A Phase III, Randomized, Multi-Center, Double-Masked, Matched-Pairs, Active-Controlled Trial to Compare the Efficacy and Safety between Neuramis Deep and Restylane in the Correction of Nasolabial Folds

BACKGROUND: We conducted this clinical study to compare the efficacy and safety between Neuramis Deep and Restylane in the correction of nasolabial folds. METHODS: In this phase III, randomized, multi-center, double-masked, matched-pairs, active-controlled trial (ClinicalTrials.gov Identifier: NCT01585220), we evaluated a total of 67 subjects (n=67). All the subjects underwent Neuramis Deep treatment on one side and Restylane on the contralateral side of the bilateral nasolabial folds at a ratio of 1:1. To compare the efficacy of Neuramis Deep and Restylane, we evaluated the Wrinkle Severity Rating Scale scores and those of the Global Aesthetic Improvement Scale. In addition, we compared the safety of Neuramis Deep and Restylane based on adverse events, physical examination, and clinical laboratory tests. RESULTS: Neuramis Deep was not inferior in improving the nasolabial folds as compared with Restylane. In addition, there was no significant difference in the efficacy between Neuramis Deep and Restylane. There were no significant differences in safety parameters between Neuramis Deep and Restylane. CONCLUSIONS: In conclusion, our results indicate that Neuramis Deep may be a safe, effective material for improving the nasolabial folds. However, further studies are warranted to compare the tolerability of Neuramis Deep and Restylane based on histopathologic findings.

CDK5-dependent inhibitory phosphorylation of Drp1 during neuronal maturation

Mitochondrial functions are essential for the survival and function of neurons. Recently, it has been demonstrated that mitochondrial functions are highly associated with mitochondrial morphology, which is dynamically changed by the balance between fusion and fission. Mitochondrial morphology is primarily controlled by the activation of dynamin-related proteins including dynamin-related protein 1 (Drp1), which promotes mitochondrial fission. Drp1 activity is regulated by several post-translational modifications, thereby modifying mitochondrial morphology. Here, we found that phosphorylation of Drp1 at serine 616 (S616) is mediated by cyclin-dependent kinase 5 (CDK5) in post-mitotic rat neurons. Perturbation of CDK5 activity modified the level of Drp1S616 phosphorylation and mitochondrial morphology in neurons. In addition, phosphorylated Drp1S616 preferentially localized as a cytosolic monomer compared with total Drp1. Furthermore, roscovitine, a chemical inhibitor of CDKs, increased oligomerization and mitochondrial translocation of Drp1, suggesting that CDK5-dependent phosphorylation of Drp1 serves to reduce Drp1's fission-promoting activity. Taken together, we propose that CDK5 has a significant role in the regulation of mitochondrial morphology via inhibitory phosphorylation of Drp1S616 in post-mitotic neurons.

Use of Behavioral Analysis in Animal Models for Schizophrenia Research / 대한정신분열병학회지

Animal models are useful tools to study the molecular basis of schizophrenia pathophysiology and efficacy of potential therapeutic agents. Schizophrenia animal models can be subdivided into three classes ; drug-induced models, genetic models, and environmental models and each model is designed based on specific traits corresponding to the characteristic symptoms of human schizophrenia patients. Psychomotor agitation and sensitivity to psychotomimetic drugs are often thought to reflect positive symptoms. Social interaction deficits and affective impairments are known to correspond to negative symptoms. Also, cognitive symptoms have been linked to the working memory impairments, attention deficits and related cognitive deficits in animals. To analyze such components in quantifiable manners, various behavioral paradigms have been developed and utilized. Here, we overview these animal models, focusing on underlying rationales for their use in the context of schizophrenia research.

Effects of Watercress Containing Rutin and Rutin Alone on the Proliferation and Osteogenic Differentiation of Human Osteoblast-like MG-63 Cells

Most known osteoporosis medicines are effective for bone resorption, and so there is an increasing demand for medicines that stimulate bone formation. Watercress (N. officinale R. Br.) is widely used as a salad green and herbal remedy. This study analyzed a watercress extract using ultra-performance liquid chromatography/mass spectrometry, and identified a rutin as one of its major constituents. Osteogenic-related assays were used to compare the effects of watercress containing rutin (WCR) and rutin alone on the proliferation and differentiation of human osteoblast-like MG-63 cells. The reported data are expressed as percentages relative to the control value (medium alone; assigned as 100%). WCR increased cell proliferation to 125.0+/-4.0% (mean+/-SD), as assessed using a cell viability assay, and increased the activity of alkaline phosphatase, an early differentiation marker, to 222.3+/-33.8%. In addition, WCR increased the expression of collagen type I, another early differentiation marker, to 149.2+/-2.8%, and increased the degree of mineralization, a marker of the late process of differentiation, to 122.9+/-3.9%. Rutin alone also increased the activity of ALP (to 154.4+/-12.2%), the expression of collagen type I (to 126.6+/-6.2%), and the degree of mineralization (to 112.3+/-5.0%). Daidzein, which is reported to stimulate bone formation, was used as a positive control; the effects of WCR on proliferation and differentiation were significantly greater than those of daidzein. These results indicate that WCR and rutin can both induce bone formation via the differentiation of MG-63 cells. This is the first study demonstrating the effectiveness of either WCR or rutin as an osteoblast stimulant.

