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Objective: Dentin hypersensitivity (DH) is characterized by a short, sharp pain in response to a thermal or tactile stimulus. The application of desensitizing agents such as GLUMA and laser is a non-invasive and safe approach to decrease sensitivity. The evidence for the efficacy of GLUMA desensitizer compared to laser desensitization in patients with DH was evaluated for 6 months., Design: In March 2022, an electronic search of PubMed, Scopus, and Web of Science databases was conducted. Articles published in English that compared GLUMA and laser in the treatment of DH with a follow-up of 6 months or more were included. Randomized, non-randomized controlled trials, and clinical trials were included. Risk of bias assessment tools developed by the Cochrane collaboration ROB 2 and ROBINS-I were used to assess the quality of studies. The GRADE assessment method was used to assess the certainty of evidence., Results: About 36 studies were identified in the search results. After applying the predefined eligibility criteria, eight studies with 205 participants and 894 sites were included in this review. Of the eight studies, four were judged to be at high risk of bias, three had some concerns, and one had a serious risk of bias. The certainty of the evidence was graded as low., Conclusion: Based on limited evidence, GLUMA and laser appear to be equally effective in providing relief from DH. GLUMA showed an immediate effect and provided pain relief. Over the course of a week, laser showed long-term stable results. GLUMA is effective in providing immediate relief.

There are many proteins and enzymes in the human body, and their dysfunction can lead to the emergence of a disease. The use of proteins as a drug is common in various diseases such as diabetes. Proteins are hydrophilic molecules whose spatial structure is critical to their correct function. There are different ways for the administration of proteins. Protein structures are degraded by gastric acid and enzymes in the gastrointestinal tract and have a slight ability to permeate from the gastrointestinal epithelium due to their large hydrophilic nature. Therefore, their oral use has limitations. Since the oral route for the administration of drugs is one of the best and easiest routes for patients, many studies have been done to increase the stability, penetration, and ultimately, the bioavailability of proteins through oral administration. One of the studied strategies for oral delivery of protein is the use of pH-sensitive polymer-based carriers. These carriers use different pH-sensitive polymers, such as eudragit®, chitosan, dextran, and alginate. The use of pH-sensitive polymer- based carriers by protecting the protein from stomach acid (low pH) and degrading enzymes, increasing permeability and maintaining the spatial structure of the protein, leads to increased bioavailability. In this review, we focus on the various polymers used to prepare pH-sensitive polymer- based carriers for the oral delivery of proteins., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Water-soluble polymer-drug conjugates were obtained and analyzed towards their potential use as prodrugs for two hydrophobic antipsoriatic agents, including methotrexate (MTX) and acitretin (AC). The conjugation efficacy of MTX decreased with a decreasing molar ratio of N,N-dimethylaminoethyl methacrylate (DMAEMA) repeating units in the polymethacrylic chains. Cytotoxicity of positively charged (from +5 to +10 mV) nano- and microparticles (3-1500 nm in DMEM at 37 °C) were estimated by in vitro MTT and Annexin-V apoptosis assays on Me45, NHDF, HaCaT and BEAS-2B cell lines. Further, cell cycle analysis revealed arrest in G0/G1 phase in melanoma cells, while neither apoptosis induction nor cell cycle arrest occurred in normal epidermal and epithelial cells. Tested conjugates displayed a novel cytostatic effect in Me45 cells and a pro-apoptotic effect in HaCaT cells. Epithelial BEAS-2B cells were the most sensitive to the tested conjugates and responded via induction of necrosis. Cell line models allowed for characterization of the biologically relevant potential action of pro-drugs. Additionally, a skin in vitro evaluation assay provided the first known evidence of side-effect reduction with pro-drug use. Histological examinations confirmed the lack of negative effects of conjugates on the skin and showed no irritating properties., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: The aim of this randomized, controlled, prospective clinical trial was to evaluate the performances of two different universal adhesives and one etch-rinse adhesive for restoration of non-carious cervical lesions (NCCLs)., Material and Methods: Twenty patients with at least seven NCCLs were enrolled. Lesions were divided into seven groups according to adhesive systems and application modes: GSE: GLUMA Universal-self-etch, GSL: GLUMA Universal-selective etching, GER: GLUMA Universal-etch-and-rinse, ASE: All-Bond Universal-self-etch, ASL: All-Bond Universal-selective etching, AER: All-Bond Universal-etch-and-rinse, SBE (Control): Single Bond2-etch-and-rinse. A total of 155 NCCLs were restored with a nano hybrid composite (Tetric N-Ceram). Restorations were scored with regard to retention, marginal discoloration, marginal adaptation, recurrent caries and post-operative sensitivity using modified United States Public Health Service (USPHS) criteria after one week, 6, 12 and 24 months. Statistical evaluations were performed using Chi-square tests (p=0.05)., Results: The recall rate was 81.9% after the 24-month follow-up. The cumulative retention rates for self-etch groups (GSE: 72.2%, ASE:75%) were significantly lower than other experimental groups (GSL: 93.7%, GER: 100%, ASL: 94.1%, AER: 100%, SBE: 100%) at the 24-month follow-up (p<0.05). Regarding marginal adaptation and marginal discoloration, GSE and ASE groups demonstrated more bravo scores after 6 and 12-month observations but differences were not significant (p>0.05). Only one restoration from ASL group demonstrated post-operative sensitivity at 6 and 12-month observations. No secondary caries was observed on the restorations at any recall. At the end of 24-month observations, no significant differences were detected among groups regarding any of the criteria assessed, except retention., Conclusion: GLUMA Universal and All-Bond Universal showed better results in etch-and-rinse and selective etching mode compared to the self-etch mode regarding retention. Etch-and-rinse and selective etching application modes of the current universal adhesives tended to provide better clinical outcomes considering the criteria evaluated at the end of 24-month evaluation.

The breakdown of the polymeric component of contemporary composite dental restorative materials compromises their longevity, while leachable compounds from these materials have cellular consequences. Thus, a new generation of composite materials needed to be designed to have a longer service life and ensure that any leachable compounds are not harmful to appropriate cell lines. To accomplish this, we have developed concurrent thiol-ene-based polymerization and allyl sulfide-based addition-fragmentation chain transfer chemistries to afford cross-linked polymeric resins that demonstrate low shrinkage and low shrinkage stress. In the past, the filler used in dental composites mainly consisted of glass, which is biologically inert. In several of our prototype composites, we introduced fluorapatite (FA) crystals, which resemble enamel crystals and are bioactive. These novel prototype composites were benchmarked against similarly filled methacrylate-based bisphenol A diglycidyl ether dimethacrylate / triethylene glycol dimethacrylate (bisGMA/TEGDMA) composite for their cytotoxicity, mechanical properties, biofilm formation, and fluoride release. The leachables at pH 7 from all the composites were nontoxic to dental pulp stem cells. There was a trend toward an increase in total toughness of the glass-only-filled prototype composites as compared with the similarly filled bisGMA/TEGDMA composite. Other mechanical properties of the glass-only-filled prototype composites were comparable to the similarly filled bisGMA/TEGDMA composite. Incorporation of the FA reduced the mechanical properties of the prototype and bisGMA/TEGDMA composite. Biofilm mass and colony-forming units per milliliter were reduced on the glass-only-filled prototype composites as compared with the glass-only-filled bisGMA/TEGDMA composite and were significantly reduced by the addition of FA to all composites. Fluoride release at pH 7 was greatest after 24 h for the bisGMA/TEGDMA glass + FA composite as compared with the similarly filled prototypes, but overall the F - release was marginal and not at a concentration to affect bacterial metabolism.

