Hyaluronate Group Research Articles

Ultrastructural findings after intraarticular application of hyaluronan in a canine model of arthropathy.

We investigated the effect of intraarticularly applied hyaluronic acid (hyaluronan) on the cartilaginous structure of experimentally induced chondromalacia patellae in dogs. For the induction of chondromalacia, we used the Pond-Nuki technique, which involved severance and resection of the anterior cruciate ligament, as a canine model of arthropathy in 27 foxhounds (three groups of nine animals each). In a pilot study, we evaluated the effect of resection of the anterior cruciate ligament with no therapy. Patellar specimens were retrieved at 3, 6, and 12 weeks postoperatively. Subsequently, we compared a treatment group that received intraarticular injections of hyaluronan with a placebo group that received saline solution. The groups were compared at 3, 6, and 12 weeks postoperatively. Three animals from the treatment and placebo groups received five injections of hyaluronan during one of the 4-week intervals (weeks 3-6, 6-9, or 12-15). Specimens were retrieved 5 weeks after the last injection. In both groups, the uninvolved contralateral knee served as a control. The specimens were taken from the medial and lateral patellar poles. Histological analysis included light microscopy and transmission electron microscopy. The structural and ultrastructural changes were assessed qualitatively and were quantified with use of a modified Mankin score. Our results indicate that chondromalacia patellae may be induced with the Pond-Nuki technique. We found a significant reduction (p < 0.01) of cartilaginous lesions in the hyaluronan group compared with the placebo group. Our results suggest that intraarticularly applied hyaluronan is effective in delaying the degenerative process of cartilage degradation. Therefore, we conclude that the use of hyaluronan may be indicated during the early stages of chondromalacia.

Viscosupplementation effect on proprioception in the osteoarthritic knee

<h2>Abstract</h2> Payne MW, Petrella RJ. Viscosupplementation effect on proprioception in the osteoarthritic knee. Arch Phys Med Rehabil 2000;81:598-603. <b>Objective:</b> To test the hypothesis that treatment of the osteoarthritic knee with intraarticular hyaluronan may improve proprioception. <b>Methods:</b> Forty-six patients with unilateral osteoarthritis of the knee were recruited for this study from primary care clinics in the Department of Family Medicine at the University of Western Ontario. Inclusion required (1) the presence of pain with activities of daily function and (2) radiographic confirmation of medial compartment osteoarthritis. Proprioception was measured with an electrogoniometer attached to the study knee. Subjects performed an angle reproduction test in the closed kinetic position. The difference between the target test angle and the reproduced angle was labeled the absolute angular error (AAE). Eleven angles were tested in random order before beginning therapy, after 3 weeks, and after 12 weeks. <b>Results:</b> Twenty-one men and 19 women completed the study (22 subjects received hyaluronan injections and 18 subjects received a placebo injection). No significant differences existed between the study groups in age, the timing of injections, or proprioceptive testing. A 2 × 3 repeated measures analysis of variance (ANOVA) comparing injection groups at all times revealed no significant differences in AAE. The AAE proprioception data was examined for differences due to fatigue caused by the number of test angles (<i>p</i> <.001) and differences explained by angulations in various divisions of the normal range of motion (<i>p</i> <.001). After accounting for these potential confounds, a two-way ANOVA still did not detect any significant differences in AAE between hyaluronan and placebo groups. <b>Conclusion:</b> Other studies have found that proprioception may be impaired in osteoarthritic knees and that viscosupplementation therapy with hyaluronan may decrease pain and increase function in these knee joints. The results of the present study suggest that this therapy does not adversely affect proprioception and that a longer, longitudinal study is required to determine if viscosupplementation treatments could attentuate proprioceptive decline. <b>© 2000 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation</b>

Dialysis solution containing hyaluronan: Effect on peritoneal permeability and inflammation in rats

