scholarly journals Cellular senescence and autophagy of myoepithelial cells are involved in the progression of in situ areas of carcinoma ex-pleomorphic adenoma to invasive carcinoma. An in vitro model

2015 ◽  
Vol 9 (3) ◽  
pp. 255-265 ◽  
Author(s):  
Carolina Amália Barcellos Silva ◽  
Elizabeth Ferreira Martinez ◽  
Ana Paula Dias Demasi ◽  
Albina Altemani ◽  
Jeruza Pinheiro da Silveira Bossonaro ◽  
...  
2005 ◽  
Vol 288 (3) ◽  
pp. L536-L545 ◽  
Author(s):  
Jackeline Agorreta ◽  
Javier J. Zulueta ◽  
Luis M. Montuenga ◽  
Mercedes Garayoa

Adrenomedullin (ADM) is upregulated independently by hypoxia and LPS, two key factors in the pathogenesis of acute lung injury (ALI). This study evaluates the expression of ADM in ALI using experimental models combining both stimuli: an in vivo model of rats treated with LPS and acute normobaric hypoxia (9% O2) and an in vitro model of rat lung cell lines cultured with LPS and exposed to hypoxia (1% O2). ADM expression was analyzed by in situ hybridization, Northern blot, Western blot, and RIA analyses. In the rat lung, combination of hypoxia and LPS treatments overcomes ADM induction occurring after each treatment alone. With in situ techniques, the synergistic effect of both stimuli mainly correlates with ADM expression in inflammatory cells within blood vessels and, to a lesser extent, to cells in the lung parenchyma and bronchiolar epithelial cells. In the in vitro model, hypoxia and hypoxia + LPS treatments caused a similar strong induction of ADM expression and secretion in epithelial and endothelial cell lines. In alveolar macrophages, however, LPS-induced ADM expression and secretion were further increased by the concomitant exposure to hypoxia, thus paralleling the in vivo response. In conclusion, ADM expression is highly induced in a variety of key lung cell types in this rat model of ALI by combination of hypoxia and LPS, suggesting an essential role for this mediator in this syndrome.


2012 ◽  
Vol 6 (2) ◽  
pp. 107-109 ◽  
Author(s):  
Elizabeth F. Martinez ◽  
Pollyanna T. Montaldi ◽  
Ney S. de Araújo ◽  
Albina Altemani ◽  
Vera C. de Araújo
Keyword(s):  

2020 ◽  
Author(s):  
Toni Wendler ◽  
Torsten Prietzel ◽  
Robert Möbius ◽  
Jean-Pierre Fischer ◽  
Andreas Roth ◽  
...  

Abstract BackgroundAll current total hip arthroplasty (THA) systems are modular in design. Only during the operation femoral head and stem get connected by a Morse taper junction. The junction is realized by hammer blows from the surgeon. Decisive for the junction strength is the maximum force acting once in direction of the neck axis, which depends both on the applied impulse and the damping of human soft tissues. This leads to large differences in assembly forces between the surgeons. The investigation of assembly forces of different surgeons under influence of soft tissue damping is subject of this study.MethodsFirst, a measuring system, consisting of a prosthesis and a hammer, was developed. Both components are equipped with a piezoelectric force sensor. Initially, in situ experiments on human cadavers were carried out using this system in order to determine the actual assembly forces and to characterize the damping properties of human soft tissue. In addition to these experiments, an in vitro model in form of an artificial femur (Sawbones Europe AB, Malmo, Sweden) with implanted measuring stem embedded in gelatine was developed. The gelatine mixture was chosen in such a way that damping properties of the model correspond to those in situ. A study with 31 surgeons was carried out on the in vitro model mentioned above, in which the assembly forces were determined.ResultsA model has been developed, that represents the physiological damping behaviour of human soft tissue. The assembly forces measured on in vitro model were on average 2037.2 N ± 724.9 N and ranged from 822.5 N to 3835.2 N. The comparison of the surgeons showed no significant differences regarding sex (p=0.09), work experience (p=0.71) and number of THAs per year (p=0.69).ConclusionsAll measured assembly forces were below 4 kN, which is recommended in the literature. This could lead to increased corrosion following fretting in the head-neck interface. In addition, there was a very wide range of assembly forces among the surgeons, although other influencing factors such as different implant sizes or materials were not taken into account. To ensure optimal assembly force, the impaction should be standardized, e.g. by an appropriate surgical instrument.


2004 ◽  
Vol 10 (2) ◽  
pp. 327-336 ◽  
Author(s):  
Arnulf Pascher ◽  
Andre F. Steinert ◽  
Glyn D. Palmer ◽  
Oliver Betz ◽  
Jean-Noel Gouze ◽  
...  

