Pharmacological research : the official journal of the Italian Pharmacological Society
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Iron is an essential biogenic element for both prokaryotic and eukaryotic cells. In humans iron is present in hundreds of different metalloproteins. ⋯ Therapeutic modulation of hepcidin is a new and promising approach to treatment of these conditions. In this review, a summary of the current knowledge of hepcidin function, regulation and pathological involvements are provided, followed by a section covering the therapeutic potential of hepcidin and the current strategies how to modulate its levels and biological functions for therapeutic purposes.
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The review focuses on the common kidney disorder of Autosomal Dominant Polycystic Kidney Disease (ADPKD). The potential pathogenetic role of the renin-angiotensin-aldosterone system (RAAS) in the renal cyst growth, the accompanying hypertension, and the frequency of increased left ventricular mass is considered. The therapeutic benefit of angiotensin converting enzyme inhibition (ACEI) in diminishing the renal cyst growth, treatment of the hypertension, and reversing the increased left ventricular mass in ADPKD is supportive of this possibility. The effects of ACEI related and unrelated to control of blood pressure are discussed.
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Meldonium (mildronate; 3-(2,2,2-trimethylhydrazinium)propionate; THP; MET-88) is a clinically used cardioprotective drug, which mechanism of action is based on the regulation of energy metabolism pathways through l-carnitine lowering effect. l-Carnitine biosynthesis enzyme γ-butyrobetaine hydroxylase and carnitine/organic cation transporter type 2 (OCTN2) are the main known drug targets of meldonium, and through inhibition of these activities meldonium induces adaptive changes in the cellular energy homeostasis. Since l-carnitine is involved in the metabolism of fatty acids, the decline in its levels stimulates glucose metabolism and decreases concentrations of l-carnitine related metabolites, such as long-chain acylcarnitines and trimethylamine-N-oxide. Here, we briefly reviewed the pharmacological effects and mechanisms of meldonium in treatment of heart failure, myocardial infarction, arrhythmia, atherosclerosis and diabetes.
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Pain is a distressing sensation, resulting from real or potential tissue damage. It is crucial to protect our body, but it can be so intense that it requires treatment. Furthermore, in some circumstances, pain can become persistent/chronic, such as that triggered by inflammatory disease or neuropathy. ⋯ In this context, there is emerging evidence indicating that C5a, a component of the complement system, and its cell membrane receptor, C5aR, play a critical role in the genesis of acute and chronic pain states. Thus, this review will describe the mechanisms by which C5a/C5aR signaling participates in the cascade of events involved in the pathophysiology of acute (postoperative), inflammatory and neuropathic pain states. Furthermore, it will also highlight the current possibilities for the development of a novel class of analgesic drugs that target C5a/C5aR signaling.
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Review Meta Analysis
A PRISMA-compliant systematic review and meta-analysis of randomized controlled trials investigating the effects of statin therapy on plasma lipid concentrations in HIV-infected patients.
Statin therapy may lower plasma lipid concentrations, but the evidence in HIV-infected patients is still unclear. Therefore, we aimed to investigate the impact of statin therapy on plasma lipid concentrations through a systematic review of the literature and meta-analysis of available randomized controlled trials (RCTs). The literature search included PUBMED, SCOPUS, Web of Science and Google Scholar up to October 30, 2015. ⋯ In subgroup analysis, no significant difference was found among different statins in terms of changing plasma concentrations of LDL-C, HDL-C and TG. However, atorvastatin was found to be more efficacious in reducing plasma total cholesterol concentrations (p<0.001). In conclusion, the meta-analysis suggested significant reductions in plasma concentrations of LDL-C, total cholesterol and non-HDL-C, and elevations in HDL-C, but no significant alteration in plasma TG following treatment with statins.