Potential of Biofermentative Unsulfated Chondroitin and Hyaluronic Acid in Dermal Repair.

Chondroitin obtained through biotechnological processes (BC) shares similarities with both chondroitin sulfate (CS), due to the dimeric repetitive unit, and hyaluronic acid (HA), as it is unsulfated. In the framework of this experimental research, formulations containing BC with an average molecular size of about 35 KDa and high molecular weight HA (HHA) were characterized with respect to their rheological behavior, stability to enzymatic hydrolysis and they were evaluated in different skin damage models. The rheological characterization of the HHA/BC formulation revealed a G' of 92 ± 3 Pa and a G″ of 116 ± 5 Pa and supported an easy injectability even at a concentration of 40 mg/mL. HA/BC preserved the HHA fraction better than HHA alone. BTH was active on BC alone only at high concentration. Assays on scratched keratinocytes (HaCaT) monolayers showed that all the glycosaminoglycan formulations accelerated cell migration, with HA/BC fastening healing 2-fold compared to the control. In addition, in 2D HaCaT cultures, as well as in a 3D skin tissue model HHA/BC efficiently modulated mRNA and protein levels of different types of collagens and elastin remarking a functional tissue physiology. Finally, immortalized human fibroblasts were challenged with TNF-α to obtain an in vitro model of inflammation. Upon HHA/BC addition, secreted IL-6 level was lower and efficient ECM biosynthesis was re-established. Finally, co-cultures of HaCaT and melanocytes were established, showing the ability of HHA/BC to modulate melanin release, suggesting a possible effect of this specific formulation on the reduction of stretch marks. Overall, besides demonstrating the safety of BC, the present study highlights the potential beneficial effect of HHA/BC formulation in different damage dermal models.

Cytochrome P450 2C9-natural antiarthritic interactions: Evaluation of inhibition magnitude and prediction from in vitro data.

Many dietary supplements are promoted to patients with osteoarthritis (OA) including the three naturally derived compounds, glucosamine, chondroitin and diacerein. Despite their wide spread use, research on interaction of these antiarthritic compounds with human hepatic cytochrome P450 (CYP) enzymes is limited. This study aimed to examine the modulatory effects of these compounds on CYP2C9, a major CYP isoform, using in vitro biochemical assay and in silico models. Utilizing valsartan hydroxylase assay as probe, all forms of glucosamine and chondroitin exhibited IC50 values beyond 1000 µM, indicating very weak potential in inhibiting CYP2C9. In silico docking postulated no interaction with CYP2C9 for chondroitin and weak bonding for glucosamine. On the other hand, diacerein exhibited mixed-type inhibition with IC50 value of 32.23 µM and Ki value of 30.80 µM, indicating moderately weak inhibition. Diacerein's main metabolite, rhein, demonstrated the same mode of inhibition as diacerein but stronger potency, with IC50 of 6.08 µM and Ki of 1.16 µM. The docking of both compounds acquired lower CDOCKER interaction energy values, with interactions dominated by hydrogen and hydrophobic bondings. The ranking with respect to inhibition potency for the investigated compounds was generally the same in both in vitro enzyme assay and in silico modeling with order of potency being diacerein/rhein > various glucosamine/chondroitin forms. In vitro-in vivo extrapolation of inhibition kinetics (using 1 + [I]/Ki ratio) demonstrated negligible potential of diacerein to cause interaction in vivo, whereas rhein was predicted to cause in vivo interaction, suggesting potential interaction risk with the CYP2C9 drug substrates.

Effects of glucosamine-chondroitin combination on synovial fluid IL-1ß, IL-6, TNF-α and PGE2 levels in internal derangements of temporomandibular joint.

