Search results for "Piperazines"
showing 10 items of 135 documents
Relaxation of the isolated human internal anal sphincter by sildenafil.
2007
Abstract Background Hypertonicity of the internal anal sphincter (IAS) appears to be involved in the pathogenesis of anal fissure. The relaxant effects of sildenafil, a selective phosphodiesterase 5 (PDE5) inhibitor, on isolated human IAS were investigated. Methods The efficacy (maximal effect, Emax) and potency (−log IC50, where IC50 is half-maximal inhibitory concentration) of the PDE5 inhibitors, sildenafil and zaprinast, and of nitric oxide donors, sodium nitroprusside and glyceryl trinitrate, as relaxants of histamine (0·1 mmol/l)-induced tone were examined in IAS strips under isometric contraction. The presence of PDE5 isoenzymes and changes in intracellular calcium and cyclic nucleot…
Sustained remissions and low rate of BCR-ABL resistance mutations with imatinib treatment chronic myelogenous leukemia in patients treated in late ch…
2007
The introduction of Imatinib (IM) has significantly altered the treatment for CML, although only limited follow-up results are available. As failure of Interferon-alpha had been associated with poor prognosis and results of IM-treatment in this patient group may allow earlier estimation of long-term benefits for early chronic phase patients. Therefore we prospectively analyzed the quality and duration of remissions and the rate of BCR-ABL resistance mutations occurring in patients treated with IM, if they were intolerant or refractory to interferon. Fifty-nine patients were included and median follow up is 4.75 years. Haematologic remission rate was 92% and 62% of patients achieved at least…
Sustained Complete Molecular Remissions After Treatment With Imatinib-Mesylate in Patients With Failure After Allogeneic Stem Cell Transplantation fo…
2005
Purpose In the era of molecular therapy of chronic myelogenous leukemia (CML) applying BCR-ABL tyrosine kinase inhibitors, the usefulness of molecular end points, in particular, quantitative polymerase chain reaction (PCR) for BCR-ABL in monitoring responses has been broadly accepted. Therefore, we have designed a prospective phase II trial in CML, which, for the first time, evaluated the feasibility and safety of molecular end points as surrogate markers to guide through a stratified treatment algorithm within a multicenter trial. Patients and Methods As a clinical model, we adopted minimal residual disease (MRD) found in relapse after allogeneic stem cell transplantation (SCT) in CML. For…
Favorable long-term follow-up results over 6 years for response, survival, and safety with imatinib mesylate therapy in chronic-phase chronic myeloid…
2008
Abstract Imatinib mesylate, a targeted inhibitor of BCR-ABL tyrosine kinase, is the standard of care for chronic myeloid leukemia (CML). A phase 2 trial of imatinib in late chronic-phase (CP) CML after interferon-α (IFNα) failure enrolled 532 patients, 454 with a confirmed diagnosis of CP CML. Median time from diagnosis was 34 months; median duration of imatinib treatment was 65 months. Cumulative best rates of major cytogenetic response (MCyR) and complete cytogenetic response (CCyR) were 67% and 57%, respectively. At the 5-year landmark, 184 (41%) of the 454 patients are in CCyR. At more than 6 years, 199 (44%) of the 454 patients remain on imatinib. Most responses occurred within 12 mont…
Current results on the use of imatinib mesylate in patients with relapsed philadelphia chromosome positive leukemia after allogeneic or syngeneic hem…
2003
Here, we describe a patient diagnosed with chronic myelogenous leukemia who relapsed after matched unrelated donor SCT. The patient was treated with imatinib mesylate and donor lymphocyte infusions, and achieved a complete molecular remission. Additionally, safety and efficacy of imatinib mesylate in a total of 134 patients from 8 centers who underwent allogeneic or syngeneic stem cell transplantation (SCT) and had a relapse of Philadelphia chromosome positive leukemia was reviewed. Data was compiled from abstracts accepted as oral or poster presentations at the ASH (American Society of Hematology) 2001 and EBMT (European Group for Blood and Marrow Transplantation) 2001 & 2002 meetings and …
Perinatal exposure to 5-methoxytryptamine, behavioural-stress reactivity and functional response of 5-HT1A receptors in the adolescent rat.
2008
Abstract Serotonin is involved in a wide range of physiological and patho-physiological mechanisms. In particular, 5-HT1A receptors are proposed to mediate stress-adaptation. The aim of this research was to investigate in adolescent rats: first, the consequences of perinatal exposure to 5-metoxytryptamine (5MT), a 5-HT1/5-HT2 serotonergic agonist, on behavioural-stress reactivity in elevated plus maze, open field and forced swim tests; secondly, whether the behavioural effects induced by perinatal exposure to 5MT on open field and forced swim tests were affected by the selective 5-HT1A receptor agonist LY 228729, a compound able to elicit a characteristic set of motor behaviours on these ex…
m-Chlorophenylpiperazine excites non-dopaminergic neurons in the rat Substantia Nigra and Ventral Tegmental Area by activating serotonin-2c receptors
2001
In vivo electrophysiological techniques were used to study the effect of m-chlorophenylpiperazine, a non-selective serotonin-2C receptor agonist, on the activity of non-dopaminergic neurons in the substantia nigra pars reticulata and the ventral tegmental area of anesthetized rats. Intravenous administration of m-chlorophenylpiperazine (5–320 μg/kg) caused a dose-dependent increase in the basal firing rate of a subpopulation of nigral neurons which do not respond to a footpinch stimulus [P(0) neurons], whereas it did not affect the activity of neurons which are responsive to the footpinch [P(+) neurons]. However, m-chlorophenylpiperazine (5–320 μg/kg) excited all non-dopaminergic neurons sa…
5-HT3 receptor-channels coupled with Na+ influx in human T cells: role in T cell activation.
1999
The study was conducted on a human (Jurkat) T cell line, loaded with a Na+ fluorescent probe, SBFI/AM. Serotonin and an agonist of 5-HT3 receptor-channels, 2-methyl-5HT, evoked Na+ influx, whereas the agonists of other serotonergic receptor subtypes, i.e., 5-HT1A and 5-HT1B receptors, failed to induce Na+ influx in these cells. By using 3H-BRL43694, an agonist of 5-HT3 receptor-channels, we characterized 5-HT3 lymphocyte receptors which exhibited a density (Bmax) of 300 +/- 20 fmol/10(6) cells and a Kd of 30 nM in Jurkat T cells. The T-cell 5-HT3 receptor-channel is not regulated either by the protein kinase C or by the free intracellular calcium concentrations as the agents known to activa…
From attraction to repulsion : anion–π interactions between bromide and fluorinated phenyl groups
2011
Anion–π interactions in crystals of fluorobenzyl ammonium salts depend on the degree of fluorination at the aromatics.
Biomimetic diels–alder cyclizations for the construction of the brevianamide, paraherquamide, sclerotamide, asperparaline and VM55599 ring systems
1998
Abstract A potentially bio-mimetic Diels–Alder cyclization to construct the bicyclo[2.2.2] ring system common to the paraherquamides, marcfortines, sclerotamides, brevianamides, VM55599, and asperparaline is reported. Epi-deoxybrevianamide E (22) is converted into the corresponding lactim ether (23) and then oxidized with DDQ to provide an azadiene (24) which is tautomerized in the presence of base to azadiene 25 which, spontaneously cyclizes to give a 2:1 mixture of cycloadducts 26 and 27. These cycloadducts are each in turn, converted into d , l -C-19-epi-brevianamide A (20) and d , l -brevianamide B (6). The stereochemical implications of the [4+2] cycloaddition is discussed in the conte…