Assessment of nicotine delivery and uptake in users of various tobacco/nicotine products.

Today various tobacco and nicotine products are available, many of them can be regarded as potentially risk-reduced products when compared to the most frequently used product, combustible cigarettes (CCs). A commonality of these products is that they deliver nicotine, although in quite different amounts and uptake routes, the most common of which are inhalation through the lung and absorption through the oral mucosa. Product-specific nicotine delivery as well as the subject-related use patterns are important factors which determine the pharmacokinetics and achieved internal dose levels of the alkaloid. The latter two parameters are highly relevant for the long-term product loyalty and, consequently, for the implicated health risks, since the risk-reduced products will replace CCs in the long-term only when users will experience a similar level of satisfaction. We measured nicotine and its major metabolites in plasma, saliva and urine samples collected in a controlled clinical study with habitual users (10 per group) of CCs, electronic cigarettes (ECs), heated tobacco products (HTP), oral tobacco (OT), and nicotine replacement therapy (NRT). Non-users (NU) of any tobacco/nicotine products served as (negative) control group. Moderate to strong correlations were observed between the daily consumption and the urinary nicotine equivalents (comprising nicotine and its 10 major metabolites, Nic + 10) or plasma and saliva cotinine concentrations. The average daily nicotine dose as measured by the urinary excretion of Nic + 10 (reflecting approximately 95 % of the absorbed nicotine) amounted to 17 and 22 mg/24 h for smokers (CC) and OT users, respectively, while it was in the range of 6-12 mg/24 h for users of ECs, HTP and NRT products, with high inter-individual variations in each user group. The individual daily nicotine intake, which was calculated by applying product-specific models, showed none to good agreement with the corresponding internal nicotine dose measured by Nic + 10 excretion. Possible reasons for the observed deviations between calculated and objectively measured nicotine doses are discussed.

Vanadium: Risks and possible benefits in the light of a comprehensive overview of its pharmacotoxicological mechanisms and multi-applications with a summary of further research trends.

BACKGROUND: Vanadium (V) is an element with a wide range of effects on the mammalian organism. The ability of this metal to form organometallic compounds has contributed to the increase in the number of studies on the multidirectional biological activity of its various organic complexes in view of their application in medicine. OBJECTIVE: This review aims at summarizing the current state of knowledge of the pharmacological potential of V and the mechanisms underlying its anti-viral, anti-bacterial, anti-parasitic, anti-fungal, anti-cancer, anti-diabetic, anti-hypercholesterolemic, cardioprotective, and neuroprotective activity as well as the mechanisms of appetite regulation related to the possibility of using this element in the treatment of obesity. The toxicological potential of V and the mechanisms of its toxic action, which have not been sufficiently recognized yet, as well as key information about the essentiality of this metal, its physiological role, and metabolism with certain aspects on the timeline is collected as well. The report also aims to review the use of V in the implantology and industrial sectors emphasizing the human health hazard as well as collect data on the directions of further research on V and its interactions with Mg along with their character. RESULTS AND CONCLUSIONS: Multidirectional studies on V have shown that further analyses are still required for this element to be used as a metallodrug in the fight against certain life-threatening diseases. Studies on interactions of V with Mg, which showed that both elements are able to modulate the response in an interactive manner are needed as well, as the results of such investigations may help not only in recognizing new markers of V toxicity and clarify the underlying interactive mechanism between them, thus improving the medical application of the metals against modern-age diseases, but also they may help in development of principles of effective protection of humans against environmental/occupational V exposure.

The human knee: A window on the microvasculature.

In synovial joints, the lining cells do not have tight junctions with their neighboring cells and they have no underlying basement membrane. Therefore, the synovial fluid within the articular cavity is continuous with the interstitial fluid of the synovial intima. These features, combined with ready access to the space via arthrocentesis, permit quantitative studies of microvascular function in the knees of unanesthetized, volunteer, human subjects both with and without chronic arthritis. This brief article reviews the principal findings of such work over ∼40 years at the University of Washington. Examined variables include bidirectional fenestral diffusion of small solutes, effective blood flow, lymphatic drainage, and endothelial pore size and permeability. The latter work introduced a new method using gel filtration chromatography of paired synovial fluid (SF) and serum (S) to obtain essentially continuous SF/S ratios over a range of radii between 1 and 12 nanometers.

Regulation of inflammation by selenium and selenoproteins: impact on eicosanoid biosynthesis.

Uncontrolled inflammation is a contributing factor to many leading causes of human morbidity and mortality including atherosclerosis, cancer and diabetes. Se is an essential nutrient in the mammalian diet that has some anti-inflammatory properties and, at sufficient amounts in the diet, has been shown to be protective in various inflammatory-based disease models. More recently, Se has been shown to alter the expression of eicosanoids that orchestrate the initiation, magnitude and resolution of inflammation. Many of the health benefits of Se are thought to be due to antioxidant and redox-regulating properties of certain selenoproteins. The present review will discuss the existing evidence that supports the concept that optimal Se intake can mitigate dysfunctional inflammatory responses, in part, through the regulation of eicosanoid metabolism. The ability of selenoproteins to alter the biosynthesis of eicosanoids by reducing oxidative stress and/or by modifying redox-regulated signalling pathways also will be discussed. Based on the current literature, however, it is clear that more research is necessary to uncover the specific beneficial mechanisms behind the anti-inflammatory properties of selenoproteins and other Se metabolites, especially as related to eicosanoid biosynthesis. A better understanding of the mechanisms involved in Se-mediated regulation of host inflammatory responses may lead to the development of dietary intervention strategies that take optimal advantage of its biological potency.