Current drug targets
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Current drug targets · Apr 2011
ReviewPathophysiology of airway colonization in critically ill COPD patient.
Although noninvasive ventilation (NIV) use in severe acute exacerbation of COPD has substantially reduced the need for intubation, an important number of COPD patients still are mechanically ventilated through a tracheal tube in the ICU. Intubation is a major risk factor for lower respiratory tract colonization (LRTC) in ICU patients. Other risk factors for LRTC include colonization of the oral cavity, nasopharynx, and gastric content. ⋯ In addition, the early use of NIV averts respiratory failure after extubation and could reduce the duration of invasive mechanical ventilation. Other measures might be efficient in preventing LRTC such as semirecumbent position, avoidance of gastric distension, polyurethane-cuffed tracheal tubes, silver-coated tracheal tubes, subglottic aspiration, and continuous control of cuff pressure. Further studies should determine the impact of preventive measures aiming at preventing LRTC on outcome of COPD patients requiring intubation and mechanical ventilation in the ICU.
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Current drug targets · Feb 2011
ReviewCombined treatment modalities for age related macular degeneration.
Age-related macular degeneration (AMD) is a condition that accounts for 75% of cases of legal blindness in individuals over the age of 50. ⋯ Combined treatments strategies are an obvious step providing disease control when it is not achieved with a single therapeutic approach. One risk of using a single therapy to control AMD is a rebound induced by compensatory stimulation of other pathogenetic pathways. Combination therapy is a logical approach to address mechanisms of disease progression that appear to be self-sustaining once initiated.
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Current drug targets · Apr 2010
Reviewgamma-Secretase as a therapeutic target in Alzheimer's disease.
gamma-Secretase is an intramembranous multi-protein complex that cleaves many type-I proteins with critical roles in neuronal function. In Alzheimer's disease (AD) interest in gamma-secretase comes, in part, from the fact that this complex is responsible for the last cleavage step of the amyloid precursor protein (APP) that generates the amyloid-beta peptide (Abeta). Abeta represents the primary component of the amyloid plaque, one of the main pathological hallmarks of AD. ⋯ Despite the fact that all clinical trials with NSAIDs or gamma-secretase modulators in AD have failed to show clinical benefit thus far, the main concern is that the Abeta-lowering potency of the tested compounds may be too low. Active efforts are being made to develop compounds able to penetrate into the brain to lower Abeta at physiological doses without interfering with the cleavage and function of other critical gamma-secretase substrates. These novel inhibitors and modulators may soon offer hope in the Alzheimer's fight.
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Current drug targets · Apr 2010
ReviewCannabinoid-opioid interactions in drug discrimination and self-administration: effect of maternal, postnatal, adolescent and adult exposure to the drugs.
Cannabinoids and opioids are known to strictly interact in many physiological and pathological functions, including addiction. The endogenous opioid system is significantly influenced by maternal or perinatal cannabinoid exposure, major changes concerning operant behaviour in adult animals. Copious data suggests that adolescence is also a particularly sensitive period of life not only for the initiation of abusing illicit drugs, but also for the effects that these drugs exert on the neural circuitries leading to drug dependence. ⋯ Overall, evidence confirms a neurobiological convergence of the cannabinoid and opioid systems that is manifest at both receptor and behavioural levels. Although discrepant results have been reported, some data support the gateway hypothesis that adolescent cannabis exposure contributes to greater opioid intake in adulthood. However, it should be kept into consideration that in humans genetic, environmental, and social factors could influence the direct neurobiological effects of early cannabis exposure to the progression to adult drug abuse.
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Current drug targets · Apr 2010
ReviewCannabinoids, opioids and MDMA: neuropsychological interactions related to addiction.
3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is an amphetamine derivative with psychostimulant properties. This substance is widely used around the world by young adults in recreational settings. One of the most remarkable characteristic of ecstasy users is the concurrent consumption of several other drugs of abuse including psychostimulants, alcohol, tobacco, LSD, cannabis and opioids. ⋯ MDMA also modulates the activity of the dynorphinergic and enkephalinergic systems in several brain structures related to addiction, as it has been shown for other psychostimulants. The work regarding the contribution of micro- and delta-opioid receptors in the rewarding effects of MDMA shows differential results in pharmacological studies in rats, with respect to studies using knock-out mice. The present review describes the behavioural and neurochemical interactions between MDMA, cannabinoids and opioids with respect to addiction processes.