Spectroscopic Properties of some Hydroxylated 2-Stilbazole Derivatives.

The spectroscopic properties for a number of new hydroxylated 2-stilbazoles were studied by absorption and fluorescence spectroscopy. The maximum absorption and emission wavelengths, the molar extinction coefficients, and the Stokes shift values of derivatives were given. The dependence of the spectral characteristics on pH was shown. The possibility of creating molecular logic systems and fluorescent dyes for bioimaging based on these derivatives was demonstrated. The dependence of fluorescence on the medium redox properties was established for an one of derivatives. The possibility of a fluorescent probe creating on its basis to assess the oxidative state of living systems was demonstrated. The probe has good biocompatibility and can be successfully used for fluorescence imaging in cells.

Concussion, microvascular injury, and early tauopathy in young athletes after impact head injury and an impact concussion mouse model.

The mechanisms underpinning concussion, traumatic brain injury, and chronic traumatic encephalopathy, and the relationships between these disorders, are poorly understood. We examined post-mortem brains from teenage athletes in the acute-subacute period after mild closed-head impact injury and found astrocytosis, myelinated axonopathy, microvascular injury, perivascular neuroinflammation, and phosphorylated tau protein pathology. To investigate causal mechanisms, we developed a mouse model of lateral closed-head impact injury that uses momentum transfer to induce traumatic head acceleration. Unanaesthetized mice subjected to unilateral impact exhibited abrupt onset, transient course, and rapid resolution of a concussion-like syndrome characterized by altered arousal, contralateral hemiparesis, truncal ataxia, locomotor and balance impairments, and neurobehavioural deficits. Experimental impact injury was associated with axonopathy, blood-brain barrier disruption, astrocytosis, microgliosis (with activation of triggering receptor expressed on myeloid cells, TREM2), monocyte infiltration, and phosphorylated tauopathy in cerebral cortex ipsilateral and subjacent to impact. Phosphorylated tauopathy was detected in ipsilateral axons by 24 h, bilateral axons and soma by 2 weeks, and distant cortex bilaterally at 5.5 months post-injury. Impact pathologies co-localized with serum albumin extravasation in the brain that was diagnostically detectable in living mice by dynamic contrast-enhanced MRI. These pathologies were also accompanied by early, persistent, and bilateral impairment in axonal conduction velocity in the hippocampus and defective long-term potentiation of synaptic neurotransmission in the medial prefrontal cortex, brain regions distant from acute brain injury. Surprisingly, acute neurobehavioural deficits at the time of injury did not correlate with blood-brain barrier disruption, microgliosis, neuroinflammation, phosphorylated tauopathy, or electrophysiological dysfunction. Furthermore, concussion-like deficits were observed after impact injury, but not after blast exposure under experimental conditions matched for head kinematics. Computational modelling showed that impact injury generated focal point loading on the head and seven-fold greater peak shear stress in the brain compared to blast exposure. Moreover, intracerebral shear stress peaked before onset of gross head motion. By comparison, blast induced distributed force loading on the head and diffuse, lower magnitude shear stress in the brain. We conclude that force loading mechanics at the time of injury shape acute neurobehavioural responses, structural brain damage, and neuropathological sequelae triggered by neurotrauma. These results indicate that closed-head impact injuries, independent of concussive signs, can induce traumatic brain injury as well as early pathologies and functional sequelae associated with chronic traumatic encephalopathy. These results also shed light on the origins of concussion and relationship to traumatic brain injury and its aftermath.awx350media15713427811001.

Pathophysiology of Concussion.

Although concussion has been a subject of interest for centuries, this condition remains poorly understood. The mechanistic underpinnings and accepted definition of concussion remain elusive. To make sense of these issues, this article presents a brief history of concussion studies, detailing the evolution of motivations and experimental conclusions over time. Interest in concussion as a subject of scientific inquiry has increased with growing concern about the long-term consequences of mild traumatic brain injury (TBI). Although concussion is often associated with mild TBI, these conditions-the former a neurological syndrome, the latter a neurological event-are distinct, both mechanistically and pathobiologically. Modern research primarily focuses on the study of the biomechanics, pathophysiology, potential biomarkers and neuroimaging to distinguish concussion from mild TBI. In addition, mild TBI and concussion outcomes are influenced by age, sex, and genetic differences in people. With converging experimental objectives and methodologies, future concussion research has the potential to improve clinical assessment, treatment, and preventative measures.

Submicron-Sized Nanocomposite Magnetic-Sensitive Carriers: Controllable Organ Distribution and Biological Effects.

Although new drug delivery systems have been intensely developed in the past decade, no significant increase in the efficiency of drug delivery by nanostructure carriers has been achieved. The reasons are the lack of information about acute toxicity, the influence of the submicron size of the carrier and difficulties with the study of biodistribution in vivo. Here we propose, for the first time in vivo, new nanocomposite submicron carriers made of bovine serum albumin (BSA) and tannic acid (TA) and containing magnetite nanoparticles with sufficient content for navigation in a magnetic field gradient on mice. We examined the efficacy of these submicron carriers as a delivery vehicle in combination with magnetite nanoparticles which were systemically administered intravenously. In addition, the systemic toxicity of this carrier for intravenous administration was explicitly studied. The results showed that (BSA/TA) carriers in the given doses were hemocompatible and didn't cause any adverse effect on the respiratory system, kidney or liver functions. A combination of gradient-magnetic-field controllable biodistribution of submicron carriers with fluorescence tomography/MRI imaging in vivo provides a new opportunity to improve drug delivery efficiency.

Amylase-Sensitive Polymeric Nanoparticles Based on Dextran Sulfate and Doxorubicin with Anticoagulant Activity.

This study looked into the synthesis and study of Dextrane Sulfate-Doxorubicin Nanoparticles (DS-Dox NP) that are sensitive to amylase and show anticoagulant properties. The particles were obtained by the method of solvent replacement. They had a size of 305 ± 58 nm, with a mass ratio of DS:Dox = 3.3:1. On heating to 37 °C, the release of Dox from the particles was equal to 24.2% of the drug contained. In the presence of amylase, this ratio had increased to 42.1%. The study of the biological activity of the particles included an assessment of the cytotoxicity and the effect on hemostasis and antitumor activity. In a study of cytotoxicity on the L929 cell culture, it was found that the synthesized particles had less toxicity, compared to free doxorubicin. However, in the presence of amylase, their cytotoxicity was higher than the traditional forms of the drug. In a study of the effect of DS-Dox NP on hemostasis, it was found that the particles had a heparin-like anticoagulant effect. Antitumor activity was studied on the model of ascitic Zaidel hepatoma in rats. The frequency of complete cure in animals treated with the DS-Dox nanoparticles was higher, compared to animals receiving the traditional form of the drug.