Macromolecular theory of solvation and structure in mixtures of colloids and polymers

The structural and thermodynamic properties of mixtures of colloidal spheres and non-adsorbing polymer chains are studied within a novel general two-component macromolecular liquid state approach applicable for all size asymmetry ratios. The dilute limits, when one of the components is at infinite dilution but the other concentrated, are presented and compared to field theory and models which replace polymer coils with spheres. Whereas the derived analytical results compare well, qualitatively and quantitatively, with mean-field scaling laws where available, important differences from ``effective sphere'' approaches are found for large polymer sizes or semi-dilute concentrations.Comment: 23 pages, 10 figure

Reovirus-induced cell-mediated immunity for the treatment of multiple myeloma within the resistant bone marrow niche

Background Multiple myeloma (MM) remains an incurable disease and oncolytic viruses offer a well-tolerated addition to the therapeutic arsenal. Oncolytic reovirus has progressed to phase I clinical trials and its direct lytic potential has been extensively studied. However, to date, the role for reovirus-induced immunotherapy against MM, and the impact of the bone marrow (BM) niche, have not been reported. Methods This study used human peripheral blood mononuclear cells from healthy donors and in vitro co-culture of MM cells and BM stromal cells to recapitulate the resistant BM niche. Additionally, the 5TGM1-Kalw/RijHSD immunocompetent in vivo model was used to examine reovirus efficacy and characterize reovirus-induced immune responses in the BM and spleen following intravenous administration. Collectively, these in vitro and in vivo models were used to characterize the development of innate and adaptive antimyeloma immunity following reovirus treatment. Results Using the 5TGM1-Kalw/RijHSD immunocompetent in vivo model we have demonstrated that reovirus reduces both MM tumor burden and myeloma-induced bone disease. Furthermore, detailed immune characterization revealed that reovirus: (i) increased natural killer (NK) cell and CD8+ T cell numbers; (ii) activated NK cells and CD8+ T cells and (iii) upregulated effector-memory CD8+ T cells. Moreover, increased effector-memory CD8+ T cells correlated with decreased tumor burden. Next, we explored the potential for reovirus-induced immunotherapy using human co-culture models to mimic the myeloma-supportive BM niche. MM cells co-cultured with BM stromal cells displayed resistance to reovirus-induced oncolysis and bystander cytokine-killing but remained susceptible to killing by reovirus-activated NK cells and MM-specific cytotoxic T lymphocytes. Conclusion These data highlight the importance of reovirus-induced immunotherapy for targeting MM cells within the BM niche and suggest that combination with agents which boost antitumor immune responses should be a priority

Prediction of Infant Drug Exposure Through Breastfeeding: Population PK Modeling and Simulation of Fluoxetine Exposure.

The likelihood of significant exposure to drugs in infants through breast milk is poorly defined, given the difficulties of conducting pharmacokinetics (PK) studies. Using fluoxetine (FX) as an example, we conducted a proof-of-principle study applying population PK (popPK) modeling and simulation to estimate drug exposure in infants through breast milk. We simulated data for 1,000 mother-infant pairs, assuming conservatively that the FX clearance in an infant is 20% of the allometrically adjusted value in adults. The model-generated estimate of the milk-to-plasma ratio for FX (mean: 0.59) was consistent with those reported in other studies. The median infant-to-mother ratio of FX steady-state plasma concentrations predicted by the simulation was 8.5%. Although the disposition of the active metabolite, norfluoxetine, could not be modeled, popPK-informed simulation may be valid for other drugs, particularly those without active metabolites, thereby providing a practical alternative to conventional PK studies for exposure risk assessment in this population

Prediction of infant drug exposure through breastfeeding: population PK modeling and simulation of fluoxetine

