Effect of obesity, dyslipidemia, and diabetes on trastuzumab-related cardiotoxicity in breast cancer.

Background: Clinical trials have demonstrated an increased risk of cardiotoxicity in patients with breast cancer (bca) receiving trastuzumab-based therapy. Diabetes, dyslipidemia, and obesity are known risk factors for cardiovascular disease. Studies have yielded conflicting results about whether those factors increase the risk of cardiotoxicity in patients with bca receiving trastuzumab. Methods: In this retrospective cohort study, data were collected for 243 patients with bca positive for her2 (the human epidermal growth factor receptor 2) who were receiving trastuzumab and who were referred to The Ottawa Hospital Cardio-oncology Referral Clinic between 2008 and 2013. The data collected included patient demographics, reason for referral, cardiac function, chemotherapy regimen (including anthracycline use), and 3 comorbidities (diabetes, dyslipidemia, obesity). Rates of symptomatic cancer treatment-related cardiac dysfunction (sctcd) and asymptomatic decline in left ventricular ejection fraction (adlvef) were calculated for patients with and without the comorbidities of interest. Results: Of the 243 identified patients, 104 had either diabetes, dyslipidemia, or obesity. In that population, the most likely reason for referral to the cardio-oncology clinic was adlvef. The combination of 2 or 3 comorbidities significantly increased the incidence of sctcd in our population, reaching a rate of 67% for patients with obesity and dyslipidemia [relative risk (rr): 2.2; p = 0.04], 69% for patients with obesity and diabetes (rr: 2.3; p = 0.02), and 72% for patients with all 3 risk factors (rr: 2.4; p = 0.08). Conclusions: The combination of 2 or 3 comorbidities significantly increases the incidence of symptomatic cancer treatment-related cardiotoxicity. Patients with bca experiencing cancer treatment-related cardiotoxicity who have a history of diabetes, dyslipidemia, and obesity might require more proactive strategies for prevention, detection, and treatment of cardiotoxicity while receiving trastuzumab-based treatment.

Ammonium 2,2'-thiodiacetates - Selective and environmentally safe herbicides.

2,2'-Thiodiacetic acid derivatives have a wide application potential, mainly in coordination chemistry. This research indicates that quaternary ammonium 2,2'-thiodiacetate salts may also be potent herbicidal agents used in agriculture. To provide a rationale for this statement, the toxic effect by a alkyl and aryl quaternary ammonium salts (QASs) on plant growth was investigated. The phytotoxicity of these compounds was tested against cultivated monocotyledonous (spring barley) and dicotyledonous (common radish) plants, whereas herbicidal activity was investigated in relation to popular weeds species (white goosefoot, sorrel and gallant-soldier). The results showed that aliphatic QASs possessed a low phytotoxicity to food crops and that some of them (in particular triethylammonium salt) had potent and selective herbicidal properties against common weeds, such as sorrel and gallant-soldier. However, the investigated compounds appeared to be ineffective herbicides against white goosefoot.

An influence of structural changes in ammonium cations on ecotoxicity of 2,2'-thiodiacetate mono and bis-salts.

2,2'-Thiodiacetates with their excellent complexing properties may be used as metal extraction agents, fluorescent and superparamagnetic materials, antibacterial and anticancer medical agents, however there are no data concerning the environmental impact of 2,2'-thiodiacetates derivatives and data definying the potential hazard connected with their use. This study describes the ecotoxicity assessment of seven 2,2'-thiodiacetates with non-metallic, alkyl and aryl ammonium cations, which were obtained in an environmentally friendly, solvent-free syntheses. The ecotoxicity of these water soluble compounds was tested in aquatic and benthic environments using luminescent marine bacteria Vibrio fischeri (Microtox® test) and the crustaceans Heterocypris incongruens (Ostracodtoxkit F™), respectively. The antimicrobial and antifungal activity against Trichoderma viridis, Aspergillus niger, Rhizoctonia solani and Escherichia coli was also investigated. The results showed how structural changes within ammonium cations themselves influence ecotoxicity: the QASs with alkylammonium cations exhibited a similar, rather low toxicity both to Vibrio fischeri and Heterocypris incongruens, and they would not pose a risk to these organisms in case of leakage. Higher toxicity was observed in case of two isoquinolinium salts, however it was rather associated with the heteroaromatic cation, than with the 2,2'-thiodiacetate anion.

