High Levels Of Hyaluronic Acid Research Articles

Hyaluronic Acid is Associated with Severity and Prognosis in Patients with Community-Acquired Pneumonia.

Hyaluronic acid (HA) is a novel inflammatory biomarker with a prognostic value for several infectious diseases. This study investigated the association of HA with severity and prognosis in hospitalized patients with community-acquired pneumonia (CAP). We analyzed the differences of HA levels in different groups. Logistic regression analysis was performed to identify independent risk factors for severe CAP (SCAP). The predictive value of HA for SCAP was assessed using receiver operating characteristic (ROC) curves. Kaplan-Meier survival analysis was used to compare 30-day mortality between the high and low HA groups. Compared to healthy controls (49.2 ± 15.3 ng/mL), patients with CAP exhibited significantly elevated levels of HA (P < 0.001). In CAP patients, increased HA levels were more pronounced in those with SCAP (SCAP vs non-SCAP:135.6 ± 51 ng/mL vs 100.7 ± 47.8 ng/mL, P < 0.001). Compared to survivors (109.9 ± 48.7 ng/mL), HA levels in non-survivors were significantly higher (180.9 ± 67.8 ng/mL) (P < 0.001). HA was an independent predictor of SCAP [odds ratio (OR): 1.013, 95% confidence interval (CI): 1.003-1.022, P = 0.011] with high diagnostic accuracy [areas under the curve (AUC): 0.709, 95% CI: 0.622-0.797, P = 0.001]. Additionally, HA was independently associated with death risk in patients with CAP (OR: 1.022, 95% CI: 1.005-1.039, P = 0.010). Kaplan-Meier survival curves indicated that CAP patients in the high HA group exhibit a higher 30-day mortality rate compared to those in the low HA group (8.6% vs 1.5%, P = 0.008). Post hoc analysis indicated that our study possessed 98.857% statistical power. In conclusion, High HA levels are associated with severity and mortality in patients with CAP, and HA could serve as a novel serum biomarker to predict the risk of CAP progression.

Clinical validation of preoperative serum markers for liver fibrosis in living donor liver transplantation recipients.

To validate the reliability of fibrosis markers as predictors of graft survival in living donor liver transplantation (LDLT) recipients. We reviewed data retrospectively, from 163 patients who underwent adult LDLT with preoperative measurements of type IV collagen (CIV), Mac-2 binding protein glycosylation isomer (M2BPGi), and hyaluronic acid (HA). Patients were divided into high and low groups for each biomarker, based on optimal cutoff values, and graft loss within 6months was evaluated in each group. The high CIV level group showed significantly lower 6-month graft survival rates and significantly higher rates of postoperative sepsis and sepsis from pneumonia. However, the groups with high and low M2BPGi levels and those with high and low HA levels did not show significant differences in 6-month graft survival rates or rates of postoperative sepsis. Multivariate analysis revealed that a CIV level ≥ 590 was a significant predictor of graft loss within 6months, postoperative sepsis, and sepsis from pneumonia. Unlike other fibrosis markers, preoperative CIV levels can predict graft survival, postoperative sepsis, and sepsis from pneumonia after LDLT.

Elevated hyaluronic acid levels in severe SARS-CoV-2 infection in the post-COVID-19 era.

