Efficacy and safety of single injection of cross-linked sodium hyaluronate vs. three injections of high molecular weight sodium hyaluronate for osteoarthritis of the knee: a double-blind, randomized, multi-center, non-inferiority study.

BACKGROUND: This randomized, double-blind, multi-center, non-inferiority trial was conducted to assess the efficacy and safety of a cross-linked hyaluronate (XLHA, single injection form) compared with a linear high molecular hyaluronate (HMWHA, thrice injection form) in patients with symptomatic knee osteoarthritis. METHODS: Two hundred eighty seven patients with osteoarthritis (Kellgren-Lawrence grade I to III) were randomized to each group. Three weekly injections were given in both groups but two times of saline injections preceded XLHA injection to maintain double-blindness. Primary endpoint was the change of weight-bearing pain (WBP) at 12 weeks after the last injection. Secondary endpoints included Western Ontario and McMaster Universities Osteoarthritis index; patient's and investigator's global assessment; pain at rest, at night, or in motion; OMERACT-OARSI responder rate; proportion of patients achieving at least 20 mm or 40% decrease in WBP; and rate of rescue medicine use and its total consumption. RESULTS: Mean changes of WBP at 12 weeks after the last injection were -33.3 mm with XLHA and -29.2 mm with HMWHA, proving non-inferiority of XLHA to HMWHA as the lower bound of 95% CI (-1.9 mm, 10.1 mm) was well above the predefined margin (-10 mm). There were no significant between-group differences in all secondary endpoints. Injection site pain was the most common adverse event and no remarkable safety issue was identified. CONCLUSIONS: This study demonstrated that a single injection of XLHA was non-inferior to three weekly injections of HMWHA in terms of WBP reduction, and supports XLHA as an effective and safe treatment for knee osteoarthritis. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT01510535 ). This trial was registered on January 6, 2012.

The role of tauroursodeoxycholic acid on adipogenesis of human adipose-derived stem cells by modulation of ER stress.

Obesity has become a serious public health problem in the developed world. Increased mass of adipose tissue in the obese is due to an increase in both the size (hypertrophy) and number (hyperplasia) of adipocytes. The chemical chaperone tauroursodeoxycholic acid (TUDCA) not only decreases endoplasmic reticulum (ER) stress, but also plays a role as a leptin-sensitizing agent for preadipocytes in mice and humans. In this study, we examine whether TUDCA has an effect on adipogenesis from human adipose-derived stem cells (hASCs). Therefore, the effect of TUDCA on ER stress, lipid accumulation, and adipogenic differentiation from hASCs was investigated using histological staining, reverse-transcriptase polymerase chain reaction (RT-PCR), and western blotting in vitro. It was found that TUDCA treatment of hASCs significantly decreases the representative ER stress marker (glucose-regulated protein 78 kDa (GRP78)), adipogenic markers (peroxisome proliferator-activated receptor gamma (PPARγ) and glycerol-3-phosphate dehydrogenase 1 (GPDH)), and lipid accumulation. Furthermore, we confirmed that TUDCA treatment of hASCs significantly decreased in vivo adipogenic tissue formation and ER stress comparing with PBS treatment of hASCs. The results indicate that TUDCA plays a critical role in adipogenesis from hASCs by modulating ER stress and, therefore, has potential pharmacologic and therapeutic applications as an anti-obesity agent.

A prospective, randomized, double-blind, multicenter comparative study on the safety and efficacy of Celecoxib and GCSB-5, dried extracts of six herbs, for the treatment of osteoarthritis of knee joint.

ETHNOPHARMACOLOGICAL RELEVANCE: This prospective, randomized, double-blind, multicenter study compared the efficacy and safety of Celecoxib and GCSB-5, a new product from extracts of six herbs, for the treatment of knee osteoarthritis. MATERIALS AND METHODS: A total of 198 eligible patients were randomly assigned to the Celecoxib group (n=99 patients) or the GCSB-5 group (n=99 patients) for the 12-week study. The amount of change and percentage of the change in Western Ontario and McMaster Universities (WOMAC) Arthritis Index from the baseline, the change in pain on walking by visual analogue scale (VAS), physician's global assessment on response to therapy (PGART) by five point Likert scale, and the amount of rescue medicine taken were used as parameters for efficacy. Adverse drug reactions (ADRs) were carefully investigated. RESULTS: The WOMAC score improved in both the Celecoxib group and GCSB-5 group by 20.5 and 21.3 (P=0.79). The percentage of the change in WOMAC score were -42.0% and -38.9% (P=0.54). The pain VAS score decreased by 29.9 and 27.9 (P=0.58). The responders by PGART were 95.3% and 93.8% (P= 0.66), and the median amount of rescue medicine taken were 2.0 and 6.5 tablets (P=0.06). The incidence of ADRs were 31.3% and 21.2% (P=0.11). The most common ADRs were gastrointestinal system related; 17.2% in GCSB-5 group and 22.2% in Celecoxib group. Any severe ADR was not observed in either group. CONCLUSIONS: The result of this study supports that GCSB-5 is comparable to Celecoxib in terms of the efficacy and safety for the treatment of osteoarthritis of knee joint.

hESC expansion and stemness are independent of connexin forty-three-mediated intercellular communication between hESCs and hASC feeder cells.

