Prevalence and pharmacological factors associated with impulse-control disorder symptoms in patients with parkinson disease

BACKGROUND: Impulse-control disorders (ICDs) occur in patients with Parkinson disease (PD), especially in younger patients on dopamine therapies. OBJECTIVE: To assess the prevalence of ICD symptoms and its pharmacological correlations in a sample of French patients with PD and without PD (poststroke). METHODS: Outpatients with PD and without PD (poststroke) were screened for compulsive behaviors related to hypersexuality, compulsive shopping, pathological gambling, or compulsive eating by means of the Questionnaire for Impulse-Control Disorders-short version. Full medical history and Unified Parkinson's Disease Rating Scale scores were also recorded. Dose of dopamine agonists were converted to defined daily doses (DDDs), according to the World Health Organization Anatomical Therapeutic Chemical classification system classification system. RESULTS: Two hundred three patients with PD and 52 patients without PD were recruited (mean ± SD age, 67 ± 1 vs 69 ± 2, P= 0.4; males: 62% vs 55% P= 0.2). Symptoms of ICDs were reported by 0% of poststroke patients and 25% of the patients with PD (P < 0.001). Hypersexuality was reported by 10% of the patients with PD, compulsive shopping by 6%, pathological gambling by 3%, and compulsive eating by 14%. A logistic regression analysis found that age younger than 68 years (odds ratio [OR], 3.3; 95% confidence interval, 1.6-6.6) and exposure to dopamine agonists (OR, 20.3; 95% confidence interval, 2.7-65.0) or monoaminooxidase-B inhibitor (OR, 3.7; 95% confidence interval, 1.1-12.6) were significant factors associated with increased ICD frequency. Patients with ICD symptoms were exposed to higher dopamine doses than those without them (1.6 ± 0.1 vs 1.0 ± 0.1 daily-defined doses; P < 0.001). A dose-response pharmacodynamic model disclosed a significant nonlinear dose-response relationship between dopamine agonists and frequency of ICD symptoms (P < 0.01). CONCLUSIONS: Impulse-control disorder symptoms were more frequent in the patients with PD than in the poststroke patients with PD. Impulse-control disorder symptoms were related to younger age and exposure to monoaminooxidase-B inhibitors, and showed a nonlinear dose-response relationship with dopamine agonists.Fil: Perez Lloret, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Inserm; FranciaFil: Rey, María Verónica. Inserm; FranciaFil: Fabre, Nelly. No especifíca;Fil: Ory, Fabienne. No especifíca;Fil: Spampinato, Umberto. No especifíca;Fil: Brefel Courbon, Christine. No especifíca;Fil: Montastruc, Jean Louis. No especifíca;Fil: Rascol, Olivier. Inserm; Franci

Molecular Architecture of the Yeast Nuclear Pore Complex: Localization of Nsp1p Subcomplexes

The nuclear pore complex (NPC), a supramolecular assembly of ∼100 different proteins (nucleoporins), mediates bidirectional transport of molecules between the cytoplasm and the cell nucleus. Extensive structural studies have revealed the three- dimensional (3D) architecture of Xenopus NPCs, and eight of the ∼12 cloned and characterized vertebrate nucleoporins have been localized within the NPC. Thanks to the power of yeast genetics, 30 yeast nucleoporins have recently been cloned and characterized at the molecular level. However, the localization of these nucleoporins within the 3D structure of the NPC has remain elusive, mainly due to limitations of preparing yeast cells for electron microscopy (EM). We have developed a new protocol for preparing yeast cells for EM that yielded structurally well-preserved yeast NPCs. A direct comparison of yeast and Xenopus NPCs revealed that the NPC structure is evolutionarily conserved, although yeast NPCs are 15% smaller in their linear dimensions. With this preparation protocol and yeast strains expressing nucleoporins tagged with protein A, we have localized Nsp1p and its interacting partners Nup49p, Nup57p, Nup82p, and Nic96p by immuno-EM. Accordingly, Nsp1p resides in three distinct subcomplexes which are located at the entry and exit of the central gated channel and at the terminal ring of the nuclear basket

Effects of chronic administration of albumin modified by advanced glycation (AGE) on the liver tissue: characterization of histological, inflammatory and antioxidant profile

