Low-molecular-weight paramagnetic 19F contrast agents for fluorine magnetic resonance imaging

Objective

¹⁹F MRI requires biocompatible and non-toxic soluble contrast agents with high fluorine content and with suitable ¹⁹F relaxation times. Probes based on a DOTP chelate with 12 magnetically equivalent fluorine atoms (DOTP-tfe) and a lanthanide(III) ion shortening the relaxation times were prepared and tested.

Methods

Complexes of DOTP-tfe with trivalent paramagnetic Ce, Dy, Ho, Tm, and Yb ions were synthetized and characterized. ¹⁹F relaxation times were determined and compared to those of the La complex and of the empty ligand. In vitro and in vivo ¹⁹F MRI was performed at 4.7 T.

Results

¹⁹F relaxation times strongly depended on the chelated lanthanide(III) ion. T₁ ranged from 6.5 to 287 ms, T₂ from 3.9 to 124.4 ms, and T₂* from 1.1 to 3.1 ms. All complexes in combination with optimized sequences provided sufficient signal in vitro under conditions mimicking experiments in vivo (concentrations 1.25 mM, 15-min scanning time). As a proof of concept, two contrast agents were injected into the rat muscle; ¹⁹F MRI in vivo confirmed the in vivo applicability of the probe.

Conclusion

DOTP-based ¹⁹F probes showed suitable properties for in vitro and in vivo visualization and biological applications. The lanthanide(III) ions enabled us to shorten the relaxation times and to trim the probes according to the actual needs. Similar to the clinically approved Gd³⁺ chelates, this customized probe design ensures consistent biochemical properties and similar safety profiles.

     

Nitrogen‐doped graphene as an alternative to ecotoxic zinc oxide in rubbers

Zinc oxide (ZnO) is an essential ingredient in industrial rubber production; it regulates the onset of vulcanization, accelerates the kinetics of vulcanization, and improves the mechanical properties of rubber. However, environmental pollution with ZnO is a concern because it is recognized to be significantly ecotoxic and might also have adverse effects on human health. One of the major sources of ZnO environmental pollution is rubber items, tires in particular. Nitrogen (N)‐doped graphene is a promising next‐generation catalyst. We show here that the replacement of 3 phr ZnO by just 0.1 phr N‐doped graphene in styrene–butadiene rubber reduced the vulcanization onset time by more than a factor of two while retaining the fast vulcanization kinetics and enhancing the tensile strength in comparison with rubber with just ZnO. A shorter vulcanization time implies energy savings, which, together with the nontoxicity of N‐graphene, should make the resulting rubbers substantially more environmentally friendly. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46116.     

Characterization of Ni-Coated WS2 Nanotubes for Hydrodesulfurization Catalysis

A reactivity screening of new nano-hydrodesulfurization (HDS) catalysts was conducted using an ambient pressure flow reactor as well as ultra-high vacuum kinetics techniques. Thiophene was used as a probe molecule. Clean multiwall WS₂ nanotubes (INT-WS₂) as well as Ni- and Co-coated INT-WS₂ were considered. In addition, undoped MoS₂ and Re-doped nanoparticles with fullerene-like structures were studied. Commercial Ni and Co HDS catalysts from Haldor Topsoe (Denmark) as well as “nano MoS₂” from Impex Corp. (USA) were considered as reference materials. The lab-synthesized and commercial systems broke down thiophene into quite similar non-sulfur containing products, as identified by a gas chromatograph. The Ni and Co promoted catalysts showed similar thiophene conversion rates. Although the commercial catalysts had larger thiophene conversion rates than the laboratory-synthesized systems, the Re-doped nano-HDS catalyst showed quite low rates of formation of H₂S, an undesirable by-product.     

