Kooperativer Bibliotheksverbund

Berlin Brandenburg


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  • 11
    In: Biometrika, 2006, Vol.93(4), pp.827-841
    Description: We consider parameter-driven models of time series of counts, where the observations are assumed to arise from a Poisson distribution with a mean changing over time according to a latent process. Estimation of these models is carried out within a Bayesian framework using data augmentation and Markov chain Monte Carlo methods. We suggest a new auxiliary mixture sampler, which possesses a Gibbsian transition kernel, where we draw from full conditional distributions belonging to standard distribution families only. Emphasis lies on application to state space modelling of time series of counts, but we show that auxiliary mixture sampling may be applied to a wider range of parameter-driven models, including random-effects models and panel data models based on the Poisson distribution.
    Keywords: Count Data; Data Augmentation; Finite Mixture Approximation; Gibbs Sampling; Partially Gaussian State Space Model.
    ISSN: 0006-3444
    E-ISSN: 1464-3510
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  • 12
    Language: English
    In: PLoS ONE, 01 January 2016, Vol.11(1), p.e0146378
    Description: Delayed graft function is a prevalent clinical problem in renal transplantation for which there is no objective system to predict occurrence in advance. It can result in a significant increase in the necessity for hospitalisation post-transplant and is a significant risk factor for other post-transplant...
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 13
    Language: English
    In: Analytica Chimica Acta, 28 September 2016, Vol.938, pp.106-113
    Description: Limited drug penetration into tumor tissue is a significant factor to the effectiveness of cancer therapy. Tumor spheroids, a 3D cell culture model system, can be used to study drug penetration for pharmaceutical development. In this study, a method for quantitative bioimaging of platinum group elements by laser ablation (LA) coupled to inductively coupled plasma mass spectrometry (ICP-MS) is presented. Different matrix-matched standards were used to develop a quantitative LA-ICP-MS method with high spatial resolution. To investigate drug penetration, tumor spheroids were incubated with platinum complexes (Pt(II)acetylacetonate, cisplatin) and the palladium tagged photosensitizer 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin ( THPP). Distribution and accumulation of the pharmaceuticals were determined with the developed method.
    Keywords: La-Icp-MS ; Quantification ; Tumor Spheroids ; Pt Cytostatics ; Photosensitizer ; Chemistry
    ISSN: 0003-2670
    E-ISSN: 1873-4324
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  • 14
    Language: English
    In: Biomaterials, 2010, Vol.31(8), pp.2388-2398
    Description: Specific transport of anti-cancer drugs into tumor cells may result in increased therapeutic efficacy and decreased adverse events. Expression of αvβ3 integrin is enhanced in various types of cancer and monoclonal antibodies (mAbs) directed against αvβ3 integrins hold promise for anti-cancer therapy. DI17E6 is a monoclonal antibody directed against αv integrins that inhibits growth of melanomas and and inhibits angiogenesis due to interference with αvβ3 integrins. Here, DI17E6 was covalently coupled to human serum albumin nanoparticles. Resulting nanoparticles specifically targeted αvβ3 integrin positive melanoma cells. Moreover, doxorubicin loaded DI17E6 nanoparticles showed increased cytotoxic activity in αvβ3-positive melanoma cells than the free drug. Therefore, DI17E6-coupled human serum albumin nanoparticles represent a potential delivery system for targeted drug transport into αvβ3-positive cells.