BACKGROUND: The aim of the present study was to evaluate the effects of glucosamine-chondroitin sulphate combination on internal derangements of temporomandibular joint in clinical and biochemical manners. MATERIAL AND METHODS: This randomized clinical study included 31 cases reporting joint tenderness, in which disc displacement was detected on MR imaging. In all patients, synovial fluid sampling was performed under local anesthesia. In the study group, the patients were prescribed a combination of 1500 mg glucosamine and 1200 mg chondroitin sulphate, while patients in the control group were only prescribed 50 mg tramadol HCl (twice daily) for pain control. After 8 weeks, synovial fluid sampling was repeated in the same manner. The levels of pain, maximum mouth opening (MMO), synovial fluid IL-1ß, IL-6, TNF-α and PGE2 measured before and after pharmacological intervention were compared. RESULTS: The reduction in pain levels was significant in both groups. There was no significant difference between two groups in terms of pain reduction. The improvement in MMO was significant in the study group but it was not in the control group. The MMO improvement was significantly higher in the study group compared to the control group. In the study group, significant decrease was observed in PGE2 level, while the decreases in IL-1ß, IL-6 and TNF-α levels were not significant. In the control group, no significant decrease was observed in any of the inflammatory cytokines after 8 weeks, moreover IL-1ß and IL-6 levels were increased. Alterations of IL-1ß and IL-6 levels were significant in study group while TNF-α and PGE2 levels were not, compared to control group. CONCLUSIONS: In conclusion, these results might suggest that glucosamine-chondroitin combination significantly increases the MMO and decreases the synovial fluid IL1ß and IL6 levels in internal derangements of TMJ compared to tramadol. The modifications of synovial fluid TNF-α and PGE2 levels do not reach statistical significance. This combination also provides efficient pain relief in similar level with tramadol, a narcotic analgesic.

Association between use of specialty dietary supplements and C-reactive protein concentrations.

Laboratory evidence suggests that certain specialty dietary supplements have antiinflammatory properties, though evidence in humans remains limited. Data on a nationally representative sample of 9,947 adults from the 1999-2004 cycles of the National Health and Nutrition Examination Survey were used to assess the associations between specialty supplement use and inflammation, as measured by serum high-sensitivity C-reactive protein (hs-CRP) concentration. Using survey-weighted multivariate linear regression, significant reductions in hs-CRP concentrations were associated with regular use of glucosamine (17%, 95% confidence interval (CI): 7, 26), chondroitin (22%, 95% CI: 8, 33), and fish oil (16%, 95% CI: 0.3, 29). No associations were observed between hs-CRP concentration and regular use of supplements containing methylsulfonylmethane, garlic, ginkgo biloba, saw palmetto, or pycnogenol. These results suggest that glucosamine and chondroitin supplements are associated with reduced inflammation in humans and provide further evidence to support an inverse association between use of fish oil supplements and inflammation. It is important to further investigate the potential antiinflammatory role of these supplements, as there is a need to identify safe and effective ways to reduce inflammation and the burden of inflammation-related diseases such as cancer and cardiovascular disease.

Gangliosides and chondroitin sulfate desensitize and internalize B2 bradykinin receptors.

Prolonged or repeated agonist activation of G-protein-coupled receptors (GPCRs) initiates their desensitization and internalization, rendering them unresponsive to agonist activation. We analyzed how gangliosides and chondroitin sulfate affect B2 bradykinin (BK) receptors (B2Rs). Gangliosides and chondroitin sulfate did not stimulate intracellular Ca(2+) release from B2R-expressing CHO-K1 cells, but repeated exposure desensitized B2Rs to BK stimulation. Microscopic observation of DsRed-fused B2Rs revealed that several gangliosides and chondroitin sulfate C (CSC) effectively internalized B2Rs. Ganglioside-CSC treatment of B2R mutant-expressing cells failed to desensitize and internalize the mutant receptors. As this mutant lacks the first extracellular domain and cannot activate GPCR kinase (GRK), gangliosides and CSC likely initiate B2R desensitization and endocytosis through GRK-mediated B2R phosphorylation.

Comparative therapeutic efficacy and safety of type-II collagen (UC-II), glucosamine and chondroitin in arthritic dogs: pain evaluation by ground force plate.

The investigation was conducted on client-owned moderately arthritic dogs with two objectives: (i) to evaluate therapeutic efficacy of type-II collagen (UC-II) alone or in combination with glucosamine hydrochloride (GLU) and chondroitin sulphate (CHO), and (ii) to determine their tolerability and safety. Dogs in four groups (n = 7-10), were treated daily for a period of 150 days with placebo (Group-I), 10 mg active UC-II (Group-II), 2000 mg GLU + 1600 mg CHO (Group-III), and UC-II + GLU + CHO (Group-IV). On a monthly basis, dogs were evaluated for observational pain (overall pain, pain upon limb manipulation, and pain after physical exertion) using different numeric scales. Pain level was also measured objectively using piezoelectric sensor-based GFP for peak vertical force and impulse area. Dogs were also examined every month for physical, hepatic (ALP, ALT and bilirubin) and renal (BUN and creatinine) functions. Based on observations, significant (p < 0.05) reduction in pain was noted in Group-II, III, and IV dogs. Using GFP, significant increases in peak vertical force (N/kg body wt) and impulse area (N s/kg body wt), indicative of a decrease in arthritis associated pain, were observed in Group-II dogs only. None of the dogs in any group showed changes in physical, hepatic or renal functions. In conclusion, based on GFP data, moderately arthritic dogs treated with UC-II (10 mg) showed a marked reduction in arthritic pain with maximum improvement by day 150. UC-II, GLU and CHO operate through different mechanisms of action, and were well tolerated over a period of 150 days.

