Disease relevance of Heteroxanthin

• Mx consumption was not related to the risk of benign breast tumors (fibroadenomas) [1].
• Pentoxifylline (PTX) is a methylxanthine which reduces IL-2 toxicity in animals [2].
• We have analyzed the effects of cAMP-elevating drugs (dibutyryl cAMP, forskolin, and isobutyl methylxanthine) on growth properties and myelin-specific gene expression in the peripheral neurinoma cell line D6P2T [3].
• Upon expression in Escherichia coli, one of them was found to encode a protein possessing 7-methylxanthine methyltransferase activity and was designated as CaMXMT [4].
• Methylxanthine therapy and reversible airway obstruction [5].

Psychiatry related information on Heteroxanthin

• The methylxanthine induces dose-response increases in locomotor activity in animals [6].
• The effects of postnatal chronic exposure to this methylxanthine on motor skills and locomotor activity were studied with a battery of motor and behavioral tests (negative geotaxis test, wire mesh ascending test, jumping down with a choice test, bar holding test, rotarod test and open field test) in rats during development [7].
• Following the injection of high doses of either methylxanthine, adult rats developed convulsions, tremors, lethargy and licking of lips [8].
• As the animal habituated to the stimulant action of the methylxanthine, however, total sleep time normalized, although time spent in Stage II slow wave sleep (S2) remained below, and Stage I slow wave sleep (S1) above, control levels throughout the period of drug administration [9].
• Odds ratios (OR) and their 95% confidence intervals (CI) according to consumption of coffee and other methylxanthine-containing beverages were derived from multiple logistic regression equations including terms for age, education, body mass index, smoking status, alcohol drinking, calcium intake, menopausal status, and estrogen replacement therapy [10].

High impact information on Heteroxanthin

• METHODS: Totally isolated rat stomachs were vascularly perfused with Krebs-Ringer buffer containing 50 mumol/L isobutyl methylxanthine at 1.4 mL.min-1 [11].
• It is possible that methylxanthine-induced small intestinal secretion may play a role in the symptoms experienced by some patients with functional diarrhea [12].
• Increasing intracellular cAMP with a permeable analog of cAMP together with the phosphodiesterase inhibitor isobutyl methylxanthine also decreased regulatory subunits, suggesting that cAMP is the second messenger mediating serotonin action [13].
• In both types of organisms, the methylxanthine caffeine overrides the synthesis (S)-M checkpoint that couples mitosis to completion of DNA S phase [14].
• In order to prevent this TNF alpha associated HCMV reactivation patients were additionally treated with pentoxifylline (PTX), a methylxanthine derivative that has been shown to suppress TNF alpha induction [15].

Chemical compound and disease context of Heteroxanthin

• Pharmacotherapy of obstructive lung disease has improved both quantitatively and qualitatively in recent decades: quantitatively with improvements in adrenergic and methylxanthine drugs and qualitatively with the addition of new classes of drugs, such as steroids, cromolyn, and, most recently, anticholinergic agents [16].
• Overall, and within the post-menopausal stratum, there was relatively little variation in the risk of breast cancer in association with total caffeine and total methylxanthine intake [17].
• The Eastern Cooperative Oncology Group (ECOG) performed a phase 2 study in B-cell chronic lymphocytic leukemia (CLL) of oral theophylline, a methylxanthine that inhibits cyclic nucleotide phosphodiesterases, thereby inducing the intracellular accumulation of cyclic adenosine monophosphate (cAMP) [18].
• The possibility that such an agent could be directed specifically against p53-defective tumor cells led us to study the new methylxanthine, Lisofylline, for its ability to sensitize ovary cancer cells to cis-diamminedichloroplatinum(II) (CDDP) [19].
• To assess the short-term effects of a methylxanthine (doxofylline) on respiratory mechanics in mechanically ventilated patients with airway obstruction and respiratory failure, nine consecutive patients were examined within three days from the onset of mechanical ventilation [20].

Biological context of Heteroxanthin

• Mitogen-induced activation of p70(s6k) is associated with the phosphorylation of specific sites which are negatively affected by the immunosuppressant rapamycin, the fungal metabolite wortmannin, and the methylxanthine SQ20006 [21].
• The kinetics of cAMP hydrolysis by the purified calf liver cGMP-stimulated cyclic nucleotide phosphodiesterase were analyzed in the absence or presence of a number of competitive inhibitors of the methylxanthine type according to a two-site competitive model for allosteric enzymes [22].
• Caffeine-induced action potentials were also eliminated, as was the response to theophylline, the methylxanthine in tea [23].
• Isobutyl methylxanthine is effective in promoting glycogenolysis in both cell lines [24].
• Initial studies showed that 24-h incubations with 8-bromo-cAMP or isobutyl methylxanthine increased cofactor levels in either culture system, whereas the stimulatory effects of forskolin or depolarization of membrane potential were only observed in cultures of hypothalamus [25].