A Phase III, Randomized, Double-Blind, Matched-Pairs, Active-Controlled Clinical Trial and Preclinical Animal Study to Compare the Durability, Efficacy and Safety between Polynucleotide Filler and Hyaluronic Acid Filler in the Correction of Crow's Feet: A

The Rejuran(R) is a new filler product made from purified polynucleotides. Here we present data from an animal study and a clinical trial to examine the durability, efficacy and safety of the Rejuran(R) on crow's feet. For the animal study, 25 mice were divided into three groups: Group 1 received phosphate buffered saline (PBS); Group 2 were treated with Yvoire(R); and Group 3 were treated with Rejuran(R). The durability and efficacy of each treatment were assessed by microscopy and staining. In the clinical trial, 72 patients were randomized to receive Rejuran(R) treatment for crow's feet on one side and Yvoire-Hydro(R) on the contralateral side, at a ratio of 1:1. Repeated treatments were performed every two weeks for a total of three times, over a total of 12 weeks' observation. All injections and observations of efficacy and safety were performed by the same two investigators. In the animal study, the Rejuran(R) group showed similar durability and inflammatory response to the Yvoire(R) group. Upon efficacy assessment, the Rejuran(R) group showed the greatest elasticity and collagen composition, and a significant difference in skin surface roughness and wrinkle depth. In the clinical trial, the primary and secondary objective efficacy outcome measure showed no statistical significance between the two groups, and in safety outcomes there were no unexpected adverse effects. Our data suggest that the Rejuran(R), as a new regenerative filler, can be useful to reduce wrinkles, by showing evidence for its efficacy and safety.

Binding Specificity of Philyra pisum Lectin to Pathogen-Associated Molecular Patterns, and Its Secondary Structure

We recently reported a Philyra pisum lectin (PPL) that exerts mitogenic effects on human lymphocytes, and its molecular characterization. The present study provides a more detailed characterization of PPL based on the results from a monosaccharide analysis indicating that PPL is a glycoprotein, and circular dichroism spectra revealing its estimated alpha-helix, beta-sheet, beta-turn, and random coil contents to be 14.0%, 39.6%, 15.8%, and 30.6%, respectively. These contents are quite similar to those of deglycosylated PPL, indicating that glycans do not affect its intact structure. The binding properties to different pathogen-associated molecular patterns were investigated with hemagglutination inhibition assays using lipoteichoic acid from Gram-positive bacteria, lipopolysaccharide from Gram-negative bacteria, and both mannan and beta-1,3-glucan from fungi. PPL binds to lipoteichoic acids and mannan, but not to lipopolysaccharides or beta-1,3-glucan. PPL exerted no significant antiproliferative effects against human breast or bladder cancer cells. These results indicate that PPL is a glycoprotein with a lipoteichoic acid or mannan-binding specificity and which contains low and high proportions of alpha-helix and beta-structures, respectively. These properties are inherent to the innate immune system of P. pisum and indicate that PPL could be involved in signal transmission into Gram-positive bacteria or fungi.

Case Report of Verrucous Carcinoma Arising in Sacral Pressure Sore

PURPOSE: Verrucous carcinoma is a rare, low-grade and well-differentiated squamous cell carcinoma, representing as a warty tumor. Estimation of the incidence for cutaneous lesions is not available because they are rare. We describe a case of verrucous carcinoma, a rare type, complication of a chronic pressure ulcer of duration more than 15 years. METHODS: A 17-year-old boy presented with a large lesion involving the sacral area, which had been neglected for about 15 years. He had a history of surgical extirpation 2 years ago, but not cured. Examination revealed a cauliflower-like mass arising from an irregularly oval-shaped tumor which was 6.0x4.5cm in size with signs of infection and ulcer. The lesion involved the sacrococcygeal area, spreading to both medial gluteal regions. The perianal skin did not appear to be directly affected. RESULTS: A preoperative punch biopsy revealed a extremely well differentiated verrucous carcinoma. There were positive results in immunohistochemistry in the items of p53, p63, Ki-67. An 'en-bloc' excision of the tumor with the clinically normal surrounding tissue was carried out. Reconstruction was achieved by local regional flap. Histopathological findings of the excised area fully confirmed the preoperative biopsy report. It remained free of recurrence for a period of about 8 months. CONCLUSION: We believe that in patients with buttock involvement, regardless of the extent of such tumors, surgical therapy should be considered as the first-choice of treatment as reconstruction can be performed without excessive impairment for the patient.