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.

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.

Mapping of phospholipids by MALDI imaging (MALDI-MSI): realities and expectations.

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) has emerged as a novel powerful MS methodology that has the ability to generate both molecular and spatial information within a tissue section. Application of this technology as a new type of biochemical lipid microscopy may lead to new discoveries of the lipid metabolism and biomarkers associated with area-specific alterations or damage under stress/disease conditions such as traumatic brain injury or acute lung injury, among others. However there are limitations in the range of what it can detect as compared with liquid chromatography-MS (LC-MS) of a lipid extract from a tissue section. The goal of the current work was to critically consider remarkable new opportunities along with the limitations and approaches for further improvements of MALDI-MSI. Based on our experimental data and assessments, improvements of the spectral and spatial resolution, sensitivity and specificity towards low abundance species of lipids are proposed. This is followed by a review of the current literature, including methodologies that other laboratories have used to overcome these challenges.

Sequences in intron 51 of the von Willebrand factor gene target promoter activation to a subset of lung endothelial cells in transgenic mice.

In vivo analyses of the VWF promoter previously demonstrated that a fragment spanning sequences -487 to +247 targets promoter activation to brain vascular endothelial cells, whereas a longer fragment including 2182 bp of the 5'-flanking sequences, the first exon, and the first intron activated expression in endothelial cells of the heart and muscles as well as the brain of transgenic mice. These results suggested that additional VWF gene sequences were required for expression in other vascular endothelial cells in vivo. We have now identified a region within intron 51 of the VWF gene that is DNase I-hypersensitive (HSS) specifically in non-endothelial cells and interacts with endothelial and non-endothelial specific complexes that contain YY1. We demonstrate that beta-actin is associated with YY1 specifically in the nucleus of non-endothelial cells and is a component of the nuclear protein complexes that interact with the DNase I-hypersensitive region. In vitro transfection analyses demonstrated that HSS sequences containing this YY1-binding site do not significantly affect VWF promoter activity. However, in vivo analyses demonstrated that addition of these sequences to the VWF promoter (-487 to +247) results in promoter activation in lung and brain vascular endothelial cells. These results demonstrate that the HSS sequences in intron 51 of the VWF gene contain cis-acting elements that are necessary for the VWF gene transcription in a subset of lung endothelial cells in vivo.