Synthesis, spectral, theoretical, and antimicrobial screening of some heterocyclic oximes

In a wide research program toward new and efficient antimicrobial agents, a series of substituted N-nitroso-3-alkyl piperidone oximes were synthesized and their antibacterial activity against Staphylococcus aureus, Pseudomonas aerugonisa, Escherichia coli, and Klbesiella pneumoniae and antifungal activity against Aspergillus niger, Aspergillus flavus, and Rhizopus were evaluated. Their structure and stereochemistry were characterized by high-resolution ¹H NMR, mass and elemental analysis. The spectra of all N-nitroso oximes reveal the presence of two isomers labeled as E (–NOH group is anti to N–N=O moiety) and Z (–NOH group is syn to N–N=O moiety) in solution and the coupling constants ruled out the possibility of normal chair conformation. From the theoretical studies and coupling constant values, it was found that all N-nitroso oximes exist as an equilibrium mixture of CA boat conformation (B ₁) and the major isomer was found to be E isomer. The molecular structure of N-nitroso oximes were also determined by semiempirical and Gaussian-03 calculation and the results are in agreement with the experimental studies.     

Incidence of non-traumatic spinal cord injury in Victoria, Australia: a population-based study and literature review

STUDY DESIGN: Data extraction from a state-wide, population-based, health-administration database of hospital admissions. OBJECTIVE: To determine the incidence of non-traumatic spinal cord injury (NTSCI).Setting:Victoria, Australia. METHODS: All patients admitted to hospital with a new onset of NTSCI, or who developed NTSCI after hospitalization, between 1 July 2000 and 30 June 2006, were identified using a population-based database. Age and gender of NTSCI patients were recorded. RESULTS: The number of adults aged 15 years and older with NTSCI in each of the 12-month periods was 82, 111, 96, 108, 133 and 101. The average age-adjusted incidence rate of NTSCI in adults was 26.3 cases per million per year. There was no statistically significant increase in the age-adjusted incidence of NTSCI over the study period (Spearman's rho=0.35, P=0.5). The incidence of NTSCI was significantly greater than the reported incidence for traumatic spinal cord injury (chi2 (1)=19.5, P<0.0000). There was a very strong correlation between age and the incidence of NTSCI, for both men (Spearman's rho=1, P<0.0000) and women (Spearman's rho=0.98, P=0.0000). Men had a statistically significantly (chi2 (1)=13.1, P=0.000) higher incidence of NTSCI (30.5 million adults per year) compared to women (22.9 million adults per year). The average incidence of NTSCI in children <15 years was 0.7 cases per million per year. CONCLUSION: NTSCI is strongly correlated with age and is more common than traumatic spinal cord injury. The method used in this study to calculate the incidence of NTSCI can be used to monitor the anticipated increase in the incidence of NTSCI in the years ahead, and can be used to in comparative studies.     

Water soluble RNA based antagonist of AMPA receptors

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are one of the important receptor classes involved in glutamate-mediated excitotoxicity. Although small molecule antagonists of this receptor have been shown to have neuroprotective properties, their low solubilities pose severe side effects in clinical trials. Here we have used the SELEX method to obtain water-soluble nuclease-resistant RNA ligands that bind to the agonist binding site of AMPA receptors. Using whole-cell current recordings, we have characterized the functional consequences of a representative aptamer from this class and show that it is a competitive antagonist of AMPA receptors and in the concentration range where it acts as an inhibitor of the AMPA receptor the RNA has no effect on the GluR6 homomeric kainate receptors. Additionally, using a fluorescence resonance energy transfer (FRET) probe, we show that this RNA ligand stabilizes the open cleft conformation of the ligand binding domain, consistent with the known structures of small antagonist-bound states of the soluble domain of this protein. Finally, using rat primary cortical neurons, we show that this RNA ligand significantly reduces neurotoxicity associated with oxygen glucose deprivation. The water-soluble and antagonistic properties of this aptamer coupled with its neuroprotective properties make it an excellent candidate for potential use in diseases or pathological conditions involving glutamate-mediated excitotoxicity.     

