Current drug targets
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Circulatory failure recognition and treatment represents an important issue in critically ill infants and children. Early diagnosis and prompt institution of adequate treatment may be life-saving for pediatric patients with cardiocirculatory instability in the setting of intensive care. However, the hemodynamic status of the critically ill child is poorly reflected by baseline vital parameters or laboratory blood tests. ⋯ Advanced hemodynamic monitoring consists - among others - of measuring cardiac output, predicting fluid responsiveness and calculating systemic oxygen delivery. Identification and quantifying of pulmonary edema has also been recently appreciated in pediatric critical care. In the last decade, the number of vasoactive drugs has increased, together with a better understanding of clinical application of both different monitoring devices and treatment strategies.
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Current drug targets · Jan 2014
ReviewOxycodone/naloxone in the management of patients with pain and opioid-induced bowel dysfunction.
Common opioids adverse effects include opioid-induced bowel dysfunction (OIBD), which comprises opioid-induced constipation, dry mouth, nausea, vomiting, gastric stasis, bloating, and abdominal pain. Traditional laxatives which are often prescribed for the prevention and treatment of OIBD possess limited efficacy and display adverse effects. A targeted approach to OIBD management is the use of a combination of an opioid agonist with opioid receptor antagonist or administration of purely peripherally acting opioid receptor antagonists. ⋯ OXN is an important drug for chronic pain management, prevention and treatment of OIBD.
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Current drug targets · May 2013
Review Historical ArticleSerotonin-kynurenine hypothesis of depression: historical overview and recent developments.
This mini-review focuses on the studies of late Prof. IP Lapin (1903 - 2012) and his research team on the role of methoxyindole and kynurenine (KYN) pathways of tryptophan (TRP) metabolism in the pathogenesis of depression and action mechanisms of antidepressant effect. In the late 60s of the last century Prof. ⋯ Lapin suggested and discovered that KYN and its metabolites affect brain functions, and proposed the role of neurokynurenines in pathogenesis of depression and action mechanisms of antidepressant effect (kynurenine hypothesis). Further research suggested the antidepressant and cognition- enhancing effects of post-serotonin metabolite, N-acetylserotonin (NAS), an agonist to tyrosine kinase B (TrkB) receptor; and link between depression and chronic inflammation-associated disorders (e.g., insulin resistance, hepatitis C virus) via inflammation-induced activation of indoleamine 2,3- dioxygenase, brain located rate-limiting enzyme of TRY - KYN metabolism. NAS and kynurenines might be the targets for prevention and treatment of depression and associated conditions.
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Cystic fibrosis (CF) is the most common life shortening autosomal inherited disorder, affecting 1 in 2500 newborns in the Caucasian population. In CF the lung pathology is associated with dehydration of the airways epithelial surface which in part results from Na(+) hyperabsorption via the epithelial sodium channel (ENaC). The molecular mechanisms of this Na(+) hyperabsorption and its correlation with the underlying genetic defect in the cystic fibrosis transmembrane conductance regulator (CFTR) are not fully understood. ⋯ Positive benefits for the inhibition of the CF related Na(+) hyperabsorption offer technologies using small molecule inhibitors like ASOs or siRNA, which target translation and knockdown of ENaC, respectively. In this review we discuss possible CFTR/ENaC interactions in the context of CF, describe ENaC structure as well as some of the numerous attempts that were performed to prevent the Na(+) hyperabsorption in CF related lung disease. Thus, we give a short summary of e.g. amiloride therapy approaches and focus on inventive blocking efforts using ASOs and siRNA.
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The incidence of sepsis and acute kidney injury (AKI) are increasing in critically ill patients and both portend a higher risk of morbidity and death. Sepsis has consistently been shown to be a key contributing factor for the development of AKI. Numerous observational studies have found septic AKI to be highly common among the critically ill. ⋯ However, survivors of septic AKI show trends for greater rates of renal recovery and dialysis independence compared with non-septic AKI. The burden of septic AKI continues to increase and remains associated with an unacceptably high attributable morbidity and mortality. Accordingly, there is continued need to understand its epidemiology, not only to guide in management of these patients at the bedside, but also to stimulate advances in understanding its pathophysiology and in therapeutic interventions to potentially mitigate prognosis.