Placenta is a special organ that contains many nutrients such as growth factors, minerals, and bioactive peptides. Dipeptides of glycine and leucine are major components of porcine placenta extracts (PPE) that has been used as an alternative of human placenta extracts. In this study, we investigated whether major peptides of PPE, Glycyl-L-Leucine (Gly-Leu), L-Leucyl-Glycine (Leu-Gly), and L-Leucyl-L-Leucine (Leu-Leu), affect skin hydration and elasticity in vitro and in vivo. We found that Gly-Leu and Leu-Gly dipeptides induced the expression of transglutaminase 1 in normal human epidermal keratinocytes (NHEKs) whereas Leu-Leu dipeptides did not. Treatment with Gly-Leu or Leu-Gly significantly increased hyaluronan (HA) synthesis in NHEKs and the upregulation of hyaluronan synthase 2 (HAS2) mRNA level was confirmed. In addition, elastase activity was inhibited in NHEKs treated with Gly-Leu or Leu-Gly dipeptides. Oral administration of Gly-Leu or Leu-Gly dipeptides increased skin hydration and elasticity in UVB-irradiated hairless mice. The significant upregulation of HA in UVB-irradiated hairless mice was observed in response to oral administration of Gly-Leu or Leu-Gly. These results suggest that the major dipeptides of porcine placenta, Gly-Leu and Leu-Gly, are potentially active ingredients for skin moisturization formulations.
Administration, Oral* ; Animals ; Dipeptides* ; Elasticity* ; Glycine* ; Humans ; Hyaluronic Acid ; In Vitro Techniques ; Intercellular Signaling Peptides and Proteins ; Keratinocytes ; Leucine* ; Mice ; Mice, Hairless* ; Minerals ; Miners ; Pancreatic Elastase ; Peptides ; Placenta ; RNA, Messenger ; Skin* ; Up-Regulation

OBJECTIVETo compare the long-term outcomes of arthroscopy and non-surgical therapy in patients with knee synovial plica syndrome (SPS).

METHODSThirty-one patients with knee SPS undergoing arthroscopic surgery and 27 SPS patients undergoing conservative treatment with articular cavity injection of sodium hyaluronate (control group) were compared for visual pain score (VAS) and the Lysholm score before and after the operation. The patients were followed-up for more than 5 years, and the long-term outcomes were compared using Kaplan-Meier survival analysis.

RESULTSs VAS and the Lysholm scores in both groups were significantly lowered after treatment (P<0.05). The postoperative VAS score was significantly lower while the Lysholm score significantly higher in arthroscopic surgery group than in the control group (P<0.05). Arithmetic mean and the median time of curative effect maintenance were 49 and 43 months in arthroscopic surgery group, as compared with 33 and 29 months in the control group, respectively; the cumulative effect maintenance rate in arthroscopic surgery group was significantly higher than that in the control group (Χ2=4.933, P=4.933).

CONCLUSIONArthroscopic treatment produces better therapeutic effect on knee joint SPS and ensures longer long-term therapeutic effect maintenance than conservative treatment.

Adult ; Arthroscopy ; Female ; Follow-Up Studies ; Humans ; Hyaluronic Acid ; administration & dosage ; Injections, Intra-Articular ; Joint Diseases ; surgery ; Knee Joint ; pathology ; surgery ; Male ; Pain, Postoperative ; Postoperative Period ; Synovectomy ; Synovial Membrane ; pathology ; Treatment Outcome

PURPOSE: Osteoarthritic (OA) pain is largely considered to be inflammatory pain. However, during the last stage of knee OA, sensory nerve fibers in the knee are shown to be significantly damaged when the subchondral bone junction is destroyed, and this can induce neuropathic pain. Several authors have reported that tumor necrosis factor-alpha (TNFalpha) in a knee joint plays a crucial role in pain modulation. The purpose of the current study was to evaluate the efficacy of etanercept, a TNFalpha inhibitor, for pain in knee OA. MATERIALS AND METHODS: Thirty-nine patients with knee OA and a 2-4 Kellgren-Lawrence grading were evaluated in this prospective study. Patients were divided into two groups; hyaluronic acid (HA) and etanercept injection. All patients received a single injection into the knee. Pain scores were evaluated before and 4 weeks after injection using a visual analogue scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and they were compared between the groups. RESULTS: Before injection, VAS and WOMAC scores were not significantly different between the groups (p>0.05). Significant pain relief was found in the etanercept group at 1 and 2 weeks by VAS, and at 4 weeks by WOMAC score, compared with the HA group (p<0.05). No adverse events were observed in either group. CONCLUSION: Direct injection of etanercept into OA knee joints was an effective treatment for pain in moderate and severe OA patients. Furthermore, this finding suggests that TNFalpha is one factor that induces OA pain.
Aged ; Etanercept/*administration & dosage/therapeutic use ; Female ; Humans ; Hyaluronic Acid/administration & dosage/*therapeutic use ; Injections, Intra-Articular ; Knee Joint/physiopathology ; Male ; Middle Aged ; Neuralgia/drug therapy ; Osteoarthritis, Knee/*drug therapy ; Pain Measurement ; Prospective Studies ; Severity of Illness Index ; Treatment Outcome ; Tumor Necrosis Factor-alpha ; Viscosupplements/administration & dosage/*therapeutic use ; Visual Analog Scale

