10 research outputs found
Absence of Pro-Apoptotic Bim Promotes Accumulation of Pulmonary T-Lymphocytes and Enhances Clearance of Pneumocystis carinii Infection in Mice.
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Working towards an ecosystem approach to North Atlantic marine aquaculture
No full text No abstracts are to be cited without prior reference to the author. Conveners: Gesche Krause (Germany), Jann Martinsohn (European Commission), Ryan B. Carnegie (USA).CM 2018/O:424. An ecosystem approach to seaweed aquaculture, a comparison of ecosystem goods and services. Richard Langton, Tammy Murphy, Lisa Milke, Thomas NojiCM 2018/O:571. Is aquaculture of the future full of gene-edited fish? eExperiences and perspectives from the CRISPR-Cas9 gene-edited sterile Norwegian salmon. Dorothy J. DankelCM 2018/O:622. Guidelines for seaweed aquaculture in Europe. : Araujo R, Abreu H, De Clerk O, Funderud J, Holdt S, Jacquemin B, Rebours C, Timmermans K, Charrier B, Barbier MCM 2018/O:155. Modelling the environmental impacts of future offshore fish farms in the inner Danish waters. Marie Maar, Janus Larsen, Karsten Dahl, Bo RiemannCM 2018/O:29. Fish efficiency; the missing part for the description of the total efficiency of fish feeding. Eckhard BethkeCM 2018/O:604. Understanding disease as a key biotic interaction between aquaculture and environment. Ryan B. CarnegieCM 2018/O:602. Kelp farming as a potential remediation strategy for coastal acidification. Nichole N. Price, Suzanne N. Arnold, Joe Salisbury, Paul Dobbins, Brittney Honisch, Christopher Hunt, Shawn Shellito, Melissa M.M. Oyola, Evangeline FachonCM 2018/O:105. Environmental impact assessment for aquaculture activities in the Macaronesia. Lydia Png-Gonzalez, Natacha Nogueira, Carlos AndradeCM 2018/O:611. Impact of global warming on diseases in aquaculture. Øivind Bergh, Lars Asplin, Nina Sandlund, Anne D. Sandvik, Sonal Patel, Joao G. Ferreira, Nick TaylorCM 2018/O:487. Using public comments to explore social licence to operate for aquaculture. Suzannah-Lynn BillingCM 2018/O:203. A heart for the Carp culture; the role of region-marketing to maintain traditional aquacultures in Europe. Tobias Lasner, Adam Mytlewski, Myriam Nourry, Marcin Rakowski, Martin OberleCM 2018/O:481. Combined nutrients effects from aquaculture and agriculture on macroalgal growth: a bioassay experiment. Michael D. Streicher, Katrin Reiss, Henning Reiss</p
Phase II trial of preoperative radiochemotherapy with concurrent bevacizumab, capecitabine and oxaliplatin in patients with locally advanced rectal cancer
No full textBackground: Preoperative radiochemotherapy (RCT) with 5-FU or capecitabine is the standard of care for patients with locally advanced rectal cancer (LARC). Preoperative RCT achieves pathological complete response rates (pCR) of 10-15%. We conducted a single arm phase II study to investigate the feasibility and efficacy of addition of bevacizumab and oxaliplatin to preoperative standard RCT with capecitabine.
Methods: Eligible patients had LARC (cT3-4; N0/1/2, M0/1) and were treated with preoperative RCT prior to planned surgery. Patients received conventionally fractionated radiotherapy (50.4 Gy in 1.8 Gy fractions) and simultaneous chemotherapy with capecitabine 825 mg/m2 bid (d1-14, d22-35) and oxaliplatin 50 mg/m2 (d1, d8, d22, d29). Bevacizumab 5 mg/kg was added on days 1, 15, and 29. The primary study objective was the pCR rate.
Results: 70 patients with LARC (cT3-4; N0/1, M0/1), ECOG < 2, were enrolled at 6 sites from 07/2008 through 02/2010 (median age 61 years [range 39–89], 68% male). At initial diagnosis, 84% of patients had clinical stage T3, 62% of patients had nodal involvement and 83% of patients were M0. Mean tumor distance from anal verge was 5.92 cm (± 3.68). 58 patients received the complete RCT (full dose RT and full dose of all chemotherapy). During preoperative treatment, grade 3 or 4 toxicities were experienced by 6 and 2 patients, respectively: grade 4 diarrhea and nausea in one patient (1.4%), respectively, grade 3 diarrhea in 2 patients (3%), grade 3 obstipation, anal abscess, anaphylactic reaction, leucopenia and neutropenia in one patient (1.4%), respectively. In total, 30 patients (46%) developed postoperative complications of any grade including one gastrointestinal perforation in one patient (2%), wound-healing problems in 7 patients (11%) and bleedings in 2 patients (3%). pCR was observed in 12/69 (17.4%) patients. Pathological downstaging (ypT < cT and ypN ≤ cN) was achieved in 31 of 69 patients (44.9%). All of the 66 operated patients had a R0 resection. 47 patients (68.1%) underwent sphincter preserving surgery.
