1,721,154 research outputs found
A holistic view of adenosine pathways in the control of intestinal neuromuscular functions: the enteric purinome concept
No full textAdenosine is involved in the modulation of enteric neuromuscular functions, operating a fine tuning of smooth muscle contractility, peristaltic reflex and transit. In this issue of the BJP, Zizzo et al. report novel findings on the expression of adenosine receptors in mouse duodenum, extending our knowledge of their involvement in the control of spontaneous and neurogenic intestinal motility. In this study, particular attention was paid to the differential activation of adenosine receptors, as a result of their interplay with regulatory systems, modulating the availability of endogenous adenosine in a compartmentalised manner. This evidence will contribute to the holistic evaluation of the role played by adenosine in the regulation of intestinal motility, in accordance with the novel concept of the enteric 'purinome'. This commentary discusses the role of the 'purinome' in the modulation of enteric neuromuscular activity, pointing out its involvement in the intestinal neuroplasticity associated with bowel dysmotility
Efficay and tolerability of meloxicam, a COX-2 preferential nonsteroidal anti-inflammatory drug: a review
No full textMeloxicam is an enolcarboxamide with preferential COX-2 inhibitory activity. In vitro studies with human tissues have confirmed the high affinity of meloxicam for COX-2, whereas COX-1 was inhibited only at the highest concentrations (ratio of 50% inhibitory concentration for COX-2 : COX-1 = 0.09 in whole blood assays).
Meloxicam has a bioavailability of 89% after oral administration, is strongly bound to plasma proteins, and its half-life is 20-24 hours. It readily penetrates into synovial fluid, reaching 45-57% of plasma concentrations. Meloxicam pharmacokinetics are not significantly altered in elderly patients or in those with mild renal/hepatic impairment.
The efficacy and tolerability of meloxicam in the treatment of pain and inflammation associated with rheumatic and musculoskeletal disorders has been evaluated in numerous studies comparing meloxicam 7.5-15 mg/day (up to 22.5 mg/day in ankylosing spondylitis), administered for 2 weeks to 12 months, with placebo or other nonsteroidal anti-inflammatory drugs (NSAIDs). Overall, the efficacy of meloxicam was significantly superior to that of placebo and similar to that of other NSAIDs, whereas the incidence of adverse events (especially gastrointestinal) was lower than with other NSAIDs. Intramuscular meloxicam provided faster pain relief than the oral drug in patients with rheumatoid arthritis. Meloxicam also appears to be effective in the prevention of postoperative pain, as shown in patients undergoing abdominal hysterectomy or inguinal hernia repair. Meloxicam may also have a cardioprotective role: in patients with acute coronary syndrome without ST-segment elevation, a lower incidence of cardiovascular events was observed in those who received meloxicam plus aspirin and heparin versus aspirin and heparin alone, both during coronary care stay and at 90-day follow-up.
Meloxicam has demonstrated a favourable tolerability profile in large-scale comparative trials, where its gastrointestinal tolerability was superior to that of nonselective NSAIDs. In particular, meloxicam 7.5 mg/day was associated with a lower incidence of gastrointestinal adverse events compared with diclofenac (13% vs 19%; p < 0.001) or piroxicam (10.3% vs 15.4%; p < 0.001). This was confirmed by a prescription-event monitoring study that found a relatively low incidence of dyspepsia, upper gastrointestinal haemorrhage and peptic ulcer (28.3, 0.4 and 0.3 per 1000 patient-months, respectively) among first-time users of meloxicam.
In conclusion, meloxicam is at least as effective as nonselective NSAIDs in the treatment of rheumatic disease or postoperative pain, but has a more favourable gastrointestinal tolerability profile. Further investigations into the potential role of meloxicam as a cardioprotective agent are warranted
Pharmacological modulation of adenosine receptor pathways and inflammatory disorders: the way towards novel therapeutics?
No full textAbstract non previsto dalla rivista per questo tipo di articol
Adenosine pathway and cancer: where do we go from here?
No full textIncreasing evidence supports the occurrence of an intriguing link between tumor
onset and development with the microenvironment in which cancer cells are embedded. In this context, a critical role of CD73, in calibrating the duration, magnitude and composition of adenosine signaling in cancer development and progression, has been identified. Adenosine levels are increased in cancer tissues as the result of genetic alterations that occur during tumor progression.
Indeed, a rearrangement of the adenosine metabolic machinery has been described within the neoplastic milieu with the aim of amplifying adenosine generation, thereby creating an immune tolerant microenvironment suitable for tumor onset and development. At the same time, adenosine, through the engagement of receptors expressed on neoplastic cells, finely tunes the growth and dissemination of tumor
mass, thus interfering with cancer proliferation, apoptosis and metastasis. Based on current knowledge, an improved understanding of how and to what extent adenosine participates to the molecular mechanisms underlying cancer development and diffusion will pave the way toward new therapeutic advances. The discovery and development of drugs targeted on this system might lead to substantial improvements in the clinical management of various cancers
Adenosine signaling and the immune system: When a lot could be too much
No full textAdenosine is increasingly recognized as a key mediator of the immune response. Signals delivered by extracellular adenosine are detected and transduced by G-protein-coupled cell-surface receptors, classified into four subtypes: A1, A2A, A2Band A3. These receptors, expressed virtually on all immune cells, modulate all aspects of immune/inflammatory responses. These immunoregulatory effects, which are mostly anti-inflammatory, contribute to the general tissue protective effects of adenosine and its receptors. In some instances, however, the effect of adenosine on the immune system is deleterious, as prolonged adenosine signaling can hinder anti-tumor and antibacterial immunity, thereby promoting cancer development and progression and sepsis, respectively
Interplay among gut microbiota, intestinal mucosal barrier and enteric neuro-immune system: a common path to neurodegenerative diseases?