Hyaluronan (HA), a high molecular weight mucopolysaccharide found in interstitial tissues and fluid, is lost from the peritoneal cavity during peritoneal dialysis. In order to determine the role of HA in peritoneal function, we investigated the effects of exogenous HA on peritoneal permeability, markers of intraperitoneal inflammation, and peritoneal morphology in rats exposed to peritoneal dialysis solution for four weeks. Wistar rats were infused intraperitoneally, twice daily, with conventional, hypertonic dialysis solution (Dianeal 3.86%; control) or Dianeal solution containing 10 mg/dL of high molecular weight HA. Peritoneal permeabilities and clearances of solutes and protein were determined using a modified peritoneal permeability test (peritoneal equilibration test) at the beginning and the end of the treatment. Peritoneal volume and ultrafiltration were determined using a macromolecular marker and by gravimetric methods. Peritoneal inflammation was determined by cell counts and differential and by the measurement of cytokine concentrations in the dialysate effluent. Peritoneal thickness and HA content were determined in liver and mesentery biopsies taken at the end of the experiment. After four weeks of exposure to the dialysis solution, transperitoneal protein equilibration was significantly lower in HA-treated rats compared with rats treated with Dianeal alone (46% lower for albumin, P < 0.003; 33% lower for total protein, P < 0.001). The total drained volume after a four hour dwell was 29% higher in the HA group compared with the control (P < 0.001), yielding a positive net ultrafiltration in the HA group versus a negative net ultrafiltration in controls. Peritoneal clearances of urea and creatinine tended to be elevated in HA-treated rats, while clearances of total protein and albumin tended to be lower. Dialysate effluent from rats exposed to HA contained a lower percentage of neutrophils (8.8 +/- 22.8 +/- 9.5%, P < 0.01) and lower levels of the cytokines, tumor necrosis factor-alpha (11.2 +/- 14.7 vs. 42.3 +/- 35.3 pg/mL, P < 0.05) and monocyte chemoattractant protein-1 MCP-1 (72.0 +/- 86.5 vs. 402.4 +/- 258.3 pg/mL, P < 0.02), compared with rats treated with Dianeal alone. The thickness of the peritoneal interstitium showed a similar increase in both groups, but mesenteric tissue from the HA group contained more HA (48%, P < 0.01) than tissue from control animals. The addition of HA to peritoneal dialysis solution decreases protein permeability, increases ultrafiltration, and decreases cytokine levels and the proportion of peritoneal neutrophils in dialysate from rats exposed to hypertonic dialysis solution. These results suggest that exogenous HA may help to protect the peritoneal membrane during exposure to dialysis solutions. These benefits, if sustained in the clinical setting, could lead to improvements in the therapy of peritoneal dialysis.

PROPRIOCEPTION IN OSTEOARTHRITIC KNEES WITH HYALURONAN INJECTIONS

1834 The purpose of this study was to examine the effect of a single series of intra-articular hyaluronan injections on proprioception in osteoarthritic knee joints. Twenty-one men and 19 women completed the study (22 subjects received hyaluronan injections and 18 subjects received a saline placebo injection). There were no significant differences in age between the study groups, the timing of injections or proprioceptive testing. Proprioception was measured with a Penny and Giles electrogoniometer attached to the study knee. Subjects performed an angle reproduction test in the closed-kinetic position. The difference between the target test angle and the reproduced angle was labeled the absolute angular error (AAE). Eleven angles were tested in random order before beginning therapy, after three weeks, and after 12 weeks. A 2×3 repeated measures ANOVA comparing injection groups at all times revealed no significant differences in AAE. The AAE proprioception data was examined for differences due to fatigue caused by the number of test angles (p < 0.001) and differences explained by angulations in various divisions of the normal range of motion (p < 0.001). After accounting for these potential confounds, two-way ANOVAs still did not detect any significant differences in AAE between hyaluronan and placebo groups. Other studies have found that viscosupplementation therapy using hyaluronan may decrease pain and increase function in knee joints. The results of this study suggest that this therapy does not adversely affect proprioception. Thus, the safety profile of hyaluronan injections may be broadened since proprioception was not impaired.

