Plasma levels of neuropeptides in Alzheimer's disease.

BACKGROUND: In the central nervous system, several neuropeptides are believed to be involved in the pathophysiology of Alzheimer's disease (AD). Indeed, previous studies have documented that glucagon-like peptide 1 (GLP-1) possesses neurotropic properties and can reduce amyloid-beta peptide levels in the brain in vivo. Moreover, the concentrations of neuropeptide Y (NPY) seem to be altered in the cerebrospinal fluid of patients with AD and in subjects with major depression. Finally, among the modifications induced by aging, a dysregulation of the ghrelin-growth hormone (GH) system has been reported. METHODS: We investigated the plasma concentrations of these neuropeptides in 14 subjects with AD. Data obtained from these patients were compared with data from an age- and weight-matched healthy group. RESULTS: No significant differences were found between the two groups in relation to plasma levels of GLP-1, NPY, ghrelin and GH. Peripheral NPY concentrations were positively correlated with ghrelin levels in both groups, and with plasma GLP-1 concentration only in controls. CONCLUSION: On the basis of our results, peripheral levels of these neuropeptides seem not to serve as biochemical markers of AD.     

Hyper-IgM syndrome with CHARGE association

A girl with coloboma of the iris, sensorineural deafness, growth delay, distinctive face, and cranial nerve dysfunction was diagnosed of CHARGE association in the first year of life. She presented with repeated otitis. At 3 yr of age, the patient suffered a septicemia ( Streptococcus pneumoniae , Corynebacterium sp.). The immunoglobulin G (IgG) and IgA serum levels were decreased, IgM increased and cellular immunity parameters were normal, supporting the diagnosis of hyper-IgM (HIM) syndrome. The sequence of CD40 ligand and cytidine deaminase genes were normal. From then on, she was receiving immunoglobulin intravenously with an excellent outcome . Here, we report the first case of CHARGE association and HIM syndrome in the same patient. Although the cause could not be identified, a non-random link is likely.     

Slow degeneration of zebrafish Rohon-Beard neurons during programmed cell death.

Rohon-Beard cells are large, mechanosensory neurons located in the dorsal spinal cord of anamniote vertebrates. In most species studied to date, these cells die during development. We followed labeled Rohon-Beard cells in living zebrafish embryos and found that they degenerate slowly, over many days. During degeneration, the soma shrinks and finally disappears, and the processes become beady in appearance and finally break apart, but they do not retract. Zebrafish Rohon-Beard cells apparently fragment their DNA, as revealed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) labeling, before undergoing degenerative morphologic changes. We also followed the development of labeled dorsal root ganglion neurons, as they are developing at the same stages that Rohon-Beard cells are degenerating. We found that, although axons of both cell types extend into similar regions, Rohon-Beard cells degenerate normally in mutants lacking dorsal root ganglia, providing evidence that interactions between the two cell types are not responsible for Rohon-Beard cell degeneration. Developmental Dynamics 229:30-41,2004.     

Wireless pH testing as an adjunct to unsedated transnasal esophagoscopy: the safety and efficacy of transnasal telemetry capsule placement.

OBJECTIVES: The introduction of 48-hour wireless pH testing offers clinicians a new alternative for the objective documentation of reflux. The success of transnasal wireless pH capsule placement has not been previously described. The purpose of this investigation was to describe our experience with transnasal wireless pH capsule placement. METHODOLOGY: All patients undergoing unsedated transnasal esophagoscopy and wireless pH capsule placement between January 1, 2003 and July 31, 2003 were prospectively evaluated. Data concerning patient tolerance, success of capsule placement and function, complications, and pH recordings were collected. RESULTS: During this time, 46 persons were evaluated. The mean age of the cohort was 52 years. Of the patients, 50% were male. The indications for the procedure were chronic cough (18/46), gastroesophageal reflux disease (18/46), and larygopharyngeal reflux (10). Of the procedures performed, 85% (39/46) were successful. Complications included epistaxis (2/46), laryngospasm (2/46), and vasovagal reaction (1/46). CONCLUSIONS: The transnasal placement of a wireless pH capsule is a safe and effective diagnostic adjunct to unsedated transnasal esophagoscopy.     

