Dispersal of human and plant pathogens biofilms via nitric oxide donors at 4°C

Recent studies suggest that nitric oxide donors capable of manipulating nitric oxide-mediated signaling in bacteria could induce dispersal of biofilms. Encased in extracellular polymeric substances, human and plant pathogens within biofilms are significantly more resistant to sanitizers. This is particularly a problem in refrigerated environments where food is processed. In an exercise aimed to study the potential of nitric oxide donors as biofilm dispersal in refrigerated conditions, we compared the ability of different nitric oxide donors (SNAP, NO-aspirin and Noc-5) to dislodge biofilms formed by foodborne, human and plant pathogens treated at 4 °C. The donors SNAP and Noc-5 were efficient in dispersing biofilms formed by Salmonella enterica, pathogenic Escherichia coli and Listeria innocua. The biomasses were decreased up to 30 % when compared with the untreated controls. When the plant pathogens Pectobacterium sp. and Xanthomonas sp. were tested the dispersion was mainly limited to Pectobacterium carotovorum biofilms, decreasing up to 15 % after exposure to molsidomine. Finally, the association of selected nitric oxide donors with sanitizers (DiQuat, H2O2, peracetic acid and PhenoTek II) was effective in dispersing biofilms. The best dispersal was achieved by pre-treating P. carotovorum with molsidomine and then peracetic acid. The synergistic effect was estimated up to ~35 % in dispersal when compared with peracetic acid alone. The association of nitric oxide donors with sanitizers could provide a foundation for an improved sanitization procedure for cleaning refrigerate environments

26 Ocena wyników pooperacyjnej radioterapii skojarzonej z 5-fluorouracylem u chorych na raka odbytnicy

Celem pracy była ocena wyników leczenia uzupełniającego z udziałem chemio- i radioterapii chorych po radykalnym zabiegu operacyjnym z powodu raka odbytnicy, ze szczególnym uwzględnieniem tolerancji leczenia. Materiał obejmuje 64 chorych leczonych w Klinice Onkologii i Radioterapii w Iatach1991–1995. Głównymi powikłaniami w czasie leczenia były biegunki (58%), nudności i wymioty (15%), objawy dyżuryczne (6%), leukopenia (33%) i niedokrwistość (5%). Do ostrych powikłań doszło ogółem 43 chorych (66%) w tym u 15 (23%) miały one charakter ciężki (stopień III i IV). Troje chorych nie ukończyło leczenia z powodu znacznego nasilenia objawów niepożądanych leczenia i pogorszenia stanu ogólnego.Późne powikłania, przede wszystkim w obrębie jelit i dróg moczowych, wystąpiły ogółem u 22 chorych (34%) w tym u 6 (9%)- w stopniu ciężkim. Spośród ocenionych 64 chorych dotychczas zmarło 19 (30%). Mediana czasu przeżycia w całej grupie wynosiła 37 miesięcy (11–60 miesięcy). Do wznowy miejscowej doszło u 15 chorych (23%) natomiast przerzuty odległe wystąpiły u 18 chorych (28%). Przedstawione wyniki, wskazujące na wysoki odsetek nawrotów oraz dużą liczbę powikłań popromiennych, skłoniły nas do zmiany techniki napromieniania. Efekty tych modyfikacji będzie można ocenić dopiero za kilka lat