Objective: Reports indicate Gluma and Duraphat are commonly used in-office agents to treat hypersensitive teeth. Considering this, the aim of this paper is to compare Gluma and Duraphat using a randomized controlled trial, meta-analysis collating evidences from previous studies and trial sequential analysis., Materials and Methods: Thirty-eight participants were randomized. Hypersensitivity and visual analog scale (VAS) scores were recorded at baseline, 5 min and 7 days. Oral health-related quality of life (OHIP) questionnaire was administered at baseline and 7 days. Statistical analysis was performed to identify significant differences between the variables. For the meta-analysis, electronic data bases were searched and eligible data was extracted and analysed using RevMan 5.0. Trial sequential analysis was performed using O'Brien-Fleming boundary approach for the primary outcome., Results: Both agents caused significant reduction in hypersensitivity and VAS score at 5 min and 7 days in the randomized trial with no superiority. The quality of life significantly improved in patients treated with both the agents. Four studies including the present trial in meta-analysis and trial sequential analysis indicated that Gluma produced significant reduction in VAS scores at 7 days., Conclusion: Gluma produces significant reduction in hypersensitivity at 7 days post treatment compared with Duraphat. There is definite lack of evidence on the long-term effect of these agents., Clinical Relevance: This paper provides strong evidence on the use of Gluma for hypersensitive teeth. This also is a way forward to future research on long-term effects, adverse effects and cost-effectiveness studies.

Objective: To evaluate the risk and intensity of bleaching-induced tooth sensitivity (TS) after in-office bleaching following topical application of a resin-based glutaraldehyde desensitizer., Methods: Thirty-three patients were randomly assigned to the experimental (Gluma Desensitizer Liquid, Heraeus Kulzer, Hanau, Germany) and placebo groups. The placebo or Gluma Desensitizer Liquid was applied for one minute prior to application of an in-office bleaching gel. Bleaching was performed with 35% hydrogen peroxide gel (three applications × 15 minutes each) over two sessions, one week apart. The color of the anterior teeth was evaluated before and 21 days after treatment using the VITA Classical shade guide, Bleachedguide 3D, and Easyshade spectrophotometer. TS during and after the bleaching was recorded according to the visual analog (VAS) and numerical rating (NRS) scales. All data were submitted to statistical analysis (α=0.05)., Results: There was no significant difference in absolute risk or intensity of TS between the two groups (risk and VAS, p=0.93 and 0.31, respectively; NRS, p≥0.45). At the end of the bleaching protocol, tooth whitening was observed in both groups, as evident from color change in shade guide units (ΔSGU, 4.1-7.1; both guides) and overall color change (ΔE, 7.4-9.3 units); however, there were no significant differences in whitening between the two groups ( p>0.11)., Conclusion: Gluma Desensitizer Liquid was not able to reduce the risk or intensity of TS. Bleaching efficacy was not affected by application of the desensitizer.

Objective: To evaluate the clinical performance of Scotchbond Universal (3M Oral Care) and Prime & Bond Elect (Dentsply Sirona) in the restoration of noncarious cervical lesions (NCCLs)., Methods and Materials: This was a randomized controlled clinical trial involving 63 subjects. Two hundred and three NCCLs were restored using Scotchbond Universal and Prime & Bond Elect using both an etch-and-rinse and a self-etch technique. Lesions were notch-shaped NCCLs, and the restorations were placed without any mechanical retention. Restorations were finished immediately after placement and scored with regard to retention, marginal discoloration, marginal adaptation, and secondary caries. Similar assessment of the restorations was performed 18 months after placement. Logistic regression was performed for each outcome separately with a compound symmetric variance-covariance structure assumed to consider a correlation of restorations within subjects. All analyses were conducted using SAS version 9.4 (SAS Inc)., Results: One hundred and fifty-eight teeth (77.8% of the restorations placed) in 46 subjects (73% of subjects enrolled) were available for the 18-month follow-up. A statistically significant difference was reached only for the comparison Scotchbond Universal/self-etch (SU&#95;SE) and Prime & Bond Elect/etch-and-rinse (PBE&#95;E&R) groups ( p=0.01), where a restoration with SU&#95;SE was 66% less likely to maintain a score of Alpha for marginal discoloration than a restoration performed with PBE&#95;E&R., Conclusions: Scotchbond Universal and Prime & Bond Elect presented acceptable clinical performance after 18 months of clinical service. However, Scotchbond Universal, when applied with a self-etch approach, did demonstrate a relatively high level of marginal discoloration when compared to the other groups.

Resin cements are often used for single crown cementation due to their physical properties. Self-adhesive resin cements gained widespread due to their simplified technique compared to regular resin cement. However, there is lacking clinical evidence about the long-term behavior of this material. The aim of this prospective clinical trial was to assess the survival rates of metal-ceramic crowns cemented with self-adhesive resin cement up to six years. One hundred and twenty-nine subjects received 152 metal-ceramic crowns. The cementation procedures were standardized and performed by previously trained operators. The crowns were assessed as to primary outcome (debonding) and FDI criteria. Statistical analysis was performed using Kaplan-Meier statistics and descriptive analysis. Three failures occurred (debonding), resulting in a 97.6% survival rate. FDI criteria assessment resulted in scores 1 and 2 (acceptable clinical evaluation) for all surviving crowns. The use of self-adhesive resin cement is a feasible alternative for metal-ceramic crowns cementation, achieving high and adequate survival rates.

Novel "zwitterionic" gold nanorods (Au NRs) were constructed through a facile ligand exchange process between cetyltrimethylammonium bromide (CTAB)-Au NRs and the zwitterionic block polymer {poly(2-methacryloyloxyethyl phosohorylcholine)-b-poly(lipoic methacrylate) (pMPC-b-pLA)}. In vitro, they exhibited low dark cytotoxicity and a high therapeutic efficacy to cancer cells. Their blood circulation half-life in vivo (t 1/2 , ∼10 h) was 20-fold longer than that of CTAB-Au NRs (t 1/2 , <30 min). After intravenous administration, they accumulated in tumour sites via an enhanced permeability and retention (EPR) effect and enabled destruction of human xenograft tumours in mice after exposure of the tumour location to NIR laser irradiation at 808 nm. These studies showed that the "zwitterionic" Au NRs had low toxicity and high photothermal efficacy both in vitro and in vivo due to the suprahydrophilic, biocompatible zwitterionic polymer coating layer. They may have the potential to be a promising NIR PTT agent in the biomedical field.

Objective: This study aimed to compare the efficacy of a 940-nm diode laser and Gluma desensitizer on post-preparation sensitivity of prepared teeth., Materials and Methods: Twenty patients with 76 teeth participated in the study. For each patient, prepared molar or premolar in one quadrant were individually irradiated by laser. In the symmetrical quadrant, Gluma was applied onto the prepared teeth. No treatment was performed in the control group. Temporary crowns were placed after preparation. Pain response to tactile stimulus was assessed at one day, one week, and two weeks using visual analog scale (VAS). Intergroup comparisons were made with Kruskal Wallis test (p < 0.05)., Results: Mean VAS scores of the control group were statistically higher than laser and Gluma groups (p < 0.017). The difference between VAS scores of the laser and Gluma groups was statistically insignificant (p > 0.05)., Conclusions: A significant reduction in level of sensitivity after both treatments was observed. The reduction of sensitivity with Gluma was not significantly superior to laser. No significant additional reduction occurred in level of sensitivity from the first day to the second week after both treatments., Clinical Significance: The application of Gluma or a 940-nm diode laser may be considered as effective in reducing sensitivity after tooth preparation without superiority of either method. (J Esthet Restor Dent 28:405-411, 2016)., (© 2016 Wiley Periodicals, Inc.)