BACKGROUND: Risks of significant infant drug exposurethrough breastmilk are poorly defined for many drugs, and largescalepopulation data are lacking. We used population pharmacokinetics(PK) modeling to predict fluoxetine exposure levels ofinfants via mother's milk in a simulated population of 1000 motherinfantpairs.METHODS: Using our original data on fluoxetine PK of 25breastfeeding women, a population PK model was developed withNONMEM and parameters, including milk concentrations, wereestimated. An exponential distribution model was used to account forindividual variation. Simulation random and distribution-constrainedassignment of doses, dosing time, feeding intervals and milk volumewas conducted to generate 1000 mother-infant pairs with characteristicssuch as the steady-state serum concentrations (Css) and infantdose relative to the maternal weight-adjusted dose (relative infantdose: RID). Full bioavailability and a conservative point estimate of1-month-old infant CYP2D6 activity to be 20% of the adult value(adjusted by weigth) according to a recent study, were assumed forinfant Css calculations.RESULTS: A linear 2-compartment model was selected as thebest model. Derived parameters, including milk-to-plasma ratios(mean: 0.66; SD: 0.34; range, 0 - 1.1) were consistent with the valuesreported in the literature. The estimated RID was below 10% in &gt;95%of infants. The model predicted median infant-mother Css ratio was0.096 (range 0.035 - 0.25); literature reported mean was 0.07 (range0-0.59). Moreover, the predicted incidence of infant-mother Css ratioof &gt;0.2 was less than 1%.CONCLUSION: Our in silico model prediction is consistent withclinical observations, suggesting that substantial systemic fluoxetineexposure in infants through human milk is rare, but further analysisshould include active metabolites. Our approach may be valid forother drugs. [supported by CIHR and Swiss National Science Foundation(SNSF)]]]> eng oai:serval.unil.ch:BIB_64448644E59E 2022-02-19T02:22:49Z <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_64448644E59E Storia linguistica di Venezia urn:isbn:9788843055128 info:eu-repo/semantics/altIdentifier/isbn/9788843055128 Tomasin, Lorenzo info:eu-repo/semantics/book book 2010 ita oai:serval.unil.ch:BIB_6444B2C2264E 2022-02-19T02:22:49Z <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_6444B2C2264E L'utilisation du laser CO2 dans le cadre d'une consultation de colposcopie Hohlfeld, P. De Grandi, P. info:eu-repo/semantics/article article 1988 Médecine et Hygiène, vol. 46, pp. 1325-1329 info:eu-repo/semantics/altIdentifier/pissn/0025-6749 fre oai:serval.unil.ch:BIB_644527E87B99 2022-02-19T02:22:49Z <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_644527E87B99 A study on the clinical significance of the who aml subtype inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and various other 3q chromosomal abnormalities in 6,819 aml cases Lugthart, S. Groeschel, S. Beverloo, H. Valk, P. Schanz, U. Bhola, S. Vellenga, E. Kayser, S. Ossenkoppele, G. Verhoef, G. Ferrant, A. van den Berg-de Ruiter, E. Ganser, A. Jotterand, M. Krauter, J. Pabst, T. Schlegelberger, B. Schlenk, R. Delwel, R. Doehner, K. Loewenberg, B. Doehner, H. info:eu-repo/semantics/conferenceObject inproceedings 2010 15th Annual Meeting of the European Hematology Association, vol. 95, pp. 482 info:eu-repo/semantics/altIdentifier/isbn/0390-6078 eng oai:serval.unil.ch:BIB_6445291F3B73 2022-02-19T02:22:49Z <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_6445291F3B73 Le politique et l’oblitération. Sur la dialectique de l’engagement Voirol, Olivier info:eu-repo/semantics/bookPart incollection 2015 Penser l’engagement, pp. 71-95 Ouelbani, Mélika (ed.) fre oai:serval.unil.ch:BIB_63D52E568CD1 2022-02-19T02:22:47Z <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_63D52E568CD1 La maladie ulcereuse gastro-duodenale: que reste-t-il des indications chirurgicales? [Gastroduodenal ulcer disease: what surgical indications are left?] info:eu-repo/semantics/altIdentifier/pmid/2569232 Cuttat, J. F. Ruchat, P. Chapuis, G. info:eu-repo/semantics/article article 1989-05 Schweizerische Medizinische Wochenschrift, vol. 119, no. 21, pp. 729-30 info:eu-repo/semantics/altIdentifier/pissn/0036-7672 <![CDATA[Between 1976, date of the introduction of anti-H2, and 1987, 716 patients were hospitalized and operated on for ulcer disease in the surgical department of this hospital. The present study shows that 1. the annual number of operations has regressed by some 30%, 2. while the number of gastric ulcers remains constant on the whole, cases of acute duodenal ulcer have diminished by half, 3. cases of chronic, recurrent, or therapy-resistent duodenal ulcer have increased some tenfold (2 out of 78 in 1976 and 14 out of 45 in 1987), 4. the same is true of perforated ulcers (12 out of 78 in 1976 and 10 out of 45 in 1987) and hemorrhages (12 out of 78 and 10 out of 45), 5. surgery for stenosis has remained constant. -Proximal selective vagotomy has been the treatment of choice since 1981 in over 80% of duodenal ulcers. Operative mortality affects only elderly patients undergoing emergency surgery for complicated ulcer (two thirds perforations, one third hemorrhages). It is 2.6%. We thus confirm the reduced role of surgery in the treatment of gastric ulcer, while redefining the present surgical indications

Internalization of Oncolytic Reovirus by Human Dendritic Cell Carriers Protects the Virus from Neutralization

Purpose: Dendritic cells (DC) may be the most effective way of delivering oncolytic viruses to patients. Reovirus, a naturally occurring oncolytic virus, is currently undergoing early clinical trials; however, intravenous delivery of the virus is hampered by pre-existing antiviral immunity. Systemic delivery via cell carriage is a novel approach currently under investigation and initial studies have indicated its feasibility by using a variety of cell types and viruses. This study addressed the efficacy of human DC to transport virus in the presence of human neutralizing serum. Experimental Design: Following reovirus-loading, DC or T cells were cocultured with melanoma cells with or without neutralizing serum; the melanoma cells were then analyzed for cell death. Following reovirus loading, cells were examined by electron microscopy to identify mechanisms of delivery. The phagocytic function of reovirus-loaded DC was investigated by using labeled tumor cells and the ability of reovirus-loaded DC to prime T cells was also investigated. Results: In the presence of human neutralizing serum DC, but not T cells, were able to deliver reovirus for melanoma cell killing in vitro. Electron microscopy suggested that DC protected the virus by internalization, whereas with T cells it remained bound to the surface and hence accessible to neutralizing antibodies. Furthermore, DC loaded with reovirus were fully functional with regard to phagocytosis and priming of specific antitumor immune responses. Conclusions: The delivery of reovirus via DC could be a promising new approach offering the possibility of combining systemic viral therapy for metastatic disease with induction of an antitumor immune response. Clin Cancer Res; 17(9); 2767-76. (C)2011 AACR.Microscopic imaging and technolog