Tissue factor-positive monocytes in children with sickle cell disease: correlation with biomarkers of haemolysis

Tissue Factor (TF) initiates thrombin generation, and whole blood TF (WBTF) is elevated in sickle cell disease (SCD). We sought to identify the presence of TF-positive monocytes in SCD and their relationship with the other coagulation markers including WBTF, microparticle-associated TF, thrombin-antithrombin (TAT) complexes and D-dimer. Whether major SCD-related pathobiological processes, including haemolysis, inflammation and endothelial activation, contribute to the coagulation abnormalities was also studied. The cohort comprised children with SCD (18 HbSS, 12 HbSC, mean age 3.6 years). We demonstrated elevated levels of TF-positive monocytes in HbSS, which correlated with WBTF, TAT and D-Dimer (p=0.02 to p=0.0003). While TF-positive monocytes, WBTF, TAT and D-dimer correlated with several biomarkers of haemolysis, inflammation and endothelial activation in univariate analyses, in multiple regression models the haemolytic markers (reticulocytes and lactate dehydrogenase) contributed exclusively to the association with all four coagulant markers evaluated. The demonstration that haemolysis is the predominant operative pathology in the associated perturbations of coagulation in HbSS at a young age provides additional evidence for the early use of therapeutic agents, such as hydroxycarbamide to reduce the haemolytic component of this disease

Stomatal behavior and components of the antioxidative system in coffee plants under water stress

Coffee (Coffea arabica) plants show a positive relationship between stomatal closure and formation and accumulation of H2O2. However, for coffee plants under water restriction such relationship has never been studied. The objective of the present study was evaluate the stomatal movement and the antioxidant capacity of coffee seedlings under different water regimes. Eight months old coffee seedlings of cv. Catuaí IAC 99 were submitted to field capacity, gradual and total suspension of irrigation during a period of 21 days. Evaluations of leaf water potential (Ψw) were performed in the beginning of the morning, and stomatal resistance, transpiration rate and vapor pressure deficit were determined at 10 am and 5 pm. All biochemical and enzymatic determinations were performed in leaves collected at 5 pm. Evaluations and samplings were performed at three days intervals. There was no variation in Ψw during the evaluated period for plants in field capacity. However, an expressive decrease of Ψw following day 12, reaching values near -2.5 MPa at the end of the experiment was observed for plants submitted to gradual suspension of irrigation. For plants submitted to total suspension of irrigation, Ψw decreases after the sixth day, reaching -2.5 MPa at day 15. The decay of Ψw in plants submitted to gradual and total suspension of irrigation reflected in increased stomatal resistance and in a decreased transpiration rate leading to an increase in hydrogen peroxide formation and, on final stages, increase in lipid peroxidation. As a conclusion, an increase in the activity of antioxidant enzymes as well as in the levels of ascorbate and dehydroascorbate was observed, which act in the detoxification of free radicals formed as result of the water stress.Para o cafeeiro (Coffea arabica) existe uma comprovada relação positiva entre fechamento estomático e formação e acúmulo de H2O2. Entretanto, tal relação para a cultura sob restrição hídrica ainda não foi estudada. Avaliou-se o movimento estomático e a capacidade antioxidante em mudas de cafeeiro sob diferentes regimes hídricos. Mudas de cafeeiro cv. Catuaí IAC 99, com oito meses de idade, foram submetidas à capacidade de campo, suspensão gradativa e suspensão total da irrigação por um período de 21 dias. Foram realizadas avaliações do potencial hídrico (Ψw) foliar na antemanhã e resistência estomática, taxa transpiratória e déficit de pressão de vapor foram avaliados as 10h00 e 17h00. As determinações bioquímicas e enzimáticas foram realizadas em folhas coletadas às 17h00. Todas as avaliações e coletas foram realizadas em intervalos de três dias. Nas plantas em capacidade de campo não houve variação no Ψw durante o período de avaliação. Para a suspensão gradativa da irrigação, houve queda expressiva a partir dos 12 dias, chegando próximo a -2,5 Mpa, ao final do experimento. Já nas plantas em suspensão total da irrigação observou-se queda no Ψw a partir do sexto dia, chegando a -2,5 MPa aos 15 dias. A queda no Ψw para as plantas em suspensão gradual e total da irrigação refletiu em aumentos na resistência estomática e diminuição da taxa transpiratória, ocasionando aumento na formação de peróxido de hidrogênio e nos períodos finais, aumentos na peroxidação de lipídios. Em conseqüência obervaram-se aumentos na atividade das enzimas antioxidantes, bem como nos teores de ascorbato e dehidroascorbato, atuando na detoxificação dos radicais livres formados em função do estresse

Astrocytes Optimize the Synaptic Transmission of Information

Chemical synapses transmit information via the release of neurotransmitter-filled vesicles from the presynaptic terminal. Using computational modeling, we predict that the limited availability of neurotransmitter resources in combination with the spontaneous release of vesicles limits the maximum degree of enhancement of synaptic transmission. This gives rise to an optimal tuning that depends on the number of active zones. There is strong experimental evidence that astrocytes that enwrap synapses can modulate the probabilities of vesicle release through bidirectional signaling and hence regulate synaptic transmission. For low-fidelity hippocampal synapses, which typically have only one or two active zones, the predicted optimal values lie close to those determined by experimentally measured astrocytic feedback, suggesting that astrocytes optimize synaptic transmission of information

Modelling Vesicular Release at Hippocampal Synapses

We study local calcium dynamics leading to a vesicle fusion in a stochastic, and spatially explicit, biophysical model of the CA3-CA1 presynaptic bouton. The kinetic model for vesicle release has two calcium sensors, a sensor for fast synchronous release that lasts a few tens of milliseconds and a separate sensor for slow asynchronous release that lasts a few hundred milliseconds. A wide range of data can be accounted for consistently only when a refractory period lasting a few milliseconds between releases is included. The inclusion of a second sensor for asynchronous release with a slow unbinding site, and thereby a long memory, affects short-term plasticity by facilitating release. Our simulations also reveal a third time scale of vesicle release that is correlated with the stimulus and is distinct from the fast and the slow releases. In these detailed Monte Carlo simulations all three time scales of vesicle release are insensitive to the spatial details of the synaptic ultrastructure. Furthermore, our simulations allow us to identify features of synaptic transmission that are universal and those that are modulated by structure