Conjugating therapeutic proteins and peptides to poly(ethylene glycol) (PEG) can improve their pharmacokinetics and therapeutic potential. However, PEGylation suffers from non-specific conjugation, low yield and immunogenicity. Herein we report a new and general methodology to synthesize a protein-polymer conjugate with site-specificity, high yield and activity, long circulation half-life and excellent therapeutic efficacy. A phospholipid polymer, poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), was grown solely from the C-terminus of interferon-alpha to form a site-specific (C-terminal) and stoichiometric (1:1) PMPC conjugate of interferon-alpha in high yield. Notably, the PMPC conjugate showed 194- and 158-fold increases in systemic exposure and tumor uptake as compared with interferon-alpha, respectively. The in vitro antiproliferative bioactivity of the PMPC conjugate was 8.7-fold higher than that of PEGylated interferon-alpha (PEGASYS). In a murine cancer model, the PMPC conjugate completely inhibited tumor growth and cured 75% mice, whereas at the same dose, no mice treated with interferon-alpha or PEGASYS survived. We believe that this new approach to synthesize C-terminal protein conjugates of PMPC may be applicable to a large subset of protein and peptide drugs, thereby providing a general platform for the development of next-generation protein therapeutics., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Previously, poly(methacrylic acid-co-methyl methacrylate) (MAA) beads were shown to improve vessel formation with a concomitant increase in the expression of the sonic hedgehog (Shh) gene, a pleiotropic factor implicated in vascularization. The aim of this study was to follow up on this observation in the absence of the confounding factors of diabetes in non-diabetic Shh-Cre-eGFP/Ptch1-LacZ mice; in this mouse, expression of GFP and β-Gal is consistent with the transcription patterns of Shh and its receptor patched 1 (Ptch1), respectively. In agreement with studies in diabetic males, MAA beads improved vascularization in large (15 mm × 15 mm) wounds in non-diabetic males at day 7. Shh pathway activation was suggested, as the numbers of GFP+ (Shh) and β-Gal+ (Ptch1, a target of the pathway) cells increased in the granulation tissue. Shh signaling pathway modulation was also suggested in the healthy skin surrounding the wound bed, as evidenced by an increase in the number of GFP+ and β-Gal+ cells in males at day 4. Gene expression analysis of the wounds confirmed increase in Ptch1 and showed the upregulation of a downstream transcription factor Gli3, involved in the vascular effect of the Shh pathway, implicating the pathway in the effect of MAA beads. The efficacy of MAA beads was also investigated in females; MAA beads modulated the Shh pathway within granulation tissue similarly as in males, but had no enhancement effect on the healthy skin and on vascularization. We believe that understanding the molecular and cellular mechanisms of MAA-based biomaterials and testing the efficacy of therapeutics in both sexes will inform the development of novel therapeutic biomaterials., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Biodegradable materials used for drug delivery are of great demand due to their ability to degrade into low molecular weight species and further excrete from the body by metabolism. Herein, we report a new kind of zinc(II) crosslinked poly(methacrylic acid) nanohydrogels (ZCLNs) inspired by zinc finger proteins with dual stimuli-triggered degradation (glutathione and pH) for the first time. Compared with the disulfide bond crosslinked nanohydrogels, this new kind of ZCLNs is beneficial to the degradation of a wide range of cells, including normal cells. Ex vivo fluorescence images showed that the DOX-loaded folate-PEG conjugated zinc(II)-crosslinked polymeric nanohydrogels (FPZCLNs-15) preferentially accumulated in tumor tissue and the accumulation in normal tissues was much less compared with DOX-loaded PZCLNs-15 (non-targeted nanohydrogels) and free DOX, the FPZCLNs-15 (targeting system) delivered DOX to the tumor site with approximately 3.6- and 1.6-fold higher than free DOX and PZCLNs-15, respectively. Meanwhile, the PZCLNs-15 and FPZCLNs-15 reduced the concentration of DOX in the heart by 3.2- and 5.0-fold respectively, as compared to the free DOX. Moreover, a superior tumor growth inhibition and negligible damage to normal organs like the heart and kidney, which is reported to be vulnerable to DOX-associated side effects, are further demonstrated., (Copyright © 2016 Elsevier B.V. All rights reserved.)

To integrate biological imaging and multimodal therapies into one platform for enhanced anti-cancer efficacy, we have designed a novel core/shell structured nano-theranostic by conjugating photosensitive Au25(SR)18 - (SR refers to thiolate) clusters, pH/temperature-responsive polymer P(NIPAm-MAA), and anti-cancer drug (doxorubicin, DOX) onto the surface of mesoporous silica coated core-shell up-conversion nanoparticles (UCNPs). It is found that the photodynamic therapy (PDT) derived from the generated reactive oxygen species and the photothermal therapy (PTT) arising from the photothermal effect can be simultaneously triggered by a single 980 nm near infrared (NIR) light. Furthermore, the thermal effect can also stimulate the pH/temperature sensitive polymer in the cancer sites, thus realizing the targeted and controllable DOX release. The combined PDT, PTT and pH/temperature responsive chemo-therapy can markedly improve the therapeutic efficacy, which has been confirmed by both in intro and in vivo assays. Moreover, the doped rare earths endow the platform with dual-modal up-conversion luminescent (UCL) and computer tomography (CT) imaging properties, thus achieving the target of imaging-guided synergistic therapy under by a single NIR light., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

It was recently reported that ethanolamine-functionalized poly(glycidyl methacrylate) (PGEA) possesses great potential applications in gene therapy due to its good biocompatibility and high transfection efficiency. Importing responsivity into PGEA vectors would further improve their performances. Herein, a series of responsive star-shaped vectors, acetaled β-cyclodextrin-PGEAs (A-CD-PGEAs) consisting of a β-CD core and five PGEA arms linked by acid-labile acetal groups, were proposed and characterized as therapeutic pDNA vectors. The A-CD-PGEAs owned abundant hydroxyl groups to shield extra positive charges of A-CD-PGEAs/pDNA complexes, and the star structure could decrease charge density. The incorporation of acetal linkers endowed A-CD-PGEAs with pH responsivity and degradation. In weakly acidic endosome, the broken acetal linkers resulted in decomposition of A-CD-PGEAs and morphological transformation of A-CD-PGEAs/pDNA complexes, lowering cytotoxicity and accelerating release of pDNA. In comparison with control CD-PGEAs without acetal linkers, A-CD-PGEAs exhibited significantly better transfection performances.

The wear and creep deformation resistances of polymeric orthopedic bearing materials are both important for extending their longevity. In this study, we evaluated the wear and creep deformation resistances, including backside damage, of different polyethylene (PE) materials, namely, conventional PE, cross-linked PE (CLPE), and poly(2-methacryloyloxyethyl phosphorylcholine)- (PMPC-) grafted CLPE, through wear tests and finite element analysis. The gravimetric and volumetric degrees of wear of disks (3 or 6 mm in thickness) of these materials against a cobalt-chromium-molybdenum alloy pin were examined using a multidirectional pin-on-disk tester. Cross-linking and PMPC grafting decreased the gravimetric wear of the PE disks significantly. The volumetric wear at the bearing surface and the volumetric penetration in the backside of the 3-mm thick PE disk were higher than those of the 6-mm thick PE disk, regardless of the bearing material. The geometrical changes induced in the PE disks consisted of creep, because the calculated internal von Mises stress at the bearing side of all disks and that at the backside of the 3-mm thick disks exceeded their actual yield strengths. A highly hydrated bearing surface layer, formed by PMPC grafting, and a cross-linking-strengthened substrate of adequate thickness are essential for increasing the wear and creep deformation resistances.

Glutaraldehyde/2-Hydroxyethylmethacrylate (GLUMA) is a chemical frequenty used for desensitization of teeth and has other uses as suggested in the literature. Some newer recommendations have been made relative to its use during tooth preparation, as a disinfectant, rewetting during bonding, prior to cementation of crowns and bridges, and in dealing with pulpal exposures. This article will explore the science behind these and other applications for this chemical and its effect on the tooth structure and its local environment.

