Synthesis, structural characterization, antimicrobial and cytotoxic effects of aziridine, 2-aminoethylaziridine and azirine complexes of copper(II) and palladium(II).

The synthesis, spectroscopic and X-ray structural characterization of copper(II) and palladium(II) complexes with aziridine ligands as 2-dimethylaziridine HNCH2CMe2 (a), the bidentate N-(2-aminoethyl)aziridines C2H4NC2H4NH2 (b) or CH2CMe2NCH2CMe2NH2 (c) as well as the unsaturated azirine NCH2CPh (d) are reported. Cleavage of the cyclometallated Pd(II) dimer [μ-Cl(C6H4CHMeNMe2-C,N)Pd]2 with ligand a yielded compound [Cl(NHCH2CMe2)(C6H4CHMe2NMe2-C,N)Pd] (1a). The reaction of the aziridine complex trans-[Cl2Pd(HNC2H4)2] with an excess of aziridine in the presence of AgOTf gave the ionic chelate complex trans-[(C2H4NC2H4NH2-N,N′)2Pd](OTf)2 (2b) which contains the new ligand b formed by an unexpected insertion and ring opening reaction of two aziridines (“aziridine dimerization”). CuCl2 reacted in pure HNC2H4 or HNCH2CMe2 (b) again by “dimerization” to give the tris-chelated ionic complex [Cu(C2H4NC2H4NH2-N,N′)3]Cl2 (3b) or the bis-chelated complex [CuCl(C2H2Me2NC2H2Me2NH2-N,N′)2]Cl (4c). By addition of 2H-3-phenylazirine (d) to PdCl2, trans-[Cl2Pd(NCH2CPh)2] (5d) was formed. All new compounds were characterized by NMR, IR and mass spectra and also by X-ray structure analyses (except 3b). Additionally the cytotoxic effects of these complexes were examined on HL-60 and NALM-6 human leukemia cells and melanoma WM-115 cells. The antimicrobial activity was also determined. The growth of Gram-positive bacterial strains (S. aureus, S. epidermidis, E. faecalis) was inhibited by almost all tested complexes at the concentrations of 37.5–300.0 μg mL−1. However, MIC values of complexes obtained for Gram-negative E. coli and P. aeruginosa, as well as for C. albicans yeast, mostly exceeded 300 μg mL−1. The highest antibacterial activity was achieved by complexes 1a and 2b. Complex 2b also inhibited the growth of Gram-negative bacteria. Graphical abstract: Synthesis, structural characterization, antimicrobial and cytotoxic effects of aziridine, 2-aminoethylaziridine and azirine complexes of copper(ii) and palladium(ii

Treatment strategies in primary vitreoretinal lymphoma: a 17-center European collaborative study.

IMPORTANCE: The best treatment option for primary vitreoretinal lymphoma (PVRL) without signs of central nervous system lymphoma (CNSL) involvement determined on magnetic resonance imaging or in cerebrospinal fluid is unknown. OBJECTIVE: To evaluate the outcomes of treatment regimens used for PVRL in the prevention of subsequent CNSL. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted at 17 referral ophthalmologic centers in Europe. We reviewed clinical, laboratory, and imaging data on 78 patients with PVRL who did not have CNSL on presentation between January 1, 1991, and December 31, 2012, with a focus on the incidence of CNS manifestations during the follow-up period. INTERVENTIONS: The term extensive treatment was used for various combinations of systemic and intrathecal chemotherapy, whole-brain radiotherapy, and peripheral blood stem cell transplantation. Therapy to prevent CNSL included ocular radiotherapy and/or ocular chemotherapy (group A, 31 patients), extensive systemic treatment (group B, 21 patients), and a combination of ocular and extensive treatment (group C, 23 patients); 3 patients did not receive treatment. A total of 40 patients received systemic chemotherapy. MAIN OUTCOMES AND MEASURES: Development of CNSL following the diagnosis of PVRL relative to the use or nonuse of systemic chemotherapy and other treatment regimens. RESULTS: Overall, CNSL developed in 28 of 78 patients (36%) at a median follow-up of 49 months. Specifically, CNSL developed in 10 of 31 (32%) in group A, 9 of 21 (43%) in group B, and 9 of 23 (39%) in group C. The 5-year cumulative survival rate was lower in patients with CNSL (35% [95% CI, 50% to 86%]) than in patients without CNSL (68% [95% CI, 19% to 51%]; P = .003) and was similar among all treatment groups (P = .10). Adverse systemic effects occurred in 9 of 40 (23%) patients receiving systemic chemotherapy; the most common of these effects was acute renal failure. CONCLUSIONS AND RELEVANCE: In the present series of patients with isolated PVRL, the use of systemic chemotherapy was not proven to prevent CNSL and was associated with more severe adverse effects compared with local treatment

Spontaneous and radiation-induced chromosomal instability and persistence of chromosome aberrations after radiotherapy in lymphocytes from prostate cancer patients