Histological characterization and development of mesial surface sulci in the human brain at 13–15 gestational weeks through high-resolution histology

Cellular-level anatomical data from early fetal brain are sparse yet critical to the understanding of neurodevelopmental disorders. We characterize the organization of the human cerebral cortex between 13 and 15 gestational weeks using high-resolution whole-brain histological data sets complimented with multimodal imaging. We observed the heretofore underrecognized, reproducible presence of infolds on the mesial surface of the cerebral hemispheres. Of note at this stage, when most of the cerebrum is occupied by lateral ventricles and the corpus callosum is incompletely developed, we postulate that these mesial infolds represent the primordial stage of cingulate, callosal, and calcarine sulci, features of mesial cortical development. Our observations are based on the multimodal approach and further include histological three-dimensional reconstruction that highlights the importance of the plane of sectioning. We describe the laminar organization of the developing cortical mantle, including these infolds from the marginal to ventricular zone, with Nissl, hematoxylin and eosin, and glial fibrillary acidic protein (GFAP) immunohistochemistry. Despite the absence of major sulci on the dorsal surface, the boundaries among the orbital, frontal, parietal, and occipital cortex were very well demarcated, primarily by the cytoarchitecture differences in the organization of the subplate (SP) and intermediate zone (IZ) in these locations. The parietal region has the thickest cortical plate (CP), SP, and IZ, whereas the orbital region shows the thinnest CP and reveals an extra cell-sparse layer above the bilaminar SP. The subcortical structures show intensely GFAP-immunolabeled soma, absent in the cerebral mantle. Our findings establish a normative neurodevelopment baseline at the early stage.     

Treatment of levodopa-induced dyskinesia

Levodopa provides the most effective symptomatic treatment for Parkinson's disease (PD). Initiation of treatment of PD too early and/or very aggressive treatment with large doses of levodopa results in severe motor fluctuations and dyskinesias in 30% of patients with PD. Chronic levodopa treatment over a period of 9 years or more will invariably result in disabling motor fluctuations in 90% of PD patients. The motor fluctuations and associated dyskinesia are due to progressive dopamine denervation, an unregulated pattern of release of dopamine in the synapse, fluctuating levels of receptor sensitivity, and fluctuating levels of dopamine receptor stimulation. Once the dyskinesias are established, they are difficult to treat. The current medical therapy is a by-product of several explorative open-label trials, as well as a few blinded and double-label placebo-controlled clinical trials, of varying duration in a small number of patients. These studies suggest that amantadine, a glutamate antagonist, may be the most effective, easily available, and inexpensive medical treatment for levodopa-induced dyskinesia. Several other drugs, already approved for other medical ailments, also have been tried but not evaluated in large-scale clinical trials. None of these drugs is approved by the US Food and Drug Administration specifically for levodopa-induced dyskinesia. By far, the most effective treatment of levodopa-induced dyskinesia appears to be deep brain stimulation, with globus pallidus interna or the subthalamic nucleus as the two major targets of placement of electrodes.     

DDEC: Dragon database of genes implicated in esophageal cancer

Background  

Esophageal cancer ranks eighth in order of cancer occurrence. Its lethality primarily stems from inability to detect the disease during the early organ-confined stage and the lack of effective therapies for advanced-stage disease. Moreover, the understanding of molecular processes involved in esophageal cancer is not complete, hampering the development of efficient diagnostics and therapy. Efforts made by the scientific community to improve the survival rate of esophageal cancer have resulted in a wealth of scattered information that is difficult to find and not easily amendable to data-mining. To reduce this gap and to complement available cancer related bioinformatic resources, we have developed a comprehensive database (Dragon Database of Genes Implicated in Esophageal Cancer) with esophageal cancer related information, as an integrated knowledge database aimed at representing a gateway to esophageal cancer related data.     

Cyclic voltammetric studies of alumina supported monometallic Pt and bimetallic PtSn catalysts using carbon paste electrodes

The present work relates to the cyclic voltammetric studies of alumina supported monometallic Pt and bimetallic PtSn catalysts using solid carbon paste electrodes. The cyclic voltammetric data of the solid catalysts, which were reproducible, were in agreement with those of electro-deposited Pt and PtSn electrode systems. The reversibility of the H-adsorption–desorption system in representative 0.3 Pt–Al₂O₃ monometallic catalyst was confirmed by the difference between the anodic and cathodic peak potentials. The unit ratio of the cathodic to anodic peak currents observed, indicated the equality of the transfer coefficient in the kinetics for the respective processes. The O₂-adsorption–desorption reaction was found to be irreversible as expected. The lower area of the curve for H-adsorption–desorption in the case of bimetallic catalysts gives an indication for the formation of alloys. The use of a carbon paste electrode in studying the cyclic voltammetric behavior of heterogenous catalysts yielded qualitative information about the activity of the catalysts. Good correlations were found between cyclic voltammetric parameters and activity results in both monometallic and bimetallic catalysts.