Current drug targets
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Acute kidney injury (AKI) associated with sepsis remains an all too common occurrence with an associated high mortality rate. However, recent developments bring hope that this scenario may be changing. ⋯ These include: (1) defining a standard definition for AKI; (2) understanding the importance of early recognition of AKI; (3) improving imaging techniques for the diagnosis of AKI; (4) improved understanding of the complex pathogenesis of AKI, especially in sepsis; (5) the development of targeted strategies to prevent and treat AKI and (6) an improved understanding of the design and implementation of clinical trials in AKI. Through advances in all of these areas it is hoped that the incidence and mortality rates associated with AKI will be improved.
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Current drug targets · Dec 2009
ReviewNovel therapeutic targets for prevention and therapy of sepsis associated acute kidney injury.
Sepsis associated Acute Kidney Injury (SA-AKI) is the leading cause of AKI in the hospital setting and its incidence is increasing. Although the exact pathophysiology and phenotype of SA-AKI are not known, it is widely accepted that SA-AKI has a multi-injury pathway. ⋯ Promising agents that are in development include toll-like receptor inhibition, IL-10 augmentation, modulators of the protein C pathway, and mesenchymal stem cell mediated therapeutics. The aim of this review is to review the pathophysiology of SA-AKI and the therapeutic interventions that are under development to treat this complex and morbid disease.
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Septic acute kidney injury (AKI) occurs between 15% and 20% of all intensive care unit admissions and its mortality ranges from 20% to 60%. The incidence and mortality of septic AKI has remained high throughout the last 10 years, whereas our understanding of septic AKI pathogenesis has remained limited. ⋯ Improvement of knowledge about this condition seems to be most important in order to find valid diagnostic exams to exactly identify septic AKI and effective therapies to treat it: both of them are currently lacking. Finally, new preventive strategies might be experimented in order to protect critically ill patients from septic AKI.
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Acute severe asthma is characterized by a state of airway inflammation and increased bronchiolar smooth-muscle tone that leads to increased resistance to expiration and lung hyperinflation. Despite the better knowledge of its pathophysiology, the incidence and severity of asthma in the last twenty years is increased worldwide, although with significant age and geographic variation. As a result, the number of patients requiring more intensive medical therapy has also increased. ⋯ The use of inhalational anesthetic agents for treatment of severe status asthmaticus has been documented in case reports, case series and small uncontrolled studies. Their use may be considered in any mechanically ventilated patients whose severe bronchospasm failed to respond to maximal medical treatment. In the present review article, we aim to provide a brief description of the physio-pathological and clinical features of acute severe asthma, and of the principles of treatment, focusing our attention on the use of the inhalational anesthetics in severe patients requiring mechanical ventilation and not responding to conventional therapy.
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Critical illness and particularly sepsis are associated with a significant redox imbalance resulting from an increased production of oxidant species and a decrease in endogenous antioxidant defences. In critical patients sources of oxidative stress include the mitochondrial respiratory electron transport chain, xanthine oxidase activation, the respiratory burst associated with neutrophil activation, and arachidonic acid metabolism. Several endogenous antioxidants have been identified including enzymes, like superoxide dismutases and glutathione peroxidase, vitamins and other molecules such as uric acid and bilirubin. ⋯ Melatonin is a promising molecule that deserves the attention of future research, as well as vitamin C. Further studied should also try to establish the more beneficial combination of antioxidants, as well as the doses, and the timing of administration. When such problems will be resolved hopefully results about antioxidant therapy in critical illness will be more univocal and promising.