To report outcome (freedom from local progression [FFLP], overall survival [OS] and toxicity) after stereotactic, palliative or highly conformal fractionated (>12) radiotherapy (SBRT, Pall-RT, 3DCRT/IMRT) for adrenal metastases in a retrospective multicenter cohort within the framework of the German Society for Radiation Oncology (DEGRO).Adrenal metastases treated with SBRT (≤12 fractions, biologically effective dose [BED10] ≥ 50 Gy), 3DCRT/IMRT (>12 fractions, BED10 ≥ 50 Gy) or Pall-RT (BED10 < 50 Gy) were eligible for this analysis. In addition to unadjusted FFLP (Kaplan-Meier/log-rank), we calculated the competing-risk-adjusted local recurrence rate (CRA-LRR). Three hundred twenty-six patients with 366 metastases were included by 21 centers (median follow-up: 11.7 months). Treatment was SBRT, 3DCRT/IMRT and Pall-RT in 260, 27 and 79 cases, respectively. Most frequent primary tumors were non-small-cell lung cancer (NSCLC; 52.5%), SCLC (16.3%) and melanoma (6.7%).Unadjusted FFLP was higher after SBRT vs Pall-RT (P = .026) while numerical differences in CRA-LRR between groups did not reach statistical significance (1-year CRA-LRR: 13.8%, 17.4% and 27.7%). OS was longer after SBRT vs other groups (P < .05) and increased in patients with locally controlled metastases in a landmark analysis (P < .0001). Toxicity was mostly mild; notably, four cases of adrenal insufficiency occurred, two of which were likely caused by immunotherapy or tumor progression.Radiotherapy for adrenal metastases was associated with a mild toxicity profile in all groups and a favorable 1-year CRA-LRR after SBRT or 3DCRT/IMRT. One-year FFLP was associated with longer OS. Dose-response analyses for the dataset are underway.

Paraoxonase-1 (PON1) is a serum esterase associated with high density lipoproteins and capable of detoxifying toxic metabolites of organophosphorus (OP) compounds. Two major polymorphisms have been described in the coding region of the PON1 gene at positions 192 and 55 and at least five in the 5 0 -regulatory region, the most important at position À108. Depending on the substrate, PON1 192 Q/R polymorphism can affect PON1 enzymatic activity. In the present study, we have determined the distribution of the PON1 192 Q/R and À108 C/T polymorphisms in a Peruvian population and compared the distribution of these polymorphisms with those of other world populations. PON1 phenotype and enzyme activity also were measured as they can influence the population resistance to the toxicity of OP compounds. The genotype distribution at position 192 was: QQ ¼ 0.236, QR ¼ 0.607, and RR ¼ 0.157; and distribution at position À108 was: CC ¼ 0.315, CT ¼ 0.596, and TT ¼ 0.089. The frequencies of the high activity R and C alleles were 0.461 and 0.613, respectively. The frequency of the PON1 192 Q allele was significantly lower than that of American, Caucasian-American, European-Brazilian, and Costa Rican samples. Outside the American continent, the frequency of this allele was lower than for all European countries, Thais, and Indians, but higher than for Chinese or Japanese. Regarding the toxicological importance of these polymorphisms, it was inferred that PON1 phenotyping (assessment of the R alloform) and genotyping (determination of the PON1 -108TT genotype) could be helpful as individual markers of susceptibility. PON1 phenotyping may be useful in further epidemiological studies involving agriculture workers occupationally exposed to OP compounds in developing countries. Environ. Mol. Mutagen. 47:699-706, 2006. V V C 2006 Wiley-Liss, Inc.

