Current pharmaceutical design
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Glioblastomas are highly lethal cancers for which conventional therapies provide only palliation. The cellular heterogeneity of glioblastomas is manifest in genetic and epigenetic variation with both stochastic and hierarchical models informing cellular phenotypes. At the apex of the hierarchy is a self-renewing, tumorigenic, cancer stem cell (CSC). ⋯ Glioma stem cells (GSCs) are enriched in functional niches--prominently the perivascular space and hypoxic regions. These niches provide instructive cues to maintain GSCs and induce cellular plasticity towards a stem-like phenotype. GSC-maintaining niches may therefore offer novel therapeutic targets but also signal additional complexity with perhaps different pools of GSCs governed by different molecular mechanisms that must be targeted for tumor control.
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Insomnia is a highly prevalent condition, and due to ongoing demand from patients suffering with this condition, new pharmacological treatments are actively being sought. As our neurophysiological understanding of insomnia grows, so too do the available treatment options. A significant advance in the treatment of insomnia came with the development of the nonbenzodiazepine hypnotic medications, zolpidem, zaleplon and eszopiclone. ⋯ Serotonin antagonists and inverse agonists have been investigated; however, a recent trial with APD125 was discontinued due to lack of efficacy. Sodium oxybate has been used off-label for insomnia by some providers, although data supporting its use are limited. While the sleep-promoting effects of GABA(A) (nonbenzodiazepines and benzodiazepines) enhancement is well-established, newer research examining other mechanisms of action suggest that agents which modulate the histaminergic, serotonergic, melontonergic, and hypocretin/orexin and perhaps GABA-B systems show promise.
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There is a dramatic increase in the number of elderly persons on a worldwide scale with an increase in chronic comorbidities, especially type 2 diabetes (T2DM) and dementia. Although cognitive faculties commonly deteriorate in non-diabetic persons as they age, several studies have concluded that diabetes is uniquely associated with cognitive decline and is associated with a two-fold risk of Alzheimer's Disease (AD). Studies have also suggested that good glycemic has shown to improve cognitive status, however whether the use of specific anti-diabetic oral agents may play an additional role in controlling against cognitive deterioration is unknown. ⋯ The literature has suggested that the use of insulin sensitizers and statins is correlated with a lower rate of cognitive decline in older persons. In this paper, we will explore recent findings regarding diverse single nucleotide polymorphisms from GWAS on T2DM, AD and both. We will also shed light on future pathways, as the basis of improving drug and diagnostics development for a better integration of genetic studies for precise drug-development focusing on the role of genetic variation in maintaining metabolic control and cognitive performance.
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Obstructive sleep apnea (OSA) is a growing public health hazard fueled by the obesity epidemic and an aging population. Untreated sleep apnea can result in significant consequences both in the short-term and long-term. ⋯ Alternative treatments include an oral appliance or surgical options. This paper discusses the pharmacologic treatment of sleep apnea: goals include medications to address the ventilatory control of breathing, treat co-morbid diseases, treat associated health problems/complaints, address special issues, such as anesthetic precautions, and propose future targets.
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Coronary heart disease (CHD) is the leading cause of death among elderly patients and >80% of all coronary deaths occur in patients >65 years. Cerebrovascular events are also associated with older age. Since elevated cholesterol concentrations are a risk factor for cardiovascular disease, lipid-lowering drugs, especially statins, are in widespread use for prevention. ⋯ Their prescription should not be denied to patients for reasons of age alone. Other lipid-lowering drugs play only a minor role in cardiovascular disease (CVD) event prevention because convincing outcome studies are largely missing. A primary prevention statin trial in the very elderly is urgently needed.