Effects of hyaluronan on periosteal grafts for large full-thickness defects in rabbit articular cartilage

We studied the effects of hyaluronan (HA) on chondrogenesis in periosteal grafts in rabbit knees to elucidate the effects of this agent in the repair of articular cartilage. Large full-thickness defects of the articular cartilage were created in the anteromedial part of the femoral articular surface of bilateral knee joints. Periosteal grafts were then harvested and sutured onto the defects. HA was injected in the right knee immediately after the operation and then once a week for 4 weeks (HA group). The same volume of saline was injected in the left knee in the control group. The animals were killed 2, 5, 8, and 12 weeks after the operation. Macroscopic and histological findings of the regenerated tissue were evaluated with a semiquantitative histological grading system. The total histological scores of the HA group were better than those in the control group at each time examination point. At 12 weeks, in particular, the scores for surface regularity and integration to adjacent articular cartilage were significantly better in the HA group than in the control group (P < 0.05). No significant differences were observed between the two groups in regard to the area healed (%). HA may have beneficial effects on the repair of large full-thickness defects of the articular cartilage with autologous periosteal grafts.

Hyaluronan decreases peritoneal fluid absorption: Effect of molecular weight and concentration of hyaluronan

We have recently shown that the addition of hyaluronan to peritoneal dialysis solution could decrease the peritoneal fluid absorption rate, possibly through decreasing peritoneal tissue hydraulic conductivity. The physical-chemical properties of hyaluronan were found to be both molecular weight and concentration dependent. In this study, we investigated the effects of different molecular weight as well as different concentrations of hyaluronan on the peritoneal fluid kinetics. A four-hour dwell study was performed in 48 male Sprague-Dawley rats (6 rats in each group) with 131I albumin (RISA) as an intraperitoneal volume marker. Each rat was intraperitoneally injected with 25 ml of 1.36% glucose dialysate alone (control) or with 0.01% hyaluronan (HA) with different molecular weights [85,000 (HA85K group), 280,000 (HA280K group), 500,000 (HA500K group), and 4,000,000 (HA4M group) molecular wt] or with a different concentrations of hyaluronan [(molecular wt 500,000); 0.01% (0.01% HA group), 0.05% (0.05% HA group), 0.1% (0.1% HA group), and 0.5% (0.5% HA group) hyaluronan]. The peritoneal fluid absorption rate (as assessed by the RISA elimination rate, KE) was significantly decreased in the HA500K and H4M groups as well as in all the different concentration groups (with molecular wt 500,000) as compared with the control group, resulting in significantly higher net fluid removal in these groups (except for the H4M group) as compared with the control group. In the 0.5% HA group (but not in the other hyaluronan groups), the direct lymphatic absorption (KEB) was also significantly decreased. The transcapillary ultrafiltration rate (Qu) was significantly lower in the HA4M group as compared with the control group but significantly higher in the 0.05% HA (and tended to be higher in the 0.1% HA group) as compared with the other groups. No difference in Qu was found between the 0.5% HA group as compared with the control group, despite a more marked decrease in KE in this group as compared with the H4M group. There were no significant differences in KE, Qu, and net fluid removal between the HA85K and HA280K groups and the control group. Our results suggest that (a) the addition of hyaluronan to dialysate could decrease peritoneal fluid absorption and thus increase the net ultrafiltration; this effect appears to be both size dependent and concentration dependent. (b) High molecular weight fraction of hyaluronan may also decrease the transcapillary Qu by decreasing tissue hydraulic conductivity. (c) A higher concentration of hyaluronan in dialysate resulted in a more marked decrease in peritoneal fluid absorption (absorption to peritoneal tissues as well as direct lymphatic absorption), possibly through both decreasing tissue hydraulic conductivity and increasing fluid viscosity. (d) Decreasing tissue hydraulic conductivity by adding a high concentration of hyaluronan to dialysate does not decrease the transcapillary ultrafiltration, possibly because the osmotic effect of hyaluronan may counterbalance the decrease in transcapillary ultrafiltration because of the decrease in tissue hydraulic conductivity.