Full text linkNeurological diseases, such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS) and multiple sclerosis, are often associated with functional gastrointestinal disorders. These gastrointestinal disturbances may occur at all stages of the neurodegenerative diseases, to such an extent that they are now considered an integral part of their clinical picture. Several lines of evidence support the contention that, in central neurodegenerative diseases, changes in gut microbiota and enteric neuro-immune system alterations could contribute to gastrointesinal dysfunctions as well as initiation and upward spreading of the neurologic disorder. The present review has been intended to provide a comprehensive overview of the available knowledge on the role played by enteric microbiota, mucosal immune system and enteric nervous system, considered as an integrated network, in the pathophysiology of the main neurological diseases known to be associated with intestinal disturbances. In addition, based on current human and pre-clinical evidence, our intent was to critically discuss whether changes in the dynamic interplay between gut microbiota, intestinal epithelial barrier and enteric neuro-immune system are a consequence of the central neurodegeneration or might represent the starting point of the neurodegenerative process. Special attention has been paid also to discuss whether alterations of the enteric bacterial-neuro-immune network could represent a common path driving the onset of the main neurodegenerative diseases, even though each disease displays its own distinct clinical features
Adenosine signaling as target in cardiovascular pharmacology
No full textIncreasing evidence demonstrated the relevance of adenosine system in the onset and development of cardiovascular dis-eases, such as hypertension, myocardial infarct, ischemia, hypertension, heart failure, and atherosclerosis. In this regard, intense research efforts are being focused on the character-ization of the pathophysiological significance of adenosine, acting at its membrane receptors named A1, A2A, A2B, and A3 receptors, in cardiovascular diseases. The present review article provides an integrated and comprehensive overview about current clinical and pre-clinical evidence about the role of adenosine in the pathophysiology of cardiovascular diseases. Particular attention has been focused on current scientific ev-idence about the pharmacological ligands acting on adenosine pathway as useful tools to manage cardiovascular diseases
Transient acute liver failure complicating transurethral resection syndrome
No full textTransurethral resection (TUR) syndrome, resulting from dilutional hyponatraemia for excessive absorption of irrigating fluid, represents the most relevant complication of transurethral resection of prostate (TURP). Ethanol is used as a tracer in the irrigant solution to monitor fluid absorption with a breathalyser. An unusual case of transient acute liver failure complicating TUR syndrome is reported. A 54-year-old male patient, without risk factors for the development of toxic hepatitis, was subjected to TURP for treatment of benign prostatic hyperplasia. Fluid absorption (2275 ml), estimated by breathalyser, exceeded maximum allowed absorption (2000 ml) only at the end of the surgical intervention. No signs of possible toxicity were evident in the few hours following the intervention. About 10 h after the end of TURP, the patient developed sweating, vomiting and diarrhoea. Laboratory analysis revealed severe hyponatraemia (116 meq/l) with signs of severe liver impairment (total bilirubin 5.8 mg/dl, alanine aminotransferase 56,500 U/l, aspartate aminotransferase 32,700 U/l), kidney failure (serum creatinine 1.93 mg/dl) and serum ethanol levels of 219 mg/dl (0.2%). The patient was treated with acetylcysteine 150 mg/kg i.v. and furosemide 50 mg i.v. Liver and renal functions improved in few days and recovered completely within 30 days. The TUR syndrome observed in this case was probably extravascular in nature, and could have been identified and prevented by measuring ethanol levels 10 min after ending the surgical procedure. The performance of such a test should be strongly recommended to all surgeons. The clinicians attributed the development of liver impairment in this case to ethanol toxicity. However, further studies are warranted to confirm whether hepatic injury can represent a possible complication of TUR syndrome when ethanol solution is used as irrigant fluid
Adenosine and inflammation: what's new on the horizon?
No full textAdenosine contributes to the maintenance of tissue integrity by modulating the immune system. Encouraging results have emerged with adenosine receptor ligands for the management of several inflammatory conditions in preclinical and clinical settings. However, therapeutic applications of these drugs are sometimes complicated by the occurrence of serious adverse effects. The scientific community is making intensive efforts to design novel adenosine receptor ligands endowed with greater selectivity or to develop innovative compounds acting as allosteric receptor modulators. In parallel, research is focusing on novel pharmacological entities (designated as adenosine-regulating agents) that can increase, in a site- and event-specific manner, adenosine concentrations at the inflammatory site, thereby minimizing the adverse systemic effects of adenosine
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