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Внеклеточные нуклеотиды являются посредником в вирусных инфекциях центральной нервной системы: ключи от нейроинфламмации и нейродегенерации.

Недавний рост инфекционных заболеваний, затрагивающих центральную нервную систему, вызвал обеспокоенность по поводу их роли в нейроинфламмации и нейродегенерации. Вирусные патогены или их продукты могут вторгаться в центральную нервную систему и вызывать повреждения, ведущие к менингиту, энцефалиту, менингоэнцефалиту, миелиту или постинфекционным демиелинизирующим заболеваниям. Хотя изначально нейроинфламмация имеет защитную функцию, хроническое воспаление может способствовать развитию нейродегенеративных заболеваний. Такие механизмы, как агрегация белков и клеточные расстройства, связаны с ко

Совпадение в аннотации оригинала
Recent increases in infectious diseases affecting the central nervous system have raised concerns about their role in neuroinflammation and … h Alzheimer's disease and multiple sclerosis, respectively. Extracellular nucleotides, particularly adenosine triphosphate and its metabolites are released from activated, infected, and dying cells, acting as alarmins mediating neuroinflammation and neurodegeneration. When viruses infect central nervous system cells, adenosine triphosphate is released as an alarmin, tri …

Metabolic effects of hyperbaric oxygen in postischemic muscle.

In traumatic injuries to the extremities, with a circulatory insufficiency, the resultant ischemia leads to decreasing levels of the energy-rich compounds adenosine triphosphate (ATP) and phosphocreatine (PCr) and increasing levels of lactate in muscle. A tourniquet model for temporary ischemia was used to determine if hyperbaric oxygen treatment could enhance the cellular metabolic restitution when the circulation was restored. The circulation of the rat hindlimb was interrupted for 1.5 and 3 hours. After 1.5 hours of ischemia, the levels of adenosine triphosphate, phosphocreatine, and lactat…

Cobra neurotoxin produces central analgesic and hyperalgesic actions via adenosine A1 and A2A receptors.

Cobra neurotoxin, a short-chain peptide isolated from snake venom of Naja naja atra, showed both a central analgesic effect and a hyperalges … tagonist (ZM241385); behaviors were scored and signal molecules such as reactive oxygen species and adenosine triphosphate levels and mitogen-activated protein kinases/extracellular signal-regulated protein kinase expression were measured. Low dose of cobra neurotoxin (25 µg/kg) had analgesic effects which were inhibited by DPCPX, while high dose of cobra neurotoxin (10 …

Peri-mortem rigidity in a fatal case of severe salicylate poisoning.

INTRODUCTION: There has been a previous case report of peri-arrest muscle rigidity in the setting of severe salicylate poisoning (serum sali … -arrest rigidity in the upper extremities. DISCUSSION: Peri-mortem rigidity is due to depletion of adenosine triphosphate. Severe salicylate poisoning causes uncoupling of oxidative phosphorylation which prevents the production of adenosine triphosphate, which is required to release myosin from actin to allow the muscle to relax. A limitation of our report is that we d …

α1 -Blocker inhibits non-voiding contractions and decreases the level of intravesical prostaglandin E2 in rats with partial bladder outlet obstruction.

OBJECTIVES: To elucidate the mechanism of action of the α1 -blocker, naftopidil, in partial bladder outlet obstruction animals, by studying non-voiding contractions, and the levels of mediators were measured with resiniferatoxin treatment. METHODS: A total of 35 female Wistar rats were randomly divided into a sham or bladder outlet obstruction group, and rats in each group were given vehicle or resiniferatoxin. Incomplete urethral ligation was applied to the bladder outlet obstruction group. After cystometry, the intravesical level of prostaglandin E2 and adenosine 5'-triphosphate was measure

Dissolved organic phosphorus bond-class utilization by Synechococcus.

Dissolved organic phosphorus (DOP) contains compounds with phosphoester, phosphoanhydride, and phosphorus-carbon bonds. While DOP holds significant nutritional value for marine microorganisms, the bioavailability of each bond-class to the widespread cyanobacterium Synechococcus remains largely unknown. This study evaluates bond-class specific DOP utilization by Synechococcus strains from open and coastal oceans. Both strains exhibited comparable growth rates when provided phosphate, a phosphoanhydride [3-polyphosphate and 45-polyphosphate], or a DOP compound with both phosphoanhydride and phos

High-energy phosphate levels in the cerebral artery during chronic vasospasm after subarachnoid hemorrhage.