Conclusions: The addition of bevacizumab and oxaliplatin to RCT with capecitabine was well tolerated and did not increase perioperative morbidity or mortality. However, the pCR rate was not improved in comparison to other trials that used capecitabine or capecitabine/oxaliplatin in preoperative radiochemotherapy
Manifestações clínicas, laboratoriais e radiológicas da tuberculose pulmonar: estudo comparativo entre individuos HIV positivos e negativos.
Get PDFTrabalho de Conclusão de Curso - Universidade Federal de Santa Catarina. Curso de Medicina. Departamento de Clinica Medica
Cigarette smoke and human pulmonary immune responses to mycobacteria
No full textRecent epidemiological evidence suggests that up to 15% of worldwide tuberculosis (TB) cases may be attributable to tobacco smoking. The aim of the studies reported here was to gain insights into the effects of exposure to cigarette smoke on human cells that form part of the innate immune system of host defence in the lung. The experiments on the pulmonary effects of cigarette smoke confirm that exposure has a significant effect upon innate host defences. Significant reductions in the production of key cytokines implicated in defences against mycobacteria were observed, not attributable to impairment of mycobacterial uptake by cigarette smoke extract exposure. Furthermore, control of intracellular mycobacterial growth was impaired by cigarette smoke extract exposure
Novel applications of biomaterials in the management of parastomal hernia and anal fistula
No full textMD (res)The aim of this thesis was to explore novel applications for both traditional and contemporary biomaterials in the management of parastomal hernia and anal fistula.
Parastomal hernias can be prevented or repaired using synthetic mesh; however, reported complications include infection, fibrosis and potential bowel erosion. The prophylactic role of a cross-linked collagen implant was assessed in terms of safety, feasibility and potential efficacy. Additionally, the human host response to this implant was evaluated. There were no complications related to infection or the implant‟s proximity to the bowel. The implant had excellent biocompatibility and resistance to degradation in most patients, and although fibrovascular in-growth and ECM deposition were limited, it seems to have excellent potential for soft tissue reinforcement and, more specifically, prevention of parastomal hernias.
Anal fistulas are in the main successfully treated by surgical fistulotomy, however damage to the anal sphincter complex and subsequent incontinence have led to the development of other techniques which aim to either lessen or avoid such disturbance. One strategy involves the traditional cutting seton, and a modification of this technique, the „snug‟ silastic seton was assessed. In the short-medium term, this modification was demonstrated to be an effective addition to the fistula surgeon‟s armamentarium, although minor incontinence remained a concern. Other approaches employing contemporary biomaterials, fibrin glue and porcine intestinal submucosa, are aimed at tissue repair, rather than minimizing destruction. Their success rates however are highly variable. A pilot study aiming to assess the safety and potential efficacy of an
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alternative biomaterial, cross-linked collagen in two different physical formats, was presented. In the short-medium term, both formats were shown to be safe, and equally effective. The results justify continued research into the use of biologically derived materials to heal anal fistulas.
In conclusion, although disparate pathologies were addressed, both they and the thesis are unified by demonstrating that an understanding of the specific disease pathology, wound healing, and the host response to materials (synthetic and biological) are central to their successful management
Studies of clinically applicable human tolerogenic dendritic cells and PD-L2 genetic modification of human islet allograft to promote graft tolerance.