PURPOSE: To investigate the therapeutic effects of mineral oil (MO) and hyaluronic acid (HA) mixture eye drops on the tear film and ocular surface in a mouse model of experimental dry eye (EDE). METHODS: Eye drops consisting of 0.1% HA alone or mixed with 0.1%, 0.5%, or 5.0% MO were applied to desiccating stress-induced murine dry eyes. Tear volume, corneal irregularity score, tear film break-up time (TBUT), and corneal fluorescein staining scores were measured at 5 and 10 days after treatment. Ten days after treatment, goblet cells in the conjunctiva were counted after Periodic acid-Schiff staining. RESULTS: There was no significant difference in the tear volume between desiccating stress-induced groups. The corneal irregularity score was lower in the 0.5% MO group compared with the EDE and HA groups. The 0.5% and 5.0% MO groups showed a significant improvement in TBUT compared with the EDE group. Mice treated with 0.1% and 0.5% MO mixture eye drops showed a significant improvement in fluorescein staining scores compared with the EDE group and the HA group. The conjunctival goblet cell count was higher in the 0.5% MO group compared with the EDE group and HA group. CONCLUSIONS: The MO and HA mixture eye drops had a beneficial effect on the tear films and ocular surface of murine dry eye. The application of 0.5% MO and 0.1% HA mixture eye drops could improve corneal irregularity, the corneal fluorescein staining score, and conjunctival goblet cell count compared with 0.1% HA eye drops in the treatment of EDE.
Animals ; Conjunctiva/*drug effects/pathology ; Cornea/metabolism ; Disease Models, Animal ; Drug Combinations ; Dry Eye Syndromes/*drug therapy/metabolism ; Emollients/administration & dosage ; Female ; Goblet Cells/drug effects/metabolism/pathology ; Hyaluronic Acid/*administration & dosage ; Mice ; Mice, Inbred C57BL ; Mineral Oil/*administration & dosage ; Ophthalmic Solutions ; Tears/*metabolism ; Viscosupplements/administration & dosage

Cosmetic facial filler-related ophthalmic artery occlusion is rare but is a devastating complication, while the exact pathophysiology is still elusive. Cerebral angiography provides more detailed information on blood flow of ophthalmic artery as well as surrounding orbital area which cannot be covered by fundus fluorescein angiography. This study aimed to evaluate cerebral angiographic features of cosmetic facial filler-related ophthalmic artery occlusion patients. We retrospectively reviewed cerebral angiography of 7 patients (4 hyaluronic acid [HA] and 3 autologous fat-injected cases) showing ophthalmic artery and its branches occlusion after cosmetic facial filler injections, and underwent intra-arterial thrombolysis. On selective ophthalmic artery angiograms, all fat-injected patients showed a large filling defect on the proximal ophthalmic artery, whereas the HA-injected patients showed occlusion of the distal branches of the ophthalmic artery. Three HA-injected patients revealed diminished distal runoff of the internal maxillary and facial arteries, which clinically corresponded with skin necrosis. However, all fat-injected patients and one HA-injected patient who were immediately treated with subcutaneous hyaluronidase injection showed preserved distal runoff of the internal maxillary and facial arteries and mild skin problems. The size difference between injected materials seems to be associated with different angiographic findings. Autologous fat is more prone to obstruct proximal part of ophthalmic artery, whereas HA obstructs distal branches. In addition, hydrophilic and volume-expansion property of HA might exacerbate blood flow on injected area, which is also related to skin necrosis. Intra-arterial thrombolysis has a limited role in reconstituting blood flow or regaining vision in cosmetic facial filler-associated ophthalmic artery occlusions.
Adipose Tissue/transplantation ; Adult ; Aged ; Arterial Occlusive Diseases/*etiology/*radiography/therapy ; Cerebral Angiography ; Cosmetic Techniques/adverse effects ; Dermal Fillers/administration & dosage/*adverse effects ; Face ; Female ; Humans ; Hyaluronic Acid/administration & dosage/adverse effects ; Hyaluronoglucosaminidase/administration & dosage ; Injections, Subcutaneous ; Ophthalmic Artery/*radiography ; Retinal Artery Occlusion/*etiology/*radiography/therapy ; Retrospective Studies ; Transplantation, Autologous/adverse effects ; Young Adult

