Current drug targets
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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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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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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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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.