High-energy phosphate levels were measured in the canine cerebral artery during chronic vasospasm. Subarachnoid hemorrhage and vasospasm were induced by percutaneous injections of autologous venous blood into the cisterna magna. Narrowing of the artery was confirmed by angiography 7 days later. Levels of adenosine phosphates (adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP)), guanosine phosphates (guanosine triphosphate (GTP) and guanosine diphosphate (GDP)), and creatine phosphate (CrP) in the basilar artery were quantified using high-performance li…

Capacitation of ram spermatozoa promotes changes in energy metabolism and aquaporin 3 and is affected by individual testosterone variations.

BACKGROUND: Recently, the metabolic pathways involved in energy production and the role of aquaglyceroporins in capacitation-associated even … 0 and 180 min of incubation in each medium, sperm viability, kinetics, chlortetracycline patterns, adenosine triphosphate concentration, lactate excretion (final subproduct of glycolysis), and immunolocalization of aquaporin 3 were evaluated. RESULTS: The increment of the capacitated spermatozoa-chlortetracycline pattern and the hyperactivated-like movement characteri …

Thiamine triphosphate deficiency in subacute necrotizing encephalomyelopathy.

Extracts of tissue fluids from a patient with subacute necrotizing encephalomyelopathy inhibit thiamine pyrophosphate-adenosine triphosphate phosphotransferase of rat brain. Brain tissue from the patient, in contrast to normal brain tissue, contained essentially no thiamine triphosphate, although thiamine and its other phosphate esters were present in normal concentrations. These findings suggest a relation between this disease and thiamine triphosphate.

Fatal respiratory failure in a full-term newborn with two ABCA3 gene mutations: a case report.

Genetic mutations associated with pulmonary surfactant protein deficiency are associated with diverse clinical phenotypes. Mutations of the surfactant protein B and C genes were the first to be described. In 2004, fatal surfactant deficiency in newborns due to mutations of the gene encoding the adenosine triphosphate-binding cassette transporter A3 (ABCA3) was first reported. Few cases of lethal adenosine triphosphate-binding cassette transporter A3 mutations have been described to date. In our report, we describe a full-term newborn that died because of respiratory failure secondary to an unc…

A novel nucleoside rescue metabolic pathway may be responsible for therapeutic effect of orally administered cordycepin.

Although adenosine and its analogues have been assessed in the past as potential drug candidates due to the important role of adenosine in physiology, only little is known about their absorption following oral administration. In this work, we have studied the oral absorption and disposition pathways of cordycepin, an adenosine analogue. In vitro biopharmaceutical properties and in vivo oral absorption and disposition of cordycepin were assessed in rats. Despite the fact that numerous studies showed efficacy following oral dosing of cordycepin, we found that intact cordycepin was not absorbed f

Relation between coronary artery stenosis and myocardial purine metabolism, histology and regional function in humans.

In 54 patients undergoing elective or emergency aortocoronary bypass grafting, angiographic and electrocardiographic changes were studied. F … of the adenylate pool. Mitochondrial function, however, remained intact: the adenosine diphosphate/adenosine triphosphate ratio, the energy charge and the creatine phosphate/adenosine triphosphate ratio were in the normal range. Histologic assessment demonstrated viable myocardium with a high incidence of atrophic cells. In evolving myocardial infarction, 170 minutes o …

P2X7 receptor-mediated depression-like reactions arising in the mouse medial prefrontal cortex.

Major depressive disorder is a frequent and debilitating psychiatric disease. We have shown in some of the acute animal models of major depressive disorder (tail suspension test and forced swim test) that depression-like behavior can be aggravated in mice by the microinjection into the medial prefrontal cortex of the P2X7R agonistic adenosine 5'-triphosphate or its structural analog dibenzoyl-ATP, and these effects can be reversed by the P2X7R antagonistic JNJ-47965567. When measuring tail suspension test, the prolongation of immobility time by the P2YR agonist adenosine 5'-[β-thio]diphosphate

Purinergic signalling in the liver in health and disease.