Human identical sequences of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) promoted the coronavirus disease 2019 (COVID-19) progression by upregulating hyaluronic acid (HA) via NamiRNA-enhancer network, based on previous experimental research. This study aimed to investigate the predictive value of HA for the severity of SARS-CoV-2 infection in the post-COVID-19 era. A total of 217 consecutive patients with COVID-19 were enrolled at Beijing Ditan Hospital between July 2023 and October 2023. HA levels were analyzed using biochemical detector. Logistic regression analysis was used to screen independent factors for severe COVID-19. The predictive performance of HA for severe infection was assessed by ROC curve. Furthermore, the relationship between HA levels and COVID-19 severity was investigated using multivariate logistic regression models after adjustment for potential confounders. According to the cut-off value of HA, COVID-19 patients were divided into HA < 90 ng/mL group (80 cases) and HA ≥ 90 ng/mL group (137 cases). High HA levels were positively associated with the severe SARS-CoV-2 infection, including elevated inflammatory indicators, severe lung involvement, prolonged clinical course, and higher incidence of respiratory failure and death (P < 0.05). Logistic regression analysis suggested that HA was an independent predictor of severe COVID-19 (OR = 4.540, 95% CI = 2.105-9.790, P < 0.001). ROC curve analysis showed that the AUC of HA for severe infection was 0.724. HA levels were significantly higher in COVID-19 cases compared to the healthy population (123.9 (82.6, 174.1) vs. 50.5 (37.8, 66.8), P < 0.001), but similar to those with non-SARS-CoV-2 lung infection (121.6 (78.5, 175.6) vs. 106.0 (66.5, 149.7), P = 0.244). We also found that the first COVID-19 infections had higher HA levels (118.8 (79.5, 174.3) vs. 85.0 (61.1, 128.8), P < 0.001) and a higher proportion of severe infection (37.1% vs. 21.3%, P = 0.043) than re-infections. However, HA expression failed to fully return to normal levels with infection recovery (204.7 (152.9, 242.2) vs. 97.0 (69.3, 137.3), P < 0.001). HA was associated with severe SARS-CoV-2 infection and could be used as a novel serum biomarker to predict the risk of COVID-19 progression in the post-COVID-19 era.

Clinical and prognostic implications of hyaluronic acid in patients with COVID-19 reinfection and first infection.

Previous research has shown that human identical sequences of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) promote coronavirus disease 2019 (COVID-19) progression by upregulating hyaluronic acid (HA). However, the association of HA with mortality and long COVID in SARS-CoV-2 reinfection and first infection is unclear. Patients with COVID-19 at Beijing Ditan Hospital from September 2023 to November 2023 were consecutively enrolled. SARS-CoV-2 reinfections were matched 1:2 with first infections using a nearest neighbor propensity score matching algorithm. We compared the hospital outcomes between patients with COVID-19 reinfection and first infection. The association between HA levels and mortality and long COVID in the matched cohort was analyzed. The reinfection rate among COVID-19 hospitalized patients was 25.4% (62 cases). After propensity score matching, we found that reinfection was associated with a better clinical course and prognosis, including lower levels of C-reactive protein and erythrocyte sedimentation rate, fewer cases of bilateral lung infiltration and respiratory failure, and shorter viral clearance time and duration of symptoms (p < 0.05). HA levels were significantly higher in patients with primary infection [128.0 (90.5, 185.0) vs. 94.5 (62.0, 167.3), p = 0.008], those with prolonged viral clearance time [90.5 (61.5, 130.8) vs. 130.0 (95.0, 188.0), p < 0.001], and deceased patients [105.5 (76.8, 164.5) vs. 188.0 (118.0, 208.0), p = 0.002]. Further analysis showed that HA was an independent predictor of death (AUC: 0.789), and the risk of death increased by 4.435 times (OR = 5.435, 95% CI = 1.205-24.510, p = 0.028) in patients with high HA levels. We found that patients with HA levels above 116 ng/mL had an increased risk of death. However, the incidence of long COVID was similar in the different HA level groups (p > 0.05). Serum HA may serve as a novel biomarker for predicting COVID-19 mortality in patients with SARS-CoV-2 reinfection and first infection. However, HA levels may not be associated with long COVID.

