Regulatory guideline for biosimilar products in Korea

AbstractThe regulatory framework of biosimilar products in Korea is a 3-tiered system: 1) Pharmaceutical Affairs Act; 2) Notification of the regulation on review and authorization of biological products; 3) Guideline on evaluation of biosimilar products. A biosimilar product is regulated under the same regulation as biological products. The difference from new biological product is that biosimilar product requires full comparability data with reference product. Based on these data, some of the non-clinical and clinical data could be abbreviated. As Korean guideline for biosimilar products was developed along with that of the WHO’s, most of the recommendations were based on similar principle except the clinical evaluation to demonstrate similarity. No biosimilar products are licensed yet, however, 4 IND products have been approved for phase I or III clinical trials. The addressed issues during review were as follows: acceptability of reference products manufactured in different sites, determination of acceptable criteria for differences and selection of analytical tests for the comparability exercise to detect potential differences in quality attributes, relevant species for non-clinical study, and duration of toxicity study, etc. These and other future issues will be dealt with scientific advancement, experiences of collaborating work with WHO or other NRAs, which will be reflected in the guidelines on regulations of biosimilar products in Korea

Symptom cluster, healthcare use and mortality in patients with severe chronic obstructive pulmonary disease

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108090/1/jocn12526.pd

IL-4 Inhibits IL-1β-Induced Depressive-Like Behavior and Central Neurotransmitter Alterations

It has been known that activation of the central innate immune system or exposure to stress can disrupt balance of anti-/proinflammatory cytokines. The aim of the present study was to investigate the role of pro- and anti-inflammatory cytokines in the modulation of depressive-like behaviors, the hormonal and neurotransmitter systems in rats. We investigated whether centrally administered IL-1β is associated with activation of CNS inflammatory pathways and behavioral changes and whether treatment with IL-4 could modulate IL-1β-induced depressive-like behaviors and central neurotransmitter systems. Infusion of IL-4 significantly decreased IL-1β-induced anhedonic responses and increased social exploration and total activity. Treatment with IL-4 markedly blocked IL-1β-induced increase in PGE2 and CORT levels. Also, IL-4 reduced IL-1β-induced 5-HT levels by inhibiting tryptophan hydroxylase (TPH) mRNA and activating serotonin transporter (SERT) in the hippocampus, and levels of NE were increased by activating tyrosine hydroxylase (TH) mRNA expression. These results demonstrate that IL-4 may locally contribute to the regulation of noradrenergic and serotonergic neurotransmission and may inhibit IL-1β-induced behavioral and immunological changes. The present results suggest that IL-4 modulates IL-1β-induced depressive behavior by inhibiting IL-1β-induced central glial activation and neurotransmitter alterations. IL-4 reduced central and systemic mediatory inflammatory activation, as well as reversing the IL-1β-induced alterations in neurotransmitter levels. The present findings contribute a biochemical pathway regulated by IL-4 that may have therapeutic utility for treatment of IL-1β-induced depressive behavior and neuroinflammation which warrants further study

Consumer Orientations of Second-Hand Shoppers by Store Type: A Profile Analysis

Second-hand clothing has long been associated with the used, worn-out, tainted and even odorous, but now consumers believe that used products have quality comparable to new clothes and even some perceive used clothing to be of superior quality than their unworn counterparts. This study examines whether consumer orientations differ among frequent shoppers of three second-hand clothing stores (consignment stores, online stores, and thrift stores). The data were collected via MTurk and consisted of 600 consumers in the US who had purchased second-hand clothing for themselves in the past 12 months. A profile analysis showed that the profiles of consumer groups in supercenters were not parallel. A subsequent ANOVA test showed that the three consumer groups exhibited significant differences in ecological consciousness, dematerialism, nostalgia proneness, and fashion-consciousness. On the contrary, the three groups did not show differences in their consumer orientations in frugality and style-consciousness

Antimicrobial HPA3NT3 peptide analogs: Placement of aromatic rings and positive charges are key determinants for cell selectivity and mechanism of action

AbstractIn an earlier study, we determined that HP(2‐20) (residues 2‐20 of parental HP derived from the N-terminus of the Helicobacter pylori ribosomal protein L1) and its analog, HPA3NT3, had potent antimicrobial effects. However, HPA3NT3 also showed undesirable cytotoxicity against HaCaT cells. In the present study, we designed peptide analogs including HPA3NT3-F1A (‐F1A), HPA3NT3-F8A (‐F8A), HPA3NT3-F1AF8A (‐F1AF8A), HPA3NT3-A1 (‐A1) and HPA3NT3-A2 (‐A2) in an effort to investigate the effects of amino acid substitutions in reducing their hydrophobicity or increasing their cationicity, and any resulting effects on their selectivity in their interactions with human cells and pathogens, as well as their mechanism of antimicrobial action. With the exception of HPA3NT3-A1, all of these peptides showed potent antimicrobial activity. Moreover, substitution of Ala for Phe at positions 1 and/or 8 of the HPA3NT3 peptides (‐F1A, -F8A and -F1AF8A) dramatically reduced their cytotoxicity. Thus the cytotoxicity of HPA3NT3 appears to be related to its Phe residues (positions 1 and 8), which strongly interact with sphingomyelin in the mammalian cell membrane. HPA3NT3 exerted its bactericidal effects through membrane permeabilization mediated by pore formation. In contrast, fluorescent dye leakage and nucleic acid gel retardation assays showed that ‐A2 acted by penetrating into the cytoplasm, where it bound to nucleic acids and inhibited protein synthesis. Notably, Staphylococcus aureus did not develop resistance to -A2 as it did with rifampin. These results suggest that the -A2 peptide could potentially serve as an effective antibiotic agent against multidrug-resistant bacterial strains

Paratracheal Air Cysts: Sonographic Findings in Two Cases

We report two cases of paratracheal air cyst discovered incidentally at neck ultrasonography and confirmed at CT. The cysts were located at the inferoposterior aspect of the right lobe of the thyroid. Ultrasonography revealed an ill-defined hypoechoic mass containing hyperechoic foci which mimicked calcifications. Neck CT confirmed the presence of an ill-defined air pocket which communicated with the trachea through a slit

MR Imaging of Medullary Streaks in Osteosclerosis: A Case Report

We present a case of medullary sclerosis of the appendicular skeleton in a patient with chronic renal insufficiency for whom MR imaging findings were characteristic. T1- and T2-weighted MR images showed multiple vertical lines (medullary streaks) of low signal intensity in the metaphyses and diaphyses of the distal femur and proximal tibia