Background and aim
Dexamethasone Suppression Test (DST), recommended for Cushing’s Syndrome (CS) diagnosis, explores the pituitary feedback to glucocorticoids. Its diagnostic accuracy could be ...affected by dexamethasone bioavailability, and therefore, we have developed and validated a dexamethasone threshold after 1-mg DST.
Materials and methods
We studied 200 subjects: 125 patients were considered retrospectively and 75 were enrolled prospectively as the validation cohort. Serum dexamethasone, Late Night Salivary Cortisol (LNSC), and Urinary Free Cortisol (UFC) were measured with LC–MS/MS. Normal LNSC and UFC levels were used to exclude CS. The lower 2.5th percentile of dexamethasone distribution in non-CS patients with cortisol ≤ 50 nmol/L after 1-mg DST was used as threshold.
Results
16 patients were CS and 184 non-CS (108 adrenal incidentaloma and 76 excluded CS); 4.5 nmol/L resulted the calculated threshold. Cortisol after 1-mg DST confirmed high sensitivity (100% at 50 nmol/L cut-off) and moderate–low specificity (63%, increased to 91% at 138 nmol/L) to diagnose CS in the whole cohort of patients. We could reduce the number of false-positive results (from 10 to 6 and from 7 to 4 in AI and excluded CS) considering adequate dexamethasone levels. Dexamethasone levels were not affected by hypercortisolism, age, gender, smoke, weight, and creatinine. 6% of non-CS patients did not achieve adequate dexamethasone levels (40% of tests with serum cortisol > 138 nmol/L after 1-mg DST).
Conclusions
We developed and validated the routine dexamethasone measurement during 1-mg DST: it is independent from patient’s clinical presentation, and it should be used to increase the specificity of serum cortisol levels.
The development of innovative nanosystems opens new perspectives for multidisciplinary applications at the frontier between materials science and nanomedicine. Here we present a novel hybrid ...nanosystem based on cytocompatible inorganic SiC/SiOx core/shell nanowires conjugated via click-chemistry procedures with an organic photosensitizer, a tetracarboxyphenyl porphyrin derivative. We show that this nanosystem is an efficient source of singlet oxygen for cell oxidative stress when irradiated with 6 MV X-Rays at low doses (0.4-2 Gy). The in-vitro clonogenic survival assay on lung adenocarcinoma cells shows that 12 days after irradiation at a dose of 2 Gy, the cell population is reduced by about 75% with respect to control cells. These results demonstrate that our approach is very efficient to enhance radiation therapy effects for cancer treatments.
First evidence of in vitro cytocompatibility of SiC/SiO2 core-shell nanowires is reported. Different internalization mechanisms by adenocarcinomic alveolar basal epithelial cells, monocytic cell line ...derived from an acute monocytic leukemia, breast cancer cells, and normal human dermal fibroblasts are shown. The internalization occurs mainly for macropinocytosis and sporadically by direct penetration in all cell models considered, whereas it occurred for phagocytosis only in monocytic leukemia cells. The cytocompatibility of the nanowires is proved by the analysis of cell proliferation, cell cycle progression, and oxidative stress on the cells treated with NWs as compared to controls. Reactive oxygen species generation was detected as an early event that then quickly run out with a rapid decrease only in adenocarcinomic alveolar basal epithelial and human dermal fibroblasts cells. In all the cell lines, the intracellular presence of NWs induce the same molecular events but to a different extent: peroxidation of membrane lipids and oxidation of proteins. The NWs do not elicit either midterm (72 h) or long-term (10 days) cytotoxic activity leading to irreversible cellular damages or death. Our results are important in view of a possible use of SiC/SiO2 core-shell structures acting as biomolecule-delivery vectors or intracellular electrodes.
Lung cancer is one of the most frequently diagnosed cancers worldwide and is still the leading cause of cancer-related deaths. There is a considerable interest in finding diagnostic methods in the ...disease's earliest stages. A complementary approach to imaging techniques could be provided by exhaled breath gas phase and exhaled breath condensate (EBC) analysis. The aim of this study was to quantify various biomarkers in the exhaled breath gas phase and EBC in suspected cases of non-small-cell lung cancer (NSCLC). The study involved 138 subjects with suspected lung cancer, 71 of whom had a subsequent diagnosis of NSCLC. The diagnostic power of a combination of hydrogen peroxide (H₂O₂)-EBC, and exhaled pentane, 2-methyl pentane, hexane, ethyl benzene, heptanal, trans-2-nonenal in distinguishing NSCLC and non-NSCLC subjects was poor-to-fair (area under the curve (AUC) = 0.68), similar to that of smoking history alone (expressed as pack-years, AUC = 0.70); a further improvement was observed when smoking history was combined with exhaled compounds (AUC = 0.80). The diagnostic power was increased in those patients with little or no past smoke exposure (AUC = 0.92) or where past smoke exposure was up to 30 pack-years (AUC = 0.85). Exhaled substances had a good accuracy in discriminating suspected cancerous cases only in those subjects with a modest smoking history (≤ 30 pack-years), but the inclusion of other exhaled biomarkers may increase the overall accuracy, regardless of tobacco smoke.
