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Calcium microdomains near R-type calcium channels control the induction of presynaptic long-term potentiation at parallel fiber to purkinje cell synapses.

R-type calcium channels in postsynaptic spines signal through functional calcium microdomains to regulate a calcium/calmodulin-sensitive potassium channel that in turn regulates postsynaptic hippocampal long-term potentiation (LTP). Here, we ask whether R-type calcium channels in presynaptic terminals also signal through calcium microdomains to control presynaptic LTP. We focus on presynaptic LTP at parallel fiber to Purkinje cell synapses in the cerebellum (PF-LTP), which is mediated by calcium/calmodulin-stimulated adenylyl cyclases. Although most presynaptic calcium influx is through N-type

Plasma metabolites associated with endometriosis in adolescents and young adults.

STUDY QUESTION: What are the plasma metabolomics profiles associated with endometriosis in adolescents and young adults? SUMMARY ANSWER: Ou … .g. eicosatrienoic acid (β = 0.61, 95% CI = 0.37, 0.86)], increased oxidative stress response [e.g. xanthine (β = 0.64, 95% CI = 0.39, 0.88)], and downregulation of metabolites related to apoptosis [glycocholic acid (β = -0.80, 95% CI = -1.04, -0.56)]. MSEA revealed increased fatty acyls (FDR = 2.3e-4) and ceramides (FDR = 6.0e-3) and decreased steroids an …

Preventive strategies for acute kidney injury in cancer patients.

Acute kidney injury (AKI) is a common complication of cancer that occurs in up to 50% of neoplastic patients during the natural history of their disease; furthermore, it has a huge impact on key outcomes such as overall prognosis, length of hospitalization and costs. AKI in cancer patients has different causes, either patient-, tumour- or treatment-related. Patient-related risk factors for AKI are the same as in the general population, whereas tumour-related risk factors are represented by compression, obstruction, direct kidney infiltration from the tumour as well by precipitation, aggregatio

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… As a xanthine analogue, allopurinol, which is converted in vivo to oxypurinol, acts as a competitive inhibitor of xanthine oxidase and blocks the conversion of purines to uric acid, thus preventing hyperuricaemia; unfortunately, however, it does not treat pre-existing hyperuricaemia. … Febuxostat is a novel xanthine oxidase inhibitor lacking the hypersensitivity profile of allopurinol; it has been recently approved for the prevention and treatment of hyperuricaemia in adult patients undergoing chemotherapy for haematologic malignancies at intermediate to high risk of developing a TLS …

Spontaneous Tumor Lysis Syndrome due to Uterine Leiomyosarcoma with Lung Metastases.

Tumor lysis syndrome (TLS) is an oncologic emergency characterized by a combination of metabolic derangements (hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia) caused by rapid turnover from cell destruction in certain cancers. These metabolic derangements can lead to seizures, cardiac arrhythmias, renal failure, and death. TLS is usually seen after the initiation of chemotherapy for hematologic malignancies. TLS occurring spontaneously, without initiation of chemotherapy, is rare and its occurrence in solid tumors is rarer still. We report a case of spontaneous TLS in a patien

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… Intravenous hydration promotes the excretion of uric acid; additionally, allopurinol blocks the production of uric acid by inhibiting xanthine oxidase. …

Molecular therapies for systemic lupus erythematosus: clinical trials and future prospects.

The prognosis of patients with systemic lupus erythematosus has greatly improved since treatment regimens combining corticosteroids and immunosuppressive medications have been widely adopted in therapeutic strategies given to these patients. Immune suppression is evidently efficient but also leads to higher susceptibility to infectious and malignant diseases. Toxic effects and sometimes unexpectedly dramatic complications of current therapies have been progressively reported. Identifying novel molecular targets therefore remains an important issue in the treatment of lupus. The aim of this rev

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… . | [ 11 ] Pentoxiphylline | Xanthine-derivative phosphodiesterase inhibitor | Open-label study: 11 SLE patients with refractory nephritis: class III, IV or V, proteinuria ≥ 3 g/24 hours. | Decrease of proteinuria (from 5.5 to 2.0, P = 0.003). … The administration of pentoxiphylline (Table 1 and Additional File 1 ), a xanthine derivative and well-known phosphodiesterase inhibitor, into MRL- lpr/lpr mice resulted in a diminution of clinical parameters of the disease [ 12 ]. …

Management of urinary stones: state of the art and future perspectives by experts in stone disease.