Integrating support vector machines and neural networks.

Support vector machines (SVMs) are a powerful technique developed in the last decade to effectively tackle classification and regression problems. In this paper we describe how support vector machines and artificial neural networks can be integrated in order to classify objects correctly. This technique has been successfully applied to the problem of determining the quality of tiles. Using an optical reader system, some features are automatically extracted, then a subset of the features is determined and the tiles are classified based on this subset.     

Localization and Quantitative Autoradiography of Glutamatergic Ligand Binding Sites in Chick Brain

The anatomical localization of glutamate receptor subtype-selective ligand binding sites was investigated in 1-day-old chick brain using quantitative autoradiography. Under the conditions used, the regional distributions of [3H]glutamate, [3H]AMPA (a selective quisqualate receptor ligand) and [3H]kainate binding sites are manifestly different. [3H]l-glutamate binding is densely localized in the telencephalon, particularly in the neostriatum (2.8 pmol/mg protein). In addition, [3H]l-glutamate labels the thalamus, the nucleus mesencephalicus lateralis pars dorsalis, the superficial layers of the optic tectum and the molecular layer of the cerebellum. [3H]AMPA binding sites are most densely localized in the hippocampus (0.90 pmol/mg protein), with an otherwise relatively uniform distribution of binding within the telencephalon. [3H]AMPA also labels the striatum griseum et fibrosum superficiale of the optic tectum and the molecular layer of the cerebellum. [3H]Kainate binding sites are extremely densely packed in the molecular layer of the cerebellum (10 pmol/mg protein). Other regions of [3H]kainate binding include the hyperstriatum and the thalamus. The binding of the NMDA receptor channel blocker [3H]MK-801 is increased in the presence of 1 mM l-glutamate. [3H]MK-801 binding is generally widespread in the telencephalon but is notably absent from the ectostriatum. No evidence of [3H]MK-801 binding sites was detected in the cerebellum, even in the presence of 1 mM l-glutamate. The relatively high densities and the well-defined localizations of the glutamate receptor subtype binding sites suggest that chick brain provides a useful system for the further study of excitatory amino acid receptors.     

Circulating inflammatory mediators during start of fever in differential diagnosis of gram-negative and gram-positive infections in leukopenic rats

Gram-negative and gram-positive infections have been considered the most important causes of morbidity and mortality in patients with leukopenia following chemotherapy. However, discrimination between bacterial infections and harmless fever episodes is difficult. Because classical inflammatory signs of infection are often absent and fever is frequently the only sign of infection, the aim of this study was to assess the significance of serum interleukin-6 (IL-6), IL-10, macrophage inflammatory protein-2 (MIP-2), procalcitonin (PCT), and C-reactive protein (CRP) patterns in identifying bacterial infections during start of fever in normal and cyclophosphamide-treated (leukopenic) rats following an injection of lipopolysaccharide (LPS) or muramyl dipeptide (MDP) as a model for gram-negative and gram-positive bacterial infections. We found that, compared to normal rats, immunosuppressed animals exhibited significantly higher fevers and lesser production of all mediators, except IL-6, after toxin challenge. Moreover, compared to rats that received MDP, both groups of animals that received an equivalent dose of LPS showed significantly higher fevers and greater increase in serum cytokine levels. Furthermore, in contrast to those in immunocompetent rats, serum levels of IL-6 and MIP-2 were not significantly changed in leukopenic animals after MDP injection. Other serum markers such as PCT and CRP failed to discriminate between bacterial stimuli in both groups of animals. These results suggest that the use of the analyzed serum markers at an early stage of fever could give useful information for the clinician for excluding gram-negative from gram-positive infections.