462 research outputs found

    RĂŽles des aquaporines dans le cerveau

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    Il y a maintenant plus d’une dizaine d’annĂ©es que l’aquaporine 1 (AQP1) a Ă©tĂ© mise en Ă©vidence et clonĂ©e Ă  partir des globules rouges. Cette dĂ©couverte majeure pour le monde du vivant a Ă©tĂ© rĂ©compensĂ©e en 2003 par le Prix Nobel de Chimie dĂ©cernĂ© au Professeur Peter Agre. Les aquaporines (AQP) sont des canaux Ă  eau. Cette famille de protĂ©ines est composĂ©e actuellement de onze sous-types diffĂ©rents exprimĂ©s chez les mammifĂšres. Les trois AQP principales caractĂ©risĂ©es dans le cerveau des mammifĂšres sont l’AQP1, l’AQP4 et l’AQP9. Les travaux rĂ©cents montrent que ces canaux sont impliquĂ©s dans diffĂ©rentes fonctions physiologiques. L’AQP1 serait importante dans la formation du liquide cĂ©phalorachidien, tandis que l’AQP4 aurait un rĂŽle dans l’homĂ©ostasie de l’eau et de la pression osmotique du tissu nerveux. L’AQP9 serait impliquĂ©e dans le mĂ©tabolisme Ă©nergĂ©tique. En condition physiologique, le niveau d’expression de ces AQP est finement rĂ©gulĂ©. Dans diffĂ©rentes maladies du systĂšme nerveux, le niveau d’expression de ces canaux est modifiĂ©, ce qui peut avoir des consĂ©quences sur la formation de l’oedĂšme cĂ©rĂ©bral en modifiant la permĂ©abilitĂ© Ă  l’eau. Actuellement, le rĂŽle de chacune de ces AQP dans ce phĂ©nomĂšne n’est pas encore compris. L’AQP4 semble avoir un rĂŽle trĂšs important dans le dĂ©veloppement de l’oedĂšme aprĂšs un traumatisme crĂąnien, une lĂ©sion ou un accident vasculaire cĂ©rĂ©bral. Une meilleure comprĂ©hension des mĂ©canismes de rĂ©gulation des AQP permettra d’envisager de nouvelles stratĂ©gies thĂ©rapeutiques pour prĂ©venir la formation de l’oedĂšme cĂ©rĂ©bral. La dĂ©couverte rĂ©cente de l’AQP9 dans les neurones catĂ©cholaminergiques a modifiĂ© la vision du rĂŽle des AQP dans le systĂšme nerveux, avec une implication possible de cette derniĂšre dans le mĂ©tabolisme Ă©nergĂ©tique cĂ©rĂ©bral.It is now over 10 years ago that aquaporin 1 (AQP1) was discovered and cloned from the red blood cells, and in 2003 the Nobel price in Chemistry was awarded to Pr. Peter Agre for his work on AQPs, highlighting the importance of these proteins in life sciences. AQPs are water channels. To date this protein family is composed of 11 sub-types in mammalians. Three main AQPs described in the mammalian brain are AQP1, AQP4 and AQP9. Several recent studies have shown that these channels are implicated in numerous physiological functions. AQP1 has a role in cerebrospinal fluid formation, whereas AQP4 is involved in water homeostasis and extracellular osmotic pressure in brain parenchyma. AQP4 seems also to have an important function in oedema formation after brain trauma or brain ischemia. AQP9 is implicated in brain energy metabolism. The level of expression of each AQP is highly regulated. After a trauma or an ischemia perturbation of the central nervous system, the level of expression of each AQP is differentially modified, resulting in facilitating oedema formation. At present, the exact role of each AQP is not yet determined. A better understanding of the mechanisms of AQP regulation should permit the development of new pharmacological strategies to prevent oedema formation. AQP9 has been recently specifically detected in the catecholaminergic neurons of the brain. This new result strengthens the hypothesis that the AQPs are not only water channels, but that some AQPs may play a role in energy metabolism as metabolite channels

    Survival Mechanisms Used by Some Leishmania Species to Escape Neutrophil Killing

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    Neutrophils are the most abundant leukocytes in human blood. Upon microbial infection, they are massively and rapidly recruited from the circulation to sites of infection where they efficiently kill pathogens. To this end, neutrophils possess a variety of weapons that can be mobilized and become effective within hours following infection. However, several microbes including some Leishmania spp. have evolved a variety of mechanisms to escape neutrophil killing using these cells as a basis to better invade the host. In addition, neutrophils are also present in unhealing cutaneous lesions where their role remains to be defined. Here, we will review recent progress in the field and discuss the different strategies applied by some Leishmania parasites to escape from being killed by neutrophils and as recently described for Leishmania mexicana, even replicate within these cells. Subversion of neutrophil killing functions by Leishmania is a strategy that allows parasite spreading in the host with a consequent deleterious impact, transforming the primary protective role of neutrophils into a deleterious one

