DID remained unchanged following HA treatment and no significant reductions in urine, sputum, or plasma DID were seen in the placebo group. ConclusionsThe results support additional clinical trials to further evaluate the therapeutic effect of HA and the use of DID as a real-time marker of drug efficacy.

Low Molecular-weight Hyaluronic Acid Versus Physiotherapy for the Treatment of Supraspinatus Tendinopathy: A Randomized Comparative Clinical Trial.

The tendons of the rotator cuff are major sources of shoulder pain. This study aimed to compare the effects of low molecular-weight hyaluronic acid with physiotherapy (PT) in patients with supraspinatus tendinopathy (ST). We carried out a parallel two-group randomized comparative clinical trial in an outpatient clinic of physical medicine and rehabilitation at a teaching hospital. In total, 51 patients (31 women) aged 20 to 55 years with ST were randomly allocated to subacromial hyaluronate injection (n = 28) and PT (n = 23) groups. For the hyaluronate group, we administered a single injection of 2 mL (20 mg) hyaluronate 1% (500 to 700 kDa). For PT, we prescribed three sessions of treatment per week for 12 weeks, totaling 36 sessions including rotator cuff activation exercises. The primary outcome was shoulder pain in the visual analog scale. The secondary outcomes included the range of movement and the disability score of the shoulder, and a World Health Organization questionnaire on quality of life. We did the measurements at the baseline and at one, four, and 12 weeks after intervention. The results showed that both interventions were beneficial in the management of ST. However, hyaluronate was more effective in reducing shoulder pain at rest and during activities (both P < 0.001, effect size = 0.52 and 0.68, respectively). The two interventions similarly decreased patients' disability (P = 0.196). Hyaluronate improved shoulder motion and the quality of life better than PT. In the treatment of ST, low molecular-weight hyaluronate is more effective than PT, at least for three months. Particularly, hyaluronate is more successful in alleviating pain.

Effect of Postoperative Administration of Hyaluronic Acid/Trehalose Drop on Corneal Healing After Phacoemulsification Surgery

This study aimed to evaluate the efficacy of hyaluronic acid/trehalose drop for corneal epithelial and stromal healing after phacoemulsification surgery at Maltepe University, Department of Ophthalmology, Istanbul, Turkey. It is a retrospective randomized comparative study.The patients had phacoemulsification surgery divided into two groups. These patients received either a mixture of sodium hyaluronate and trehalose (HT, Thealoz Duo®, Thea)(Group 1) or sodium hyaluronate 0.15% (Eye Still®; Teka) (Group 2) postoperatively. Effect on corneal epithelial and stromal healing was evaluated using Oxford staining and the vertical scar length measured by optic coherence tomography (OCT) respectively. Preoperative and postoperative findings for Oxford staining, Schirmer’s test, tear film break-uptime (TBUT) and ocular surface disease index(OSDI) scores were also evaluated. The correlation between scar length and tear film parameters was examined. The effect of trehalose on the epithelial healing and stromal scar formation was evaluated. Group 1 and 2 each had 30 eyes. The two groups were similar according to age and sex distribution. In terms of epithelial healing, it was faster in the trehalose group, although there was no statistical difference between the two groups. The length of the stromal scar was not significantly different between groups, though a smaller scar formation was observed in group 1 compared to those in group 2 at both 1 week and 1 month postoperatively. There was also no significant difference between the groups in tear film parameters. The stromal scar length was correlated with the Schirmer test on the 15th day. Although it was not statistically significant, the hyaluronic acid/trehalose may affect epithelial healing and stromal scar formation in a positive way after phacoemulsification surgery. Larger and longer studies are needed.

Topical application of cervix with hyaluronan improves fertility in goats inseminated with frozen-thawed semen.

ObjectiveArtificial insemination plays an important role in genetic improvement in the goat farming system. The aim of this study was to investigate the effect of cervical application of hyaluronan (HA) on the fertility in goats after cervical artificial insemination using frozen-thawed (F-T) semen.MethodsAfter oestrous synchronisation with progesterone sponges and pregnant mare serum gonadotropin injection, both nulli- and multi-parous goats, were randomly allocated to 2 groups, and were inseminated with 0.25 mL of F-T semen (150×106 spermatozoa) twice at 52 h and 56 h after sponge removal. Prior to the insemination, goats in Group 1 only were given topical cervical HA application at 48 h after sponge removal. Site of insemination was recorded as os-cervix or intra-cervix or intra-uterus. Pregnancy was tested ultrasonographically 42 days after insemination. The data on pregnancy rates and percentage of animals according to the site of semen deposition were compared by Chi-square analysis.ResultsThe overall pregnancy rate was significantly (p<0.004) higher in goats with prior application to the cervix with HA (63.3%) than without (36.0%). Same pattern was observed in the pregnancy rates of nulli- and multi-parous goats in both the groups. Percentage of nulliparous goats according to the site of insemination in the HA group did not differ between first and the second insemination. However, in multiparous goats the percentage of animals inseminated intra-cervically was significantly increased (p≤0.05) between the first and the second inseminations.ConclusionThe results suggest that significantly higher fertility rate in the “HA goats” compared to the “without HA” group was because of deeper insemination facilitated by topical cervical application of HA. The deeper insemination into the cervical canal increase the rate of fertilisation when the cervical artificial insemination is performed.

Effect of hyaluronate and splinting alone &lt;em&gt;versus&lt;/em&gt; combined treatment (splinting and hyaluronate) on thumb carpometacarpal osteoarthritis

Thumb carpometacarpal osteoarthritis can lead to global hand dysfunctions and its symptoms are pain and inability. The purpose of this study is to determine the effectiveness of hyaluronate in relieving these symptoms, and to compare it to orthosis and combined treatment (orthosis and hyaluronate). We enrolled 39 patients, evaluated at the baseline by using numeric rating scale (NRS) for pain, Disability of the Arm, Shoulder and Hand (DASH) and Dreiser Scale for disability degree, and Digital Hydraulic Pinch Gauge for grip strength. Eligible participants were randomly assigned to one of the three treatments: injection of hyaluronate (group I), combined treatment (hyaluronate and orthosis, Group II) and orthosis (hard-resting splint, Group III). Patients of Group I and Group II were injected by low molecular weight Hyaluronate once a week for three consecutive weeks. Injections were performed by means of the so-called blind technique. The data analysis indicated a significant decrease (P&lt;0.01) of pain at week 4, further manifested at week 26 by all groups treated. The same occurred for functional symptoms, and grip strength. This improvement appears more evident in group I that received HA.