Abstract 212: Association of Glycocalyx Shedding and Outcomes in Patients After Cardiac Arrest: A Prospective Observational Study

Background: The glycocalyx sheds early after cardiac arrest (CA). However, the potential value of elevated serum glycocalyx components remains unknown. Methods: This prospective observational study included patients who suffered CA and survived over 24 hours in the ICU of the Affiliated Hospital of Xuzhou Medical University from September 2021 to October 2022. Serum samples were collected 24 hours post CA to assess the concentration of glycocalyx shedding, including Heparan Sulfate (HS), Hyaluronic Acid (HA) and Syndecan-1 (Sdc-1). Patients were followed for 30 days or until death after CA. Outcome measures were 30-day Cerebral Performance Categories scale (CPC≤2, good function group; CPC&gt;2, poor function group), and 30-day mortality. Logistic regression was used to assess the association of glycocalyx shedding with the 30-day CPC scale. COX regression was used to assess the association of glycocalyx shedding with 30-day mortality. Results: we included 71 patients. Compared with good function group (n=22), poor function group (n=49) had significantly higher levels of HS. Adjusted logistic regression showed that the high level of HS was associated with poor functional outcome (Figure1A, OR=0.41, 95% CI=0.21-0.79, p&lt;0.01). Compared with the survival group (n=39), non-survival group (n=32) had higher levels of HA. Adjusted Cox regression indicated that high levels of HA was associated with mortality (Figure1B,Figure2, HA: HR=1.69,95%, CI=1.13-2.56, p&lt;0.05). Conclusions: Elevated serum HS levels in the early stages post-CA have an association with poor functional outcomes. Increased levels of serum HA post-CA are associated with a higher 30-day mortality.

Occult Hepatitis B Virus Infection and Liver Fibrosis in Chinese Patients.

The impact of hepatitis B surface antigen (HBsAg)-negative/hepatitis B virus (HBV) DNA-positive occult HBV infection (OBI) on the severity of liver fibrosis remains unclear. A total of 1772 patients negative for HBsAg but positive for antibody to hepatitis B core antigen (HBcAg), stratified by the presence or absence of OBI, were selected for long-term carriage leading to elevation of ≥2 of 4 liver fibrosis indexes-hyaluronic acid (HA), laminin, type III procollagen peptide (PCIII), and type IV collagen (CIV)-at testing in a Chinese hospital. Patients were tested for serum viral load, HBV markers, and histopathological changes in liver biopsy specimens. OBI was identified in 148 patients with liver fibrosis (8.4%), who had significantly higher levels of HA, laminin, PCIII, and CIV than 1624 fibrotic patients without OBI (P < .05). In 36 patients with OBI who underwent liver biopsy, significant correlations were observed between OBI viral load and serum HA levels (P = .01), PCIII levels (P = .01), and pathological histological activity index (HAI) scores (P < .001), respectively; HAI scores and PCIII levels (P = .04); HBcAg immunohistochemical scores and HA levels (P < .001); and HBcAg immunohistochemical scores and PCIII levels (P = .03). Positive fluorescent in situ hybridization results were significantly more frequent in patients with OBIs (80.6% vs 37.5% in those without OBIs). Among patients with OBIs, HBcAg was detected in the liver tissue in 52.8% and HBsAg in 5.6%. OBI status appears to be associated with liver fibrosis severity.

Role of Hyaluronic Acid in Selected Malignant Neoplasms in Women

Hyaluronic acid (HA) is a significant glycosaminoglycan component of the extracellular matrix, playing an essential role in cell localization and proliferation. However, high levels of HA may also correlate with multidrug resistance of tumor cells, an increased tendency to metastasize, or cancer progression, and thus represent a very unfavorable prognosis for cancer patients. The purpose of this review article is to summarize the results of studies describing the relationship between HA, the main ligand of the CD44 receptor, or other components of the HA signaling pathway. In addition, we review the course of selected female malignancies, i.e., breast, cervical, endometrial, and ovarian cancer, with the main focus on the mechanisms oriented to CD44. We also analyze reports on the beneficial use of HA-containing preparations in adjuvant therapy among patients with these types of cancer. Data from the literature suggest that HA and its family members may be critical prognostic biomarkers of selected malignancies among women. Nevertheless, the results of the available studies are inconclusive, and the actual clinical significance of HA expression analysis is still quite enigmatic. In our opinion, the HA-CD44 signaling pathway should be an attractive target for future research related to targeted therapy in gynecological cancers.

