10 research outputs found

    Pharmacological hypothesis: A recombinant probiotic for taming bacterial ÎČ-glucuronidase in drug-induced enteropathy

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    Advances in pharmacomicrobiomics have shed light on the pathophysiology of drug-induced enteropathy associated with the therapeutic use of certain non-steroidal anti-inflammatory drugs, anticancer chemotherapies and immunosuppressants. The toxicity pathway results from the post-glucuronidation release and digestive accumulation of an aglycone generated in the context of intestinal dysbiosis characterized by the expansion of ÎČ-glucuronidase-expressing bacteria. The active aglycone could trigger direct or indirect inflammatory signaling on the gut epithelium. Therefore, taming bacterial ÎČ-glucuronidase (GUS) activity is a druggable target for preventing drug-induced enteropathy. In face of the limitations of antibiotic strategies that can worsen intestinal dysbiosis and impair immune functions, we hereby propose the use of a recombinant probiotic capable of mimicking repressive conditions of GUS through an inducible plasmid vector

    Is Intestinal Dysbiosis-Associated With Immunosuppressive Therapy a Key Factor in the Pathophysiology of Post-Transplant Diabetes Mellitus?

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    Post-transplant diabetes mellitus (PTDM) is one of the most common and deleterious comorbidities after solid organ transplantation (SOT). Its incidence varies depending on the organs transplanted and can affect up to 40% of patients. Current research indicates that PTDM shares several common features with type 2 diabetes mellitus (T2DM) in non-transplant populations. However, the pathophysiology of PTDM is still poorly characterized. Therefore, ways should be sought to improve its diagnosis and therapeutic management. A clear correlation has been made between PTDM and the use of immunosuppressants. Moreover, immunosuppressants are known to induce gut microbiota alterations, also called intestinal dysbiosis. Whereas the role of intestinal dysbiosis in the development of T2DM has been well documented, little is known about its impacts on PTDM. Functional alterations associated with intestinal dysbiosis, especially defects in pathways generating physiologically active bacterial metabolites (e.g., short-chain fatty acids, trimethylamine N-oxide, indole and kynurenine) are known to favour several metabolic disorders. This publication aims at discussing the potential role of intestinal dysbiosis and dysregulation of bacterial metabolites associated with immunosuppressive therapy in the occurrence of PTDM

    Meteorological influences on sea surface temperatures in Queen Charlotte Sound

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    Short-term variations of sea surface temperatures (SST) over Queen Charlotte Sound have been poorly understood, mainly due to the lack of data, and therefore hardly predictable. A potentially important consequence of SST variations is the choice of salmon homeward migratory route, which has a significant impact on commercial fisheries. Until recently, predictions of fish migration routes have been made by using SST data at Kains Island, one of the lighthouse stations at the northern end of Vancouver Island. Since the early nineties, AES buoy stations have provided a new set of hourly SST in offshore waters, which may be a better representation of the fish marine environment. This thesis is using visual inspection, statistical analysis and AVHRR satellite imagery to show that the SST at Kains Island do not represent those over the main portion of the Queen Charlotte Sound, but only the SST within 20 km to 30 km from the coast. The SST at the buoy 46207 gives a better representation of the area. Furthermore, the most significant SST variations are caused by upwelling associated with an offshore high pressure system and a lee trough along the west coast of Vancouver Island.Science, Faculty ofEarth, Ocean and Atmospheric Sciences, Department ofGraduat

    Feedback Optimization Strategy for Rotational Alignment Echo Spectroscopy

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    The recent discovery of rotational echoes has contributed to extend the applications of field‐free molecular alignment to short time scales, namely to a temporal region preceding the first alignment revival of the molecule. Most echo measurements require adjusting the position of the echo over time, which in the case of molecular alignment echo unavoidably leads to a change in its amplitude, unless the intensity of the pulse sequence triggering the echo is properly modified. Herein, it is proposed to avoid this drawback by using an optical pulse shaper steered by a learning algorithm. It is demonstrated that a temporal shaping, whose characteristics are optimized to maintain a constant echo amplitude regardless of its creation time, can be generated by controlling the spectral phase and amplitude of the laser pulse which are then used in an open‐loop control system. As a proof of principle, the optimization strategy is applied to the observation of short‐term dissipative dynamics of laser‐aligned molecules exposed to collisions and to the measurement of associated decoherence and population decay time constants

    Pharmacological hypothesis: A recombinant probiotic for taming bacterial ÎČ-glucuronidase in drug-induced enteropathy

    No full text
    Advances in pharmacomicrobiomics have shed light on the pathophysiology of drug-induced enteropathy associated with the therapeutic use of certain non-steroidal anti-inflammatory drugs, anticancer chemotherapies and immunosuppressants. The toxicity pathway results from the post-glucuronidation release and digestive accumulation of an aglycone generated in the context of intestinal dysbiosis characterized by the expansion of ÎČ-glucuronidase-expressing bacteria. The active aglycone could trigger direct or indirect inflammatory signaling on the gut epithelium. Therefore, taming bacterial ÎČ-glucuronidase (GUS) activity is a druggable target for preventing drug-induced enteropathy. In face of the limitations of antibiotic strategies that can worsen intestinal dysbiosis and impair immune functions, we hereby propose the use of a recombinant probiotic capable of mimicking repressive conditions of GUS through an inducible plasmid vector

    Is Intestinal Dysbiosis-Associated With Immunosuppressive Therapy a Key Factor in the Pathophysiology of Post-Transplant Diabetes Mellitus?

    No full text
    Post-transplant diabetes mellitus (PTDM) is one of the most common and deleterious comorbidities after solid organ transplantation (SOT). Its incidence varies depending on the organs transplanted and can affect up to 40% of patients. Current research indicates that PTDM shares several common features with type 2 diabetes mellitus (T2DM) in non-transplant populations. However, the pathophysiology of PTDM is still poorly characterized. Therefore, ways should be sought to improve its diagnosis and therapeutic management. A clear correlation has been made between PTDM and the use of immunosuppressants. Moreover, immunosuppressants are known to induce gut microbiota alterations, also called intestinal dysbiosis. Whereas the role of intestinal dysbiosis in the development of T2DM has been well documented, little is known about its impacts on PTDM. Functional alterations associated with intestinal dysbiosis, especially defects in pathways generating physiologically active bacterial metabolites (e.g., short-chain fatty acids, trimethylamine N-oxide, indole and kynurenine) are known to favour several metabolic disorders. This publication aims at discussing the potential role of intestinal dysbiosis and dysregulation of bacterial metabolites associated with immunosuppressive therapy in the occurrence of PTDM

    Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients

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    International audienceThe aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed

    Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients

    No full text
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