Monocyte distribution width (MDW) as an infection indicator in severe patients attending in the Emergency Department: a pilot study.

OBJECTIVE: The aim of the present study was to evaluate the diagnostic performance of monocyte distribution width (MDW) as a biomarker for sepsis diagnosis in severe patients attended in the Emergency Department for different conditions and not only infections. METHODS: We performed an observational study in a consecutive prospective cohort including severe patients attending the Emergency Department with different conditions. MDW and other biomarkers were determined from samples obtained during the first care of patients. The diagnostic performance of the different biomarkers was determined based on the final diagnosis at patient discharge. RESULTS: One hundred two patients, with a mean age of 76.7 (SD 16.5) years were included, 53 being (51.9%) male. Among the patients included, 65 (63.7%) had an infectious disease while the remaining had other different conditions. A MDW cut-off of 20.115 provided the best accuracy to identify infected patients, with a sensitivity of 89.2 (95% CI 79.4-94.7), a specificity of 89.2 (95% CI 75.3-95.7), a positive predictive value of 93.5 (95% CI 84.6-97.5), a negative predictive value of 82.5% (95% CI 68.0-91.3), a positive likelihood ratio of 8.25 (3.26-20.91), and a negative likelihood ratio of 0.12 (0.06-0.24). The area under the receiver operating characteristic curve for infection according to MDW was 0.943 (95% CI 0.897-0.989; p<0.001). CONCLUSIONS: A MDW > 20.115 may be associated with infection and could help to distinguish between infected and non-infected patients in severe patients. These results must be confirmed in new studies due to the limited patient sample included.

Effect of cadmium on the concentration of essential metals in a human chondrocyte micromass culture.

BACKGROUND: An essential element imbalance in the joint might favor gradual degeneration of the articular cartilage. It has been reported that cadmium (Cd) plays an antagonistic role with regards to the presence of essential elements, such as zinc (Zn), iron (Fe), and manganese (Mn), which may favor the development of disabling diseases, like osteoarthritis (OA) and osteoporosis. METHODS: 3D cultures of human chondrocytes were phenotyped with the Western blot technique and structurally evaluated with histological staining. The samples were exposed to 1, 5, and 10 µM of CdCl2 for 12 h, with a non-exposed culture as control. The concentration of Cd, Fe, Mn, Zn, chromium (Cr), and nickel (Ni) was quantified through plasma mass spectrometry (ICP-MS). The data were analyzed with a Kruskal Wallis test, a Kendall's Tau test and Spearman's correlation coefficient with the Stata program, version 14. RESULTS: Our results suggest that Cd exposure affects the structure of micromass cultures and plays an antagonistic role on the concentration of essential metals, such as Zn, Ni, Fe, Mn, and Cr. CONCLUSION: Cd exposure may be a risk factor for developing joint diseases like OA, as it can interfere with cartilage absorption of other essential elements that maintain cartilage homeostasis.

Evaluation of possible impact on human health of atmospheric mercury emanations from the Popocatépetl volcano.

The contribution of Hg from volcanic emanations is decisive for assessing global mercury emissions given the impact of this highly toxic contaminant on human health and ecosystems. Atmospheric Hg emissions from Popocatépetl volcano and their dispersion were evaluated carrying out two gaseous elemental mercury (GEM) surveys during a period of intense volcanic activity. Continuous GEM measurements were taken for 24 h using a portable mercury vapor analyzer (Lumex RA-915M) at the Altzomoni Atmospheric Observatory (AAO), 11 km from the crater. In addition, a long-distance survey to measure GEM was conducted during an automobile transect around the volcano, covering a distance of 129 km. The evaluation of the GEM data registered in the fixed location showed that heightened volcanic activity clearly intensifies the concentration of atmospheric Hg, extreme values around 5 ng m-3. Highest concentrations of GEM recorded during the mobile survey were about 10 ng m-3. In both surveys, the recorded concentrations during most of the measurement time were below 2 ng m-3, but measurements were taken at a considerable distance from the crater, and GEM is subject to dilution processes. During both surveys, recorded GEM did not exceed the 200 ng m-3 concentration recommended by the WHO (Air quality guidelines for Europe, 2000) as the regulatory limits for Hg in the atmospheric environment for long-term inhalation. Because this study was carried out in inhabited areas around the volcano during a period of intense volcanic activity, it can be concluded that the Popocatépetl does not represent a risk to human health in terms of Hg.

