Clinical and experimental pharmacology & physiology
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Clin. Exp. Pharmacol. Physiol. · Jun 2012
ReviewTargeting metabolic inflammation in Parkinson's disease: implications for prospective therapeutic strategies.
1. Parkinson's disease (PD) is one of the most common neurodegenerative disorders and is characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Although the aetiology of PD has not been clarified as yet, it is believed that ageing, diet, diabetes and adiposity are associated with PD. 2. ⋯ Therapeutic strategies aimed at stopping or modifying disease progression are still being sought. Most recent studies suggest that both central and peripheral inflammation may be dysregulated in PD. Therefore, therapeutic strategies aimed at modulating systemic inflammatory reactions or energy metabolism may represent a goal in neuroprotection in PD.
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Clin. Exp. Pharmacol. Physiol. · Jun 2012
ReviewTargeting gaseous molecules to protect against cerebral ischaemic injury: mechanisms and prospects.
1. Ischaemic brain injury is a leading cause of death and disability in many countries. However, the pathological mechanisms underlying ischaemic brain injury, including oxidative stress, calcium overload, excitotoxicity and neuronal apoptosis, are perplexing and this makes it difficult to find effective novel drugs for the treatment of the condition. 2. ⋯ Emerging evidence indicates that gaseous molecules are involved in the pathological processes of ischaemic brain damage. 3. In the present review, we summarize evidence regarding the involvement of gaseous molecules in ischaemic brain injury and discuss the therapeutic potential of targeting gaseous molecules. 4. Collectively, the available data suggest that the application of these biological gas molecules and their pharmacological regulators may be a potential therapeutic approach for the treatment of ischaemic brain injury.
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Clin. Exp. Pharmacol. Physiol. · Jun 2012
ReviewContrast-induced nephropathy: protective role of fenoldopam.
1. Contrast-induced nephropathy (CIN) often occurs after contrast media-related procedures and is associated with increased morbidity and mortality. The acute renal failure observed after administration of contrast media is usually transient but, in some cases, it can be severe enough to lead to permanent renal damage with life-long dialysis. 2. ⋯ Initial studies have shown the safety of and favourable results with direct infusion of fenoldopam into the renal arteries using the Benephit renal infusion system (FlowMedica-AngioDynamics, Latham, NY, USA). These results are encouraging and suggest that intrarenal delivery of fenoldopam has an advantage in patients with a high risk of developing CIN. 4. A randomized controlled study comparing intrarenal fenoldopam with placebo is warranted.
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Clin. Exp. Pharmacol. Physiol. · Jun 2012
Reviewβ-lactam pharmacokinetics and pharmacodynamics in critically ill patients and strategies for dose optimization: a structured review.
1. Infections and related sepsis are two of the most prevalent issues in the care of critically ill patients, with mortality as high as 70%. Appropriate antibiotic selection, as well as adequate dosing, is important to improve the clinical outcome for these patients. 2. β-Lactams are the most common antibiotic class used in critically ill sepsis patients because of their broad spectrum of activity and high tolerability. β-Lactams exhibit time-dependent antibacterial activity. ⋯ Critically ill patients experience a myriad of physiological changes that result in changes in the pharmacokinetics (PK) of hydrophilic drugs such as β-lactams. A different approach to dosing with β-lactams may increase the likelihood of positive outcomes considering the pharmacodynamics (PD) of β-lactams, as well as the changes in PK in critically ill patients. 4. The present review describes the strategies for dose optimization of β-lactams in critically ill patients in line with the PK and PD of these drugs.