Current drug targets
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Current drug targets · Aug 2012
Bacterial cell wall compounds as promising targets of antimicrobial agents I. Antimicrobial peptides and lipopolyamines.
The first barrier that an antimicrobial agent must overcome when interacting with its target is the microbial cell wall. In the case of Gram-negative bacteria, additional to the cytoplasmic membrane and the peptidoglycan layer, an outer membrane (OM) is the outermost barrier. The OM has an asymmetric distribution of the lipids with phospholipids and lipopolysaccharide (LPS) located in the inner and outer leaflets, respectively. ⋯ Therefore, a given antimicrobial agent must ideally have a double character, namely, it must overcome the bacterial cell wall barrier, without inducing the liberation of the pro-inflammatory amphiphiles. Here, new data are presented which describe the development and use of membrane-active antimicrobial agents, in particular antimicrobial peptides (AMPs) and lipopolyamines. In this way, essential progress was achieved, in particular with respect to the inhibition of deleterious consequences of bacterial infections such as severe sepsis and septic shock.
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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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Almost all children in the pediatric intensive care (PICU) need analgesia and/or sedation. Analgesics drugs are used to control pain from surgical incisions, drainages, vascular access or endotracheal suctioning. Sedatives are used to facilitate the delivery of nursing care, to facilitate mechanical ventilation, prevent self-extubation and to minimize patient discomfort. ⋯ However, behavioral evaluation tools based on patient responsiveness, cannot be used during the administration of neuromuscular blocking agents. Under this conditions it could be difficult to interpret the degree of sedation. EEG derived Monitoring devices may represents an useful tools of assessing the level of sedation, but there is insufficient evidence to support the routine use of the BIS monitor in PICU.
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Current drug targets · Jun 2012
Ultrasound guided central vascular access in neonates, infants and children.
Ultrasound guided central venous cannulation is rapidly becoming the standard technique for achieving a central line in neonates, infants and children. Older techniques such as surgical cutdown and 'blind' percutaneous venipuncture have many disadvantages: they are time consuming, vein consuming and/or associated with dangerous immediate or late complications. On the other hand, ultrasound has only advantages, giving the operator the possibility of (a) choosing the most appropriate and safest venous access on the basis of ultrasound assessment, (b) performing a 100% safe insertion, (c) ruling out malpositions or pleuro-pulmonary damages, during and after the procedure. ⋯ Ultrasound can be used for puncturing many different deep veins of the arm, neck, groin and thorax. The vein can be visualized either in short axis or in long axis, while the puncture can be performed 'in-plane' (when the needle trajectory is included in the plane of the ultrasound probe) or 'out-of-plane' (when the needle trajectory is not in that plane). Though, the best clinical results of ultrasound guidance can be achieved - particularly in neonates and infants - only if the operator has been properly trained in this technique through an appropriate curriculum that should include theory lessons, simulation practice and a tutored learning curve.
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The pediatric loco-regional techniques are considered very safe and effective, first of all because they target the therapy directly to the site of surgery, decreasing the risks of intravenous analgesia. The quality of local anesthesia is influenced by structural and biophysical characteristics of local anesthetics drug, dose, site of injection, mixture of local anesthetics and possible addition of a vasoconstrictor or an adjuvant to prolong the analgesic effect. In children, unlike adults, small nerve diameters and short distance between Ranvier nodes permit to use large volumes and low concentrations of local anesthetics. ⋯ Among the adjuvant, clonidine and ketamine showed the best pharmacokinetic and pharmacodynamic profiles of effective and safety, improving and prolonging the action of associated local anesthetics. Therefore, the use of enantiomers, in association with adjuvants as clonidine or ketamine, using the multimodal approach of integrated anesthesia, makes the clinical practice effective and safe in the pediatric operating rooms. This review focuses on the overview of local anesthetics and adjuvants used today in locoregional pediatric anesthesia, with an emphasis on the advantages and disadvantages of each drug.