Specialty supplements and prostate cancer risk in the VITamins and Lifestyle (VITAL) cohort.

Although there is evidence from studies of prostate cancer cell lines and rodent models that several supplements may have antiinflammatory, antioxidant, or other anticancer properties, few epidemiologic studies have examined the association between nonvitamin, nonmineral, "specialty" supplement use and prostate cancer risk. Participants, 50-76 yr, were 35,239 male members of the VITamins and Lifestyle (VITAL) cohort who were residents of western Washington state, and who completed an extensive baseline questionnaire in 2000-2002. Participants responded about their frequency (days/wk) and duration (yr) of specialty supplement uses. 1,602 incident invasive prostate cancers were obtained from the Surveillance, Epidemiology, and End Results registry. Multivariate-adjusted hazards ratios (HR) and 95% confidence intervals (95% CI) were estimated by Cox proportional hazards models. Any use of grapeseed supplements was associated with a 41% (HR 0.59, 95% CI: 0.40-0.86) reduced risk of total prostate cancer. There were no associations for use of chondroitin, coenzyme Q10, fish oil, garlic, ginkgo biloba, ginseng, glucosamine, or saw palmetto. Grapeseed may be a potential chemopreventive agent; however, as current evidence is limited, it should not yet be promoted for prevention of prostate cancer.

In vitro inhibitory effects of glucosamine, chondroitin and diacerein on human hepatic CYP2D6.

OBJECTIVES: Glucosamine, chondroitin and diacerein are natural compounds commonly used in treating osteoarthritis. Their concomitant intake may trigger drug-natural product interactions. Cytochrome P450 (CYP) has been implicated in such interactions. Cytochrome P450 2D6 (CYP2D6) is a major hepatic CYP involved in metabolism of 25% of the clinical drugs. This study aimed to investigate the inhibitory effect of these antiarthritic compounds on CYP2D6. METHODS: CYP2D6 was heterologously expressed in Escherichia coli. CYP2D6-antiarthritic compound interactions were studied using in vitro enzyme kinetics assay and molecular docking. RESULTS: The high-performance liquid chromatography (HPLC)-based dextromethorphan O-demethylase assay was established as CYP2D6 marker. All glucosamines and chondroitins weakly inhibited CYP2D6 (IC50 values >300 µM). Diacerein exhibited moderate inhibition with IC50 and Ki values of 34.99 and 38.27 µM, respectively. Its major metabolite, rhein displayed stronger inhibition potencies (IC50=26.22 µM and Ki =32.27 µM). Both compounds exhibited mixed-mode of inhibition. In silico molecular dockings further supported data from the in vitro study. From in vitro-in vivo extrapolation, rhein presented an area under the plasma concentration-time curve (AUC) ratio of 1.5, indicating low potential to cause in vivo inhibition. CONCLUSIONS: Glucosamine, chondroitin and diacerein unlikely cause clinical interaction with the drug substrates of CYP2D6. Rhein, exhibits only low potential to cause in vivo inhibition.

Effects of an oral administration of glucosamine-chondroitin-quercetin glucoside on the synovial fluid properties in patients with osteoarthritis and rheumatoid arthritis.

The effects of an orally administered combination of a glucosamine-chondroitin-quercetin glucoside (GCQG) supplement on the synovial fluid properties of patients with osteoarthritis (OA) and rheumatoid arthritis (RA) were investigated from the clinical nutrition view point. In this study, forty-six OA and twenty-two RA patients were administered with the GCQG supplement orally for 3 months. Several parameters of the knee joints were monitored before and after supplementation. The OA patients showed a significant improvement in pain symptoms, daily activities (walking and climbing up and down stairs), and visual analogue scale, and changes in the synovial fluid properties with respect to the protein concentration, molecular size of hyaluronic acid, and chondroitin 6-sulphate concentration were also observed. However, no such effects were observed in the RA patients. These results suggest that the GCQG supplement exerted a special effect on improving the synovial fluid properties in OA patients.

