Diamond nanoparticles, so-called nanodiamonds (NDs), are attracting growing attention, because they have the intrinsic characteristics of diamond together with the unique properties of nanometer-sized particles. In particular, biomedical applications of NDs have been investigated extensively owing to their low toxicity and amenability to various surface functionalizations. [1][2][3][4][5][6][7] One of the most promising applications of ND is biomedical imaging on the basis of nonbleaching fluorescence from the diamond core (nitrogen-vacancy, or N-V, center). [4,8,9] In such biomedical applications of ND, it should form a stable hydrosol in a physiological environment, as pointed out by Xing and Dai, [2] and Shenderova et al. [3] in their recent reviews.Although we successfully prepared a very stable hydrosol of ND functionalized with polyethylene glycol (PEG), [5] its solubility was not sufficient for biomedical applications, for example, as a platform for an imaging probe and drugdelivery system. To increase the solubility, we changed the molecular design and exchanged the linear polyethers PEG for hyperbranched polyols, because the hydroxy group is more hydrophilic than an ether group, and the hyperbranched structure can cover the nanoparticle surface much more densely than a linear chain. Polyglycerol (PG) was adopted as the hyperbranched polyol to be grafted onto the ND surface for the following three reasons: 1) PG shows high biocompatibility as well as high hydrophilicity, [10][11][12][13] 2) a PG layer can be readily constructed on the ND surface through ringopening multibranching polymerization of glycidol initiated at the functional groups on the ND surface, [14,15] and 3) PG can be functionalized further by derivatizing the periphery. [12,13] The recent use of PG for the functionalization of various nanoparticles with potential biological applications [14][15][16][17][18] prompted us to communicate our results. Herein, we report the preparation of PG-functionalized ND (ND-PG). Its extremely high solubility not only in pure water but also in buffer solutions enabled chromatographic separation of the NDs according to size. In view of cancer imaging, size control of nanoparticles is important because of enhanced permeability and retention (EPR) in solid tumors. [19] The ND used for PG functionalization, designated as ND30 herein, has a 30 nm median diameter and is prepared from bulk diamond synthesized by a static high-pressurehigh-temperature (HPHT) method. ND-PG was synthesized through ring-opening multibranching polymerization of glycidol at high temperature (Scheme 1). When the polymerization was initiated at the surface functional groups, such as hydroxy and carboxylic acid groups, the ND surface was covered with PG. However, PG without the ND core, designated as free PG, was also obtained as a side product through self-ring-opening polymerization of glycidol. To retard the side reaction initiated not from the ND surface but from glycidol, we examined the reaction conditions, including the solvent, t...

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Imparting multiple functions to nanoparticles through organic functionalization has been attracting significant interest, particularly in terms of biomedical applications. Among them, diamond nanoparticles;the so-called nanodiamond (ND);have been recognized as one of the best platforms, because of its nontoxic or low-toxicity properties, as well as its organic characteristics that enable covalent bonding with introduced functionalities. Here, we show multistep organic transformations on the ND surface that amass the requisite functions layer by layer through covalent bonds. The functionalities introduced onto the ND surface were well-characterized by solution-phase 1 H NMR and 13 C NMR spectroscopies, recently developed by us and other groups, as well as conventional infrared (IR), fluorescence microscopy and spectroscopy, and elemental analysis. As a result, hydrophilic and fluorescent characteristics were incorporated onto the ND surface by adding polyethylene glycol (PEG) and fluorescein segments, providing fluorescent ND stably dispersed under a physiological environment. ND has been confirmed to be viable for use as a cellular imaging agent by introducing them into HeLa cells.

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An 83-year-old female, who had a history of anterior myocardial infarction, was treated for Alzheimer's disease with donepezil. She suffered from repeated diarrhea and vomiting, and experienced syncope. She was admitted to our hospital and was diagnosed with acute colitis and syncope. On admission, her heart rate was 54 beats/min with regular rhythm. Laboratory data showed a low plasma potassium level. Electrocardiogram (ECG) showed poor R progression, ST elevation, negative T in precordial leads, and marked QT prolongation. Transthoracic echocardiogram showed the enlargement of the left atrium and aneurysmal area at the apex. Torsades de Pointes (TdP) with syncope and convulsion were confirmed on ECG monitoring twice after admission. We treated her with potassium chloride and started magnesium sulfate and lidocaine, and then added isoprenaline injection. After these treatments, her heart rate increased and we did not detect TdP again. With the aging population in Japan, prescriptions for donepezil are increasing. We have to be vigilant for syncope in patients taking donepezil, which is possibly related to QT prolongation and TdP.

Using the immunohistochemical technique, we attempted to identify the source of secretion of steroid hormones between the mid- and late-terms of gestation in dogs by investigating steroid converting enzymes such as cholesterol side-chain cleavage enzyme (SCC), 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta-HSD), 17 alpha-hydroxylase/C17, 20lyase (c17), and aromatase in the ovaries and placenta. Aromatase positive cells were slightly confirmed in luteal cells in the mid-term of gestation (day 40), whereas, in the late-stage (day 50 and 60), the number of aromatase positive cells had increased. However, the oestrogen precursor (c-17 positive cells), could barely be identified in the marginal regions of the corpora lutea (CL) and completely disappeared in the late-stage of gestation. The androgen precursors, convertase SCC and 3 beta-HSD, were confirmed in all regions of the CL during the mid-stage of gestation (day 40), showing particularly strong cell reactions in the marginal region of the CL. Yet, these positive reactions of SCC and 3 beta-HSD in the marginal region of the CL disappeared in the late-stage of gestation. Moreover, it was discovered that the number of SCC and 3 beta-HSD positive cells had decreased in all regions of the CL. None of the enzymes were detected in the placenta. The above results indicated that the source of oestrogen secretion in pregnant dogs is considered to be the CL, and that, compared with the mid-stage of gestation, there was an increased number of oestrogen synthesizing cells within the CL in the late-stage. However, the biosynthetic site of oestrogen precursors from the luteal cells during the late-stage of gestation is still unknown.

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The isothermal phase relations for the