1.Protection of nigral dopaminergic neurons by AAV1 transduction with Rheb(S16H) against neurotoxic inflammation in vivo
Sehwan KIM ; Gyeong Joon MOON ; Yong Seok OH ; Jungha PARK ; Won Ho SHIN ; Jae Yeong JEONG ; Kwang Shik CHOI ; Byung Kwan JIN ; Nikolai KHOLODILOV ; Robert E BURKE ; Hyung Jun KIM ; Chang Man HA ; Seok Geun LEE ; Sang Ryong KIM
Experimental & Molecular Medicine 2018;50(2):e440-
We recently reported that adeno-associated virus serotype 1 (AAV1) transduction of murine nigral dopaminergic (DA) neurons with constitutively active ras homolog enriched in brain with a mutation of serine to histidine at position 16 [Rheb(S16H)] induced the production of neurotrophic factors, resulting in neuroprotective effects on the nigrostriatal DA system in animal models of Parkinson’s disease (PD). To further investigate whether AAV1-Rheb(S16H) transduction has neuroprotective potential against neurotoxic inflammation, which is known to be a potential event related to PD pathogenesis, we examined the effects of Rheb(S16H) expression in nigral DA neurons under a neurotoxic inflammatory environment induced by the endogenous microglial activator prothrombin kringle-2 (pKr-2). Our observations showed that Rheb(S16H) transduction played a role in the neuroprotection of the nigrostriatal DA system against pKr-2-induced neurotoxic inflammation, even though there were similar levels of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1-beta (IL-1β), in the AAV1-Rheb(S16H)-treated substantia nigra (SN) compared to the SN treated with pKr-2 alone; the neuroprotective effects may be mediated by the activation of neurotrophic signaling pathways following Rheb(S16H) transduction of nigral DA neurons. We conclude that AAV1-Rheb(S16H) transduction of neuronal populations to activate the production of neurotrophic factors and intracellular neurotrophic signaling pathways may offer promise for protecting adult neurons from extracellular neurotoxic inflammation.
2.Safety and pharmacokinetic comparison between fenofibric acid 135 mg capsule and 110 mg entericcoated tablet in healthy volunteers
Yu-Bin SEO ; Jae Hoon KIM ; Ji Hye SONG ; WonTae JUNG ; Kyu-Yeol NAM ; Nyung KIM ; Youn-Woong CHOI ; SangMin CHO ; Do-Hyung KI ; Hye Jung LEE ; JungHa MOON ; SeungSeob LEE ; JaeHee KIM ; Jang Hee HONG ; Sunwoo JUNG ; Jin-Gyu JUNG
Translational and Clinical Pharmacology 2023;31(2):95-104
This study aimed to compare the pharmacokinetic (PK) and safety profiles of 2 fenofibric acid formulations under fasting and fed conditions. The reference was a 135 mg capsule, while the test was a 110 mg enteric-coated tablet. This randomized, open-label, two-sequence, two-period crossover phase 1 clinical trial was conducted in healthy Korean men. Sixty participants were enrolled in each of the fasting and feeding groups. Blood samples were collected 72 hours after drug administration. PK parameters were calculated using a noncompartmental method with Phoenix WinNonlin ® . A total of 53 and 51 participants from the fasting and feeding groups, respectively, completed the study. The geometric mean ratio and 90% confidence intervals of the maximum concentration (C max ) and area under the concentration-time curve to the last measurable plasma concentration were 0.9195 (0.8795–0.9614) and 0.8630 (0.8472–0.8791) in the fasting study and 1.0926 (1.0102–1.1818) and 0.9998 (0.9675–1.0332) in the fed study, respectively. The time to reach C max of the enteric-coated tablet compared to that of the capsule was extended by 1 and 3 hours under fasting and fed conditions, respectively. In conclusion, enteric-coated tablets have a higher bioavailability than capsules. In addition, the enteric-coated tablet was smaller than the capsule, making it easier for patients to swallow.