Background and Purpose: We have developed a new thermosensitive liquid embolic agent, PIB nanogel, that can be solidified at body temperature. We thus further investigated the distribution, durability of vascular occlusion, and inflammatory reactions of PIB in embolization of the renal artery of rabbits., Materials and Methods: The bilateral renal arteries of 9 rabbits were first embolized with PIB at different injection rates. The distribution pattern of PIB was investigated by contact radiography and histology 1 hour after embolization. The right renal arteries of 20 rabbits were then embolized with PIB at the proper injection rate. Angiography and pathologic examination of the kidneys were performed at 1 week and 1, 2, and 3 months after embolization to evaluate the long-term outcomes., Results: With the injection rate increasing, PIB could reach the more distal branch of the renal artery. The proper injection rate was chosen as 0.10 mL/s due to the homogeneous distribution of PIB from the main renal artery to the precapillary level at this rate. During a 3-month follow-up observation period, no angiographic recanalization was observed. Histologically, we found no disruption of the vessel wall or subintimal bleeding, no extravasation of PIB, and no evidence of neovascularization. Moreover, there was only a mild inflammatory response, manifested by few lymphocytic and monocellular infiltration, without foreign body granuloma formation., Conclusions: Embolization of the renal artery with PIB was easy and controllable, which could lead to a homogeneous and persistent occlusion without severe inflammatory changes. PIB might be a suitable material for intravascular embolization.

A novel actively targeted polymer carrier for anticancer drugs based on an N-(2-hydroxypropyl)methacrylamide copolymer (PHPMA) is proposed. An oligopeptide sequence GE7, attached to the polymer, is a specific ligand for the EGF receptor overexpressed on most tumor cells. Co-attachment of selected chemotherapeutics will therefore lead to formation of tumor-specific polymer therapeutics, further enhanced by the EPR effect. FACS measurements prove elevated binding activity of the fluorescently labeled PHPMA/GE7 conjugate in EGFR-rich cells (FaDu, MCF-7), compared to conjugates of scrambled peptides. Cell lines with low EGFR level (SW620, B16F10) bind the GE7 conjugate significantly less., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

When the intervertebral disc is removed to relieve chronic pain, subsequent segment stabilization should restore the functional mechanics of the native disc. Because of partially constrained motions and the lack of intrinsic rotational stiffness ball-on-socket implants present many disadvantages. Composite disc substitutes mimicking healthy disc structures should be able to assume the role expected for a disc substitute with fewer restrictions than ball-on-socket implants. A biomimetic composite disc prototype including artificial nucleus fibre-reinforced annulus and endplates was modelled as an L4-L5 disc substitute within a L3-L5 lumbar spine finite element model. Different device updates, i.e. changes of material properties fibre distributions and volume fractions and nucleus placements were proposed. Load- and displacement-controlled rotations were simulated with and without body weight applied. The original prototype reduced greatly the flexibility of the treated segment with significant adjacent level effects under displacement-controlled or hybrid rotations. Device updates allowed restoring large part of the global axial and sagittal rotational flexibility predicted with the intact model. Material properties played a major role, but some other updates were identified to potentially tune the device behaviour against specific motions. All device versions altered the coupled intersegmental shear deformations affecting facet joint contact through contact area displacements. Loads in the bony endplates adjacent to the implants increased as the implant stiffness decreased but did not appear to be a strong limitation for the implant biomechanical and mechanobiological functionality. In conclusion, numerical results given by biomimetic composite disc substitutes were encouraging with greater potential than that offered by ball-on-socket implants.

Purpose: To compare the desensitizing effects of a glutaraldehyde-based desensitizing system (Gluma) and an Er:YAG laser treatment on cervically exposed hypersensitive dentin., Methods: A total of 22 subjects (mean age: 39 +/- 13.7 years; 15 females, 7 males) suffering from cervical dentin hypersensitivity was included in a prospective, split-mouth clinical study. The teeth were treated on one side of the mouth with the glutaraldehyde-based desensitizing system and on the other side with the Er:YAG laser. Sensitivity perception was recorded before treatment (baseline), during and immediately after treatment, after 1 week, 1 month, 3 months and 6 months. The subjects were asked to rate the sensitivity experienced during air stimulation by placing a mark on a visual analogue scale (VAS)., Results: Both techniques showed an effective reduction of cervical dentin hypersensitivity. The subjects experienced equal improvements compared to their status before and 6 months after treatment with both methods (P<0.001).

The authors report their experience with the application of the local antiseptic preparation Ambipor for the treatment of operative wound infection in the patients presenting with malignant neoplasms. Ambipor was used in 23 patients receiving surgical treatment of locally advanced intranasal and paranasal tumours. It was shown that the application of ambipor allows decreasing the risk of development of wound infection in the postoperative period.

Background: Different oral formulations of 'mesalazine (mesalamine)' may have different efficacy in distal ulcerative colitis., Aim: To evaluate the efficacy of mesalazine granules (Salofalk granules) vs. mesalazine tablets (Salofalk tablets) as induction therapy in patients with distinct extensions of ulcerative colitis., Methods: A pooled analysis of 705 patients from four prospective, randomised, double-blind phase III trials was performed. The efficacy of 8 weeks' induction with 3 g/day mesalazine granules [3 g once daily (o.d.) or 1 g three times daily (t.d.s)] vs. 3 g/day mesalazine tablets (1 g t.d.s.) was compared in terms of clinical remission (CR: CAI ≤ 4) and endoscopic remission (ER: EI ≤ 3) (both according to Rachmilewitz) in subgroups with pancolitis, left-sided colitis, or proctosigmoiditis., Results: Mesalazine granules were equipotent to mesalazine tablets in pancolitis regarding CR (72% vs. 71%, P = 0.909) and ER (58% vs. 49%, P = 0.338). In left-sided colitis, both mesalazine formulations were equipotent regarding CR (66% vs. 67%; P = 0.843) but mesalazine granules were superior regarding ER (56% vs. 37%; P = 0.025). In proctosigmoiditis, mesalazine granules were significantly more effective than mesalazine tablets regarding CR (78% vs. 55% P < 0.001) and ER (67% vs. 43% P < 0.001). Furthermore, o.d. application of mesalazine granules was more effective than t.d.s. dosing in left-sided colitis (CR 73% vs. 62%, P = 0.181; ER 71% vs. 48% P = 0.005) and proctosigmoiditis (CR 86% vs. 73%, P = 0.020; ER 75% vs. 61%, P = 0.021), but not in pancolitis., Conclusion: This pooled analysis supports the hypothesis that mesalazine granules are superior to mesalazine tablets in induction of remission in distal colitis and should be taken once daily., (© 2011 Blackwell Publishing Ltd.)

