101 research outputs found

    Prothymosin α receptors on peripheral blood mononuclear cells

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    Abstract125I-Labeled prothymosin α (ProTα) was used to study the presence and characteristics of receptors for ProTα on human peripheral blood mononuclear cells (PBMC). The kinetics of 125I-ProTα binding to PBMC was fast at 37°C, whilst it required 50 min to reach equilibrium at 4°C and room temperature. Analysis of steady state binding data by the method of Scatchard and by unlabeled ProTα competition experiments identified two binding sites with an apparent equilibrium dissociation constant of 216–321 pM for the high-affinity receptor and of 11.4–21.1 nM for the low-affinity one; the sites per cell ranged from 1,479 to 1,519 and from 47,547 to 56,169, respectively. The kinetically derived equilibrium dissociation constant agreed with these data and showed no interaction between receptors

    Mechanisms underlying cytotoxicity induced by engineered nanomaterials: a review of in vitro studies

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    Engineered nanomaterials are emerging functional materials with technologically interesting properties and a wide range of promising applications, such as drug delivery devices, medical imaging and diagnostics, and various other industrial products. However, concerns have been expressed about the risks of such materials and whether they can cause adverse effects. Studies of the potential hazards of nanomaterials have been widely performed using cell models and a range of in vitro approaches. In the present review, we provide a comprehensive and critical literature overview on current in vitro toxicity test methods that have been applied to determine the mechanisms underlying the cytotoxic effects induced by the nanostructures. The small size, surface charge, hydrophobicity and high adsorption capacity of nanomaterial allow for specific interactions within cell membrane and subcellular organelles, which in turn could lead to cytotoxicity through a range of different mechanisms. Finally, aggregating the given information on the relationships of nanomaterial cytotoxic responses with an understanding of its structure and physicochemical properties may promote the design of biologically safe nanostructures

    Comparative sensitivity of tumor and non-tumor cell lines as reliable approach for in vitro cytotoxicity screening of lysine-based surfactants with potential pharmaceutical applications

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    Surfactants are used as additives in topical pharmaceuticals and drug delivery systems. The biocompatibility of amino acid-based surfactants makes them highly suitable for use in these fields, but tests are needed to evaluate their potential toxicity. Here we addressed the sensitivity of tumor (HeLa, MCF-7) and non-tumor (3T3, 3T6, HaCaT, NCTC 2544) cell lines to the toxic effects of lysine-based surfactants by means of two in vitro endpoints (MTT and NRU). This comparative assay may serve as a reliable approach for predictive toxicity screening of chemicals prior to pharmaceutical applications. After 24-h of cell exposure to surfactants, differing toxic responses were observed. NCTC 2544 and 3T6 cell lines were the most sensitive, while both tumor cells and 3T3 fibroblasts were more resistant to the cytotoxic effects of surfactants. IC50-values revealed that cytotoxicity was detected earlier by MTT assay than by NRU assay, regardless of the compound or cell line. The overall results showed that surfactants with organic counterions were less cytotoxic than those with inorganic counterions. Our findings highlight the relevance of the correct choice and combination of cell lines and bioassays in toxicity studies for a safe and reliable screen of chemicals with potential interest in pharmaceutical industry

    A qualitative study exploring the patients' perspective from the 'Reserved Therapeutic Space' nursing intervention in acute mental health units

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    This study aimed to explore the perspective of people who had experienced treatment as patients at acute mental health units, regarding an intervention model to improve therapeutic relationships in the units, which had been previously designed by the nurses. The study participants were people linked to collectives for social activism in mental health. Six focus groups were held. The results were classified into three themes: (a) the meaning of a space to enable the establishment of a therapeutic relationship, (b) the procedures to implement the space, and (c) the difficulties to overcome to establish the space. For the participants, the Reserved Therapeutic Space intervention was perceived as a space where they could share expectations and needs with the nurses, considering it as both valid and useful to improve the therapeutic relationship in acute units. For the participants, the intervention should be structured in three stages: orientation, follow-up, and discharge. The content of the intervention should be proposed by the patients based on their needs and concerns. The barriers identified for carrying out the intervention were the lack of relational competence, the violation of rights, and the lack of accessibility of nurses. The facilitating elements were the availability of nurses, active listening, and empathy. The resulting intervention model includes realities of both groups, providing insights for nurses to initiate a space with patients and improve their therapeutic relationship. This intervention model could be used by managers to test its effectiveness

