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Background: L-carnitine can be metabolized to trimethylamine N-oxide (TMAO), a molecule that promotes atherogenesis through its interaction with macrophages and lipid metabolism. Objective: The aim of the present study was to assess whether L-carnitine supplementation may promote changes in selected serum biomarkers of atherosclerosis. Methods: Before the start, in the mid-point and after completing the 24-weeks supplementation protocol, fasting blood samples were taken from the antecubital vein. Plasma free L-carnitine and TMAO were determined by the UPLC/MS/MS method. Serum proteins were determined by the enzyme immunoassay method using commercially available kits. Total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and triglycerides have been determined using standard automatic analyzer. Results: L-carnitine supplementation elevated fasting plasma carnitine in the mid-point of our study and it remained increased until the end of supplementation period. Moreover, it induced tenfold increase in plasma TMAO concentration but did not affect serum C-reactive protein, interleukin-6, tumour necrosis factor-α, L-selectin, P-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1 or lipid profile markers. Conclusion: We demonstrated that ­although oral L-carnitine supplementation significantly ­increased plasma TMAO concentration, no lipid profile changes or other markers of adverse cardiovascular events were detected in healthy aged women over the period of 24 weeks.

Genetic factors are major determinants of plasma leptin levels in humans and may account for as much as half of the variance in leptin levels.

Skeletal muscle wasting, associated with aging, may be regulated by the inflammatory cytokines as well as by insulin-like growth factor 1 (IGF-1). l-carnitine possesses anti-inflammatory properties and increases plasma IGF-1 concentration, leading to the regulation of the genes responsible for protein catabolism and anabolism. The purpose of the present study was to evaluate the effect of a 24-week l-carnitine supplementation on serum inflammatory markers, IGF-1, body composition and skeletal muscle strength in healthy human subjects over 65 years of age. Women between 65 and 70 years of age were supplemented for 24 weeks with either 1500 mg l-carnitine-l-tartrate or an isonitrogenous placebo per day in a double-blind fashion. Before and after the supplementation protocol, body mass and composition, as well as knee extensor and flexor muscle strength were determined. In the blood samples, free carnitine, interleukin-6, tumor necrosis factor-α, C-reactive protein and IGF-1 were determined. A marked increase in free plasma carnitine concentration was observed due to l-carnitine supplementation. No substantial changes in other parameters were noted. In the current study, supplementation for 24 weeks affected neither the skeletal muscle strength nor circulating markers in healthy women over 65 years of age. Positive and negative aspects of l-carnitine supplementation need to be clarified.

Inhibition of the renin-angiotensin-aldosterone system (RAAS) with angiotensin converting enzyme inhibitors (ACEI) and/or angiotensin II subtype 1 receptor antagonists (ARB) is a common strategy used in the management of patients with chronic kidney disease (CKD). However, there is no universal therapy that can stop progression of CKD. Pentoxifylline (PTE) is a non-specific phosphodiesterase inhibitor with anti-inflammatory properties. It has been reported to have promising effects in CKD treatment. In a placebo-controlled, randomized, cross-over study we evaluated the influence of PTE (1200 mg/day) added to RAAS blockade on proteinuria, surrogate markers of tubular injury and oxidative stress-dependent products in 22 non-diabetic patients with proteinuria (0.4-4.3 g per 24 h) with normal or declined kidney function [eGFR 37-178 mL/min]. In an eight-week run-in period, therapy using ACEI and/or ARB was adjusted to achieve a blood pressure below 130/80 mm Hg. Next, patients were randomly assigned to one of two treatment sequences: PTE/washout/placebo or placebo/washout/PTE. Clinical evaluation and laboratory tests were performed at the randomization point and after each period of the study. The PTE therapy reduced proteinuria (by 26%) as compared to placebo. There were no differences in alpha(1)-microglobulin, urine excretion of N-acetyl-beta-d-glucosaminidase (NAG), hsCRP, the urinary excretion of 15-F(2)t-isoprostane, blood pressure (BP), eGFR and serum creatinine between the PTE and placebo groups. Pentoxifylline may decrease proteinuria in non-diabetic patients with CKD.

Plasminogen activator inhibitor (PAI-1) is an anticancer agent that inhibits plasmin driven proteolysis, limiting angiogenesis and metastasis. In low concentrations it could induce cancer cell motility by interacting with urokinase (uPA), its receptor (uPAR), vitronectin and integrins. Active PAI-1 binds to uPA forming a complex with uPAR, while the latent form of PAI-1 does not. PAI-1 is found in both forms in the circulation. It is not clear which form acts as an anticancer agent and how it interacts with malignant cells. To investigate how these forms reduce angiogenesis or metastasis, we have created PAI-1 cysteine mutants in the active conformation (VLHL PAI-1) with an extended half-life that reaches ~700 h and its R369A mutant, which has an active conformation but cannot bind to uPA (VLHL NS PAI-1). Both VLHL PAI-1s convert into the latent form when treated with a reducing agent (DTT) that breaks disulfide bridges. Unexpectedly, during routine investigation of LnCAP cell proliferation, we have found that cells detach from the culture vessels regardless of PAI-1 conformation or activity. Further investigation showed that treatment of cancer cells with VLHL PAI-1 downregulated nucleophosmin, while all forms of PAI-1 downregulated fortilin. These two proteins are implicated in important cellular processes (cell growth, cell cycle, malignant transformation). This suggests that PAI-1, in addition to its well-known anticancer properties, plays an important role in cell signaling. We hope that by exploring PAI-1's structure and function we might be able to understand and separate the different effects of PAI-1 on cancer cells and develop more effective therapeutic strategies in cancer treatment.

Awareness of healthy lifestyle behaviour is not sufficient to maintain optimal body mass. Knowledge about proper eating habits is better among girls than among boys, especially in the older age groups. However, in older groups, there was less physical activity due to spending more time in front of TV or the computer. High percentage of obese/overweight children and insufficient knowledge of nutrition may consequently result in increased risk of cardio-vascular diseases in adult population.