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Severe combined immunodeficiency and adenosine deaminase deficiency: failure of enzyme replacement therapy.

A first-born baby boy presented at age 3 months with persistent diarrhoea, failure to thrive, and recurrent bacterial and fungal infections. Severe combined immunodeficiency was demonstrated. A deficiency of adenosine deaminase (ADA) activity was suggested by the presence of extensive skeletal abnormalities, and the ADA activity in erythrocyte and leucocyte lysates was < 0.005 nmol/h per mg protein. Culture of ADA-negative peripheral blood mononuclear cells, together with purified calf ADA, did not alter the absent phytohaemagglutinin response. Treatment with immunoglobulin, pentamidine, and c…

Urinary adenosine 3',5'-monophosphate (cyclic AMP) in normal and cryptorchid boys.

The 24-hour urinary excretion of cyclic AMP was determined in 102 normal boys aged 1.9-16.9 years and in 136 cryptorchids aged 2.5-16.9 years. A marked increase of the normal cyclic AMP excretion was found in pubertal years. There was a positive correlation between urinary excretion of cyclic AMP and the excretion of testosterone, androstenedione, LH and FSH. A positive correlation was also found between cyclic AMP excretion and height and weight, respectively. Mean cyclic AMP excretion of bilateral and unilateral cryptorchids was normal in all bone age groups except in unilateral cases with b

Erythrocyte membrane Na+ and K+ activated adenosine triphosphatase in protein-calorie malnutrition.

Total, ouabain insensitive and ouabain sensitive Na+ and K+ adenosine triphosphatase activity in the erythrocyte membrane of protein-calorie malnourished children with marasmus and kwashiorkor was compared with the enzyme activity in apparently healthy children (normals). Na+ and K+ contents of erythrocyte and plasma were also determined in these patients. Specific activity (units per milligram of membrane protein) of ouabain sensitive Na+ and K+ adenosine triphosphatase was significantly higher in erythrocyte membrane preparations from children with kwashiorkor but not from children with mara…

Adenosine 5'-monophosphate-stimulated cyanide-insensitive respiration in mitochondria of Moniliella tomentosa.

Mitochondria of the yeastlike fungus Moniliella tomentosa oxidize reduced nicotinamide adenine dinucleotide, reduced nicotinamide adenine di … can be blocked by salicyl hydroxamic acid. The alternate oxidase can be specifically stimulated by adenosine 5'-monophosphate and this provides a new method for the characterization of the alternate oxidase in mitochondria of M. tomentosa.

Adenosine 3',5'-monophosphate in nervous tissue: increase associated with synaptic transmission.

Brief periods of stimulation of the preganglionic nerve fibers produced a severalfold increase in the content of adenosine 3',5'-monophosphate in superior cervical sympathetic ganglia, whereas postganglionic stimulation did not. These and other experiments indicated that the increased concentrations of adenosine 3'5'-monophosphate were closely associated with the process of synaptic transmission. This increase occurred primarily in postsynaptic cells.

Inhibition of thyrotropin-stimulated adenosine 3',5'-monophosphate formation in rat thyroid cells by an adenosine analog. Evidence that the inhibition is mediated by the putative inhibitory guanine nucleotide regulatory protein.

Addition of N6-(L-2-phenylisopropyl)-adenosine (PIA) to cultured FRTL-5 rat thyroid cells led to a concentration-dependent inhibition of TSH-stimulated cAMP formation. Half-maximal inhibition was attained with approximately 0.5 nM PIA. Forskolin and cholera toxin-stimulated cAMP production were also inhibited by PIA. 3-Isobutyl-methylxanthine inhibited the effect of PIA. These results are consistent with the presence of inhibitory adenosine receptors (Ri). Ri-sites were further demonstrated by the binding of 3H-cyclohexyl-adenosine to FRTL-5 plasma membranes. High (Kd = 0.50 +/- 0.07 nM) and l…

Urtica dioica inhibits cell growth and induces apoptosis by targeting Ornithine decarboxylase and Adenosine deaminase as key regulatory enzymes in adenosine and polyamines homeostasis in human breast cancer cell lines.