    Keywords: Albumin ; Chemotherapy ; Drug Delivery ; Ecm (Extracellular Matrix) ; Integrin ; Nanoparticles ; Medicine ; Engineering
    ISSN: 0142-9612
    E-ISSN: 1878-5905
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  • 15
    Language: English
    In: Toxicology Letters, 2011, Vol.206(1), pp.60-66
    Description: • We loaded the oxime HI 6 on human serum albumin nanoparticles. • We investigated the physico-chemical properties of the HI 6-loaded nanoparticles. • The transfer through an blood–brain barrier model was increased with HI 6-loaded nanoparticles. The standard treatment of intoxication with organophosphorus (OP) compounds includes the administration of oximes acting as acetylcholinesterase (AChE) reactivating antidotes. However, the blood–brain barrier (BBB) restricts the rapid transport of these drugs from the blood into the brain in therapeutically relevant concentrations. Since human serum albumin (HSA) nanoparticles enable the delivery of a variety of drugs across the BBB into the brain, HI 6 dimethanesulfonate and HI 6 dichloride monohydrate were bound to these nanoparticles in the present study. The resulting sorption isotherms showed a better fit to Freundlich's empirical adsorption isotherm than to Langmuir's adsorption isotherm. At the pH of 8.3 maximum drug binding capacities of 344.8 μg and 322.6 μg per mg of nanoparticles were calculated for HI 6 dimethanesulfonate and HI 6 dichloride monohydrate, respectively. These calculated values are higher than the adsorption capacity of 93.5 μg/mg for obidoxime onto HSA nanoparticles determined in a previous study. testing of the nanoparticulate oxime formulations in primary porcine brain capillary endothelial cells (pBCEC) demonstrated an up to two times higher reactivation of OP-inhibited AChE than the free oximes. These findings show that nanoparticles made of HSA may enable a sufficient antidote OP-poisoning therapy with HI 6 derivatives even within the central nervous system (CNS).
    Keywords: Nanoparticles ; Human Serum Albumin ; Hi 6 ; Adsorption Isotherm ; In Vitro Blood–Brain Barrier Model ; Drug Delivery ; Pharmacy, Therapeutics, & Pharmacology ; Public Health
    ISSN: 0378-4274
    E-ISSN: 1879-3169
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  • 16
  • 17
    Language: English
    In: Nanomedicine: Nanotechnology, Biology, and Medicine, 2011, Vol.7(4), pp.454-463
    Description: The specific application and transport of drugs into malignant tissue is a critical point during diagnosis and therapy. Nanoparticles are known as excellent drug carrier systems and offer the possibility of surface modification with targeting ligands, leading to a specific accumulation in the targeted tissue. First, the specificity of such a carrier system has to be proven. In this study, cetuximab-modified nanoparticles based on biodegradable human serum albumin (HSA) are investigated regarding their cellular binding and intracellular accumulation. Different EGFR-expressing colon carcinoma cells were used to test possible cytotoxic potential, specific binding and intracellular accumulation. A specific accumulation targeting the EGFR could be shown. These results emphasize that cetuximab-modified HSA-nanoparticles are a promising carrier system for later drug transport. To our knowledge, this is the first study investigating the specific accumulation of HSA nanoparticles into different EGFR-expressing colon carcinoma cells. In this study, cetuximab-modified nanoparticles based on human serum albumin (HSA) are investigated regarding their cellular binding and intracellular accumulation. The results suggest that these nanoparticles are a promising carrier system for EGFR overexpressing colon carcinoma cells. Specific cellular accumulation of cetuximab-modified nanoparticles based on human serum albumin in different EGFR-expressing colon carcinoma cell lines. HSA-cetuximab nanoparticles show a cell specific accumulation depending the cellular EGFR-expression.