The aim of the study was to compare the spontaneous and ex vivo radiation-induced chromosomal damage in lymphocytes of untreated prostate cancer patients and age-matched healthy donors, and to evaluate the chromosomal damage, induced by radiotherapy, and its persistence. Blood samples from 102 prostate cancer patients were obtained before radiotherapy to investigate the excess acentric fragments and dicentric chromosomes. In addition, in a subgroup of ten patients, simple exchanges in chromosomes 2 and 4 were evaluated by fluorescent in situ hybridization (FISH), before the onset of therapy, in the middle and at the end of therapy, and 1 year later. Data were compared to blood samples from ten age-matched healthy donors. We found that spontaneous yields of acentric chromosome fragments and simple exchanges were significantly increased in lymphocytes of patients before onset of therapy, indicating chromosomal instability in these patients. Ex vivo radiation-induced aberrations were not significantly increased, indicating proficient repair of radiation-induced DNA double-strand breaks in lymphocytes of these patients. As expected, the yields of dicentric and acentric chromosomes, and the partial yields of simple exchanges, were increased after the onset of therapy. Surprisingly, yields after 1 year were comparable to those directly after radiotherapy, indicating persistence of chromosomal instability over this time. Our results indicate that prostate cancer patients are characterized by increased spontaneous chromosomal instability. This instability seems to result from defects other than a deficient repair of radiation-induced DNA double-strand breaks. Radiotherapy-induced chromosomal damage persists 1 year after treatment

Systemic immune-inflammation index (SII) and neutrophil to lymphocyte ratio (NLR) are useful markers for assessing effects of anti-inflammatory diet in patients before coronary artery bypass grafting

Background. One of the risk factors responsible for coronary artery disease (CAD) is an inadequate diet that is frequently deficient in anti-inflammatory components, such as polyphenols and omega-3 fatty acids. The neutrophil to lymphocyte ratio (NLR) and the systemic immune-inflammation index (SII) are inflammatory markers that may reflect a diet’s anti- inflammatory potential. Objective. The aim of this study was to evaluate the effects that CAD patients’ nutrition patterns have on NLR and SII. Material and methods. A retrospective study assessed the dietary habits and inflammatory marker levels in patients with advanced CAD before they underwent coronary artery bypass grafting (CABG) (n=101). Patients were divided into subgroups based on their NLR and SII levels. Results. Subgroups with lower NLR and SII levels had consumed significantly more eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (p=0.02). The group with alower ratio of omega-6 to omega-3 fatty acids (<4:1) also had lower NLR and SII levels (p=0.007 and p=0.01, respectively). Statistically significant negative correlations were found between EPA and DHA, as well as omega-3 intake, and both NLR and SII values. No statistically significant differences were found between the subgroups with lower and higher NLR and SII values for polyphenol intakes. Conclusions. Inflammatory markers such as NLR and SII may reflect an anti-inflammatory diet consumed by cardiac patients. A simultaneous assessment of dietary habits and inflammatory parameters is beneficial in the possible prevention of adverse cardiovascular incidents after CABG. There is also a need to establish reference values for SII and NL

Polyphenol-rich diet is associated with decreased level of inflammatory biomarkers in breast cancer patients

Background. The study investigated the relationship between dietary intake of polyphenols and inflammatory markers: CRP, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), medium platelet volume/lymphocyte ratio (MPVRL), in newly-diagnosed breast cancer patients. Objectives. The aim of this work was to verify whether diet rich in plant polyphenols affects inflammatory markers in breast cancer patients. Materials and methods. 78 patients (55.3±14.5 years) treated surgically for breast cancer were studied. A modified FFQ and authorial worksheet based on the Phenol Explorer database was used to measure the amount of plant polyphenols in a diet. Basing on the median of polyphenols intake (1780 mg/day), the group was divided into two subgroups: low- and high- dietary intake of polyphenols (LDIP and HDIP, respectively). Plasma CRP level was measured and NLR, PLR and MPVLR were calculated using results from peripheral blood morphology. Results. LDIP was associated with significantly higher CRP (elevated in 34.5% LDIP patients vs. 8.3% HDIP, p<0.003), NLR (elevated in 46.2% LDIP patients vs. 25.6% HDIP, p<0.006) and PLR level (elevated in 25.6% LDIP patients vs. 12.8% HDIP, p<0.03). MPVLR was not significantly different between both the subgroups. Conclusion. High dietary intake of polyphenols remarkably reduced process of inflammation in breast cancer patients, which has important clinical implications. The study demonstrated also an usefulness of simple, cheap and commonly available biomarkers for monitoring anti-inflammatory effects of diet.Wprowadzenie. Badano zależność pomiędzy pobraniem polifenoli wraz z dietą a poziomem markerów stanu zapalnego: CRP, wskaźnika neutrofile/limfocyty (NLR), płytki/limfocyty (PLR) oraz średnia objętość płytek/limfocyty (MPVLR) wśród nowo zdiagnozowanych pacjentek z rakiem piersi. Cel. Celem pracy było zweryfikowanie czy dieta bogata w polifenole roślinne wpływa na parametry stanu zapalnego u pacjentek z rakiem piersi. Materiały i metody. Do badania włączono 78 pacjentek (55.3±14.5 lat) klasyfikowanych do leczenia chirurgicznego raka piersi. Do oszacowania zawartości polifenoli w diecie użyto zmodyfikowanego zwalidowanego FFQ i autorskiego arkusza opartego na bazie Phenol Explorer. Po wyliczeniu median spożycia polifenoli (1780mg/dobę), podzielono pacjentki na dwie grupy: niskiego i wysokiego spożycia polifenoli (odpowiednio LDIP I HDIP). Zmierzono stężenie CRP oraz na podstawie wyników morfologii krwi obwodowej wyliczono wskaźniki NLR, PLR oraz MPVLR. Wyniki. W grupie z niższym pobraniem polifenoli zaobserwowano znacząco wyższe wartości CRP (podwyższone u 34.5% vs grupa wysokiego spożycia 8.3%, p<0.003), NLR (podwyższone w 46.2% vs 25.6%, p<0.006) oraz poziom PLR (podwyższone u 25.6% vs 12.8%, p<0.03). Wartości MPVLR nie różniły się istotnie pomiędzy podgrupami. Wnioski. Wysokie spożycie polifenoli znacząco redukowało proces zapalny u pacjentek z rakiem piersi, co ma znaczące implikacje kliniczne. Badanie przedstawiło również użyteczność prostych, tanich i powszechnie dostępnych biomarkerów do monitorowania przeciwzapalnego wpływu diety

