Segmental bioelectrical impedance analysis to assess perioperative fluid changes.

OBJECTIVES: Perioperative fluid accumulation determination is a challenge for the clinician. Bioelectrical impedance analysis (BIA) is a noninvasive method based on the electrical properties of tissues, which can assess body fluid compartments. The study aimed at assessing their changes in three types of surgery (thoracic, abdominal, and intracranial) requiring various regimens of fluid administration. DESIGN: Prospective descriptive trial. PATIENTS: A total of 26 patients scheduled for elective surgery were separated into three groups according to site of surgery: thoracic (n = 8), abdominal aortic (n = 8), and brain surgery (n = 10). SETTING: University teaching hospital. INTERVENTION: None. MEASUREMENTS: Whole body, segmental (arm, trunk, and legs) BIA at multiple frequency (0.5, 50, 100 kHz) was used to assess perioperative fluid accumulation after surgery. The fluid balances were calculated from the charts. RESULTS: The patients were aged 62+/-4 yrs. Fluid balances were 4.8+/-1.0 L, 4.1+/-0.5 L, and 1.9+/-0.3 L, respectively, in the three groups. In trunk surgery patients, fluid accumulation was detected as a drop in impedance in the operated area at all frequencies. In the operated area, there was an expansion of both intra- and extracellular compartments. A reduction in high frequencies' impedance in the legs was only detected after aortic surgery. Fluid accumulation and trunk impedance changes were strongly correlated. Neurosurgery only induced minor body fluid changes. CONCLUSIONS: Segmental BIA is able to detect and localize perioperative fluid accumulation. It may become a bedside tool to quantify and to localize fluid accumulation.

Prevalence and levels of IgG and IgM antibodies against Plasmodium falciparum and P. vivax in blood donors from Rondônia, Brazilian Amazon

Antibodies of IgG and IgM isotopes reacting with Plasmodium falciparum and P. vivax thick-smear antigens were searched for by the indirect fluorescent antibody test (IFAT) in a random sample of 230 blood donors at the transfusion centre of Porto Velho (HEMERON), Rondônia State, western Brazilian Amazon. A high prevalence of IgG seropositivity (32% against P. falciparum, 24% against P. vivax and 37% against either P. falciparum or P. vivax antigens) was detected among them, despite the fact that candidates reporting recent (<12 months) malaria attacks were not elegible. Only a small proportion of them had also detectable IgM antibodies to these antigens. These data suggest an intense, relatively recent exposure to malaria in such an urban population sample. However, parasitaemia (as detected by microscopical examination of Giemsa-stained thick smears) was patent in only one prospective donor. The antibody profile of blood donors was compared with that of healthy subjects of all age groups, living in a close endemic area (Candeias village, 21 km east of Porto Velho). The villagers were classified into two groups according to their history of a recent (<12 months) or a remote (>12 months) past malaria attack due to either P. falciparum or P. vivax. Extensive overlapping was observed when the distribution of antibody titres of healthy subjects from Candeias village with a recent and remote malaria history was compared. In conclusion, subjects with a recent or a remote malaria history could not be distinguished by sorological criteria alone.

A simple and economic slide micro-immunoenzymatic (Micro-SIA) test for epidemiological studies of toxoplasmosis

A slide micro-immunoenzymatic assay (micro-SIA) to detectantibodies to non-particulate Toxoplasma gondii antigens is described. This assay allows the diagnosis of toxoplasmosis infection in about 1 hr. Twenty-four determinations can be performed per slide. Five hundred ng of antigen and 5 or 10 µl drop of each reactive are necessary per well. The clear contrast of colours obtained for negative and positive sera after the test is finished, allows direct discrimination of the results. However, it is possible to quantify the results of the reaction using a minireader. Sera dilution cutoff value, determined as themost frequent titre for the general population, is 1:100. The toxoplasma micro-SIA correlates well with indirect immunofluorescence (IIF), its sensitivity is atleast three times as much as IIF. The test has an intra and inter assay variation coefficient of 5.46 per cent and of 6.24 per cent respectively. Sera obtained at random from argentinian people were analyzed and a 56 per cent of infection was found. The main features of the Toxoplasma micro-SIA are its simplicity, sensitivity, reproducibility, and the virtual absence of background making it very suitable for screening tests.

