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Therefore, the results of this first exploratory work highlight the possibility of characterising white truffles of different provenance, and suggest widening the scope of the survey throughout Italy and foreign regions.Recent studies have identified the 8C alkyl chain methylimidazolium ionic liquid 1-octyl-3-methylimidazolium in the environment and its potential to trigger the auto-immune liver disease primary biliary cholangitis. The toxicity of a range of methylimidazolium ionic liquids were therefore examined. Oxygen consumption was rapidly inhibited, with potency increasing with alkyl chain length. This preceded caspase 3/7 induction and DNA fragmentation. Time- and dose-dependent loss of dye reduction capacities reflected these effects, with a >700 fold difference in potency between 2C and 10C alkyl chain liquids. None of the ionic liquids directly inhibited mitochondrial complexes I-IV or complex V (F0F1-ATPase). However, dithionite reduction and ESR spectroscopy studies indicate a one electron reduction of oxygen in the presence of a methylimidazolium ionic liquid, suggesting methylimidazolium ionic liquids function as mitochondrial electron acceptors. However, only longer chain ionic liquids form a non-aqueous phase or micelle under aqueous physiological conditions and lead to increases in reactive oxygen species in intact cells. These data therefore suggest that the longer chain methylimidazolium liquids are toxic in sensitive liver progenitor cells because they both readily integrate within the inner mitochondrial membrane and accept electrons from the electron chain, leading to oxidative stress.The T-2 toxin (T-2) is a type A trichothecene produced by Fusarium species, and the most cytotoxic mycotoxin of the group. A study was made to determine T-2 cytotoxicity in human hepatocarcinoma (HepG2) cells; evaluate whether there is an adaptive response of HepG2 cells exposed to low concentrations of T-2; identify the T-2 metabolites by LC-Q-TOF MS; and determine whether T-2 disrupts cell proliferation in HepG2 cells. The IC50 values obtained ranged from 61.9 ± 2.4 nM to 70.7 ± 7.4 nM. buy Ziprasidone No adaptive response was observed. There was no evidence of extra- or intracellular accumulation of T-2 after 24 h of exposure as determined by LC-Q-TOF MS. However, some T-2 metabolites such as HT-2 toxin, neosolaniol and T-2 triol showed important (>75%) intracellular accumulation. Cell distribution was significantly increased in SubG0/G1 phase (11.8-fold higher) and decreased (12%) in G2/M phase at 60 nM T-2, versus the control. Simultaneously, increased necrosis (238%) and apoptosis/necrosis (up to 35.5%) were observed in HepG2 cells exposed to T-2. In conclusion, the results show that T-2 leads to loss of cell viability without an adaptive response, and that the metabolites generated play an important role in T-2 cytotoxicity, increasing HepG2 cell damage.
The optimal timing of adjuvant radiation therapy (RT) in the management of atypical meningiomas remains controversial. We compared the outcomes of atypical meningiomas managed with upfront adjuvant RT versus postoperative surveillance.
Patients with intracranial atypical meningiomas who underwent resection between 2000 and 2015 at a single institution were identified. Patients receiving adjuvant RT (n = 51), defined as RT within the first year of surgery before tumor progression/recurrence (P/R), were compared with those undergoing initial surveillance (n = 179). The primary endpoints were radiographic evidence of P/R and time to P/R from surgery.
A total of 230 patients were identified. Fifty-one (22%) patients received upfront adjuvant RT, and 179 (78%) underwent surveillance. Compared with the surveillance group, patients who received adjuvant RT had larger tumors (5.2 cm vs 4.6 cm; P = .04), were more likely to have undergone subtotal resection (65% vs 26%; P < . 01), and more often had bone invasion (18% vs 7%; P = .02). On multivariable analysis, receipt of adjuvant RT was associated with a lower risk of P/R compared with surveillance (hazard ratio, 0.21; 95% confidence interval, 0.11-0.41; P < .01). Patients who initially underwent surveillance and then received salvage RT at time of P/R had a shorter median time to local progression after RT compared with patients who developed local P/R after upfront adjuvant RT (19 vs 64 months, respectively; P < . 01).
Upfront adjuvant RT was associated with improved local control in atypical meningiomas irrespective of extent of initial resection compared with surveillance. Early adjuvant RT should be strongly considered after gross total resection of atypical meningiomas.
Upfront adjuvant RT was associated with improved local control in atypical meningiomas irrespective of extent of initial resection compared with surveillance. Early adjuvant RT should be strongly considered after gross total resection of atypical meningiomas.
Although 24 Gy single-dose radiation therapy (SDRT) renders >90% 5-year local relapse-free survival in human solid tumor lesions, SDRT delivery is not feasible in ∼50% of oligometastatic lesions owing to interference by dose/volume constraints of a serial organ at risk (OAR). Conformal OAR avoidance is based on a hypothetical model positing that the recently described SDRT biology specifically permits volumetric subdivision of the SDRT dose, such that high-intensity vascular drivers of SDRT lethality, generated within a major tumor subvolume exposed to a high 24 Gy dose (high-dose planning target volume [PTV
), would equilibrate SDRT signaling intensity throughout the tumor interstitial space, rendering bystander radiosensitization of a minor subvolume (perfusion-modulated dose sculpting PTV [PTV
]), dose-sculpted to meet a serial OAR dose/volume constraint. An engineered PTV
may thus yield tumor ablation despite PMDS dose reduction and conformally avoiding OAR exposure to a toxic dose.
Dose fall-odose, adapted to conformally meet OAR dose/volume constraints. The SDRT-PMDS approach thus provides a therapeutic resolution to otherwise radioablation-intractable oligometastatic disease.
The study provides compelling clinical support for the bystander radiosensitization hypothesis, rendering local cure of tumor lesions despite a ≥25% PTVPMDS dose reduction of the 24 Gy PTVHD dose, adapted to conformally meet OAR dose/volume constraints. The SDRT-PMDS approach thus provides a therapeutic resolution to otherwise radioablation-intractable oligometastatic disease.
Website: https://www.selleckchem.com/products/ziprasidone.html
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