A doença hepática gordurosa não alcoólica (DHGNA) compreende um espectro de alterações que inclui a esteatose simples e a esteatohepatite não alcoólica e é considerada o componente hepático da Síndrome Metabólica. Estudos já demonstraram que os produtos finais de glicação avançada (AGEs) estimulam a produção de proteínas de matriz extracelular, a geração de espécies reativas de oxigênio e de citocinas pró-inflamatórias por células hepáticas e que poderiam participar da patogênese da DHGNA. Em vista da escassez de informações sobre os efeitos metabólicos dos AGEs no fígado, apesar do seu potencial para causar dano hepático, nós avaliamos os efeitos da administração crônica de albumina modificada por glicação avançada sobre: (1) variáveis associadas com a homeostase glicêmica e a sensibilidade à insulina; (2) a expressão hepática de genes envolvidos na via dos AGEs, no metabolismo da glicose e de lípides, no estresse oxidativo e na inflamação; (3) a ativação de proteínas envolvidas na via de sinalização insulínica; (4) a morfologia e o conteúdo de glicogênio hepático. O estudo foi realizado em ratos Wistar que receberam, por via intraperitoneal, 20 mg/kg/peso corporal de albumina de rato modificada (AlbAGE) ou não (AlbCTRL) por glicação avançada durante 12 semanas. A administração crônica de AlbAGE não alterou as concentrações de alanina aminotransferase (ALT) e aspartato aminotransferase (AST) ou outras variáveis analisadas, mas induziu a resistência insulínica, conforme detectado pelo teste de tolerância à insulina (ITT). Os demais resultados, no entanto, sugerem um aumento da sensibilidade insulínica no território hepático, conforme evidenciado pela ativação da serine/threoninespecific protein kinase (AKT), inativação da glicogênio sintase cinase (GSK3), aumento do conteúdo do glicogênio hepático e a diminuição da expressão dos genes da via da gliconeogênese Pck1 e G6pc. Outros resultados observados foram uma redução no conteúdo de gordura hepatica e na expressão dos genes lipogênicos Acaca e Fasn e dos genes pró-inflamatórios Nfkb1, Tnf e Il6. Os mecanismos que poderiam explicar a melhora concomitante da sensibilidade hepática à insulina e do perfil inflamatório após exposição crônica aos AGEs não estão claros, mas incluem a inativação da GSK3beta, enzima que exerce efeitos metabólicos e anti-inflamatórios. Nossos achados devem estar relacionados com a via de administração intraperitoneal empregada neste estudo, que resulta na absorção direta dos AGEs para a circulação portal, o que, por sua vez, torna o fígado a primeira linha de defesa contra a toxicidade desses compostos. Uma vez no fígado, os AGEs desencadeiam respostas adaptativas para contrabalançar os seus efeitos potencialmente prejudiciaisThe Nonalcoholic fatty liver disease (NAFLD) comprises a spectrum of conditions that includes simple steatosis and nonalcoholic steatohepatitis and it is considered the hepatic component of the Metabolic syndrome. Studies have shown that advanced glycation end products (AGEs) stimulate the production of extracellular matrix proteins, the generation of reactive oxygen species and of proinflammatory cytokines by liver cells, and that they could participate in NAFLD pathogenesis. In view of the paucity of information regarding the metabolic effects of AGEs on the liver, despite their potential to cause hepatic injury, we evaluated the effects of chronic administration of albumin modified by advanced glycation in (1) variables associated with glucose homeostasis and insulin sensitivity; (2) hepatic expression of genes involved in AGEs, glucose and fat metabolism, oxidative stress and inflammation; (3) activation status of proteins involved in insulin signaling and; (4) hepatic morphology and glycogen content. The study was performed in Wistar rats receiving, by intraperitoneal route, 20 mg/kg/body weight of rat serum albumin modified (AlbAGE) or not (AlbCTRL) by advanced glycation for 12 weeks. Chronic administration of AlbAGE did not alter alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations or other evaluated variables, but induced insulin resistance, as detected by the insulin tolerance test. The remaining results, however, suggested an increase in insulin sensitivity in the hepatic territory, evidenced by activation of serine/threonine-specific protein kinase (AKT), inactivation of glycogen synthase kinase (GSK3), increased hepatic glycogen content, and decreased expression of the gluconeogenesis genes Pck1 and G6pc. Other observed findings were a reduction in hepatic fat content, in the expression of the lipogenic genes Acaca and Fasn and of the proinflammatory genes Nfkb, Tnf, and Il6 genes. Mechanisms that could explain the concomitant improvement in hepatic insulin sensitivity and in the inflammatory profile after chronic exposure to AGEs are not clear, but include inactivation of GSK3beta which exerts metabolic and anti-inflammatory effects. Our findings may be related to the intraperitoneal route of administration employed in this study, which results in direct absorption of AGEs into the portal circulation and, it turn, makes the liver the first-line of defense against the toxicity of these compounds. Once in the liver, AGEs trigger adaptive responses to counterbalance their potentially damaging effect

Crise de migraine spontanée (étude en tomographie par émission de positons)