Cutaneous leishmaniasis (CL) is a neglected tropical disease that causes prominent skin scaring. No water soluble, non-toxic, short course and low cost treatment exists. We developed a new water soluble amphotericin B-polymethacrylic acid (AmB-PMA) using established and scalable chemistries. AmB-PMA was stable for 9 months during storage. In vitro, it was effective against Leishmania spp. promastigotes and amastigote infected macrophages. It was also less toxic and more effective than deoxycholate-AmB, and similar to liposomal AmB. Its in vivo activity was determined in both early and established CL lesion models of Leishmania major infection in genetically susceptible non-healing BALB/c mice. Intradermal AmB-PMA at a total dose of 18 mg of AmB/kg body weight led to rapid parasite killing and lesion healing. No toxicity was seen. No parasite relapse occurred after 80 days follow-up. Histological studies confirmed rapid parasite clearance from macrophages followed by accelerated fibroblast mediated tissue repair, regeneration and cure of the infection. Quantitative mRNA studies of the CL lesions showed that accelerated healing was associated with increased Tumour Necrosis Factor-α and Interferon-γ, and reduced Interleukin-10. These results suggest that a cost-effective AmB-PMA could be used to pharmacologically treat and immuno-therapeutically accelerate the healing of CL lesions., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Polymethylmethacrylate (PMMA) assisted ventral discectomy has been criticized for high rates of graft migration and pseudarthrosis when compared with various other fusion procedures for the treatment of cervical degenerative disc disease (DDD), therefore rendering it not the preferred choice of treatment today. Recently however spine surgery has been developing towards preservation rather than restriction of motion, indicating that fusion might not be necessary for clinical success. This study presents a long term comparison of clinical and radiological data from patients with pseudarthrosis and solid arthrodesis after PMMA assisted ventral discectomy was performed., Methods: From 1986 to 2004 416 patients underwent ventral discectomy and PMMA interposition for DDD. The clinical and radiological outcome was assessed for 50 of 127 eligible patients after a mean of 8.1 years. Based on postoperative radiographs the patients were dichotomized in those with a pseudarthrosis (group A) and those with solid arthrodesis (group B)., Results: Pseudarthrosis with movement of more than 2 of the operated segment was noted in 17 cases (group A). In 33 cases no movement of the vertebral segment could be detected (group B). The analysis of the clinical data assessed through the neck disability index (NDI), the visual analogue scale (VAS) of neck and arm pain and Odom's criteria did not show any significant differences between the groups.Patients from group B showed a trend to higher adjacent segment degeneration (ASD) than group A (p = 0.06). This correlated with the age of the patients., Conclusions: PMMA assisted discectomy shows a high rate of pseudarthrosis. But the clinical long-term success does not seem to be negatively affected by this.

Tumor progression is dependent on neoangiogenesis for blood supply. Neovasculature over-express α(v)β(3) integrins which recognize the Arg-Gly-Asp (RGD) sequence in the extracellular matrix. N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers containing side chains terminated in cyclic RGD analogs such as RGDfK show increased accumulation in prostate tumors. Geldanamycin and their derivatives (e.g., aminohexylgeldanamycin (AH-GDM)) are benzoquinone ansamycins that have both antiangiogenic and antitumor activity. In this work the antiangiogenic and antitumor activities of targetable HPMA copolymer-RGDfK-AH-GDM conjugates were compared with non-targetable systems in vitro and in vivo. Copolymer-drug conjugates containing RGDfK in the side chains showed superior activity against endothelial and prostate cancer cell lines in vitro, as well as higher inhibition of angiogenesis in vivo. At equimolar doses of the drug, the RGDfK containing conjugates showed significantly higher antitumor activity in nude mice bearing DU-145 human prostate cancer xenografts. These findings suggest the utility of HPMA copolymer-RGDfK conjugates for targeted delivery of geldanamycin analogs with a dual mode of action., (Copyright © 2011 Elsevier B.V. All rights reserved.)

We report the synthesis of poly(methacrylic acid)-co-(oleyl methacrylate) with three different amounts of oleyl methacrylate and compare the ability of these polymers with that of poly(methacrylic acid)-co-(cholesteryl methacrylate) (PMA(c)) to noncovalently anchor liposomes to polymer layers. We subsequently assembled ∼1 μm diameter PMA(c)-based capsosomes, polymer hydrogel capsules that contain up to ∼2000 liposomal subcompartments, and investigate the potential of these carriers to deliver water-insoluble drugs by encapsulating two different antitumor compounds, thiocoraline or paclitaxel, into the liposomes. The viability of lung cancer cells is used to substantiate the cargo concentration-dependent activity of the capsosomes. These findings cover several crucial aspects for the application of capsosomes as potential drug delivery vehicles.

The instrumentation of the osteoporotic spine may sometimes result in failure due to the loosening or pullout of the conventional pedicle screw. Moreover, augmentation of screws with polymethylmethacrylate (PMMA) has risks of complications. We developed a new and original pedicle nail system with PMMA for osteoporotic vertebral fractures. A clinical evaluation of this novel pedicle nail system utilized in patients with an osteoporotic vertebral collapse was performed to determine the effectiveness and safety of this technique. Thirty-four elderly patients who suffered from osteoporotic compression fractures were treated by posterolateral fusion using the pedicle nail system. The mean follow-up period was 37 months. Of the 25 patients with neurological symptoms, two patients improved two stages at the Frankel level. Fifteen patients improved one stage at the Frankel level, and eight other patients improved, however, their improvement did not exceed a Frankel level. Nine cases with neuralgia symptoms improved from 4.4 to 2.2 points on average on the Denis pain scale (p < 0.01). The fusion rate was 94% as determined by X-rays of flexion and extension, and the correction of the compression fracture site was maintained well. A pedicle nail system stabilizes the spinal column with osteoporosis and reduces the instrumentation failure. The technique for the insertion of the pedicle nail reduces complication from cement augmentation. The authors speculate that the strategy using the pedicle nail system for osteoporotic spine may be effective and safe when the surgery is performed through a posterior approach.

Previously, we reported that human mesenchymal stem cells (hMSCs) that were cultivated in growing embryos differentiated in an appropriate developmental milieu, thereby facilitating the development of a functional renal unit. However, this approach required transfection with an adenovirus that expressed glial cell line-derived neurotrophic factor (GDNF) to enhance the development of hMSC-derived renal tissue, and safety issues restrict the clinical use of such viral vectors. To circumvent this problem, we tested an artificial polymer as a means to diffuse GDNF. This GDNF-polymer, which exists in liquid form at 4 degrees C but becomes a hydrogel upon heating to 37 degrees C, was used as a thermoreversible switch, allowing the injection of hMSCs at low viscosity using a mouth pipette, with subsequent slow diffusion of GDNF as it solidified. The polymer, which was dissolved in a solution of GDNF at 4 degrees C and then maintained at 37 degrees C, acted as a diffuser of GDNF for more than 48 h. LacZ-transfected hMSCs and the GDNF-polymer (at 4 degrees C) were placed in the nephrogenic sites of growing rat embryos that were maintained at 37 degrees C. Forty-eight hours later, the resultant kidney anlagen were dissected out and allowed to continue developing for 6 days in vitro. Whole-organ X-Gal staining and fluorescence activated cell sorter analysis showed that the number of hMSC-derived cells was significantly increased in developed anlagen that have been generated from hMSCs plus GDNF-polymer compared with those from hMSCs plus GDNF-containing medium and was comparable to those from adenovirus-transfected hMSCs. These findings suggest that the GDNF-polymer can be used as a diffuser of GDNF for kidney organogenesis.

Purpose: The aim of this study was to investigate the effect of Prime and Bond adhesive on preventing postcementation hypersensitivity of vital abutment teeth restored with a full-coverage restoration using the immediate dentin sealing (IDS) technique., Materials and Methods: Twenty-five male patients received 25 three-unit fixed partial dentures. A split-mouth design was used and two vital abutment teeth in each patient were allocated randomly into Groups A or B. Teeth in Group A were treated with Prime and Bond using the IDS technique while teeth in Group B were used as a control and left untreated. The discomfort interval scale, ranging from 0 to 4, was adopted to evaluate hypersensitivity. The double-blind method was applied during the operation so that neither the patient nor the clinician knew which abutment had been treated. The sensitivity assessment was performed 1 week, and 1, 6, 12, and 24 months after cementation. RESULTS were analyzed using the sign test., Results: Scores for teeth in Group A were statistically significantly lower than those in Group B at 1 week and 1 month postcementation (P < .05), whereas there was no significant difference between Groups A and B at the end of 6, 12, and 24 months (P > .05)., Conclusion: Preventive treatment with Prime and Bond using the IDS technique can significantly reduce postcementation hypersensitivity. Int J Prosthodont 2010;23:49-52.

