Semmelweiss University

Budapest, Hungary

Semmelweiss University

Budapest, Hungary
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Remenyi A.,Óbuda University | Szenasi S.,Óbuda University | Bandi I.,Óbuda University | Vamossy Z.,Óbuda University | And 4 more authors.
LINDI 2011 - 3rd IEEE International Symposium on Logistics and Industrial Informatics, Proceedings | Year: 2011

The main aim of this work is to show, how GPGPUs can facilitate certain type of image processing methods. The software used in this paper is used to detect special tissue part, the nuclei on (HE - hematoxilin eosin) stained colon tissue sample images. Since pathologists are working with large number of high resolution images - thus require significant storage space -, one feasible way to achieve reasonable processing time is the usage of GPGPUs. The CUDA software development kit was used to develop processing algorithms to NVIDIA type GPUs. Our work focuses on how to achieve better performance with coalesced global memory access when working with three-channel RGB tissue images, and how to use the on-die shared memory efficiently. © 2011 IEEE.

PubMed | Adipocyte and Fat Biology Laboratory, University Paul Sabatier, San Jorge University, CNRS Institute of Chemistry and 2 more.
Type: | Journal: Chemico-biological interactions | Year: 2016

Piceatannol is a hydroxylated derivative of resveratrol. While both dietary polyphenols coexist in edible plants and fruits, and share equivalent concentrations in several wines, the influence of piceatannol on adiposity has been less studied than that of resveratrol. Though resveratrol is now recognized to limit fat deposition in various obesity models, the benefit of its dietary supplementation remains under debate regarding human obesity treatment or prevention. The research for more potent resveratrol analogs is therefore still undergoing. This prompted us to compare various effects of piceatannol and resveratrol directly on human adipose tissue (hAT). Hydrogen peroxide release was measured by Amplex Red-based fluorescence in subcutaneous hAT samples from obese patients. Interactions of stilbenes with human amine oxidases and quinone reductase were assessed by radiometric methods, computational docking and electron paramagnetic resonance. Influences on lipogenic and lipolytic activities were compared in mouse adipocytes. Resveratrol and piceatannol inhibited monoamine oxidase (MAO) with respective IC50 of 18.5 and 133.7M, but not semicarbazide-sensitive amine oxidase (SSAO) in hAT. For both stilbenes, the docking scores were better for MAO than for SSAO. Piceatannol and resveratrol similarly hampered hydrogen peroxide detection in assays with and without hAT, while they shared pro-oxidant activities when incubated with purified quinone reductase. They exhibited similar dose-dependent inhibition of adipocyte lipogenic activity. Only piceatannol inhibited basal and stimulated lipolysis when incubated at a dose 100M. Thus, piceatannol exerted on fat cells dose-dependent effects similar to those of resveratrol, except for a stronger antilipolytic action. In this regard, piceatannol should be useful in limiting the lipotoxicity related to obesity when ingested or administered alone - or might hamper the fat mobilization induced by resveratrol when simultaneously administered with it.

PubMed | University Paul Sabatier, Semmelweiss University, French Institute of Health and Medical Research and University of the Basque Country
Type: | Journal: Oxidative medicine and cellular longevity | Year: 2016

Resveratrol has been reported to inhibit monoamine oxidases (MAO). Many substrates or inhibitors of neuronal MAO interact also with other amine oxidases (AO) in peripheral organs, such as semicarbazide-sensitive AO (SSAO), known as primary amine oxidase, absent in neurones, but abundant in adipocytes. We asked whether phenolic compounds (resveratrol, pterostilbene, quercetin, and caffeic acid) behave as MAO and SSAO inhibitors. AO activity was determined in human adipose tissue. Computational docking and glucose uptake assays were performed in 3D models of human AO proteins and in adipocytes, respectively. Phenolic compounds fully inhibited the fluorescent detection of H2O2 generated during MAO and SSAO activation by tyramine and benzylamine. They also quenched H2O2-induced fluorescence in absence of biological material and were unable to abolish the oxidation of radiolabelled tyramine and benzylamine. Thus, phenolic compounds hampered H2O2 detection but did not block AO activity. Only resveratrol and quercetin partially impaired MAO-dependent [(14)C]-tyramine oxidation and behaved as MAO inhibitors. Phenolic compounds counteracted the H2O2-dependent benzylamine-stimulated glucose transport. This indicates that various phenolic compounds block downstream effects of H2O2 produced by biogenic or exogenous amine oxidation without directly inhibiting AO. Phenolic compounds remain of interest regarding their capacity to limit oxidative stress rather than inhibiting AO.