BACKGROUND: Septic arthritis of the knee has been reported recently in adult patients who were administered hyaluronate. We evaluated the incidence of septic knees and the utilization of hyaluronate in the Korean adult population using nationwide data from the Health Insurance Review and Assessment Service (HIRA). METHODS: All new admissions to the clinics or hospitals for septic knees were recorded in the HIRA database which was established by the Korean government and covers the Korean population using the International Classification of Diseases-10 revision code. We evaluated the incidence of septic arthritis of the knees in the population above 50 years of age. Hyaluronate prescription data was also collected from the HIRA database. RESULTS: In 2012, the incidence of septic knees was 2.7 per 100,000 persons in men and 4.2 per 100,000 persons in women, respectively. The age-adjusted incidence of septic knees increased by 6.7% per year (95% confidence interval, 3.3 to 10.1), and the annual number of prescriptions of hyaluronate increased about 1.5-fold during the study period. CONCLUSIONS: Cautious aseptic technique is required when hyaluronate is administered in adult patients with osteoarthritis of the knee due to the concerns of the risk of septic arthritis.
Arthritis, Infectious/*epidemiology/etiology ; Female ; Humans ; Hyaluronic Acid/administration & dosage/*therapeutic use ; Incidence ; Injections, Intra-Articular/*adverse effects/statistics & numerical data ; Knee Joint/physiopathology ; Male ; Middle Aged ; Osteoarthritis, Knee/drug therapy ; Republic of Korea/epidemiology

OBJECTIVETo investigate the biocompatibility and degradation rate of crosslinking sodium hyaluronate gel with different ratio of molecular weight, so as to choose the effective, safe and totally degraded hyaluronate gel for aesthetic injection.

METHODS(1) Compound colloid was formed by cross-linking the divinyl sulphone and sodium hyaluronate with different molecular weight (4 x 10(5), 8 x 10(5), 10 x 10(5), 12 x 10(5)). (2) Healthy level KM mice was randomly divided into two groups to receive hyaluronic acid gel or liquid injection. Each group was subdivided into three subgroup to receive hyaluronic acid with different molecular weight. The biocompatibility and degradation rate, of hyaluronate were observed at 7, 90, 180 days after injection. At the same time, different molecular weight of sodium hyaluronate gel is sealed or exposed respectively under the low temperature preservation to observe its natural degradation rate. (3) The most stable colloid was selected as aesthetic injector for volunteers to observe the aesthetic effect.

RESULTSThe sodium hyaluronate gel with molecular of 4 x 10(5) was completely degraded 90 days later. The sodium hyaluronate gel with molecular of 8 x 10(5) was completely degraded 180 days later. The sodium hyaluronate gel with molecular of 10 x 10(5) was degraded to 90.0% after 180 days. The sodium hyaluronate liquid can be degraded completely within 7 days. The colloid could be kept for at least 12 months when sealed under low temperature, but was totally degraded when exposed for I d. Sodium hyaluronate gel with molecular 10 x 10(5) was confirmed to be kept for at least 6 months in animal experiment and clinical trials.

CONCLUSIONSUnder the same condition of material ratio, the higher the molecular weight is, the lower the degradation rate is. But the liquidity of gel is not good for injection when molecular weight is too large. It suggests that Sodium hyaluronate gel with molecular 10 x 10(5) maybe the best choice in cosmetic injections.