Intraperitoneal Addition of Hyaluronan Improves Peritoneal Dialysis Efficiency

It has been shown that hyaluronan (HA) can decrease peritoneal fluid absorption. It is not known, however, how various molecular weights and various concentrations of hyaluronan affect peritoneal fluid absorption rate. A study of 4-hour dwells, with frequent dialysate and blood sampling, was performed in male Sprague-Dawley rats (6-7 rats in each group) with 131I albumin as an intraperitoneal volume marker. Each rat was infused intraperitoneally with 25 mL of 1.5% glucose solution alone or 1.5% glucose solution containing hyaluronan at various molecular weights (MW-85 kD, 280 kD, 500 kD, and 4 MD) or containing hyaluronan of MW 500 kD at various concentrations (0.01%, 0.05%, 0.1%, 0.5%). Two additional groups were infused with 40 mL of 1.36% glucose dialysate alone or 1.36% glucose dialysate with 0.01% hyaluronan (MW 500 kD) to test the effect of hyaluronan when high dialysate fill volume was used. Addition of 0.01% hyaluronan significantly decreased peritoneal fluid absorption rate (K(E)) (by 22%, p < 0.01). The decrease was more marked with hyaluronan at high MW or high concentration, or with high dialysate fill volume. The net ultrafiltration tended to be higher in all hyaluronan groups compared to their control groups except in the 4 MD group; this difference was mainly due to a lower K(E) in all the hyaluronan groups. The direct lymphatic flow was significantly decreased in the 0.5% HA group. The transcapillary ultrafiltration rate (Qu) was significantly lower in the 4 MD group as compared to the control group. No difference in Qu was found between the other groups as compared to their control groups. (1) Intraperitoneal addition of hyaluronan may increase net peritoneal fluid removal, mainly because hyaluronan decreases peritoneal fluid absorption rate. The decrease was more marked when high dialysate fill volume was used, indicating that intraperitoneal addition of hyaluronan can prevent the decreased net ultrafiltration caused by an increase in dialysate fill volume. (2) The decrease in peritoneal fluid absorption rate may be both MW-dependent and concentration-dependent: that is, a higher MW as well as a higher concentration of hyaluronan result in a more marked decrease in peritoneal fluid absorption rate. (3) Low concentrations of high MW hyaluronan may also decrease Qu. However, Qu did not decrease when high concentrations of hyaluronan were used despite a significant decrease in peritoneal fluid absorption rate.

Hyaluronan prevents the decreased net ultrafiltration caused by increased peritoneal dialysate fill volume