Anti-TNF Therapy in the Swiss Inflammatory Bowel Disease G8 Cohort

Background: A nti-TNF d rugs (Infliximab (IFX), Adalimumab (ADA), Certolizumab pegol (CZP)) are effective in inducing and maintaining response a nd remission in i nflammatory bowel disease (IBD). Insufficient response or side effects may lead to a switch o f the anti-TNF d rug. W e aimed to e valuate the frequency and reasons for anti-TNF switches. Methods: Analysis of data from the Swiss Inflammatory Bowel Disease Cohort (SIBDCS). Eighty percent of included patients were recruited in hospitals and 20% from private practice. Results: From 2,058 patients ( 1,172 with Crohn's disease (CD), 842 with ulcerative colitis (UC) and 44 with indeterminate colitis (IC)), 772 received at least one anti-TNF. Forty-eight % of patients w ith CD, 23% with U C, a nd 30% with IC w ere ever treated with an anti-TNF drug. There was no gender difference with respect to the frequency of a nti-TNF treatment. A total of 584 patients (76%) were treated with one, 142 (18%) with two, and 46 (6%) with three anti-TNF (of which 32 were female). A total of 89% patients were treated with IFX, 28% ADA and 13% with CZP. Overall response rate (defined as drop in CDAI >100 points) to anti-TNF was 50%, with best response rates for the first used anti-TNF. Reasons t o switch t he anti-TNF w ere in 11% a primary non-response, in 38% a loss of response and in 36% anti-TNF s ide effects o r intolerance ( reasons for 15% of treatment failures not documented). Conclusion: A nti-TNF d rugs were used in h alf of the CD patients a nd in o ne quarter of U C patients. Anti-TNF d rug switch d ue to insufficient response a nd/or side effects w as necessary in one quarter of IBD patients. IFX was mainly used as first-line therapy. Best response rates were observed for the first used anti-TNF. Following analyses will identify risk median treatment duration as well as risk factors for anti-TNF switch.

Immune mechanisms underlying the premunition against Plasmodium falciparum malaria

The most unique characteristic of a parasite when it is in its normal host is the ability to make itself tolerated, which clearly indicates that it has sophisticated means to ensure the neutrality of its host. This is true also in the case of Plasmodium falciparum, since after numerous malaria attacks an equilibrium is reached with a chronic stage of infection, characterized by a relatively low parasitemia, and low or no disease (Sergent & Parrot 1935). We shall briefly review the main characteristics of this state of "premunition", and present data suggesting that the underlying mechanisms of defense rely on the cooperation between cell and antibodies, leading to an antibody dependent cellular inhibition of the intra-erythrocytic growth of the parasite.

Functional effects of Na+,K+-ATPase gene mutations linked to familial hemiplegic migraine.

Familial hemiplegic migraine type 2, an autosomal dominant form of migraine with aura, has been associated with four distinct mutations in the alpha2-subunit of the Na+,K+-ATPase. We have introduced these mutations in the alpha2-subunit of the human Na+,K+-ATPase and the corresponding mutations in the Bufo marinus alpha1-subunit and studied these mutants by expression in Xenopus oocyte. Metabolic labeling studies showed that the mutants were synthesized and associated with the beta-subunit, except for the alpha2HW887R mutant, which was poorly synthesized, and the alpha1BW890R, which was partially retained in the endoplasmic reticulum. [3H]ouabain binding showed the presence of the alpha2HR689Q and alpha2HM731T at the membrane, whereas the alpha2HL764P and alpha2HW887R could not be detected. Functional studies with the mutants of the B. marinus Na+,K+-ATPase showed a reduced or abolished electrogenic activity and a low K+ affinity for the alpha1BW890R mutant. Through different mechanisms, all these mutations result in a strong decrease of the functional expression of the Na+,K+-pump. The decreased activity in alpha2 isoform of the Na+,K+-pump expressed in astrocytes seems an essential component of hemiplegic migraine pathogenesis and may be responsible for the cortical spreading depression, which is one of the first events in migraine attacks.