Adjuvant treatment of patients with rectal cancer

Adjuvant postoperative radiotherapy combined with chemotherapy is considered a standard management of rectal cancer patients with increased risk of local recurrence. In this study we evaluated the results of adjuvant chemo- and radiotherapy after radical surgery in 64 patients with rectal carcinoma with special reference to tolerance of treatment. All patients underwent radical surgery: anterior abdominal resection in 26, abdominoperineal resection in 19 and Hartman resection in one. Thirty three patients were postoperatively staged as Dukes B2 and 31 patients – as Dukes C. All patients received postoperative chemo-radiotherapy. Treatment included megavoltage irradiation with two parallel opposed fields to small pelvis at a dose of 45 Gy in 23–25 fractions and concomitant chemotherapy with 5-Fluorouracil during first three and last three days of irradiation.Main early complications from chemoradiation included diarrhea (58%), nausea and vomiting (15%), dysuria (6%), leukopenia (31%) and anaemia (4%). In total, acute side effects occured in 42 patients (66%) and in 16 of them (25%) were of grade 3 or 4. Three patients did not complete the treatment due to exacerbation of side effects and/or serious deterioration of performance status. Late complications, mainly from bowels and urinary bladder, occured in 19 patients (30%) and six of then (9%) were severe.Nineteen of the 64 evaluated patients have deceased ill now. Median survival was 29 months (4 to 50 months). Local recurrence was seen in 14 patients (22%) and distant metastases – in 18 (28%).Results of our study show that postoperative radiochemotherapy in rectal cancer patients is accompanied by a large number of acute and late complications. Literature data demonstrate that better tolerance of treatment may be achieved with the use of special surgical techniques preventing the replacement of small intestines to the pelvis after rectal amputation. Further improvement may be achieved with the use of multiple radiation fields, computerized treatment planning and customized blocking. Another option is an application of preoperative radiotherapy – the approach becoming recently more commonly used

Imbalance in Coagulation/Fibrinolysis Inhibitors Resulting in Extravascular Thrombin Generation in Gliomas of Varying Levels of Malignancy.

Neoplastic processes are integrally related to disturbances in the mechanisms regulating hemostatic processes. Brain tumors, including gliomas, are neoplasms associated with a significantly increased risk of thromboembolic complications, affecting 20-30% of patients. As gliomas proliferate, they cause damage to the brain tissue and vascular structures, which leads to the release of procoagulant factors into the systemic circulation, and hence systemic activation of the blood coagulation system. Hypercoagulability in cancer patients may be, at least in part, a result of the inadequate activity of coagulation inhibitors. The aim of the study was to evaluate the expression of the inhibitors of the coagulation and fibrinolysis systems (tissue factor pathway inhibitor, TFPI; tissue factor pathway inhibitor-2 TFPI-2; protein C, PC; protein S, PS, thrombomodulin, TM; plasminogen activators inhibitor, PAI-1) in gliomas of varying degrees of malignancy. Immunohistochemical studies were performed on 40 gliomas, namely on 13 lower-grade (G2) gliomas (8 astrocytomas, 5 oligodendrogliomas) and 27 high-grade gliomas (G3-12 anaplastic astrocytomas, 4 anaplastic oligodendrogliomas; G4-11 glioblastomas). A strong expression of TFPI-2, PS, TM, PAI-1 was observed in lower-grade gliomas, while an intensive color immunohistochemical (IHC) reaction for the presence of TFPI antigens was detected in higher-grade gliomas. The presence of PC antigens was found in all gliomas. Prothrombin fragment 1+2 was observed in lower- and higher-grade gliomas reflecting local activation of blood coagulation. Differences in the expression of coagulation/fibrinolysis inhibitors in the tissues of gliomas with varying degrees of malignancy may be indicative of their altered role in gliomas, going beyond that of their functions in the hemostatic system

Absence of Staphylococcus aureus in Wild Populations of Fish Supports a Spillover Hypothesis

Staphylococcus aureus is a human commensal and opportunistic pathogen that also infects other animals. In humans and livestock, where S. aureus is most studied, strains are specialized for different host species. Recent studies have also found S. aureus in diverse wild animals. However, it remains unclear whether these isolates are also specialized for their hosts or whether their presence is due to repeated spillovers from source populations. This study focuses on S. aureus in fish, testing the spillover hypothesis in two ways. First, we examined 12 S. aureus isolates obtained from the internal and external organs of a farmed fish. While all isolates were from clonal complex 45, genomic diversity indicates repeated acquisition. The presence of a φSa3 prophage containing human immune evasion genes suggests that the source was originally human. Second, we tested for S. aureus in wild fish that were isolated from likely sources. In particular, we sampled 123 brown trout and their environment at 16 sites in the remote Scottish Highlands with variable levels of exposure to humans, birds, and livestock. This screen found no S. aureus infection in any of the wild populations or their environment. Together, these results support that the presence of S. aureus in fish and aquaculture is due to spillover from humans rather than specialization. Given the trends of increasing fish consumption, a better understanding of the dynamics of S. aureus spillover in aquaculture will mitigate future risks to fish and human health. IMPORTANCE Staphylococcus aureus is a human and livestock commensal but also an important pathogen responsible for high human mortality rates and economic losses in farming. Recent studies show that S. aureus is common in wild animals, including fish. However, we do not know whether these animals are part of the normal host range of S. aureus or whether infection is due to repeated spillover events from true S. aureus hosts. Answering this question has implications for public health and conservation. We find support for the spillover hypothesis by combining genome sequencing of S. aureus isolates from farmed fish and screens for S. aureus in isolated wild populations. The results imply that fish are unlikely to be a source of novel emergent S. aureus strains but highlight the prominence of the spillover of antibiotic-resistant bacteria from humans and livestock. This may affect both future fish disease potential and the risk of human food poisoning