In the present study, we investigated (1) the effect of an increase in dialysate fill volume on peritoneal fluid and solute transport using a 1.36% glucose solution, and (2) the effect of intraperitoneal administration of hyaluronan on peritoneal transport characteristics when different fill volumes were used. A four-hour dwell study with frequent dialysate and blood sampling was performed in 26 male Sprague-Dawley rats with 131I albumin as the intraperitoneal volume marker. Each rat was injected intraperitoneally with 25 ml (group Con25, N = 6) or 40 ml (group Con40, N = 7) of 1.36% glucose dialysis solution alone or 25 ml (group HA25, N = 6) or 40 ml (Group HA40, N = 7) of 1.36% glucose dialysis solution with 0.01% hyaluronan. The peritoneal transport of fluid, glucose, urea, and total protein as well as the intraperitoneal hydrostatic pressure (IPP) with different fill volumes were evaluated. We found that IPP and peritoneal fluid absorption rate significantly increased with the increase in fill volume (P < 0.01), and therefore the net ultrafiltration volume was significantly lower in the Con40 group compared to the Con25 group despite a higher transcapillary ultrafiltration rate in the Con40 group. The addition of hyaluronan to dialysate significantly (P < 0.01) decreased the peritoneal fluid absorption rate (by 22% in HA25 vs. Con25 and by 29% in HA40 vs. Con40) and thus significantly increased the net peritoneal fluid removal. The diffusive mass transport coefficients for glucose, urea and total protein did not differ between the Con25 and Con40 groups or between the two hyaluronan groups as compared to their respective control groups. The peritoneal clearance of urea increased significantly in the high fill volume group (by 58% in Con40 vs. Con25) and in the two hyaluronan groups (by 21% in HA25 vs. Con25 and by 16% in HA40 vs. Con40). We conclude that: (1) An increase in dialysate fill volume using 1.36% glucose dialysis solution results in higher intraperitoneal hydrostatic pressure and higher peritoneal fluid absorption rate, and therefore lower net ultrafiltration. (2) Intraperitoneal addition of hyaluronan significantly decreases the peritoneal fluid absorption rate, and the decreasing effect is even more marked when a high fill volume is used. (3) Small solute clearances increase markedly with increases in fill volume, and then further increase by adding hyaluronan to the dialysate due to the increase in drainage volume. Thus, intraperitoneal administration of hyaluronan during a single peritoneal dialysis exchange may significantly increase the peritoneal fluid and solute removal by decreasing peritoneal fluid absorption, and may thereby prevent the decreased net ultrafiltration caused by an increase in dialysate fill volume.

高位けい骨骨切り術後患者に対するヒアルロン酸ナトリウムの効果

We studied the clinical effects of sodium hyaluronate (HA) on patients treated with high tibial osteotomy (HTO). Nine knees from 9 patients with osteoarthritis (OA) were selected randomly as a case group, and were injected with HA into the affected knee inter-articularly once a week for five weeks after HTO (HA group). Nine knees from 9 patients with OA of the knee without HA injection were selected as a control group (non-HA group). Controls were matched to cases for age, body weight, range of motion (ROM) and JOA score before HTO. ROM at five weeks and one year after HTO, and JOA score at one year after HTO were compared between the two groups. ROM at five weeks for HA group and non-HA group (118° and 93°, respectively) reached statistical significance (P<0.03). ROM at one year for HA group and non-HA group were 134° and 132°, respectively without statistical significance. JOA score at one year for HA group and non-HA group were 82 and 86, respectively without statistical significance. Intra-articular injection of HA after HTO is effective on the early achievement of full ROM.

Hyaluronan decreases peritoneal fluid absorption in peritoneal dialysis.

Hyaluronan, exhibiting a high resistance against water flow, acts in the tissue as a barrier against rapid changes in water content. To test whether hyaluronan has any effect on the peritoneal fluid and solute transport, and, in particular, on the peritoneal fluid absorption, a 4-h dwell study with an intraperitoneal volume marker (radiolabeled human serum albumin [RISA]) was conducted in 21 male Sprague Dawley rats (three groups, seven rats in each group). Each rat was injected intraperitoneally with 25 ml of 1.36% glucose solution alone (control group), with 0.005% hyaluronan (HA1 group), or with 0.01% hyaluronan (HA2 group). Dialysate and blood samples were taken frequently for analyses of fluid and solute (urea, glucose, and protein) transport. The intraperitoneal volume was calculated from the dilution of RISA with a correction for RISA disappearance from the peritoneal cavity. This study shows that adding hyaluronan to peritoneal dialysis solution significantly (P < 0.01) increased the net peritoneal fluid removal, mainly due to a significant decrease in the peritoneal fluid absorption rate (P < 0.01). The diffusive mass transfer coefficients for glucose, urea, and protein did not differ between the three groups. The peritoneal clearance of urea increased significantly in the two hyaluronan groups compared with the control group, due to the increased net fluid removal in the hyaluronan groups. These results suggest that intraperitoneal administration of hyaluronan during a single peritoneal dialysis exchange may significantly increase the peritoneal fluid and solute removal by decreasing peritoneal fluid absorption.