Study Design: In vitro biomechanical study on 6 fresh frozen human thoracolumbar spine specimens., Objective: Using a novel high viscosity polymethylmethacrylate (PMMA) cement and vertebroplasty kit to correct the kyphosis angle of wedge compression fractures (AO/ASIF 1.2)., Summary of Background Data: Vertebroplasty is typically used to stabilize vertebral compression fractures in situ without correcting kyphosis, with the main target to reduce pain and disability. The vertebroplasty system investigated in this study comprises a high viscosity PMMA cement and uses a hydrostatic pressure hand piece for enhanced cement allocation and flow control. A recent clinical trial demonstrated a significantly reduced incidence of cement leakage with this system., Methods: Six spinal segments (Th11-L1 and Th12-L2) were loaded in a spine tester with pure moments of 7.5 Nm in lateral bending, flexion/extension and axial rotation. The segmental range of motion (ROM) was continuously recorded. The tested states of the specimens were: intact (a), fractured (b), treated with vertebroplasty (c), after loading with 50 to 250 N (d), 50 to 450 N (e) and 50 to 650 N (f) of 1000 cycles each. In each state (a-f), the kyphosis angle was documented fluoroscopically., Results: Kyphosis angle was significantly reduced between intact and fractured states (P<0.02). Between treated and fractured states, we found highly significant difference (P<0.001), indicating full correction. During 3000 loading cycles (50-250, 50-450, and 50-650 N), the kyphosis angle remained constant compared to the treated state (P=1.0). We noted a logistic relationship between injected cement volume and extent of kyphosis correction (R=0.89, P<0.001). In the fractured state, the ROM in flexion/extension increased to 252% of the intact state (P<0.001). The vertebroplasty treatment decreased ROM to 72% of fractured state in flexion/extension (P<0.001). Macroscopic inspection of the vertebrae after testing showed an intact interface and tight mechanical interlocking of cement filling and trabecular bone., Conclusion: High viscosity vertebroplasty effectively reduced and stabilized thoracolumbar wedge compression fractures and may represent a one-step solution for restoring vertebral body dimensions following thoracolumbar compression fractures, while minimizing the risk of cement leakage and associated complications in vivo.

Study Design: A biomechanical study using human cadaveric thoracolumbar spinal columns., Objective: To compare the effect of treatment by vertebroplasty (VP) with polymethylmethacrylate cement and VP with calcium phosphate cement on the creation of adjacent vertebral body fracture following VP., Summary of Background Data: Adjacent vertebral body fractures have been reported as a complication following VP., Methods: Twenty-four spinal columns (T10-L2) from human cadavers were subjected to dual energy radiograph absorptiometry to assess bone mineral density. They were divided into the P group and C group, and experimental vertebral compression fractures were created at T12 vertebrae. T12 vertebrae were augmented with polymethylmethacrylate and calcium phosphate cement in the P group and C group, respectively. Each spinal column was compressed until a new fracture occurred at any vertebra, and the location of newly fractured vertebra and failure load was investigated., Results: There was no significant difference in bone mineral density at each level within each group. In the P group, a new fracture occurred at T10 in 2 specimens, T11 in 8, and L1 in 2. In the C group, it occurred at T10 in 1 specimen, T11 in 2, L1 in 1, and T12 (treated vertebra) in 8. The failure loads of the spinal column were 1774.8+/-672.3 N and 1501.2+/-556.5 N in the P group and C group, respectively. There was no significant difference in the failure load of the spinal column between each group., Conclusion: New vertebral fractures occurred at the vertebra adjacent to augmented vertebrae in the P group and in the augmented vertebrae in the C group. The difference in the fractured site may be because of the difference in strength between the 2 bone filler materials. Therefore, the strength of bone filler materials is considered a risk factor in developing adjacent vertebral body fractures after VP.

This paper reviews an early clinical experience with anthracycline (epirubicin; Epi or doxorubicin; Dox) containing an N-(2-hydroyxypropyl)methacrylamide copolymer carrier targeted with autologous or commercial human immunoglobulin in six patients aged 28-55 suffering from therapy-resistant metastatic cancer. More than 100 biochemical, hematological and immunological parameters, including nine tumor markers, were tested in blood samples taken 24 h after the first and up to 10 months after the last application. The intravenous application proceeded without serious adverse or side effects and did not require hospitalization. Cardiotoxicity was not observed. Four of six monitored patients attained stabilization of disease (liver ultrasound scan and bone computer tomography) with a very good quality of life lasting from seven up to 18 months. Positive response to the treatment was, among others, evaluated as decreased CA 15-3 and CEA tumor markers. In three of five tested patients the serum level of C-reactive protein was temporarily increased 72 h after the treatment. A stable or elevated number of peripheral blood reticulocytes together with activation of natural killer (NK) cells and lymphokine-activated killer (LAK) cells supports the data previously obtained in experimental animals pointing to a dual role, i.e. the cytotoxic and immunomobilizing character of doxorubicin-HPMA conjugates.

Vertebroplasty, the augmentation of vertebral compression fractures by image-controlled intracorporeal injection of polymethylmethacrylate cement, has shown a steady increase in use. Its chief indication is to palliate pain after a failure of noninvasive therapies. Other benefits include preventing further compression of the treated vertebra and fusing unstable fractures. Controversies include questions regarding its long-term benefit compared with natural history, claims of height restoration, biomechanical compromise of adjacent vertebrae, and its performance compared with kyphoplasty. Complications are uncommon but can be devastating with reported cases of procedural death and paralysis. New operators should be adequately trained and respect the dangers of this procedure.

Background Context: Because posterior decompression and fusion for vertebral collapse in an osteoporotic spine sometimes results in a pullout of the pedicle screw. Several authors reported that fixation of pedicle screws in severely osteoporotic bone could be improved by inserting polymethylmethacrylate (PMMA) into the hole before inserting the screw. However, pedicle screws were not designed to be used with PMMA., Purpose: To report a patient with vertebral collapse who were treated using a novel-concept, pedicle nail using with PMMA., Study Design: Case report., Methods: The patient was a 74-year-old female who experienced back pain after some heavy lifting 3 months before. She was laid up for 2 months because of the back pain and weakness of her lower legs. Radiographs and magnetic resonance imaging showed vertebral collapse and neural severe compression from the posterior wall of vertebra T12. The pedicle nail consists of an outer sheath with evenly spaced holes and an internal, removable, threaded component. The outer sheath and the internal component were connected before insertion. The pedicle nail attaches to and is bound by the PMMA through the holes of the outer sheath. We performed a T11-L1 posterior fusion and laminectomy using the pedicle nail, and we used a hydroxyapatite block to perform a transpedicular vertebroplasty of T12., Results: Bone union was observed on a lateral radiograph without pedicle nail loosening., Conclusions: The authors speculate that posterior spinal fusion and vertebroplasty using the pedicle nail will be a reasonable choice for delayed paraplegia after osteoporotic vertebral fracture.