peri‐xanthenoxanthene (PXX): a versatile organic photocatalyst in organic synthesis

Recent years have witnessed a continuous development of photocatalysts to satisfy the growing demand of photophysical and redox properties in photoredox catalysis, with complex structures or alternative strategies devised to access highly reducing or oxidising systems. We report herein the use of peri‐xanthenoxanthene (PXX), a simple and inexpensive dye, as an efficient photocatalyst. Its highly reducing excited state allows activation of a wide range of substrates, thus triggering useful radical reactions. Benchmark transformations such as the addition of organic radicals, generated by photoreduction of organic halides, to radical traps are initially demonstrated. More complex dual catalytic manifolds are also shown to be accessible: the β‐arylation of cyclic ketones is successful when using a secondary amine as organocatalyst, while cross‐coupling reactions of aryl halides with amines and thiols are obtained when using a Ni co‐catalyst. Application to the efficient two‐step synthesis of the expensive fluoro‐tetrahydro‐1H‐pyrido[4,3‐b]indole, a crucial synthetic intermediate for the investigational drug setipiprant, has been also demonstrated

37. Multicenter, randomized study assessing the impact of amifostine on normal tissue radiation tolerance during head and neck cancer radiotherapy

A prospective, randomized multicenter study was conducted to assess the value of amifostine (Ethyol®) as a radioprotectant in head and neck cancer radiotherapy. The aim of the study was to evaluate the impact of the addition of daily amifostine (150 mg/m2) on the degree of early (mucositis, dysphagia, xerostomia) and late (mucosal, cutaneous, salivary gland, mandible and spinal cord) radiation reactions. Assessed were also patients’ quality of life, local control and overall survival. Sixty two patients from five Polish institutions were randomly assigned to radiotherapy alone (Arm A – 28 patients) or radiotherapy + amifostine (Arm B – 34 patients). There were 43 men and 19 women. Primary tumor was located in the oral cavity (27 patients), oropharynx (25 patients), nasopharynx (2 patients) and larynx/hypopharynx (8 patients). In 43 patients radiotherapy was used as the sole modality of treatment and 19 patients were irradiated postoperatively. The side effects of amifostine were manageable. In 6 patients amifostine infusion had to be temporarily stopped due to hypotension and in 5 patients its administration was permanently terminated due to hypotension, nausea and vomiting, septicemia or fever and visual disturbances. The early results of the study, focusing on early radiation reactions, will be presented at the conference

Heterogeneous Expression of Proangiogenic and Coagulation Proteins in Gliomas of Different Histopathological Grade.

Brain gliomas are characterized by remarkably intense invasive growth and the ability to create new blood vessels. Angiogenesis is a key process in the progression of these tumors. Coagulation and fibrinolysis factors play a role in promoting angiogenesis. The aim of the study was to evaluate the expression of proangiogenic proteins (VEGF and bFGF) and hemostatic proteins (TF, fibrinogen, fibrin, D-dimers) associated with neoplastic cells and vascular endothelial cells in brain gliomas of various degrees of malignancy. Immunohistochemical tests were performed using the ABC method with the use of mono- and polyclonal antibodies. The obtained results indicated that both neoplastic cells and vascular endothelial cells in gliomas of various degrees of malignancy are characterized by heterogeneous expression of proteins of the hemostatic system and angiogenesis markers. The strongest expression of proangiogenic factors and procoagulant factors was demonstrated in gliomas of higher-grade malignancy