Physical Properties of La1−xEuxPO4,0 ≤ x ≤ 1, Monazite‐Type Ceramics

Synthetic La_1?xEu_xPO₄ monazite‐type ceramics with 0 ≤ x ≤ 1 have been characterized by ultrasound techniques, dilatometry, and micro‐calorimetry. The coefficients of thermal expansion and the elastic properties are, to a good approximation, linearly dependent on the europium concentration. Elastic stiffness coefficients range from 182(1) to 202(1) GPa for c₁₁ and from 53.8(7) to 61.1(4) GPa for c₄₄. They are strongly dependent on the density of the sample. The coefficient of thermal expansion at 673 K is 8.4(3)  × 10^?6 K^?1 for LaPO₄ and 9.9(3)  × 10^?6 K^?1 for EuPO₄, respectively. The heat capacities at ambient temperature are between 101.6(8) J·(mol·K)^?1 for LaPO₄ and 110.1(8) J·(mol·K)^?1 for EuPO₄. The difference between the heat capacity of LaPO₄ and the Eu‐containing solid solutions is dominated by electronic transitions of the 4f‐electrons at temperatures above 75 K.     

Cobalt-Catalyzed Green Cross-Dehydrogenative C(sp<Superscript>2</Superscript>)-H/P-H Coupling Reactions

Joined electrolysis of arenes (benzene or coumarin derivatives) and diethyl-H-phosphonate (EtO)₂P(O)H in the presence of [CoCl₂(bpy)] catalyst (5%) in an ethanol-aqueous solution in reductive conditions allows obtaining the desired products in a single step by aromatic C–H bonds phosphonation with yields up to 70%. The only by-product is hydrogen; the reaction proceeds at room temperature and does not require specially added reducing agents and oxidants or other initiators. Radical mechanism has been confirmed for the catalytic reaction proceeding via bicobalt phosphonates with Co–P bond, the structure of which also has been identified.     

Interactive image directed neurosurgery: patient registration employing the Laitinen stereo-adapter

Fiducial markers visible on both imaging scans and the patient are a convenient and accurate method to register the patients head in stereotactic space preceeding an interactive image directed neurosurgical procedure. We have been using the Laitinen non-invasive relocatable stereo-adapter to carry the fidcucial markers both during the imaging and patient registration process. Since the adapter can be accurately remounted the surgical procedure can take place at any time interval after the imaging study. To compare registration accuracy studies were performed using a phantom carrying both surface fiducial markers and fiducial markers mounted on the stereo adapter. We have found that total system accuracy using either surface or adapter mounted markers and an optical tracking system is in the range of 3-5 mm and is acceptable for a broad range of neurosurgical applications.     

The establishment of a radioactive waste disposal facility in Western Australia for low level waste

Core needle biopsies (CNB) are often used for the diagnosis of breast lesions. In some breast cancer patients, e.g., those treated with preoperative chemotherapy, the CNB specimen might be the only pretreatment tissue sample available for studies of prognostic and predictive markers. Our purpose was to evaluate whether marker studies performed on CNB specimens accurately reflect the marker status of the tumor. Immunostaining for five commonly used prognostic and predictive markers was performed on both CNB and subsequent excision specimens from 56 consecutive patients who had a CNB with carcinoma followed by excision of the tumor. None of the patients received radiotherapy or chemotherapy between the CNB and the excision. Paraffin sections of the CNB and excision specimens were immunostained for bcl-2, estrogen receptor (ER), c-erbB-2, and p53. These markers were scored as positive or negative. Microvessel density (MVD) was scored as a continuous variable on sections immunostained for Factor VIII-related antigen by calculating the average number of microvessels in three 224x fields of highest tumor vascularity ("hot spots"). Immunostaining results for bcl-2, ER, c-erbB-2, and p53 on the CNB and the corresponding excision specimens were 100% concordant. Although there was significant correlation between MVD on the CNB specimens and the corresponding excisions (r = 0.507, P = 0.0002), the mean MVD on the CNB and corresponding excision specimens differed by more than 10% in 85.7% of cases, with differences ranging from 4.3 to 233.3%. MVD was higher in the CNB than in the excision specimens in 30 (61.2%) of 49 cases. In conclusion, in all of the cases studied, accurate results for the dichotomously scored markers bcl-2, ER, c-erbB-2, and p53 were obtained on CNB specimens. In contrast, in most cases, MVD, which was scored as a continuous variable, could not be reliably assessed on the CNB specimen.     