Breast cancer is a heterogeneous and multifactorial disease with variable disease progression risk, and treatment response. Urtica dioica is a traditional herb used as an adjuvant therapeutic agent in cancer. In the present study, we have evaluated the effects of the aqueous extract of Urtica dioica on Adenosine deaminase (ADA) and Ornithine decarboxylase (ODC1) gene expression in MCF-7, MDA-MB-231, two breast cancer cell lines being estrogen receptor positive and estrogen receptor negative, respectively.  Cell lines were cultured in suitable media. After 24 h, different concentrations of the …

Structure-activity relationships of BnOCPA derivatives at native pre- and postsynaptic adenosine A1Rs.

The addition of a benzyloxy group to the adenosine A1R agonist cyclopentyladenosine (CPA) produces a compound (BnOCPA) that selectivity activates A1R signalling via the G protein alpha subunit Gob. In rat hippocampus, BnOCPA inhibits CA3-CA1 synaptic transmission (IC50 65 nM) likely via Gob, with no effect on Goa-mediated postsynaptic membrane electrophysiology at concentrations up to 1 μM. We have investigated how modifications of the benzyloxy group of BnOCPA affects signalling: addition of methoxy group, MBnOCPA, substituting a phenoxy group, PhOCPA; and addition of bromide to the phenoxy g…

Stromal Spatial Signatures of the Classical Adenosine Pathway Dictate Prognosis in Hepatocellular Carcinoma.

BACKGROUND: The classical adenosinergic pathway (CD39/CD73/A2BR) plays a pivotal role in regulating tumor immune evasion in hepatocellular carcinoma (HCC). However, the prognostic significance of the specific spatial coordination of these enzymes within the tumor microenvironment remains elusive. METHODS: We retrospectively included 92 patients with HCC who underwent curative hepatectomy. Multiplex immunohistochemistry was used to assess the in situ expression of CD39, CD73, A2BR, and cytokeratin (CK). Digital pathology was employed to segment the tissue into tumor parenchyma (CK+) and stroma…

Доклад по делу: Эхокардография эхокардиоскопии аденосинового стресса, свидетельствующая о микроваскулярной дисфункции сердца AL Amiloidosis.

Сердечный амилоидоз (CA) является редкой, но все чаще признанной причиной ограничительной кардиомиопатии. Неинвазивная оценка коронарной микрососудистой дисфункции в CA может облегчить раннюю диагностику и улучшить мониторинг заболеваний. Мы представляем случай легкоцепных (AL) кардиологических амилоидозов, проявляющихся как напряженная ангина с неинтрузивными эпикардиальными коронарными артериями, в которых контрастная эхокардическая эхокардия аденосинового стресса в сочетании с эхокардическим измерением коронарного потока (CFVR) выявила нарушение миокардного перфузиона и сокращение CFVR. Пол

Совпадение в аннотации оригинала
Cardiac amyloidosis (CA) is a rare but increasingly recognized cause of restrictive cardiomyopathy. Noninvasive assessment of coronary micro … nifesting as exertional angina with non-obstructive epicardial coronary arteries, in which contrast adenosine stress echocardiography combined with Doppler-derived coronary flow velocity reserve (CFVR) measurement revealed impaired myocardial perfusion and reduced CFVR. The findings were consistent with cardiac magnetic resonance (CMR) and laboratory result …

40 Hz flicker preconditioning protects nonarteritic anterior ischemic optic neuropathy via adenosine signaling.

Nonarteritic anterior ischemic optic neuropathy (NAION) is a leading cause of sudden, painless vision loss in the elderly, yet no proven intervention exists. Ischemic preconditioning (IPC) is a promising neuroprotective strategy, but defining an effective clinical protocol remains a major challenge in fulfilling its translational potential. We recently discovered that 40 Hz flicker induces extracellular adenosine, a key neurochemical underpinning of IPC, in the visual pathway, suggesting a previously unexplored non-invasive IPC approach. Here, we demonstrated that 3-day 40 Hz flicker precondit…

Celastrol Ameliorates Systemic Lupus Erythematosus via Restoring Nt5e/ adenosine-dependent Th17/Treg Balance.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the breakdown of immune tolerance, systemic inflammation, and multi-organ damage. The imbalance between T helper 17 (Th17) cells and regulatory T (Treg) cells is a key driver in SLE pathogenesis. PURPOSE: This study aimed to investigate whether Celastrol (Cel), a natural triterpenoid derived from Tripterygium wilfordii, exerts therapeutic effects in SLE by modulating the Th17/Treg balance, and to explore the underlying molecular mechanism. STUDY DESIGN: An in vivo study using the MRL/lpr lupus-pro

Adenosine signaling in tumor immune escape: metabolic checkpoints, myeloid suppression, and combination immunotherapy.