Oxidative stress and 8-oxoguanine repair are enhanced in colon adenoma and carcinoma patients.

Oxidative stress is involved in the pathogenesis of colon cancer. We wanted to elucidate at which stage of the disease this phenomenon occurs. In the examined groups of patients with colorectal cancer (CRC, n = 89), benign adenoma (AD, n = 77) and healthy volunteers (controls, n = 99), we measured: vitamins A, C and E in blood plasma, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanine (8-oxoGua) in leukocytes and urine, leukocyte 8-oxoGua excision activity, mRNA levels of APE1, OGG1, 8-oxo-7,8-dihydrodeoxyguanosine 5'-triphosphate pyrophosphohydrolase (MTH1) and OGG1 polymorphism. The vitamin levels decreased gradually in AD and CRC patients. 8-OxodG increased in leukocytes and urine of CRC and AD patients. 8-OxoGua was higher only in the urine of CRC patients. 8-OxoGua excision was higher in CRC patients than in controls, in spite of higher frequency of the OGG1 Cys326Cys genotype, encoding a glycosylase with decreased activity. mRNA levels of OGG1 and APE1 increased in CRC and AD patients, which could explain increased 8-oxoGua excision rate in CRC patients. MTH1 mRNA was also higher in CRC patients. The results suggest that oxidative stress occurs in CRC and AD individuals. This is accompanied by increased transcription of DNA repair genes, and increased 8-oxoGua excision rate in CRC patients, which is, however, insufficient to counteract the increased DNA damage

Eating Disorder Quality of Life Scale (EDQLS) in ethnically diverse college women: an exploratory factor analysis

Abstract Background Extant research suggests that disordered eating is common in college women and is associated with decreased quality of life. The Eating Disorder Quality of Life Scale (EDQLS) examines impairment to disordered eating-related quality of life, but has not been validated in college women. Accordingly, the purpose of this study was to examine the reliability, validity, and factor structure of the EDQLS in a diverse sample of 971 college women. Method Students from a large United States university completed questionnaires examining disordered eating and the EDQLS online. Results The EDQLS demonstrated excellent internal consistency and good convergent validity with the Eating Disorder Examination Questionnaire (EDEQ). Contrary to the original 12-domain design of the EDQLS, principal component analyses suggested five factors that mapped onto the following constructs: (1) Positive Emotionality; (2) Body/Weight Dissatisfaction; (3) Disordered Eating Behaviors; (4) Negative Emotionality; and (5) Social Engagement. However, 15 of the 40 items loaded onto multiple factors. Conclusions Total scores on the EDQLS are reliable and valid when used with diverse samples of college women, but some revisions are needed to create subscales than can justifiably be used in clinical practice

Bereavement-related regret trajectories among widowed older adults

Objectives. Although regrets and unfinished business with a deceased spouse are frequently discussed as crucial determinants of one’s postloss adjustment, there have been few empirical investigations of bereavement-related regrets. This present study aimed to investigate the longitudinal course of these regrets and their correlates among widowed older adults. Methods. Drawing upon information from 201 widowed older adults in the Changing Lives of Older Couples study, this present study used latent class growth analysis to identify unique longitudinal trajectories of regret from 6 to 48 months postloss and examine differences between these trajectories with regard to grief and depressive symptomatology. Results. Three distinct bereavement-related regret trajectories were identified, characterized by Stable Low Regret, Stable High Regret, and Worsening High Regret. Results revealed that those in the Worsening High Regret group, whose bereavement-related regrets were exacerbated during the study, had the poorest grief outcomes. No differences were observed between these groups with regard to depressive symptoms, indicating that regret may be a unique marker of difficulties in the grieving process. Discussion. These findings highlight the importance of periodically reassessing bereavement-related regrets (and perhaps other aspects of the continued relationship with the deceased) over time and support the rationale behind interventions designed to facilitate resolution of these issues