Intrathecal administration of autologous mesenchymal stromal cells for spinal cord injury: Safety and efficacy of the 100/3 guideline

Background aims

Cell therapy with autologous mesenchymal stromal cells (MSCs) in patients with spinal cord injury (SCI) is beginning, and the search for its better clinical application is an urgent need.

Secondary heterologous dengue infection risk: Disequilibrium between immune regulation and inflammation?

Increased serum levels of cytokines released by cells of the immune response have been detected in patients suffering from dengue disease. Likewise, secondary infections by a different dengue virus serotype result in a highest risk of development of the severe dengue disease. Both findings suggest that the memory immune response is one of the key players in the pathogenesis of this disease. Here we take advantage of the particular Cuban epidemiological situation in dengue to analyze a broad spectrum of cell-mediated immune response mediators at mRNA and protein level. Evidences for a regulatory immune pattern in homologous (TGF-β, IL-10) vs. pro-inflammatory pattern (IFN-γ, TNF-α) in heterologous dengue virus re-challenge were found, suggesting a possible association with the higher incidence of severe dengue cases in the latter case.     

Specificity of the rapid rK39 antigen-based immunochromatographic test Kalazar Detect(r) in patients with cutaneous leishmaniasis in Brazil

The aim of this study was to evaluate the specificity of a rapid immunochromatographic test that was developed to detect antibodies against the rK39 antigen for the diagnosis of visceral leishmaniasis (VL). This evaluation was performed using sera from patients with a confirmed diagnosis of active cutaneous leishmaniasis. The sera from 272 patients with a confirmed diagnosis of localised cutaneous leishmaniasis (CL) who resided in an area endemic for Leishmania braziliensis in Brazil were obtained before the initiation of antileishmanial treatment. Kalazar Detect^(r)(InBios, Seattle, WA) recombinant K39 antigen-based immunochromatographic strips were used according to the manufacturer''s instructions. The test results were evaluated independently by two examiners in sequential order. The positive controls for the test included five serum samples from five patients with parasitologically confirmed diagnosis of VL caused by Leishmania infantum in Brazil. Overall, 100% of the samples obtained from patients with CL were negative, confirming the absence of a serological cross-reaction for individuals with cutaneous disease when these patients were evaluated using the rapid test. The lack of a cross-reaction in patients who were infected by parasites of the same genus highlights the specificity of the rK39 antigen for the diagnosis of VL in areas with the sympatric circulation of L. braziliensis and L. infantum.     

Amphetamine Administration into the Ventral Striatum Facilitates Behavioral Interaction with Unconditioned Visual Signals in Rats

Background

Administration of psychomotor stimulants like amphetamine facilitates behavior in the presence of incentive distal stimuli, which have acquired the motivational properties of primary rewards through associative learning. This facilitation appears to be mediated by the mesolimbic dopamine system, which may also be involved in facilitating behavior in the presence of distal stimuli that have not been previously paired with primary rewards. However, it is unclear whether psychomotor stimulants facilitate behavioral interaction with unconditioned distal stimuli.

Principal Findings

We found that noncontingent administration of amphetamine into subregions of the rat ventral striatum, particularly in the vicinity of the medial olfactory tubercle, facilitates lever pressing followed by visual signals that had not been paired with primary rewards. Noncontingent administration of amphetamine failed to facilitate lever pressing when it was followed by either tones or delayed presentation or absence of visual signals, suggesting that visual signals are key for enhanced behavioral interaction. Systemic administration of amphetamine markedly increased locomotor activity, but did not necessarily increase lever pressing rewarded by visual signals, suggesting that lever pressing is not a byproduct of heightened locomotor activity. Lever pressing facilitated by amphetamine was reduced by co-administration of the dopamine receptor antagonists SCH 23390 (D1 selective) or sulpiride (D2 selective).

Conclusions

Our results suggest that amphetamine administration into the ventral striatum, particularly in the vicinity of the medial olfactory tubercle, activates dopaminergic mechanisms that strongly enhance behavioral interaction with unconditioned visual stimuli.     

