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Lithium has been successfully employed therapeutically for treatment of bipolar depressive illness; however, its mechanism of action is poorly understood. Recently, it has been demonstrated by us that lithium can prevent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) dopaminergic neurotoxicity in mice. From analyzing the pattern of protection in various parameters, we suggest that lithium protects against MPTP-induced depletion of striatal dopamine (DA) by preventing free radical-induced inactivation of tyrosine hydroxylase (TH), the rate limiting enzyme in dopamine synthesis. Possible neuroprotective effect of lithium against H(2)O(2)-induced cell death was assessed in human neuroblastoma; SH-SY5Y cell line. Pretreatment with LiCl (2mM and 4mM) for 7 days protected against H(2)O(2) neurotoxicity in a dose-dependent manner. However, this protection could not be achieved through short-term incubation with LiCl. In agreement; we found that lithium lacks immediate antioxidant activity using the in vitro lipid peroxidation essay indicating that not acute but chronic treatment with lithium allows cells to deal better with oxidative stress., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Introduction: The metabolic deregulation associated with diabetes mellitus (DM) causes secondary pathophysiologic changes in multiple organ systems. Endothelial injury is induced by oxidative stress (OS) and inflammation. We have previously shown that DM type 2 patients are exposed to increased OS and inflammation contributed in part by primed peripheral polymorphonuclear leukocytes (PMNLs)., Aims: To characterize the effect of oral medication on PMNL priming, on PMNL-related and on systemic inflammation, in correlation to changed diabetes parameters in patient with newly diagnosed type 2 DM., Methods: PMNLs were separated from DM patient's prior and following treatment with either metformin (Glucophage), or Thiazolidinedione (rosiglitazone) and from healthy control subjects (HC). Rate of superoxide release from phorbol ester-stimulated PMNLs and CD11b on PMNLs assessed PMNL priming. White blood cells (WBC) and PMNL counts and apoptosis reflected PMNL-related inflammation. CRP, fibrinogen, transferrin and albumin blood levels reflected systemic inflammation., Results: Both metformin and rosiglitazone treatments reduced significantly the high levels of glucose and HbA1c, and slightly improved lipid profile during 2 months. PMNL priming parameters, higher compared to HC, increased after 2 months of metformin treatment. Rosiglitazone treatment decreased PMNL priming. ALP, higher in DM, significantly decreased following 2 months of both treatments. Systemic inflammation markers (fibrinogen, CRP), higher in DM, decreased following both treatments. Transferrin and albumin were similar to HC. PMNL-related inflammation markers were higher in DM; however, only PMNL apoptosis decreased after both treatments. Monocyte counts, higher in DM compared to HC, decreased following both treatments. Serum insulin levels, higher in DM compared to HC, decreased following both treatments. PMNL-related priming and inflammation parameters positively correlated with HbA1c., Conclusion: The present research adds new facet in evaluating anti-hyperglycemic treatment in type 2 DM patients. Despite sufficient glycemic control using both treatments, some PMNL-related parameters deteriorated. Thus, anti hyperglycemic treatment should be favored due to its combined anti-PMNL priming and anti-inflammatory effect, in addition to its anti-hyperglycemic characteristics, according to the correlation among these parameters. Such combined treatment may reduce morbidity and mortality common in DM patients.

Background: Oxidative stress (OS) and chronic inflammation are involved and contribute to the development of atherosclerosis. Primed polymorphonuclear leukocytes (PMNLs) are a possible source for superoxide radicals and inflammatory mediators, hence can promote OS and inflammation. The involvement of primed PMNLs in clinical states associated with high risk for developing cardiovascular disease and atherosclerosis, such as hypertension, renal failure and diabetes has been described, however, little is known about PMNLs characteristics in hyperlipidemic patients., Methods: Hyperlipidemic patients and healthy control (HC) subjects were enrolled in this cross-sectional study. PMNL priming was estimated by measuring the rate of superoxide release and by levels of membrane CD11b. PMNL priming and myeloperoxidase (MPO) levels served as OS indices. Inflammation was linked to peripheral white blood cells and PMNL counts and to apoptosis. Systemic inflammation was estimated by blood levels of fibrinogen, C-reactive protein (CRP), transferrin and albumin. PMNL priming and inflammation parameters were related to the severity of hyperlipidemia., Results: PMNLs from hyperlipidemic patients are primed compared to HC. A decrease in PMNL-MPO levels with increased levels of serum MPO were found in hyperlipidemic patients. Leukocyte counts tended to be higher in hyperlipidemic patients with increased PMNL apoptosis. PMNL priming and fibrinogen levels correlated positively with the severity of hyperlipidemia (r=0.32, P=0.02 for CD11b vs. cholesterol and r=0.38, P=0.009 for CD11b vs. LDL-c; r=0.35, P=0.01 for fibrinogen vs. cholesterol and r=0.3, P=0.03 for superoxide release vs. LDL-c)., Conclusion: PMNLs are primed in hyperlipidemic patients contributing to OS and inflammation in these patients. This study highlights primed PMNLs as an additional risk factor for promoting atherosclerosis in hyperlipidemic patients.

Current research efforts on neurological diseases are focused on identifying novel disease biomarkers to aid in diagnosis, provide accurate prognostic information and monitor disease progression. With advances in detection and quantification methods in genomics, proteomics and metabolomics, saliva has emerged as a good source of samples for detection of disease biomarkers. Obtaining a sample of saliva offers multiple advantages over the currently tested biological fluids as it is a non-invasive, painless and simple procedure that does not require expert training or harbour undesirable side effects for the patients. Here, we review the existing literature on salivary biomarkers and examine their validity in diagnosing and monitoring neurodegenerative and neuropsychiatric disorders such as autism and Alzheimer's, Parkinson's and Huntington's disease. Based on the available research, amyloid beta peptide, tau protein, lactoferrin, alpha-synuclein, DJ-1 protein, chromogranin A, huntingtin protein, DNA methylation disruptions, and micro-RNA profiles provide display a reliable degree of consistency and validity as disease biomarkers.