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 0.1 ml/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.     

Viscosupplementation in the olderpatient with osteoarthritis

Osteoarthritis of the knee is the leading cause of disability in the elderly. This localized, painful condition is oftenaccompanied by decreased elastoviscosity of the intraarticular synovial fluid due to decreased hyaluronan molecular weight and/or concentration. Viscosupplementation attempts to restore viscoelastic homeostasis to the arthritic joint to reduce pain and restore function. Recently, two low-molecular weight (MW) hyaluronans and one cross-linked high-MW hyaluronan(hylan) have been approved for the intraarticular treatment of this disease in the United States. Five weekly intraarticular injections are recommended for both low-MW hyaluronans. They have been proven effective in reducing knee pain in mild to moderate disease, equivalent to NSAIDS. They are as effective as corticosteroids, are of slower onset, and have longer duration of effect. Three weekly injections are recommended for the hylan product. It has been proven effective in mild to advanced disease and is as or more effective than NSAIDS and more effective than corticosteroids. Definitive comparative studies of these products have not been published. Viscosupplementation has been shown to be very safe. Local transient knee pain and/or swelling (2–4%) per injection, without long-term sequelae have been the only significant adverse events No systemic effects, viral transmission, drug interaction, or mortality have been associated with this treatment. It is recommended that viscosupplementation be considered after the failure of exercise and local or systemic analgesic treatment in the elderly osteoarthritic knee, particularly when gastrointestinal, renal, or cardiovascular comorbidities or drug interactions may exist.     

Schistosoma mansoni infection in a recently exposed community in Senegal: lack of correlation between liver morphology in ultrasound and connective tissue metabolites in serum

Summary Four hundred and seventy villagers of Ndombo, a village with recently established intensive transmission of Schistosoma mansoni in the Senegal River Basin, were enrolled in a study with the intention to assess hepatosplenic morbidity. All patients were examined parasitologically and by ultrasound. Hepatic fibrosis serum markers were determined in 153 adult patients (aminoterminal propeptide of procollagen type III, hyaluronan and laminin). By ultrasound, about 60% of the patients showed early stages of hepatic involvement, 3% of the patients unequivocally showed severe hepatosplenic pathology (grade 3 according to the Managil classification), whereas in another study performed in the same village 3 years earlier, no patients with severe hepatosplenic pathology had been found. No correlation between the aminoterminal propeptide of procollagen type III, hyaluronan or laminin and the ultrasound findings could be established. These hepatic fibrosis serum markers do not seem to be a sensitive method to detect early hepatic fibrosis in schistosomiasis.     

Sperm binding to hyaluronan is an excellent predictor of Nili-Ravi buffalo bull fertility

This study reports the first evaluation of sperm hyaluronan binding assay (HBA) for predicting the fertility of Nili-Ravi buffalo bulls in relation to standard parameters of sperm quality. Cryopreserved semen doses of low (n = 6), medium (n = 3) and high fertility (n = 8) bulls based on their respective return rates were used. Significantly, more spermatozoa bound to hyaluronan from the most fertile bulls (57.15% ± 1.44) compared with medium (42.46% ± 1.08) and low fertility bulls (29.70% ± 0.78). A strongly positive correlation (r = .824, p < .01) was found between HBA and fertility that predicts a 67.9% variability (r² = .679, p < .01) in fertility. HBA was also strongly positively correlated with sperm viability (r = .679, p < .01) followed by their live/dead ratio (r = .637, p < .01), uncapacitated spermatozoa (r = .631, p < .01), normal apical ridge (r = .459, p < .01), motility (r = .434, p < .01), mature spermatozoa with low residual histones (r = .364, p < .01), high plasma membrane integrity (r = .316, p < .01) and nonfragmented DNA levels (r = .236, p < .05). It was negatively correlated with spermatozoa having reacted acrosome (r = −.654, p < .01). A fertility model built using a combination of sperm HBA and either sperm livability or viability predicts, respectively, 86.1% (r² = .861, p < .01) and 85.9% (r² = .859, p < .01) variability in buffalo bull fertility. In conclusion, sperm HBA may prove to be a single robust predictor of Nili-Ravi buffalo bull fertility.     

