Current drug targets
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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.
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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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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.
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Current drug targets · Dec 2011
ReviewSelective estrogen receptor modulators and aromatase inhibitors for breast cancer chemoprevention.
In premenopausal women, tamoxifen for 5 years reduces the risk of estrogen receptor (ER) - positive breast cancer for at least 10 years. Women < 50 years of age experience fewer serious side effects. Vascular and vasomotor events do not persist after treatment regardless of age. ⋯ No evidence exists establishing whether a reduction in breast cancer risk from either agent translates into reduced breast cancer mortality. Overall quality of life is similar with raloxifene or tamoxifen, but the incidence of dyspareunia, weight gain, and musculoskeletal complaints is higher with raloxifene use, whereas vasomotor symptoms, bladder incontinence, gynecologic symptoms, and leg cramps were higher with tamoxifen use. Ongoing randomized, placebo-controlled trials investigating the use of third-generation aromatase inhibitors in the chemoprevention of breast cancer in postmenopausal women include the NCIC Clinical Trials Group MAP3 (ExCel) Trial (Exemestane in Preventing Cancer in Postmenopausal Women at Increased Risk of Developing Breast Cancer), and the IBIS-II trial.71 The North American MAP3 study randomized patients to exemestane or placebo in patients who refuse treatment with a SERM, and the international IBIS-II trial compares anastrozole for 5 years versus placebo for chemoprevention in patients at increased risk.
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Current drug targets · Dec 2011
Role of advanced glycation end products (AGEs) in osteoporosis in diabetes.
Recent meta-analyses have revealed that the risk of bone fracture is increased in both type 1 and type 2 diabetic patients. Low bone mineral density (BMD) can not necessarily explain the link, because BMD is increased rather than decreased in type 2 diabetes, while it is consistently low in type 1 diabetes subjects. Although multiple factors could influence the quality of bone and increase the bone fragility in diabetes, there is accumulating evidence for the association between osteoporosis and vascular calcification, which is an independent predictor of cardiovascular disease morbidity and mortality. ⋯ Further, cross-linking in the organic bone matrix by AGEs could adversely affect the fracture resistance of bone. Therefore, in this paper, I review the pathophysiological role of the AGEs-RAGE-oxidative stress system in decreased BMD and increased bone fragility in diabetes. I also discuss here the potential therapeutic interventions of the AGEs-RAGE axis for preventing osteoporosis in diabetes.