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252724
Author(s):  
Moris Topaz ◽  
Abed Athamna ◽  
Itamar Ashkenazi ◽  
Baruch Shpitz ◽  
Sarit Freimann

Background Pseudomonas aeruginosa (P. aeruginosa), Escherichia coli (E. coli), and Staphylococcus aureus (S. aureus) are common pathogens encountered in infected cardiovascular-implantable electronic device (CIED). Continuous, in-situ targeted, ultra-high concentration antibiotic (CITA) treatment is a novel antibiotic treatment approach for localized infections. CITA provides sufficient local antibiotic concentrations to heavily infected cavities while avoiding systemic toxicity. Aim In-vitro confirmation of the efficacy of the CITA treatment approach in simulated compartmentalized infections. Materials and methods A rapid automated bacterial culture analyzing system) Uro4 HB&L™ (was applied to compare the efficacy of selected antibiotics at a standard minimal inhibitory concentration (1MIC), 4MIC, and CITA at 103MIC, for growth inhibition of high bacterial loads (106 colony-forming-units/ml) of ATCC strains of P. aeruginosa, E. coli, and S. aureus. Results The addition of gentamicin and amikacin at 1MIC concentrations only temporarily inhibited the exponential growth of E. coli and P. aeruginosa. 4MIC level extended the delay of exponential bacterial growth. Increasing concentrations of vancomycin similarly temporarily delayed S. aureus growth. All tested antibiotics at CITA of 103MIC totally inhibited the exponential growth of the tested bacteria through 72 hours of exposure. (P<0.001). Conclusion In this in-vitro model, CITA at 103MIC effectively inhibited exponential bacterial growth of high loads of P. aeruginosa, E. coli, and S. aureus. This model offers preliminary laboratory support for the benefit of the in-situ antibiotic treatment, providing ultra-high concentrations directly at the compartmentalized infection site, not achievable by the conventional intravenous and oral routes.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jianyang Liu ◽  
Jialin He ◽  
Lite Ge ◽  
Han Xiao ◽  
Yan Huang ◽  
...  

Abstract Background Intracerebral hemorrhage (ICH) is a major public health concern, and mesenchymal stem cells (MSCs) hold great potential for treating ICH. However, the quantity and quality of MSCs decline in the cerebral niche, limiting the potential efficacy of MSCs. Hypoxic preconditioning is suggested to enhance the survival of MSCs and augment the therapeutic efficacy of MSCs in ICH. MicroRNAs (miRNAs) are known to mediate cellular senescence. However, the precise mechanism by which miRNAs regulate the senescence of hypoxic MSCs remains to be further studied. In the present study, we evaluated whether hypoxic preconditioning enhances the survival and therapeutic effects of olfactory mucosa MSC (OM-MSC) survival and therapeutic effects in ICH and investigated the mechanisms by which miRNA ameliorates hypoxic OM-MSC senescence. Methods In the in vivo model, ICH was induced in mice by administration of collagenase IV. At 24 h post-ICH, 5 × 105 normoxia or hypoxia OM-MSCs or saline was administered intracerebrally. The behavioral outcome, neuronal apoptosis, and OM-MSC survival were evaluated. In the in vitro model, OM-MSCs were exposed to hemin. Cellular senescence was examined by evaluating the expressions of P16INK4A, P21, P53, and by β-galactosidase staining. Microarray and bioinformatic analyses were performed to investigate the differences in the miRNA expression profiles between the normoxia and hypoxia OM-MSCs. Autophagy was confirmed using the protein expression levels of LC3, P62, and Beclin-1. Results In the in vivo model, transplanted OM-MSCs with hypoxic preconditioning exhibited increased survival and tissue-protective capability. In the in vitro model, hypoxia preconditioning decreased the senescence of OM-MSCs exposed to hemin. Bioinformatic analysis identified that microRNA-326 (miR-326) expression was significantly increased in the hypoxia OM-MSCs compared with that of normoxia OM-MSCs. Upregulation of miR-326 alleviated normoxia OM-MSC senescence, whereas miR-326 downregulation increased hypoxia OM-MSC senescence. Furthermore, we showed that miR-326 alleviated cellular senescence by upregulating autophagy. Mechanistically, miR-326 promoted the autophagy of OM-MSCs via the PI3K signaling pathway by targeting polypyrimidine tract-binding protein 1 (PTBP1). Conclusions Our study shows that hypoxic preconditioning delays OM-MSC senescence and augments the therapeutic efficacy of OM-MSCs in ICH by upregulating the miR-326/PTBP1/PI3K-mediated autophagy.


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