Degradation Processes of Pesticides Used in Potato Cultivations.

Potato is one of the most important crops, after maize, rice and wheat. Its global production is about 300 million tons per year and is constantly increasing. It grows in temperate climate and is used as a source of starch, food, and in breeding industry.Potato cultivation requires application of numerous agro-technical products, including pesticides, since it can be affected by insects, weeds, fungi, and viruses. In the European Union the most frequently used pesticides in potato cultivations check are: thiamethoxam, lambda-cyhalothrin and deltamethrin (insecticides), rimsulfuron (herbicide) and metalaxyl (fungicide).Application of pesticides improves crop efficiency, however, as pesticides are not totally selective, it affects also non-target organisms. Moreover, the agrochemicals may accumulate in crops and, as a consequence, negatively influence the quality of food products and consumer health. Additional risks of plant protection products are related to their derivatives, that are created both in the environment (soil, water) and in plant organisms, since many of these compounds may exhibit toxic effects.This article is devoted to the degradation processes of pesticides used in potato crop protection. Attention is also paid to the toxicity of both parent compounds and their degradation products for living organisms, including humans. Information about the level of pesticide contamination in the environment (water, soil) and accumulation level in edible plants complement the current knowledge about the risks associated with widespread use of thiamethoxam, lambda-cyhalothrin and deltamethrin, rimsulfuron and metalaxyl in potato cultivation.

The Prospective External Validation of International Ovarian Tumor Analysis (IOTA) Simple Rules in the Hands of Level I and II Examiners.

Objective: To externally validate the International Ovarian Tumor Analysis (IOTA) Simple Rules (SR) by examiners with different levels of sonographic experience defined by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) and to assess the morphological ultrasound features of the adnexal tumors classified as inconclusive based on IOTA SR. Materials and Methods: In the two-year prospective study adnexal tumors were assessed preoperatively with transvaginal ultrasound by examiners with different levels of experience (level 1- IOTA SR1, level 2-IOTA SR2). Additionally, an expert (level 3) evaluated all tumors by subjective assessment (SA). If the rules could not be applied, the tumors were considered inconclusive. The final diagnosis was based on the histopathological result of the removed mass. The diagnostic performance measures for the assessed model were sensitivity, specificity, negative (LR-) and positive(LR+) likelihood ratios, accuracy (ACC) and diagnostic odds ratio (DOR). Results: 226 women with adnexal tumors scheduled for surgery were included in the stutdy. The prevalence of malignancy was 36.3 % in the group of all studied tumors and was 52.5 % in the inconclusive group (n = 40) (p = 0.215). Fewer tumors were classified as inconclusive by level 2 examiners compared to level 1 examiners [20 (8.8 %) vs. 40 (17.7 %); p = 0.008], resulting from the discrepancy in the evaluation of acoustic shadows and the vascularization within the tumor. For level 1 examiners a diagnostic strategy using IOTA SR1 +MA (assuming malignancy when SR inconclusive) achieved a sensitivity, specificity and DOR of 96.3 %, 81.9 %, 13.624 respectively. For level 2 examiners the diagnostic strategy for IOTA SR2 +MA achieved a sensitivity, specificity and DOR of 95.1 %, 89.6 %, 137,143, respectively. Adding SA by an expert (or level 3 examiner) when IOTA SR were not applicable improved the specificity of the test and achieved a DOR of 505.137 (SR1 +SA) and 293.627 (SR2 +SA). The SA by an expert proved to have the best diagnostic performance with a DOR of 5768.857, and a sensitivity and specificity of 97.6 % and 99.3 % respectively. Within the inconclusive group the most common tumors were unilocular-solid (n-13), solid (n-8) and multilocular-solid (n-10) ones. All multilocular tumors were classified as inconclusive because of their size (≥ 100 mm) and were found to be benign by pathology. Most of the inconclusive tumors with cystic content presented low-level (43.75 %) echogenicity, followed by ground-glass (34.37 %), mixed (12.5 %) and anechoic (9.4 %). Conclusion: The study results show excellent diagnostic performance of IOTA Simple Rules followed by subjective expert assessment in inconclusive tumors irrespective of the level of experience, while subjective assessment by an expert still has the highest diagnostic odds ratio. The number of inconclusive cases seems to depend on the level of ultrasound expertise and less experienced examiners have a tendency to overestimate blood flow and a presence of acoustic shadows within the tumors. IOTA SR were not applicable either because no benign or malignant features were found or both were identified. Within inconclusive tumors the majority of cases comprise malignant masses that are either unilocular-solid, solid tumors or small multilocular-solid ones with a diameter of less than 100 mm.

