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1.
Tran Thi Hien Ines Ambite Murphy Lam Yim Wan Michele Cavalera Parisa Esmaeili Arunima Chaudhuri Samudra Sabari Marek Babjuk Catharina Svanborg 《International journal of cancer. Journal international du cancer》2023,153(3):584-599
Bladder cancer is common and one of the most costly cancer forms, due to a lack of curative therapies. Recently, clinical safety and efficacy of the alpha1-oleate complex was demonstrated in a placebo-controlled study of nonmuscle invasive bladder cancer. Our study investigated if long-term therapeutic efficacy is improved by repeated treatment cycles and by combining alpha1-oleate with low-dose chemotherapy. Rapidly growing bladder tumors were treated by intravesical instillation of alpha1-oleate, Epirubicin or Mitomycin C alone or in combination. One treatment cycle arrested tumor growth, with a protective effect lasting at least 4 weeks in mice receiving 8.5 mM of alpha1-oleate alone or 1.7 mM of alpha-oleate combined with Epirubicin or Mitomycin C. Repeated treatment cycles extended protection, defined by a lack of bladder pathology and a virtual absence of bladder cancer-specific gene expression. Synergy with Epirubicin was detected at the lower alpha1-oleate concentration and in vitro, alpha1-oleate was shown to enhance the uptake and nuclear translocation of Epirubicin, by tumor cells. Effects at the chromatin level affecting cell proliferation were further suggested by reduced BrdU incorporation. In addition, alpha1-oleate triggered DNA fragmentation, defined by the TUNEL assay. The results suggest that bladder cancer development may be prevented long-term in the murine model, by alpha1-oleate alone or in combination with low-dose Epirubicin. In addition, the combination of alpha1-oleate and Epirubicin reduced the size of established tumors. Exploring these potent preventive and therapeutic effects will be of immediate interest in patients with bladder cancer. 相似文献
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Böthig Ralf Schöps Wolfgang Zellner Michael Fiebag Kai Kowald Birgitt Hirschfeld Sven Thietje Roland Kurze Ines Böhme Holger Kaufmann Albert Jungmann Olaf Zumbé Jürgen Porres Daniel Nehiba Marcus Kadhum Thura Golka Klaus Forchert Martin 《Trauma und Berufskrankheit》2019,21(1):61-73
Trauma und Berufskrankheit - Zur Zusammenhangsbeurteilung traumatisch bedingter Querschnittlähmungen und Jahre später auftretender Harnblasenkarzinome gibt es keine aussagefähige... 相似文献
6.
Ángela Delucchi Luis Toro Rodrigo Alzamora Victor Barrientos Magdalena González Rodrigo Andaur Pablo León Francisco Villanueva Mario Galindo Facundo Las Heras Martín Montecino Daniel Moena Andrea Lazcano Viola Pinto Paulina Salas María Loreto Reyes Verónica Mericq Luis Michea 《Journal of bone and mineral research》2019,34(10):1851-1861
Renal transplantation (RTx) is an effective therapy to improve clinical outcomes in pediatric patients with terminal chronic kidney disease. However, chronic immunosuppression with glucocorticoids (GCs) reduces bone growth and BMD. The mechanisms causing GC-induced growth impairment have not been fully clarified. Fibroblast growth factor 23 (FGF23) is a peptide hormone that regulates phosphate homeostasis and bone growth. In pathological conditions, FGF23 excess or abnormal FGF receptors (FGFR) activity leads to bone growth impairment. Experimental data indicate that FGF23 expression is induced by chronic GC exposure. Therefore, we hypothesize that GCs impair bone growth by increasing FGF23 expression, which has direct effects on bone growth plate. In a post hoc analysis of a multicentric randomized clinical trial of prepubertal RTx children treated with early GC withdrawal or chronic GC treatment, we observed that GC withdrawal was associated with improvement in longitudinal growth and BMD, and lower plasma FGF23 levels as compared with a chronic GC group. In prepubertal rats, GC-induced bone growth retardation correlated with increased plasma FGF23 and bone FGF23 expression. Additionally, GC treatment decreased FGFR1 expression whereas it increased FGFR3 expression in mouse tibia explants. The GC-induced bone growth impairment in tibiae explants was prevented by blockade of FGF23 receptors using either a pan-FGFR antagonist (PD173074), a C-terminal FGF23 peptide (FGF23180-205) which blocks the binding of FGF23 to the FGFR-Klotho complex or a specific FGFR3 antagonist (P3). Finally, local administration of PD173074 into the tibia growth plate ameliorated cartilage growth impairment in GC-treated rats. These results show that GC treatment partially reduces longitudinal bone growth via upregulation of FGF23 and FGFR3 expression, thus suggesting that the FGF23/Klotho/FGFR3 axis at the growth plate could be a potential therapeutic target for the management of GC-induced growth impairment in children. 相似文献
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Johannes Poms Stephan Sacher Matthias Nixdorf Michael Dekner Sabine Wallner-Mang Ines Janssen 《Pharmaceutical development and technology》2019,24(6):739-750