PubMed | Materials Dei Hospital, Columbus University, University of Milan, Inflammatory Bowel Disease Unit and 9 more.
Type: Journal Article | Journal: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association | Year: 2016

Infliximab is a safe and effective therapy for ulcerative colitis (UC). We conducted a multicenter retrospective cohort study that included 7 European countries and Israel to examine whether infliximab discontinuation can be considered for patients who achieve sustained remission.We performed a retrospective cohort study, collecting medical records from 13 tertiary care referral inflammatory bowel disease centers of all patients with UC treated with infliximab (n= 193). We compared the disease course of patients with at least 12 months of clinical remission who discontinued infliximab (n= 111) with that of patients who continued scheduled treatment (controls, n= 82). We examined the incidence rates of relapse, hospitalization and colectomy, the comparative effectiveness of different therapeutic strategies after discontinuation, and assessed the rates of response, remission, and adverse effects after infliximab re-initiation. Statistical analyses used time-to-event methods.In the entire cohort, 67 patients (34.7%) relapsed during the follow-up period. The incidence rate of relapse was significantly higher after discontinuation (23.3 per 100 person-years) compared with the control group (7.2 per 100 person-years) in univariable analysis (log-rank P < .001; hazard ratio, 3.41; 95% confidence interval, 1.88-6.20) and multivariable analysis (hazard ratio, 3.70; 95% confidence interval, 2.02-6.77). Rates of hospitalization and colectomy did not differ between groups. Thiopurines appeared to be the best treatment option after infliximab discontinuation (incidence of relapse: 15.0 per 100 person-years for thiopurines, 27.4 per 100 person-years for thiopurines plus aminosalicylates, and 31.2 per 100 person-years for aminosalicylates alone; log-rank P= .032). Response was regained in 77.1% of patients and remission in 51.4% of patients who re-initiated infliximab. However, 17.1% had infusion reactions and 17.1% reported other adverse events.In a multinational retrospective cohort study of patients with UC in sustained clinical remission, we associated discontinuation of infliximab with an increased risk of relapse. Treatment re-initiation is effective and safe.

Kristensen S.L.,University of Glasgow | Kristensen S.L.,Copenhagen University | Preiss D.,University of Glasgow | Jhund P.S.,University of Glasgow | And 17 more authors.
Circulation: Heart Failure | Year: 2016

The prevalence of pre-diabetes mellitus and its consequences in patients with heart failure and reduced ejection fraction are not known. We investigated these in the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. Methods and Results-We examined clinical outcomes in 8399 patients with heart failure and reduced ejection fraction according to history of diabetes mellitus and glycemic status (baseline hemoglobin A1c [HbA1c]: <6.0% [<42 mmol/mol], 6.0%-6.4% [42-47 mmol/mol; pre-diabetes mellitus], and ≥6.5% [≥48 mmol/mol; diabetes mellitus]), in Cox regression models adjusted for known predictors of poor outcome. Patients with a history of diabetes mellitus (n=2907 [35%]) had a higher risk of the primary composite outcome of heart failure hospitalization or cardiovascular mortality compared with those without a history of diabetes mellitus: adjusted hazard ratio, 1.38; 95% confidence interval, 1.25 to 1.52; P<0.001. HbA1c measurement showed that an additional 1106 (13% of total) patients had undiagnosed diabetes mellitus and 2103 (25%) had pre-diabetes mellitus. The hazard ratio for patients with undiagnosed diabetes mellitus (HbA1c, >6.5%) and known diabetes mellitus compared with those with HbA1c<6.0% was 1.39 (1.17-1.64); P<0.001 and 1.64 (1.43-1.87); P<0.001, respectively. Patients with pre-diabetes mellitus were also at higher risk (hazard ratio, 1.27 [1.10-1.47]; P<0.001) compared with those with HbA1c<6.0%. The benefit of LCZ696 (sacubitril/valsartan) compared with enalapril was consistent across the range of HbA1c in the trial. Conclusions-In patients with heart failure and reduced ejection fraction, dysglycemia is common and pre-diabetes mellitus is associated with a higher risk of adverse cardiovascular outcomes (compared with patients with no diabetes mellitus and HbA1c <6.0%). LCZ696 was beneficial compared with enalapril, irrespective of glycemic status. © 2015 American Heart Association, Inc.

