1,720,980 research outputs found

    Application of Critical Energy Density concept for Minimum Ignition Energy determination

    No full text
    This study presents a new concept, referred to as Critical Energy Density (CED), for estimating the Minimum Ignition Energy (MIE) of organic powders. Only readily experimental data, such as granulometric analysis, thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC), are required for running the mathematical model. The algorithm simulates the heating of a dust cloud exposed to an electrical spark and detects the ignition by comparing the energy released by the volatiles’ homogeneous combustion with a threshold value corresponding to the minimum energy required to sustain the flame propagation (that is, the CED). Validation was performed on six different organic powders, with estimated MIE values showing good agreement with experimental data. This approach provides a cost-effective tool for early-stage hazard assessment in industrial environments where combustible powders are present and supports the development of a safer process design

    Connecting standards and theoretical models for minimum ignition energy Estimation: a procedure to optimize the number of experimental tests

    No full text
    Dust explosions pose a significant concern in the process industry, particularly in the context of risk assessment. Such explosions can be initiated by various ignition sources, including electrical (e.g., static discharges, arcs, equipment-generated sparks) and thermal (e.g., hot surfaces, flame pockets) triggers. Assessing the likelihood and severity of dust explosions is inherently complex. However, the experimental determination of key dust parameters can greatly support the risk evaluation process. Among these parameters, electrical resistivity and Minimum Ignition Energy (MIE) are crucial. Unfortunately, a regular MIE testing demands up to 1 kg of powder, and no existing standard outlines how to reduce the number of required tests. However, EN ISO/IEC 80079-20-2 does not require to carry out a full screening on every possible combination of parameters, but to identify non-combustion and combustion regions. In this framework, theoretical models may offer preliminary MIE estimates, optimizing the experimental procedure. This study proposes a screening flow chart that integrates MIE and electrical resistivity values along with process-specific information (e.g., quantity of dust handled, presence of ignition sources). The aim is to prioritize potentially hazardous substances in the plant for detailed safety evaluation. The advantages and limitations of the proposed flow chart are also discussed

    ADOPTIVE TRANSFER OF LYMPHOKINE-ACTIVATED KILLER-CELLS LOADED WITH 4'-DEOXY-4'-IODODOXORUBICIN - THERAPEUTIC EFFECT IN MICE BEARING LUNG METASTASES

    Full text link
    We studied the potential use of lymphokine-activated killer (LAK) cells loaded with 4'-deoxy-4'-iododoxorubicin (IDX) in adoptive immunotherapy experiments. Because LAK cells preferentially locate in the lung, we evaluated the therapeutic effect of IDX-loaded LAK cells in mice bearing lung metastases induced by B16F1 tumor cell injection. In vitro studies showed that LAK cells rapidly incorporated IDX, with maximum uptake at 15 min, followed by a plateau; drug efflux was initially rapid and then continued at a much slower rate. Evaluation of LAK cell cytotoxic activity against relevant target cells showed a 30% decrease after IDX treatment that progressed with time over the next 6 h. P388 tumor cell growth was inhibited by coculture with IDX-loaded LAK cells, thus demonstrating that the released IDX maintained its pharmacological activity. Finally, high performance liquid chromatography analysis of tissue IDX concentration revealed a considerably higher and long-lasting concentration in the lungs of mice receiving IDX-loaded LAK cells, compared to mice given injections of a comparable amount of free drug. Moreover, adoptive transfer of IDX-loaded LAK cells into tumor-bearing mice caused a significant reduction in the number of lung metastases versus control mice given injections of even higher doses of free drug

    4'-Iodo-4'-deoxydoxorubicin disrupts the fibrillar structure of transthyretin amyloid

    No full text
    Transthyretin (TTR) is a tetrameric protein synthesized mainly by the liver and the choroid plexus, from where it is secreted into the plasma and the cerebrospinal fluid, respectively. Some forms of polyneuropathy, vitreopathy, and cardiomyopathy are caused by the deposition of normal and/or mutant TTR molecules in the form of amyloid fibrils. Familial amyloidotic polyneuropathy is the most common form of TTR amyloidosis related to the V30M variant. It is still unclear the process by which soluble proteins deposit as amyloid. The treatment of amyloid-related disorders might attempt the stabilization of the soluble protein precursor to retard or inhibit its deposition as amyloid; or aim at the resorption of the deposited amyloid. The anthracycline 4'-iodo-4'-deoxydoxorubicin (I-DOX) has been shown to reduce the amyloid load in immunoglobulin light-chain amyloidosis. We investigated 1) whether I-DOX has affinity for TTR amyloid in tissues, 2) determined the I-DOX binding constants to TTR synthetic fibrils, and 3) determined the nature of the effect of I-DOX on TTR fibrils. We report that 1) I-DOX co-localizes with amyloid deposits in tissue sections of patients with familial amyloidotic polyneuropathy; 2) I-DOX strongly interacts with TTR amyloid fibrils and presents two binding sites with k(d) of 1.5 x 10(-11) mol/L and 5.6 x 10(-10) mol/L, respectively; and 3) I-DOX disrupts the fibrillar structure of TTR amyloid into amorphous material, as assessed by electron microscopy but does not solubilize the fibrils as confirmed by filter assays. These data support the hypothesis that I-DOX and less toxic derivatives can prove efficient in the treatment of TTR-related amyloidosis

    Delivery of methoxymorpholinyl doxorubicin by interleukin 2-activated NK cells: effect in mice bearing hepatic metastases

    Full text link
    The possibility of using interleukin 2 (IL-2)-activated natural killer cells (A-NK) to carry methoxymorpholinyl doxorubicin (MMDX; PNU 152243) to liver-infiltrating tumours was explored in mice bearing 2-day established M5076 reticulum cell sarcoma hepatic metastases. In vitro, MMDX was 5.5-fold more potent than doxorubicin against M5076 tumour cells. MMDX uptake by A-NK cells correlated linearly with drug concentration in the incubation medium [correlation coefficient (r) = 0.999]; furthermore, as MMDX incorporation was readily reproducible in different experiments, the amount of drug delivered by A-NK cells could be modulated. In vivo experiments showed that intravenous (i.v.) injection of MMDX-loaded A-NK cells exerted a greater therapeutic effect than equivalent or even higher doses of free drug. The increase in lifespan (ILS) following A-NK cell delivery of 53 microg kg(-1) MMDX, a dosage that is ineffective when administered in free form, was similar to that observed in response to 92 microg kg(-1) free drug, a dosage close to the 10% lethal dose (ILS 42% vs. 38% respectively). These results correlated with pharmacokinetic studies showing that MMDX encapsulation in A-NK cells strongly modifies its organ distribution and targets it to tissues in which IL-2 activated lymphocytes are preferentially entrapped after i.v. injection
    corecore