Synergistic chondroprotective effect of alpha-tocopherol, ascorbic acid, and selenium as well as glucosamine and chondroitin on oxidant induced cell death and inhibition of matrix metalloproteinase-3--studies in cultured chondrocytes.

Overproduction of reactive oxygen species and impaired antioxidant defence accompanied by chronic inflammatory processes may impair joint health. Pro-inflammatory cytokines such as interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) stimulate the expression of metalloproteinases which degrade the extracellular matrix. Little is known regarding the potential synergistic effects of natural compounds such as alpha-tocopherol (alpha-toc), ascorbic acid (AA) and selenium (Se) on oxidant induced cell death. Furthermore studies regarding the metalloproteinase-3 inhibitory activity of glucosamine sulfate (GS) and chondroitin sulfate (CS) are scarce. Therefore we have studied the effect of alpha-toc (0.1-2.5 micromol/L), AA (10-50 micromol/L) and Se (1-50 nmol/L) on t-butyl hydroperoxide (t-BHP, 100-500 micromol/L)-induced cell death in SW1353 chondrocytes. Furthermore we have determined the effect of GS and CS alone (100-500 micromol/L each) and in combination on MMP3 mRNA levels and MMP3 secretion in IL-1beta stimulated chondrocytes. A combination of alpha-toc, AA, and Se was more potent in counteracting t-BHP-induced cytotoxicity as compared to the single compounds. Similarly a combination of CS and GS was more effective in inhibiting MMP3 gene expression and secretion than the single components. The inhibition of MMP3 secretion due to GS plus CS was accompanied by a decrease in TNF-alpha production. Combining natural compounds such as alpha-toc, AA, and Se as well as GS and CS seems to be a promising strategy to combat oxidative stress and cytokine induced matrix degradation in chondrocytes.

Chain structure and immunomodulatory activity of a fructosylated chondroitin from an engineered Escherichia coli K4.

Polysaccharide K4 expressed from E. coli K4 has a similar structure with chondroitin, which can be used as a precursor to produce chondroitin sulfates. Here, we investigated the structure, conformation and biological activity of K4 from an engineered strain with high productivity. The NMR analysis suggested that K4 from wild-type strain with a low yield was a partially fructosylated chondroitin. While K4 from engineered strain was a fully fructosylated chondroitin. Light scattering analysis gave the Mw values of 6.15 × 104, 8.23 × 104 and 1.92 × 104 for K4-1, K4-2 and defructosylated K4 (DK4), respectively. The exponents of functions z1/2 = f(Mw) were in the range of 0.643-0.608, suggesting a random coil conformation for K4 and DK4. And the random coils K4 easily self-assembled into sphere-like aggregates in the dilute aqueous solution. Both K4 and DK4 exhibited significant immunomodulatory activities on RAW 264.7 cells at the dosage range of 5-500 µg/mL.

The influence of viscoelastic substances on the corneal endothelium during cataract surgery by phacoemulsification.

PURPOSE: To compare the ability of different ophthalmic viscoelastic devices to protect the corneal endothelium following in-the-bag phacoemulsification with posterior chamber intraocular lens (IOL) implantation. MATERIAL & METHODS: We studied 50 patients with soft to moderately dense (Grade 1-3) cataract and corneal endothelial cell density of >2000 cells/mm2. The corneal response to surgery was evaluated by measuring the endothelial cell loss, the variation in the mean cell area of the endothelial cells (CV), and the central corneal thickness, all that by using a TOPCON SP 2000P noncontact, specular microscope. Data were recorded preoperatively and postoperatively. RESULTS: Preoperatively no statistical significant difference was observed in cell count, CV or pachymetry among groups. Postoperatively, all the groups had a statistically significant decrease (p < 0.001) in endothelial cell count. There was an equal and significant (p < 0.001) increase in visual acuity. Between groups there was no statistically significant difference (p > 0.17) in any of the parameters we studied. CONCLUSIONS: Between the OVDs we used, either DisCoVisc or ProVisc & VisCoat, there was no statistical significant difference neither in surgical outcome nor in endothelial layer aspect and function. DisCoVisc protected better the endothelium cells even if it was not statistically significant, and is the one that can be used for the entire surgical procedure.

