Search results for "Nucleotides"
showing 10 items of 297 documents
Rat liver preservation by hypothermic oscillating liver perfusion compared to simple cold storage.
1998
Rat livers were preserved hypothermically for 10 or 24 h in vitro as if for transplantation. Two methods of preservation were compared using physiological and biochemical parameters: simple storage and oscillating perfusion. By measuring the nucleotides after preservation the calculated energy charge was significantly higher after 10 and 24 h of oscillating perfusion compared to the simple storage group. In addition, a significant energy charge loading was demonstrated by 10 h oscillating perfusion compared to the initial value prior to perfusion. The oscillating, computer-controlled perfusion permits continuous monitoring of perfusate temperature, O2 consumption, pCO2, portal vein pressure…
Comparison of the effects of valproate, ethosuximide, phenytoin, and pentobarbital on cerebral energy metabolism in the rat.
1987
The acute effects of valproate (200 and 400 mg/kg), ethosuximide (200 and 400 mg/kg), phenytoin (25 and 50 mg/kg), and pentobarbital (30 and 60 mg/kg) on cerebral energy metabolism of rats were studied by measuring the cerebral content of energy metabolites and by evaluating the rate of metabolite utilization following decapitation. The treatments did not affect the levels of phosphocreatine (PCr), ATP, ADP, and AMP, but did enhance the glycogen or glucose stores. Pentobarbital induced a decrease in lactate, whereas valproate led to a decrease in pyruvate and an increase in lactate. Calculation of the metabolite fluxes after decapitation showed that all treatments delayed the rate of ATP ut…
Down-regulation of Glutathione and Bcl-2 Synthesis in Mouse B16 Melanoma Cells Avoids Their Survival during Interaction with the Vascular Endothelium
2003
B16 melanoma (B16M) cells with high GSH content show high metastatic activity. However, the molecular mechanisms linking GSH to metastatic cell survival are unclear. The possible relationship between GSH and the ability of Bcl-2 to prevent cell death was studied in B16M cells with high (F10) and low (F1) metastatic potential. Analysis of a Bcl-2 family of genes revealed that B16M-F10 cells, as compared with B16M-F1 cells, overexpressed preferentially Bcl-2 (approximately 5.7-fold). Hepatic sinusoidal endothelium-induced B16M-F10 cytotoxicity in vitro increased from approximately 19% (controls) to approximately 97% in GSH-depleted B16M-F10 cells treated with an antisense Bcl-2 oligodeoxynucl…
Bcl-2 and Mn-SOD antisense oligodeoxynucleotides and a glutamine-enriched diet facilitate elimination of highly resistant B16 melanoma cells by tumor…
2005
Mitochondrial glutathione (mtGSH) depletion increases sensitivity of Bcl-2-overexpressing B16 melanoma (B16M)-F10 cells (high metastatic potential) to tumor necrosis factor-alpha (TNF-alpha)-induced oxidative stress and death in vitro. In vivo, mtGSH depletion in B16M-F10 cells was achieved by feeding mice (where the B16M-F10 grew as a solid tumor in the footpad) with an L-glutamine (L-Gln)-enriched diet, which promoted in the tumor cells an increase in glutaminase activity, accumulation of cytosolic L-glutamate, and competitive inhibition of GSH transport into mitochondria. L-Gln-adapted B16M-F10 cells, isolated using anti-Met-72 monoclonal antibodies and flow cytometry-coupled cell sortin…
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 …
Activation of P2Y receptors by ATP and by its analogue, ADPbetaS, triggers two calcium signal pathways in the longitudinal muscle of mouse distal col…
2008
Our previous research showed that ATP and adenosine 5'-O-2-thiodiphosphate (ADPbetaS) induce contractile effects in the longitudinal muscle of mouse distal colon via activation of P2Y receptors which are not P2Y(1) or P2Y(12) subtypes. This study investigated the nature of the P2Y receptor subtype(s) and the mechanisms leading to the intracellular calcium concentration increase necessary to trigger muscular contraction. Motor responses of mouse colonic longitudinal muscle to P2Y receptor agonists were examined in vitro as changes in isometric tension. ATP or ADPbetaS induced muscular contraction, which was not affected by P2Y(11) or P2Y(13) selective antagonists. Calcium-free solution or th…
The hMTH1 paradox: antioxidants recommended in cancer?
2014
Summary Activated Ras GTPase signalling is a critical driver of oncogenic transformation and malignant disease. Cellular models of RAS-dependent cancers have been used to identify experimental small-molecules, such as SCH51344, but their molecular mechanism of action remains generally enigmatic. Here, using a chemical proteomic approach we identify the target of SCH51344 as the human mutT homologue MTH1, a nucleotide pool sanitising enzyme. Loss-of-function of MTH1 impaired growth of KRAS tumour cells whereas MTH1 overexpression mitigated sensitivity toward SCH51344. Searching for more drug-like inhibitors, we identified the kinase inhibitor crizotinib as a nanomolar suppressor of MTH1 acti…
Mongersen, an oral SMAD7 antisense oligonucleotide, and crohn's disease
2015
Crohn's disease-related inflammation is characterized by reduced activity of the immunosuppressive cytokine transforming growth factor β1 (TGF-β1) due to high levels of SMAD7, an inhibitor of TGF-β1 signaling. Preclinical studies and a phase 1 study have shown that an oral SMAD7 antisense oligonucleotide, mongersen, targets ileal and colonic SMAD7.In a double-blind, placebo-controlled, phase 2 trial, we evaluated the efficacy of mongersen for the treatment of persons with active Crohn's disease. Patients were randomly assigned to receive 10, 40, or 160 mg of mongersen or placebo per day for 2 weeks. The primary outcomes were clinical remission at day 15, defined as a Crohn's Disease Activit…
Effects of nitric oxide-active drugs on the discharge of subthalamic neurons: microiontophoretic evidence in the rat.
2006
The presence of nitric oxide (NO) synthase and of soluble guanylyl cyclase, the main NO-activated metabolic pathway, has been demonstrated in many cells of the subthalamic nucleus. In this study, the effects induced on the firing of 96 subthalamic neurons by microiontophoretically administering drugs modifying NO neurotransmission were explored in anaesthetized rats. Recorded neurons were classified into regularly and irregularly discharging on the basis of their firing pattern. Nω-nitro-l-arginine methyl ester (L-NAME; a NO synthase inhibitor), 3-morpholino-sydnonimin-hydrocloride (SIN-1; a NO donor), S-nitroso-glutathione (SNOG; another NO donor) and 8-Br-cGMP (a cell-permeable analogue o…
Mouse photoreceptor synaptic ribbons lose and regain material in response to illumination changes
2004
Abstract Chemical synapses equipped with ribbons are tonically active, high-output synapses. The ribbons may play a role in the trafficking of synaptic vesicles. Recent findings in retinal rod cells of BALB/c mice indicate that ribbons are large and smooth in the dark phase, and, due to the formation and release of protrusions, small during the light phase. As a consequence of these changes, ribbons may traffick fewer vesicles in the light than in the dark phases. The aim of the present study was to find out whether the above ribbon changes in this mouse strain are strictly illumination-dependent and which signalling processes may be involved. Here, we show that ribbons form protrusions and…