Left Ventricular Assist Device Implantation Combined with Surgical Ventricular Reconstruction

Nine months after sustaining a transmural anteroseptal myocardial infarction, a 45-year-old man presented with ischemic heart disease, severe mitral valve insufficiency, New York Heart Association functional class IV congestive heart failure, and a left ventricular aneurysm. Coronary angiography revealed 3-vessel disease. Echocardiography showed severe left ventricular impairment, pronounced thrombosis in the left ventricular apex, and low myocardial reserve. To reduce the high risk of performing left ventricular and mitral valve reconstruction concurrently with revascularization, we decided to perform ventricular reconstruction and to implant a Berlin Heart INCOR left ventricular assist device as a bridge to heart transplantation. The patient had an uncomplicated recovery, was discharged from the hospital with symptomatic improvement after 20 days, and was placed on the list for heart transplantation. We describe the patient''s case, the surgical procedure, and the reasoning behind the chosen course of treatment.Key words: Cardiac surgical procedures/methods, cardiac volume/physiology, heart aneurysm/surgery, heart failure/complications, heart-assist devices, prosthesis implantation/methods, reconstructive surgical procedures, treatment outcome, ventricular dysfunction, left/surgeryLeft ventricular (LV) reconstructive surgery is one method of treatment for patients who have ischemic heart disease with LV aneurysm and concomitant congestive heart failure.^1–3 However, preoperative deterioration of hemodynamic status is associated with high risk in such patients, who are candidates for heart transplantation. We present the case of a man who underwent LV reconstructive surgery combined with LV bypass with use of the Berlin Heart INCOR® LV assist device (LVAD) (Berlin Heart GmbH; Berlin, Germany).     

Hybrid fluorescent liquid crystalline composites: directed assembly of quantum dots in liquid crystalline block copolymer matrices

Hybrid fluorescent liquid crystalline (LC) composites containing inorganic quantum dots (QDs) are promising materials for many applications in optics, nanophotonics and display technology, combining the superior emission capability of QDs with the externally controllable optical properties of LCs. In this work, we propose the hybrid LC composites that were obtained by embedding CdSe/ZnS QDs into a series of host LC block copolymers of different architectures by means of a two-stage ligand exchange procedure. The ABA/BAB triblock copolymers and AB diblock copolymers with different polymerization degrees are composed of nematogenic phenyl benzoate acrylic monomer units and poly(4-vinylpyridine) blocks, which are capable of binding to the QD surface. Our results clearly show that the spatial distribution of QDs within composite films as well as the formation of QD aggregates can be programed by varying the structure of the host block copolymer. The obtained composites form a nematic LC phase, with isotropization temperatures being close to those of the initial host block copolymers. In addition, the influence of the molecular architecture of the host block copolymers on fluorescence properties of the obtained composites is considered. The described strategy for the QD assembly should provide a robust and conventional route for the design of highly ordered hierarchical hybrid materials for many practical applications.

Spatial distribution of QDs within hybrid composite films was programed by varying the molecular architecture of the host LC block copolymers.     

Design and synthesis of lipid-mimetic cationic iridium complexes and their liposomal formulation for in vitro and in vivo application in luminescent bioimaging

Two iridium [Ir(N^C)₂(N^N)]⁺ complexes with the diimine N^N ligand containing a long polymethylene hydrophobic chain were synthesized and characterized by using NMR and ESI mass-spectrometry: N^N – 2-(1-hexadecyl-1H-imidazol-2-yl)pyridine, N^C – methyl-2-phenylquinoline-4-carboxylate (Ir1) and 2-phenylquinoline-4-carboxylic acid (Ir2). These complexes were used to prepare the luminescent PEGylated DPPC liposomes (DPPC/DSPE-PEG2000/Ir-complex = 95/4.5/1 mol%) using a thin film hydration method. The narrowly dispersed liposomes had diameters of about 110 nm. The photophysics of the complexes and labeled liposomes were carefully studied. Ir1 and Ir2 give red emission (λ_em = 667 and 605 nm) with a lifetime in the microsecond domain and quantum yields of 4.8% and 10.0% in degassed solution. Incorporation of the complexes into the liposome lipid bilayer results in shielding of the emitters from interaction with molecular oxygen and partial suppression of excited state nonradiative relaxation due to the effect of the relatively rigid bilayer matrix. Delivery of labeled liposomes to the cultured ARPE-19 cells demonstrated the usefulness of Ir1 and Ir2 in cellular imaging. Labeled liposomes were then injected intravitreally into rat eyes and imaged successfully with optical coherence tomography and funduscopy. In conclusion, iridium complexes enabled the successful labeling and imaging of liposomes in cells and animals.

Novel lipoidal Ir(iii) phosphorescent labels were embedded into liposomes and used for imaging in cells and animals.     

Osteoblast Malfunction Caused by Cell Stress Response to Procollagen Misfolding in α2(I)‐G610C Mouse Model of Osteogenesis Imperfecta

Glycine (Gly) substitutions in collagen Gly‐X‐Y repeats disrupt folding of type I procollagen triple helix and cause severe bone fragility and malformations (osteogenesis imperfecta [OI]). However, these mutations do not elicit the expected endoplasmic reticulum (ER) stress response, in contrast to other protein‐folding diseases. Thus, it has remained unclear whether cell stress and osteoblast malfunction contribute to the bone pathology caused by Gly substitutions. Here we used a mouse with a Gly610 to cysteine (Cys) substitution in the procollagen α2(I) chain to show that misfolded procollagen accumulation in the ER leads to an unusual form of cell stress, which is neither a conventional unfolded protein response (UPR) nor ER overload. Despite pronounced ER dilation, there is no upregulation of binding immunoglobulin protein (BIP) expected in the UPR and no activation of NF‐κB signaling expected in the ER overload. Altered expression of ER chaperones αB crystalline and HSP47, phosphorylation of EIF2α, activation of autophagy, upregulation of general stress response protein CHOP, and osteoblast malfunction reveal some other adaptive response to the ER disruption. We show how this response alters differentiation and function of osteoblasts in culture and in vivo. We demonstrate that bone matrix deposition by cultured osteoblasts is rescued by activation of misfolded procollagen autophagy, suggesting a new therapeutic strategy for OI. © 2016 American Society for Bone and Mineral Research.     

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.