Masitinib mesylate does not enhance sensitivity to radiation in three feline injection-site sarcoma cell lines under normal growth conditions.

Masitinib, a selective tyrosine kinase inhibitor, was investigated as a radiosensitizer in three primary feline injection-site sarcoma (ISS) cell lines. Sensitivity to masitinib was previously assessed via cell growth inhibition assays with mean IC50 values of 5.5-8.6µM. Clonogenic assays were performed to determine the effect of masitinib and radiation on cell survival. Single dose radiation (0-12Gy) experiments were carried out under normal growth conditions in control ISS cells and in cells incubated with 1 or 6µM masitinib for 72h prior to irradiation. Radiation administered either alone or in combination with masitinib induced a dose-dependent reduction in clonogenic survival. Survival from the combined masitinib and radiation treatment was not significantly different from that of radiation alone. Results suggest that masitinib does not directly enhance ISS cell radiosensitivity under normal in vitro conditions, although this does not preclude the utility of further investigations to assess sensitization properties under altered conditions.

Changes in γ-H2AX expression in irradiated feline sarcoma cells: an indicator of double strand DNA breaks.

Feline injection site sarcoma (ISS) is a highly invasive soft tissue tumor that is commonly treated with radiation. Cellular deoxyribonucleic acid (DNA) is the principal target for the biologic effects of radiation with cell killing correlating to the number of double stranded DNA breaks (DSBs). The objective of this study was to determine if radiation-induced damage to feline ISS cells could be detected using a commercially available DNA DSB detection kit. Feline ISS cells were irradiated and evaluated for extent of DSB induction with a γ-H2AX chemiluminescent kit; results were validated by Western Blot analysis. Irradiated cells showed a significant increase in double strand break induction compared to control cells, which was supported by Western Blot. DNA damage in feline sarcoma cells following single exposure of radiation can be indirectly detected using a commercially available mouse anti-human monoclonal antibody for γ-H2AX.

[The surgical procedure of mini-sling antiincontinence procedure AJUST, recommendations and ways of solution of possible special situations]. / Operacní postup mini-páskové antiinkontinentní operace AJUST, doporucení a zpusoby resení mozných nestandardních situací

The objective of our work was to present and summarize the course of a joint meeting of surgeons with experience with AJUST in SUI anti-incontinence treatment. We would like to discuss the operation procedure and its individual steps. Further aim was to determine the optimal operation procedure, step by step, avoiding possible complications in the course of the procedure; simplifying the technique and publishing the recommendations how to solve possible complications in the course of, or after, the operation procedure, was important outcome of the meeting.

Simulations of ionization in a hot cavity surface ion source.

A new numerical Monte Carlo method based model of a hot cavity surface ionization ion source is presented in this paper. The model, intended to support the studies on ionization phenomena in a widely used class of ion sources, takes into account geometry of the ion source and extraction system, ionizer temperature and other features. The results of ion source efficiency calculations for various configurations of the extraction field are reviewed. The dominant role of the ionizer region near the extraction opening is described. Simulated dependences of ionization efficiency on the working parameters like ionizer length and temperature, ionization potential of the substance, and extraction voltage are discussed. A good agreement of the experimental data (e.g., influence of ionizer temperature, current-voltage curve) and the predictions of the model is found. It is also shown that the contribution to the ionization yield from impact of thermionic electrons accelerated by the extraction field may be significant, especially for the substances of small surface ionization coefficient. The simulation results are compared to the predictions of different theoretical models of the ion source--the obtained simulation data are in accordance both with a well-known Kirchner formula and the so called spherical ionizer model.

Masitinib demonstrates anti-proliferative and pro-apoptotic activity in primary and metastatic feline injection-site sarcoma cells.

