Comprehensive in vitro and in ovo assessment of cytotoxicity: Unraveling the impact of sodium fluoride, xylitol, and their synergistic associations in dental products.

Over the past several decades, dental health products containing fluoride have been widely employed to mitigate tooth decay and promote oral hygiene. However, concerns regarding the potential toxicological repercussions of fluoride exposure have incited continuous scientific inquiry. The current study investigated the cytotoxicity of sodium fluoride (NaF) and xylitol (Xyl), both individually and in combination, utilizing human keratinocyte (HaCaT) and osteosarcoma (SAOS-2) cell lines. In HaCaT cells, NaF decreased proliferation in a concentration-dependent manner and induced apoptosis-related morphological changes at low concentrations, whereas Xyl exhibited dose-dependent cytotoxic effects. The combination of NaF and Xyl reduced cell viability, particularly at higher concentrations, accompanied by apoptosis-like morphological alterations. Sub-cytotoxic NaF concentrations (0.2%) significantly affected caspase activity and the expression of pro-apoptotic genes. Conversely, Xyl demonstrated no discernible effect on these biological parameters. In SAOS-2 cells, NaF increased proliferation at high concentrations, contrasting with Xyl's concentration-dependent cytotoxic effects. The combination of NaF and Xyl had a minimal impact on cell viability. Sub-cytotoxic NaF concentrations did not influence caspase activity or gene expression, while Xyl induced dose-dependent morphological alterations, increased caspase activity, and upregulated pro-apoptotic gene expression. In ovo experiments on the chorioallantoic membrane (CAM) revealed that only NaF induced irritant effects, suggesting potential vascular adverse outcomes. This study advocates for the combined use of NaF and Xyl, highlighting their cytotoxicity benefits in healthy cells while maintaining safety considerations for tumor cells.

A Preliminary Report Regarding the Morphological Changes of Nano-Enabled Pharmaceutical Formulation on Human Lung Carcinoma Monolayer and 3D Bronchial Microtissue.

Background and Objectives: Nowadays, the development of enabled pharmaceutical nanoparticles of solid lipid type is continuously growing, because they have the potential to be used for targeted drug release leading to an increased effect of chemotherapy, being used in lung cancer nano-diagnosis and nano-therapy. The current study reports the preliminary results obtained regarding the biological effect of a new nano-enabled pharmaceutical formulation in terms of its cytotoxic and biosafety profile. Materials and Methods: The pharmaceutical formulations consist of solid lipid nanoparticles (SLN) obtained via the emulsification-diffusion method by loading green iron oxide nanoparticles (green-IONPs) with a pentacyclic triterpene (oleanolic acid-OA). Further, a complex biological assessment was performed, employing three-dimensional (3D) bronchial microtissues (EpiAirwayTM) to determine the biosafety profile of the SLN samples. The cytotoxic potential of the samples was evaluated on human lung carcinoma, using an in vitro model (A549 human lung carcinoma monolayer). Results: The data revealed that the A549 cell line was strongly affected after treatment with SLN samples, especially those that contained OA-loaded green-IONPs obtained with Ocimum basilicum extract (under 30% viability rates). The biosafety profile investigation of the 3D normal in vitro bronchial model showed that all the SLN samples negatively affected the viability of the bronchial microtissues (below 50%). As regards the morphological changes, all the samples induce major changes such as loss of the surface epithelium integrity, loss of epithelial junctions, loss of cilia, hyperkeratosis, and cell death caused by apoptosis. Conclusions: In summary, the culprit for the negative impact on viability and morphology of 3D normal bronchial microtissues could be the too-high dose (500 µg/mL) of the SLN sample used. Nevertheless, further adjustments in the SLN synthesis process and another complex in vitro evaluation will be considered for future research.

Hepatic arterial variations detected at multidetector computer tomography angiography in the Romanian population.

BACKGROUND: Our purpose was to determine the prevalence of normal hepatic vascularization and variations of the hepatic arteries using multidetector computed tomography (MDCT) angiography. These variants should be known before any surgery of the upper abdomen, the downside being that there aren't many studies on large groups of patients using high-specialized imaging. MATERIALS AND METHODS: This study was carried out on 4192 patients. We performed MDCT angiography on each one of the patients and had a specialized team observe the images. RESULTS: Using Michels' classification, the normal anatomy (type I) was present in 3392 (80.91%) cases, while abnormal hepatic arteries were observed in 800 (19.08%) cases. The variations were distributed as follows: type II in 40 (0.95%) cases, type III in 442 (10.54%) cases, type IV in 13 (0.31%) cases, type V in 285 (6.79%) cases, type VI in 12 (0.28%) cases, type VII in 3 (0.07%) cases, type VIII in 108 (2.57%) cases, type IX in 6 (0.14%) cases and type X in one case (0.02%). 170 (4.05%) unclassified cases were observed. Using Hiatt's classification, the variations were: type II in 325 (7.75%) cases, type III in 454 (10.83%) cases, type IV in 124 (2.95%) cases, type V in 6 cases (0.14%) and type VI in 69 (1.64%) cases. 102 (2.43%) unclassified cases were observed. CONCLUSIONS: We observed well-known variations of the hepatic arterial pattern and also found a large number of rare, unclassified cases.