    Efficacy and complications associated with a modified inferior alveolar nerve block technique. A randomized, triple-blind clinical trial

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    Objectives: To compare the efficacy and complication rates of two different techniques for inferior alveolar nerve blocks (IANB). Study D esign: A randomized, triple-blind clinical trial comprising 109 patients who required lower third molar removal was performed. In the control group, all patients received an IANB using the conventional Halsted technique, whereas in the experimental group, a modified technique using a more inferior injection point was performed. Results: A total of 100 patients were randomized. The modified technique group showed a significantly higher onset time in the lower lip and chin area, and was frequently associated to a lingual electric discharge sensation. Three failures were recorded, 2 of them in the experimental group. No relevant local or systemic complications were registered. Conclusions: Both IANB techniques used in this trial are suitable for lower third molar removal. However, perform - ing an inferior alveolar nerve block in a more inferior position (modified technique) extends the onset time, does not seem to reduce the risk of intravascular injections and might increase the risk of lingual nerve injuries

    Membrane-destabilizing activity of pH-responsive cationic lysine-based surfactants: role of charge position and alkyl chain length

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    Many strategies for treating diseases require the delivery of drugs into the cell cytoplasm following internalization within endosomal vesicles. Thus, compounds triggered by low pH to disrupt membranes and release endosomal contents into the cytosol are of particular interest. Here, we report novel cationic lysine-based surfactants (hydrochloride salts of N¿- and N¿-acyl lysine methyl ester) that differ in the position of the positive charge and the length of the alkyl chain. Amino acid-based surfactants could be promising novel biomaterials in drug delivery systems, given their biocompatible properties and low cytotoxic potential. We examined their ability to disrupt the cell membrane in a range of pH values, concentrations and incubation times, using a standard hemolysis assay as a model of endosomal membranes. Furthermore, we addressed the mechanism of surfactant-mediated membrane destabilization, including the effects of each surfactant on erythrocyte morphology as a function of pH. We found that only surfactants with the positive charge on the ¿-amino group of lysine showed pH-sensitive hemolytic activity and improved kinetics within the endosomal pH range, indicating that the positive charge position is critical for pH-responsive behavior. Moreover, our results showed that an increase in the alkyl chain length from 14 to 16 carbon atoms was associated with a lower ability to disrupt cell membranes. Knowledge on modulating surfactant-lipid bilayer interactions may help us to develop more efficient biocompatible amino acid-based drug delivery devices

    Efficacy and complications associated with a modified inferior alveolar nerve block technique. A randomized, triple-blind clinical trial

    Get PDF
    Objectives: To compare the efficacy and complication rates of two different techniques for inferior alveolar nerve blocks (IANB). Study Design: A randomized, triple-blind clinical trial comprising 109 patients who required lower third molar removal was performed. In the control group, all patients received an IANB using the conventional Halsted technique, whereas in the experimental group, a modified technique using a more inferior injection point was performed. Results: A total of 100 patients were randomized. The modified technique group showed a significantly higher onset time in the lower lip and chin area, and was frequently associated to a lingual electric discharge sensation. Three failures were recorded, 2 of them in the experimental group. No relevant local or systemic complications were registered. Conclusions: Both IANB techniques used in this trial are suitable for lower third molar removal. However, performing an inferior alveolar nerve block in a more inferior position (modified technique) extends the onset time, does not seem to reduce the risk of intravascular injections and might increase the risk of lingual nerve injuries
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