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a complex consisting of an organic base in association with hydrogen chloride

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1. 狭心症の新しい治療法 new therapies for angina pectoris
2. 血管攣縮性狭心症 vasospastic angina
3. 初期治療に抵抗性を示したレイノー現象の治療 treatment of the raynaud phenomenon resistant to initial therapy
4. 肝線維症の新しい治療法 emerging therapies for hepatic fibrosis
5. 過敏性腸症候群に対するアロセトロン塩酸塩（Lotronex） alosetron hydrochloride lotronex for irritable bowel syndrome

English Journal

Rho kinase inhibition modulates microglia activation and improves survival in a model of amyotrophic lateral sclerosis.

Tönges L, Günther R, Suhr M, Jansen J, Balck A, Saal KA, Barski E, Nientied T, Götz AA, Koch JC, Mueller BK, Weishaupt JH, Sereda MW, Hanisch UK, Bähr M, Lingor P.Author information Department of Neurology, University Medicine Göttingen, Robert-Koch-Str. 40, Göttingen, Germany.AbstractDisease progression in amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motoneurons (MN) and their axons, but is also influenced by neighboring cells such as astrocytes and microglial cells. The role of microglia in ALS is complex as it switches from an anti-inflammatory and neuroprotective phenotype in early disease to a proinflammatory and neurotoxic phenotype in later stages. Our previous studies in models of neurodegeneration identified rho kinase (ROCK) as a target, which can be manipulated to beneficially influence disease progression. Here, we examined the neuroprotective potential of the ROCK inhibitor Fasudil to target the central pathogenic features of ALS. Application of Fasudil to kainic acid-lesioned primary MN in vitro resulted in a strong prosurvival effect. In vivo, SOD1(G93A) mice benefited from oral treatment with Fasudil showing prolonged survival and improved motor function. These findings were correlated to an improved survival of motor neurons and a pronounced alteration of astroglial and microglial cell infiltration of the spinal cord under Fasudil treatment. Modeling a proinflammatory microglial phenotype by stimulation with LPS in vitro, Fasudil decreased the release of proinflammatory cytokines and chemokines TNFα, Il6, CCL2, CCL3, and CCL5 while CXCL1 release was only transiently suppressed. In sciatic nerve motor axons, neuromuscular junction remodeling processes were increased. In conclusion, we provide preclinical and neurobiological evidence that inhibition of ROCK by the clinically approved small molecule inhibitor Fasudil may be a novel therapeutic approach in ALS combining both neuroprotection and immunomodulation for the cure of this devastating disease. GLIA 2014;62:217-232.
Glia.Glia.2014 Feb;62(2):217-32. doi: 10.1002/glia.22601. Epub 2013 Dec 6.
Disease progression in amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motoneurons (MN) and their axons, but is also influenced by neighboring cells such as astrocytes and microglial cells. The role of microglia in ALS is complex as it switches from an anti-inflammatory and n
PMID 24311453

High‑dose fasudil preconditioning and postconditioning attenuate myocardial ischemia‑reperfusion injury in hypercholesterolemic rats.

Wu N1, Zhang X2, Jia D1.Author information 1Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.2Department of Medical Genetics, China Medical University, Shenyang, Liaoning 110001, P.R. China.AbstractFasudil may induce preconditioning and postconditioning against myocardial ischemia‑reperfusion injury in normal rats, however, their effectivenesses in hypercholesterolemia remains to be determined. The study aimed to investigate whether fasudil induces preconditioning and postconditioning in hypercholesterolemic rats and to determine the roles of the phosphoinositol 3‑kinase (PI3K)/Akt/endothelial nitric oxide synthase (eNOS) pathway and mitochondrial KATP (m‑KATP) channels in this process. Isolated rat hearts underwent 30 min global ischemia and 120 min reperfusion. Low‑ (1 mg/kg) or high‑dose (10 mg/kg) fasudil was administered 15 min prior to ischemia and at the initial onset of reperfusion. 5‑Hydroxydecanoic acid (5HD), an m‑KATP channel blocker, at 10 mg/kg was administered 5 min prior to reperfusion. Myocardial infarct size was estimated by 2,3,5‑triphenyltetrazolium chloride (TTC) staining and lactate dehydrogenase (LDH) and creatine kinase‑MB (CK‑MB) were analyzed from coronary effluents. Phosphorylation of Akt and eNOS was measured by immunoblotting. High‑dose fasudil‑induced preconditioning and postconditioning significantly reduced infarct size and the release of LDH and CK‑MB and increased the phosphorylation of Akt and eNOS compared with the control group, whereas low‑dose fasudil did not exert these beneficial effects. In addition, the cardioprotection of high‑dose fasudil‑induced preconditioning and postconditioning are blocked by 5HD. Low‑dose fasudil‑induced preconditioning and postconditioning are abrogated by hypercholesterolemia, while high‑dose fasudil restores the cardioprotection, which is involved in upregulation of the PI3K/Akt/eNOS pathway and inducing the opening of the m‑KATP channel.
Molecular medicine reports.Mol Med Rep.2014 Feb;9(2):560-6. doi: 10.3892/mmr.2013.1818. Epub 2013 Nov 20.
Fasudil may induce preconditioning and postconditioning against myocardial ischemia‑reperfusion injury in normal rats, however, their effectivenesses in hypercholesterolemia remains to be determined. The study aimed to investigate whether fasudil induces preconditioning and postconditioning in hyp
PMID 24271017

Fasudil improves short-term echocardiographic parameters of diastolic function in patients with type 2 diabetes with preserved left ventricular ejection fraction: a pilot study.

Guo R, Su Y, Yan J, Sun H, Wu J, Liu W, Xu Y.Author information Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yan Chang Zhong Road, Shanghai, 200072, China.AbstractLeft ventricular (LV) diastolic dysfunction is observed frequently in patients with type 2 diabetes; however, few studies have focused on the effect of the Rho-associated kinase inhibitor fasudil on cardiac performance in humans. We conducted a prospective pilot study to assess the impact of fasudil on LV diastolic function in patients with diabetes without systolic dysfunction. Two hundred and fifty eligible patients with type 2 diabetes (149 men [61.3 %] and 94 women [38.7 %]) with a mean age of 57.2 years were randomly assigned to fasudil (n = 122, 30 mg intravenously twice a day for 14 days) or placebo (n = 121) groups. Echocardiographic variables were measured at the baseline and 1 month after the intervention. Compared with the placebo group, the fasudil group showed a significant decrease in diastolic blood pressure and in the peak of late diastolic transmitral flow (Am) (P < 0.05 for both). Deceleration time (DT), isovolumic relaxation time (IVRT), the peak of early diastolic annular velocity (e'), the peak of late diastolic annular velocity, and E/e' also exhibited a significant improvement (all, P < 0.05) after fasudil administration. Furthermore, the Em/Am ratio and IVRT, DT, and E/e' values recorded after fasudil treatment in the subgroup with impaired LV relaxation significantly differed from the corresponding values in the subgroup with normal LV relaxation (all, P < 0.05). Fasudil improves short-term echocardiographic parameters of LV diastolic function in patients with type 2 diabetes with preserved left ventricular ejection fraction.
Heart and vessels.Heart Vessels.2014 Jan 5. [Epub ahead of print]
Left ventricular (LV) diastolic dysfunction is observed frequently in patients with type 2 diabetes; however, few studies have focused on the effect of the Rho-associated kinase inhibitor fasudil on cardiac performance in humans. We conducted a prospective pilot study to assess the impact of fasudil
PMID 24390764