Hyaluronic acid skin penetration evaluated by tape stripping using ELISA kit assay

Hyaluronic Acid (HA) is an endogenous skin matrix component with moisturizing and anti-inflammatory and healing properties. Cosmetic formulations containing HA aim to enhance skin structure, hydrate skin and reduce wrinkles. Therefore, the skin diffusion of HA into stratum corneum after application of a formulation containing two different size of HA, High Molecular weight (HMW-HA) and Low Molecular Weight (LMW-HA)) was evaluated. Ex vivo human skin samples were used to validate an ELISA assay measuring HA in the stratum corneum (SC), viable epidermis and dermis, and to identify optimal washing and extraction methods. These methods were used to measure HA levels in the SC of subjects before and after daily topical application of an HA-containing formulation for 7 days. Samples of SC (5 tape strips) were taken before and 2 h after the application on D0, D1 and D7. The ELISA assay was suitable for measuring HA in the SC but not epidermal or dermal layers. The upper and lower limits of quantitation were the same for both sizes of HA (200 and 3.1 ng/ml, respectively). In both ex vivo human skin and human volunteers, the “dry method” of removing the formulation led to much higher levels of HA in the SC samples, whereas the “wet method” involving one cotton swab soaked with an aqueous solution containing 10% soap and a second cotton swab for drying, was effective in removing the formulation and more relevant to simulate washing/showering. In the clinical study, the amount of HA in SC layers 3–5 were used to represent the HA level in the SC, whereas layers 1 and 2 were considered as surface “residual film”. After each application, there was a significantly higher amount of HA compared to the amount before application, which was observed using both wash methods. The residual level 24 h after the first application was at least 8 times higher than before the first application and at least 31 times higher after 7 applications. In conclusion, these investigations validated the use of the ELISA method for the measurement of HA in SC samples. The ex vivo experiments provided recommendations for the clinical study, including the preferred cleansing and optimal sampling methods. The clinical study demonstrated the diffusion, accumulation and maintenance of HA levels in the SC after repeated application of the formulation containing HMW-HA and LMW-HA.

Seventy Hyal 2000: review of a new skinbooster treatment and case study

Within the aesthetics sector, the popularity of skinboosters is increasing, with the benefits of hyaluronic acid, particularly its hydrating effect, being sought after among patients who are looking for improved skin complexion. Seventy Hyal 2000 is a new skinbooster in the market that is particularly promising due to high levels of hyaluronic acid (30 mg/2 ml) and its high-molecular weight when compared to other products. This article will aim to outline the mechanism of action and review the evidence base behind skinboosters, before looking more specifically at Seventy Hyal 2000. This will include a review of the treatment protocols used thus far in the four UK clinics trialling the product, as well as feedback from treatments performed and an overview of a case study from one of the aforementioned clinics.

Ortho Isomeric Mn(III) N-Alkyl- and Alkoxyalkylpyridylporphyrins-Enhancers of Hyaluronan Degradation Induced by Ascorbate and Cupric Ions.

High levels of hyaluronic acid (HA) in tumors correlate with poor outcomes with several types of cancers due to HA-driven support of adhesion, migration and proliferation of cells. In this study we explored how to enhance the degradation of HA into low-molecular fragments, which cannot prevent the immune system to fight tumor proliferation and metastases. The physiological solution of HA was exposed to oxidative degradation by ascorbate and cupric ions in the presence of either one of three ortho isomeric Mn(III) substituted N-alkyl- and alkoxyalkylpyridylporphyrins or para isomeric Mn(III) N-methylpyridyl analog, commonly known as mimics of superoxide dismutase. The changes in hyaluronan degradation kinetics by four Mn(III) porphyrins were monitored by measuring the alteration in the dynamic viscosity of the HA solution. The ortho compounds MnTE-2-PyP5+ (BMX-010, AEOL10113), MnTnBuOE-2-PyP5+ (BMX-001) and MnTnHex-2-PyP5+ are able to redox cycle with ascorbate whereby producing H2O2 which is subsequently coupled with Cu(I) to produce the •OH radical essential for HA degradation. Conversely, with the para analog, MnTM-4-PyP5+, no catalysis of HA degradation was demonstrated, due to its inertness towards redox cycling with ascorbate. The impact of different Mn(III)-porphyrins on the HA decay was further clarified by electron paramagnetic resonance spectrometry. The ability to catalyze the degradation of HA in a biological milieu, in the presence of cupric ions and ascorbate under the conditions of high tumor oxidative stress provides further insight into the anticancer potential of redox-active ortho isomeric Mn(III) porphyrins.