Adenosine is a central metabolic regulator of tumor immune escape, shaping the tumor microenvironment (TME) through suppression of effector lymphocytes and reprogramming of myeloid populations. Extracellular adenosine is generated primarily via the ectonucleotidases CD39 and CD73 and signals through A2A (A2AR) and A2B (A2BR) receptors on T cells, NK cells, tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and dendritic cells. This pathway promotes T-cell exhaustion, inhibits cytotoxicity, and enhances myeloid-driven immunosuppression, creating metabolic and spatial…

Extracellular Vesicle-Derived Adenosine as a Diagnostic Metabolic Biomarker for Pancreatic Ductal Adenocarcinoma.

PURPOSE: Current non-invasive diagnostic tools for pancreatic ductal adenocarcinoma (PDAC) exhibit limited sensitivity and specificity. This … proteomic profiling to identify disease-specific biomarkers. RESULTS: A biomarker panel comprising adenosine, adenine, and N-acetylneuraminate (AAN) demonstrated outstanding diagnostic performance, achieving an area under the receiver operating characteristic curve (AUC) of 0.968 (95% CI: 0.92-1.00). At a fixed specificity of 96.8%, the panel yielded a sen …

Adenosine-assisted embolization of cerebral arteriovenous malformations: a systematic review and meta-analysis.

BACKGROUND: Cerebral arteriovenous malformations (AVMs) are complex lesions that can cause hemorrhagic stroke and significant neurological disability. Adenosine induces cardiac standstill and hypotension, which are thought to be useful during cerebral AVM embolization. Herein, we conducted a systematic review and meta-analysis of the technique's safety. METHODS: Following PRISMA guidelines, four databases were queried for studies describing the use of adenosine-assisted embolization of cerebral AVMs. Adenosine-related intraoperative complications, permanent neurological outcomes, morbidity, a…

Adenosine A3 Receptor and Its Potential Role in Cancer Treatment: A Narrative Review.

Found in all human cells, the purine nucleoside adenosine plays various roles in different metabolic pathways. Adenosine is not stored in vesicles but is released continuously, based on metabolic demands. Essential in energy production, adenosine is a full agonist at four known receptors (A1, A2A, A2B, and A3), and is produced either intracellularly or in the extracellular space. Adenosine is the building block for adenosine triphosphate (ATP), a vasodilator that inhibits certain cerebral neurotransmissions. Adenosine diphosphate (ADP) releases energy via its phosphate bonds and can "recharge"…

Ultrasound-activated nanovesicles for adenosine exhaustion and immune checkpoint blockade in cancer immunotherapy.

Conventional antitumor therapies induce immunogenic cell death (ICD), releasing large amounts of ATP that are rapidly converted into immunosuppressive adenosine within the tumor microenvironment (TME). This accumulation of adenosine promotes tumor immune evasion by inhibiting effector immune cells and upregulating inhibitory immune checkpoints. To overcome this challenge, we designed ultrasound (US)-activated nanovesicle system ADA/Ce6@tLipo which is composed of T cell membranes displaying multiple immune checkpoint molecules and a liposome encapsulating chlorin e6 (Ce6) and adenosine deaminas…

Adenosine Receptor Mechanisms Underlying Bladder Dysfunction in Male Rats With Bladder Outlet Obstruction.

AIMS: We examined the role of subtypes of adenosine receptors in bladder dysfunction and changes in the adenosine receptor expression in the bladder using male rats with partial bladder outlet obstruction (BOO). METHODS: In Sprague-Dawley rats (male 8-weeks old), BOO was produced by a partial ligation of the urethra along a metal rod of a 1.2 mm outer diameter. Control rats underwent sham operation. Awake cystometrograms (CMG) were first recorded during saline instillation, and then an adenosine A1 receptor agonist (CCPA, 4.1 μM), an adenosine A2A antagonist (ZM241385, 15 μM), or inosine (1 m…