Current pharmaceutical design
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A robust circadian timekeeping system is important for human health and well-being. Inappropriately timed light exposure can cause circadian and sleep disruption, which has been shown to have negative health consequences. ⋯ Cycled lighting and increased exposure to sunlight in medical care facilities have been shown to have positive effects on patient recovery and well-being, and expedite hospital discharge. Additional clinical research is needed to determine the optimal light exposure timing, duration, intensity, and spectrum to best promote recovery, health and well-being in the context of medical care.
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Neuronal injury not only results in severe alteration in the function of primary sensory neurons and their central projection pathway, but is also associated with a robust immune response at almost every level of the somatosensory system. Evidence from animal studies suggests undoubtedly that bi-directional signalling between the immune system and the nervous system contribute to the development and maintenance of chronic neuropathic pain. Non-neuronal cells, including peripheral immune cells, CNS/PNS glial cells and endothelial cells play important roles in the neuroimmune interaction and subsequent persistent hypersensitivity. ⋯ Therapeutic agents targeting inflammation provide an exciting prospect. Yet, considering the heterogeneous conditions presented in neuropathic pain, no matter the etiologies, or the pathophysiology during different stages of the disease; and the complexity of the immune response to the damage on the nervous system, it appears that finely tuned strategies of modulating inflammation are essential to warrant an effective treatment for neuropathic pain. We want to reduce pain; we also want to promote tissue repair and functional recovery.
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Diabetic macular edema (DME) represents the most common cause of vision loss in patients affected by diabetes mellitus. Although the pathophysiology of DME is not wholly understood, vascular endothelial growth factor (VEGF) has been identified as a key contributor to the development of DME. ⋯ In particular, VEGF-inhibitors that have been studied for diabetic retinopathy include pegaptanib, ranibizumab, bevacizumab, and aflibercept. The present review analyzes the main characteristics of each molecule, describing the most important results of clinical trails.
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Staphylococci, in particular Staphylococcus aureus and Staphylococcus epidermidis, are a leading cause of healthcare-associated infections. Patients who have a medical device inserted are at particular risk of an infection with these organisms as staphylococci possess a wide range of immune evasion mechanisms, one of which being their ability to form biofilm. Once embedded in a biofilm, bacteria are inherently more resistant to treatment with antibiotics. ⋯ Several obstacles need to be overcome in the further development of these and other novel anti-biofilm agents. Most notably, although in vitro investigation has progressed over recent years, the need for biofilm models to closely mimic the in vivo situation is of paramount importance followed by controlled clinical trials. In this review we highlight the issues associated with staphylococcal colonisation of medical devices and potential new treatment options for the prevention and control of these significant infections.
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Recent investigations of the cellular and molecular mechanisms of pain provide new hopes for more effective treatments for patients with chronic pain. At the molecular and genetic levels, new proteins and genes related to sensory sensation have been identified. ⋯ This disconnect between discovery and better treatment options is due, in part to the negative side effects associated with new treatment options, and also as a result of the ineffectiveness of these new drugs for inhibiting chronic pain. In this review, I will explore this disconnect between discovery and treatment, and propose that the failure of previous medicines can be due to their limited effects on injury-related plasticity, and question the common misperception of seeking compounds for high efficacy before understanding basic mechanisms of the target proteins in pain-related plasticity.