Get PDFIslet transplantation is a developing therapy for type 1 diabetic patients (T1D), which has been limited by problems associated with hypoxia, poor revascularisation and allograft rejection. Immunosuppressive agents used to prevent rejection are associated with severe side effects including islet toxicity, increased susceptibility to the development of cancer, infections and cardio-vascular problems. In order for islet transplantation to be used widely as a potentially curative treatment for T1D there is a need to develop novel therapies to treat allograft rejection without the use of immunosuppressive agents. In chapter 3, the immunomodulatory effects of IFN-γ on human monocyte-derived DC were investigated, using a standard 7-day in vitro DC propagation protocol. IFN-γ was shown to exert its immunomodulatory function on monocytes early during DC differentiation (IFNγ-DC[subscript]D0), resulting in an immature DC (iDC) phenotype with reduced expression of maturation markers CD83 and RelB. IFNγ-DC[subscript]D0 induced a state of T-cell hyporesponsiveness in a MLR, whilst IFN-γ treatment at day 5 (IFNγ-DC[subscript]D5) did not modulate DC function. The ability of IFN-γ to promote the generation of maturation arrested DC, could potentially serve as a cellular therapy for transplant rejection. However DC propagation using the standard 7-10 day protocol is not clinically applicable in the islet transplant setting. In chapter 4, a 'FAST-DC' protocol to promote the rapid generation of tolerogenic DC was investigated and used to generate IFNγ modulated DC in 48h. These IFNγ-DC featured an iDC phenotype similar to that seen in chapter 3. Maturation arrested IFNγ-DC caused significant T-cell hyporesponsiveness and promoted a higher frequency of CD4+CD25+ Foxp3[superscript]HI T-regulatory cells. IFNγ-DC primed T-cells were shown to be functionally suppressive in an antigen specific manner. It was also confirmed that IFN-γ reduced the phosphorylation of IL-4 activated STAT-6, which in turn affected the downstream gene expression of Interferon regulatory factor 4 (IRF4). IFNγ-DC were also investigated in vivo, where a humanised model of islet allo-transplantation model was developed. Diabetic NOD-SCID mice were transplanted with human islets and challenged with donor-derived DC and allogeneic PBMNC. After 21 days post transplantation, there was no significant change to euglycaemic state, between the tested groups. Genetic modification of the allograft is an alternative therapy to protecting the graft from the recipient‟s immune system. In chapter 5, human islets were genetically modified with programmed cell death ligand 2 (PD-L2), an inhibitory molecule known inhibit T-cell immune responses. Two recombinant adenovirus constructs carrying the PD-L2 gene were generated. One construct encoded a soluble isoform, while the other expressed a full transmembrane PD-L2 molecule. Adenoviral transduction did not affect the viability or insulin producing capacity of islets. Interestingly, soluble PD-L2 was more efficient at inducing signalling by 1000 fold, compared to the transmembrane isoform. In summary, this thesis demonstrated the timing of IFN-γ exposure is crucial in determining the function of DC and their maturational state, where IFN-γ exposure only during DC differentiation resulted in the inhibition of DC maturation. Secondly, the combination of IFN-γ and a FAST-DC protocol, enabled the generation of tolerogenic DC in 48h, making DC therapy more clinically applicable. Finally, the induced expression of soluble PD-L2 by human islets potently signals through human PD-1, which may provide the basis for the protection of islets from allo- and auto T-cell responses.Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 201
Desarrollo de linfomas y leucemias mediado por disbiosis intestinal derivada de la administración prolongada de antibióticos. Revisión narrativa de la literatura
No full textEste artículo de revisión tiene como objetivo establecer la conexión entre los cambios de la microbiota gastrointestinal inducidos por el consumo prolongado de antibióticos y su impacto en el proceso de hematopoyesis, y cómo esto conduce al desarrollo de neoplasias de línea blanca como leucemias y linfomas. Para lograr este objetivo, se realizó una búsqueda bibliográfica en diversas bases de datos electrónicas como PubMed, Scopus, ClinicalKey y AccessMedicine, centrándose en estudios de la última década, de 2014 a 2024. Mediante el empleo de los descriptores en salud MeSH (“gastrointestinal microbiome”, “mielopoiesis”, “dysbiosis”, “anti-bacterial agents”, “leukemia”) y DeCS (“microbioma gastrointestinal”, “mielopoyesis”, “disbiosis”, “antibacterianos”, “leucemia”), se seleccionaron estudios clínicos aleatorizados controlados y revisiones de la literatura. Los resultados obtenidos revelan que la disbiosis intestinal, provocada por la administración descontrolada y prolongada de antibióticos, interfiere con procesos inmunológicos críticos, que inducen a alteraciones en la hematopoyesis y predisponen al desarrollo de malignidades hematológicas. Se concluye que existe una relación significativa entre la perturbación de la microbiota gastrointestinal y la incidencia de trastornos oncólogo-hematológicos, subrayando la necesidad de moderar el uso de agentes antibacterianos para mitigar estos efectos adverso