Clinical Consideration of Anatomical Variations in the Common Hepatic Arteries: An Analysis Using MDCT Angiography.

PURPOSE: The purpose of this study was to determine the prevalence of normal hepatic vascularization and variations in the common hepatic arteries using multidetector computer tomography angiography. These variants should be acknowledged before any surgery of the upper abdomen. The aim of our work was to analyze the variations in the hepatic arteries and their possible clinical and surgical implications. MATERIALS AND METHODS: This study was carried out on 4192 patients who underwent 64-slice MDCT angiography, from August 2015 to December 2021. We used surface and volume-rendering techniques in order to post-process images of the vascular components in the desired area. RESULTS: We highlighted 76 cases with replaced common hepatic arteries, which are characterized by the origin of the common hepatic artery trunk located outside the classical composition of the celiac trunk. We identified three levels of origin: the abdominal aorta, the superior mesenteric artery and the left gastric artery. We observed six different aspects of the morphological variability of the celiac trunk and the superior mesenteric artery. The trajectory of the artery trunk, between the aortic origin and the hepatic pedicle portion of the hepatic portal vein, is variable and we analyzed the pancreatic trajectory accordingly. CONCLUSIONS: The prevalence of hepatic arterial variants found during this study was similar to that in other specialized studies. We came across variants that have not been described in the well-known classification of Michels and even described extremely rare variations. The study of abnormal hepatic vascularization plays an important role in the surgical planning of hepatic transplantation, liver and pancreatic resection and extrahepatic upper abdominal surgeries.

Critical Overview of HER2 Assessement in Bladder Cancer: What Is Missing for a Better Therapeutic Approach?

BACKGROUND/AIM: To assess the concordance between IHC and FISH and its influence on tumor type, grade and lympho-vascular invasion (LVI). MATERIALS AND METHODS: HER2 immunohistochemistry (IHC) to 45 cases of bladder carcinoma, followed by fluorescent in situ hybridization (FISH) were applied. RESULTS: 31.12% cases were IHC positive. Less than 35% of HER2-negative cases presented LVI and this percent increased to 54.54% for +1 HER2 cases. LVI increases up to 57.14% for +2 HER2 cases and slightly decreased for +3 HER2 cases to 42.85%. IHC/FISH concordance was found for 73.34% cases but 31.57% were previously negative and 36.36% scored as +1 by IHC had gene amplification as shown by FISH analysis. T3 was correlated with HER2-IHC (p=0.05) and HER2-FISH (p=0.01). CONCLUSION: Improved HER2 assessement is needed for urothelial carcinomas. HER2-IHC scored as 0-2 should be validated by and reclassified according to FISH analysis.

[Computer tomography in primary orbital tumors]. / Importanta examinarii computer tomografice în patologia tumorala primara a cavitatilor orbitale.

PURPOSE: The aim of this study is to observe the anatomical changes that occur in the tumoral pathology of the orbit, as well as to underline the importance of computed tomographic examination in the investigation of the orbital tumoral pathology. MATERIAL AND METHOD: This study has been conducted in the Military Hospital of Timisoara by a team made of anatomists, radiologists and ophthalmologists. A number of 215 patients were examined over a period of six years, between 1998-2002. The computed tomography examinations were made with Picker IQ Premier equipment, using contiguous native axial sections of 2 to 5 mm thick, after intravenous injection of non-ionic contrast-enhancing substance for vascular identification and iodophilic quantification specific to each structure. RESULTS: From the 215 patients that had undergone a CT examination of the orbits, 41 cases had positive orbital tumoral pathology. The primary tumors of the optic nerve had the highest incidence being present in 12 cases, of which 9 with glioma and 3 with meningioma. The second most frequent were the vascular tumors revealed in 11 cases. CONCLUSION: Due to its diagnosis performances CT has to be considered as a routine investigation method, recommended as a method of choice in orbital tumoral pathology.