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For a period of 12 months all samples submitted for serum prolactin (PRL) assay and with PRL > 700 mU/L were examined by gel filtration chromatography. In 17 (25%) of 69 samples we found macroprolactin. The Delfia and Immuno 1 immunoassay systems gave similar PRL results with samples containing macroprolactin whereas the ACS 180 system gave lower results. With the Delfia and Immuno 1 systems samples containing substantial quantities of macroprolactin showed low recovery of PRL after precipitation with polyethylene glycol 6000 (PEG 6000) and this technique can be used as a screening test for macroprolactinaemia. We conclude that macroprolactinaemia is a common phenomenon and, in assays which detect this species, is a common cause of hyperprolactinaemia. Macroprolactinaemia may contribute to the difficulty in establishing an upper limit of the reference range for serum PRL. In our experience, patients with macroprolactinaemia do not exhibit features of the hyperprolactinaemia syndrome and it is important to recognize macroprolactin as the cause of hyperprolactinaemia to avoid unnecessary investigation and treatment.
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PMID:Macroprolactinaemia: contribution to hyperprolactinaemia in a district general hospital and evaluation of a screening test based on precipitation with polyethylene glycol. 936 16

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abiraterone acetate, acyline, adalimumab, adenosine triphosphate, AEE-788, AIDSVAX gp120 B/B, AK-602, alefacept, alemtuzumab, alendronic acid sodium salt, alicaforsen sodium, alprazolam, amdoxovir, AMG-162, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, aminophylline hydrate, anakinra, anecortave acetate, anti-CTLA-4 MAb, APC-8015, aripiprazole, aspirin, atazanavir sulfate, atomoxetine hydrochloride, atorvastatin calcium, atrasentan, AVE-5883, AZD-2171; Betamethasone dipropionate, bevacizumab, bimatoprost, biphasic human insulin (prb), bortezomib, BR-A-657, BRL-55730, budesonide, busulfan; Calcipotriol, calcipotriol/betamethasone dipropionate, calcium folinate, capecitabine, capravirine, carmustine, caspofungin acetate, cefdinir, certolizumab pegol, CG-53135, chlorambucil, ciclesonide, ciclosporin, cisplatin, clofarabine, clopidogrel hydrogensulfate, clozapine, co-trimoxazole, CP-122721, creatine, CY-2301, cyclophosphamide, cypher, cytarabine, cytolin; D0401, darbepoetin alfa, darifenacin hydrobromide, DASB, desipramine hydrochloride, desloratadine, desvenlafaxine succinate, dexamethasone, didanosine, diquafosol tetrasodium, docetaxel, doxorubicin hydrochloride, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Ecallantide, efalizumab, efavirenz, eletriptan, emtricitabine, enfuvirtide, enoxaparin sodium, estramustine phosphate sodium, etanercept, ethinylestradiol, etonogestrel, etonogestrel/ethinylestradiol, etoposide, exenatide; Famciclovir, fampridine, febuxostat, filgrastim, fludarabine phosphate, fluocinolone acetonide, fluorouracil, fluticasone propionate, fluvastatin sodium, fondaparinux sodium; Gaboxadol, gamma-hydroxybutyrate sodium, gefitinib, gelclair, gemcitabine, gemfibrozil, glibenclamide, glyminox; Haloperidol, heparin sodium, HPV 16/HPV 18 vaccine, human insulin, human insulin; Icatibant, imatinib mesylate, indium 111 (111In) ibritumomab tiuxetan, infliximab, INKP-100, iodine (I131) tositumomab, IoGen, ipratropium bromide, ixabepilone; L-870810, lamivudine, lapatinib, laquinimod, latanoprost, levonorgestrel, licochalcone a, liposomal doxorubicin, lopinavir, lopinavir/ritonavir, lorazepam, lovastatin; Maraviroc, maribavir, matuzumab, MDL-100907, melphalan, methotrexate, methylprednisolone, mitomycin, mitoxantrone hydrochloride, MK-0431, MN-001, MRKAd5 HIV-1 gag/pol/nef, MRKAd5gag, MVA.HIVA, MVA-BN Nef, MVA-Muc1-IL-2, mycophenolate mofetil; Nelfinavir mesilate, nesiritide, NSC-330507; Olanzapine, olmesartan medoxomil, omalizumab, oral insulin, osanetant; PA-457, paclitaxel, paroxetine, paroxetine hydrochloride, PCK-3145, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, perillyl alcohol, pexelizumab, pimecrolimus, pitavastatin calcium, porfiromycin, prasterone, prasugrel, pravastatin sodium, prednisone, pregabalin, prinomastat, PRO-2000, propofol, prostate cancer vaccine; Rasagiline mesilate, rhBMP-2/ACS, rhBMP-2/BCP, rhC1, ribavirin, rilpivirine, ritonavir, rituximab, Ro-26-9228, rosuvastatin calcium, rosuvastatin sodium, rubitecan; Selodenoson, simvastatin, sirolimus, sitaxsentan sodium, sorafenib, SS(dsFv)-PE38, St. John's Wort extract, stavudine; Tacrolimus, tadalafil, tafenoquine succinate, talaglumetad, tanomastat, taxus, tegaserod maleate, telithromycin, tempol, tenofovir, tenofovir disoproxil fumarate, testosterone enanthate, TH-9507, thalidomide, tigecycline, timolol maleate, tiotropium bromide, tipifarnib, torcetrapib, trabectedin, travoprost, travoprost/timolol, treprostinil sodium; Valdecoxib, vardenafil hydrochloride hydrate, varenicline, VEGF-2 gene therapy, venlafaxine hydrochloride, vildagliptin, vincristine sulfate, voriconazole, VRX-496, VX-385; Warfarin sodium; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan; Zanolimumab, zidovudine.
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PMID:Gateways to clinical trials. 1608 22