The Effect of Intraoperative Injection of Hyaluronan under a One-Piece Glaucoma Filtration Implant in the Rabbit Eye

The effect of a single intraoperative injection of hyaluronan on intraocular pressure (IOP) and postsurgical tissue healing was evaluated on 18 rabbits with an aqueous drainage implant. During the follow-up period IOP was recorded and analysed. Furthermore, inflammatory reaction and appearance of the fibrous tissue around the implants were studied in histological sections. In both the hyaluronan and control groups the operation lowered the average IOP statistically significantly for the whole follow-up period when compared with preoperative values. From days 7 to 60 the mean IOP values of the hyaluronan injected eyes stayed at a lower level than in the control eyes, but with no statistical difference between the 2 groups. The connective tissue layer around the implants appeared less dense during the first 17 postoperative days in the sodium-hyaluronate group; in addition, the inflammatory cell reaction showed a tendency to remain acute longer.

高分子量ヒアルロン酸ナトリウムの膝関節腔内投与効果の検討

The effect of high-molecular-weight sodium hyaluronate (HA) on osteoarthrosis was investigated. Thirty-eight knees were divided into two groups. 21 knees of the HA group were administered with HA and 17 other knees were administered with 1% mepivacaine. The administration was performed once a week and continued for 12 weeks. At one week and three months after the administration the clinical effect was assessed using the JOA-score and the joint fluid was aspirated for biochemical analysis. One week after administration the JOA-score was higher than prior administration for both the HA and control group. The level of chondroitin sulfate isomers was lower in the HA group. Three months later the continuity of the effect was confirmed using the JOA-score and in the level of chondroitin sulfate isomers only in the HA group.

Effect of hyaluronan on the healing of partially ruptured anterior cruciate ligament of rabbits

The midportion of the anterior cruciate ligament (ACL) of rabbits was partially transected, and the effect of hyaluronan (HA) on its healing was determined. A 1% solution of HA (HA group) or physiological phosphate-buffered saline (control group) was administered intraarticularly, at 0.1ml/kg body weight, once a week from 1 week after the operation. Two, 4, and 6 weeks after the initiation of HA administration, the ACLs were examined grossly, histologically and immunohistochemically. At 2 weeks, the lacerated portions were completely covered with scar-like tissue in both groups. These tissue areas were smaller in the HA group than in the control group. Histologically in the HA group, the regularity of collagen fibers (indicating the maturity of regenerated collagen fibers) had increased compared to findings in the control group, and the number of fibroblastic cells decreased gradually at a significantly faster rate. The number of inflammatory cells and blood vessels decreased gradually in both groups, with these values being lower in the HA group at each time point but not significantly so. Immunohistochemical examination of the repaired tissue revealed strong staining with anti-chondroitin sulfate proteoglycan antibody in the HA group 2 weeks after the first HA administration. The staining gradually became reduced, with the rate of reduction being faster in the HA group than in the control group. The stimulation of chondroitin sulfate proteoglycan production and the faster reduction of it in the HA group suggests that HA facilitated tissue repair and inhibited the formation of scar tissue.

Analysis of glycosaminoglycans and their oligosaccharide fragments by capillary electrophoresis.