Dysregulation of platelet-derived growth factor receptor (PDGFR) may play a role in feline injection-site sarcoma (ISS) cell growth and viability. Masitinib, a tyrosine kinase inhibitor approved for treatment of canine mast cell tumours, is highly selective for the PDGFR signalling pathway and may offer a new therapeutic approach for this disease. The in vitro effects of masitinib on growth, apoptosis and PDGFR signalling in two novel ISS cell lines were investigated. PDGFR expression was confirmed by Western blot in cell lines derived from a primary ISS tumour (JB) and a corresponding, histologically confirmed ISS lung metastasis (JBLM). Masitinib inhibited cell growth and PDGFR phosphorylation in both cell lines. Higher drug concentrations were required to inhibit growth than to modulate ligand-induced autophosphorylation of PDGFR. These in vitro data suggest that masitinib displays activity against both primary and metastatic ISS cell line and may aid in the clinical management of ISS.

All-electrical measurement of the density of states in (Ga,Mn)As.

We report on electrical measurements of the effective density of states in the ferromagnetic semiconductor material (Ga,Mn)As. By analyzing the conductivity correction to an enhanced electron-electron interaction the electrical diffusion constant was extracted for (Ga,Mn)As samples of different dimensionality. Using the Einstein relation allows us to deduce the effective density of states of (Ga,Mn)As at the Fermi energy.

Arc discharge ion source for europium and other refractory metals implantation.

The best method for the impurity doping to the host material is the ion implantation. Due to high melting point of the rare earth standard metal ion sources are useless. One of the solution is to use chemical compounds of rare earths characterized by low melting point. In this paper we describe the novel design of the ion source suitable for refractory metal (e.g., rare earths) ion implantation. The dependencies of Eu(+) current on cathode and arc currents as well as on hydrogen flow are presented. Europium (III) chloride as the source of the europium atoms was used. Europium ions were produced during collisions of evaporated and decomposed EuCl(3) molecules with fast electrons. The typical current of the europium ion beam extracted from the ion source was 25 microA for the extraction voltage of 25 kV. The ion source works without maintenance breaks for approximately 50 h, which enables high dose implantation. The presented ion source needs neither advanced high power supplies nor high vacuum regime.

Boron removal from wastewater using adsorbents.

In the present study, boron adsorption on activated alumina and activated carbon impregnated with calcium chloride, tartaric acid and mannitol was investigated. The adsorbate in question was the wastewater from the chemical landfill in Tarnowskie Gory of 25-70 mg l(-1) boron content. The removal of boron from the above-described wastewater was examined in the static (batch) and dynamic (column) experiments. The static experiments were carried out to assess boron adsorption isotherms, based on which the most efficient adsorbent as well as the rough resin load was determined. On the basis of the dynamic experiment results, the boron adsorptive capacities of the examined resins were deduced. It was concluded that the use of the impregnants increased the ability of activated carbon to adsorb boron. Granulated activated carbon WG-12 impregnated with mannitol was found to be the most promising for the boron removal from wastewater of the Chemical Wastewater Plant in Tarnowskie Gory.

Human granulocyte-macrophage colony-stimulating factor DNA cationic-lipid complexed autologous tumour cell vaccination in the treatment of canine B-cell multicentric lymphoma.

This study describes the development of an human granulocyte-macrophage colony-stimulating factor DNA cationic-lipid complexed autologous tumour cell vaccine (hGM-CSF CLDC ATCV) and its implementation, following a chemotherapy treatment protocol, in a randomized, placebo-controlled, double-blinded clinical trial in pet dogs with naturally occurring lymphoma. We hypothesized that the use of this vaccine would result in an antitumour immune response leading to improved first remission duration and overall survival in dogs with B-cell lymphoma when compared with chemotherapy alone. Immune stimulation generated by hGM-CSF CLDC ATCV was assessed by means of surrogate in vivo analysis (delayed-type hypersensitivity [DTH]) as well as an ex vivo cellular assay (lymphocyte proliferation assay). The vaccine approach considered in the current report did not result in clinically improved outcomes. A small measure of immunomodulation was documented by DTH and several modifications to the approach are suggested. This report illustrates the feasibility of clinical trials with vaccine strategies using companion animals with non-Hodgkin's lymphoma.

Evaluation of the gene for inducible nitric oxide synthase as a radiosensitizer under hypoxic and oxic conditions.