Infusion of atrial natriuretic peptide to patients with congestive heart failure.

Atrial natriuretic peptides (ANP) exert vasodilating and natriuretic actions. The present study was undertaken to test the effect of low dose infusions of synthetic ANP on hemodynamic and humoral variables of patients with severe heart failure. Eight patients, aged 26 to 71 years, with severe congestive heart failure due to ischemic heart disease or idiopathic dilated cardiomyopathy were included in the study. Synthetic human (3-28) ANP was infused at doses ranging from 0.5 to 2 micrograms/min for up to 3 h. Pulmonary capillary wedge pressure fell from 24 +/- 1 to 16 +/- 2 mm Hg (mean +/- SEM) (p less than 0.01) and cardiac index tended to rise from 2 +/- 0.2 to 2.3 +/- 0.2 L/min/m2 (NS), while blood pressure and heart rate did not change. One patient experienced a marked drop in pulmonary capillary wedge and arterial blood pressure that necessitated the administration of saline. ANP infusion did not alter plasma renin activity or plasma aldosterone, norepinephrine, or vasopressin levels. It decreased plasma epinephrine levels from 0.472 +/- 0.077 to 0.267 +/- 0.024 nmol/L (p less than 0.05). Plasma ANP levels were markedly elevated in all patients before initiating the infusion. They had no predictive value for the hemodynamic response to exogenous ANP. No correlation was observed between the hemodynamic effects of ANP and those induced by the subsequently administered converting enzyme inhibitor captopril, which seemed to improve cardiac function more consistently.(ABSTRACT TRUNCATED AT 250 WORDS)

QUALITEL : Qualitat Docent als estudis d'Enginyeria de Telecomunicació

L'objectiu del projecte QUALITEL dut a terme durant el curs 2007/2008 fou millorar l'aprenentatge dels estudiants de primer curs (fase selectiva) d'enginyeria de telecomunicació de l'ETSETB, introduint una nova metodologia docent basada en l'EEES. Es a dir, programació del treball de l'estudiant dins i fora de l'aula, increment de la interacció entre el professors i els seus estudiants mitjançant un sistema de tutories i la utilització d'eines de suport a l'aprenentatge com la utilització del Campus Digital ATENEA. La millora de l'aprenentatge s'hauria de traduir en un augment significatiu del percentatge d'aprovats a la fase selectiva que permetés capgirar la dinàmica de l'ETSETB en els darrers anys que ha sofert una davallada molt important d'estudiants matriculats. Aquesta davallada es va originar per una disminució de la demanda dels nostres estudis, la qual va provocar una baixada de la nota de tall que, a la seva vegada, va comportar un elevat fracàs a la fase selectiva.

Does terrorism create terror?

The conceptual and etymological meaning of the terms 'terror' and 'terrorism' is so closely connected that it seems difficult to distinguish the one from the other. How- ever, by comparing the idea that terrorism inevitably creates terror with the results of recent empirical studies of the psychological effects of terrorist attacks, four different points of view emerge corresponding to four distinct interpretations of the results. It is thus clearly necessary to redefine the terminology relating to terrorism, in order to con- duct the discussion on a more rigorous basis.

