Inflammation, edema and poor outcome are associated with hyperthermia in hypertensive intracerebral hemorrhages.

BACKGROUND AND PURPOSE: The deleterious effect of hyperthermia on intracerebral hemorrhage (ICH) has been studied. However, the results are not conclusive and new studies are needed to elucidate clinical factors that influence the poor outcome. The aim of this study was to identify the clinical factors (including ICH etiology) that influence the poor outcome associated with hyperthermia and ICH. We also tried to identify potential mechanisms involved in hyperthermia during ICH. METHODS: We conducted a retrospective study enrolling patients with non-traumatic ICH from a prospective registry. We used logistic regression models to analyze the influence of hyperthermia in relation to different inflammatory and endothelial dysfunction markers, hematoma growth and edema volume in hypertensive and non-hypertensive patients with ICH. RESULTS: We included 887 patients with ICH (433 hypertensive, 50 amyloid, 117 by anticoagulants and 287 with other causes). Patients with hypertensive ICH showed the highest body temperature (37.5 ± 0.8°C) as well as the maximum increase in temperature (0.9 ± 0.1°C) within the first 24 h. Patients with ICH of hypertensive etiologic origin, who presented hyperthermia, showed a 5.3-fold higher risk of a poor outcome at 3 months. We found a positive relationship (r = 0.717, P < 0.0001) between edema volume and hyperthermia during the first 24 h but only in patients with ICH of hypertensive etiologic origin. This relationship seems to be mediated by inflammatory markers. CONCLUSION: Our data suggest that hyperthermia, together with inflammation and edema, is associated with poor outcome only in ICH of hypertensive etiology.

Shape effect in active targeting of nanoparticles to inflamed cerebral endothelium under static and flow conditions.

Endothelial cells represent the first biological barrier for compounds, including nanoparticles, administered via the intravascular route. In the case of ischemic stroke and other vascular diseases, the endothelium overexpresses specific markers, which can be used as molecular targets to facilitate drug delivery and imaging. However, targeting these markers can be quite challenging due to the presence of blood flow and the associated hydrodynamic forces, reducing the likelihood of adhesion to the vessel wall. To overcome these challenges, various parameters including size, shape, charge or ligand coating have been explored to increase the targeting efficiency. Geometric shape can modulate nanoparticle binding to the cell, especially by counteracting part of the hydrodynamic forces of the bloodstream encountered by the classical spherical shape. In this study, the binding affinity of polystyrene nanoparticles with two different shapes, spherical and rod-shaped, were compared. First, vascular adhesion molecule-1 (VCAM-1) was evaluated as a vascular target of inflammation, induced by lipopolysaccharide (LPS) stimulation. To evaluate the effect of nanoparticle shape on particle adhesion, nanoparticles were coated with anti-VCAM-1 and tested under static conditions in cell culture dishes coated with cerebral microvasculature cells (bEnd.3) and under dynamic flow conditions in microfluidic channels lined with hCMEC/D3 cells. Effect of particle shape on accumulation was also assessed in two in vivo models including systemic inflammation and local brain inflammation. The elongated rod-shaped particles demonstrated greater binding ability in vitro, reaching a 2.5-fold increase in the accumulation for static cultures and 1.5-fold for flow conditions. Anti-VCAM-1 coated rods exhibited a 3.5-fold increase in the brain accumulation compared to control rods. These results suggest shape offers a useful parameter in future design of drug delivery nanosystems or contrast agents for neurovascular pathologies.

The effect of changing the microstructure of a microemulsion on chemical reactivity.

A kinetic study was carried out on various solvolytic reactions in water/ NH4OT /isooctane microemulsions. The NH4OT surfactant is a derivative of the sodium salt of bis(2-ethylhexyl) sulfosuccinate (NaOT or AOT), where the Na+ counterion has been replaced by NH4+. The counterion substitution effects the phase diagram of the system, and therefore, NH4OT-based microemulsions with high water content reaching values of W = 350 (W = [H2O]/[NH4OT]) can be obtained. The presence of high W values suggests a transition in the microemulsion microstructure from water-in-oil (w/o) to oil-in-water (o/w), as was confirmed by conductivity and 1H NMR self-diffusion measurements. The interpretation of the kinetic studies in terms of pseudophase formalism allows us to analyze the effect of the microemulsion on chemical reactivity, regardless of its microstructure. It has been confirmed that the values of the solvolytic rate constants at the interphase of oil-in-water microemulsions are similar to those obtained for aqueous SDS systems, showing that the hydration degree of the interphase of the oil-in-water microemulsions is independent of W. The influence of the surfactant counterion on the solvolytic rate constants was analyzed by comparing HOT-, NaOT-, and NH4OT-based microemulsions. An important influence on the rate constants caused by the changes in the structural properties of water has been observed as was confirmed by the water 1H NMR signals.

Solvolysis of benzoyl halides in water/NH4DEHP/isooctane microemulsions.

A study was carried out on the solvolysis reactions of different benzoyl halides in microemulsions of water/NH4DEHP/isooctane, where NH4DEHP is ammonium bis(2-ethylhexyl) phosphate. Because of the low solubility of benzoyl halides in water, they are distributed between the continuous medium and the interface of the microemulsion, where the reaction takes place. The application of the pseudophase model has allowed us to obtain the distribution constants and the rate constants at the interface for the benzoyl halides. Reaction mechanisms and the changes in these mechanisms in terms of the water content of the microemulsion have been determined on the basis of kinetic data. The influence of the substituent and the leaving group on the reaction rate has been investigated. A comparison of kinetic results with those previously obtained in water/AOT/isooctane microemulsions allows a kinetic evaluation of the change in the microemulsion properties with the surfactant.