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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Current drug targets · Jun 2012
ReviewGeneral anesthetics in pediatric anesthesia: influences on the developing brain.
Millions of newborn and infants receive anesthetic, sedative and analgesic drugs for surgery and painful procedures on a daily basis. However, recent laboratory reports clearly demonstrate that anesthetic and sedative drugs induced both neuroapoptosis and neurocognitive deficits in laboratory models. This issue is of paramount interest to pediatric anesthesiologists and intensivists because it questions the safety of anesthetics used for fetal and neonatal anesthesia. ⋯ Conversely, painful stimuli without analgesia and anesthesia have been implicated in triggering neuro-apoptosis in juvenile mammalian models. Published retrospective reviews demonstrate temporary neurological sequelae after prolonged anesthetic exposure in young children and larger studies identify long-term neurodevelopmental impairment after neonatal surgery and anesthesia. This paper examines the evidence for the effects of commonly used anesthetics on neuronal structure and neurocognitive function in laboratory models and reviews the relevant clinical human epidemiologic data.
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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
ReviewIs preoperative endoscopic biliary drainage indicated for jaundiced patients with resectable pancreatic cancer?
The role of preoperative biliary drainage (PBD) in the management of jaundiced patients with resectable pancreatic cancer (RPC) is controversial. Obstructive jaundice determines hepatic dysfunction which can increase the operative risks. Experimental studies demonstrated that PBD could be associated with improved surgical outcomes. ⋯ The latter is still considered the first step for jaundiced patients when they present with cholangitis, intense pruritus or severe jaundice; surgery cannot be scheduled within 7-10 days from the diagnosis; neoadjuvant chemoradiation is planned, as part of the treatment. While endoscopic PBD is considered the preferred approach, there is still controversy about the type of biliary stent which should be used. Emerging data support the insertion of short (4-6 cm) biliary self-expandable metallic stent, especially if surgery is not immediately planned.
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Hypovolemia is the most common cause of circulatory failure in children and may lead to critical tissue perfusion and eventually multiple-organ failure. Administration of fluids to maintain or restore intravascular volume represents a common intervention after hemorrhagic shock occurring during surgical procedures or in patients with trauma. Notwithstanding, there is uncertainty whether the type of fluid may significantly influence the outcome, especially in pediatrics. ⋯ Hydroxyethylstarch (HES) preparations have been introduced recently, becoming very popular for vascular loading both in adults and children. However, the number of pediatric studies aimed at evaluating HES efficacy and tolerance is limited. Given the ongoing controversies on the use of colloids in childhood, this review will focus on the pharmacodynamics of synthetic and non synthetic colloids for the treatment of critical blood loss in pediatrics.