Ambivalenzen in der Klassifizierung von Behinderung

Definition of the problem: In May 2001, the World Health Assembly of the World Health Organization (WHO) approved the final version of the new "International Classification of Functioning, Disability and Health (ICF)". The ICF is supposed to offer a better framework to classify disability than the former classification of the WHO (1980), the "International Classification of Impairments, Disabilities and Handicaps (ICIDH)". In contrast to the "consequences of disease" -approach, as in the ICIDH, a "biopsychosocial" approach is used in the ICF. By integrating the medical and the social model of disability in the ICF the WHO attempts to achieve a synthesis of these opposing models. This attempt is analysed aiming to attain a realistic integration of both models. The combination of the models contains structural problems. Conclusion: Viewing the approach critically, internal ambiguities are identified. The ambivalence of the new approach must therefore be reviewed, as the medical model of disability is still dominant compared to the social model of disability. Regarding the practical application of the ICF the analysed ambivalence has to be taken into consideration.     

Analysis of Antidepressant-like Effects and Action Mechanisms of GSB-106, a Small Molecule,Affecting the TrkB Signaling

Induction of BDNF-TrkB signaling is associated with the action mechanisms of conventional and fast-acting antidepressants. GSB-106, developed as a small dimeric dipeptide mimetic of BDNF, was previously shown to produce antidepressant-like effects in the mouse Porsolt test, tail suspension test, Nomura water wheel test, in the chronic social defeat stress model and in the inflammation-induced model of depression. In the present study, we evaluated the effect of chronic per os administration of GSB-106 to Balb/c mice under unpredictable chronic mild stress (UCMS). It was observed for the first time that long term GSB-106 treatment (1 mg/kg, 26 days) during ongoing UCMS procedure ameliorated the depressive-like behaviors in mice as indicated by the Porsolt test. In addition, chronic per os administration of GSB-106 resulted in an increase in BDNF levels, which were found to be decreased in the prefrontal cortex and hippocampus of mice after UCMS. Furthermore, prolonged GSB-106 treatment was accompanied by an increase in the content of pTrkB^706/707 in the prefrontal cortex and by a pronounced increase in the level of pTrkB⁸¹⁶ in both studied brain structures of mice subjected to UCMS procedure. In summary, the present data show that chronic GSB-106 treatment produces an antidepressant-like effect in the unpredictable chronic mild stress model, which is likely to be associated with the regulation of the BDNF-TrkB signaling.     

Neuroprotective Properties of Quinone Reductase 2 Inhibitor M-11, a 2-Mercaptobenzimidazole Derivative

The ability of NQO2 to increase the production of free radicals under enhanced generation of quinone derivatives of catecholamines is considered to be a component of neurodegenerative disease pathogenesis. The present study aimed to investigate the neuroprotective mechanisms of original NQO2 inhibitor M-11 (2-[2-(3-oxomorpholin-4-il)-ethylthio]-5-ethoxybenzimidazole hydrochloride) in a cellular damage model using NQO2 endogenous substrate adrenochrome (125 µM) and co-substrate BNAH (100 µM). The effects of M-11 (10–100 µM) on the reactive oxygen species (ROS) generation, apoptosis and lesion of nuclear DNA were evaluated using flow cytometry and single-cell gel electrophoresis assay (comet assay). Results were compared with S29434, the reference inhibitor of NQO2. It was found that treatment of HT-22 cells with M-11 results in a decline of ROS production triggered by incubation of cells with NQO2 substrate and co-substrate. Pre-incubation of HT-22 cells with compounds M-11 or S29434 results in a decrease of DNA damage and late apoptotic cell percentage reduction. The obtained results provide a rationale for further development of the M-11 compound as a potential neuroprotective agent.