Mg Of Hyaluronic Acid Research Articles

Hyaluronic acid attenuates osteoarthritis development in the anterior cruciate ligament‐transected knee: Association with excitatory amino acid release in the joint dialysate

We previously reported increased release of the excitatory amino acid (EAA) neurotransmitters, glutamate and aspartate, during the early stage of experimental osteoarthritis (OA). Our present objective was to study the effect of intraarticular injection of hyaluronic acid (HA) on OA development, and to analyze concomitant changes in EAA levels in dialysates of anterior cruciate ligament-transected (ACLT) knee joints. OA was induced in Wistar rats by ACLT of one hindlimb; the knee of the other hindlimb was used as the sham-operated control. HA group (n = 12) were injected intraarticularly in the ACLT knee with 1 mg of HA once a week for 5 consecutive weeks, starting at 8 weeks after surgery. Saline group (n = 12) were injected as above with normal saline. The sham-operated group, underwent arthrotomy, but not ACLT, and received no treatment (n = 14). Twenty weeks after surgery, knee joint dialysates were collected by microdialysis and EAA levels assayed by high-performance liquid chromatography, and gross morphological examination and histopathological evaluation were performed on the medial femoral condyles and synovia. Rats receiving intraarticular HA injections showed a significantly lower degree of cartilage degeneration on the medial femoral condyle at both the macroscopic level and on the Mankin grading scale than rats receiving saline injections. Intraarticular HA treatment also suppressed synovitis. Moreover, glutamate and aspartate levels were significantly reduced in the HA group compared to the saline group. Intraarticular injection of HA limits articular cartilage and synovium damage and OA formation, and, in parallel, reduces EAA levels in ACLT joint dialysates. This study suggests that the underlying mechanism of the anti-inflammatory effect of HA is to inhibit glutamate and aspartate release in ACLT knee joints, which attenuates the early development of OA.

A Comparison of the Therapeutic Effects of Hyaluronic Acid and Triamcinolone Used in an Intra-articular Injection for Knee Osteoarthritis

Background: Both steroid and hyaluronic acid (HA) are effective therapeutic regimens when used as intra-articular (IA) injections for knee osteoarthritis. This study was performed to re-estimate the hypothesis that the IA injection of HA is more effective than that of steroid. Methods: A retrospective study was conducted by reviewing the medical records of osteoarthritis of the knee patients treated only by IA injection with HA or triamcinolone (Triam) at our pain clinic over the last 28 months. The HA group (N = 17) received an IA injection of 25 mg of HA followed by a 5 ml injection of 1% lidocaine once a week for 5 weeks. The triam group (N = 34) received an IA injection of a mixed solution of 5-10 mg of triamcinolone and 6-8 ml of 1% lidocaine 3 to 5 times at one or two week intervals. Pain improvement was compared using pain relief scale (PRS) scores at the end of a series of IA injections in each patient. Results: Both groups showed significant pain improvement following a series of IA injection, compared to the pre-treatment pain state; mean PRS post-injections was 5.1 2.6 in the HA group and 6.1 2.9 in the Triam group (P

The hyaluronic acid receptor (CD44) is expressed in bovine oocytes and early stage embryos

Hyaluronic acid (HA) is a high molecular weight polysaccharide found in the extracellular matrix of most animal tissues, that exerts a profound influence on cell behavior. HA is one of the most abundant glycosaminoglycans (GAGs) in the uterine, oviductal and follicular fluids in mouse, pig, human and cattle. CD44, the principal cell membrane receptor for HA, is expressed from the 1- to 8-cell stage in human embryos, during post-implantation mouse embryogenesis and on the surface of differentiated embryonic stem cells. In the present study, we have analyzed by immunofluorescence, whether CD44 is present in bovine oocytes, fertilized oocytes and early stage embryos. Bovine cumulus–oocyte complexes (COCs) were aspirated from follicles (2–5 mm) and were selected for IVM and incubated for 24 h. Oocytes showing an expanded cumulus (generally 90–95%) were used for IVF. Fertilized oocytes were separated for immunofluorescence assay after 16 h of sperm incubation in order to fix the eggs at the pronuclear stage. The embryos were cultured for 8 days and the different stages of development for immunofluorescence assay were separated every 24 h of culture. The CD44 receptor was detected at every observation time examined. Fluorescence-tagged HA for the internalization assay was prepared by mixing fluorescein amine, Isomer I and 1 mg of HA from umbilical cord. Fluorescence-tagged HA was internalized in 2-, 4-, 8- and 16-cell-stage embryos, morulae and blastocysts. CD44 is expressed on the surface and in the cytoplasm of bovine oocytes and embryos in different stages of development.

