Search results for "Hydrazines"

Mildronate: An Antiischemic Drug for Neurological Indications

2005

Mildronate (3-(2,2,2-trimethylhydrazinium)propionate; MET-88; meldonium, quaterine) is an antiischemic drug developed at the Latvian Institute of Organic Synthesis. Mildronate was designed to inhibit carnitine biosynthesis in order to prevent accumulation of cytotoxic intermediate products of fatty acid beta-oxidation in ischemic tissues and to block this highly oxygen-consuming process. Mildronate is efficient in the treatment of heart ischemia and its consequences. Extensive evaluation of pharmacological activities of mildronate revealed its beneficial effect on cerebral circulation disorders and central nervous system (CNS) functions. The drug is used in neurological clinics for the trea…

Crystal structure of human gamma-butyrobetaine hydroxylase.

2010

Gamma-butyrobetaine hydroxylase (GBBH) is a 2-ketoglutarate-dependent dioxygenase that catalyzes the biosynthesis of l-carnitine by hydroxylation of gamma-butyrobetaine (GBB). l-carnitine is required for the transport of long-chain fatty acids into mitochondria for generating metabolic energy. The only known synthetic inhibitor of GBBH is mildronate (3-(2,2,2-trimethylhydrazinium) propionate dihydrate), which is a non-hydroxylatable analog of GBB. To aid in the discovery of novel GBBH inhibitors by rational drug design, we have solved the three-dimensional structure of recombinant human GBBH at 2.0A resolution. The GBBH monomer consists of a catalytic double-stranded beta-helix (DBSH) domai…

Swellable microparticles containing Suprofen: evaluation of in vitro release and photochemical behaviour

1998

Suprofen, an anti-inflammatory drug was incorporated in polymer networks based on biocompatible macromolecules, such as alpha,beta-polyasparthydrazide (PAHy) and alpha,beta-poly(N-hydroxyethyl)-DL-aspartamide (PHEA) crosslinked by glutaraldehyde or gamma-rays, respectively. Swelling tests carried out in aqueous media showed that pH value affects the swelling degree of the prepared hydrogels. In vitro release tests were performed in simulated gastrointestinal fluids (pH 1/6.8) using the pH variation method and in phosphate-buffered saline, pH 7.4. Experimental data indicated that Suprofen was released in a sustained way both from PAHy and PHEA microparticles. Further, incorporation of Suprof…

From 2000 to Mid-2010: A Fruitful Decade for the Synthesis of Pyrazoles

2011

Reproductive effects in German cockroaches by ecdysteroid agonist RH-0345, juvenile hormone analogue methoprene and carbamate benfuracarb

2004

1379-1176 (Print) Journal Article Research Support, Non-U.S. Gov't; Blatta germanica is the more prevalent cockroach species in Algeria. In the present study, we tested the effect on reproduction in B. germanica of two insect growth regulators, RH-0345, a benzoylhydrazine analogue that mimics the action of 20-hydroxyecdysone, and methoprene, one of the most commercially important juvenile hormone analogues, and a novel carbamate insecticide, benfuracarb. The compounds were applied topically (10 and 20 microg/insect for RH-0345, and 1 and 10 microg/insect for methoprene) or orally administrated (at 2% for benfuracarb) on newly emerged females and evaluated on reproductive events during the a…

15N NMR: Substituent effect analysis inpara-andmeta-substituted phenylhydrazines

1994

15N NMR spectra of phenylhydrazine and of 14 para- and meta-substituted phenylhydrazines were measured at natural isotope abundance in DMSO-d6 solution. The substituent present exerts a larger influence on the chemical shift of the nitrogen atom directly bound to the aromatic ring (N-1) than on the second one (N-2), which shows an attenuated and inverted trend. The chemical shifts of N-1 and N-2 give a good cross correlation in both series of compounds if p-NO2 and m-F derivatives are excluded from the correlations of para- and meta-substituted phenylhydrazines, respectively. Moreover, N-1 SCS values show good linear correlations with Hammett substituent constants, with SCSs of directly bou…

Eltrombopag before procedures in patients with cirrhosis and thrombocytopenia

2012

Eltrombopag is an oral thrombopoietin-receptor agonist. This study evaluated the efficacy of eltrombopag for increasing platelet counts and reducing the need for platelet transfusions in patients with thrombocytopenia and chronic liver disease who are undergoing an elective invasive procedure.We randomly assigned 292 patients with chronic liver disease of diverse causes and platelet counts of less than 50,000 per cubic millimeter to receive eltrombopag, at a dose of 75 mg daily, or placebo for 14 days before a planned elective invasive procedure that was performed within 5 days after the last dose. The primary end point was the avoidance of a platelet transfusion before, during, and up to 7…

12 weeks of interferon-based therapy is feasible in patients with hepatitis C-related cirrhosis and thrombocytopenia: A post hoc analysis of eltrombo…

2015

Background: A 24-48-week course of interferon-based therapy poorly tolerated in hepatitis C virus (HCV) cirrhosis patients with thrombocytopenia. Aim of the study was to identify patients at low-risk of liver-related complications over a 12-week course of interferon-based therapy. Methods: We assessed the rate of complications and death during the first 12 weeks of interferon-based therapy in HCV cirrhotics with thrombocytopenia (platelets ≤75×109/L) enrolled in the ENABLE-1 and -2 phase 3 randomised controlled trials. Results: Overall, among 1441 patients, 89 complications (6.9%) and 10 deaths (0.7%) were observed within the first 12 weeks of therapy. At univariate analysis baseline albumi…

Tumor dedifferentiation: an important step in tumor invasion.

1985

Tumor invasion in vivo was studied by light and electron microscopy as well as by immunofluorescence microscopy. Special regard was paid to the grade of tumor differentiation. Dimethylhydrazine-induced murine colonic carcinomas comprising a differentiated and an undifferentiated tumor type with low and high invasiveness respectively, were used. At the invasion front of both tumor types a striking dissociation of the organized tumor cell complexes into isolated tumor cells was found together with a loss of most of the cytological features of differentiation. It is supposed that this process mobilizes the tumor cells from the main tumor bulk enabling them to invade the host tissue by active l…

Neuroprotective properties of mildronate, a mitochondria-targeted small molecule.

2010

Mildronate, a representative of the aza-butyrobetaine class of drugs with proven cardioprotective efficacy, was recently found to prevent dysfunction of complex I in rat liver mitochondria. The present study demonstrates that mildronate also acts as a neuroprotective agent. In a mouse model of azidothymidine (anti-HIV drug) neurotoxicity, mildronate reduced the azidothymidine-induced alterations in mouse brain tissue: it normalized the increase in caspase-3, cellular apoptosis susceptibility protein (CAS) and iNOS expression assessed by quantitative and semi-quantitative analysis. Mildronate also normalized the changes in cytochrome c oxidase (COX) expression, reduced the expression of glia…