Search results for "Purines"
showing 10 items of 49 documents
Glucose-independent improvement of vascular dysfunction in experimental sepsis by dipeptidyl-peptidase 4 inhibition.
2012
Aims Dipeptidyl peptidase-4 (DPP-4) inhibitors are a novel class of drugs for the treatment of hyperglycaemia. Preliminary evidence suggests that their antioxidant and anti-inflammatory effects may have beneficial effects on the cardiovascular complications of diabetes. In the present study, we investigate in an experimental sepsis model whether linagliptin exerts pleiotropic vascular effects independent of its glucose-lowering properties. Methods and results Linagliptin (83 mg/kg chow for 7days) was administered in a rat model of lipopolysaccharide (LPS) (10 mg/kg, single i.p. dose/24 h)-induced sepsis. Vascular relaxation, reactive oxygen species (ROS) formation, expression of NADPH oxida…
An approach to the evaluation of the activity of the DNA repair enzyme O6-methylguanine-DNA-methyl-transferase in tumor tissue in vivo: syntheses of …
2002
Abstract The resistance of tumor cells to the cytostatic activity of methylating and chloroethylating anticancer drugs is determined by the level of expression of the DNA repair protein O 6 -methylguanine-DNA-methyl-transferase (MGMT). The synthesis of labelled 6-benzyloxy-9H-purin-2-ylamine derivatives should hence allow a quantification of the MGMT status of tumor and non-target tissue in vivo. 6-benzyloxy-9-(2-fluoroethyl)-9H-purin-2-yl-amine and 6-benzyloxy-7-(2-fluoroethyl)-7H-purin-2-yl-amine were synthesized and evaluated in vitro, both showing an affinity of 1.8 μM. 6-benzyloxy-9-(2-[ 18 F]fluoroethyl)-9H-purin-2-yl-amine and 6-benzyloxy-7-(2-[ 18 F]fluoroethyl)-7H-purin-2-yl-amine …
Late-onset Crohn's disease: a comparison of disease behaviour and therapy with younger adult patients: the Italian Group for the Study of Inflammator…
2019
BACKGROUND Disease phenotype and outcome of late-onset Crohn's disease are still poorly defined. METHODS In this Italian nationwide multicentre retrospective study, patients diagnosed ≥65 years (late-onset) were compared with young adult-onset with 16-39 years and adult-onset Crohn's disease 40-64 years. Data were collected for 3 years following diagnosis. RESULTS A total of 631 patients (late-onset 153, adult-onset 161, young adult-onset 317) were included. Colonic disease was more frequent in late-onset (P < 0005), stenosing behaviour was more frequent than in adult-onset (P < 0003), but fistulising disease was uncommon. Surgery rates were not different between the three age groups. Syste…
PURINE AND PYRIMIDINE NUCLEOTIDES IN THE BRAIN OF NORMAL AND CONVULSANT RATS
1969
— Purine and pyrimidine nucleotides were measured in the brain of normal and electroshocked rats after chromatographic separation on ion-exchange resin of mono-, di- and tri-phosphorylated derivatives. CMP, IMP and NAD did not show any significant quantitative change. Adenine nucleotides showed an abrupt change followed by a rapid return to the control value. GTP was the only purine nucleotide exhibiting a relatively slow return to its starting concentration. The greatest percentage increase after electroshock was observed in UMP, which returned to its control value only after 5 min; UDPCoenzymes (i.e. UDPA plus UDPG) showed a relatively small drop during the development of the seizure and …
Increased risk for nonmelanoma skin cancers in patients who receive thiopurines for inflammatory bowel disease.
2011
International audience; BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) who have been exposed to thiopurines might have an increased risk of skin cancer. We assessed this risk among patients in France. METHODS: We performed a prospective observational cohort study of 19,486 patients with IBD, enrolled from May 2004 to June 2005, who were followed up until December 31, 2007. The incidence of nonmelanoma skin cancer (NMSC) in the general population, used for reference, was determined from the French Network of Cancer Registries. RESULTS: Before the age of 50 years, the crude incidence rates of NMSC among patients currently receiving or who previously received thiopurines wer…
Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study.
2009
International audience; BACKGROUND: Reports of an increased risk of lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease are controversial. We assessed this risk in a prospective observational cohort study. METHODS: 19,486 patients with inflammatory bowel disease, of whom 11,759 (60.3%) had Crohn's disease and 7727 (39.7%) had ulcerative colitis or unclassified inflammatory bowel disease, were enrolled in a nationwide French cohort by 680 gastroenterologists, who reported details of immunosuppressive therapy during the observation period, cases of cancer, and deaths. The risk of lymphoproliferative disorder was assessed according to thiopurine expos…
Role of K+ and Ca2+ fluxes in the cerebroarterial vasoactive effects of sildenafil
2007
The aim of this study was to assess the role of K(+) and Ca(2+) fluxes in the cerebroarterial vasoactive effects of the phosphodiesterase-5 inhibitor sildenafil. We used isolated rabbit basilar arteries to assess the effects of extracellular K(+) raising on sildenafil-induced vasodilatation, and studied the pharmacological interaction of sildenafil with selective modulators of membrane K(+) and Ca(2+) channels. Expression of Kv1 subunits of K(+) channels was assessed at messenger and protein levels. Parallel experiments were carried out with zaprinast for comparison. Sildenafil (10 nM-0.1 mM) induced concentration-dependent relaxation of endothelin-1 (10 nM)-precontracted arteries, which wa…
Lower self-reported depression in patients with erectile dysfunction after treatment with sildenafil
2001
Abstract Background: Depressive symptoms in men with erectile dysfunction (ED) may improve under successful ED treatment. Self-reported depressive symptoms were compared in men with ED after sildenafil treatment to a group of untreated patients. Methods: In an open study, self-reported depressive symptoms of 54 men after successful treatment with sildenafil (>4 weeks) and 51 men awaiting ED treatment were investigated with the Center of Epidemiologic Studies–Depression Scale (CES–D). CES–D items were subjected to an exploratory factor analysis and group differences in CES–D items and factors were analyzed. Results: Groups were comparable with respect to demographic characteristics and illne…
Relaxant effect of sildenafil in the rabbit basilar artery
2005
We hypothesized that sildenafil, inhibitor of phosphodiesterase-5 (PDE-5), interacts with the nitric oxide (NO)-cGMP pathway in the cerebral arteries and shows vasoactive effects. To prove it in the isolated rabbit basilar artery, we compared the effects of sildenafil with other PDE-5 inhibitors, assessed the endothelial dependence of the vasoactive responses, and used modulators of the cGMP and cAMP signaling processes. Sildenafil (10 nM-0.1 mM) induced concentration-dependent relaxations of endothelin-1 (10 nM)-precontracted basilar artery, which were partially inhibited both in endothelium-denuded arteries and in arteries precontracted by depolarization with KCl (50 mM). Endothelin-1 (1 …
Quality of partnership in patients with erectile dysfunction after sildenafil treatment.
2001
OBJECTIVE A comprehensive investigation on the quality of partnership of male patients with erectile dysfunction (ED) after treatment with sildenafil vs. untreated patients, as perceived by both the patients and their female partners. METHODS This report describes an observational, cross-sectional exploratory study comparing ED patients responsive to sildenafil with ED patients prior to therapy. Assessments included the 'International Index of Erectile Function' (IIEF) and the 'Partnerschaftsfragebogen' (PFB), a partnership questionnaire used in German-speaking countries. The comparability of the two study groups was examined using a stepwise logit model. Significant intergroup differences …