Correlation analysis of the prognostic value of serum hyaluronic acid for breast cancer patients

Objective: To explore the correlation between preoperative serum hyaluronic acid (HA) level and prognosis of breast cancer patients. Methods: The 98 patients with breast cancer who underwent surgical treatment in the Oncology Department of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from January 2004 to November 2014 in a historical cohort were included, aged (52.5±9.4) years.The preoperative serum HA contents of the patients were detected. According to the median of 53.7 μg/L, the patients were divided into high and low groups with 49 patients in each group.The χ2 test was used to analyze the correlation between the serum HA content and the general clinical data of the patients, and the Kaplan-Meier method, Log-rank test and multivariate Cox regression model wereusedto analyze the correlation between HA content and patients' survival. Results: The percentages of patients with high HA levels in menopause and non-menopause patientswere 55.7% and 40.5%, respectively; in progesterone receptor (PR) positive and negative patients were 54.1% and 43.2%, respectively; in estrogen receptor (ER) positive and negative patients were 45.7% and 60.7%, respectively; in Ki-67 positive and negative patients were 55.6% and 43.2%, respectively; in the tumor size stage TⅠ, TⅡ, TⅢ, and TⅣ patients were 50.0%, 41.7%, 72.7%, and 1/1, respectively; in lymph node metastasis and non-metastasispatients were 45.7% and 53.8%, respectively. There was no significant correlation between the level of HA and the menopausal status, the expressions of PR, ER and Ki-67, tumor size, and lymph node metastasis in breast cancer patients (χ²=2.128, 1.086, 1.800, 1.485, 4.273, 0.656, P>0.05). Patients with high HA levels accounted for 30.9% of patients aged 52 years or less and 74.4% of patients older than 52 years (χ²=18.274, P=0.000); 43.4% of patients with early TNM and 72.7% of patients with advanced TNM (χ²=5.861, P=0.015); 45.2% of patients without distant metastasis and 78.6% of patients with distant metastasis (χ²=5.333, P=0.023); 38.1% of Her-2 negative patients and 58.9% of Her-2 positive patients(χ²=4.167, P=0.041); and the median survival of patients with high HA levels was 70 months, which was shorter than 83 months for patients with low HA levels (χ²=6.799, P=0.007). Therefore, ahigh HA content predicts an older age, a later tumor stage, higher risk of distant metastasis, positive expression of Her-2 and shorter survival. Multivariate Cox regression model analysis suggested that high levels of serum HA may be a risk factor for patients' survival, with HR (95%CI) value of 9.98 (1.16-85.88) and P value of 0.036. Conclusion: The high level of preoperative serum HA has a certain correlation with the poor prognosis of breast cancer patients.

Enhanced hyluronic acid production in Streptococcus zooepidemicus by over expressing HasA and molecular weight control with Niscin and glucose

Hyaluronic acid (HA) is a high molecular weight linear polysaccharide, endowed with unique physiological and biological properties. Given its unique properties, HA have unprecedented applications in the fields of medicine and cosmetics. The ever growing demand for HA production is the driving force behind the need for finding and developing novel and amenable sources of the HA producers. Microbial fermentation of Streptococcus zooepidemicus deemed as one the most expeditious and pervasive methods of HA production. Herein, a wild type Streptococcus zooepidemicus, intrinsically expressing high levels of HA, was selected and optimized for HA production. HasA gene was amplified and introduced into the wild type Streptococcus zooepidemicus, under the control of Nisin promoter. The HasA over-expression increased the HA production, while the molecular weight was decreased. In order to compensate for molecular weight loss, the glucose concentration was increased to an optimum amount of 90g/L. It is hypostatizes that excess glucose would rectify the distribution of the monomers and each HasA molecule would be provided with sufficient amount of substrates to lengthen the HA molecules. Arriving at an improved strain and optimized cultivating condition would pave the way for industrial grade HA production with high quality and quantity.