    GewaltstraftÀter mit und ohne Antisoziale Persönlichkeitsstörung: Ein Vergleich

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    Zusammenfassung: Hintergrund: Die diagnostische Wertigkeit von wiederholten GesetzesĂŒbertretungen im Kontext der Antisozialen Persönlichkeitsstörung (ASPD) wird seit lĂ€ngerem kritisch diskutiert. Um festzustellen, ob sich Probanden mit einer ASPD auch abseits straffĂ€lligen Verhaltens von StraftĂ€tern unterscheiden, wurden inhaftierte StraftĂ€ter mit und ohne diese Diagnose untersucht. Material und Methoden: Sechsunddreißig inhaftierte GewalttĂ€ter mit der Diagnose einer ASPD sowie 29 GewaltstraftĂ€ter ohne ASPD der Justizvollzugsanstalt Straubing nahmen an der Studie teil. Die 28 strafrechtlich unauffĂ€lligen Kontrollprobanden wurden aus der deutschen Normalbevölkerung rekrutiert. Alle Probanden wurden hinsichtlich soziodemographischer, kriminologischer und klinischer Eigenschaften mit dem SKID-I und SKID-II, dem GAF, BIS-11, K-FAF und EPI untersucht. Ergebnisse: GewaltstraftĂ€ter mit ASPD unterscheiden sich bezĂŒglich folgender Parameter von Delinquenten ohne diese Diagnose: erhöhte Erregbarkeit, niedriges psychosoziales Funktionsniveau, gehĂ€ufte "Broken-home-Merkmale" und antisoziales Verhalten vor dem 11.Lebensjahr ("early starters"). Schlussfolgerung: Es konnten Merkmale identifiziert werden, die zwischen GewaltstraftĂ€tern mit und ohne ASPD unterscheiden. In der Gesamtschau scheint allerdings weniger eine kategoriale als vielmehr eine dimensionale, d.h. am AusprĂ€gungsgrad der AuffĂ€lligkeiten ausgerichtete Unterscheidung zwischen GewaltstraftĂ€tern mit und ohne ASPD sinnvoll zu sei

    Developing Intelligent Interviewers to Collect the Medical History: Lessons Learned and Guidelines

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    Background: Physicians spend a lot of time in routine tasks, i.e. repetitive and time consuming tasks that are essential for the diagnostic and treatment process. One of these tasks is to collect information on the patient's medical history. Objectives: We aim at developing a prototype for an intelligent interviewer that collects the medical history of a patient before the patient-doctor encounter. From this and our previous experiences in developing similar systems, we derive recommendations for developing intelligent interviewers for concrete medical domains and tasks. Methods: The intelligent interviewer was implemented as chatbot using IBM Watson assistant in close cooperation with a family doctor. Results: AnCha is a rule-based chatbot realized as decision tree with 75 nodes. It asks a maximum of 44 questions on the medical history, current complaints and collects additional information on the patient, social details, and prevention. Conclusion: When developing an intelligent digital interviewer it is essential to define its concrete purpose, specify information to be collected, design the user interface, consider data security and conduct a practice-oriented evaluation

    Effect of obesity and site of surgery on perioperative lung volumes

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    Background. Although obese patients are thought to be susceptible to postoperative pulmonary complications, there are only limited data on the relationship between obesity and lung volumes after surgery. We studied how surgery and obesity affect lung volumes measured by spirometry. Methods. We prospectively studied 161 patients having either breast surgery (Group A, n=80) or lower abdominal laparotomy (Group B, n=81). Premedication and general anaesthesia were standardized. Spirometry was measured with the patient supine, in a 30° head‐up position. We measured vital capacity (VC), forced vital capacity, peak expiratory flow and forced expiratory volume in 1 s at preoperative assessment (baseline), after premedication (before induction of anaesthesia) and 10-20 min, 1 h and 3 h after extubation. Results. Baseline spirometric values were all within the normal range. All perioperative values decreased significantly with increasing body mass index (BMI). The greatest reduction of mean VC (expressed as percentage of baseline values) occurred after extubation, and was more marked after laparotomy than after breast surgery (23 (sd 14)% vs 20 (14)%). Considering patients according to BMI (30), VC decreased after surgery by 12 (7)%, 24 (8)% and 40 (10)%, respectively. VC recovered more rapidly in Group A. Conclusion. Postoperative reduction in spirometric volumes was related to BMI. Obesity had more effect on VC than the site of surgery. Br J Anaesth 2004; 92: 202-

    Is pretreatment with Beta-blockers beneficial in patients with acute coronary syndrome?