We show that large surface areas exist for supramolecular chemistry on single-walled carbon nanotubes (SWNTs) prefunctionalized noncovalently or covalently by common surfactant or acid-oxidation routes. Water-soluble SWNTs with poly(ethylene glycol) (PEG) functionalization via these routes allow for surprisingly high degrees of pi-stacking of aromatic molecules, including a cancer drug (doxorubicin) with ultrahigh loading capacity, a widely used fluorescence molecule (fluorescein), and combinations of molecules. Binding of molecules to nanotubes and their release can be controlled by varying the pH. The strength of pi-stacking of aromatic molecules is dependent on nanotube diameter, leading to a method for controlling the release rate of molecules from SWNTs by using nanotube materials with suitable diameter. This work introduces the concept of "functionalization partitioning" of SWNTs, i.e., imparting multiple chemical species, such as PEG, drugs, and fluorescent tags, with different functionalities onto the surface of the same nanotube. Such chemical partitioning should open up new opportunities in chemical, biological, and medical applications of novel nanomaterials.
ACS Nano 2007 Aug
PMID:Supramolecular chemistry on water-soluble carbon nanotubes for drug loading and delivery. 1920 29

We report the synthesis and characterization of DNA-grafted poly(N-isopropylacrylamide) (PNIPAM) micelles, their assembly into multilayered thin films, and the subsequent generation and poly(ethylene glycol) (PEG) functionalization of DNA-PNIPAM microcapsules. Multilayer films were assembled by sequentially depositing DNA-grafted PNIPAM micelles containing the cDNA sequences polyA(30) or polyT(30) (i.e., PNIPAM-A(30) or PNIPAM-T(30)). DNA-polymer microcapsules were obtained by the alternate deposition of PNIPAM-A(30) and PNIPAM-T(30) onto silica particles, followed by removal of the template core. Upon removal of the silica core particle, shrinkage of between 30 and 50% was observed for the microcapsules. The presence of PNIPAM within the DNA-polymer hybrid film reduces the permeability of the microcapsules to macrosolutes (e.g., dextran) compared with microcapsules made solely of DNA. The hydrophobic core of the DNA-grafted PNIPAM micelles was designed to contain alkyne "click" groups, which were exploited to covalently couple azide-bearing low-fouling PEG to the DNA-PNIPAM microcapsules. The combination of hydrophobic and reactive "click" nanodomains, along with the degradability of DNA, offers a multifunctional and versatile DNA-polymer capsule system that is envisioned to find applications in the controlled delivery of therapeutics.
ACS Nano 2009 Jan 27
PMID:Assembly and functionalization of DNA-polymer microcapsules. 1920 71