Biomarkers of carotenoid bioavailability.

The use of biomarkers constitutes an essential tool to assess the bioavailability of carotenoids in humans. The present article aims to review several methodological, host-related and modulating factors relevant on assessing and interpreting carotenoid bioavailability. Markers for carotenoid bioavailability can be broadly divided into direct, biochemical or "analytical" markers and indirect, physiological or "functional" indicators. Analytical markers usually refer to biochemical indicators of intake and/or status (short and long term exposure) while functional measures may be interpreted in terms of cumulative exposure, biological effect (bioactivity) or modification of risk factors. Both types of markers display advantages and limitations but, in general, a relationship exists among the type of marker, the biological specimen needed and the time required for a change. Humans may absorb a wide range of carotenes and xanthophylls and many of them may be found in serum and tissues. However, under physiological conditions, the several classes of dietary carotenoids may behave unequally leading to a different systemic profile and, moreover, they can be selectively accumulated at target tissues. In addition, some carotenoids may be chemically and enzymatically modified generating different oxidative metabolites and apocarotenoids. Quantitatively, the biological response upon carotenoid intervention (assessed by analytical and functional markers) is highly variable but the use of large doses and long-term protocols may lead to saturation effects and the loss of linearity in the response. Also, despite carotenoid exposition is considered to be safe, markers of overexposure include clinical signs (i.e. carotenodermia, corneal rings and retinopathy) and biochemical indicators (hypercarotenemia, xanthophyll esters). Overall, both host-related and methodological factors may influence analytical and functional markers to assess carotenoid bioavailability although the different subclasses of carotenoids may not be equally affected.

In vitro digestion-assisted development of a ß-cryptoxanthin-rich functional beverage; in vivo validation using systemic response and faecal content.

Bioavailability of carotenoids is low and significant amounts reach the colon where they may be biologically active. We aimed to optimize a previously developed beverage designed to improve cardiovascular and bone remodelling markers in post-menopausal women. By assessing different lipid emulsions (soy lecithin, milkfat globule membrane (MFGM) and olive oil) on the in vitro bioaccessibility of ß-Cryptoxanthin and phytosterols, a MFGM containing beverage was selected and resulted stable over time (recovery >95%) under in vitro digestion and simulated anaerobic conditions. This beverage was tested in a randomized human trial (n=38) by evaluating systemic response and the colonic availability of ß-Cryptoxanthin. Consumption for six weeks provoked an increment in serum ß-Cryptoxanthin of 38.9µg/dl (CI 95%; 31.0, 46.8; p<0.001). In faeces, free ß-Cryptoxanthin, tentatively identified ß-Cryptoxanthin esters and the ratio cis-/trans-ß-carotene approached the profile in the beverage and after in vitro digestion but it was different from serum. In conclusion, in vitro digestion-assisted approach appears adequate to develop functional foods although in vivo validation should consider both systemic response and the availability at the colon.

Prevalence of hypercalcemia related to hypervitaminosis D in clinical practice.

