Effect of some "strong" excitants of central neurones on the uptake of L-glutamate and L-aspartate by synaptosomes

"Strong" excitants of central neurones such as β N-oxalyl L α,β-diaminopropionic acid (ODAP), N-methyl-D-aspartic acid (NMDA) and kainic acid (KA) were found to inhibit the high affinity uptake of glutamate and aspartate in synaptosomes isolated from young rat brain. The potency of these "strong" excitants as convulsants appear to parallel their ability to inhibit glutamate uptake by synaptosomes. The data suggest the possibility that the convulsive effect of these "strong" excitants could be mediated by glutamate/aspartate.

Tissue thickness calculation in ocular optical coherence tomography

Thickness measurements derived from optical coherence tomography (OCT) images of the eye are a fundamental clinical and research metric, since they provide valuable information regarding the eye’s anatomical and physiological characteristics, and can assist in the diagnosis and monitoring of numerous ocular conditions. Despite the importance of these measurements, limited attention has been given to the methods used to estimate thickness in OCT images of the eye. Most current studies employing OCT use an axial thickness metric, but there is evidence that axial thickness measures may be biased by tilt and curvature of the image. In this paper, standard axial thickness calculations are compared with a variety of alternative metrics for estimating tissue thickness. These methods were tested on a data set of wide-field chorio-retinal OCT scans (field of view (FOV) 60° x 25°) to examine their performance across a wide region of interest and to demonstrate the potential effect of curvature of the posterior segment of the eye on the thickness estimates. Similarly, the effect of image tilt was systematically examined with the same range of proposed metrics. The results demonstrate that image tilt and curvature of the posterior segment can affect axial tissue thickness calculations, while alternative metrics, which are not biased by these effects, should be considered. This study demonstrates the need to consider alternative methods to calculate tissue thickness in order to avoid measurement error due to image tilt and curvature.

Thickness metrics in posterior segment optical coherence tomography

To develop and compare a set of metrics for calculating tissue thickness in wide-field OCT data.

Foreign Capital and Finland : Central government's first period of reliance on international financial markets, 1862-1938

The main objective of the study is to evaluate the Finnish central government s foreign borrowing between the years 1862 and 1938. Most of this period was characterised by deep capital market integration that bears resemblance to the liberal world financial order at the turn of the millennium. The main aim is to analyse the credit risk associated with the state and its determination by evaluating the world financial market centres perception of Finland. By doing this, the study is also expected to provide an additional dimension to Finland s political and economic history by incorporating into the research the assessments of international capital markets regarding Finland during a period that witnessed profound political and economic changes in Finnish society. The evaluation of the credit risk mainly relies on exchange-rate risk free time series of the state s foreign bonds. They have been collected from quotations in the stock exchanges in Helsinki, Hamburg, Paris and London. In addition, it investigates Finland s exposure to short-term debt and Moody s credit ratings assigned to Finland. The study emphasises the importance of the political risk. It suggests that the hey-day of the state s reliance on foreign capital markets took place during last few decades of the 19th century when Finland enjoyed a wide autonomy in the Russian Empire and prudently managed its economy, highlighted in Finland s adherence to the international gold standard. Political confrontations in Finland and, in particular, in Russia and the turbulence of the world financial system prevented the return of this beneficial position again. Through its issuance of foreign bonds the state was able to import substantial amounts of foreign capital, which was sorely needed to foster economic development in Finland. Moreover, the study argues that the state s presence in the western capital markets not only had economic benefits, but it also increased the international awareness of Finland s distinct and separate status in the Russian Empire and later underlined its position as an independent republic.

Heparin versus 0.9% sodium chloride intermittent flushing for the prevention of occlusion in long term central venous catheters in infants and children: A systematic review

Background Around the world, guidelines and clinical practice for the prevention of complications associated with central venous catheters (CVC) vary greatly. To prevent occlusion, most institutions recommend the use of heparin when the CVC is not in use. However, there is debate regarding the need for heparin and evidence to suggest normal saline may be as effective. The use of heparin is not without risk, may be unnecessary and is also associated with increased costs. Objectives To assess the clinical effects (benefits and harms) of heparin versus normal saline to prevent occlusion in long-term central venous catheters in infants, children and adolescents. Design A Cochrane systematic review of randomised controlled trials was undertaken. - Data sources: The Cochrane Vascular Group Specialised Register (including MEDLINE, CINAHL, EMBASE and AMED) and the Cochrane Register of Studies were searched. Hand searching of relevant journals and reference lists of retrieved articles was also undertaken. - Review Methods: Data were extracted and appraisal undertaken. We included studies that compared the efficacy of normal saline with heparin to prevent occlusion. We excluded temporary CVCs and peripherally inserted central catheters. Rate ratios per 1000 catheter days were calculated for two outcomes, occlusion of the CVC, and CVC-associated blood stream infection. Results Three trials with a total of 245 participants were included in this review. The three trials directly compared the use of normal saline and heparin. However, between studies, all used different protocols with various concentrations of heparin and frequency of flushes. The quality of the evidence ranged from low to very low. The estimated rate ratio for CVC occlusion per 1000 catheter days between the normal saline and heparin group was 0.75 (95% CI 0.10 to 5.51, two studies, 229 participants, very low quality evidence). The estimated rate ratio for CVC-associated blood stream infection was 1.48 (95% CI 0.24 to 9.37, two studies, 231 participants; low quality evidence). Conclusions It remains unclear whether heparin is necessary for CVC maintenance. More well-designed studies are required to understand this relatively simple, but clinically important question. Ultimately, if this evidence were available, the development of evidenced-based clinical practice guidelines and consistency of practice would be facilitated.

