PubMed Health⌕ Search

Biomedical subjects

Norio Seki

Publications and source records attributed to Norio Seki.

7 recordsLinked to original sources
PubMed2006

Lig-8, a bioactive lignophenol derivative from bamboo lignin, protects against neuronal damage in vitro and in vivo.

Lig-8, a lignophenol derivative from bamboo lignin, potently suppresses oxidative stress-induced apoptosis. Here, we first examined in vitro whether lig-8 protects against neuronal damage induced by oxygen-glucose deprivation (OGD) followed by reoxygenation, tunicamycin [endoplasmic reticulum (ER)-stress inducer], or PSI (proteasome inhibitor). In pheochromocytoma (PC12) cell cultures, lig-8 (1 to 30 microM) concentration-dependently inhibited OGD- and tunicamycin (2 microg/ml)-induced cell deaths (significant at >/=3 microM and >/=1 microM, respectively). In human neuroblastoma (SH-SY5Y) cell culture, the PSI-induced apoptotic cell death and fusion protein accumulation (revealing reduced proteasome activity) was inhibited by lig-8 (30 microM). On the other hand, lig-8 at 30 microM alone did not affect any proteasome activity under resting conditions. In vivo, lig-8 (0.1 nmol/eye) reduced intravitreal N-methyl-D-aspartate (NMDA, 20 nmol)-induced retinal damage (decreases in retinal ganglion cells and inner plexiform layer thickness). Hence, lig-8 protects, partly by inhibiting excessive ER-stress, against neuronal damage in vitro and in vivo.

Animals↗
PubMed2006

Design, synthesis and biological activity of selective and orally available TF/FVIIa complex inhibitors containing non-amidine P1 ligands.

We found the novel selective and orally available non-amidine TF/FVIIa complex inhibitor 21e, 4-({[(1S)-(aminocarbonyl)-3-methylbutyl]amino}carbonyl)-2'-({[4- (aminomethyl)phenyl]amino}carbonyl)-4'-(methylamino)biphenyl-2- carboxylic acid. The derivatives were synthesized by conversions of the isobutyl moiety and the introduction of alkylamino groups to 4'-position of the central phenyl ring of compounds 2a and 2b reported previously. Some compounds show increased in vitro anti-TF/FVIIa and PT prolongation activities. Among them, compound 21e reached and sustained micromolar plasma concentration levels of up to 2h after oral administration in mice. Moreover, compound 21e did not prolong the bleeding time even at the highest dose level in cynomolgus monkeys, while PT was prolonged 3.7-fold increases at this dose.

Administration, Oral↗
PubMed2006

Potent and selective TF/FVIIa inhibitors containing a neutral P1 ligand.

Inhibition of tissue factor/factor VIIa complex (TF/FVIIa) is an attractive strategy for antithrombotic therapies. We began with an investigation of a non-amidine TF/FVIIa inhibitor based on a modification of amidine compound 1. Optimization of the substituents on the P1 phenyl portion of the compound 1 led to a neutral or less basic alternative for the 4-amidinophenyl moiety. By further optimization of the substituents on the central phenyl ring, a highly potent and selective TF/FVIIa inhibitor 17d was discovered.

Amidines↗
PubMed2005

Physiologic aspects in human lung transplantation.

Heart-lung transplantation (HLT), followed by single lung transplantation (SLT) and subsequently bilateral lung transplantation (BLT) have been developed as treatments for patients with end-stage pulmonary diseases. Initially, SLT was limited to idiopathic pulmonary fibrosis (IPF) cases and thought to be contraindicated not only for infectious diseases, but also for non-infectious diseases, including pulmonary emphysema (PE) and primary pulmonary hypertension (PPH), based on physiologic points of view. However, SLT is now widely performed for those non-infectious diseases and most of the recipients return to a normal active life. It is quite possible that BLT is superior to SLT in terms of pulmonary function, and it has been reported that BLT is better for PE and PPH patients in regards to perioperative course, postoperative exercise capacity, and long-term survival. For those situations and because of the present scarcity of donor organs, SLT must be utilized for selected non-infectious diseases for which it is safe and effective. When a single lung is replaced for IPF, PE, and PPH recipients, different physiologic situations are produced postoperatively, the understanding of which is extremely important to achieve good results, not only in the perioperative but also in the long term.

Graft Rejection↗
PubMed2004

A highly bioactive lignophenol derivative from bamboo lignin exhibits a potent activity to suppress apoptosis induced by oxidative stress in human neuroblastoma SH-SY5Y cells.

Approaches to protection against neurodegenerative diseases, in which oxidative stress and inflammation are implicated, should be based on the current concept on the etiology of these diseases. Recently, a new therapeutic strategy has been proposed to protect neurons from cell death by attenuating the apoptotic signal transduction. Lignin, a durable aromatic network polymer second to cellulose in abundance, was able to be converted into highly active lignophenol derivatives with antioxidant activity by using our newly developed phase-separation technique. These lignophenol derivatives were found to show the potent neuroprotective activity against oxidative stress. Among the compounds examined, a lignocresol derivative from bamboo (lig-8) exhibited the most potent neuroprotective activity against hydrogen peroxide (H(2)O(2))-induced apoptosis in human neuroblastoma cell line SH-SY5Y by preventing the caspase-3 activation via either caspase-8 or caspase-9. Furthermore, it was found that lig-8 exerted the antiapoptotic effect by inhibiting dissipation of the mitochondrial membrane permeability transition induced by H(2)O(2) or by the peripheral benzodiazepin receptor ligand PK11195. Lig-8 was also shown to be potent in the antioxidant activity in the cells exposed to H(2)O(2), as assessed by flow cytometry using 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate and in vitro reactive oxygen species-scavenging potency. These data suggest that lig-8 is a promising neuroprotector, which affects the signaling pathway of neuronal cell death and that it would be of benefit to delay the progress of neurodegenerative diseases.

Apoptosis↗
PubMed2003

Needlescopic operation for partial lung resection.

Needlescopic operation using instruments with a diameter of 2 mm has not been applied to partial lung resection because of the difficulty in grasping the lung firmly or the possibility of injuring the lung easily with 2-mm forceps. We have developed a technique using a mini-loop retractor and successfully performed partial lung resection in 35 patients with pneumothorax, small lung tumor, or interstitial pneumonia.

Humans↗