Drug Des Dev Ther
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Randomized Controlled Trial
Paracetamol sharpens reflection and spatial memory: a double-blind randomized controlled study in healthy volunteers.
Acetaminophen (APAP, paracetamol) mechanism for analgesic and antipyretic outcomes has been largely addressed, but APAP action on cognitive function has not been studied in humans. Animal studies have suggested an improved cognitive performance but the link with analgesic and antipyretic modes of action is incomplete. This study aims at exploring cognitive tests in healthy volunteers in the context of antinociception and temperature regulation. A double-blind randomized controlled study (NCT01390467) was carried out from May 30, 2011 to July 12, 2011. ⋯ This study shows for the first time that APAP sharpens decision making and planning strategy in healthy volunteers and that cognitive performance and antinociception are independent of APAP effect on thermogenesis. We suggest that cognitive performance mirrors the analgesic rather than thermic cascade of events, with possibly a central role for serotonergic and cannabinoid systems that need to be explored further in the context of pain and cognition.
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Review
Spotlight on valsartan-sacubitril fixed-dose combination for heart failure: the evidence to date.
Heart failure is a global problem with elevated prevalence, and it is associated with substantial cardiovascular morbidity and mortality. Treating heart-failure patients has been a very challenging task. This review highlights the main pharmacological developments in the field of heart failure with reduced ejection fraction, giving emphasis to a drug that has a dual-acting inhibition of the neprilysin and renin-angiotensin-aldosterone system. ⋯ This drug is composed of two molecular moieties in a single crystalline complex: a neprilysin-inhibitor prodrug (sacubitril) and the angiotensin-receptor blocker (valsartan). The PARADIGM-HF trial demonstrated that this drug was superior to an angiotensin-converting enzyme inhibitor (enalapril) in reducing mortality in patients with heart failure with reduced ejection fraction. The ability to block the angiotensin receptor and augment the endogenous natriuretic peptide system provides a distinctive mechanism of action in cardiovascular disease.
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Somatostatin analogs (SSAs), which were initially used to control hormonal syndromes associated with neuroendocrine neoplasms (NENs), have been successfully proposed as antiproliferative agents, able to control tumor growth in patients affected by gastroenteropancreatic (GEP)-NENs. The development of long-acting formulations of SSAs which require only weekly or monthly injections can improve patient compliance. ⋯ Although there is no evidence of an overall survival benefit, these studies confirm the efficacy of LAN Autogel in terms of benefit in progression-free survival, and in more than half of cases, a reduction of tumor markers can be observed during treatment with this drug. Moreover, LAN Autogel is widely recognized to be effective in controlling tumor-related symptoms in the majority of patients affected by GEP tumors, especially in patients affected by carcinoid syndrome, improving considerably patients' quality of life.
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This paper reports the results of a clinical study that tested the effect of suppressive treatment with the botanical product Gene-Eden-VIR/Novirin on the number of genital herpes outbreaks. The results in this study were compared to those published in clinical studies of acyclovir, valacyclovir, and famciclovir. ⋯ The clinical study showed that the natural Gene-Eden-VIR/Novirin decreases the number of genital herpes outbreaks without any side effects. The study also showed that the clinical effects reported in this study are mostly better than those reported in the reviewed studies of acyclovir, valacyclovir, and famciclovir.
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Burgeoning antibiotic resistance and unfavorable outcomes of inflammatory injury after Pseudomonas aeruginosa infection have necessitated the development of novel agents that not only target quorum sensing (QS) but also combat inflammatory injury with the least risk of resistance. This study aimed to assess the anti-QS and anti-inflammatory activities of baicalein, a traditional herbal medicine that is widely used in the People's Republic of China, against P. aeruginosa infection. We found that subminimum inhibitory concentrations of baicalein efficiently interfered with the QS-signaling pathway of P. aeruginosa via downregulation of the transcription of QS-regulated genes and the translation of QS-signaling molecules. ⋯ Baicalein reduced the P. aeruginosa-induced secretion of the inflammatory cytokines IL-1β, IL-6, IL-8, and TNFα. In addition, baicalein suppressed P. aeruginosa-induced activation of the MAPK and NFκB signal-transduction pathways in cocultured macrophages; this may be the mechanism by which baicalein inhibits the production of proinflammatory cytokines. Therefore, our study demonstrates that baicalein represents a potential treatment for P. aeruginosa infection because it clearly exhibits both antibacterial and anti-inflammatory activities.