Zinc deficiency. Symptoms, causes, diagnosis and therapy

Zinc is an essential trace element being required for numerous metabolic processes. The diagnosis of zinc deficiency is based on four main criteria, namely anamnesis, symptomatology, belonging to well-defined risk groups and the determination of biomarkers. The diagnosis of overt zinc deficiency is unproblematic in contrast to moderate states. The review presented here shall help to detect the latter ones. The pharmacotherapy of of zinc deficiency consists in oral administration of zinc salts.     

Nucleosome-induced neutrophil activation occurs independently of TLR9 and endosomal acidification: implications for systemic lupus erythematosus

The nucleosome is a major autoantigen known to activate PMN in systemic lupus erythematosus (SLE). TLR9 recognizes bacterial and even mammalian DNA under certain circumstances. Nevertheless, the role of TLR9 in SLE development is still unclear. Since nucleosomes are composed of DNA, we investigated whether TLR9 is required for nucleosome-induced PMN activation. Isolated neutrophils were cultured with nucleosomes, plasma from lupus patients and other stimuli in the presence/absence of various inhibitors. Cells were analyzed by flow cytometry, ELISA and confocal microscopy. We found that nucleosomes circulating in lupus plasma induce the secretion of pro-inflammatory cytokines by PMN. Nucleosomes activate human PMN independently of unmethylated CpG sequences in nucleosomal DNA, leading to IL-8/IL-6/TNF secretion and CD11b up-regulation. Nucleosomes accumulate in the cytoplasm of PMN upon endocytosis, induce TLR9 up-regulation and act synergistically with TLR9 ligands. Nucleosome-induced activation was not inhibited by polymyxin B (PB), chloroquine (CQ), ammonium chloride (AC) or a TLR9 antagonist. Moreover, both PMN isolated from WT and TLR9-KO mice were activated by nucleosomes, as detected by MIP-2 secretion and CD11b up-regulation. Activation occurred therefore independently of endotoxins, endosomal acidification, TLR9 and CpG motifs. TLR9 may thus be differently required in the triggering of nucleosome-induced innate immunity and anti-nucleosome B-cell autoimmunity.     

A demographic analysis of the fitness cost of extended longevity in Caenorhabditis elegans

We monitored survival and reproduction of 1000 individuals of Caenorhabditis elegans wild type (N2) and 800 individuals of clk-1 and daf-2, and used biodemographic analysis to address fitness as the integrative consequence of the entire age-specific schedules of survival and reproduction. Relative to N2, the mutants clk-1 and daf-2 extended average life span by 27% and 111%, respectively, but reduced net reproductive rate by 44% and 18%. The net result of differences in survival and fertility was a significant differential in fitness, with both clk-1 (lambda = 2.74) and daf-2 (lambda = 3.78) at a disadvantage relative to N2 (lambda = 3.85). Demographic life table response experiment (LTRE) analysis revealed that the fitness differentials were due to negative effects in mutants on reproduction in the first 6-7 days of life. Fitness costs in clk-1 and daf-2 of C. elegans are consistent with the theory of antagonistic pleiotropy for the evolution of senescence.     

Reliability of neuronavigation-assisted trans-sphenoidal tumor resections

OBJECTIVE: To analyse the surgical reliability of neuronavigation-assisted trans-sphenoidal tumor resections. METHOD: In the past 7 years, all patients, who underwent neuronavigation-assisted trans-sphenoidal tumor resection in our department, were additionally intraoperatively controlled with a radioscopic device. Tumor removal was repeatedly checked up with the navigator and the tip of the pointer was correlated with the lateral intraoperative skull radiologic examination to confirm the real pointer deepness, spatial location and trajectory. The reliability of these assessments was analysed by simple images comparison and searching for tumor-related differences, and controlled with post-operative magnetic resonance studies. RESULTS: During the analysed period, a total of 36 patients were treated in our department. Diagnosis included 14 non-secreting adenomas, 18 secreting adenomas and four non-pituitary tumors. Tumors diameter ranged from 1.4 to 4.5 cm. A mean accuracy of 0.8 mm could be achieved for all patients. In all cases, the real deepness, position and trajectory of the navigator were identical to those observed with X-ray examinations. At least nine from ten pointer determinations were identical in all cases. Particularly, all pituitary tumors with suprasellar extension could be safely controlled, even during advanced stages of resection and before the tumor capsule detached from suprasellar neighbor structures. Intrasellar, clival and suprasellar tumors were adequately removed as confirmed with MRI. CONCLUSIONS: Radioscopic controlled neuronavigation shows high reliability and allows surgeons to be more confident during the trans-sphenoidal resection of skull base tumors. This offers the advantage to reduce the patient's X-ray exposure and the possibility of simultaneous multiplanar images evaluation.     