Knowles H.J.,University of Oxford | Knowles H.J.,Nuffield Orthopaedic Center | Moskovsky L.,Semmelweiss University | Thompson M.S.,University of Oxford | And 9 more authors.
Virchows Archiv | Year: 2012

Multinucleated cells termed chondroclasts have been observed on the deep surface of resorbed hyaline cartilage but the relationship of these cells to macrophages and osteoclasts and their role in rheumatoid arthritis (RA) and other arthritic conditions is uncertain. Multinucleated cells in RA and other arthritic conditions showing evidence of cartilage resorption were characterised immunohistochemically for expression of macrophage/osteoclast markers. Mature human osteoclasts formed from circulating monocytes and tissue macrophages were cultured for up to 4 days on slices of human cartilage and glycosaminoglycan (GAG) release was measured. Multinucleated cells resorbing unmineralised cartilage were seen in osteoarthritis, RA, septic arthritis, avascular necrosis and in four cases of giant cell tumour of bone that had extended through the subchondral bone plate. Chondroclasts expressed an osteoclast-like phenotype (TRAP+, cathepsin K+, MMP9+, CD14-, HLADR-, CD45+, CD51+ and CD68+). Both macrophages and osteoclasts cultured on cartilage released GAG. These findings indicate that chondroclasts have an osteoclast-like phenotype and that mature human osteoclasts are capable of cartilage matrix resorption. Resorption of unmineralised subchondral cartilage by chondroclasts and macrophages can be a feature of joint destruction in inflammatory and non-inflammatory arthropathies as well as inflammatory and neoplastic subchondral bone lesions. © Springer-Verlag 2012.

Boshier P.R.,Imperial College London | Mistry V.,Imperial College London | Cushnir J.R.,Imperial College London | Kon O.M.,Imperial College London | And 6 more authors.
Journal of Surgical Research | Year: 2015

Background Esophagectomy and gastrectomy are associated with profound metabolic changes and significant postoperative morbidity. The aim of this prospective clinical study was to determine whether breath analysis can offer novel insight into the surgical metabolic response and identify biomarkers of postoperative complications, including lung injury.Methods Breath samples were collected preoperatively and at 24, 48, 72, 96 and 168 h after esophagectomy (n = 25) and gastrectomy (n = 15). Targeted analysis of four prominent breath metabolites was performed by selected ion flow-tube mass spectrometry. Patients with nonsurgical lung injury (community-acquired pneumonia) were recruited as positive controls.Results Perioperative starvation and subsequent reintroduction of nutritional input were associated with significant changes in breath acetone levels. Breath acetone levels fell after esophagectomy (P = 0.008) and were significantly lower than in gastrectomy patients at postoperative time points 48 (P < 0.001) and 72 h (P < 0.001). In contrast, concentrations of isoprene increased significantly after esophagectomy (P = 0.014). Pneumonia was the most frequently observed postoperative complication (esophagectomy 36% and gastrectomy 7%). The concentration of hydrogen cyanide was significantly lower in the breath of patients who developed pneumonia, 72 h after surgery (P = 0.008). Exhaled hydrogen cyanide (P = 0.001) and isoprene (P = 0.014) were also reduced in patients with community-acquired pneumonia compared with healthy controls.Conclusions Selected ion flow-tube mass spectrometry can be used as a totally noninvasive resource to monitor multiple aspects of metabolic alterations in the postoperative period. Exhaled concentrations of several prominent metabolites are significantly altered after major upper gastrointestinal surgery and in response to pneumonia. © 2015 Elsevier Inc. All rights reserved.