The radiosensitizing effect of inducible nitric oxide synthase (iNOS) was evaluated, in vitro, in a feline vaccine-associated sarcoma (VAS) cell line and a canine osteosarcoma cell line (D17). The gene encoding the human iNOS was cloned into an expression plasmid under the control of a cytomegalovirus immediate early promoter. Transient transfections were performed in feline VAS cells and D17 cells. Nitric oxide was measured in the supernatant media 48 h later as an indirect measurement of iNOS expression. Cells were irradiated using cobalt-60 under hypoxic or oxic conditions, and clonogenic assays were used to evaluate the effects of gene transfer on the sensitivity of cells to radiation. The results demonstrated that iNOS had no significant effect on improving the radiosensitivity of cells under oxic conditions. However, under hypoxic conditions, iNOS gene transfer significantly improved radiosensitization in osteosarcoma cells. These results demonstrate the feasibility of improving the outcome of radiotherapy in dogs with large bulky tumours using iNOS gene therapy.

Response of canine cutaneous epitheliotropic lymphoma to lomustine (CCNU): a retrospective study of 46 cases (1999-2004).

BACKGROUND: Epitheliotropic lymphoma (ELSA) is an uncommon cutaneous canine malignancy of T lymphocytes. A consensus regarding the therapeutic standard of care is lacking, warranting evaluation of chemotherapeutic agents traditionally employed against canine nodal lymphoma in the treatment of ELSA. HYPOTHESIS: The purpose of this retrospective, multi-institutional study was to evaluate the efficacy of 1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea (CCNU) in the treatment of ELSA. ANIMALS: Forty-six dogs with adequate follow-up and treatment response information. METHODS: All cases were diagnosed histopathologically. Immunohistochemisty (CD3, CD79a) was performed on 42/46 samples. RESULTS: Presenting skin lesions included generalized scales (25/46), plaques or nodules (22/46), mucocutaneous lesions (14/ 46), and corneal involvement (1/46). Lymph node involvement and Sézary syndrome were documented in 7 and 2 dogs, respectively. The median number of CCNU treatments was 4 (range, 1-11), with a median starting dose of 60 mg/m(2) (range, 30-95). Of the 46 dogs, 15 achieved complete remission, 23 achieved partial remission, 5 had stable disease, and 3 had progressive disease, for an overall response rate of 83%. The median number of treatments to achieve a response was 1 (range, 1-6). The overall median duration of response was 94 days (range, 22-282). Sixteen dose reductions were required because of neutropenia (10/46), thrombocytopenia (1/46), anemia (1/46), increased liver enzyme activity (3/46), or unspecified reasons (1/46). CONCLUSIONS AND CLINICAL IMPLICATIONS: Given the high response rate and well tolerated protocol, prospective studies are warranted to investigate the utility of CCNU alone or in multi-agent protocols for the treatment of ELSA.

Outcome and prognostic factors following adjuvant prednisone/vinblastine chemotherapy for high-risk canine mast cell tumour: 61 cases.

The medical records of 61 dogs with MCT at high risk for metastasis that were treated with prednisone and VBL following excision+/-radiation therapy were reviewed, and median disease-free interval (DFI), median overall survival time (OS) and prognostic factors assessed. Adverse effects, mostly mild, were noted in 26% of patients, usually after the first VBL dose. 6.5% experienced severe neutropenia. The DFI was 1305 days, and the OS was not reached, with 65% alive at 3 years. 100% of dogs with "high-risk" grade II MCT were alive at 3 years. The OS for dogs with grade III MCT was 1374 days. Histologic grade, location (mucous membrane vs. skin) and use of prophylactic nodal irradiation predicted outcome. Prednisone and VBL chemotherapy is well tolerated, and results in good outcomes following surgery in dogs with MCT at high risk for metastasis. High-grade and mucocutaneous tumors had a worse outcome, and the use of prophylactic nodal irradiation appeared to improve outcome in this group of dogs.

Experimental apparatus for investigation of sputtering and secondary ion emission induced by energetic ion beams.

The construction of an experimental apparatus, for investigation of implantation, secondary ion emission and sputtering processes, during irradiation of samples with an ion beam of up to 70 keV energy, is described. The basis of the apparatus is an electromagnetic mass separator equipped with a quadrupole mass spectrometer located in the collector chamber. The computer data acquisition control system makes it possible to perform the experimental measurements with high accuracy and precision. Preliminary results of secondary ion mass spectral measurements, obtained for C, Al, Si and Cu targets bombarded with Ar(+) and Kr(+) ions, are presented.