Glycosaminoglycans are high molecular mass polymers found in living tissues. They are degraded by site specific enzymes to oligosaccharide fragments. Polymers and oligomers all carry negative charge and are found as salts soluble in water. Consequently, capillary electrophoresis has come to the fore as an analytical technique in this field. This review discusses application of the technique to the chondroitin-dermatan, heparin and hyaluronan groups of polymer and the derived oligosaccharides. Direct and indirect UV detection are discussed as well as detection methods involving precolumn derivatization. Capillary electrophoresis has found use in the characterisation of heparin and in following the changes in chondroitin and hyaluronan during the onset of arthritic disease in humans. Some glycosaminoglycans have been used as asymmetric anions in the separation of enantiomers of low molecular mass compounds by capillary electrophoresis.

Acute effects of perineural administration of sodium hyaluronate on palmar digital neurectomy sites in horses

Summary Biaxial palmar digital neurectomy of all limbs was performed on 6 mixed-breed castrated adult male horses, using a standard guillotine method. Using a Teflon catheter, 20 mg (2 ml) of sodium hyaluronate (group 1), 2 ml of phosphate-buffered saline solution (group 2), or catheter placement with no infusion (group 3) was applied to 4 (group 1) or 2 (groups 2 and 3) of 8 incisions/horse. Treatments were administered after closure of the neurectomy incision, and the catheter was removed. Horses were evaluated daily for 1 week, then weekly over a 9- week period for evidence of lameness, swelling, and ultrasonographic changes. On week 9, horses were euthanatized and neurectomy sites were removed en bloc for histologic evaluation of axonal regrowth, inflammation, and fibrosis. Neither lameness nor sign of painful neuroma was observed clinically in any of the horses. Neurectomy eliminated cutaneous heel sensation in all limbs for the duration of the study. Swelling was evident at all neurectomy sites. There were no significant differences between treatment sites for measurement of pastern circumference or ultrasonographic evaluation of incisional swelling. Foci of ultrasonographic hyperechogenicity increased over time, but there was no significant difference in hyperechogenicity between treatment groups. Histologic evidence of neuroma formation was observed at all sites. Morphometric assessment of neuroma cross-sectional areas revealed no significant difference between the groups, as did subjective histologic assessment of neuroma density and fibrous tissue content. We conclude that there are no clinical, ultrasonographic, or histologic effects on neuroma formation and fibrosis at sites of palmar digital neurectomy associated with a single perineural administration of sodium hyaluronate or phosphate-buffered saline solution.

Effects of High-Molecular-Weight Sodium Hyaluronate on Experimental Osteoarthrosis Induced by the Resection of Rabbit Anterior Cruciate Ligament

Sodium hyaluronate (HA) with a molecular weight of 202 x 10(4) (HA-202) was administered into the right knees of mature rabbits for the treatment of experimental osteoarthrosis induced by resection of the anterior cruciate ligament. At six and 12 weeks after the initiation of administration, the test group was compared with a group administered physiological saline solution to determine the effects on articular cartilage and synovial tissue. In both the six- and the 12-week period, cartilage degeneration proceeded with the lapse of time in both groups; however at 12 weeks, the efficacy of HA-202 in inhibiting degeneration was clearly observed at the lateral condyle of the femur and tibia where relatively marked degeneration was observed in the saline group. A comparison was also made among three groups administered HA-95 (sodium hyaluronate with a molecular weight of 95 x 10(4)), HA-202, and saline, respectively, for 12 weeks. The saline group showed the greatest cartilage degeneration accompanied by complete disorganization of the cartilage layer and the disappearance of chondrocytes. The degeneration was less in the HA groups, and it was more significantly inhibited in the HA-202 group than in the HA-95 group.