Study Design: A prospective observational cohort study of consecutive osteoporotic patients with sacral insufficiency fractures (SIFs)., Objective: Assess the safety and efficacy of sacroplasty in treating osteoporotic SIFs., Summary of Background Data: SIFs can cause low back pain in osteoporotic patients. Symptomatic improvement may require up to 12 months. Treatment includes limited weight-bearing and bed rest, oral analgesics, and sacral corsets. Significant mortality and morbidity are associated with pelvic insufficiency fractures. Percutaneous sacroplasty is an alternative treatment for SIF patients, and initial reports have documented its safe and effective performance. Yet, follow-up intervals have been short, and study cohorts small precluding definitive assessment of sacroplasty's safety and efficacy., Methods: Baseline Visual Analogue Scale (VAS), analgesic usage, and duration of symptoms were recorded. Subsequent VAS ratings were assessed at 30 minutes and at 2, 4, 12, 24, and 52 weeks postprocedure. Analgesic usage and patient satisfaction were assessed at final follow-up. Each procedure was performed under intravenous conscious sedation using fluoroscopy. Two bone trochars were inserted between the sacral foramen and sacroiliac joint through which 2 to 3 mL of polymethylmethacrylate was injected., Results: Thirty-seven patients, 27 females, were treated. Mean age was 76.6 years, and mean symptom duration was 34.4 days. All patients were available at each follow-up interval except 1 patient who died due to unrelated pulmonary disease before the 4-week follow-up. The mean VAS score at baseline was 7.7 and 3.2 within 30 minutes, and 2.1 at 2, 1.7 at 4, 1.3 at 12, 1.0 at 24, and 0.7 at 52 weeks postprocedure. Improvement at each interval and overall was statistically significant using the Wilcoxon Rank Sum Test. One case of transient S1 radiculitis was encountered., Conclusions: Sacroplasty appears to be a safe and effective treatment for painful SIF. The rate of improvement is rapid and sustained through 1 year.

Aim: To evaluate treatment outcome after using a resin composite (Retroplast, RP) in combination with a dentine-bonding agent (GLUMA) as root-end filling material after 1 year as well as after more than 5 years (final examination). Also, the influence of various pre-, intra- and postoperative factors on the treatment outcome was studied., Methodology: All patients (87) undergoing root-end resection consecutively treated by root-end filling with RP on an incisor, canine, pre-molar, or first molar (87 teeth, 118 roots) were initially enrolled in the study. RP was applied on the entire resected surface that was prepared to a slightly concave shape and after conditioning with EDTA and GLUMA. The treatment outcome involving subjective, clinical and radiographic parameters was evaluated after 1 year and at the final examination. A total of 27 patients (36 roots) were excluded from the study because of unavailability of follow-up (19) and extraction of the operated tooth for reasons other than failed surgery (8). Consequently, 60 patients (82 roots) were included in the final material. The mean follow-up period at the final examination was 8 years (range: 6.5-9 years)., Results: The radiographic evaluation at the final examination revealed that 77%, 5%, 7% and 11% of the treated roots were characterized by complete, incomplete, uncertain and unsatisfactory healing, respectively. A total of 95% of the roots classified as completely healed at the 1-year control were also completely healed at the final examination. Two roots (5%) showing complete healing at the 1-year control revealed unsatisfactory healing at the final examination because of displaced or lost RP-filling. Moreover, 60% of the roots with uncertain healing at the 1-year control demonstrated complete or incomplete healing at the final examination. The classification according to subjective, clinical and radiographic parameters revealed that 78% of the teeth were characterized by a successful treatment outcome at the final examination. Evaluation of the influence of various pre-, intra- and postoperative factors on the treatment outcome revealed that the radiographic classification at the final examination was exclusively influenced by the radiographic classification at the 1-year control (P < 0.001)., Conclusions: The present long-term study indicates that RP can be used for root-end filling with a successful treatment outcome.

In the recent years, percutaneous vertebroplasty is available for the treatment of the vertebral fractures, primarily to relieve pain related to the lesion. In order to evaluate the efficacy and the safety of this technique, we have treated with percutaneous vertebroplasty, using polymethylmethacrylate, 22 patients, affected by one or more vertebral fractures caused by osteoporosis. All the patients satisfied the inclusion criteria of the American College of Radiology for percutaneous vertebroplasty. These patients were compared with a control group of 23 not treated subjects with vertebral fractures, using questionnaires for assessment of pain and quality of life, drug intake, use of corset, and tolerability of the surgery. In the large majority of patients, the treatment of osteoporotic vertebral fractures with percutaneous vertebroplasty resulted in a prompt, marked and sustained relief of vertebral pain with a persistent improvement of quality of life.

Linkage of doxorubicin (Dox) to a water-soluble synthetic N-(2-hydroxypropyl)methacrylamide copolymer (PHPMA) eliminates most of the systemic toxicity of the free drug. In EL-4 lymphoma-bearing C57BL/6 mice, a complete regression of pre-established tumours has been achieved upon treatment with Dox-PHPMA-HuIg conjugate. The treatment was effective using a range of regimens and dosages, ranging from 62.5 to 100% cured mice treated with a single dose of 10-20 mg of Dox eq./kg, respectively. Fractionated dosages producing lower levels of the conjugate for a prolonged time period had substantial curative capacity as well. The cured mice developed anti-tumour protection as they rejected subsequently re-transplanted original tumour. The proportion of tumour-protected mice inversely reflected the effectiveness of the primary treatment. The treatment protocol leading to 50% of cured mice produced only protected mice, while no mice treated with early treatment regimen (i.e. starting on day 1 after tumour transplantation) rejected the re-transplanted tumour. Exposure of the host to the cancer cells was a prerequisite for developing protection. The anti-tumour memory was long lasting and specific against the original tumour, as the cured mice did not reject another syngeneic tumour, melanoma B16-F10. The immunity was transferable to naïve recipients in in vivo neutralization assay by spleen cells or CD8(+) lymphocytes derived from cured animals. We propose an effective treatment strategy which eradicates tumours without harming the protective immune anti-cancer responses.

Eudragit L100 microspheres were prepared using water-in-oil-in water (w/o/w) emulsion-solvent evaporation with polysorbate 20 as dispersing agent in the internal aqueous phase, and PVA/PVP as stabilizer in the external aqueous phase. Smaller internal and external aqueous phases provided higher drug encapsulation. The PVA-stabilized microspheres having maximum drug encapsulation (84.5 2.8%) released 7% insulin at pH 1.0 in 2 h. In phosphate buffer (pH 7.4), microspheres showed an initial burst release of 21% in 1 h with additional 35% release in the next 5 h. The smaller the volumes of internal and external aqueous phases, the lower the initial burst release. The release of drug from microspheres followed Higuchi kinetics. Scanning electron microscopy of PVA stabilized microspheres demonstrated spherical particles with smooth surface and laser diffractometry revealed a mean particle size (V(m)) of 59.11 30 m.

Background: Nicotine polacrilex lozenges deliver 25% to 27% more nicotine compared with equivalent doses of nicotine polacrilex gum. The increased nicotine exposure from the lozenge has raised questions about the relative safety of the lozenge and gum., Objective: The objective of this study was to compare the safety profiles of the 4-mg nicotine lozenge and 4-mg nicotine gum in smokers with selected label-restricted diseases., Methods: This was a multicenter, randomized, open-label study in adult smokers with heart disease, hypertension not controlled by medication, and/or diabetes mellitus. Patients were randomized in a 1:1 ratio to receive the 4-mg nicotine lozenge or 4-mg nicotine gum. Safety assessments were made at baseline and at 2, 4, 6, and 12 weeks after the start of product use., Results: Nine hundred one patients were randomized to treatment, 447 who received the lozenge and 454 who received the gum (safety population). The majority were women (52.7%). Patients' mean age was 53.9 years, their mean weight was 193.9 pounds, and they smoked a mean of 25.2 cigarettes per day at baseline. Five hundred fifty-three patients, 264 taking the lozenge and 289 taking the gum, used the study product for > or =4 days per week during the first 2 weeks (evaluable population). The nicotine lozenge and nicotine gum were equally well tolerated, despite increased nicotine exposure from the lozenge. The incidence of adverse events in the 2 groups was similar during the first 2 weeks of product use (evaluation population: 55.3% lozenge, 54.7% gum), as well as during the entire study (safety population: 63.8% and 58.6%, respectively). Stratification of patients by sex, age, extent of concurrent smoking, extent of product use, and severity of adverse events revealed no clinically significant differences between the lozenge and gum. The most common adverse events were nausea (17.2% and 16.1%; 95% CI, -3.7 to 6.0), hiccups (10.7% and 6.6%; 95% CI, 0.5 to 7.8), and headache (8.7% and 9.9%; 95% Cl, -5.0 to 2.6). Serious adverse events were reported in 11 and 13 patients in the respective groups. Fewer than 6% of patients in either group were considered by the investigator to have a worsening of their overall disease condition during the study. The majority of patients (>60%) experienced no change in their disease status from baseline., Conclusion: The 4-mg nicotine lozenge and 4-mg nicotine gum had comparable safety profiles in these patients with label-restricted medical conditions.

