Sex and Genetics are Important Cofactors in Assessing the Impact of Iron Deficiency on the Developing Mouse Brain

The present study was designed to investigate the possible role of genetic background and sex in the behavioral and neurochemical responses to early iron deficiency. Male and female C57 and DBA mice were provided either an iron deficient (ID) or control (CN) diet during early growth periods. Dopamine D₂ receptor densities, and dopamine and serotonin transporter densities were determined in specific brain regions. Iron deficient DBA mice had significantly lower D₂ receptor densities in the frontal cortex (FC) and caudate putamen (CP) (19 vs. 35fmol/mg and 145 vs. 215 fmol/mg, respectively). Serotonin (5-HT) transporter densities in FC of iron deficient C57 mice tended to be lower than in control animals (40 vs. 60 fmol/mg) while in the nucleus accumbens (NA) the 5-HT transporter increased in density relative to controls (350 vs. 210 fmol/mg). Open field behaviors in naïve and cocaine treated mice were also affected by diet, suggesting that iron deficiency causes decreased dopamine output. These data indicate a substantial genetic-based variability in brain responses to iron deficiency anemia, some of which are in direct contrast to what other experimental data would have predicted. Future studies clearly need to consider genetic background and sex in their analytical approach.     

Quantitative genetic analysis of brain copper and zinc in BXD recombinant inbred mice

Abstract

Copper and zinc are trace nutrients essential for normal brain function, yet an excess of these elements can be toxic. It is important therefore that these metals be closely regulated. We recently conducted a quantitative trait loci (QTL) analysis to identify chromosomal regions in the mouse containing possible regulatory genes. The animals came from 15 strains of the BXD/Ty recombinant inbred (RI) strain panel and the brain regions analyzed were frontal cortex, caudate-putamen, nucleus accumbens and ventral midbrain. Several QTL were identified for copper and/or zinc, most notably on chromosomes 1, 8, 16 and 17. Genetic correlational analysis also revealed associations between these metals and dopamine, cocaine responses, saccharine preference, immune response and seizure susceptibility. Notably, the QTL on chromosome 17 is also associated with seizure susceptibility and contains the histocompatibility H2 complex. This work shows that regulation of zinc and copper is under polygenic influence and is intimately related to CNS function. Future work will reveal genes underlying the QTL and how they interact with other genes and the environment. More importantly, revelation of the genetic underpinnings of copper and zinc brain homeostasis will aid our understanding of neurological diseases that are related to copper and zinc imbalance.     

Detection and quantitation of infectious human adenoviruses and JC polyomaviruses in water by immunofluorescence assay

Human adenoviruses (HAdV) and JC polyomaviruses (JCPyV) have been proposed as markers of fecal/urine contamination of human origin. An indirect immunofluorescence assay has been developed to quantify infectious human adenoviruses types 2 and 41 and JC polyomaviruses strain Mad-4 in water samples. The immunofluorescence assay was compared with other quantitative techniques used commonly such as plaque assay, tissue culture infectious dose-50 and quantitative PCR (qPCR). The immunofluorescence assays showed to be specific for the detection of infectious viruses, obtaining negative results when UV or heat-inactivated viruses were analyzed. The assays required less time and showed higher sensitivity for the detection of infectious viral particles than other cell culture techniques (1 log₁₀ more) evaluated. River water samples spiked previously with human adenoviruses and raw sewage samples were also analyzed using the proposed immunofluorescence assay as well as by qPCR. The results show quantitations with 2 log₁₀ reduction in the numbers of infectious viruses compared with the number of genome copies detected by qPCR. The immunofluorescence assay developed is fast, sensitive, specific, and a standardizable technique for the quantitation and detection of infectious viruses in water samples.     

Value of cerebral perfusion computed tomography in the management of intensive care unit patients with suspected ischaemic cerebral pathology after cardiac surgery.

OBJECTIVE: Adverse neurologic outcomes, like stroke, in intensive care unit (ICU) patients after cardiac surgery can have devastating consequences, among them increased mortality risk and, among survivors, loss of independence and a diminished quality of life. Non-contrast computed tomography (CT) remains a widely utilised modality for assessing stroke; however, it has a low sensitivity in the acute phase. Perfusion CT (PCT) has the potential of imaging stroke in its hyperacute phase. We evaluated the feasibility and results of the method among patients from the ICU. METHODS: The NCCT and PCT images of 33 retrospectively identified patients were included in this study. The diagnostic contribution of the PCT to patient management was classified according to one of three categories: (A) those that changed the preliminary (NCCT) diagnosis; (B) those that revealed additional pathology and/or specified more exactly findings that have been detected by NCCT or clinically suspected; and (C) confirmed the preliminary diagnosis. Neurologic outcome variables were also documented and associated with PCT lesions. RESULTS: Fifteen patients after coronary artery bypass graft (CABG) operation, 14 patients after CABG and valve surgery, and 4 patients after an aortic dissection (Type A) surgery underwent a NCCT with PCT 2.4+/-1.3 days after the operation. Twenty patients had bilateral internal carotid artery (ICA) stenosis (>50%), 11 patients had unilateral ICA stenosis (>75%), and 2 patients had no ICA stenosis. In nine patients (27.2%) the PCT changed the initial diagnosis of the NCCT and revealed ischaemic pathology. In 24 patients (72.7%), the performed PCT revealed additional pathology and/or more completely characterised findings that have been detected by the initial NCCT. In nine patients, PCT confirmed only the initial diagnosis. Patients with normal PCT findings had a favourable outcome; patients with large lesions in PCT in one or more vascular territories had an unfavourable outcome; seven patients with lesions in basal ganglia and/or semioval centre had a favourable outcome. CONCLUSIONS: PCT shows a greater sensitivity in detecting and mapping acute ischaemic stroke in ICU patients (after cardiac surgery) in whom conventional imaging findings are not in line with the severity of the clinical condition.