Purinergic signalling is involved in both the physiology and pathophysiology of the liver. Hepatocytes, Kupffer cells, vascular endothelial cells and smooth muscle cells, stellate cells and cholangiocytes all express purinoceptor subtypes activated by adenosine, adenosine 5'-triphosphate, adenosine diphosphate, uridine 5'-triphosphate or UDP. Purinoceptors mediate bile secretion, glycogen and lipid metabolism and indirectly release of insulin. Mechanical stress results in release of ATP from hepatocytes and Kupffer cells and ATP is also released as a cotransmitter with noradrenaline from sympa

Purinergic Signaling in the Regulation of Gout Flare and Resolution.

Gout flares require monosodium urate (MSU) to activate the NLRP3 inflammasome and secrete sufficient IL-1β. However, MSU alone is not sufficient to cause a flare. This is supported by the evidence that most patients with hyperuricemia do not develop gout throughout their lives. Recent studies have shown that, besides MSU, various purine metabolites, including adenosine triphosphate, adenosine diphosphate, and adenosine bind to different purine receptors for regulating IL-1β secretion implicated in the pathogenesis of gout flares. Purine metabolites such as adenosine triphosphate mainly activat…

Minoxidil-induced hair growth is mediated by adenosine in cultured dermal papilla cells: possible involvement of sulfonylurea receptor 2B as a target of minoxidil.

The mechanism by which minoxidil, an adenosine-triphosphate-sensitive potassium channel opener, induces hypertrichosis remains to be elucidated. Minoxidil has been reported to stimulate the production of vascular endothelial growth factor, a possible promoter of hair growth, in cultured dermal papilla cells. The mechanism of production of vascular endothelial growth factor remains unclear, however. We hypothesize that adenosine serves as a mediator of vascular endothelial growth factor production. Minoxidil-induced increases in levels of intracellular Ca(2+) and vascular endothelial growth fac

Platelet aggregation: Part I Some effects of the adenosine phosphates, thrombin, and cocaine upon platelet adhesiveness.

PLATELETS IN NATIVE BLOOD ADHERE SPONTANEOUSLY TO GLASS INDEPENDENTLY OF TEMPERATURE: if adenosine diphosphate is added to the blood the adhesiveness of the platelets is increased and this effect is largely independent of temperature. The mono- and triphosphates decrease adhesiveness at 20 degrees C. and 37 degrees C. but have no effect at 0 degrees C.; cocaine inhibits adhesion at 37 degrees C. and at 0 degrees C. Aggregation and viscous metamorphosis of platelets in native plasma is induced at 37 degrees C. by adenosine diphosphate or by thrombin; these reactions do not occur at 0 degrees C.

Targeted disruption of cd39/ATP diphosphohydrolase results in disordered hemostasis and thromboregulation.

CD39, or vascular adenosine triphosphate diphosphohydrolase, has been considered an important inhibitor of platelet activation. Unexpectedly, cd39-deficient mice had prolonged bleeding times with minimally perturbed coagulation parameters. Platelet interactions with injured mesenteric vasculature were considerably reduced in vivo and purified mutant platelets failed to aggregate to standard agonists in vitro. This platelet hypofunction was reversible and associated with purinergic type P2Y1 receptor desensitization. In keeping with deficient vascular protective mechanisms, fibrin deposition wa…

A 7-deaza-adenosine analog is a potent and selective inhibitor of hepatitis C virus replication with excellent pharmacokinetic properties.

Improved treatments for chronic hepatitis C virus (HCV) infection are needed due to the suboptimal response rates and deleterious side effects associated with current treatment options. The triphosphates of 2'-C-methyl-adenosine and 2'-C-methyl-guanosine were previously shown to be potent inhibitors of the HCV RNA-dependent RNA polymerase (RdRp) that is responsible for the replication of viral RNA in cells. Here we demonstrate that the inclusion of a 7-deaza modification in a series of purine nucleoside triphosphates results in an increase in inhibitory potency against the HCV RdRp and improve

A study of patients with alcoholic liver disease by 31P nuclear magnetic resonance spectroscopy.

1. Patients with a history of alcohol abuse were studied by 31P n.m.r. spectroscopy of the liver in vivo, and the results were related to the pattern of disease assessed by standard biochemical and histological techniques. 2. The ratios of metabolites measured from the 31P n.m.r. spectra were abnormal in patients with alcoholic hepatitis but not in those with fatty change or cirrhosis in the absence of hepatitis. In particular, the levels of phosphomonoesters were raised, with respect either to Pi, or to adenosine 5'-triphosphate. The level of phosphomonoesters showed a significant positive co