Heterogeneous response of individual multicellular tumour spheroids to immunotoxins and ricin toxin.

The cytoreductive effects of anti-transferrin receptor (anti-TfnR) immunotoxins (ITs) and of ricin toxin against tumour micromasses have been evaluated in a multicellular tumour spheroid (MTS) model. More than 600 (656) MTSs obtained with human breast carcinoma (MCF7) or rat glioblastoma (9L) cell lines were treated individually with ITs or toxin and the effects induced by the treatment were measured for each MTS as volume variation vs time by applying the Gompertz growth model. Two dose-dependent patterns of MTS growth were observed in MTSs of both cell lines in response to IT or toxin treatment: (1) complete inhibition of MTS growth (''sterilisation''); and (2) partial/complete inhibition (''heterogeneous response''). Within the range of IT or toxin concentrations resulting in partial inhibition of MTS growth, the sensitivity of treated MTSs was extremely heterogeneous (the cytoreductive effects varying between 0.1 and 4 logs of cells killed for a given IT or toxin concentration). Analysis of the post-treatment regrowth kinetics indicated that treated non-sterilised and control MTSs reached the same final limiting volumes. However, the doubling time estimated for the surviving cells of treated MCF7 and 9L MTSs ranged between 15 and 50 h, indicating that each MTS had individual growing potential. In conclusion, our results indicate that at substerilising IT concentrations individual heterogenicity of MTSs may greatly influence the cytoreductive potential of ITs. An implication of our study is that the efficacy of an IT treatment in eradicating disseminated micrometastases may not be predictable a priori. The MTS model that we describe in this paper may help in dissecting out factors limiting the effect of ITs in three-dimensional tumours.     

Influence of glutathione administration on the disposition of free and total platinum in patients after administration of cisplatin

Summary The kinetics of platinum (Pt) was studied in 12 patients suffering from non-small-cell lung cancer or pleural mesothelioma. Each subject received an infusion of cisplatin (CDDP, 80 mg/m²), and six patients were pretreated with glutathione (GSH, 2.5 g given i.v.) at 15 min prior to the cisplatin infusion. After a 3- to 4-week interval, all patients were given a second course of treatment on the same schedule. A biexponential model was fitted to plasma concentrations of total and ultrafilterable Pt. The excretion of Pt in urine was evaluated during the first 48 h after the CDDP infusion. Following the administration of CDDP alone or with GSH pretreatment, the pharmacokinetic parameters of Pt did not significantly differ between the treatments. Also, the unbound fraction determined at each sampling time did not vary significantly between the treatments. However, it is noteworthy that the mean values obtained for the terminal half0life, the volume of distribution, the renal clearance, the percentage of the dose excreted in the urine, and the mean residence time of total Pt were higher in patients who had been pretreated with GSH, suggesting that SGH might increase both the rate of Pt elimination and the extent of Pt distribution and, as a consequence of the latter, might prolong the residence time of Pt in the body. In addition, the unbound fraction of Pt from the 4th to the 48th h was higher following the first dose of CDDP+GSH than after treatment with CDDP alone. Because of the rather high variability in the values of the parameters obtained, further work is planned using a larger number of patients.     

Different biological properties of paired HIV-1 isolates from peripheral blood mononuclear cells and cerebrospinal fluid.

Seven paired HIV-1 isolates from peripheral blood mononuclear cells (PMCs) and cerebrospinal fluid (CSF) of infected subjects at various stages of the disease were studied for their capacity to replicate in continuous cell lines (Molt-3 and U-937 cells) and to induce cytopathic effects "in vitro". Obtained results indicate that paired HIV-1 isolates from PMCs and CSF of the same patient can differ in their replicative activity "in vitro", suggesting that, at least in some cases, CSF isolates may represent a distinct subtype of HIV-1.     

Überrollung eines Radfahrers

As road users cyclists are particularly exposed to extraordinary hazards in accidents with heavy vehicles. Vehicular accident reconstruction is essential in criminal and civil proceedings. This article presents the case of a young cyclist who was run over by a cement mixer truck. A music player (iPod®) with connected headphones was found at the scene in the trousers of the victim. The forensic pathology services were asked by the police if the man had had the headphones in the ears when the truck collision occurred. At autopsy unusual tyre tread marks were detected on the neck, the left ear and the chest region. Furthermore, an imprint of the headphone cable could be traced to the ear on one side.     

Postmortem coronary artery calcium score in cases of myocardial infarction

International Journal of Legal Medicine - Sudden cardiac death (SCD) related to atherosclerotic coronary artery disease (ACAD) resulting in myocardial infarction is the most prevalent cause of...     

The Effect of Taurine on Hepatic Steatosis Induced by Thioacetamide in Zebrafish (<Emphasis Type="Italic">Danio rerio</Emphasis>)

Background  

Nonalcoholic fatty liver disease is one of the most prevalent forms of chronic liver disease in the Western world. Taurine is a conditionally essential amino acid in humans that may be a promising therapy for treating this disease.     

Modelling and Performance Analysis of MgB2 and Hybrid Magnetic Shields

Superconductors are strategic materials for the fabrication of magnetic shields, and within this class, MgB2 has been proven to be a very promising option. However, a successful approach to produce devices with high shielding ability also requires the availability of suitable simulation tools guiding the optimization process. In this paper, we report on a 3D numerical model based on a vector potential (A)-formulation, exploited to investigate the properties of superconducting (SC) shielding structures with cylindrical symmetry and an aspect ratio of height to diameter approaching one. To this aim, we first explored the viability of this model by solving a benchmark problem and comparing the computation outputs with those obtained with the most used approach based on the H-formulation. This comparison evidenced the full agreement of the computation outcomes as well as the much better performance of the model based on the A-formulation in terms of computation time. Relying on this result, the latter model was exploited to predict the shielding properties of open and single capped MgB2 tubes with and without the superimposition of a ferromagnetic (FM) shield. This investigation highlighted that the addition of the FM shell is very efficient in increasing the shielding factors of the SC screen when the applied magnetic field is tilted with respect to the shield axis. This effect is already significant at low tilt angles and allows compensating the strong decrease in the shielding ability that affects the short tubular SC screens when the external field is applied out of their axis.