Pretransplant Serum Hyaluronic Acid Can Be a Biomarker as a Prognostic Predictor in Adult-to-Adult Living Donor Liver Transplantation

ObjectiveThe goal of this study was to evaluate whether pretransplant serum hyaluronic acid (HA) levels can predict outcomes after adult-to-adult living donor liver transplantation (LDLT). MethodsIn study I, 21 patients who underwent LDLT (March 2002-February 2004) were divided into 2 groups: the H-I group (HA ≥500 ng/mL; n = 12) and the L-I group (HA <500 ng/mL; n = 9). The influence of pretransplantation HA levels on short-term surgical outcome was investigated. In study II, 77 LDLT patients (May 2004-December 2014) were also divided into 2 groups: the H-II group (HA ≥500 ng/mL; n = 40) and the L-II group (HA <500 ng/mL; n = 37). We compared long-term survival and investigated prognostic factors. ResultsIn study I, HA levels significantly decreased after LDLT, and those in the H-I group were significantly higher compared with the L-I group at 1, 3, 5, and 7 days after LDLT. There were significant differences in postoperative peak total bilirubin levels (H-I vs L-I, 17.2 vs 6.2 mg/dL; P = .013), peak ascitic fluid volume (1327 vs 697 mL/d; P = .005), and the hepatocyte growth factor levels at 3 days after LDLT (1879 vs 1092 pg/mL; P = .03). In study II, the 1- and 5-year survival rates were significantly lower in the H-II group than in the L-II group (H-II vs L-II, 65.0% and 48.5% vs 86.5% and 80.8%; P = .004). In multivariate analysis, significant prognostic factors were preoperative HA ≥500 ng/mL (P = .004) and graft to recipient body weight ratio <0.8 (P = .042). ConclusionsPreoperative HA level can be a prognostic risk factor. Patients with high HA levels are vulnerable and should be carefully managed after LDLT.

Highly efficient production of hyaluronic acid by Streptococcus zooepidemicus R42 derived from heterologous expression of bacterial haemoglobin and mutant selection.

During Streptococcus zooepidemicus fermentation, most carbon sources are used to synthesize lactic acid, which can inhibit strain growth and hyaluronic acid production. Here, we expressed bacterial haemoglobin (Vhb) in Strep.zooepidemicus. Due to highly efficient oxygen use, only 15·26gl(-1) lactic acid was produced, which is 0·73 times the quantity produced by the control strain. Compared with the control strain (1·61gl(-1) ), hyaluronic acid (HA) production in this strain did not substantially increase, only to 2·16gl(-1) . Next, we used a series of N-methyl-N'-nitro-N-nitroso-guanidine (NTG) treatments and selection programmes. Finally, we generated a hyaluronidase-negative and rifampin-resistant mutant strain that produces high levels of HA. The optimum carbon concentration for maximum hyaluronic acid production is only 30gl(-1) of sucrose, which is lower than the control strain (60gl(-1) ). The oxygen transfer rate coefficient KL a increased significantly to 372±53h(-1) from 18±4h(-1) of the control. The optimum carbon source for this strain is 21gl(-1) of sucrose, 9gl(-1) of maltose and 5gl(-1) of glutamic acid. Hyaluronic acid accumulated at 6·7gl(-1) in the culture broth. However, the molecular weight of HA decreased from 1835KDa (Control) to 429kDa. The prepared low-molecular weight HA could function as potential antiangiogenic substances, antiviral and antitumour agents to possibly be used as functional food ingredients. Hyaluronic acid (HA) has been used for a wide range of applications in health, cosmetic and clinical fields. During fermentation of Streptococcus to produce HA, 80-85% of the carbon source is used to produce lactic acid and acetic acid, and only approx. 5 and 10% of the carbon source is used to produce HA and biomass respectively. Here, we expressed bacteria haemoglobin (Vhb) in Streptococcus zooepidemicus, which can dramatically inhibit lactic acid production. After NTG treatments and selection programmes, we identified a mutant strain with highly efficient hyaluronic acid production (6·7gl(-1) ) under economic fermentation conditions.

