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.

Animal models of prenatal immune challenge and their contribution to the study of schizophrenia: a systematic review

Prenatal immune challenge (PIC) in pregnant rodents produces offspring with abnormalities in behavior, histology, and gene expression that are reminiscent of schizophrenia and autism. Based on this, the goal of this article was to review the main contributions of PIC models, especially the one using the viral-mimetic particle polyriboinosinic-polyribocytidylic acid (poly-I:C), to the understanding of the etiology, biological basis and treatment of schizophrenia. This systematic review consisted of a search of available web databases (PubMed, SciELO, LILACS, PsycINFO, and ISI Web of Knowledge) for original studies published in the last 10 years (May 2001 to October 2011) concerning animal models of PIC, focusing on those using poly-I:C. The results showed that the PIC model with poly-I:C is able to mimic the prodrome and both the positive and negative/cognitive dimensions of schizophrenia, depending on the specific gestation time window of the immune challenge. The model resembles the neurobiology and etiology of schizophrenia and has good predictive value. In conclusion, this model is a robust tool for the identification of novel molecular targets during prenatal life, adolescence and adulthood that might contribute to the development of preventive and/or treatment strategies (targeting specific symptoms, i.e., positive or negative/cognitive) for this devastating mental disorder, also presenting biosafety as compared to viral infection models. One limitation of this model is the incapacity to model the full spectrum of immune responses normally induced by viral exposure.

Lesch-Nyhan syndrome and purine and pyrimidine metabolism didorders / 한양의대학술지

Purine & pyrimidine nucleotides are basic constituents of cellular DNA and RNA polynucleotides. Their function includes regulation of cell metabolism and function, energy conservation and transport and formation of coenzymes and active intermediates of phospholipids and carbohydrate metabolism. The origin of cellular purines and pyrimidines is almost exclusively endogenous source, and the dietary purines play only a minor role. Diagnostic and clinical markers of purine and pyrimidine nucleotide disorders are the level of uric acid, xanthine, hypoxanthine, orotic acid, uracil, thymine, dihydrouracil, dihydrothymine, and succinyladenosine. Clinical manifestations of purine and pyrimidine metabolic disorders are crystalluria and acute renal failure, infections, failure to thrive, and anemia. One of purine metabolic disorders, Lesch-Nyhan disease, is X-linked recessive disorder, presenting motor delay, cerebral palsy, involuntary movements, self-injurious behavior, hyperurcemia, uricosuria, urinary calculi and gouty arthritis. Hypoxanthine-guanine phosphoribosyl transferase(HPRT) is deficient.

Interaction of yeast elongation factor 3 with polynucleotides, ribosomal RNA and ribosomal subunits.

In addition to the two usual eukaryotic elongation factors (EF-1 alpha and EF-2) fungal ribosomes need a third protein, elongation factor 3, for translation. EF-3 is essential for in vivo and in vitro protein synthesis. Functionally, EF-3 stimulates EF-1 alpha dependent binding of aminoacyl-tRNA to the ribosomal A site when E site is occupied by deacylated tRNA. EF-3 has intrinsic ATPase activity which is regulated by the functional state of the ribosome. EF-3 ATPase is activated by both 40S and 60S ribosomal subunits. However intact 80S ribosomes are needed for efficient activation of EF-3 ATPase. EF-3 appears to be an RNA binding protein with high affinity for polynucleotides containing guanosine rich sequences. To determine whether guanosine rich sequence of ribosomal RNA is involved in EF-3 binding, an antisense oligonucleotide dC6 was used to block EF-3 interaction with the ribosome. The oligonucleotide suppresses activation of EF-3 ATPase by 40S ribosomal subunit and not by the 60S or the 80S particles. Poly(U)-directed polyphenylalanine synthesis by yeast ribosomes is inhibited by dC6. To define the binding site of the oligonucleotide and presumably of EF-3 on 18S ribosomal RNA, hydrolysis of rRNA by RNase H was followed in the presence of dC6. These experiments reveal an RNase H cleavage site at 1094GGGGGG1099 sequence of 18S ribosomal RNA. This guanosine rich sequence of rRNA is suggested to be involved in EF-3 binding to yeast ribosome. Data presented in this communication suggest that the activity of EF-3 involved a direct interaction with the guanosine rich sequence of rRNA.

Temperature-absorption transition spectroscopy: a technique for estimating the relative charge densities on thiolated phosphate groups in nucleic acid analogues.

Various polynucleotides with well-defined sequences at low salt concentration have been studied using temperature-absorbtion transition spectroscopy to understand their conformations. It has been observed that the adopted technique can fairly estimate the relative charge densities at the thiolated phosphate groups in nucleic acid analogues at low salt concentrations.