Use of sodium hyaluronate in treating temporomandibular joint disorders: A randomized, double-blind, placebo-controlled clinical trial

This study assessed the efficacy of high-molecular-weight sodium hyaluronate as a treatment for certain intracapsular temporomandibular joint (TMJ) disorders. One hundred twenty-one patients were studied at three test sites using a randomized, double-blind, placebo-controlled experimental design. Patients were selected on the basis of 1) confirmed diagnosis of either degenerative joint disease (DJD), reducing displaced disc (DDR), or nonreducing displaced disc (DDN); 2) nonresponsiveness to nonsurgical therapies; and 3) severe dysfunction as established by the Helkimo indices (HI), visual analog scales (VASs), and physical measurements of joint movement and joint noise (arthrophonometry [APM]). Subjects received a unilateral upper joint space injection of either 1) 1% sodium hyaluronate in physiologic saline (MedChem Products, Woburn, MA) or 2) USP physiologic saline. Clinical evaluations were performed using HI, VAS, and APM at weekly intervals for the first month and then at monthly intervals up to 6 months postinjection. Statistical analyses for both categorical and continuous variables were performed for each diagnostic category at each examination interval. For DJD, no difference in outcome was seen between treatment groups. For DDN, significant between-group differences were seen through 1 month; however, beyond this time point, the number of DDN patients was insufficient to draw meaningful conclusions concerning efficacy. For DDR, statistically significant within-group and between-group improvement in all three measures (HI, VAS, APM) was seen for the hyaluronate group compared to the saline group throughout the 6-month test period. At the month-2 and month-3 examination intervals, twice as many patients treated with hyaluronate (90%) showed improvement compared to patients given placebo. Further, only 3% of patients with DDR who were treated with hyaluronate relapsed compared with 31% of patients with DDR given placebo.

Comparison of the protective effects of methylcellulose and sodium hyaluronate on corneal swelling following phacoemulsification of senile cataracts

The protective effects of two viscoelastic substances (hvdroxypropyl methylcellulose and sodium hyaluronate) on the cornea during phacoemulsification of senile cataracts were investigated in a prospective, randomized, clinical study. The viscoelastic substances were placed in the anterior chamber before and during phacoemulsification. The mean increase in central corneal thickness (measured by ultrasonic pachymetry) on the first postoperative day was statistically significantly higher (P<.05) in the methylcellulose group (35 eyes) than in the sodium hyaluronate group (35 eyes). Five weeks postoperatively the difference in mean central corneal thickness between the two groups was not statistically significant. However, one eye in the methylcellulose group developed bullous keratopathy. The present study indicates that methylcellulose does not protect the corneal endothelium as effectively as sodium hyaluronate during phacoemulsification procedures.

Effects of Sodium Hyaluronate on Peridural Fibrosis After Lumbar Laminotomy and Discectomy

Sodium hyaluronate, 1.9% solution, was evaluated for its ability to retard peridural fibrosis after unilateral lumbar hemilaminotomy, anular fenestration, and nuclectomy in dogs. Three materials: fat grafts, gelfoam, and sodium hyaluronate, were compared with empty controls for their ability to inhibit peridural fibrosis. Each dog served as his own internal control and the formation of fibrosis was evaluated at 2, 4, 12, and 26 weeks. Sodium hyaluronate was found to inhibit fibrosis more than the other materials on both a macroscopic and microscopic level. The area of fibrosis and tenacity of the adhesions on dissection were notably less in the sodium hyaluronate group. Microscopically, the thickness of collagen and number of fibroblasts were decreased with the use of 1.9% sodium hyaluronate. The peridural fibrosis occurred equally both anteriorly and posteriorly to the nerve roots and correlated with the area of surgical dissection. Fat grafts were not effective in preventing fibrosis anteriorly, especially in the region of the exiting nerve roots. Gelfoam did not inhibit but actually appeared to increase fibrosis formation. Interposition materials currently used in humans to prevent scar formation such as gelfoam and fat grafts have only addressed the posterior scar formation, which do little to alter the fibrosis anteriorly. The adhesions between the nerve root and the anulus fibrosus bind the nerve root down anteriorly, making it more vulnerable to recurrent disc herniation. Sodium hyaluronate, 1.9% solution, with its viscous semifluid properties, coats the nerve roots and dura anteriorly and posteriorly.(ABSTRACT TRUNCATED AT 250 WORDS)