Increased incidence of antiretroviral drug discontinuation among patients with viremic hepatitis C virus coinfection and high hyaluronic acid, a marker of liver fibrosis

Most antiretroviral drugs are metabolized by the liver; hepatic disease or liver damage as a result of hepatitis C virus (HCV) could impair this metabolism leading to an increased risk of drug toxicity. This study aimed to determine the risk of antiretroviral drug discontinuation among HCV/HIV coinfected patients. EuroSIDA patients taking combination antiretroviral therapy were included. Poisson regression identified factors associated with antiretroviral treatment discontinuation. A total of 9535 HIV-positive patients with known HCV status were included (6939 HCVAb-negative; 2596 HCVAb-positive at baseline). Viremic HCV infection was associated with a 44% increased risk of antiretroviral drug discontinuation compared with aviremic infection [adjusted incidence rate ratio, aIRR: 1.44 (95% confidence interval, CI 1.22-1.69)]; this relationship was largest among nonnucleoside reverse transcriptase inhibitors [aIRR: 1.59 (95% CI 1.18-2.14)]. In the subset of 935 HIV-positive patients also HCV-positive or HBV-positive with plasma hyaluronic acid measured, hyaluronic acid more than 100 ng/ml was associated with a 37% increased risk of antiretroviral drug discontinuation [aIRR: 1.37 (95% CI 1.08-1.73) vs. hyaluronic acid ≤100 ng/ml] and the effect of HCV viremia became nonsignificant; the largest drug association was seen for protease inhibitors [aIRR: 1.40 (95% CI 1.04-1.89)]. HCV viremia and high levels of hyaluronic acid predict antiretroviral drug discontinuation. Evidence was also found to suggest a link between impaired liver function and protease inhibitor toxicity.

Age effects on extracellular matrix production of vocal fold scar fibroblasts in rats

Vocal fold (VF) fibroblasts are the central subject of interest in fibrogenesis and wound healing after VF injury. Scar fibroblasts (SF) exhibit an aberrant production of several extracellular matrix (ECM) components which lead either to VF fibrosis or scarless wound healing. This study aimed to investigate the role of age at the time of injury on ECM production of SF. This is designed as an animal study. VF injury was established unilaterally in eight male Sprague-Dawley rats [3 months of age (n = 4), 11 months of age (n = 4)], while the other side was left intact. Three months after injury the larynges were excised and fibroblasts were extracted from VF [normal fibroblasts (NF)–scar fibroblasts (SF)] and cultured in vitro. After first passage, VF fibroblasts were plated in 24-well plates and levels of hyaluronic acid (HA) and collagen type I were determined enzymatically from supernatant after 24 and 72 h. Cultured SF from younger animals produced significantly higher levels of HA compared to NF fibroblasts from the same animals. HA concentrations of the older animals did not differ significantly between the NF and SF cultures, but the range in SF cultures was large. In contrast to previous studies, we found that even 3 months after VF injury cultured SF from young animals expressed higher levels of HA in comparison to SF from older animals. No difference in collagen levels were observed between the younger and older animals. Age of animals is an essential factor during VF healing and has to be considered for study design.