    Keywords: Nanoparticles ; Human Serum Albumin ; Colon Carcinoma ; Egfr ; Cetuximab ; Medicine
    ISSN: 1549-9634
    E-ISSN: 1549-9642
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  • 18
    Language: English
    In: European Journal of Pharmaceutics and Biopharmaceutics, October 2014, Vol.88(2), pp.510-517
    Description: Severe intoxications with organophosphates require the immediate administration of atropine in combination with acetyl cholinesterase (AChE) reactivators such as HI-6. Although this therapy regimen enables the treatment of peripheral symptoms, the blood–brain barrier (BBB) restricts the access of the hydrophilic antidotes to the central nervous system which could lead to a fatal respiratory arrest. Therefore, HI-6-loaded albumin nanoparticles were previously developed to enhance the transport across this barrier and were able to reactivate organophosphate-(OP)-inhibited AChE in an BBB model. Since HI-6 is known to be moisture-sensitive, the feasibility of freeze-drying of the HI-6-loaded nanoparticles was investigated in the present study using different cryo- and lyoprotectants at different concentrations. Trehalose and sucrose (3%, w/v)-containing formulations were superior to mannitol concerning the physicochemical parameters of the nanoparticles whereas trehalose-containing samples were subject of a prolonged storage stability study at temperatures between −20 °C and +40 °C for predetermined time intervals. Shelf-life computations of the freeze-dried HI-6 nanoparticle formulations revealed a shelf-life time of 18 months when stored at −20 °C. The formulations’ efficacy was proven by reactivation of OP-inhibited AChE after transport over a porcine brain capillary endothelial cell layer model.
    Keywords: Nanoparticles ; Recombinant Human Serum Albumin ; Hi-6 ; Drug Delivery ; Freeze-Drying ; Storage Stability ; Organophosphate Intoxication ; Oximes ; Blood–Brain Barrier (BBB) ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0939-6411
    E-ISSN: 1873-3441
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  • 19
    In: Anti-Cancer Drugs, 2015, Vol.26(7), pp.728-736
    Description: In vitro, treosulfan (TREO) has shown high effectiveness against malignant gliomas. However, a first clinical trial for newly diagnosed glioblastoma did not show any positive effect. Even though dosing and timing might have been the reasons for this failure, it might also be that TREO does not reach the brain in sufficient amount. Surprisingly, there are no published data on TREO uptake into the brain of patients, despite extensive research on this compound. An in-vitro blood–brain barrier (BBB) model consisting of primary porcine brain capillary endothelial cells was used to determine the transport of TREO across the cell monolayer. Temozolomide (TMZ), the most widely used cytotoxic drug for malignant gliomas, served as a reference. An HPLC-ESI-MS/MS procedure was developed to detect TREO and TMZ in cell culture medium. Parallel to the experimental approach, the permeability of TREO and the reference substance across the in-vitro BBB was estimated on the basis of their physicochemical properties. The detection limit was 30 nmol/l for TREO and 10 nmol/l for TMZ. Drug transport was measured in two directions: influx, apical-to-basolateral (A-to-B), and efflux, basolateral-to-apical (B-to-A). For TREO, the A-to-B permeability was lower (1.6%) than the B-to-A permeability (3.0%). This was in contrast to TMZ, which had higher A-to-B (13.1%) than B-to-A (7.2%) permeability values. The in-vitro BBB model applied simulated the human BBB properly for TMZ. It is, therefore, reasonable to assume that the values for TREO are also meaningful. Considering the lack of noninvasive, significant alternative methods to study transport across the BBB, the porcine brain capillary endothelial cell model was efficient to collect first data for TREO that explain the disappointing clinical results for this drug against cerebral tumors.
    Keywords: Antineoplastic Agents, Alkylating -- Metabolism ; Blood-Brain Barrier -- Metabolism ; Busulfan -- Analogs & Derivatives ; Dacarbazine -- Analogs & Derivatives ; Endothelial Cells -- Metabolism;
    ISSN: 0959-4973
    E-ISSN: 14735741
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  • 20
    Language: English
    In: Journal of Microencapsulation, 01 September 2010, Vol.27(6), pp.506-513
    Description: The standard treatment of poisoning by organophosphorous compounds such as paraoxon includes the administration of oximes. Due to their inability to rapidly cross the blood-brain barrier (BBB) in therapeutically relevant concentrations, these drugs possess insufficient activity in the central...
    Keywords: Nanoparticles ; Human Serum Albumin ; Obidoxime ; Adsorption Isotherm ; Langmuir ; Medicine ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0265-2048
    E-ISSN: 1464-5246
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