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Current pharmaceutical design [journal]
- Pleiotropic Effects of Platelet P2Y12 Receptor Inhibitors: Fact or Fiction? [JOURNAL ARTICLE]
- Curr Pharm Des 2014 Apr 14.
P2Y12 inhibitors constitute an essential part of the antithrombotic treatment, with proven clinical benefit in acute coronary syndromes and after percutaneous coronary interventions. Substantial evidence has emerged that, apart from their primary antiplatelet action, P2Y12 receptor inhibitors exhibit several off-target effects. In this review, we present the supporting evidence of P2Y12 inhibitors' pleiotropic actions, discuss their clinical implications and underscore the necessity for further research on this issue.
- Association between MTHFR Gene Polymorphism and the Risk of Ovarian Cancer: A Meta-analysis of the Literature. [Journal Article]
- Curr Pharm Des 2014; 20(11):1632-8.
Objectives:Methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme for DNA biosynthesis and the epigenetic process of DNA methylation. MTHFR gene polymorphisms have been implicated as risk factors for several types of cancers. However, reports on the association of MTHFR polymorphisms with ovarian cancers are inconclusive. The aim of this study is to summarize on the reported data and meta-analytically investigate the relationship between the MTHFR C677T and A1298C polymorphism and the risk of ovarian cancer.
Methods:We searched for all published articles indexed in MEDLINE (1950-2012), EMBASE (1974-2012), and CNKI (1994-2012). Case-control or cohort studies that relating to MTHFR polymorphism and ovarian cancer women were included and data were extracted independently by two reviewers. The search yielded 21 articles, from which 7 studies met the inclusion criteria. We performed a metaanalysis involving 3493 patients with ovarian cancer and 3863 controls with Review Manager 5.1 software. Odds ratio (OR) and 95% confidence intervals (CIs) were used to evaluate the ovarian cancer risk.
Results:All the available data considered together, no association between the MTHFR C677T polymorphism and ovarian cancer risk was found in any genetic variations. However, in the subgroup analysis by ethnicity of Asian and Caucasian, MTHFR 677T was associated with significantly increased ovarian cancer risk among Asian [T allele vs. C allele: OR=1.50, 95% CI: 1.25-1.81, P<0.0001; CT + TT vs. CC (dominant model): OR=1.49, 95% CI: 1.18-1.88, P=0.0009; TT vs. CT + CC (recessive model): OR=2.33, 95% CI: 1.57-3.45, P<0.00001], while, there was no significant increased risk in Caucasian. As for MTHFR A1298C polymorphism, no marked association was found in either group of Caucasian population, while no data was available to analyze in Asian population.
Conclusions:The C677T polymorphism of the MTHFR gene is associated with the susceptibility of ovarian cancer in Asian population, suggesting that TT genotype may serve as a risk factor of ovarian cancer among Asian but not Caucasians. In addition, there is no association between A1298C gene polymorphism and ovarian cancer, including Caucasian and Asian women.
- Effects of Remifentanil on the Cardiac Conduction System. Our Experience in the Study of Remifentanil Electrophysiological Properties. [JOURNAL ARTICLE]
- Curr Pharm Des 2014 Mar 24.
Remifentanil is a selective mu-opioid receptor agonist characterized by a rapid onset and ultrashort predictable duration of action providing intense analgesia without prolonged respiratory depression. Remifentanil has been implicated in the causation of intraoperative bradyarrhythmias and asystole both in adults and in pediatric patients. Electrophysiological studies in humans and animals show that remifentanil provokes a dose-dependent depressor effect on sinus and AV node function, manifested by a significant prolongation of sinus node recovery time, sino-atrial conduction time and Wenckebach cycle length. These electrophysiologic effects of remifentanil suggest that it should be used with attention in vulnerable patients with predisposition to bradiarritmias during anesthesia.
- The Effects of Sevoflurane or Remifentanil on the Stress Response to Surgical Stimulus. [JOURNAL ARTICLE]
- Curr Pharm Des 2014 Mar 24.
Tissue injury secondary to surgical lesion produces profound changes in endocrine-metabolic function and defence mechanisms in the patient (inflammatory, immunological), leading to an increase in catabolism, immunosuppression and postoperative morbidity. The best anaesthetic and surgical technique should be capable of modulating this response, especially in major surgery, where it can be most harmful and increase patient morbidity. Many of the changes that maintain homeostasis are controlled by the hypothalamic-pituitary-adrenal axis. The autonomic-adrenal response is usually immediate, compared to the hypothalamus-pituitary gland, which is slower and longer lasting. Cytokine synthesis and release is one of the earliest stages in the response to tissue lesion. The most frequently studied cytokines in surgical stress response are IL-6 and TNF-α. Inflammatory mediator concentrations are direct indicators of perioperative stress, while haemodynamic changes are considered the indirect indicators of this response. Multiple anaesthetic techniques have been described to modify the stress response in patients undergoing elective surgery. The aim of this review is to present clinical evidence on perioperative stress modulation with different anesthetics. We also describe a different point of view in immunomodulation with the intraoperative management of haemodynamic responses with inhalational bolus of sevoflurane or with remifentanil intravenous bolus. The effects of sevoflurane used as an inhalational bolus to counteract patients' intraoperative haemodynamic responses modulates the immune response the same than opioid remifentanil.