Role of the hypocretin system in cocaine- and alcohol-related behaviors : evidence from hypocretin-deficient mice

RésuméL'addiction aux drogues est une maladie multifactorieile affectant toutes les strates de notre société. Cependant, la vulnérabilité à développer une addiction dépend de facteurs environnementaux, génétiques et psychosociaux. L'addiction aux drogues est décrite comme étant une maladie chronique avec un taux élevé de rechutes. Elle se caractérise par un besoin irrépressible de consommer une drogue et une augmentation progressive de la consommation en dépit des conséquences néfastes. Les mécanismes cérébraux responsables des dépendances aux drogues ne sont que partiellement élucidés, malgré une accumulation croissante d'évidences démontrant des adaptations au niveau moléculaire et cellulaire au sein des systèmes dopaminergique et glutamatergique. L'identification de nouveaux facteurs neurobiologiques responsables de la vulnérabilité aux substances d'abus est cruciale pour le développement de nouveaux traitements thérapeutiques capables d'atténuer et de soulager les symptômes liés à la dépendance aux drogues.Au cours des dernières années, de nombreuses études ont démontré qu'un nouveau circuit cérébral, le système hypocrétinergique, était impliqué dans plusieurs fonctions physiologiques, tel que l'éveil, le métabolisme énergétique, la motivation, le stress et les comportements liés aux phénomènes de récompense. Le système hypocrétinergique est composé d'environ 3000-4000 neurones issus de l'hypothalamus latéral projetant dans tout ie cerveau. Des souris transgéniques pour le gène des hypocrétines ont été générées et leur phénotype correspond à celui des animaux sauvages, excepté le fait qu'elles soient atteintes d'attaques de sommeil similaires à celles observées chez les patients narcoleptiques. H semblerait que les hypocrétines soient requises pour l'acquisition et l'expression de la dépendance aux drogues. Cependant, le mécanisme précis reste encore à être élucidé. Dans ce rapport, nous rendons compte des comportements liés aux phénomènes de récompense liés à l'alcool et à la cocaine chez les souris knock-out (KO), hétérozygotes (HET) et sauvages (WT).Nous avons, dans un premier temps, évalué l'impact d'injections répétées de cocaïne (15 mg/kg, ip) sur la sensibilisation locomotrice et sur le conditionnement place préférence. Nous avons pu observer que les souris WT, HET et KO exprimaient une sensibilisation locomotrice induite par une administration chronique de cocaïne, cependant les souris déficientes en hypocrétines démontraient une sensibilisation retardée et atténuée. Π est intéressant de mentionner que les mâles HET exprimaient une sensibilisation comportementale intermédiaire. Après normalisation des données, toutes les souris exprimaient une amplitude de sensibilisation similaire, excepté les souris mâles KO qui affichaient, le premier jour de traitement, une sensibilisation locomotrice réduite et retardée, reflétant un phénotype hypoactif plutôt qu'une altération de la réponse aux traitements chroniques de cocaïne. Contre toute attente, toutes les souris femelles exprimaient un pattern similaire de sensibilisation locomotrice à la cocaïne. Nous avons ensuite évalué l'effet d'un conditionnement comportemental à un environnement associé à des injections répétées de cocaine (15 mg / kg ip). Toutes les souris, quelque soit leur sexe ou leur génotype, ont manifesté une préférence marquée pour l'environnement apparié à la cocaïne. Après deux semaines d'abstinence à la cocaïne, les mâles et les femelles déficientes en hypocrétines n'exprimaient plus aucune préférence pour le compartiment précédemment associé à la cocaïne. Alors que les souris WT et HET maintenaient leur préférence pour le compartiment associé à la cocaïne. Pour finir, à l'aide d'un nouveau paradigme appelé IntelliCage®, nous avons pu évaluer la consommation de liquide chez les femelles WT, HET et KO. Lorsqu'il n'y avait que de l'eau disponible, nous avons observé que les femelles KO avaient tendance à moins explorer les quatre coins de la cage. Lorsque les souris étaient exposées à quatre types de solutions différentes (eau, ImM quinine ou 0.2% saccharine, alcool 8% et alcool 16%), les souris KO avaient tendance à moins consommer l'eau sucrée et les solutions alcoolisées. Cependant, après normalisation des données, aucune différence significative n'a pu être observée entre les différents génotypes, suggérant que la consommation réduite d'eau sucrée ou d'alcool peut être incombée à l'hypoactivité des souris KO.Ces résultats confirment que le comportement observé chez les souris KO serait dû à des compensations développementales, puisque la sensibilisation locomotrice et le conditionnement comportemental à la cocaïne étaient similaires aux souris HET et WT. En ce qui concerne la consommation de liquide, les souris KO avaient tendance à consommer moins d'eau sucrée et de solutions alcoolisées. Le phénotype hypoactif des souris déficientes en hypocrétine est probablement responsable de leur tendance à moins explorer leur environnement. Il reste encore à déterminer si l'expression de ce phénotype est la conséquence d'un état de vigilance amoindri ou d'une motivation diminuée à la recherche de récompense. Nos résultats suggèrent que les