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    OBJECTIVES: The role of beta-blockers in the treatment of hypertension is discussed controversially and the data showing a clear benefit in acute coronary syndromes (ACS) were obtained in the thrombolysis era. The goal of this study was to analyze the role of pretreatment with beta-blockers in patients with ACS. METHODS: Using data from the Acute Myocardial Infarction in Switzerland (AMIS Plus) registry, we analyzed outcomes of patients with beta-blocker pretreatment in whom they were continued during hospitalization (group A), those without beta-blocker pretreatment but with administration after admission (group B) and those who never received them (group C). Major adverse cardiac events defined as composed endpoint of re-infarction and stroke (during hospitalization) and/or in-hospital death were compared between the groups. RESULTS: A total of 24,709 patients were included in the study (6,234 in group A, 12,344 in group B, 6,131 in group C). Patients of group B were younger compared to patients of group A and C (62.5, 67.6 and 68.4, respectively). In the multivariate analysis, odds ratio for major adverse cardiac events was 0.59 (CI 0.47-0.74) for group A and 0.66 (CI 0.55-0.83) for group B, while group C was taken as a reference. CONCLUSIONS: beta-Blocker therapy is beneficial in ACS and they should be started in those who are not pretreated and continued in stable patients who had been on chronic beta-blocker therapy before

    Resistance of Leishmania (Viannia) Panamensis to Meglumine Antimoniate or Miltefosine Modulates Neutrophil Effector Functions.

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    Leishmania (Viannia) panamensis (L. (V.) p.) is the main causative agent of cutaneous leishmaniasis in Colombia and is usually treated with either meglumine antimoniate (MA) or miltefosine (MIL). In recent years, there has been increasing evidence of the emergence of drug-resistance against these compounds. Neutrophils are known to play an important role in immunity against Leishmania. These cells are rapidly recruited upon infection and are also present in chronic lesions. However, their involvement in the outcome of infection with drug-resistant Leishmania has not been examined. In this study, human and murine neutrophils were infected in vitro with MA or MIL drug-resistant L. (V.) p. lines derived from a parental L. (V.) p. drug-susceptible strain. Neutrophil effector functions were assessed analyzing the production of reactive oxygen species (ROS), the formation of neutrophil extracellular trap (NET) and the expression of cell surface activation markers. Parasite killing by neutrophils was assessed using L. (V.) p. transfected with a luciferase reporter. We show here that MA and MIL-resistant L. (V.) p. lines elicited significantly increased NET formation and MA-resistant L. (V.) p. induced significantly increased ROS production in both murine and human neutrophils, compared to infections with the parental MIL and MA susceptible strain. Furthermore, neutrophils exposed to drug-resistant lines showed increased activation, as revealed by decreased expression of CD62L and increased expression of CD66b in human neutrophils yet presented higher survival within neutrophils than the drug-susceptible strain. These results provide evidence that parasite drug-susceptibility may influences neutrophil activation and function as well as parasite survival within neutrophils. Further investigaton of the inter-relationship of drug susceptibility and neutrophil effector function should contribute to better understanding of the factors involved in susceptibility to anti-Leishmania drugs

    Aquaporins in the brain: from aqueduct to "multi-duct"

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    The aquaporin channel family was first considered as a family of water channels, however it is now clear that some of these channels are also permeable to small solutes such glycerol, urea and monocarboxylates. In this review, we will consider AQP4 and AQP9 expressed in the rodent brain. AQP4 is present on astrocytic end-feet in contact with brain vessels and could be involved in ionic homeostasis. However, AQP4 may also be involved in cell adhesion. AQP4 expression is highly modified in several brain disorders and it can play a key role in the cerebral edema formation. However, the exact role of AQP4 in edema formation is still debated. Recently, AQP4 has been shown to be also involved in astrocyte migration during glial scar formation. AQP9 is expressed in astrocytes and in catecholaminergic neurons. Two isoforms of AQP9 are expressed in brain cells, the shortest isoform is localized in the inner membrane of mitochondria and the longest in the cell membrane. The level of expression of AQP9 is negatively regulated by high concentrations of insulin. Taken together, these results suggest that AQP9 could be involved in brain energy metabolism. The induction of AQP9 in astrocytes is observed with time after stroke onset suggesting participation in the clearance of excess lactate in the extracellular space. These recent exciting results suggest that AQPs may not only be involved in water homeostasis in the brain but could also participate in other important physiological functions
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