Acceleration of Wound Healing with Stem Cell–Derived Growth Factors

Recently, it has been revealed that bone marrow-derived mesenchymal stem cells (MSCs) accelerate the healing of skin wounds. Although the proliferative capacity of MSCs decreases with age, MSCs secrete many growth factors. The present study examined the effect of mesenchymal stem cell-conditioned medium (MSC-CM) on wound healing. The wound-healing process was observed macroscopically and histologically using an excisional wound-splinting mouse model, and the expression level of hyaluronic acid related to the wound healing process was observed to evaluate the wound-healing effects of MSC, MSC-CM, and control (phosphate-buffered saline). The MSC and MSC-CM treatments accelerated wound healing versus the control group. At 7 days after administration, epithelialization was accelerated, thick connective tissue had formed in the skin defect area, and the wound area was reduced in the MSC and MSC-CM groups versus the control group. At 14 days, infiltration of inflammatory cells was decreased versus 7 days, and the wounds were closed in the MSC and MSC-CM groups, while a portion of epithelium was observed in the control group. At 7 and 14 days, the MSC and MSC-CM groups expressed significantly higher levels of hyaluronic acid versus the control group (P < .05). The expression level of hyaluronic acid was lower at 14 days than at 7 days in all three groups. Both the MSC and MSC-CM groups accelerated wound healing versus the control group to a similar degree. Accordingly, it is suggested that the MSC-CM contains growth factor derived from stem cells, is able to accelerate wound healing as well as stem cell transplantation, and may become a new therapeutic method for wound healing in the future.

Correlation between an absence of cervical gland area on transvaginal sonography and cervical mucus hyaluronic acid levels in women with threatened preterm delivery

Transvaginal sonographic findings of an absent cervical gland area (CGA) and a short cervical length (CL) are frequently observed in patients with threatened preterm delivery. The present study aimed to clarify whether sonographic findings are due to active production of hyaluronic acid (HA)in the cervix. Possible relationships between sonographic findings of the presence or absence of the CGA and/or a short CL and cervical mucus HA concentration were investigated in 68 women with threatened preterm delivery at 22 – 31 weeks’ gestation and 136 women without threatened preterm delivery as controls. HA levels were higher in women with threatened preterm delivery (68.0 ng/mL) than in controls (39.0 ng/mL; P = 0.001). Similarly, HA levels were higher in women with preterm labor showing an absent CGA and a short CL than in women with threatened preterm delivery without such findings (P < 0.01). Stepwise multivariate logistic regression identified an absent CGA and threatened preterm delivery as independent predictors of high HA levels (P = 0.04). HA concentration was not predictive for preterm delivery. A sonographic finding of an absent CGA reflects high HA levels in the cervix with threatened preterm delivery.

P06 Role of serum hyaluronic acid in predicting mortality in patients with chronic liver disease

IntroductionCurrently liver biopsies are used to assess extent of liver fibrosis and provide prognostic information in liver disease. Hyaluronic acid (HA) is a non-invasive serum marker that has been shown...

Impaired antigen presentation and potent phagocytic activity identifying tumor-tolerant human monocytes: demonstration in isolated cells from Mature B-cell neoplasms. (66.47)

Abstract Monocyte exposure to tumor cells induces a transient state in which these cells are refractory to further exposition to cancer. This phenomenon, termed “tumor tolerance”, is characterized by a decreased production of proinflammatory cytokines in response to tumors. We have established a human model of tumor tolerance and have observed a marked downregulation of MHCII molecules as well as the MHCII master regulator, CIITA. These cells combine an impaired capability for antigen presentation, with potent phagocytic activity and exhibit an M2-like phenotype. We also show that circulating monocytes, isolated from patients who suffer from mature B-cell neoplasm, share all the determinants that characterize cells locked in a tumor tolerance state. In addition, lymphocytes from these patients and supernatants from their in vitro culture, induced a tumor tolerance state in control monocytes. Finally, our results indicated that both, serum from mature B-cell neoplasm patients and supernatants from tumor cells exhibit high levels of Hyaluronic Acid in contrast to control serum from healthy voluteers. Hyaluronic Acid was able to induce a tumor tolerance phenotype in human naïve monocytes.