The role of statins in the differentiation and function of bone cells.

BACKGROUND: Statins are 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors blocking cholesterol biosynthesis in hepatic cells, thereby causing an increase in low-density lipoprotein (LDL) receptors resulting in enhanced uptake and clearance of atherogenic LDL-cholesterol (LDL-C) from the blood. Accordingly, statins decrease the risk of developing atherosclerosis and its acute complications, such as acute myocardial infarction and ischaemic stroke. Besides the LDL-C-lowering impact, statins also have other so-called pleiotropic effects. Among them, the ability to modulate differentiation and function of bone cells and exert direct effects on osteosynthesis factors. Specifically, earlier studies have shown that statins cause in vitro and in vivo osteogenic differentiation. DESIGN: The most relevant papers on the bone-related 'pleiotropic' effects of statins were selected following literature search in databases and were reveiwed. RESULTS: Statins increase the expression of many mediators involved in bone metabolism including bone morphogenetic protein-2 (BMP-2), glucocorticoids, transforming growth factor-beta (TGF-ß), alkaline phosphatase (ALP), type I collagen and collagenase-1. As a result, they enhance bone formation and improve bone mineral density by modulating osteoblast and osteoclast differentiation. CONCLUSION: This review summarizes the literature exploring bone-related 'pleiotropic' effects of statins and suggests an anabolic role in the bone tissue for this drug class. Accordingly, current knowledge encourages further clinical trials to assess the therapeutic potential of statins in the treatment of bone disorders, such as arthritis and osteoporosis.

Resolution of Inflammation in Neurodegenerative Diseases: The Role of Resolvins.

Acute inflammation has been described as a reactive dynamic process, promoted by the secretion of proinflammatory mediators, including lipid molecules like leukotrienes and prostaglandins, and counterbalanced by proresolving mediators including omega-3 polyunsaturated fatty-acid- (PUFA-) derived molecules. The switch from the initiation to the resolution phase of acute inflammatory response is crucial for tissue homeostasis, whereas the failure to resolve early inflammation by specialized proresolving mediators leads to chronic inflammation and tissue damage. Among PUFA-derived proresolving mediators, different eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) derivatives have been described, namely, resolvins (resolution phase interaction products), which exert their anti-inflammatory and immune-regulatory activities through specific G-protein-coupled receptors. In recent years, compelling evidence has shown that impairment of resolution of inflammation is a crucial pathogenic hallmark in different neurodegenerative disorders, including Alzheimer's disease and Parkinson's disease. This review summarizes current knowledge on the role of resolvins in resolution of inflammation and highlights available evidence showing the neuroprotective potential of EPA- and DHA-derived resolvins (E-series and D-series resolvins, respectively) in neurodegenerative diseases.

Heavy metals in contact dermatitis: A review.

Contact dermatitis is an inflammatory skin reaction caused by direct contact with chemical substances in the environment and can either be irritant or allergic in nature. The clinical symptoms of contact dermatitis, include local skin rash, itching, redness, swelling, and lesions. Nowadays, 15-20% of people have some degree of contact dermatitis, which can be more or less severe. Immune responses in allergic contact dermatitis (ACD) are due to the effects of cytokines and allergen-specific CD4+ and CD8+ T cells on the skin. Acids and alkalis such as drain cleaners, plants such as poinsettias, hair colors, and nail polish remover, are all prominent causes of irritant contact dermatitis (ICDs). Heavy metals are metallic elements with a high atomic weight that are hazardous in low quantities and are known to cause dermatitis after systemic or local exposure. Nickel (Ni), chromium (Cr), lead (Pb), and copper (Cu) are among the most common heavy metals used in various industries. Metal allergies may cause ACD and also systemic contact dermatitis (SCD). Contact dermatitis is detected by laboratory tests such as patch testing, lymphocyte stimulation test (LST), and evaluation of cytokine production by primary cultures of peripheral blood mononuclear cells. This article presents an update on the epidemiological and clinical characteristics of ACD and SCD caused by three heavy metals (Cr, Cu, and Pb). Ni is not discussed due to recent coverage. Furthermore, the effects of contact sensitivity to some other heavy metals, such as gold (Au), cobalt (Co), palladium (Pd), and mercury (Hg) are discussed.

Systemic allergic contact dermatitis to palladium, platinum, and titanium: mechanisms, clinical manifestations, prevalence, and therapeutic approaches.

Contact dermatitis (CD) is an inflammatory skin disease of eczema that is elicited by chemicals or metal ions that have toxic effects without eliciting a T-cell response (contact elicitation) or by small reactive chemicals that modify proteins and induce innate and adaptive immune responses (contact allergens). The clinical condition is characterized by localized skin rash, pruritus, redness, swelling, and lesions, which are mainly detected by patch tests and lymphocyte stimulation. Heavy metals such as palladium (Pd), platinum (Pt), and titanium (Ti) are ubiquitous in our environment. These heavy metals have shown CD effects as allergic agents. Immunological responses result from the interaction of cytokines and T cells. Occupational metal CD accounts for most cases of work-related cutaneous disorders. In this systematic review, the allergic effects of heavy metals, including Pd, Pt, and Ti, and the mechanisms, clinical manifestations, prevalence, and therapeutic approaches are discussed in detail. Furthermore, the therapeutic approaches introduced to treat CD, including corticosteroids, topical calcineurin inhibitors, systemic immunosuppressive agents, phototherapy, and antihistamines, can be effective in the treatment of these diseases in the future. Ultimately, the insights identified could lead to improved therapeutic and diagnostic pathways.