Effects of cytotoxic cis- and trans-diammine monochlorido platinum(II) complexes on selenium-dependent redox enzymes and DNA.

Here we present the preparation of 14 pairs of cis- and trans-diammine monochlorido platinum(II) complexes, coordinated to heterocycles (i.e., imidazole, 2-methylimidazole and pyrazole) and linked to various acylhydrazones, which were designed as potential inhibitors of the selenium-dependent enzymes glutathione peroxidase 1 (GPx-1) and thioredoxin reductase 1 (TrxR-1). However, no inhibition of bovine GPx-1 and only weak inhibition of murine TrxR-1 was observed in in vitro assays. Nonetheless, the cis configured diammine monochlorido Pt(II) complexes exhibited cytotoxic and apoptotic properties on various human cancer cell lines, whereas the trans configured complexes generally showed weaker potency with a few exceptions. On the other hand, the trans complexes were generally more likely to lack cross-resistance to cisplatin than the cis analogues. Platinum was found bound to the nuclear DNA of cancer cells treated with representative Pt complexes, suggesting that DNA might be a possible target. Thus, detailed in vitro binding experiments with DNA were conducted. Interactions of the compounds with calf thymus DNA were investigated, including Pt binding kinetics, circular dichroism (CD) spectral changes, changes in DNA melting temperatures, unwinding of supercoiled plasmids and ethidium bromide displacement in DNA. The CD results indicate that the most active cis configured pyrazole-derived complex causes unique structural changes in the DNA compared to the other complexes as well as to those caused by cisplatin, suggesting a denaturation of the DNA structure. This may be important for the antiproliferative activity of this compound in the cancer cells.

Hydroxyl radical scavenging activity of a new ophthalmic viscosurgical device.

PURPOSE: To quantify the hydroxyl radical scavenging activity of a new ophthalmic viscosurgical device (OVD) based on sodium hyaluronate and hydroxypropylmethylcellulose (named VISC28) in comparison with Viscoat, Healon, and Amvisc Plus. METHODS: The hydroxyl radicals that represent the principal free-radical species generated during phacoemulsification were produced by the Fenton reaction, and the scavenging activity of the tested viscoelastic substances was evaluated in vitro by the 2-deoxy-D-ribose (2-DR) oxidation method that produces the thiobarbituric acid-malondialdehyde (TBA-MDA), complex. An aliquot of viscosurgical formulation was added to phosphate buffer and mixed with 2-DR, Fe2 +/ethylenediaminetetraacetic acid (EDTA), and H2O2. The sample mix was incubated and thiobarbituric acid-trichloroacetic acid solution was added. The sample was then incubated for 30 min, and a chromatographic analysis was performed to quantify the TBA-MDA complex. The data were expressed as micromoles of MDA per milliliter of sample. RESULTS: All tested OVDs showed a marked hydroxyl radical scavenging activity. The MDA level was significantly lower in VISC28 (0.045 +/- 0.007 micromol/ml) compared with Viscoat (0.070 +/- 0.012 micromol/ ml, p < 0.05), Amvisc Plus (0.111 +/- 0.008 micromol/ml, p < 0.001), and Healon (0.175 +/- 0.016 micromol/ml, p < 0.001). A reduced scavenging activity was shown by VISC28 phosphate-buffered solution (PBS) (no TRIS and no sorbitol) compared with VISC28 (p < 0.001). CONCLUSIONS: The new OVD, VISC28, showed significantly higher hydroxyl radical inhibition compared with the other viscosurgical formulations. The following rank order for the scavenging activity was established: VISC28 > Viscoat > Amvisc Plus > Healon.

Protective effect of viscoelastics against retina lipid peroxidation.

Viscoelastics or ophthalmic viscosurgical devices are routinely used during anterior segment surgery and also in posterior segment surgery. Studies of the harmful effects of phacoemulsification on corneal endothelial cells suggest that much of this damage is mediated by free radicals. In this study, we compare the possible effects against lipid peroxidation in the retina of three different viscoelastic substances: Viscoat, Healon and Visiol. Herein we demonstrate for the first time that viscoelastics are effective to protect the retina against lipid peroxidation, as can be seen by the slight increase of malondialdehyde in the homogenates incubated with viscoelastic exposed to light and to a temperature of 37 degrees C when compared with the control homogenates.