AIM: To present state of the art on the management of urinary stones from a panel of globally recognized urolithiasis experts who met during … infection stones (struvite), uric acid and urates, cystine and other rare stones (dihydroxyadenine, xanthine). Patients at "high-risk" forming calcium stones require a more difficult diagnosis by clinical and laboratory evaluation. Particularly, patients with cystinuria and primary hyperoxaluria should be actively searched. FUTURE RESEARCH: Application of …

Stevens - Johnson Syndrome and Toxic Epidermal Necrolysis; Extensive Review of Reports of Drug-Induced Etiologies, and Possible Therapeutic Modalities.

Stevens - Johnson Syndrome and Toxic Epidermal Necrolysis are adverse hypersensitivity reactions that affect the skin and mucous membranes. They are characterised by erythematous macules and hemorrhagic erosions of the mucous membranes. Epidermal detachments of varying degrees of severity also occur in these conditions. Various aetiologies are associated with these conditions, with adverse drug reaction being the most common. Though the worldwide incidence of these conditions is recorded as low, diverse types of medication are being observed to lead to these conditions. This review compiles in

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… Table 2 Reported cases of drug-induced sjs/ten Drug Classification | References Antibiotics | 23-34 Anticonvulsants | 35-41 Sulfonylureas | 42 Diuretics | 43-44 Analgesics | 45-48 Antidepressants | 49-50 Tyrosine Kinase Inhibitors | 51-54 Xanthine Oxidase Inhibitors | 55 Androgenic hormones | 56-57 Antineoplastic … Xanthine oxidase inhibitor Allopurinol: Commonly used in the treatment of chronic gout. …

Recent Advances on the Pathobiology and Treatment of Multiple Myeloma.

Worldwide experts in the field of multiple myeloma (MM) have promptly answered to the call in the Special Issue entitled "Recent advances on the pathobiology and treatment of multiple myeloma", submitting basic, translational or clinical works under the form of original article, review or perspective [...].

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… Ashtar et al. reported that febuxostat, a xanthine oxidase inhibitor used for prevention of tumor lysis syndrome, antagonized RANKL-dependent osteoclastogenesis through inhibition of RANKL-induced ROS production and OC formation in vitro and in ovariectomized mice. …

Analgesic Alkaloids Derived From Traditional Chinese Medicine in Pain Management.

Chronic pain is one of the most prevalent health problems. The establishment of chronic pain is complex. Current medication for chronic pain mainly dependent on anticonvulsants, tricyclic antidepressants and opioidergic drugs. However, they have limited therapeutic efficacy, and some even with severe side effects. We turned our interest into alkaloids separated from traditional Chinese medicine (TCM), that usually act on multiple drug targets. In this article, we introduced the best-studied analgesic alkaloids derived from TCM, including tetrahydropalmatine, aloperine, oxysophocarpine, matrine

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… /xanthine oxidase in vitro ( Shi et al., 1995 ); Reducting hexose-monophosphate shunt activity and hydrogen peroxide production in vitro ( Seow et al., 1988 ); Inhibiting the H2O2-induced generation of reactive oxygen species (ROS) in cultured rat cerebellar granule neurons ( Koh et al., 2003 ) | Suppress … Tetrandrine also scavenged superoxide radicals produced from xanthine/xanthine oxidase (Model: freshly fractured quartz-induced lipid peroxidation; Dosage: 60 mM) ( Shi et al., 1995 ), reduced hexose-monophosphate shunt activity, and inhibited superoxide anion generation ( Seow et al., 1988 ). …

A Trial of Favipiravir and Hydroxychloroquine combination in Adults Hospitalized with moderate and severe Covid-19: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The selected combination was based on limited evidence clinically and in vitro on the efficacy of the Favipiravir and Hydroxychl … stigational drug • Gout/history of Gout or hyperuricemia (above the ULN), hereditary xanthinuria or xanthine calculi of the urinary tract. INTERVENTION AND COMPARATOR: The treatment intervention would be for a maximum of 10 days from randomization and it would be as follows: Favipiravir for 10 days: Administer 1800 mg (9 tablets) by mouth twice daily for …

Platinum-induced ototoxicity and hearing impairment in children and adolescents.