A recurrent and localized dinoflagellate bloom in a Mediterranean beach

A recurrent, prolonged and singular bloom of Alexandrium tayloriBalech in an open beach (La Fosca, Spain, NW Mediterranean)is described. Alexandrium taylori appears at several placesalong a wide area of the NW Mediterranean (Costa Brava) duringthe summer, reaching concentrations up to 10⁵ cells l^–1,but it only proliferates persistently, massively (densities>10⁶ cells l^–1) and recurrently during August in LaFosca beach. The A.taylori bloom can be considered a manifestationof large-scale proliferation in a restricted area, where couplingbetween resting cysts in the sediment and bloom outbreak isnot a major factor compared to the interaction of local environmentalconditions with the planktonic organism's life history. Fromobservations of environmental conditions (the environmentalwindow) and the multiscale spatio-temporal distributions andlife history of A.taylori, we describe the bloom dynamics andanswer some critical questions about the different phases ofthe bloom. Some of these answers are: (i) the source of theA.taylori population is widespread offshore and is not locateddirectly at the beach; (ii) high cell densities are reachedand maintained with a moderate in situ growth and low loss rates;(iii) temporary cysts act as a reserve of the population.     

Hypophagia and induction of serotonin transporter gene expression in raphe nuclei of male and female rats after short-term fluoxetine treatment

Serotonin (5-HT) is one of the regulators of feeding in humans. Drugs acting on the serotoninergic system are used to treat bulimia nervosa and to enhance the effect of hypocaloric diets in overweight subjects. They act rapidly to normalise feeding when used to treat eating-related problems. To explore the role of the 5-HT transporter (serotonin transporter (SERT)) in the short-term action of serotonin selective reuptake inhibitor fluoxetine, rats were i.p. given the drug for five consecutive days. Acute administration of fluoxetine in male and female rats produced a strong reduction in food intake, an effect that held up when daily treatment was maintained for five consecutive days. This reduction translated into a diminution of body weight that was statistically significant in the case of the males. As a reflection of the body weight change in rats killed after the fifth daily drug injection, retroperitoneal fat pad also decreased; a diminution that was statistically significant in the case of male rats. In these conditions, plasma leptin levels of both male and female rats were lower than in untreated animals. While acute fluoxetine administration did not modify SERT gene expression, subchronic drug treatment increased the content of SERT mRNA in the midbrain raphe complex of both rat genders. These findings may contribute to explain the role of SERT in fluoxetine action on binging and as an adjunct to hypocaloric diets.     

A kinetic comparison between E2P and the E2P-like state induced by a beryllium fluoride complex in the Na,K-ATPase. Interactions with Rb+

Metal-fluoride complexes have been used to induce E2P-like states with the aim of studying the events that occur during E2P hydrolysis in P-type ATPases. In the present work, we compared the E2P-like state induced by a beryllium fluoride complex (BeF_x) with the actual E2P state formed through backdoor phosphorylation of the Na,K-ATPase. Formation of E2P and E2P-like states were investigated employing the styryl dye RH421. We found that BeF_x is the only fluorinated phosphate analog that, like Pi, increases the RH421 fluorescence. The observed rate constant, k_obs, for the formation of E2P decreases with [Pi] whereas that of E2BeF_x increases with [BeF_x]. This might wrongly be taken as evidence of a mechanism where the binding of BeF_x induces a conformational transition. Here, we rather propose that, like for Pi, binding of BeF_x follows a conformational-selection mechanism, i.e. it binds to the E2 conformer forming a complex that is much more stable than E2P, as seen from its impaired capacity to return to E1 upon addition of Na⁺. Although E2P and E2BeF_x are able to form states with 2 occluded Rb⁺, both enzyme complexes differ in that the affinity for the binding and occlusion of the second Rb⁺ is much lower in E2BeF_x than in E2P. The higher rates of Rb⁺ occlusion and deocclusion observed for E2BeF_x, as compared to those observed for other E2P-like transition and product states suggest a more open access to the cation transport sites, supporting the idea that E2BeF_x mimics the E2P ground state.