Ablation of the cholesterol transporter adenosine triphosphate-binding cassette transporter G1 reduces adipose cell size and protects against diet-induced obesity

The ATP-binding cassette transporter G1 (ABCG1) catalyzes export of cellular cholesterol from macrophages and hepatocytes. Here we identify an additional function of ABCG1 in the regulation of adiposity in screens of the Drosophila melanogaster and the New Zealand obese (NZO) mouse genomes. Insertion of modified transposable elements of the P-family upstream of CG17646, the Drosophila ortholog of Abcg1, generated lines of flies with increased triglyceride stores. In NZO mice, an Abcg1 variant was identified in a suggestive adiposity quantitative trait locus and was associated with higher expression of the gene in white adipose tissue. Targeted disruption of Abcg1 in mice resulted in reduced body weight gain (8.42+/-0.6 g in Abcg1-/- vs. 13.07+/-1.1 g in Abcg1+/+ mice) and adipose tissue mass gain (3.78+/-1.3 g in Abcg1-/- vs. 9.39+/-1.6 g in Abcg1+/+ mice) detected over a period of 12 wk. The reduction of adipose tissue mass in Abcg1-/- mice was associated with markedly decreased size of the adipocytes. In contrast to their wild-type littermates, male Abcg1-/- mice exhibited no high-fat diet-induced impairment of glucose tolerance and fatty liver. Furthermore, Abcg1-/- mice possess decreased food intake and elevated total energy expenditure (Abcg1-/- mice, 748.1+/-5.4 kJ/kg metabolic body mass; Abcg1+/+ mice, 684.3+/-5.0 kJ/kg metabolic body mass; P=0.011), body temperature (Abcg1-/- mice, 37.82+/-0.29 C; Abcg1+/+ mice, 36.83+/-0.24 C; P<0.05), and locomotor activity (Abcg1-/- mice, 3655+/-189 counts/12 h during dark phase; Abcg1+/+ mice, 2445+/-235 counts/12 h during dark phase; P<0.01). Our data indicate a previously unrecognized role of ABCG1 in the regulation of energy balance and triglyceride storage.     

'Prefrontal' cognitive performance of healthy subjects positively correlates with cerebral FDOPA influx: an exploratory [18F]-fluoro-L-DOPA-PET investigation

Dopamine neurotransmission influences those cognitive processes, which are generally regarded as prefrontal cortical functions. In previous positron-emission-tomography (PET) studies, net blood-brain clearance of [18F]-fluoro-l-DOPA (FDOPA) correlated with impaired cognitive performance in patients with Parkinson's disease or schizophrenia. We hypothesized that FDOPA influx also correlates with performance of cognitive tasks associated with prefrontal functioning in healthy volunteers. The net blood-brain clearance of FDOPA (K(in)(app)) was mapped in a group of 11 healthy volunteers and calculated in striatal volumes-of-interest. The Wisconsin-Card-Sorting-Test (WCST), Stroop-Test, Trail-Making-Test (TMT-A/B), and Continuous-Performance-Test (CPT-M) had been administered previously to the same subjects. No correlation of K(in) (app) with perseverative errors in WCST or age could be found. However, there were significant positive correlations between the magnitude of K(in)(app) in caudate nucleus, putamen, and midbrain with performance of the TMT-B, CPT-M, and the Stroop test. Highest correlations were found between the time needed to perform the Stroop interference task and the K(in)(app) of striatal areas (Caudate nucleus: -0.780, P = 0.005; putamen: -0.870, P < 0. 001). Thus, the present findings reveal a strong correlation between dopamine synthesis capacity in striatum of healthy volunteers and performance of cognitive tasks linked to the prefrontal cortex.     

Interleukin-6 serum level assessment using a new qualitative point-of-care test in sepsis: A comparison with ELISA measurements

ObjectivesInterleukin-6 (IL-6) is involved in inflammatory diseases, provides prognostical information, and allows the early identification and monitoring of septic patients. We investigated whether IL-6 can be assessed using a new densitometric point-of-care (POC) bedside assay.Design and methods392 samples were prospectively collected from 57 intensive care unit patients (38 male, age: 45.2 ± 16.9years, APACHE II score: 25.4 ± 4.8). Blinded IL-6 measurements were performed using conventional semiautomatic enzyme-linked immunosorbent assays (ELISA) and the POC test.ResultsMean IL-6 levels were 102.9 ± 388.6pg/mL (ELISA) and 97.0 ± 535.5 (POC). A significant correlation was found (p < 0.0001, r = 0.92). The sensitivity/specificity for sepsis was 82.6%/86.5% (ELISA, AUC: 0.881), and 76.4%/95.0% (POC, AUC: 0.868).ConclusionsHere we demonstrate significant correlations of IL-6 levels determined using a POC test and semiautomatic ELISA. ROC analyses revealed no significant differences between the two tests. With a turn-around time of 20min, the bedside IL-6 test is a new tool that may help to initiate early goal-directed therapy.