Animals ; Cross-Linking Reagents ; administration & dosage ; chemistry ; Hyaluronic Acid ; administration & dosage ; chemistry ; Injections, Subcutaneous ; Mice ; Molecular Weight ; Random Allocation

The present study was designed to develop and evaluate glycyrrhetinic acid-graft-hyaluronic acid (HGA) conjugate for intravenous paclitaxel (PTX) delivery. Lyophilized PTX-loaded self-assembled HGA nanoparticles (PTX/HGAs) were prepared and characterized by dynamic light scattering measurements. Hemolysis test, intravenous irritation assessment, and in vitro and in vivo pharmacodynamic studies were carried out. B16F10 and HepG2 cells were used in the cell apoptosis analysis. The mouse MDA-MB-231 xenograft model was used for the evaluation of in vivo anticancer activity of the drugs, by the analysis of tumor growth and side effects on other tissues. PTX/HGAs showed high stability and good biocompability. Compared with PTX plus GA plus HA solution, PTX/HGAs displayed obvious superiority in inducing the apoptosis of the cancer cells. Following systemic administration, PTX/HGAs efficiently suppressed tumor growth, with mean tumor inhibition ratio (TIR) being 65.08%, which was significantly higher than that of PTX plus GA plus HA treatment. In conclusion, PTX/HGAs demonstrated inhibitory effects tumor growth without unwanted side effects, suggesting that HGA conjugates hold a great potential as a delivery carrier for cancer chemotherapeutics to improve therapeutic efficacy and minimize adverse effects.
Animals ; Antineoplastic Agents ; administration & dosage ; adverse effects ; chemistry ; Apoptosis ; drug effects ; Drug Carriers ; chemistry ; Drug Delivery Systems ; instrumentation ; methods ; Drug Synergism ; Female ; Glycyrrhetinic Acid ; chemistry ; Hep G2 Cells ; Humans ; Hyaluronic Acid ; chemistry ; Male ; Mice ; Paclitaxel ; administration & dosage ; adverse effects ; chemistry

Soft tissue filler injection has been a very common procedure worldwide since filler injection was first introduced for soft tissue augmentation. Currently, filler is used in various medical fields with satisfactory results, but the number of complications is increasing due to the increased use of filler. The complications after filler injection can occur at any time after the procedure, early and delayed, and they range from minor to severe. In this review, based on our experience and previously published other articles, we suggest a treatment algorithm to help wound healing and tissue regeneration and generate good aesthetic results with early treatment in response to the side effects of filler. Familiarity with the treatment of these rare complications is essential for achieving the best possible outcome.
Algorithms ; Biocompatible Materials/*therapeutic use ; Connective Tissue/*surgery ; Face/surgery ; Guided Tissue Regeneration/*methods ; Humans ; Hyaluronic Acid/administration & dosage ; Injections ; Skin Aging ; Surgery, Plastic/*methods ; Tissue Engineering/*methods ; Wound Healing

PURPOSE: To determine the efficacy of intravesical hyaluronic acid (HA) instillation in treating patients with refractory interstitial cystitis/painful bladder syndrome (IC/PBS) and to identify any related factors that influence its therapeutic effect. METHODS: Thirty-three female IC/PBS patients who demonstrated poor or unsatisfactory responses to previous treatments between December 2010 and October 2012 were enrolled. Despite previous treatments, the enrolled patients had visual analogue scale (VAS) pain scores > or =4 and total scores (symptom and bother scores) > or =13 on the pelvic pain and urgency/frequency (PUF) questionnaire and > or =12 on the O'Leary-Sant interstitial cystitis symptoms index (ICSI)/problems index (ICPI). All patients received once weekly intravesical instillations of 40-mg HA diluted in 50-mL saline for 4 weeks. The efficacy of the HA instillation was evaluated by comparing the mean changes in the scores of the VAS and questionnaires from baseline to 4 weeks after treatment. Improvement was defined as a > or =2 decrease in the VAS. Moreover, we investigated the effects of the presence of Hunner's ulcer and previous treatment modalities on the therapeutic outcome of HA instillation. RESULTS: The mean age was 57.0+/-1.8 years (range, 28-75 years). The VAS score significantly decreased from baseline to 4 weeks after treatment (-2.5, P<0.001). The mean changes in the PUF, ICSI, and ICPI from baseline to 4 weeks after the treatment were -3.8 (P<0.001), -2.3 (P<0.001), and -2.7 (P<0.001), respectively. Twenty patients (61%) showed improvements. Previous treatment modalities did not affect the efficacy of HA instillation and the presence of Hunner's ulcer was unrelated to outcomes. No complications were observed. CONCLUSIONS: These results show that intravesical HA instillation is an effective and safe treatment for patients with refractory IC/PBS. Previous treatment modalities and presence of Hunner's ulcer do not affect the efficacy of HA instillation.
Administration, Intravesical ; Cystitis, Interstitial ; Female ; Humans ; Hyaluronic Acid* ; Pelvic Pain ; Sperm Injections, Intracytoplasmic ; Ulcer ; Urinary Bladder*