BACKGROUND & AIMS: Recent interest in vitamin D has led to a substantial increase in the use of vitamin D supplements. Vitamin D intoxication may be a concern as hypervitaminosis D can result in irreversible calcification of soft tissues so that it is important to detect early markers of vitamin D intoxication. Our aim was to assess the simultaneous presence of biochemical markers of vitamin D toxicity (i.e. hypervitaminosis D, hypercalcemia) and determine the concentrations of 25-OH-vitamin D at which the risk of hypercalcemia, and thus toxicity, might begin. METHODS: We evaluated retrospectively a 6-year period during which 25.567 samples were assessed for 25-OH-vitamin D status by UHPLC. Hypervitaminosis D was defined at serum 25-OH-vitamin D >160 nmol/L. Serum and urine calcium, phosphorus and iPTH were also recorded, if available. Medical history revision was performed in subjects displaying simultaneously hypervitaminosis D and hypercalcemia. RESULTS: Overall, hypervitaminosis D was found in 475 samples (1.86%) of which 51 displayed hypercalcemia (11.1%). A total of 382 samples were identified as the first record of hypervitaminosis D and 39 presented hypercalcemia (10.2%), most of them at 25-OH-vitamin D levels between 161 and 375 nmol/L. Only in 15 subjects, hypercalcemia could be directly attributed to vitamin D and serum 25-OH-vitamin D ranged between 164 and 1139 nmol/l. In no case, serum calcium achieved concentrations considered as critical values (>13 mg/dl). CONCLUSION: Hypercalcemia due to vitamin D represented <4% of the total hypervitaminosis D detected and <0.1% of the tests performed. However, a highly variable response was observed and most subjects presented hypercalcemia at serum concentrations of 25-OH-vitamin D < 375 nmol/L.

Analysis of microsamples of human faeces: a non-invasive approach to study the bioavailability of fat-soluble bioactive compounds.

INTRODUCTION: Bioavailability is a critical feature in the assessment of the role of micronutrients in human health. Poorly bioavailable micronutrients like carotenoids may reach significant concentrations in the gastrointestinal tract where they may exert biological actions. PURPOSE: We evaluated a simple collection protocol to determine vitamin A, E and carotenoids in microsamples of human faeces as a non-invasive approach for nutritional studies. METHODS: Microsamples of human faeces were collected using a commercially available device, extracted and analysed on two LC systems. Suitability of the protocol was assessed by evaluating several factors including the effect of simulated colonic conditions and two nutritional scenarios with different dietary components, chemical forms, nutritional goals and target groups. RESULTS: The protocol was reproducible and representative of a faeces sample. The major dietary and serum carotenoids, and several "unidentified" compounds (possibly metabolites) could be detected, and cis-/trans-ß-carotene profile reflected dietary intervention. In faeces of neonates, free retinol, retinyl and α-tocopheryl acetate (from infant formula), long-chain fatty acid retinyl esters (from human milk), free γ-tocopherol and α-tocopherol could be detected. CONCLUSION: Our results show that the analysis of vitamin A, E and carotenoids in microsamples of human faeces is a suitable, non-invasive approach that may provide relevant information regarding responsiveness, nutrient stability and metabolism and may help assess adequacy of chemical forms and delivery systems reaching the colon.

Tissue-nonspecific alkaline phosphatase promotes axonal growth of hippocampal neurons.

Axonal growth is essential for establishing neuronal circuits during brain development and for regenerative processes in the adult brain. Unfortunately, the extracellular signals controlling axonal growth are poorly understood. Here we report that a reduction in extracellular ATP levels by tissue-nonspecific alkaline phosphatase (TNAP) is essential for the development of neuritic processes by cultured hippocampal neurons. Selective blockade of TNAP activity with levamisole or specific TNAP knockdown with short hairpin RNA interference inhibited the growth and branching of principal axons, whereas addition of alkaline phosphatase (ALP) promoted axonal growth. Neither activation nor inhibition of adenosine receptors affected the axonal growth, excluding the contribution of extracellular adenosine as a potential hydrolysis product of extracellular ATP to the TNAP-mediated effects. TNAP was colocalized at axonal growth cones with ionotropic ATP receptors (P2X7 receptor), whose activation inhibited axonal growth. Additional analyses suggested a close functional interrelation of TNAP and P2X7 receptors whereby TNAP prevents P2X7 receptor activation by hydrolyzing ATP in the immediate environment of the receptor. Furthermore inhibition of P2X7 receptor reduced TNAP expression, whereas addition of ALP enhanced P2X7 receptor expression. Our results demonstrate that TNAP, regulating both ligand availability and protein expression of P2X7 receptor, is essential for axonal development.