Zinc deficiency enhances sensitivity to influenza A associated bacterial pneumonia in mice.

Although zinc deficiency (secondary to malnutrition) has long been considered an important contributor to morbidity and mortality of infectious disease (e.g. diarrhea disorders), epidemiologic data (including randomized controlled trials with supplemental zinc) for such a role in lower respiratory tract infection are somewhat ambiguous. In the current study, we provide the first preclinical evidence demonstrating that although diet-induced acute zinc deficiency (Zn-D: ~50% decrease) did not worsen infection induced by either influenza A (H1N1) or methicillin-resistant staph aureus (MRSA), Zn-D mice were sensitive to the injurious effects of superinfection of H1N1 with MRSA. Although the mechanism underlying the sensitivity of ZnD mice to combined H1N1/MRSA infection is unclear, it was noteworthy that this combination exacerbated lung injury as shown by lung epithelial injury markers (increased BAL protein) and decreased genes related to epithelial integrity in Zn-D mice (surfactant protein C and secretoglobins family 1A member 1). As bacterial pneumonia accounts for 25%-50% of morbidity and mortality from influenza A infection, zinc deficiency may be an important pathology component of respiratory tract infections.

The role of dietary magnesium deficiency in inflammatory hypertension.

Nearly 30% of adults consume less than the estimated average daily requirement of magnesium (Mg2+), and commonly used medications, such as diuretics, promote Mg2+ deficiency. Higher serum Mg2+ levels, increased dietary Mg2+ in-take, and Mg2+ supplementation are each associated with lower blood pressure, suggesting that Mg2+-deficiency contributes to the pathogenesis of hypertension. Antigen-presenting cells, such as monocytes and dendritic cells, are well-known to be involved in the pathogenesis of hypertension. In these cells, processes implicated as necessary for increased blood pressure include activation of the NLRP3 inflammasome, IL-1ß production, and oxidative modification of fatty acids such as arachidonic acid, forming isolevuglandins (IsoLGs). We hypothesized that increased blood pressure in response to dietary Mg2+-depletion leads to increased NLRP3, IL-1ß, and IsoLG production in antigen presenting cells. We found that a Mg2+-depleted diet (0.01% Mg2+ diet) increased blood pressure in mice compared to mice fed a 0.08% Mg2+ diet. Mg2+-depleted mice did not exhibit an increase in total body fluid, as measured by quantitative magnetic resonance. Plasma IL-1ß concentrations were increased (0.13 ± 0.02 pg/mL vs. 0.04 ± 0.02 pg/mL). Using flow cytometry, we observed increased NLRP3 and IL-1ß expression in antigen-presenting cells from spleen, kidney, and aorta. We also observed increased IsoLG production in antigen-presenting cells from these organs. Primary culture of CD11c+ dendritic cells confirmed that low extracellular Mg2+ exerts a direct effect on these cells, stimulating IL-1ß and IL-18 production. The present findings show that NLRP3 inflammasome activation and IsoLG-adduct formation are stimulated when dietary Mg2+ is depleted. Interventions and increased dietary Mg2+ consumption may prove beneficial in decreasing the prevalence of hypertension and cardiovascular disease.

Are plasma mineral levels related to antibody response to influenza vaccination in older adults?

INTRODUCTION: An effective immune response to vaccination may be related to nutritional status. This study examined the association of plasma mineral levels with hemagglutination inhibition (HI) titers produced in response to influenza vaccine in older adults. METHODS: Prior to (Day 0) and 21 (range = 19-28) days after receiving the 2013-14 influenza vaccine, 109 adults ages 51-81 years, provided blood samples. Serum samples were tested for HI activity against the A/H1N1 and A/H3N2 2013-2014 vaccine virus strains. Plasma minerals were collected in zinc-free tubes and assayed by inductively coupled plasma mass spectrometry. HI titers were reported as seroprotection (≥1:40) and seroconversion (≥ 4-fold rise from Day 0 (minimum HI = 1:10) to Day 21). Both HI titers and mineral values were skewed and thus log2 transformed. Magnesium (Mg), phosphorus (P), zinc (Zn), copper (Cu), iron (Fe), potassium (K) and the Cu to Zn ratio were tested. Logistic regression analyses were used to determine the associations between mineral levels and seroconversion and seroprotection of HI titers for each influenza A strain. RESULTS: Participants were 61% white, 28% male, 39% diabetic, and 81% overweight/obese with a mean age of 62.6 y. In logistic regression, Day 21 A/H1N1 seroprotection was associated with P and Zn at Day 21(P < 0.05). Seroconversion of A/H1N1 was associated with Day 21 Cu, P, and Mg (P < 0.03). Day 21 A/H3N2 seroprotection and seroconversion were associated with Day 21 P (P < 0.05). CONCLUSIONS: Phosphorus was associated with seroprotection and seroconversion to influenza A after vaccination; these associations warrant additional studies with larger, more diverse population groups.

Well water contamination in a rural community in southwestern Pennsylvania near unconventional shale gas extraction.

Reports of ground water contamination in a southwestern Pennsylvania community coincided with unconventional shale gas extraction activities that started late 2009. Residents participated in a survey and well water samples were collected and analyzed. Available pre-drill and post-drill water test results and legacy operations (e.g., gas and oil wells, coal mining) were reviewed. Fifty-six of the 143 respondents indicated changes in water quality or quantity while 63 respondents reported no issues. Color change (brown, black, or orange) was the most common (27 households). Well type, when known, was rotary or cable tool, and depths ranged from 19 to 274 m. Chloride, sulfate, nitrate, sodium, calcium, magnesium, iron, manganese and strontium were commonly found, with 25 households exceeding the secondary maximum contaminate level (SMCL) for manganese. Methane was detected in 14 of the 18 houses tested. The 26 wells tested for total coliforms (2 positives) and E. coli (1 positive) indicated that septic contamination was not a factor. Repeated sampling of two wells in close proximity (204 m) but drawing from different depths (32 m and 54 m), revealed temporal variability. Since 2009, 65 horizontal wells were drilled within a 4 km (2.5 mile) radius of the community, each well was stimulated on average with 3.5 million gal of fluids and 3.2 million lbs of proppant. PA DEP cited violations included an improperly plugged well and at least one failed well casing. This study underscores the need for thorough analyses of data, documentation of legacy activity, pre-drill testing, and long term monitoring.