souris déficientes en hypocrétine affichent une motivation certaine à la recherche de récompense lorsqu'elles sont exposées à des environnements où peu d'efforts sont à fournir afin d'obtenir une récompense.AbstractDrug addiction is a multifactorial disorder affecting human beings regardless their education level, their economic status, their origin or even their gender, but the vulnerability to develop addiction depends on environmental, genetic and psychosocial dispositions. Drug addiction is defined as a chronic relapsing disorder characterized by compulsive drug seeking, with loss of control over drug intake and persistent maladaptive decision making in spite of adverse consequences. The brain mechanisms responsible for drug abuse remain partially unknown despite accumulating evidence delineating molecular and cellular adaptations within the glutamatergic and the dopaminergic systems. However, these adaptations do not fully explain the complex brain disease of drug addiction. The identification of other neurobiological factors responsible for the vulnerability to substance abuse is crucial for the development of promising therapeutic treatments able to alleviate signs of drug dependence.For the past few years, growing evidence demonstrated that a recently discovered brain circuit, the hypocretinergic system, is implicated in many physiological functions, including arousal, energy metabolism, motivation, stress and reward-related behaviors. The hypocretin system is composed of a few thousands neurons arising from the lateral hypothalamus and projecting to the entire brain. Hypocretin- deficient mice have been generated, and unexpectedly, their phenotype resembles that of wild type mice excepting sleep attacks strikingly similar to those of human narcolepsy patients. Evidence suggesting that hypocretins are required for the acquisition and the expression of drug addiction has also been reported; however the precise mechanism by which hypocretins modulate drug seeking behaviors remains a matter of debate. Here, we report alcohol and cocaine reward-related behaviors in hypocretin-deficient mice (KO), as well as heterozygous (HET) and wild type (WT) littermates.We first evaluated the impact of repeated cocaine injections (15 mg/kg, ip) on locomotor sensitization and conditioned place preference. We observed that WT, HET and KO mice exhibited behavioral sensitization following repeated cocaine administrations, but hypocretin deficient males displayed a delayed and attenuated response to chronic cocaine administrations. Interestingly, HET males exhibited an intermediate pattern of behavioral sensitization. However, after standardization of the post-injection data versus the period of habituation prior to cocaine injections, all mice displayed similar amplitudes of behavioral sensitization, except a reduced response in KO males on the first day, suggesting that the delayed and reduced cocaine-induced locomotor sensitization may reflect a hypoactive phenotype and probably not an altered response to repeated cocaine administrations. Unexpectedly, all female mice exhibited similar patterns of cocaine-induced behavioral sensitization. We then assessed the behavioral conditioning for an environment repeatedly paired with cocaine injections (15 mg/kg ip). All mice, whatever their gender or genotype, exhibited a robust preference for the environment previously paired with cocaine administrations. Noteworthy, following two weeks of cocaine abstinence, hypocretin-deficient males and females no longer exhibited any preference for the compartment previously paired with cocaine rewards whereas both WT and HET mice continued manifesting a robust preference. We finally assessed drinking behaviors in WT, HET and KO female mice using a novel paradigm, the IntelliCages®. We report here that KO females tended to less explore the four cage comers where water was easily available. When exposed to four different kinds of liquid solutions (water, ImM quinine or saccharine 0.2%, alcohol 8% and alcohol 16%), KO mice tended to less consume the sweet and the alcoholic beverages. However, after data standardization, no significant differences were noticed between genotypes suggesting that the hypoactive phenotype is most likely accountable for the trend regarding the reduced sweet or alcohol intake in KO.Taken together, the present findings confirm that the behavior seen in Hcrt KO mice likely reflects developmental compensations since only a slightly altered cocaine-induced behavioral sensitization and a normal behavioral conditioning with cocaine were observed in these mice compared to HET and WT littermates. With regards to drinking behaviors, KO mice barely displayed any behavioral changes but a trend for reducing sweet and alcoholic beverages. Overall, the most striking observation is the constant hypoactive phenotype seen in the hypocretin-deficient mice that most likely is accountable for their reduced tendency to explore the environment. Whether this hypoactive phenotype is due to a reduced alertness or reduced motivation for reward seeking remains debatable, but our findings suggest that the hypocretin-deficient mice barely display any altered motivation for reward seeking in environments where low efforts are required to access to a reward.