BACKGROUND: Human embryonic stem cells (hESCs) are a promising and powerful source of cells for applications in regenerative medicine, tissue engineering, cell-based therapies, and drug discovery. Many researchers have employed conventional culture techniques using feeder cells to expand hESCs in significant numbers, although feeder-free culture techniques have recently been developed. In regard to stem cell expansion, gap junctional intercellular communication (GJIC) is thought to play an important role in hESC survival and differentiation. Indeed, it has been reported that hESC-hESC communication through connexin 43 (Cx43, one of the major gap junctional proteins) is crucial for the maintenance of hESC stemness during expansion. However, the role of GJIC between hESCs and feeder cells is unclear and has not yet been reported. METHODOLOGY/PRINCIPAL FINDINGS: This study therefore examined whether a direct Cx43-mediated interaction between hESCs and human adipose-derived stem cells (hASCs) influences the maintenance of hESC stemness. Over 10 passages, hESCs cultured on a layer of Cx43-downregulated hASC feeder cells showed normal morphology, proliferation (colony growth), and stemness, as assessed by alkaline phosphatase (AP), OCT4 (POU5F1-Human gene Nomenclature Database), SOX2, and NANOG expression. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that Cx43-mediated GJIC between hESCs and hASC feeder cells is not an important factor for the conservation of hESC stemness and expansion.

The Pattern of Use of Oral NSAIDs with or without Co-prescription of Gastroprotective Agent for Arthritic Knee by Korean Practitioners.

PURPOSE: The aim of this study was to describe the patterns of use of non-steroidal anti-inflammatory drugs (NSAIDs) for arthritic knees in clinical practice, particularly focusing on the co-prescription of gastroprotective agents for patients with risk factors for adverse gastrointestinal (GI) events. MATERIALS AND METHODS: Each cross-sectional cohort was a group of outpatients visiting 111 physicians who had prescribed NSAIDs for the patients' arthritic knees for more than three consecutive months. A self-administered questionnaire was completed by each patient and physician. RESULTS: Nine hundred and forty five patients (48%) of the whole 1,960 patients belonged to the group with a high or very high risk for NSAID-induced gastropathy determined by northern California Health Maintenance Organization guidelines. Overall, only less than half of the patients were given co-prescription of gastroprotective agents, regardless of the presence or absence of GI symptoms and irrespective of the level of risk for NSAID-induced gastropathy. CONCLUSIONS: The physician prescribing NSAIDs for arthritic knees should monitor any GI symptoms and the patient monitor anylevel for NSAIDinduced gastropathy, and be willing to add gastroprotective agents as necessary in order to prevent serious adverse GI events.

Development of Korean Academy of Medical Sciences Guideline for rating physical disability of upper extremity.

While the lower extremities support the weight and move the body, the upper extremities are essential for the activities of daily living, which require many detailed movements. Therefore, a disability of the upper extremity function should include a limitation of all motions of the joints and sensory loss, which affects the activities. In this study, disabilities of the upper extremities were evaluated according to the following conditions: 1) amputation, 2) joint contracture, 3) diseases of upper extremity, 4) weakness, 5) sensory loss of the finger tips, and 6) vascular and lymphatic diseases. The order of 1) to 6) is the order of major disability and there is no need to evaluate a lower order disability when a higher order one exists in the same joint or a part of the upper extremity. However, some disabilities can be either added or substituted when there are special contributions from multiple disabilities. An upper extremity disability should be evaluated after the completion of treatment and full adaptation when further functional changes are not expected. The dominance of the right or left hand before the disability should not be considered when there is a higher rate of disability.

Development of Korean Academy of Medical Sciences Guideline rating the physical impairment: lower extremities.

Lower Extremities Committee of Korean Academy of Medical Sciences Guideline for Impairment Rating develops new guidelines which are based on McBride method, American Medical Association Guides, Disability evaluation by The Korean Orthopaedic Association, The Korean Neurosurgery Society, and Korean Academy of Rehabilitation Medicine. The committee analyzed and discussed to create an ideal method practical in Korea. Our committee endeavors to develop new methods which are easy to use, but are suitable for professional use and also independent from the examinee's intentions. The lower extremities are evaluated on the basis of anatomic change, functional change, and diagnosis based evaluation. Nine methods are used to assess the lower extremities. Anatomic assessment includes leg length discrepancy, ankylosis, amputation, skin loss, peripheral nerve injury, and vascular disease. In functional assessment, range of motion and muscle strength are included. Diagnosis-based assessments are used to evaluate impairment caused by specific fractures, deformities, ligament instability, meniscectomies, post-traumatic arthritis, fusion of the foot, and lower extremity joint replacements.