Interactions of nandrolone and psychostimulant drugs on central monoaminergic systems

It has been hypothesized that abuse of supra-therapeutic doses of anabolic androgenic steroids (AASs) can lead to dependence and function as a gateway to abuse of other drugs. This is supported by behavioral studies on animal models and psychiatric evaluations of human subjects, although their neurochemical effects remain largely unknown. A large body of evidence suggests that the ability of the drugs to induce a strong elevation of extracellular dopamine (DA) levels in the nucleus accumbens (NAc), especially, plays a crucial role in their reinforcing effects. -- This study had four main aims. The first was to explore the effects of nandrolone decanoate on dopaminergic and serotonergic activities in the brains of rats. The second aim was to assess whether or not nandrolone pre-exposure modulates the acute neurochemical and behavioral effects of psychostimulant drugs in experimental animals. The third was to investigate if the AAS-pre-treatment induced changes in brain reward circuitry are reversible. And the fourth main goal was to evaluate the role of androgen and estrogen receptors in the modulation of the dopaminergic and serotonergic effects of acute injections of stimulant drugs by sub-chronic nandrolone treatment. The results showed that nandrolone decanoate at doses, high enough to induce erythropoiesis, significantly increased the levels of DOPAC and 5-HT in the cerebral cortex. Co-administration of AAS and psychostimulant drugs showed that the increase in extracellular DA and 5-HT concentration evoked by amphetamine, MDMA and cocaine in the NAc was attenuated dose-dependently by pretreatment with nandrolone. Nandrolone pre-exposure also attenuated the ability of stimulants to cause increased stereotyped behavior and locomotor activity. Despite the significant decrease in nandrolone concentration in blood, the attenuation of cocaine’s effects remained unchanged after a fairly long period without nandrolone, suggesting that nandrolone effects could be long lasting. Blockade of androgen receptors with flutamide abolished the attenuating effect of nandrolone pretreatment on amphetamine-induced elevation of extracellular DA concentration. --- In conclusion, the results show that AAS-pretreatment is able to inhibit the reward-related neurochemical and behavioral effects of amphetamine, MDMA and cocaine in experimental animals. Furthermore, it seems that these effects could be long lasting and it appears that the ability of nandrolone to modulate reward-related effects of stimulants is dependent on activation of androgen receptors.

Role of the Central Metal Ion and Ligand Charge in the DNA Binding and Modification by Metallosalen Complexes

Several metal complexes of three different functionalized salen derivatives have been synthesized. The salens differ in terms of the electrostatic character and the location of the charges. The interactions of such complexes with DNA were first investigated in detail by UV−vis absorption titrimetry. It appears that the DNA binding by most of these compounds is primarily due to a combination of electrostatic and other modes of interactions. The melting temperatures of DNA in the presence of various metal complexes were higher than that of the pure DNA. The presence of additional charge on the central metal ion core in the complex, however, alters the nature of binding. Bis-cationic salen complexes containing central Ni(II) or Mn(III) were found to induce DNA strand scission, especially in the presence of co-oxidant as revealed by plasmid DNA cleavage assay and also on the basis of the autoradiogram obtained from their respective high-resolution sequencing gels. Modest base selectivity was observed in the DNA cleavage reactions. Comparisons of the linearized and supercoiled forms of DNA in the metal complex-mediated cleavage reactions reveal that the supercoiled forms are more susceptible to DNA scission. Under suitable conditions, the DNA cleavage reactions can be induced either by preformed metal complexes or by in situ complexation of the ligand in the presence of the appropriate metal ion. Also revealed was the fact that the analogous complexes containing Cu(II) or Cr(III) did not effect any DNA strand scission under comparable conditions. Salens with pendant negative charges on either side of the precursor salicylaldehyde or ethylenediamine fragments did not bind with DNA. Similarly, metallosalen complexes with net anionic character also failed to induce any DNA modification activities.