Femtosecond laser preparation of donor tissue from the endothelial side.

PURPOSE: The femtosecond laser (Intralase) may provide advantages for dissecting a thin, uniform thickness posterior lamellar disk of donor tissue to be used for endothelial transplantation. We investigated the use of the Intralase to dissect the donor cornea from the posterior side to better obtain a thin and uniform lamellar disk. We investigated the use of a viscoelastic "cushion" to protect the endothelium during applanation and laser delivery. METHODS: Human eye bank donor buttons were placed endothelial side up, covered with a thin coat of viscoelastic, and brought into contact with the Intralase applanation lens. A 7-mm diameter, 100-microm lamellar disk was cut from the endothelial side. The endothelial viability after these procedures was determined using a live cell/dead cell assay. Controls were designed to assess the endothelial viability after applanation and laser application using only a balanced salt solution (BSS) cushion instead of viscoelastic material. Additionally, applanation without lasering using either BSS or a viscoelastic cushion was studied. RESULTS: The average endothelial cell loss in the laser experiment sets were 10% (n = 5, range of 4-17%, Sodium Hyaluronate), 14% (n = 5, range of 7-19%, Sodium Hyaluronate-Sodium Chondroitin) and 6% (n = 5, range of 3-11%, Hydroxypropylmethyl-cellulose). In the controls, laser and applanation with BSS resulted in an average endothelial loss of 18% (n = 5, range of 14-26%). Applanation alone without laser dissection resulted in cell loss of 9% (n = 5, range of 7-12%) using BSS and 9% (n = 6, range 1-42%) Hydroxypropylmethyl-cellulose. CONCLUSIONS: The technique of using a viscoelastic "cushion" to protect endothelial cells from damage during posterior laser dissection prior to transplantation is promising. Viscoelastic coating protects the endothelial layer from damage from the coupling lens better than a layer of BSS. The lasering process, however, causes damage in addition to applanation with the laser lens. Further studies are warranted to optimize reproducibility of endothelial cell survival and evaluate the smoothness of stromal dissections in the posterior cornea.

Effect of glycosaminoglycans and enzymes on the integrity of human placental amnion as a barrier to cell invasion.

The effects of glycosaminoglycans and several enzymes on the integrity of the human placental amnion and the consequent effects on the permeability of this structure to virally transformed cells and their parent line were examined. Treatment of the amnion with hyaluronate, heparin, and chondroitin ABC lyase affected the structure of both the epithelium and the extracellular matrix and resulted in a significant increase in tumor cell invasion, but it had no significant effect on the invasion of the parent cell line. These polymers promoted the disorganization of the epithelial cell layer, and their presence resulted both in the matting of collagen fibrils in the stroma and in the loosening of the basement membrane. Pronase treatment removed epithelial cells and stripped collagen fibrils of granules, but it did not promote tumor or parent cell invasion, perhaps as a result of loss of attachment factors. Chondroitin sulfate did not affect the epithelial structure or the rate of tumor invasion and had only slight effects on the structure of the basement membrane and the stroma. These results are consistent with the thesis that the continuity of epithelium is critical to resisting tumor cell invasion and suggest that glycosaminoglycans, in addition to certain enzymes, can alter this integrity.

Comparison of the effect of Healon, Healon GV, Healon 5, Viscoat, and Ocucoat on platelet aggregation under in vitro conditions.

