Occurrence and co-localization of amyloid beta-protein and apolipoprotein E in perivascular drainage channels of wild-type and APP-transgenic mice

The deposition of the amyloid beta-protein (Abeta) is a hallmark of Alzheimer's disease (AD). One reason for Abeta-accumulation and deposition in the brain may be an altered drainage along perivascular channels. Extracellular fluid is drained from the brain towards the cervical lymph nodes via perivascular channels. The perivascular space around cerebral arteries is the morphological correlative of these drainage channels. Here, we show that Abeta is immunohistochemically detectable within the perivascular space of 25 months old wild-type and amyloid precursor protein (APP)-transgenic mice harboring the Swedish double mutation driven by a neuron specific promoter. Only small amounts of Abeta can be detected immunohistochemically in the perivascular space of wild-type mice. Cerebrovascular and parenchymal Abeta-deposits were absent. In APP-transgenic mice, large amounts of Abeta were found in the perivascular drainage channels accompanied with cerebrovascular and parenchymal Abeta-deposition. The apolipoprotein E (apoE) immunostaining within the perivascular channels did not vary between wild-type and APP-transgenic mice. Almost 100% of the area that represents the perivascular space was stained with an antibody directed against apoE. Here, Abeta co-localized with apoE indicating an involvement of apoE in the perivascular clearance of Abeta. Fibrillar congophilic amyloid was not seen in wild-type mice. In APP-transgenic animals, congophilic fibrillar amyloid material was seen in the wall of cerebral blood vessels but not in the perivascular space. In conclusion, our results suggest that non-fibrillar forms of Abeta are drained along perivascular channels and that apoE is presumably involved in this clearance mechanism. Overloading such a clearance mechanism in APP-transgenic mice appears to result in insufficient Abeta-clearance, increased Abeta-levels in the brain and the perivascular drainage channels, and finally in Abeta-deposition. In so doing, our results strengthen the hypothesis that an alteration of perivascular drainage supports Abeta-deposition and the development of AD.     

NK-1 receptors modulate the excitability of ON cells in the rostral ventromedial medulla

The role of neurokinin-1 (NK-1) receptors in the rostral ventromedial medulla (RVM) was studied using extracellular single-unit recording combined with microiontophoresis. In rats, on- and off-type neurons were identified using noxious heat or mechanical stimuli applied to the tail. Responses evoked by iontophoretic application of N-methyl-d-aspartate (NMDA) were determined before and after intraplantar injection of capsaicin or iontophoretic application of substance P. In off cells, capsaicin produced an extended pause in ongoing activity but did not alter the subsequent spontaneous discharge rate or NMDA-evoked responses. In contrast, spontaneous discharge rates of on cells increased after capsaicin, and their responses to NMDA increased >100% above control values. The increased responses to NMDA after capsaicin were attenuated by iontophoretic application of the selective NK-1 receptor antagonist L-733,060. Similarly to capsaicin, iontophoretic application of the selective NK-1 receptor agonist, [Sar(9),Met(O(2))(11)]-substance P (SM-SP), increased the spontaneous discharge rate and NMDA-evoked responses of on cells by >100% of control values. These effects were antagonized by L-733,060. Immunohistochemical studies showed that a subset of neurons in the RVM labeled NK-1 receptors and that nearly all of these neurons were immunoreactive for the NMDAR1 subunit of the NMDA receptor. These results demonstrate that activation of NK-1 receptors in the RVM enhances responses of on cells evoked by NMDA. It is suggested that activation of NK-1 receptors in the RVM and the ensuing sensitization of on cells may contribute to the development of central sensitization and hyperalgesia after tissue injury and inflammation.     

Synthesis,structure, antioxidant activity,and water solubility of trolox ion conjugates

The interaction of trolox with ammonia, alkylamines of different classes, and amino derivatives of heterocyclic compounds, including nitroxyl radicals and alkaloids, led to the production of ammonium salts called ion conjugates (ICs). Five ICs were characterised by X-ray diffraction. This is the first time a wide range of ICs were made from trolox with amines, and ESI-MS data demonstrated they have the potential to generate pseudomolecular [(A^?B⁺)?+?H]⁺ ions. For all obtained trolox ICs, a significant increase (1–3 orders of magnitude) in water solubility was achieved while retaining high antioxidant activity. ICs synthesised from two biologically active fragments may be used to create polyfunctional agents with varying solubility and bioavailability.     

Nanomagnetic Modulation of Tumor Redox State

Modulation of reactive oxygen and nitrogen species in a tumor could be exploited for nanotherapeutic benefits. We investigate the antitumor effect in Walker-256 carcinosarcoma of magnetic nanodots composed of doxorubicin-loaded Fe₃O₄ nanoparticles combined with electromagnetic fields. Treatment using the magnetic nanodot with the largest hysteresis loop area (3402 erg/g) had the greatest antitumor effect with the minimum growth factor 0.49 ± 0.02 day^–1 (compared to 0.58 ± 0.02 day^–1 for conventional doxorubicin). Electron spin resonance spectra of Walker-256 carcinosarcoma treated with the nanodots, indicate an increase of 2.7 times of free iron (that promotes the formation of highly reactive oxygen species), using the nanodot with the largest hysteresis loop area, compared to conventional doxorubicin treatment as well as increases in ubisemiquinone, lactoferrin, NO-FeS-proteins. Hence, we provide evidence that the designed magnetic nanodots can modulate the tumor redox state. We discuss the implications of these results for cancer nanotherapy.     

The first case of combined heart-liver transplantation in a patient with alveolar echinococcosis

We report a rare case of liver alveolar echinococcosis with an invasion of the hepaticocaval confluence, inferior vena cava, pericardium, right atrium, atrial septum, and superior vena cava, and its successful treatment by combined heart-liver transplantation.     

Magnetically Induced Transparency in Media with Helical Dichroic Structure

In our paper, the magneto-optical properties of a dichroic cholesteric liquid crystal layer with large values of magneto-optical parameter g and low values of dielectric permittivity were investigated. The solutions of the dispersion equation and their peculiarities were investigated in detail. The specific properties of reflection, transmission, absorption, rotation, ellipticity spectra and also the spectra of ellipticity and azimuth of eigen polarization were investigated. The existence of a tunable linear and nonreciprocal transmission band was shown.     

The ringed esophagus

Abdominal Radiology -