Chromosomal rearrangements, phenotypic variation and modularity: A case study from a contact zone between house mouse Robertsonian races in Central Italy

The Western European house mouse, Mus musculus domesticus, is well-known for the high frequency of Robertsonian fusions that have rapidly produced more than 50 karyotipic races, making it an ideal model for studying the mechanisms of chromosomal speciation. The mouse mandible is one of the traits studied most intensively to investigate the effect of Robertsonian fusions on phenotypic variation within and between populations. This complex bone structure has also been widely used to study the level of integration between different morphogenetic units. Here, with the aim of testing the effect of different karyotypic assets on the morphology of the mouse mandible and on its level of modularity, we performed morphometric analyses of mice from a contact area between two highly metacentric races in Central Italy. We found no difference in size, while the mandible shape was found to be different between the two Robertsonian races, even after accounting for the genetic relationships among individuals and geographic proximity. Our results support the existence of two modules that indicate a certain degree of evolutionary independence, but no difference in the strength of modularity between chromosomal races. Moreover, the ascending ramus showed more pronounced interpopulation/race phenotypic differences than the alveolar region, an effect that could be associated to their different polygenic architecture. This study suggests that chromosomal rearrangements play a role in the house mouse phenotypic divergence, and that the two modules of the mouse mandible are differentially affected by environmental factors and genetic makeup.

A combination of local inflammation and central memory T cells potentiates immunotherapy in the skin

Adoptive T cell therapy uses the specificity of the adaptive immune system to target cancer and virally infected cells. Yet the mechanism and means by which to enhance T cell function are incompletely described, especially in the skin. In this study, we use a murine model of immunotherapy to optimize cell-mediated immunity in the skin. We show that in vitro - derived central but not effector memory-like T cells bring about rapid regression of skin-expressing cognate Ag as a transgene in keratinocytes. Local inflammation induced by the TLR7 receptor agonist imiquimod subtly yet reproducibly decreases time to skin graft rejection elicited by central but not effector memory T cells in an immunodeficient mouse model. Local CCL4, a chemokine liberated by TLR7 agonism, similarly enhances central memory T cell function. In this model, IL-2 facilitates the development in vivo of effector function from central memory but not effector memory T cells. In a model of T cell tolerogenesis, we further show that adoptively transferred central but not effector memory T cells can give rise to successful cutaneous immunity, which is dependent on a local inflammatory cue in the target tissue at the time of adoptive T cell transfer. Thus, adoptive T cell therapy efficacy can be enhanced if CD8+ T cells with a central memory T cell phenotype are transferred, and IL-2 is present with contemporaneous local inflammation. Copyright © 2012 by The American Association of Immunologists, Inc.

Road kills of amphibians in different land use areas from Sharavathi river basin, central Western Ghats, India

A survey of amphibian mortality on roads was carried out in the Sharavathi river basin in the central Western Ghats. Road kills in three different land use areas: agricultural fields, water bodies and forests were recorded for four days along three 100m stretches in each type of area. One-hundred-and-forty-four individuals belonging to two orders, eight families, 11 genera and 13 species were recorded in the survey. Kills/km observed were: in forest 55, agricultural fields 38 and water bodies 27, for an overall average of 40 kills/km. Kill species compositions varied significantly between land use areas, but not overall kill rates.

Multivalent ligand presentation as a central concept to study intricate carbohydrate-protein interactions

Studying the weak binding affinities between carbohydrates and proteins has been a central theme in sustained efforts to uncover intricate details of this class of biomolecular interaction. The amphiphilic nature of most carbohydrates, the competing nature of the surrounding water molecules to a given protein receptor site and the receptor binding site characteristics led to the realization that carbohydrates are required to exert favorable interactions, primarily through clustering of the ligands. The clustering of sugar ligands has been augmented using many different innovative molecular scaffolds. The synthesis of clustered ligands also facilitates fine-tuning of the spatial and topological proximities between the ligands, so as to allow the identification of optimal molecular features for significant binding affinity enhancements. The kinetic and thermodynamic parameters have been delineated in many instances, thereby allowing an ability to correlate the multivalent presentation and the observed ligand-receptor interaction profiles. This critical review presents various multivalent ligands, synthetic and semisynthetic, and mechanisms by which the weak binding affinities are overcome, and the ligand-receptor complexation leads to significantly enhanced binding affinities (157 references).

Performance Analysis of Reconstruction Techniques for Frequency-Domain Optical-Coherence Tomography

We address the issue of noise robustness of reconstruction techniques for frequency-domain optical-coherence tomography (FDOCT). We consider three reconstruction techniques: Fourier, iterative phase recovery, and cepstral techniques. We characterize the reconstructions in terms of their statistical bias and variance and obtain approximate analytical expressions under the assumption of small noise. We also perform Monte Carlo analyses and show that the experimental results are in agreement with the theoretical predictions. It turns out that the iterative and cepstral techniques yield reconstructions with a smaller bias than the Fourier method. The three techniques, however, have identical variance profiles, and their consistency increases linearly as a function of the signal-to-noise ratio.