Considerations of critical quality attributes in the analytical comparability assessment of biosimilar products.

Based on experience in clinical trial approvals and marketing authorizations for biosimilar products in Korea, we suggest principles for the analytical comparability assessment of biosimilar products with respect to regulatory considerations. The composition and manufacturing processes of biosimilar products can differ from those of the reference product depending on the information available for the reference product and the time of product development; however, the analytical characteristics of biosimilar products should be highly similar to those of the reference product. Although manufacturing an identical product in terms of the quality profile is nearly impossible due to the high molecular weight and complex structure of biological products, the developer of the biosimilar product should attempt to establish a quality level as similar to that of the reference product as possible.

Regulatory guideline for biosimilar products in Korea.

The 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.

Butorphanol dependence increases hippocampal kappa-opioid receptor gene expression.

Butorphanol is a synthetic opioid agonist/antagonist analgesic agent, which exerts its effects mainly via kappa-opioid receptors. Characterizations of the gene expression levels of the mRNA for and protein levels of the kappa-opioid receptor in different brain regions of rats are essential for investigating possible mechanisms in the development of physical dependence on and withdrawal from butorphanol. Animals were rendered dependent by intracerebroventricular (i.

The effect of PARP inhibitor on ischaemic cell death, its related inflammation and survival signals.

Poly(ADP-ribose) polymerase (PARP) plays an important role in ischaemic cell death, and 3-aminobenzamide (3-AB), one of the PARP inhibitors, has a protective effect on ischaemic stroke. We investigated the neuroprotective mechanisms of 3-AB in ischaemic stroke. The occlusion of middle cerebral artery (MCA) was made in 170 Sprague-Dawley rats, and reperfusion was performed 2 h after the occlusion.

3-monochloropropane-1,2-diol does not cause neurotoxicity in vitro or neurobehavioral deficits in rats.

3-monochloro-1,2-propanediol (3-MCPD) is a contaminant of acid-hydrolyzed vegetable protein. Several reports have suggested that chronic exposure to 3-MCPD could produce neurotoxicity in vitro or neurobehavioral effects in experimental animals. The present study further explored the in vitro neurotoxic effects of 0.

Epigallocatechin gallate protects nerve growth factor differentiated PC12 cells from oxidative-radical-stress-induced apoptosis through its effect on phosphoinositide 3-kinase/Akt and glycogen synthase kinase-3.

The effects of epigallocatechin gallate (EGCG) on the phosphoinositide 3-kinase (PI3K)/Akt and glycogen synthase kinase-3 (GSK-3) pathway during oxidative-stress-induced injury were studied using H2O2-treated PC12 cells, which were differentiated by nerve growth factor (NGF). Following 100 microM H2O2 exposure, the viability of differentiated PC12 cells (EGCG or z-VAD-fmk pretreated vs. not pretreated) was evaluated the number of viable cell with Trypan blue and 3,4,5-dimethylthiazol-2-yl (MTT).

Increased dopamine D2 receptor binding and enhanced apomorphine-induced locomotor activity in mu-opioid receptor knockout mice.

Previous studies from our laboratory have indicated possible interactions between opioidergic and dopaminergic neurons in the central nervous system. In this study, apomorphine-induced locomotor activity and the D1 and D2 subtype dopamine receptor binding were examined in mice lacking the mu-opioid receptor genes. The ambulatory time, vertical time and total motor distance of locomotor activity were measured after administration of apomorphine (2mg/kg, i.

Enhanced binding of nor-binaltorphimine to kappa-opioid receptors in rats dependent on butorphanol.

Autoradiographic characterization of binding for brain kappa(1) ([(3)H]CI-977) and kappa(2) ([(3)H]bremazocine) in the presence of DAMGO ([D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin), DPDPE ([D-Pen(2), D-Pen(5)]-enkephalin), and U-69,593 opioid receptors, in the presence of different concentrations of a selective unlabeled kappa-opioid receptor antagonist, nor-binaltorphimine (nor-BNI), was performed in rats in which dependence on or withdrawal from butorphanol had been established. Dependence was induced by a 72 hr intracerebroventricular (i.c.

Regional specific increases of [3H]AMPA binding and mRNA expression of AMPA receptors in the brain of mu-opioid receptor knockout mice.

Previous pharmacological studies have indicated the possible existence of functional interactions between opioidergic and glutamatergic neurons in the CNS. In the present study, [(3)H]AMPA binding and the expression of mRNAs encoding flip and flop variants of three subtypes of AMPA glutamate receptor GluR1-3 were examined by in situ hybridization technique in order to investigate whether there is a change in the AMPA receptor system of mice lacking the mu-opioid receptor. In the mu-opioid receptor knockout mice, [(3)H]AMPA binding was increased in the hippocampal CA1 and dentate gyrus, cortex, and caudate putamen compared with that of the wild-type animals.

Butorphanol dependence and withdrawal decrease hippocampal kappa 2-opioid receptor binding.

The present study examines the degree and distribution of alterations in the expression of kappa-opioid receptor subtypes using a model of chronic intracerebroventricular (i.c.v.

Aroclor 1254-induced cytotoxicity in catecholaminergic CATH.a cells related to the inhibition of NO production.

The neuronal nitric oxide synthase (nNOS) specific inhibitor, 7-nitroindazole (7-NI), and the nitric oxide (NO) donor (S-nitroso-N-acetylpenicillarnine, SNAP) were used to study the role of NO in polychlorinated biphenyl (PCB: Aroclor 1254)-induced cytotoxicity in the immortalized dopaminergic cell line (CATH.a cells), derived from the central nervous system of mice. Treatment of the dopaminergic cells with various concentrations of Aroclor 1254 (0.