Certains noyaux du tronc cérébral joueraient un rôle de " générateur " spécifique de la crise de migraine. L'objectif principal est d'étudier des crises de migraine spontanées en Tomographie par Emission de Positons pour confirmer l'implication du tronc cérébral. Sept patients, présentant une migraine sans aura, ont été étudiés dans les 6 premières heures d'une crise spontanée, avant et après sumatriptan, et en intercrise. Des activations significatives ont été retrouvées au niveau du tronc cérébral et de l'hypothalamus lors de la crise par rapport à l'intercrise. Ces activations persistaient après disparition de la douleur par l'injection de sumatriptan. Ces résultats confirment l'implication des noyaux du tronc cérébral, mais également de l'hypothalamus dans la physiopathologie de la migraine. L'hypothalamus pourrait être le " générateur " de la crise de migraine comme le suggère les prodromes de la crise tels que la modification de la faim ou de la soif.TOULOUSE3-BU Santé-Centrale (315552105) / SudocTOULOUSE3-BU Santé-Allées (315552109) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Troubles du sommeil dans la maladie de Parkinson (rôle des traitements)

TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Hypersensibilité a la lumière chez les migraineux (une étude en tomographie par émission de positon)

Dans la migraine la photophobie repose sur une interaction entre la vision et la nociception. Nous avons employé des stimuli favorisant l'habituation (aucun contraste, thermode dans le territoire du V1), décrite comme déficitaire chez les migraineux en intercrise. Chez les sujets sains, nous avons observé une interaction synergique des stimulations douloureuse et lumineuse : la stimulation lumineuse mettait en jeu un réseau de modulation impliquant des activations/déactivations du cortex visuel, des noyaux du pont, du thalamus postérieur, et de l'insula. Chez les migraineux, la stimulation lumineuse a entraîné une hyperactivation du cortex visuel, augmentée en synergie lors de la stimulation douloureuse. Le réseau de modulation des sujets sains n'était pas retrouvé. Notre hypothèse est qu'un dysfonctionnement des noyaux du tronc cérébral est à l'origine de cette perte du réseau de modulation, qui serait elle-même à l'origine de l'hyperactivation du cortex visuel et de la photophobie.TOULOUSE3-BU Santé-Centrale (315552105) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Le syndrome de dysrégulation dopaminergique dans la maladie de Parkinson

TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Prise en charge et conseil officinaux des complications non motrices de la maladie de Parkinson

The aim of this retrospective study is to evaluate the efficacy and safety of this new surgical technic, to determinate it interest versus the already known sorts of vitrectomy. Twenty-nine eyes requiring vitrectomy have been operated by the same surgeon : epiretinal membranes 82,7%, vitreomacular traction syndrom 10,3%, Terson syndrom 3,4%, lens fragment posterior luxation 3,4%. We used a one step cannulated system twenty gauge transconjunctival stureless vitrectomy. Mean operative time was 19 minutes. We reported 2 patients with postoperative hypotony. Suture rate was 4,6%. At the end of follow-up (mean 7,4 month), two serious postoperative complications were observed, included 1 endophtalmitis and 1 retinal detachment. In conclusion, transconjunctival sutureless 20 gauge vitrectomy is useful and safety.TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Les algies vasculaires de la face

Dans une première partie, nous retracerons l'histoire de l'algie vasculaire de la face, ses différents types et les éléments intervenant dans la physiopathologie. Dans une deuxième partie, nous analyserons les traitements de la crise, de fond et perspectives ainsi que les problèmes qu'ils posent. Enfin, dans une troisième partie, nous étudierons trois cas d'AVF chroniques et invalidants traitées par stimulation cérébrale profonde, le protocole opératoire et les résultatsTOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Étude exploratoire par accélérométrie de l’activité physique et du temps sédentaire de médecins généralistes libéraux du sud-ouest de la France en mars 2019

Objectives. - Physical inactivity is the leading cause of preventable death worldwide. A sedentary lifestyle is a new identified risk factor for cardiovascular diseases, diabetes and some cancers. The international recommendations for adults preconize at least 30 mins of moderate to vigorous physical activity (MVPA) per day and a daily sedentary time of less than 7 hours. General Practitioners (GPs) have a mission to promote these recommendations but it is not clear that they apply them to themselves. The aim of this exploratory study was to evaluate the respect of the international recommendations concerning the physical activity and the sedentary lifestyle of a group of GPs in the south-west of France.Equipment and methods. - The physical activity of 94 GPs (55.3% women) averaging 42.7 years of age was measured with Actigraph (R) GT3X accelerometers for seven consecutive days. The recording of their sedentary time and their usual level of MVPA was completed by a self-questionnaire covering working time and physical activity. Data collection took place in March 2019 in five French departments (Landes, Gironde, Pyrenees-Atlantiques, Hautes-Pyrenees and Gers).Results. - GPs were significantly more sedentary and more inactive on workdays than days off. Women were significantly more sedentary and less active than men on workdays. Only 51.1% of GPs adhered to international recommendations for physical activity during workdays, while 77.6% adhered to recommendations during their days off. All GPs were sedentary for more than 7 hours on a workday and 94.7% were sedentary for more than 7 hours on a day off.Conclusion. - General Practitioners should increase their level of moderate to vigorous physical activity and decrease their daily sedentary time. This data must be taken into account for the improvement of their working conditions