Platinum compounds play a crucial role in the treatment of solid tumours in paediatric patients, significantly improving survival rates. However, these treatments can result in hearing loss as a side-effect that can significantly impact the quality of life of young cancer survivors. Whilst the therapeutic benefits of platinum compounds in paediatric oncology are indisputable, addressing the challenge of ototoxicity remains a priority. Early and regular auditory function assessments, with tools such as audiometry, otoacoustic emissions and auditory brainstem response testing, are critical durin

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… mitochondrial damage and oxidative stress ultimately culminates in cellular demise ( Figure 1 ). 19 , 20 Additionally, molecular mechanisms leading to oxidative stress after the exposure of inner ear tissues to cisplatin include the activation of nicotinamide adenine dinucleotide phosphate oxidase 3 and xanthine … Platinum compounds also activate the nicotinamide adenine dinucleotide phosphate oxidase 3 and xanthine oxidase and inhibit the glutathione peroxidases, increasing reactive oxygen species (ROS) formation (blue arrow). …

Synthetic nickel-containing superoxide dismutase attenuates para-phenylenediamine-induced bladder dysfunction in rats.

Para (p)-phenylenediamine and its toxic metabolites induce excess reactive oxygen species formation that results in bladder voiding dysfunction. We determined the effects of synthetic Ni-containing superoxide dismutase mimics and the role of oxidative stress in p-phenylenediamine-induced urinary bladder dysfunction. P-phenylenediamine (60 μg/kg/day) was intraperitoneally administered for 4 weeks to induce bladder injury in female Wistar rats. Synthetic Ni-containing superoxide dismutase mimics, WCT003 (1.5 mg/kg) and WCT006 (1.5 mg/kg), were then intraperitoneally administered for 2 weeks. Tra

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… The chemiluminescence of 0.2 mL saline in 1 mL of MCLA (0.2 mg/mL) served as the negative control and 0.2 mL xanthine (0.75 mg/kg body weight)/xanthine oxidase (24.8 mU/kg body weight) in 1 mL of MCLA (0.2 mg/mL) was the positive control [ 52 ]. …

Concurrent evolution of cancer cachexia and heart failure: bilateral effects exist.

Cancer cachexia is defined as a multifactorial syndrome of involuntary weight loss characterized by an ongoing loss of skeletal muscle mass and progressive functional impairment. It is postulated that cardiac dysfunction/atrophy parallels skeletal muscle atrophy in cancer cachexia. Cardiotoxic chemotherapy may additionally result in cardiac dysfunction and heart failure in some cancer patients. Heart failure thus may be a consequence of either ongoing cachexia or chemotherapy-induced cardiotoxicity; at the same time, heart failure can result in cachexia, especially muscle wasting. Therefore, t

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… Springer et al. [ 35 ] showed that the xanthine oxidase inhibitor, oxypurinol, partially recovered left ventricular (LV) mass ( p < 0.05) and LVEF ( p < 0.05) in Yoshida AH-130 hepatoma cachexia rat model. … The xanthine oxidase inhibitor oxypurinol reduces cancer cachexia-induced cardiomyopathy. Int J Cardiol. 2013. 36. Piepoli MF, Kaczmarek A, Francis DP, Davies LC, Rauchhaus M, Jankowska EA, et al. Reduced peripheral skeletal muscle mass and abnormal reflex physiology in chronic heart failure. …

Chemotherapy-Induced Tissue Injury: An Insight into the Role of Extracellular Vesicles-Mediated Oxidative Stress Responses.

The short- and long-term side effects of chemotherapy limit the maximum therapeutic dose and impair quality of life of survivors. Injury to normal tissues, especially chemotherapy-induced cardiomyopathy, is an unintended outcome that presents devastating health impacts. Approximately half of the drugs approved by the Food and Drug Administration for cancer treatment are associated with the generation of reactive oxygen species, and Doxorubicin (Dox) is one of them. Dox undergoes redox cycling by involving its quinone structure in the production of superoxide free radicals, which are thought to

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… O 2 • − can also be generated by other enzymatic reactions such as cytochrome P450 reductase, xanthine oxidase, and uncoupled nitric oxide synthase, as well as non-enzymatic reactions from redox cycling of Dox-Fe 3+ complex [ 6 ]. … O 2 • − generated by Xanthine oxidase, NADPH oxidase, and uncoupled endothelial nitric oxide synthase interacts with •NO forming ONOO − , which in turn oxidizes various biomolecules, leading to vascular dysfunction. …

Nucleotide Metabolism in Health and Disease.

