Search results for "Nucleoside"
showing 10 items of 166 documents
Can guanine-based purines be considered modulators of intestinal motility in rodents?
2010
Adenine-based purines play a pivotal role in the control of gastrointestinal motility in rodents. Recently, guanine-based purines have been also shown to exert extracellular effects in the central nervous system raising the possibility of the existence of distinct receptors for guanine-based purines. Thus, it seems likely to speculate that also guanine-based purines may play a role in the modulation of the intestinal contractility. Spontaneous and neurally-evoked mechanical activity was recorded in vitro as changes in isometric tension in circular muscle strips from mouse distal colon. Guanosine up to 3 mM or guanine up to 1 mM failed to affect the spontaneous mechanical activity, but reduc…
Nucleoside phosphotransferase in animal tissues. Tissue distribution and kinetic properties
1985
Amphibian, avian and mammal tissues contain a nucleoside phosphotransferase clearly different from those previously described in vegetables and bacteria. Whatever the animal source, the enzyme showed many similar characteristics as far as substrate specificity, dependence upon Mg2+, instability at 37 degrees C, and the protecting effect of nucleotides were concerned. Moreover, when submitted to gel filtration, the enzyme behaved in all cases as a dissociable high molecular weight protein, whose degree of association was controlled by nucleotides. In amphibian and avian tissues multiple forms of the enzyme seem to be present which differ for the substrate concentration at half-maximal veloci…
Efficacy and tolerability of EH301 for amyotrophic lateral sclerosis: a randomized, double-blind, placebo-controlled human pilot study
2019
Background: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, characterized by progressive loss of spinal and cortical motor neurons, leading to muscular atrophy, respiratory failure, and ultimately death. There is no known cure, and the clinical benefit of the two drugs approved to treat ALS remains unclear. Novel disease-modifying therapeutics that are able to modulate the disease course are desperately needed. Our objective was to evaluate the efficacy and tolerability of Elysium Health's candidate drug EH301 in people with ALS (PALS). Methods: This was a single-center, prospective, double-blind, randomized, placebo-controlled pilot study. Thirty-two PALS we…
Effectiveness of dolutegravir-based regimens as either first-line or switch antiretroviral therapy: data from the Icona cohort
2019
Introduction: Concerns about dolutegravir (DTG) tolerability in the real-life setting have recently arisen. We aimed to estimate the risk of treatment discontinuation and virological failure of DTG-based regimens from a large cohort of HIV-infected individuals. Methods: We performed a multicentre, observational study including all antiretroviral therapy (ART)-naïve and virologically suppressed treatment-experienced (TE) patients from the Icona (Italian Cohort Naïve Antiretrovirals) cohort who started, for the first time, a DTG-based regimen from January 2015 to December 2017. We estimated the cumulative risk of DTG discontinuation regardless of the reason and for toxicity, and of virologica…
Pre- and postjunctional effects of diadenosine polyphosphates in the guinea-pig vas deferens.
1995
Abstract The pre- and postjunctional activities of a number of diadenosine polyphosphates were examined in the guinea-pig isolated vas deferens at the level of the membrane-potential, using a modified sucrose-gap technique. P1,P3-Di(adenosine 5′)triphosphate (Ap3A), P1,P4-di(adenosine 5′)tetraphosphate (Ap4A) and P1,P5-di(adenosine 5′)pentaphosphate (Ap5 A) all caused concentration-dependent depolarization of the smooth muscle membrane. The potency order was: Ap5A > Ap4A. Ap3A. P1, P2-Di(adenosine 5′)pyrophosphate (Ap2A) did not evoke depolarization even at the highest concentration tested (1 mM). All the dinucleotides caused a reduction in the amplitude of evoked excitatory junction…
Guanosine negatively modulates the gastric motor function in mouse
2013
The aim of the present study was to evaluate if guanine-based purines may affect the gastric motor function in mouse. Thus, the influence of guanosine on the gastric emptying rate in vivo was determined and its effects on spontaneous gastric mechanical activity, detected as changes of the intraluminal pressure, were analyzed in vitro before and after different treatments. Gastric gavage of guanosine (1.75-10 mg/kg) delayed the gastric emptying. Guanosine (30 μM-1 mM) induced a concentration-dependent relaxation of isolated stomach, which was not affected by the inhibition of the purine nucleoside phosphorylase enzyme by 4'-deaza-1'-aza-2'-deoxy-1'-(9-methylene)-immucillin-H. The inhibitory …
Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe
2014
Background: One out of ten newly diagnosed patients in Europe was infected with a virus carrying a drug resistant mutation. We analysed the patterns over time for transmitted drug resistance mutations (TDRM) using data from the European Spread program.Methods: Clinical, epidemiological and virological data from 4317 patients newly diagnosed with HIV-1 infection between 2002 and 2007 were analysed. Patients were enrolled using a pre-defined sampling strategy.Results: The overall prevalence of TDRM in this period was 8.9% (95% CI: 8.1-9.8). Interestingly, significant changes over time in TDRM caused by the different drug classes were found. Whereas nucleoside resistance mutations remained con…
New Imidazo[2,1-b][1,3,4]Thiadiazole Derivatives Inhibit FAK Phosphorylation and Potentiate the Antiproliferative Effects of Gemcitabine Through Modu…
2020
Background/aim A new class of imidazo[2,1-b][1,3,4]thiadiazole compounds have recently been evaluated as inhibitors of phosphorylation of focal adhesion kinase (FAK) in pancreatic cancer. FAK is overexpressed in mesothelioma and has recently emerged as an interesting target for the treatment of this disease. Materials and methods Ten imidazo[2,1-b][1,3,4]thiadiazole compounds characterized by indole bicycle and a thiophene ring, were evaluated for their cytotoxic activity in two primary cell cultures of peritoneal mesothelioma, MesoII and STO cells. Results Compounds 1a and 1b showed promising antitumor activity with IC50 values in the range of 0.59 to 2.81 μM in both cell lines growing as …
Unzipping Nucleoside Channels by Means of Alcohol Disassembly
2013
Gold nanoparticles capped with simple adenosine derivatives can form colloidal aggregates in nonpolar solvents. Theoretical calculations indicate the formation of organic channels by the supramolecular assembly of the nanoparticles by means of hydrogen bonds between the adenine moieties. The aggregates were only negligibly sensitive to nPrOH, iPrOH, and tBuOH, whereas some showed a similar response to MeOH and EtOH, and others showed high selectivity toward MeOH. DNA nucleoside derivatives (1-(2-deoxy-β-D-ribofuranosyl)-5-methyluracil and 2′,3′-O-isopropylideneadenosine) as well as thymine and other aromatic compounds such as pyrene derivatives (pyrene, 1-chloropyrene, 1-hydroxypyrene, (1-p…
Chronic hepatitis B: who to treat and which choice of treatment?
2009
The goal of antiviral therapy in patients with chronic hepatitis B is to prevent, through persistent suppression of HBV replication, cirrhosis and hepatocellular carcinoma. Currently, seven drugs are available: IFN-alpha, pegylated interferon, lamivudine, adefovir dipivoxil, entecavir, telbivudine and tenofovir. The choice of the drugs should always take into consideration the clinical features of patients, the antiviral efficacy of each drug, the risk of developing resistance, the long-term safety profile, the method of administration and the cost of therapy. Ideal candidates for treatment are hepatitis B e antigen-positive patients with a prolonged phase of immune clearance and hepatitis …