BACKGROUND: Oxidative reactions are responsible for the changes in quality during food processing and storage. Oxidative stress is also involved in multiple chronic diseases, such as cardiovascular and neurodegenerative disorders, diabetes, cancer, and aging. The consumption of dietary antioxidants has been demonstrated to help to reduce the oxidative damage in both the human body and food systems. In this study, the potential of Erythrina edulis (pajuro) protein as source of antioxidant peptides was evaluated.RESULTS: Pajuro protein concentrate hydrolyzed by alcalase for 120 min showed potent ABTS ·+ and peroxyl radical scavenging activity with Trolox equivalent antioxidant capacity (TEAC) and oxygen radical absorbance capacity (ORAC) values of 1.37 ± 0.09 mol TE mg −1 peptide and 2.83 ± 0.07 mol TE mg −1 peptide, respectively. Fractionation of the hydrolyzate to small peptides resulted in increased antioxidant activity. De novo sequencing of most active fractions collected by chromatographic analysis enabled 30 novel peptides to be identified. Of these, ten were synthesized and their radical activity evaluated, demonstrating their relevant contribution to the antioxidant effects observed for pajuro protein hydrolyzate. CONCLUSIONS: The sequences identified represent an important advance in the molecular characterization of the pajuro protein, demonstrating its potential as a source of antioxidant peptides for food and nutraceutical applications. Oxygen radical absorbance capacity (ORAC) assayThe oxygen radical absorbance capacity (ORAC) was determined following the protocol described by Hernández-Ledesma et al. 26 The final assay mixture (200 μL) contained FL (30 nmol L −1 ), AAPH (12 mmol L −1 ), and antioxidant (Trolox (0-5 nmol L −1 ) or sample J Sci Food Agric 2019; 99: 2420-2427 Identification of antioxidant peptidesFraction UF-3, containing peptides < 3 kDa, was selected for further purification. The different fractions collected by elution wileyonlinelibrary.com/jsfa

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Nicotine-induced catecholamine (CA) secretion and inward ionic currents were inhibited by the opioid antagonist naloxone in cultured bovine chromaffin cells. Naloxone inhibited nicotine-induced CA secretion, as detected by an on-line real-time electrochemical technique, in a dose-dependent manner (IC(50)=29 microM). In voltage-clamped chromaffin cells, nicotine (10 microM) evoked an average peak inward current of -146 pA that was inhibited by low concentrations of naloxone (42% at 0.1 microM). The antagonist also inhibited total charge influx associated with nicotinic receptor activation (53% at 0.1 microM). This provides strong evidence that naloxone modulation of nicotine-induced CA secretion does not involve opioid receptors but results from the direct interaction with the nicotinic receptor itself, which might also be the case for other related opioid compounds.

We have studied the contribution of P-type voltagedependent Ca 2+ channels to both catacholamine (CA) and ATP secretion from bovine chromaffin cells induced by high K ÷ or nicotine using ¢o-agatoxin IVA, a selective blocker of P-type voltage-dependent Ca 2÷ channels. We found that high K ÷ (75 raM) induced the release of about 13% of norepinephrine, 5% epinephrine and 11% ATP, and that ¢o-agatoxin (100 nM) did not affect this secretion. However, both nicotine-induced CA and ATP secretion were significantly blocked (about 50%) by ¢o-agatoxin IVA (100 nM). In addition, this toxin also reversibly blocked (about 70%) the inward current induced by nicotine in bovine chromaffin cells. The results suggest that, besides its known action of blocking P-type voltage-dependent channels, ¢o-agatoxin is a potent and reversible blocker of the nicotinic receptor channel in chromaffin cells, and that this action would explain the blockade of nicotine-induced secretion.

The role of postoperative radiotherapy delivered as external-beam radiotherapy (EBRT), vaginal brachytherapy (VBT) or a combination of both, in the management of carcinosarcoma of the uterus is not clearly defined, as only limited randomized trial data are available, indicating a reduction in locoregional recurrences after EBRT. We performed a structured review of data published from 2010. Although no relevant new data from prospective trials or meta-analyses were identified, 14 analyses of cancer registry data from the United States or Europe, focusing predominantly on the endpoint for overall survival, were identified, four of them using propensity-score matching to compare subgroups treated with vs. without radiotherapy. Although stage-by-stage data are rare, the registry analyses support the idea of a beneficial effect, especially of VBT, on overall survival in International Federation of Gynecology and Obstetrics (FIGO) stage IA patients (to a lesser extent in stage IB). For stages II to III, the data sets indicate the largest effects on overall survival for the combination of EBRT and VBT. In all stages, survival effects of radiotherapy apparently persist when given in addition to chemotherapy. Whereas some studies see the strongest survival effects in patients with positive lymph nodes, propensity-score matched data indicate an overall survival effect of radiotherapy (EBRT + VBT or VBT alone) in FIGO stages I to III regardless of lymph node surgery.

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