Intravesical hyaluronic acid in the treatment of refractory interstitial cystitis

Objectives On the assumption that interstitial cystitis (IC) is the result of a defective mucous lining of the bladder epithelium, a study was carried out to investigate the activity of hyaluronic acid (HA) in the treatment of IC. HA is an important glycosaminoglycan (GAG) present in all connective tissues, including the GAG layer of the vesical mucosa. It exhibits a variety of pharmacologic properties that enhance its appeal for the therapy of IC. Methods A total of 25 patients, with the characteristic picture of IC and refractory to other medical treatments, participated in a trial of HA. Patients received 40 mg of HA intravesically on a weekly basis for 4 weeks, then monthly. Response to therapy was evaluated by symptom score, voiding diaries, and visual analog scales. Results An initial positive (complete + partial) response of 56% at week 4 increased to 71% by week 12. This response was maintained until week 20; beyond week 24 there appears to be a moderate decrease in the effectiveness of the medication. There was no significant toxicity attributable to the presence of HA in the bladder. Conclusions The response of refractory IC patients to the intravesical administration of HA was gratifying. In the past, many therapies for IC that were initially considered promising failed the test of a controlled study. Further studies will establish the effectiveness of this particular preparation of HA in the treatment of IC.

Further Investigation of the Use of Intratracheally Administered Hyaluronic Acid to Ameliorate Elastase-Induced Emphysema

Previously, this laboratory has shown that intratracheally administered hyaluronic acid (HA) significantly reduces air-space enlargement in a hamster model of emphysema induced with pancreatic elastase. Whereas HA was given immediately following elastase in those initial studies, the current investigation determined the effect of instilling HA up to 2 h before or after intratracheal administration of elastase to hamsters. Both 1 and 2 mg HA, given 2 h before pancreatic elastase, significantly decreased (p < .05) air-space enlargement compared to controls (as measured by the mean linear intercept). Instillment of 2 mg HA, 1 h after pancreatic elastase, had a similar effect (p < .05). In contrast, 1 mg HA, given 1 or 2 h after pancreatic elastase, did not significantly affect the mean linear intercept. Against human neutrophil elastase, HA exhibited the same protective effect. While neutrophil elastase induced less air-space enlargement than pancreatic elastase, both 1 and 4 mg of HA, given 2 h prior to the enzyme, still produced a significant reduction (p < .05) in the mean linear intercept. HA exerted this effect despite the fact that it initiates a transient influx of neutrophils into the lung. Since HA does not slow the clearance of intratracheally instilled [14C] albumin from the lung, its mechanism of action may not involve physical interference with the movement of elastase through the lung, but may instead depend on interaction with elastic fibers. Evidence for an association between these two matrix constituents was provided by studies using fluorescein-labeled HA. Overall, these results further suggest that HA may be useful in preventing lung injury by elastases.

Immunolocalization of stromelysin, tumor necrosis factor (TNF) α, and TNF receptors in atrophied canine articular cartilage treated with hyaluronic acid and transforming growth factor β

Abstract Objective To evaluate the ability of hyaluronic acid (HA), with and without transforming growth factor β (TGF-β), to stabilize the catabolic processes associated with atrophy of articular cartilage. Animals 20 adult, skeletally normal, hound-type dogs. Procedure Dogs (20 to 30 kg) were randomly assigned to 1 of 5 groups. One group served as untreated controls. Bivalve casts were placed on the left hind limbs of the remaining 16 dogs to limit weightbearing and motion of the limb for 92 days. One group served as the cast control. Beginning on day 56, 3 groups received aseptic intra-articular injections in the left stifles of either 5 mg of HA or 5 mg of HA containing either 20 or 50 μg of TGF-β. Intra-articular injections were repeated at 4-day intervals until the end of the study. On day 92, stifles were harvested at necropsy. Medial femoral condyles were histologically processed, and the articular cartilage was stained for the presence of proteoglycans, stromelysin, tumor necrosis factor (TNF) α, and TNF receptors (p55 and p75). Results Decreased metachromasia was evident in the cartilage matrix of all cast groups, with the smallest decrease in the HA-treated group. Stromelysin was immunolocalized in articular cartilage of the cast (left) limbs of cast control and both HA/TGF-β-treated groups. TNF-α was localized in articular cartilage of all cast (left) and right limbs, except those of the HA-treated group. Receptors for TNF were observed in both limbs of untreated control and cast control groups and cast limbs of HA/TGF-β-treated groups. The receptors were not localized in the right limbs of the HA with or without TGF-β-treated groups. TGF-β did not decrease stromelysin or TNF-α or receptors at the doses used. Conclusions HA may mediate a chondrostabilizing influence on articular cartilage by down-regulating TNF-α. Importantly, HA appeared to exert its inhibitory influence on TNF-α, as well as stromelysin and TNF receptors, on a systemic basis. Clinical Relevance Results provide insight into the mode of action of HA as a therapeutic agent for arthritis and its stabilizing influence on cartilage metabolism. (Am J Vet Res 1996;57:1488-1496)

Fingerprinting the hyaluronic acid component of normal and pathological synovial fluids

The hyaluronic acids from samples of synovial fluids from ‘normals’ and patients with rheumatoid arthritis, osteoarthritis, rheumatic fever and other joint disorders, have been fingerprinted by their turbidity curves. The technique, applicable to about I mg of hyaluronic acid, is useful for the classification of synovial fluids, for assessing the size and molecular distribution of the hyaluronic acid and for ascertaining the effect of therapy on these properties.