Recently, studies on inositol supplementation during in vitro fertilization program (IVF) have gained particular importance due to the effect of this molecule on reducing insulin resistance improving ...ovarian function, oocyte quality, and embryo and pregnancy rates and reducing gonadotropin amount during stimulation. Inositol and its isoforms, especially myoinositol (MYO), are often used as prestimulation therapy in infertile patients undergoing IVF cycle. Inositol supplementation started three months before ovarian stimulation, resulting in significant improvements in hormonal responses, reducing the amount of FSH necessary for optimal follicle development and serum levels of 17beta-estradiol measured the day of hCG injection. As shown by growing number of trials, MYO supplementation improves oocyte quality by reducing the number of degenerated and immature oocytes, in this way increasing the quality of embryos produced. Inositol can also improve the quality of sperm parameters in those patients affected by oligoasthenoteratozoospermia.
•Combined overexpression of miR-16 and miR-34a impairs malignant pleural mesothelioma (MPM) cell cycle progression.•p53 and HMGB1 expressions are modulated by miR-16 and miR-34a in MPM cells.•miRs ...co-transfection does not enhance MPM sensitivity to CDDP than the single ones.
The prognosis of patients affected by malignant pleural mesothelioma (MPM) is presently poor and no therapeutic strategies have improved their survival yet. Introduction of miRNA mimics to restore their reduced or absent functionality in cancer cells is considered an important opportunity and a combination of miR's might be even more effective. In the present study, miR-16 and miR-34a were transfected, singularly and in combination, in MPM cell lines H2052 and H28, and their effects on cell proliferation and sensitivity to cisplatin are reported. Interestingly, the overexpression of both miRs, alone or combined, slows down the cell cycle progression, modulates the p53 and HMGB1 expression and increases the sensitivity of cells to cisplatin, producing a marked impairment of cell proliferation and strengthening the apoptotic effect of the drug. However, the co-overexpression of the two miRs results more effective only in the regulation of the cell cycle, but does not enhance the sensitivity of MPM cells to cisplatin. Consequently, although the potential of miR-16 and miR-34a is confirmed, we must conclude that their combination does not improve the response of MPM to chemotherapy.
9-
cis-Retinal thiosemicarbazone and its Co(III), Ni(II) and Cu(II) complexes are synthesized and characterized. Central Co(III) atom is in an octahedral environment while Ni(II) and Cu(II) atoms are ...in a square planar environment. DNA binding constants and spectroscopic data show an intercalative behavior for the nickel complex; an external binding mode is envisaged for the ligand and its copper complex. No DNA interaction can be hypothesized for the cobalt complex. The free ligand and its Ni(II) and Cu(II) complexes have a good lipophilic degree for an efficient uptake by the cells. The metal complexes exhibit a proliferation inhibition action against cell line U937 at micromolar concentration. Cu(II) complex also induces apoptosis, while Ni(II) complex has a strong interaction with CT-DNA.
Display omitted The syntheses and characterization of 9-
cis-retinal thiosemicarbazone Hret and its Co(III), Ni(II) and Cu(II) complexes are reported. The metal complexes exhibit a proliferation inhibition action against human tumor cell line U937 at micromolar concentration. Cu(II) complex also induces apoptosis.
MAS063D (Atopiclair is a hydrolipidic cream that has been developed for the management of atopic dermatitis (AD). The putative active ingredients of MAS063D are hyaluronic acid, telmesteine, Vitis ...vinifera, glycyrrhetinic acid. A five-week study in 30 adult patients with mild to moderate AD showed that MAS063D offered significant benefits over a vehicle-only control. MAS063D improved the total body area affected (17.2% --> 13.2%, p < 0.001), itch score (2.7 --> 1.3 on a 10-point scale, p = 0.001) and EASI score (28.3 --> 24.3, p = 0.024) after 22 days treatment compared to baseline. The patients' opinion of MAS063D (patient's view of itch control, and view of study substance) was rated by participating patients as significantly better than control (p = 0.008, p = 0.042 respectively). Based on these preliminary results in a small scale study, it is suggested that MAS063D is a possible new treatment option for improving signs and symptoms in adults with mild to moderate AD.
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