Anatomical context of Heteroxanthin

• Previous research with pentoxifylline (PTX), a methylxanthine phosphodiesterase inhibitor, suggests that this drug may be capable of suppressing the activation of Kupffer cells and thereby help decrease liver injury after transplantation [26].
• Methylxanthine bronchodilators potentiate multiple human neutrophil functions [27].
• Characterization of basal and methylxanthine-stimulated Ca2+ transport in abalone spermatozoa [28].
• Pentoxifylline, a methylxanthine derivative, prevents leukocyte adherence to vascular endothelium and protects organs from shock by reducing tumour necrosis factor alpha (TNF alpha) concentrations [29].
• We found that pentoxifylline, a methylxanthine derivative already reported to regulate some monocyte functions, inhibits the procoagulant activity developed by U937 cells and monocytes in vitro in response to endotoxin [30].

Associations of Heteroxanthin with other chemical compounds

• The Gr66a mutant exhibited normal tastant-induced action potentials upon presentation of theobromine, a methylxanthine in cocoa [23].
• Preincubation of neutrophils with adenosine deaminase mimicked the methylxanthine potentiation, whereas addition of adenosine (3 X 10(-8) to 3 X 10(-7) M) reversed the methylxanthine-induced potentiation in a concentration-dependent manner [27].
• The bacterially expressed protein exhibited an optimal pH for activity ranging between 7 and 9 and methylated almost exclusively 7-methylxanthine with low activity toward paraxanthine, indicating a strict substrate specificity regarding the 3-N position of the purine ring [4].
• Alveolar macrophages from patients with asthma accumulated less cyclic adenosine monophosphate when these macrophages were exposed to isobutyl methylxanthine, salbutamol, or prostaglandin E2, compared to cells from control subjects without asthma, and the degree of the hyporesponsiveness was related to the severity of asthma [31].
• Metabolism and kinetics of a single oral dose of 30 microCi 8-14C-theobromine with 10 mg/kg theobromine sodium acetate were studied in six healthy, nonmedicated, nonsmoking men after 14 days' abstention from all methylxanthine sources [32].

Gene context of Heteroxanthin

• Some quinolones preferentially inhibit CYP1A2, which is partially responsible for methylxanthine metabolism [33].
• Pentoxifylline (PTX), a methylxanthine derivative, significantly inhibited the hypoxia-induced increase in PCA as well as VEGF release in all three cell lines tested [34].
• Pentoxifylline (PTX), which is a methylxanthine-derived inhibitor of phosphodiesterases (PDEs), or vehicle, was injected (5, 25, 50, 100, 200, and 300 mg/kg body weight/day) into the mice subcutaneously once a day for 3 weeks from the day of implantation of the bone morphogenetic protein (BMP)-laden disks [35].
• Enhanced release of interleukin-10 and soluble tumor necrosis factor receptors as novel principles of methylxanthine action in murine models of endotoxic shock [36].
• Pentoxifylline (PTX) is a methylxanthine compound known to inhibit the production of tumour necrosis factor-alpha (TNF-alpha), which is an important inflammatory mediator [37].

Analytical, diagnostic and therapeutic context of Heteroxanthin

• Acetylator status was determined by use of HPLC to assay 5-acetylamino-6-formylamino-3-methyluracil/methylxanthine (AFMU/MX) and AFMU/(AFMU + MX) ratios in urine 1 to 4 hours after drinking a strong cup of coffee (caffeine) [38].
• To examine the contribution of paraxanthine to the pharmacologic activity of caffeine, we administered to 12 subjects in a crossover design oral caffeine (2 or 4 mg/kg) versus placebo or oral paraxanthine (same dose as caffeine) versus placebo, each after 3 days of methylxanthine abstinence [39].
• We investigated the relationship between methylxanthine consumption and breast cancer using data from a case-control study which included 1,510 cases and 1,882 controls identified through a nation-wide breast cancer screening program [40].
• Rate of DNA synthesis was measured by 3H-thymidine incorporation in quiescent cells prepared by a low-serum treatment (0.4%) for 48 h after reaching confluency in microtiter wells. cAMP accumulation was measured in acetylated cell extracts in the presence of isobutyl methylxanthine (100 microM) by radioimmunoassay using 125I-cAMP as tracer [41].
• CONCLUSIONS: Substantial improvements in tumor oxygenation and perfusion were observed after administration of the methylxanthine derivatives [42].

References