Search results for "Azine"

Dual role of the p38 MAPK/cPLA2 pathway in the regulation of platelet apoptosis induced by ABT-737 and strong platelet agonists.

2013

p38 Mitogen-activated protein (MAP) kinase is involved in the apoptosis of nucleated cells. Although platelets are anucleated cells, apoptotic proteins have been shown to regulate platelet lifespan. However, the involvement of p38 MAP kinase in platelet apoptosis is not yet clearly defined. Therefore, we investigated the role of p38 MAP kinase in apoptosis induced by a mimetic of BH3-only proteins, ABT-737, and in apoptosis-like events induced by such strong platelet agonists as thrombin in combination with convulxin (Thr/Cvx), both of which result in p38 MAP kinase phosphorylation and activation. A p38 inhibitor (SB202190) inhibited the apoptotic events induced by ABT-737 but did not influ…

Eltrombopag in chronic hepatitis C

2014

Chronic hepatitis C is a public health problem worldwide. Unfortunately, not all patients may benefit from antiviral therapy due to thrombocytopenia. Its causes are represented by portal hypertension and platelet sequestration in the spleen, decreased serum levels or activity of thrombopoietin, the bone marrow suppression induced by hepatitis C virus and a possible adverse effect of interferon. Thrombopoietin receptor analogs may contribute to increase platelet counts in these patients. Eltrombopag binds to another region of the thrombopoietin receptor compared to endogenous thrombopoietin and stimulates the proliferation and maturation of megakaryocytes and the platelet production in a dos…

COX-1/COX-2 inhibitors based on the methanone moiety

2002

This paper focuses on the synthesis and the in vitro testing of dual COX-1/COX-2 inhibitors. Starting from structures of non-steroidal anti-inflammatory drugs (NSAIDs) the diaryl methanone element was chosen as a lead. Modifications were carried out on this scaffold to obtain potent inhibitors of the COX enzymes. The N-(2-aroylphenyl)sulphonamides and -amides were studied in detail, and to consolidate the data evaluated the corresponding 3- and 4-regioisomers were also investigated. The potency and the enzyme selectivity were varied by structural modifications of the lead.

Pharmacokinetics of acute and sub-chronic aripiprazole in P-glycoprotein deficient mice

2010

Abstract Background P-glycoprotein (P-gp), an efflux transporter localized in the blood–brain barrier, limits the access of multiple xenobiotics to the central nervous system (CNS). For the new antipsychotic aripiprazole and its active metabolite dehydroaripiprazole differences in disposition in blood and brain were investigated after acute and sub-chronic administration in a P-gp knockout mouse model. Methods Serum and brain concentrations of both drugs were measured at several time points 1–24 h after i.p. injection of 10 mg/kg aripiprazole and after 11 days of sub-chronic administration in several tissues. Moreover, the expression of P-gp was determined by Western blot analysis after sub…

Synthesis, crystal structure and magnetic properties of the complex [ReCl3(tppz)]·MeCN

2015

The reaction of the starting materials [ReIIICl3(MeCN)(PPh3)2] or [ReVOCl3(PPh3)2] with 2,3,5,6-tetrakis(2-pyridyl)pyrazine (tppz) in acetonitrile yielded the Re(III) complex [ReCl3(tppz)]·MeCN (1). This complex crystallizes in the monoclinic space group P21/n and its crystal structure consists of neutral mononuclear entities with meridional geometry of the chloride ligands, and the six-coordination of the Re(III) ion being completed by the tridentate tppz ligand. Each metal centre exhibits a highly distorted octahedral coordination with Re–Cl and Re–Ntppz bond lengths covering the ranges 2.3590(9)–2.3606(8) and 1.971(2)–2.096(2) A, respectively. The magnetic properties of 1 have been inves…

Use of intrapleural bortezomib in myelomatous pleural effusion [1]

2007

Mildronate treatment improves functional recovery following middle cerebral artery occlusion in rats

2011

Mildronate (3-(2,2,2-trimethylhydrazinium) propionate) is an inhibitor of l-carnitine biosynthesis and an anti-ischemic drug. In the present study, we investigated the effects of mildronate in rats following focal cerebral ischemia. Male Wistar rats were subjected to transient occlusion of the middle cerebral artery (MCAO) for 90min, followed by the intraperitoneal administration of mildronate at doses of 100 and 200mg/kg 2h after reperfusion and then daily for an additional 14days. The beam-walking, rota-rod and cylinder tests were used to assess sensorimotor function, and vibrissae-evoked forelimb-placing and limb-placing tests examined responses to tactile and proprioceptive stimulation.…

Two mesalazine regimens in the prevention of the post-operative recurrence of Crohn's disease: a pragmatic, double-blind, randomized controlled trial

2003

Summary Background : The role of mesalazine in preventing the clinical recurrence of Crohn's disease after surgery has been shown in a meta-analysis of all published studies. No clear relationship, however, has been shown between dosage and response. Aim : To evaluate whether 4.0 g/day of mesalazine may offer therapeutic advantages over 2.4 g/day in the prevention of both endoscopic and clinical post-operative recurrence of Crohn's disease. Methods : The study was a double-blind, randomized, multi-centre, prospective, controlled clinical trial. Two hundred and six patients, submitted to first or second intestinal resection for Crohn's disease limited to the terminal ileum, with or without i…

Investigation of Diketopiperazines Containing a Guanidino-Functionalized Sidechain as Potential Catalysts of Enantioselective Strecker Reactions

2005

Diketopiperazine 1 consisting of L-(γ-guanidino-α-amino)butyric acid and L-phenylalanine was synthesized as the hydroacetate and as the hydronitrate. Its structure was confirmed by X-ray analysis. In contrast to reports in the literature (Lipton et al.), compound 1 does not induce enantioselevtive catalysis of Strecker reactions. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Evidence for a modulatory role of cannabinoids on the excitatory NANC neurotransmission in mouse colon

2007

Abstract It is well accepted that endogenous cannabinoids and CB1 receptors are involved in the regulation of smooth muscle contractility and intestinal motility, through a mechanism mainly related to reduction of acetylcholine release from cholinergic nerve endings. Because, few data exist on a possible modulatory action of the cannabinoid agents on the non-adrenergic non-cholinergic (NANC) excitatory and inhibitory neurotransmission, the aim of the present study was to investigate the effects of cannabinoid drugs on the NANC responses elicited by electrical field stimulation (EFS) in the circular muscle of mouse proximal colon. Colonic contractions were monitored as changes in endoluminal…