Objectives: The aim of this study was to compare the interaction of dentin with 2 different self-etch resin bonding systems, as well as with a total-etch resin bonding system., Method and Materials: Nine recently extracted, unerupted third molars, roots, and occlusal thirds were used. A standardized smear layer was produced on the occlusal dentin surface exposed. The specimens were split into 3 groups of 3 specimens each, 1 group for each bonding agent: Clearfil Liner Bond 2, Prime & Bond 2.1, and Scotchbond Multipurpose (control group). After the tooth was briefly sprayed with an air/water mixture, 1 of the experimental adhesive systems was applied on the dentin surface. A 2-mm layer of composite was applied over the adhesive system layer. After 7 days in distilled water at 37 degrees C, the specimens were cross-sectioned perpendicular to the resin-dentin interface. The crosssections were mounted on aluminum stubs, etched with 2% hydrochloridric acid, and studied using scanning electron microscopy. A descriptive analysis of the images of the interdiffusion zone characteristics was done first. Afterwards, statistical analyses of the measurements of the interdiffusion zone structures-hybrid layer thickness, resin tags penetration, and adhesive layer thickness using analysis of variance, followed by "post hoc" test-were carried out to compare the bonding systems' interactions., Results: The descriptive analysis of the self-etch bonding systems studied showed a good interlocking of Clearfil Liner Bond 2 with dentin, similar to Scotchbond Multipurpose and better than Prime & Bond 2.1. The analysis of variance, followed by the "post hoc" test, identified statistical differences just for the adhesive layer thickness that was thicker for Scotchbond than for Prime & Bond (P = .020). The "post hoc" test also showed a strong tendency to identify differences between the Scotchbond and the Prime & Bond groups (P = .062), and the Clearfil and the Prime & Bond groups (P = .069)., Conclusion: Within the limitations of this study, Clearfil Liner Bond 2 produced the thickest hybrid layer with deepest tag formation and good interlocking with dentin, similar to the control. Statistical differences among the interdiffusion zone of the 3 bonding systems studied were identified just for the adhesive layer thickness, which was thicker for Scotchbond than for Prime & Bond.

This study evaluated the clinical performance of a posterior resin composite used with a fourth- and fifth-generation bonding agent. Sixty-two Class I and II restorations were placed with half the restorations restored with Gluma Solid Bond (a fourth-generation bonding system, or total etch two-step system) and the other half restored with Gluma Comfort Bond and Desensitizer (a fifth-generation bonding system, or total etch one-step system). Solitaire 2 was used as the restorative material for all restorations. The bonding systems and resin composite were used according to the manufacturer's instructions and all procedures were performed with rubber dam isolation. All restorations were evaluated at baseline, six months and one and two years. A modified USPHS scale was used to evaluate the restorations for marginal discoloration, recurrent caries, anatomic form, marginal adaptation and proximal contact. Statistical analysis revealed that at two years no significant differences were found between the two bonding agents. Overall, Solitaire 2 performed well clinically whether Gluma Solid Bond or Gluma Comfort Bond and Desensitizer was used. It was thus concluded that Solitaire 2 functions successfully when used as a posterior restorative material for at least two years.

Objective: This study evaluated the biocompatibility of a one-step dentin bonding agent (Prime&Bond 2.1) in pulp capping compared with calcium hydroxide [Ca(OH)2]., Method and Materials: Thirty sheep teeth and 20 intact human premolars were used. After cavity preparation, pulp exposure was achieved with a bur (#390). Adhesive pulp capping was performed in 25 teeth (15 sheep and 10 human). In the control group (12 sheep and 10 human teeth), pulps were capped with Ca(OH)2 and all of the cavities in both groups were sealed with resin composite. Three of the sheep teeth were used as intact controls. Teeth were extracted 7 or 90 days following treatment and prepared for histological examination and bacterial detection., Results: At 7 days, severe inflammatory responses underlying the bonding agent and in the coronal pulp were observed with soft tissue disorganization in both human and sheep teeth capped with Prime&Bond 2.1. All of the teeth capped with Ca(OH)2 exhibited mild inflammatory reactions limited with the perforation area. After 90 days with the bonding agent, in 3 of 9 sheep teeth, chronic inflammatory reactions were significant, while slight pulpal reactions were observed in the others and dentin bridge formation in all of the sheep teeth was found. However, in human pulps, persistent, unresolved inflammation with the lack of dentin bridge formation was observed. In the Ca(OH)2 group, pulp repair with dentin bridging was found in all of the teeth, both sheep and human. No correlation was found between the presence of inflammation and bacterial staining using Spearman rank correlation test (P > .05)., Conclusion: Prime&Bond 2.1 facilitates enhanced pulp healing and bridge formation in sheep teeth, but in human teeth it was not as successful as Ca(OH)2 as a pulp capping agent.

Hydrogel nanospheres composed of methacrylic acid and poly(ethylene glycol) were loaded with bleomycin and tested as a potential oral delivery system for chemotherapeutic agents. The gastrointestinal epithelium was modeled through the use of Caco-2 monolayers for studies of permeation enhancement by the carriers as well as bleomycin transport. Bleomycin efficacy following release from the carrier was evaluated with a DLD-1 tumor cell model. The nanospheres release bleomycin in response to a pH increase similar to that seen when passing from the stomach into the upper small intestine. These carriers can also increase the permeability of a model of the epithelial barrier, which would hopefully improve drug transport into the bloodstream. Efficacy studies using a tumor cell model showed retention of activity for bleomycin following loading and release from the nanospheres. The carriers described performed well during in vitro evaluation and can hopefully expand the spectrum of chemotherapeutic agents capable of being administered orally., (Copyright (c) 2005 Wiley Periodicals, Inc.)

The objective of this study was to synthesize and characterize particles as a drug-delivery platform for gliomas, a highly advanced and invasive stage of brain tumor with poor prognosis. Poly(aminoethyl methacrylate-co-methyl methacrylate) particles were prepared by suspension polymerization and poly(aminoethyl methacrylate-co-poly(ethylene glycol) methacrylate) particles were prepared by emulsion (w/o) polymerization. Amine groups of the particles were complexed with tetrachloroplatinate to form a cisplatin-like molecule. Particles were characterized with respect to size, zeta-potential, amine content, loading efficiency and drug release. Poly(aminoethyl methacrylate-co-methyl methacrylate) particles had diameters of below 10 microm, whereas the poly(aminoethyl methacrylate-co-poly(ethylene glycol) methacrylate) particles had diameters of approx. 1 microm. Poly(aminoethyl methacrylate-co-poly(ethylene glycol) methacrylate) particles had a more positive zeta-potential as compared to poly(aminoethyl methacrylate-co-methyl methacrylate) particles, although the amino-group content of both particles was almost equivalent. The net positive charge on the particles decreased after complexation with tetrachloroplatinate for both types of particles. Both particles had very high platinum-loading efficiency (>85%) and showed slow release of platinum over time. Particles had relatively low cytotoxicity (LC50 > 100 microg/ml) and demonstrated a high degree of association with cells. Complexation with poly(aminoethyl methacrylate-co-methyl methacrylate) particles significantly reduced the toxicity of platinum. The poly(aminoethyl methacrylate-co-poly(ethylene glycol) methacrylate) particles have potential for being an effective drug-delivery platform and continued investigation is warranted.