PURPOSE: To study the effect of Healon, Healon GV, Healon 5, Viscoat, and OcuCoat on platelet aggregation under in vitro conditions. METHODS: Ocular viscoelastic devices including Healon, Healon GV, Healon 5, Viscoat, and OcuCoat were studied to investigate the effect of these agents on platelet aggregation under in vitro conditions. The experiments were performed by using platelet-rich plasma with an aggregometer. Aggregation was induced with three different agonists including 5''-adeno-sinediphosphate (ADP), epinephrine (EPI), and collagen (Col ). The results were obtained as a percentage of maximal aggregation and compared with controls using one-way analysis of variance (ANOVA) test. RESULTS: The tests with ADP as aggregating agent revealed that the percentages of maximal aggregation were a mean of 75 +/- 4.35% for ADP only, 67 +/- 4.35% for Healon, 59.33 +/- 3.51% for Healon GV, 70 +/- 3% for Healon 5, 58 +/- 3.46% for Viscoat, and 64 +/- 2% for OcuCoat. Kruskal-Wallis one-way ANOVA test revealed no significant decrease in the percentage of maximal aggregation for all tested substances. With EPI, aggregation was induced in all control samples with a mean of 80.66 +/- 2.08%. The mean percentage of maximal aggregation was 67 +/- 3% for Healon, 77.66 +/- 4.04% for Healon GV, 77 +/- 4% for Healon 5, 80.6 +/- 4.04% for Viscoat, and 65 +/- 5% for OcuCoat. Statistical analysis showed no significant difference. With collagen, maximum aggregation was 74 +/- 5.29% for controls, 65 +/- 4.35% for Healon, 54 +/- 2% for Healon GV, 51 +/- 2.64% for Healon 5, 59 +/- 2% for Viscoat, and 72.66 +/- 1.52% for OcuCoat. Kruskal -Wallis one-way ANOVA test revealed no significant change in the percentage of maximal aggregation for all tested substances in the experiments. CONCLUSIONS: Ophthalmic viscosurgical devices like Healon, Healon GV, Healon 5, and Viscoat that contain glycosaminoglycans and OcuCoat that contains hydroxypropyl methylcellulose have inhibitory effects on platelet aggregation but the effect is not statistically significant and there is no difference among the ocular viscoelastic devices in regard to inhibitory effect on platelet aggregation.

[Protective effect on the corneal endothelium and remaining effect at the anterior chamber for three different kinds of viscoelastic devices].

PURPOSE: The present study was performed to evaluate the corneal endothelium protection and anterior chamber stagnation abilities of three different types of viscoelastic substances (Healon, Viscoat, HealonV). METHODS: Viscoelastic substances were selected at random for 120 eyes with cataracts, and the postoperative reduction rates of the corneal endothelium cells were compared. The residual viscoelastic substances after filling of the anterior chamber of pig eyes and aspiration with a handpiece were measured by an anterior eye segment image analysis system. The same procedures were performed in rabbit eyes and the residual levels of viscoelastic substances on the corneal endothelium were photographed histologically. RESULTS: The reduction rate of endothelium corneal cells tended to decrease with Viscoat three months after surgery. The results obtained with the anterior eye segment image analysis system showed that the residual level in the anterior chamber was higher with Healon. Histological analyses demonstrated residual Viscoat at the center of the corneal endothelium after perfusion. CONCLUSION: HealonV was superior in terms of spatial retention and Viscoat had corneal endothelium protection potential.

Randomized trial of glucosamine and chondroitin supplementation on inflammation and oxidative stress biomarkers and plasma proteomics profiles in healthy humans.

BACKGROUND: Glucosamine and chondroitin are popular non-vitamin dietary supplements used for osteoarthritis. Long-term use is associated with lower incidence of colorectal and lung cancers and with lower mortality; however, the mechanism underlying these observations is unknown. In vitro and animal studies show that glucosamine and chondroitin inhibit NF-kB, a central mediator of inflammation, but no definitive trials have been done in healthy humans. METHODS: We conducted a randomized, double-blind, placebo-controlled, cross-over study to assess the effects of glucosamine hydrochloride (1500 mg/d) plus chondroitin sulfate (1200 mg/d) for 28 days compared to placebo in 18 (9 men, 9 women) healthy, overweight (body mass index 25.0-32.5 kg/m2) adults, aged 20-55 y. We examined 4 serum inflammatory biomarkers: C-reactive protein (CRP), interleukin 6, and soluble tumor necrosis factor receptors I and II; a urinary inflammation biomarker: prostaglandin E2-metabolite; and a urinary oxidative stress biomarker: F2-isoprostane. Plasma proteomics on an antibody array was performed to explore other pathways modulated by glucosamine and chondroitin. RESULTS: Serum CRP concentrations were 23% lower after glucosamine and chondroitin compared to placebo (P = 0.048). There were no significant differences in other biomarkers. In the proteomics analyses, several pathways were significantly different between the interventions after Bonferroni correction, the most significant being a reduction in the "cytokine activity" pathway (P = 2.6 x 10-16), after glucosamine and chondroitin compared to placebo. CONCLUSION: Glucosamine and chondroitin supplementation may lower systemic inflammation and alter other pathways in healthy, overweight individuals. This study adds evidence for potential mechanisms supporting epidemiologic findings that glucosamine and chondroitin are associated with reduced risk of lung and colorectal cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT01682694.