Carbon nanotubes (CNTs) have been shown to cross cell membranes and can mediate the internalization of macromolecules. These characteristics have constituted CNTs as an exciting new tool for drug delivery and biological sensing. While CNTs exhibit great potential in biomedical and pharmaceutical applications, neither the cell penetration mechanism of CNTs nor the intracellular fate of the internalized CNTs are fully understood. In this study, time-lapse fluorescence microscopy was used to investigate the intracellular distribution of FITC labeled PEGylated single-walled CNTs (FITC-PEG-SWCNTs) in living cells and shown that PEGylated SWCNTs entered the nucleus of several mammalian cell lines in an energy-dependent process. The presence of FITC-PEG-SWCNTs in the cell nucleus did not cause discernible changes in the nuclear organization and had no effect on the growth kinetics and cell cycle distribution for up to 5 days. Remarkably, upon removal of the FITC-PEG-SWCNTs from the culture medium, the internalized FITC-PEG-SWCNTs rapidly moved out of the nucleus and were released from the cells. Thus, the intracellular PEGylated SWCNTs were highly dynamic and the cell penetration of PEGylated SWCNTs appeared as bidirectional. These observations suggest SWCNTs may be used as an ideal nanovector in biomedical and pharmaceutical applications.
ACS Nano 2008 Oct 28
PMID:Reversible accumulation of PEGylated single-walled carbon nanotubes in the mammalian nucleus. 1920 55

We present a method providing synchronized measurements using the two techniques: quartz crystal microbalance with dissipation (QCM-D) monitoring and localized surface plasmon resonance (LSPR). This was achieved by letting a thin gold film perforated with short-ranged ordered plasmon-active nanoholes act as one of the electrodes of a QCM-D crystal. This enabled transmission-mode optical spectroscopy to be used to temporally resolve colorimetric changes of the LSPR active substrate induced upon biomolecular binding events. The LSPR response could thus be compared with simultaneously obtained changes in resonance frequency, Deltaf, and energy dissipation, DeltaD, of the QCM-D device. Since the LSPR technique is preferentially sensitive to changes within the voids of the nanoholes, while the QCM-D technique is preferentially sensitive to reactions on the planar region between the holes, a surface chemistry providing the same binding kinetics on both gold and silica was used. This was achieved by coating the substrate with poly(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG), which was shown to bind in the same manner on silica and gold modified with a carboxyl-terminated thiol. In this way, the combined setup provided new information about structural changes upon PLL-g-PEG adsorption. We also demonstrate subsequent binding of NeutrAvidin and an immunoreaction utilizing biotin-modified IgG. The combined information from the synchronized measurements was also used in a new way to estimate the sensing volume of the LSPR sensor.
ACS Nano 2008 Oct 28
PMID:Synchronized quartz crystal microbalance and nanoplasmonic sensing of biomolecular recognition reactions. 1920 65

Rare earth cerium oxide (ceria) nanoparticles are stabilized using end-functional phosphonated-PEG oligomers. The complexation process and structure of the resulting hybrid core-shell singlet nanocolloids are described, characterized, and modeled using light and neutron scattering data. The adsorption mechanism is nonstoichiometric, yielding the number of adsorbed chains per particle N(ads) = 270 at saturation. Adsorption isotherms show a high affinity of the phosphonate head for the ceria surface (adsorption energy DeltaG(ads) approximately -16kT) suggesting an electrostatic driving force for the complexation. The ease, efficiency, and integrity of the complexation is highlighted by the formation of nanometric sized cerium oxide particles covered with a well anchored PEG layer, maintaining the characteristics of the original sol. This solvating brushlike layer is sufficient to solubilize the particles and greatly expand the stability range of the original sol (<pH 3) up to pH = 9. We underscore two key attributes of the tailored sol: (i) strong UV absorption capability after functionalization and (ii) ability to redisperse after freeze-drying as powder in aqueous or organic solvents in varying concentrations as singlet nanocolloids. This robust platform enables translation of intrinsic properties of mineral oxide nanoparticles to critical end use.
ACS Nano 2008 May
PMID:Redispersible hybrid nanopowders: cerium oxide nanoparticle complexes with phosphonated-PEG oligomers. 1920 84