Nucleotide metabolism is a fundamental biochemical process, providing the building blocks for DNA and RNA synthesis while driving critical cellular functions like energy transfer, signal transduction, and coenzyme synthesis. The precise regulation of nucleotide de novo synthesis, salvage, and degradation pathways is imperative for maintaining genomic stability and tissue homeostasis. Aberrations in these networks are increasingly recognized as primary drivers in various pathologies; notably, cancer cells exploit metabolic-functional reprogramming to enable rapid proliferation and therapeutic r

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… The simplified pathway is as follows: AMP is converted to hypoxanthine, which is then oxidized to xanthine by xanthine oxidase (XO), eventually forming uric acid. GMP is converted to guanine, which is subsequently converted to xanthine, and finally to uric acid. … Xanthine and hypoxanthine are more water soluble than uric acid and do not form crystals. …

Cancer chemopreventive activities of S-3-1, a synthetic derivative of danshinone.

Salvia miltiorrhiza is a traditional Chinese medicine which has been well documented for its anti-cancer effects. Based on the structure of danshinone, one of the active compounds derived from Salvia miltiorrhiza, we synthesized a simplified phenolic analog, S-3-1, and tried to explore its possible actions in preventing the development of cancer. With the Ames test, S-3-1 was found to efficiently suppress the mutagenicity of benzo[alpha]pyrene. This result is consistent with the inhibitory effect of S-3-1 on the activation of benzo[alpha]pyrene by hepatic microsomal enzymes. Besides the anti-i

Invited Lectures : Overviews Purinergic signalling: past, present and future.

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… Compounds presenting an additional fused ring on the xanthine nucleus have been reported to exhibit antagonistic activity with various levels of affinity and selectivity towards the four adenosine receptors subtypes [ 4 ]. … In the search for improved selective A2B antagonists for the treatment of asthma [ 8 ], we synthesized a variety of new 1,3-dipropyl-8-heterocyclic-substituted xanthines [ 9 ]. …

A1 adenosine receptors accumulate in neurodegenerative structures in Alzheimer disease and mediate both amyloid precursor protein processing and tau phosphorylation and translocation.

Immunostaining of adenosine receptors in the hippocampus and cerebral cortex from necropsies of Alzheimer disease (AD) patients shows that there is a change in the pattern of expression and a redistribution of receptors in these brain areas when compared with samples from controls. Adenosine A1 receptor (A1R) immunoreactivity was found in degenerating neurons with neurofibrillary tangles and in dystrophic neurites of senile plaques. A high degree of colocalization for A1R and betaA4 amyloid in senile plaques and for A1R and tau in neurons with tau deposition, but without tangles, was seen. Add

Cardiac Cachexia: Unaddressed Aspect in Cancer Patients.

Tumor-derived cachectic factors such as proinflammatory cytokines and neuromodulators not only affect skeletal muscle but also affect other organs, including the heart, in the form of cardiac muscle atrophy, fibrosis, and eventual cardiac dysfunction, resulting in poor quality of life and reduced survival. This article reviews the holistic approaches of existing diagnostic, pathophysiological, and multimodal therapeutic interventions targeting the molecular mechanisms that are responsible for cancer-induced cardiac cachexia. The major drivers of cardiac muscle wasting in cancer patients are au

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… In addition to mitochondrial dysfunction, xanthine oxidase in the peroxisomal matrix and the peroxisomal membranes could be the source of ROS because it is possible to reduce cardiac atrophy via the administration of the xanthine oxidase inhibitor in rats that have been inoculated with AH-130 Yoshida … The xanthine oxidase inhibitor oxypurinol reduces cancer cachexia-induced cardiomyopathy. Int. J. Cardiol. 2013;168:3527–3531. doi: 10.1016/j.ijcard.2013.05.063. 36. Min K., Kwon O.S., Smuder A.J., Wiggs M.P., Sollanek K.J., Christou D.D., Yoo J.K., Hwang M.H., Szeto H.H., Kavazis A.N. …

Keyword Index for Volume 88

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… , 1453 VIN 251 vinorelbine 1281 viral gene expression 1566 visible reflectance spectroscopy 760 vitamin D receptor 928 vitamin E analogues 1948 vitamin E succinate 153 vulval cancer 251 vulval intraepithelial neoplasia (VIN) 257 warts 1702 weekly chemotherapy 808 women 1381 X-rays 447 xanthine …