Initial clinical experience with the admiral oxygenator combined with separated suction.

The Admiral, a new microporous membrane oxygenator with a low surface area, decreased priming volume and two separate reservoirs, was tested in 30 adult patients. This study was undertaken to evaluate blood path resistance, gas exchange capabilities and blood trauma in clinical use, with and without shed blood separation. Patients were divided into 3 groups. Group 1 had valve surgery without separation of suction, Group 2 had coronary artery bypass grafting (CABG) with direct blood aspiration and Group 3 had coronary artery bypass grafting with shed blood separation. The suctioned, separated, cardiotomy blood in Group 3 was treated with an autotransfusion device at the end of bypass before being returned to the patient. Theoretical blood flow could be achieved in all cases without problem. The pressure drop through the oxygenator averaged 88 +/- 13 mmHg at 4 l/min and 109 +/- 12 mmHg at 5 l/min. O(2) transfer was 163 +/- 27 ml/min. Free plasma haemoglobin rose in all groups, but significantly less in group 3. Lactate dehydrogenase (LDH) rose significantly in Groups 1 and 2. Platelets decreased in all groups without significant differences. Clinical experience with this new oxygenator was safe, the reduced membrane surface did not impair gas exchange and blood trauma could be minimized easily by separating shed blood, using the second cardiotomy reservoir.

Three Generation Family With Pattern Dystrophy and a Successful Treatment of Subfoveal Cnv Related to Pattern Dystrophy With Anti-vegf Intravitreal Injections

Purpose: To phenotype a large 3 generation Swiss family with pattern dystrophy and to report a successful result of treatment with ranibizumab of a subfoveal choroidal neovascularisation (CNV) associated with pattern dystrophy in 1 patient Patients and methods: 4 affected and 3 unaffected patients (3 female 4 male, age range: 19 - 80 years) were assessed with a complete ophthalmologic examination. AF images were taken using Heidelberg Retina Angiograph and the digital color photos, fluorescein angiogragraphy (FFA) using the same TOPCON 501 camera. Electroretinogram (full-field and multifocal) was performed in 1 affected patient. One 48 years old patient developed a subfoveal CNV, which was treated with 2 injections of ranibizumab, at 3 months interval. Blood sample was taken for molecular analysis (screening of the gene RDS). Results: Two patients had a typical fundoscopic appearance of pattern dystrophy with butterfly shaped deposit at the fovea and some peripheral flecks, as shown with AF imaging.. Two others affected patients had a more unusual appearance with some macular atrophy in one or both eyes, surrounded by flecks. The visual acuity ranged from 1.0 to 0.1 according to Snellen EDTRS chart. The patient with subfoveal CNV presented a drop of vision form 1.0 to 0.6 within 10 days prior to the diagnosis and also reported some metamorphopsia. FFA and optical computerized tomography (OCT) confirmed a classic CNV. After the 1st injection her vision improved to 1.0 but persistent metamorphopsia and fluid on OCT motivated a second injection. One month after the second injection the OCT was flat and the patient had no symptoms. The results of RDS screening will be presented at the meeting. Conclusion: We present a family with pattern dystrophy, with some members having an unusual fundus appearance, which was mistaken for an early onset dry AMD. The AF imaging is a useful tool in diagnosing this condition. A CNV associated with pattern dystrophy a rare. This is the first report of a successful treatment of the CNV with anti-VEGF intravitreal injections.