An undesirable characteristic in lyophilized parenteral products is the potential presence of particulate matter in the final product, which may affect patient safety. In this study, quality risk management tools described in the International Conference on Harmonization Guideline Q9 were used to estimate the risks for a pharmaceutical manufacturing line, based on three critical quality attributes: (1) visible particulate matter; (2) lyo-cake collapse traces; and (3) lyo-cake melt-back traces. Together with a Process Failure Mode Effect Analysis (PFMEA), an input-output analysis of the individual unit operations identified seven major material classes of extrinsic particulate matter. In addition to the process assessment, an experimental investigation of the location of impurities in lyophilized products was performed. To that end, intentionally contaminated vials were examined to locate the particulate matter and its possible migration. The results emphasize the importance of a full transmission mode release testing since the particles may enter the interior of the lyo-cake. A theoretical explanation of the observed impurity locations is provided. 相似文献
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Ines Dallel Intidhar Ben Salem Abderrahmen Merghni Wassim Bellalah Fadoua Neffati Samir Tobji Maha Mastouri Adel Ben Amor 《The Angle orthodontist》2020,90(4):532
ObjectivesTo evaluate the effect of orthodontic appliances on physicochemical, biochemical, and oxidative stress changes in salivary parameters during treatment.Materials and MethodsA cohort study was conducted with 112 healthy patients. Salivary samples were taken at baseline, 1 month, and 9 months after placement of the orthodontic appliances used in treatment.ResultsA statistically significant difference was observed in certain examined salivary parameters, including enzymes, electrolytes, and oxidative stress markers.ConclusionsThe use of aligners had a lower prevalence of disturbing salivary parameters. Orthodontist must consider these changes to prevent the occurrence of white spot lesions. 相似文献
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Hana Sahli Asma Bachali Raoudha Tekaya Ines Mahmoud Yassine Sedki Olfa Saidane Leila Abdelmoula 《Foot and Ankle Surgery》2019,25(2):226-230
Background
The purpose of this study was to evaluate the foot involvement in a group of patients with spondyloarthritis in regard to symptoms, type and frequency of deformities, location and radiological changes.Methods
We conducted a cross sectional study including 60 patients with spondyloarthritis over a period of six months. Anamnesis, clinical examination, podoscopic examination, biological tests and X-rays of feet were done for each patient.Results
Foot involvement was found in 31 patients (52%). It was symptomatic in 35% of cases and inaugural in 42% of cases. The most frequent site was the hindfoot (22 patients/31). Radiological findings were: erosion (17%), reconstruction (33%), erosion and reconstruction (50%). Forefoot involvement was found in 18/31 patients. Forefoot deformities were found in 9 patients. Two patients had sausage toe and feet skin abnormalities were observed in 12 patients. At podoscopic examination, 23 patients had abnormal footprints. Foot involvement was more frequent in peripheral spondyloarthritis (p = 0.008). Patients with foot involvement had an advanced age of disease onset (p = 0.05), a shorter disease duration (p = 0.038) and more comorbidities (p = 0.039). Foot involvement was correlated with C Reactive protein (p = 0.043).Conclusion
In our study, foot involvement and foot symptoms were seen frequently in spondyloarthritis and it is associated with late onset of the disease and with higher inflammation in blood tests. 相似文献10.
Kaylah Curtis Christopher J. Stewart Meghan Robinson David L. Molfese Savannah N. Gosnell Thomas R. Kosten Joseph F. Petrosino Richard De La Garza Ramiro Salas 《The European journal of neuroscience》2019,50(3):2446-2452
The gut microbiota has recently gained attention as a possible modulator of brain activity. A number of reports suggest that the microbiota may be associated with neuropsychiatric conditions such as major depressive disorder, autism and anxiety. The gut microbiota is thought to influence the brain via vagus nerve signalling, among other possible mechanisms. The insula processes and integrates these vagal signals. To determine if microbiota diversity and structure modulate brain activity, we collected faecal samples and examined insular function using resting state functional connectivity (RSFC). Thirty healthy participants (non‐smokers, tobacco smokers and electronic cigarette users, n = 10 each) were studied. We found that the RSFC between the insula and several regions (frontal pole left, lateral occipital cortex right, lingual gyrus right and cerebellum 4, 5 and vermis 9) were associated with bacterial microbiota diversity and structure. In addition, two specific bacteria genera, Prevotella and Bacteroides, were specifically different in tobacco smokers and also associated with insular connectivity. In conclusion, we show that insular connectivity is associated with microbiome diversity, structure and at least two specific bateria genera. Furthemore, this association is potentially modulated by tobacco smoking, although the sample sizes for the different smoking groups were small and this result needs validation in a larger cohort. While replication is necessary, the microbiota is a readily accessible therapeutic target for modulating insular connectivity, which has previously been shown to be abnormal in anxiety and tobacco use disorders. 相似文献