Boshier P.R.,Imperial College London | Hanna G.B.,Imperial College London | Marczin N.,Imperial College London | Marczin N.,Harefield Hospital | Marczin N.,Semmelweiss University
Journal of Breath Research | Year: 2013

The discovery of nitric oxide (NO) as a signalling and regulatory molecule and its subsequent detection in the exhaled breath has not only yielded new mechanistic insights but also diagnostic opportunities and therapeutic targets in several important medical conditions. In diseases involving chronic pulmonary inflammation such as asthma that affects millions worldwide, exhaled NO has achieved spectacular successes with patients currently owning handheld devices and monitoring inflammatory aspects of their conditions in their own homes. This has been facilitated by recognition by regulatory bodies, scientific and clinical societies and insurance companies. While characteristic changes in exhaled NO have also been observed in acute lung injury (ALI), the promise of exhaled NO as a surrogate biomarker of this life-threatening disease has not been achieved. In this work, we have analysed factors contributing to successes of exhaled NO in the asthma field and contrasted these on the ALI field. We provide a snapshot of current status of exhaled NO field in ALI and propose a framework for definite evaluation of exhaled NO as a clinically useful biomarker. © 2013 IOP Publishing Ltd.

Kovacs J.B.,Semmelweiss University | Branstetter G.,Semmelweiss University | Piros L.,Semmelweiss University | Deak P.A.,Semmelweiss University
Transplantation Proceedings | Year: 2012

Between March 2008 and March 2011, hand-assisted laparoscopic donor nephrectomles were performed on 70 patients. Following the first 26 cases undertaken based on guidelines in the literature, we modified the procedure to avoid barotrauma to the kidney caused by the usual 12-13 mm Hg CO2 pneumoperitoneum or pneumoretroperitoneum. The perirenal CO2 pressure, therefore, was decreased to 8 mm Hg from the beginning of the surgery; the operation was performed without using a handport. Our early experience with the modified technique suggested that the safety and duration of the procedure were not affected but the incidence of delayed graft function due to barotrauma was decreased, a cost-effective improvement. © 2012 Elsevier Inc. All rights reserved.

PubMed | Semmelweiss University
Type: | Journal: Sexual medicine reviews | Year: 2016

Hormonal imprinting occurs perinatally, when the developing hormone receptors connect to their target hormones. This is required for the normal development of the receptor-hormone connection. At this time, the selectivity of receptors is weak and can be misdirected to related endogenous or exogenous molecules, such as other members of the same hormone family, synthetic hormones, drugs, hormone-like environmental pollutants, and endocrine disruptors. In this situation, faulty hormonal imprinting develops with lifelong consequences, which are manifested by altered receptor binding capacity, hormone production, changed bone formation, and brain neurotransmitter content. The effect of faulty imprinting is epigenetically inherited and manifested in progeny.To evaluate the effects of hormonal imprinting on sexuality based on published results.Review of perinatal (mainly single) treatment of experimental animals with hormones or hormone-like materials and the study of their effects in adulthood and in progeny.Consistency of experimental results with the previous information and expectations.In each published experiment, perinatal treatments with hormones acting on members of a steroid receptor superfamily or endocrine disruptors (eg, bisphenol A, vinclozolin, benzpyrene or soybean genistein) caused faulty imprinting with altered sexual hormone receptor binding and sexual function. Indices of sexual activity showed the strong influence of these treatments.Sexuality is influenced by perinatal faulty hormonal imprinting at the receptor and behavioral levels. Because faulty imprinting is an epigenetic process, it is transmitted to the members of cell line and to progeny. In the modern age, the amount of artificial (industrial, communal, and medical) imprinters and their effects on the human organism are increasing enormously. This is likely to change human sexuality now and in the future.

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