Impending status epilepticus and anxiety in a pregnant woman treated with levetiracetam.

Levetiracetam (LEV) has been considered to undergo no significant change in bioavailability during pregnancy; however, it was recently demonstrated to display modifications leading to a drop in its serum level. We describe a patient who displayed impending status epilepticus following a fall in her LEV level during the first trimester. The oral LEV dosage was increased, and phenytoin and benzodiazepines were transiently prescribed. She experienced severe anxiety and an unbearable fear over the deleterious consequences for her baby despite repeated, reassuring explanations. Her anxiety was so strong that she aborted electively shortly after leaving the hospital. This observation emphasizes the need for LEV level monitoring during pregnancy to prevent unexpected seizure relapses. The rapid increase in levetiracetam dosage in parallel with the loss of seizure control is suspected of facilitating the induction of significant psychiatric changes.

Cross-talk between glutamate and potassium regulation at the astrocyte membrane

Astrocytes play a central role in the brain by regulating glutamate and extracellular potassium concentrations ([K+]0), both released by neurons into the extracellular space during neuronal activity. Glutamate uptake is driven by the inwardly directed sodium gradient across the astrocyte membrane and involves the influx of three sodium ions and one proton and the efflux of one K+ ion per glutamate molecule. The glutamate transport induced rise in intracellular sodium stimulates the Na+/K+-ATPase which leads to significant energetic costs in astrocytes. To evaluate how these two fundamental functions of astrocytes, namely glutamate transport and K+ buffering, which are directly associated with neuronal activity, coexist and if they influence each other, in this thesis work we examined different cellular parameters of astrocytes. We therefore investigated the impact of altered [K+]0 on glutamate transporter activity. To assess this question we measured intracellular sodium fluctuations in mouse primary cultured astrocytes using dynamic fluorescence imaging. We found that glutamate uptake was tightly modulated both in amplitude and kinetics by [K+]0. Elevated [K+]0 strongly decreased glutamate transporter activity, with significant consequences on the cells energy metabolism. To ultimately evaluate potential effects of [K+]0 and glutamate on the astrocyte mitochondrial energy production we extended these studies by investigating their impact on the cytosolic and mitochondrial pH. We found that both [K+],, and glutamate strongly influenced cytosolic and mitochondrial pH, but in opposite directions. The effect of a simultaneous application of K+ and glutamate, however, did not fit with the arithmetical sum of each individual effects, suggesting that an additional non¬linear process is involved. We also investigated the impact of [K+]0 and glutamate transport, respectively, on intracellular potassium concentrations ([K+]0 in cultured astrocytes by characterizing and applying a newly developed Insensitive fluorescent dye. We observed that [K+]i followed [K+]0 changes in a nearly proportional way and that glutamate superfusion caused a reversible, glutamate-concentration dependent drop of [K+],, Our study shows the powerful influence of [K+]u on glutamate capture. These findings have strong implications for our understanding of the tightly regulated interplay between astrocytes and neurons in situations where [K+]0 undergoes large activity-dependent fluctuations. However, depending on the extent of K+ versus glutamate extracellular rise, energy metabolism in astrocytes will be differently regulated. Moreover, the novel insights obtained during this thesis work help understanding some of the underlying processes that prevail in certain pathologies of central nervous system, such as epilepsy and stroke. These results will possibly provide a basis for the development of novel therapeutic strategies. -- Les astrocytes jouent un rôle central dans le cerveau en régulant les concentrations de potassium (K+) et de glutamate, qui sont relâchés par les neurones dans l'espace extracellulaire lorsque ceux- ci sont actifs. La capture par les astrocytes du glutamate est un processus secondairement actif qui implique l'influx d'ions sodium (Na+) et d'un proton, ainsi que l'efflux d'ions K+, ce processus entraîne un coût métabolique important. Nous avons évalué comment ces fonctions fondamentales des astrocytes, la régulation du glutamate et du K+ extracellulaire, qui sont directement associés à l'activité neuronale, coexistent et si elles interagissent, en examinant différents paramètres cellulaires. Dans ce projet de thèse nous avons évalué l'impact des modifications de la concentration de potassium extracellulaire ([K+],,) sur le transport du glutamate. Nous avons mesuré le transport du glutamate par le biais des fluctuations internes de Na+ grâce à un colorant fluorescent en utilisant de l'imagerie à fluorescence dynamique sur des cultures primaires d'astrocytes. Nous avons trouvé que la capture du glutamate était étroitement régulée par [K+]0 aussi bien dans son amplitude que dans sa cinétique. Par la suite, nous avons porté notre attention sur l'impact de [K+]0 et du glutamate sur le pH cytosolique et mitochondrial de l'astrocyte dans le but, in fine, d'évaluer les effets potentiels sur la production d'énergie par la mitochondrie. Nous avons trouvé qu'autant le K+ que le glutamate, de manière individuelle, influençaient fortement le pH, cependant dans des directions opposées. Leurs effets individuels, ne peuvent toutefois pas être additionnés ce qui suggère qu'un processus additionnel non-linéaire est impliqué. En appliquant une nouvelle approche pour suivre et quantifier la concentration intracellulaire de potassium ([K+]0 par imagerie à fluorescence, nous avons observé que [K+]i suivait les changements de [K+]0 de manière quasiment proportionnelle et que la superfusion de glutamate induisait un décroissement rapide et réversible de [K+]i, qui dépend de la concentration de glutamate. Notre étude démontre l'influence de [K+]0 sur la capture du glutamate. Ces résultats permettent d'améliorer notre compréhension de l'interaction entre astrocytes et neurones dans des situations où [K+]0 fluctue en fonction de l'activité neuronale. Cependant, en fonction de l'importance de l'augmentation extracellulaire du K+ versus le glutamate, le métabolisme énergétique des astrocytes va être régulé de manière différente. De plus, les informations nouvelles que nous avons obtenues durant ce travail de thèse nous aident à comprendre quelques- uns des processus sous-jacents qui prévalent dans certaines pathologies du système nerveux central, comme par exemple l'épilepsie ou l'accident vasculaire cérébral. Ces informations pourront être importantes à intégrer dans la cadre du développement de nouvelles stratégies thérapeutiques.

