Tracing of zinc using the ZnSe^AMG method.

<p>(A) Cryo-section: Wild Type mouse 24 hours after TBI. Asterisks denote lesion tract; a distinct layering of the neocortex is noticeable. Closest to the lesion tract no AMG development is possible because all cells are severely damaged. This is shown as a little tint of white on both sides of the lesion tract. Scale bar: 1 mm. (B) Cryo-section: ZnT3-KO mouse 24 hours after TBI. Asterisks denote lesion. In the periphery of the lesion a number of ZnSe nanocrystals containing neurons are just visible. These somata marked neurons border the area between morphologically damaged tissue and morphologically intact tissue. (C) Semi-thin section: Wild Type mouse, a close-up of what is seen in A. There is a distinct neuropil stain; the tissue is oedematous with bleeding. The neurons are distorted, with vacuolation of their cytoplasm and some with eccentrically placed, pycnotic nuclei; none of the neuronal cell-bodies contain any ZnSe nanocrystals. Scale bar: 30 µm. (D_1–2) Semi-thin sections: ZnT3-KO mouse. In the periphery of the lesion some neurons containing ZnSe nanocrystals in their somata can be seen. Going towards the lesion tract most cells are heavily distorted with condensed, eccentrically placed nuclei. The tissue is severely damaged with massive oedema. Scale bar: 30 µm. Tracing of dead and dying neurons with Fluorojade B (FJB). (E) Cryo-section: Wild Type mouse stained with FJB; fluorescent neurons border the lesion tract. Scale bar: 300 µm. (F) Cryo-section: ZnT3-KO mouse stained with FJB; numerous neurons line the lesion tract. Scale bar: 300 µm.</p

Students t-test.

<p>FluoroJade B staining of cryo sections.</p><p>* Indicates statistically significant difference, <i>p</i><0.05.</p

GFAP; only the group o66–70 contains more GFAP positive cells although a tendency towards the cells becoming more GFAP positive after chelation therapy is noted.

<p>GFAP; only the group o66–70 contains more GFAP positive cells although a tendency towards the cells becoming more GFAP positive after chelation therapy is noted.</p

Control sections.

<p>Sections are toluidine stained in (A-H). Both the WT mice and The ZnT3-KO mice display a normal morphology 24 hours after respectively DEDTC and selenite treatment. The tissue is without oedema and the cells are all intact with normal configuration. A, B, E, F are Cryo-sections 30 µm thick. C, D, G, H are semi-thin sections 3 µm thick. No major differences between the ZnT3-KO and the WT mice are noticeable. Scale bar A,B: 100 µm. Scale bar E: 200 µm. Scale bar F: 300 µm. Scale bar C, D, G, H: 30 µm. Control sections, FJB stained (I-L). Sections I, J are pretreated with DEDTC and sections K, L are pretreated with selenite. All sections are FJB negative. Control sections, TUNEL stained (M-P). Sections M, N are pretreated with DEDTC and sections O, P are pretreated with selenite. All sections are TUNEL negative. M, P depict part of the hippocampus formation and N, O depict all the six neocortical layers. Scale bar I-P: 200 µm.</p

TUNEL; the group o46–50 has significantly more apoptotic neurons than o41–45, this difference equalizes after chelator application [o51–55;o56–60], [o61–65;o66–70].

<p>TUNEL; the group o46–50 has significantly more apoptotic neurons than o41–45, this difference equalizes after chelator application [o51–55;o56–60], [o61–65;o66–70].</p

Caspase 3; the chelator treated groups o61–65 and o66–70 contains significantly more apoptotic neurons than the remaining groups.

<p>Caspase 3; the chelator treated groups o61–65 and o66–70 contains significantly more apoptotic neurons than the remaining groups.</p

Additional file 1: of Gene expression of the zinc transporter ZIP14 (SLC39a14) is affected by weight loss and metabolic status and associates with PPARγ in human adipose tissue and 3T3-L1 pre-adipocytes

Primer sequences. Forward and reverse primer sequences are shown together with the annealing temperature. h, human primer; m, murine primer. In human adipose tissue, expression of the zinc transporter ZIP14 was investigated together with that of peroxisome proliferator-activated receptor γ isoform 1 (PPARγ1) and isoform 2 (PPARγ2). Low-density lipoprotein receptor-related protein 10 (LRP10) was used as a housekeeping gene. In 3T3-L1 cells, expression of the zinc transporter ZIP14 was investigated together with that of the adipocytic differentiation markers PPARγ and fatty-acid binding protein 4 (A-FABP). Cyclophilin A (Cyc-A), hypoxanthine guanine phosphoribosyl transferase (HPRT), and ubiquitin conjugase-7 (UBC-7) were used as housekeeping genes. (PDF 58 kb

Data on the study subjects according to <i>CD300LG</i> rs72836561 CC, CT, and TT genotype.