Environmental legacy of copper metallurgy and Mongol silver smelting recorded in Yunnan Lake sediments.

Geochemical measurements on well-dated sediment cores from Lake Er (Erhai) are used to determine the timing of changes in metal concentrations over 4500 years in Yunnan, a borderland region in southwestern China noted for rich mineral deposits but with inadequately documented metallurgical history. Our findings add new insight into the impacts and environmental legacy of human exploitation of metal resources in Yunnan history. We observe an increase in copper at 1500 BC resulting from atmospheric emissions associated with metallurgy. These data clarify the chronological issues related to links between the onset of Yunnan metallurgy and the advent of bronze technology in adjacent Southeast Asia, subjects that have been debated for nearly half a century. We also observe an increase from 1100 to 1300 AD in a number of heavy metals including lead, silver, zinc, and cadmium from atmospheric emissions associated with silver smelting. Culminating during the rule of the Mongols, known as the Yuan Dynasty (1271-1368 AD), these metal concentrations approach levels three to four times higher than those from industrialized mining activity occurring within the catchment today. Notably, the concentrations of lead approach levels at which harmful effects may be observed in aquatic organisms. The persistence of this lead pollution over time created an environmental legacy that likely contributes to known issues in modern day sediment quality. We demonstrate that historic metallurgical production in Yunnan can cause substantial impacts on the sediment quality of lake systems, similar to other paleolimnological findings around the globe.

Nickel accumulation in leaves, floral organs and rewards varies by serpentine soil affinity.

Serpentine soils are edaphically stressful environments that host many endemic plant species. In particular, serpentine soils are high in several heavy metals (e.g. nickel, cobalt and chromium) and these high heavy metal concentrations are thought, in part, to lead to varying levels of plant adaptation and soil affinities (i.e. endemic vs. non-endemic plant species). It is unclear, however, whether serpentine endemics vs. non-endemics differ with respect to heavy metal uptake into either vegetative or reproductive organs. Here, we use nickel as a model to determine whether plant heavy metal uptake varies with the level of endemism in several non-hyperaccumulating species. Under controlled greenhouse conditions, we grew seven plant species from the Brassicaceae family that vary in their degrees of affinity to serpentine soil from low (indifferent) to medium (indicator) and high (endemic) in soil that was nickel supplemented or not. We quantified nickel concentrations in leaves, pistils, anthers, pollen and nectar. While nickel concentrations did not vary across organs or affinities when grown in control soils, under conditions of nickel supplementation endemic species had the lowest tissue concentrations of nickel, particularly when considering leaves and pistils, compared with indifferent/indicator species. Species indifferent to serpentines incorporated higher concentrations of nickel into reproductive organs relative to leaves, but this was not the case for indicator species and endemics where nickel concentration was similar in these organs. Our findings suggest that endemic species possess the ability to limit nickel uptake into above-ground tissues, particularly in reproductive organs where it may interfere with survival and reproduction. Indifferent species accumulated significantly more nickel into reproductive organs compared with leaves, which may limit their reproductive potential relative to endemic species when growing on serpentine soils. Additional work determining the fitness consequences of these differences will further our understanding of edaphic endemism.

Decreased reticuloendothelial system clearance and increased blood half-life and immune cell labeling for nano- and micron-sized superparamagnetic iron-oxide particles upon pre-treatment with Intralipid.

BACKGROUND: Superparamagnetic iron-oxide nanoparticles are useful as contrast agents for anatomical, functional and cellular MRI, drug delivery agents, and diagnostic biosensors. Nanoparticles are generally cleared by the reticuloendothelial system (RES), in particular taken up by Kupffer cells in the liver, limiting particle bioavailability and in-vivo applications. Strategies that decrease the RES clearance and prolong the circulation residence time of particles can improve the in-vivo targeting efficiency. METHODS: Intralipid 20.0%, an FDA approved nutritional supplement, was intravenously administered in rats at the clinical dose (2g/kg) 1h before intravenous injection of ultra-small superparamagnetic iron-oxide (USPIO) or micron-sized paramagnetic iron-oxide (MPIO) particles. Blood half-life, monocyte labeling efficiency, and particle biodistribution were assessed by magnetic resonance relaxometry, flow cytometry, inductively-coupled plasma MS, and histology. RESULTS: Pre-treatment with Intralipid resulted in a 3.1-fold increase in USPIO blood half-life and a 2-fold increase in USPIO-labeled monocytes. A 2.5-fold increase in MPIO blood half-life and a 5-fold increase in MPIO-labeled monocytes were observed following Intralipid pre-treatment, with a 3.2-fold increase in mean iron content up to 2.60pg Fe/monocyte. With Intralipid, there was a 49.2% and 45.1% reduction in liver uptake vs. untreated controls at 48h for USPIO and MPIO, respectively. CONCLUSIONS: Intralipid pre-treatment significantly decreases initial RES uptake and increases in-vivo circulation and blood monocyte labeling efficiency for nano- and micron-sized superparamagnetic iron-oxide particles. GENERAL SIGNIFICANCE: Our findings can have broad applications for imaging and drug delivery applications, increasing the bioavailability of nano- and micron-sized particles for target sites other than the liver.