Recurrent idiopathic neuroretinitis: natural history and effect of treatment.

BACKGROUND: Previous reports have emphasized the self-limited nature of idiopathic neuroretinitis. There is less information about a subgroup of patients who suffer recurrent episodes with worse visual outcome. We sought to better characterize the clinical features of recurrent idiopathic neuroretinitis including the effects of immunosuppressive treatment. METHODS: Retrospective chart review of neuroretinitis patients from a single institution from 1983 to 2008. Inclusion criteria included two or more episodes of acute visual loss with disc oedema and macular exudates in a star pattern. Cases due to a specific infectious or inflammatory aetiology were excluded. RESULTS: Forty-one patients were included with an average follow up of 67 months. Median age at the time of the first episode was 28 years (range 10-54 years). Attacks were bilateral sequential in 34 patients (83%). We documented a total of 147 episodes in 75 eyes with an average of 3.6 attacks per patient. The average interval between attacks was 3 years. Visual field loss had a nerve fibre bundle pattern in most cases. Only 36% of eyes retained 6/12 or better visual acuity and greater than two-thirds of their visual field. Long-term immunosuppressive treatment in 13 patients decreased the attack rate by 72%. CONCLUSIONS: Recurrent idiopathic neuroretinitis typically affects young adults, with no gender preference. Recovery is limited and visual loss is cumulative with repeated attacks, often resulting in severe permanent visual loss. Immunosuppressive treatment appears to lessen the attack frequency.