- Neuroprotective Effects of Intravenous Anesthetics: A New Critical Perspective. [JOURNAL ARTICLE]
- Curr Pharm Des 2014 Mar 25.
Perioperative cerebral damage can result in various clinical sequela ranging from minor neurocognitive deficits to catastrophic neurological morbidity with permanent impairment and death. The goal of neuroprotective treatments is to reduce the clinical effects of cerebral damage through two major mechanisms: increased tolerance of neurological tissue to ischemia and changes in intra-cellular responses to energy supply deprivation. In this review, we present the clinical evidence of intravenous anesthetics on perioperative neuroprotection, and we also provide a critical perspective for future studies. The neuroprotective efficacy of the intravenous anesthetics thiopental, propofol and etomidate is unproven. Lidocaine may be neuroprotective in non-diabetic patients undergoing cardiac surgery with cardiopulmonary bypass (CBP) or with a 48-hour infusion, but conclusive data are lacking. There are several limitations of clinical studies that evaluate postoperative cognitive dysfunction (POCD), including difficulties in identifying patients at high-risk and a lack of consensus for defining the "gold-standard" neuropsychological testing. Although a battery of neurocognitive tests remains the primary method for diagnosing POCD, recent evidence suggests a role for novel biomarkers and neuroimaging to preemptively identify patients more susceptible to cognitive decline in the perioperative period. Current evidence, while inconclusive, suggest that intravenous anesthetics may be both neuroprotective and neurotoxic in the perioperative period. A critical analysis on data recorded from randomized control trials (RCTs) is essential in identifying patients who may benefit or be harmed by a particular anesthetic. RCTs will also contribute to defining methodologies for future studies on the neuroprotective effects of intravenous anesthetics.
- Pharmacological Strategies For The Prevention Of Acute Kidney Injury Following Cardiac Surgery: An Overview Of Systematic Reviews. [JOURNAL ARTICLE]
- Curr Pharm Des 2014 Mar 25.
Context: Post cardiac surgery acute kidney injury (AKI) is common, poorly understood and associated with a significant increase in morbidity and mortality. Objectives: An overview of systematic reviews that have evaluated pharmacological agents for the prevention of AKI post cardiac surgery. Data Sources: We searched electronic databases (PubMed and the Cochrane Database of Systematic Reviews) from inception to January 2014. Study selection: Systematic reviews of randomized controlled trials that have evaluated pharmacological agents for the prevention of AKI in adult patients undergoing cardiac surgery. Data analysis: Numbers needed to treat (NNT) or harm (NNH) were calculated from pooled events given in each meta-analysis. Primary outcome measures were defined as (i) mortality, (ii) need for renal replacement therapy (RRT), and (iii) acute kidney injury. Results: Data from 7 systematic reviews evaluating 6 different pharmacological renoprotective agents were included. Dopamine, fenoldopam and N-acetylcysteine did not demonstrate any benefit in terms of mortality, need for RRT or incidence of AKI. Atrial natriuretic peptide reduced the need for RRT (NNT = 22 (95% CI: 13 to 73) and brain natriuretic peptide reduced the incidence of AKI (NNT = 11 (95% CI: 6 to 32), although both agents did not demonstrate any effect on mortality. Loop diuretics demonstrated increased incidence of AKI (NNH = 8 (95% CI: 5 to 15). Conclusion: There is a paucity of effective renoprotective agents that can be used in adult cardiac surgical patients. There is an urgent need to develop novel renoprotective strategies.
- Is Time To Change To Halogenated Drugs In Cardiac Surgery, What Do We Have To Do With Propofol? [JOURNAL ARTICLE]
- Curr Pharm Des 2014 Jan 22.
There is initial evidence, at least in cardiac surgery, that total intra-venous anesthesia (usually a propofol-based total intra-venous anesthesia) is associated with an increased mortality when compared to an anesthetic plan including an halogenated anesthetics. The cardiac protective properties of halogenated agents (desflurane, isoflurane and sevoflurane) have not been confirmed in non-cardiac surgery and mixed results exist for patients admitted in postoperative intensive care units. This article summarizes the papers with the most impressive findings in favor of halogenated anesthetics, but it recognizes that, at the same time, there is no evidence based medicine against the use of propofol, highlighting the need for large randomized trials that should focus on survival.
- Preoperative Levosimendan. A New Way For Organoprotection" [JOURNAL ARTICLE]
- Curr Pharm Des 2014 Mar 25.
Preoperative use of levosimendan in cardiac surgery patients is one of the most attractive therapeutic alternatives in subjects with left or right ventricular dysfunction. Our review explores the pharmacological bases and clinical evidence for the use of levosimendan, with the intention of making a series of recommendations regarding its use in preoperative optimization prior to cardiac surgery. We carried out a survey of 102 Spanish anesthesiologists in order to shed light on the grey areas regarding the use of this drug prior to surgery. Our findings suggest that levosimendan is recommended for patients with severe left or right ventricular dysfunction, moderate left ventricular dysfunction in which Intra-aortic Balloon Counterpulsation (IABC) and severe pulmonary hypertension. Administration of levosimendan prior to surgical cardiac intervention without an initial bolus reduces the likelihood of complications.
- Perioperative Organoprotection, Something New And Something Wrong. [EDITORIAL]
- Curr Pharm Des 2014 Mar 25.