This paper presents the first steps toward the development of a new type of high-resolution AFM-SECM microscopy which relies on the use of tip-attached redox-labeled polymer chains as mediators to probe the local electrochemical reactivity of a planar substrate at the nanoscale. Submicrometer-sized combined gold AFM-SECM probes were functionalized by linear, nanometer-sized, flexible, PEG3400 chains bearing a ferrocene (Fc) redox label at their free end. Analysis of the force and current approach curves recorded when such Fc-PEGylated probes (tips) were approached to a bare gold substrate allowed the presence of the Fc-PEG chains at the very tip end of the combined probes to be specifically demonstrated. It also allowed the chain coverage, configuration, and dynamics to be determined. When the Fc-PEGylated probe is positioned some approximately 5 nm above the substrate, only a few hundred chains are actually electrochemically contacting the surface, thus reducing the size of the tip-substrate interaction area to 20-40 nm. Most importantly, we have shown that the tip-borne PEG chains are flexible enough to allow their Fc heads to efficiently "sense" locally the electrochemical reactivity of the substrate, thus validating the working principle of the new AFM-SECM microscopy we propose. This innovative microscopy, we label Tarm (for tip-attached redox mediator)/AFM-SECM, should be particularly suitable for probing the activity of slowly functioning nanometer-sized active sites on surfaces, such as individual enzyme molecules, because it is, by design, free of the diffusional constraints which hamper the characterization of such nanosystems by classical SECM.
ACS Nano 2009 Apr 28
PMID:Electrochemical atomic-force microscopy using a tip-attached redox mediator. Proof-of-concept and perspectives for functional probing of nanosystems. 1928 Dec 24

Tailoring the interaction between surfaces and nanoparticles (NPs) affords great opportunities for a range of applications, including sensors, information storage, medical diagnostics, and filtration membranes. In addition to controlling local ordering and microscale patterning of the NPs, manipulating the temporal factors determining the strength of the interaction between NP and surface enables dynamic modulation of these structural characteristics. In this contribution we demonstrate robust polymer brush-NP hybrids that exhibit both reversible swelling and reversible NP adsorption/desorption. Polymer brush functionality is tailored through post-functionalization of poly(2-hydroxyethyl methacrylate) (PHEMA) brushes on flat solid substrates with alpha-amine conjugates ranging from perfluoro alkanes to poly(ethylene glycol) of varying molecular weights. The type of functionality controls NP affinity for the surfaces. In the case of poly(ethylene glycol) (PEG), the molecular weight (MW) of the PEG dictates adsorption and desorption phenomena. Higher MW PEG chains possess increased binding affinity toward NPs, which leads to higher relative Au-NP densities on the PHEMA-g-PEG brushes and concurrent sluggish desorption of NPs by thermal stimulus. Adsorption and desorption phenomena are further modulated by NP size yielding a system where adsorption and desorption are controlled by a delicate balance between the competitive energetics of polymer brush chelation versus solvation.
ACS Nano 2009 Apr 28
PMID:Tuning gold nanoparticle-poly(2-hydroxyethyl methacrylate) brush interactions: from reversible swelling to capture and release. 1933 84

Honokiol (HK) can efficiently inhibit the growth of tumors. However, its clinical applications have been restricted by its extreme hydrophobicity. We hope to improve its water solubility by nanotechnology. And we wonder whether a novel honokiol nanoparticles-loaded thermosensitive poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) hydrogel (HK-hydrogel) could improve the therapeutic efficacy on malignant pleural effusion (MPE). To evaluate the therapeutic effects of HK-hydrogel on MPE, MPE-bearing mice were administered intrapleurally with HK-hydrogel, HK nanoparticles (HK-NP), blank hydrogel, or normal saline (NS) at days 4 and 11 after Lewis lung carcinoma (LLC) cells inoculation, respectively. Pleural tumor foci and survival time were observed, and antiangiogenesis of HK-hydrogel was determined by CD31. Histological analysis and assessment of apoptotic cells were also conducted in tumor tissues. HK-hydrogel reduced the number of pleural tumor foci, while prolonging the survival time of MPE-bearing mice, more effectively, as compared with control groups. In addition, HK-hydrogel successfully inhibited angiogenesis as assessed by CD31 (P < 0.05). Histological analysis of pleural tumors exhibited that HK-hydrogel led to the increased rate of apoptosis. This work is important for the further application of HK-hydrogel in the treatment of MPE.
ACS Nano 2009 Dec 22
PMID:Honokiol nanoparticles in thermosensitive hydrogel: therapeutic effects on malignant pleural effusion. 1992 11


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