<p>Mean and 95% confidence interval. P-values obtained from Students t-test.</p>1<p>Median and interquartile range. P-value obtained from Students t-test of log-transformed data.</p>2<p>Median and interquartile range. P-value obtained from linear regression on rank normalized data adjusted for age.</p><p>Data on the study subjects according to <i>CD300LG</i> rs72836561 CC, CT, and TT genotype.</p

Positron emission tomography.

<p>Myocardial glucose uptake (MGU) during normoglycemia and hypoglycemia (A and B). ¹⁸F-FDG clearance (K) during normoglycemia and hypoglycemia (C and D). Relation between placebo MGU and change in MGU during GLP-1 infusion in the normoglycemia study (E), placebo MGU and change in MGU during GLP-1 infusion in the hypoglycemia study (F). Relation between placebo K and change in K during GLP-1 infusion in the normoglycemia study (G), placebo K and change in K during GLP-1 infusion in the hypoglycemia study (H). HOMA 2IR and the change of MGU during GLP-1 infusion in the hypoglycemia study (I). HOMA 2IR and the change of K during GLP-1 infusion in the hypoglycemia study (J). Data are mean ± SD. Regression lines with 95% confidence intervals.</p

Influence of GLP-1 on Myocardial Glucose Metabolism in Healthy Men during Normo- or Hypoglycemia

<div><p>Background and Aims</p><p>Glucagon-like peptide-1 (GLP-1) may provide beneficial cardiovascular effects, possibly due to enhanced myocardial energetic efficiency by increasing myocardial glucose uptake (MGU). We assessed the effects of GLP-1 on MGU in healthy subjects during normo- and hypoglycemia.</p><p>Materials and Methods</p><p>We included eighteen healthy men in two randomized, double-blinded, placebo-controlled cross-over studies. MGU was assessed with GLP-1 or saline infusion during pituitary-pancreatic normo- (plasma glucose (PG): 4.5 mM, n = 10) and hypoglycemic clamps (PG: 3.0 mM, n = 8) by positron emission tomography with ¹⁸fluoro-deoxy-glucose (¹⁸F-FDG) as tracer.</p><p>Results</p><p>In the normoglycemia study mean (± SD) age was 25±3 years, and BMI was 22.6±0.6 kg/m² and in the hypoglycemia study the mean age was 23±2 years with a mean body mass index of 23±2 kg/m². GLP-1 did not change MGU during normoglycemia (mean (+/− SD) 0.15+/−0.04 and 0.16+/−0.03 µmol/g/min, P = 0.46) or during hypoglycemia (0.16+/−0.03 and 0.13+/−0.04 µmol/g/min, P = 0.14). However, the effect of GLP-1 on MGU was negatively correlated to baseline MGU both during normo- and hypoglycemia, (P = 0.006, r² = 0.64 and P = 0.018, r² = 0.64, respectively) and changes in MGU correlated positively with the level of insulin resistance (HOMA 2IR) during hypoglycemia, P = 0.04, r² = 0.54. GLP-1 mediated an increase in circulating glucagon levels at PG levels below 3.5 mM and increased glucose infusion rates during the hypoglycemia study. No differences in other circulating hormones or metabolites were found.</p><p>Conclusions</p><p>While GLP-1 does not affect overall MGU, GLP-1 induces changes in MGU dependent on baseline MGU such that GLP-1 increases MGU in subjects with low baseline MGU and decreases MGU in subjects with high baseline MGU. GLP-1 preserves MGU during hypoglycemia in insulin resistant subjects.</p><p>ClinicalTrials.gov registration numbers: <a href="http://clinicaltrials.gov/show/NCT00418288" target="_blank">NCT00418288:</a> (hypoglycemia) and <a href="http://clinicaltrials.gov/show/NCT00256256" target="_blank">NCT00256256:</a> (normoglycemia).</p></div