过氧化氢氧化降解法制备低分子玻璃酸

目的制备低分子玻璃酸 (HA)。方法过氧化氢氧化降解法。结果随着过氧化氢浓度增加 ,反应温度的升高 ,降解速率加快。中性条件下HA的氧化降解速率较快 ,而酸性或碱性时却较慢。为了方便降解过程的可控性 ,过氧化氢浓度选 0 .0 5 % ,反应温度定为 5 0℃ ,反应pH为中性。随着HA相对分子质量的降低 ,运动黏度迅速下降 ,而糖醛酸含量基本不变。不同过氧化氢浓度降解时 ,低分子HA收率基本相同。结论过氧化氢氧化降解法可用于制备低分子HA。     

Brief overview of selected approaches in targeting pancreatic adenocarcinoma

Introduction: Pancreatic adenocarcinoma (PDAC) has the worst prognosis of any major malignancy, with 5-year survival painfully inadequate at under 5%. Investigators have struggled to target and exploit PDAC unique biology, failing to bring meaningful results from bench to bedside. Nonetheless, in recent years, several promising targets have emerged.

Areas covered: This review will discuss novel drug approaches in development for use in PDAC. The authors examine the continued efforts to target Kirsten rat sarcoma viral oncogene homolog (KRas), which have recently been successfully abated using novel small interfering RNA (siRNA) eluting devices. The authors also discuss other targets relevant to PDAC including those downstream of mutated KRas, such as MAPK kinase and phosphatidylinositol 3-kinase.

Expert opinion: Although studies into novel biomarkers and advanced imaging have highlighted the potential new avenues toward discovering localized tumors earlier, the current therapeutic options highlight the fact that PDAC is a highly metastatic and chemoresistant cancer that often must be fought with virulent, systemic therapies. Several newer approaches, including siRNA targeting of mutated KRas and enzymatic depletion of hyaluronan with PEGylated hyaluronidase are particularly exciting given their early stage results. Further research should help in elucidating their potential impact as therapeutic options.     

Altered expression of hyaluronan synthase and hyaluronidase mRNA may affect hyaluronic acid distribution in keloid disease compared with normal skin

Keloid disease (KD) is a fibroproliferative disorder characterised partly by an altered extracellular matrix (ECM) profile. In fetal scarring, hyaluronic acid (HA) expression is increased, but is reduced in KD tissue compared with normal skin (NS). The expression of Hyaluronan Synthase (HAS) and hyaluronidase (HYAL) in KD and NS tissue were investigated for the first time using a range of techniques. Hyaluronan synthase and HYAL mRNA expression were significantly increased in NS tissue compared with KD tissue (P < 0.05). Immunohistological analysis of tissue indicated an accumulation of HAS and HYAL protein expression in KD compared with NS due to the thicker epidermis. No differences were observed in mRNA or protein expression in KD and NS fibroblasts. Reduced expression of HAS and HYAL may alter HA synthesis, degradation and accumulation in KD. Better understanding of the role of HA in KD may lead to novel therapeutic approaches to address the resulting ECM imbalance.     

Cross-linked hyaluronan versus collagen for injection treatment of glottal insufficiency: 2-year follow-up

Objectives—To evaluate the long-term (24 months) clinical performance (vocal fold function) and safety of hylan B gel as compared with bovine cross-linked collagen in the treatment of patients with glottal insufficiency.

Material and Methods—In a prospective trial, 70 patients with glottal insufficiency due to unilateral vocal fold paresis (n=35) or atrophy (n=35) were randomized to received either hylan B gel (n=47) or collagen (n=23) injections into 1 vocal fold. Forty-two of the patients were examined 24 months after treatment. Evaluations were made based on patients’ subjective ratings, digitized videostroboscopic measurements, maximum phonation time and phonation quotient.

Results—The patients’ self-ratings were significantly improved in both the hylan B gel and collagen groups. Videostroboscopic measurements of glottal closure were significantly improved for both groups. The hylan B gel group showed a trend towards less resorption at the injected vocal fold edge in comparison with the collagen group (p=0.05). No serious adverse events were observed. Twenty-eight patients dropped out of the study after 12 months: 18 had been re-injected or operated on with medialization laryngoplasty due to insufficient voice and 10 had either died of causes unrelated to the study or refused to attend follow-up.

Conclusions—No long-term side-effects were found for either the hylan B gel or collagen groups after injection treatment. Both treatments resulted in significantly improved voice as rated by the patients and significantly improved glottal closure. Some resorption was noted for both substances, and ≈25% of the patients chose re-treatment 2 years after the initial treatment.