Myelin basic protein-reactive T cells induce conduction failure in vivo but not in vitro

The ability of myelin basic protein (MBP)-reactive T cells to induce conduction failure was investigated and. With the model, somatosensory evoked potentials (SEP) were recorded before and during adoptively transferred experimental autoimmune encephalomyelitis (EAE) in Lewis rats. Maximum amplitude SEP were reached within 15 min of anesthesia. During EAE, the SEP decreased considerably and their onset was delayed. However, the compound action potentials (CAPs) recorded from Lewis rat optic nerves incubated with encephalitogenic T cells were not affected, emphasizing the importance of environmental factors. This study shows that the model described here is an useful means of investigating the neurological disorders associated with EAE.     

Influence of very low dietary intake of marine oil on some functional aspects of immune cells in healthy elderly people

Ageing is a multifactorial process involving decreased antioxidant defences and immune functions. n-3 Polyunsaturated fatty acids have been associated with human health benefits, especially against inflammatory and autoimmune diseases. However, their immunomodulatory effects were usually observed with high dosages (>2 g/d) known to increase lipid peroxidation. In contrast, very low doses, that may prevent lipid peroxidation, might affect the immune system differently. To study the latter hypothesis further, we investigated whether the supplementation of healthy elderly people with very low doses of marine oil (MO), a docosahexaenoate (DHA)- and eicosapentaenoate (EPA)-rich triacylglycerol, was able to affect lymphocyte proliferation and biochemical markers known to be altered with age. In a randomized, double-blind design, twenty healthy elderly subjects were assigned to a placebo group (600 mg sunflower oil/d) or to a group consuming 600 mg MO/d providing 150 mg DHA + 30 mg (EPA) for 6 weeks. At day 42, the proliferative responses of lymphocytes to several mitogens were significantly (P<0.01) decreased in the MO group compared with control values. This was accompanied by a slight lowering of their cytosolic cyclic nucleotide phosphodiesterase (PDE) activity, a marked and significant (P<0.05) increase of their particulate PDE activity (+56-57 %) and a slight but significant (P<0.05) increase in cyclic nucleotide intracellular levels. At the same time, the glutathione peroxidase activity was markedly and significantly (P<0.01) depressed in the MO group. None of these modifications could be seen in the placebo group. Collectively, these results demonstrate that even very low doses of n-3 fatty acids are sufficient to affect the immune responses of elderly subjects.     

The opening interrupter technique for respiratory resistance measurements in children

Background and objective: The interrupter resistance (Rint) can be calculated from various estimates of alveolar pressure based on mouth pressure during occlusion. We compared Rint, as measured by the opening interrupter technique (Rint1), and the linear back‐extrapolation method (Rint2), with the ‘gold standard’ airway resistance measured by plethysmography (Raw). Methods: The study included 32 asthmatic children and 11 children with cystic fibrosis, aged 5 to 18 years, who were categorized into non‐obstructed (NObs) (n = 27) and obstructed (Obs) (n = 16) groups. Spirometry and the three different resistance measurements were performed on all children. Rint1 and Raw were assessed after a bronchodilator (BD) test in 16 and nine children, respectively, in the Obs group. Results: Raw (0.48 ± 0.20 kPa.s/L) was lower than Rint1 (1.04 ± 0.34 kPa.s/L) and Rint2 (0.63 ± 0.18 kPa.s/L) (P < 0.001). Raw, but neither Rint1 nor Rint2, was significantly higher in the Obs group than in the NObs group (0.57 ± 0.23 vs 0.42 ± 0.16 kPa.s/L, P < 0.05). The differences Rint1‐Raw and Rint2‐Raw were correlated with FEV₁/VC (P < 0.01 and P < 0.001), and Rint1‐Raw was correlated with height (P < 0.001). After BD significant changes in Rint1 and Raw were observed in 5/9 and 7/9 children, respectively. Conclusions: Rint2, as well as Rint1, may be underestimated in the most Obs children and may therefore fail to detect severe obstruction. Rint1 is likely to include a non‐negligible contribution from the tissue component, especially in the youngest children. Although not different between Obs and NObs children at baseline, Rint1 did detect bronchodilation in some Obs children.     

Essential role of Notch signaling in apoptosis of human pancreatic tumoral cells mediated by exosomal nanoparticles

We previously reported that exosomal nanoparticles secreted by human pancreatic tumoral cell lines decrease tumoral cell proliferation through the mitochondria‐dependent apoptotic pathway, because of activation of pro‐apoptotic phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and of glucose synthase kinase‐3β (GSK‐3β). Interactions between exosomal nanoparticles and cells are thought to involve membrane lipid rafts. However, the underlying mechanism is unknown. Here, we report that the interaction of exosomal nanoparticles with pancreatic cancer cells led to decreased expression of hairy and enhancer‐of‐split homolog‐1 (Hes‐1), the intranuclear target of Notch‐1 signaling pathway, and to activation of the apoptotic pathway after a cell cycle arrest in G₀G₁ phase. Strikingly, the expression level of Notch‐1 pathway components was critical, because exosomal nanoparticles decreased the proliferation of cells in which these partners are either weakly represented, in differentiated adenocarcinoma cells, or inhibited, in poorly differentiated carcinoma cells, by blocking presenilin in the γ‐secretase complex that regulates the Notch‐1 pathway. Overexpression of Notch‐1 intracellular domain resulted in the reversion of the cell proliferation inhibition promoted by exosomal nanoparticles. Blocking presenilin unexpectedly resulted in activation of PTEN and GSK‐3β. Conversely, inhibiting either PTEN or GSK‐3β increased Hes‐1 expression and partially counteracted the inhibition of proliferation promoted by exosomal nanoparticles, highlighting reciprocal regulations between Notch signaling and PTEN/GSK‐3β. We concluded that interactions of exosomal nanoparticles with target cells, at lipid rafts where Notch‐1 pathway partners are localized, hampered the functioning of the Notch‐1 survival pathway and activated the apoptotic pathway, which determines tumoral cell fate. © 2009 UICC     

Influence d'une supplémentation en vitamine E sur le sélénium au cours d'une nutrition parentérale exclusive chez l'enfant

Double supplementation in selenium and vitamin E during total parenteral nutrition (TPN) now appears essential to avoid clinical manifestations of their deficiencies. We studied children of 1 month to 12 years of age deficient in selenium (plasmatic selenium : P-Se : 40–80 μg/L) and vitamin E (ratio vitamin E on total lipids : VE/LT = 1.10 − 1.80 mg/g). Prior to supplementation, the ratio VE/LT is negatively correlated to P-Se (r = −0.81) and positively to erythrocyte selenium (RBC-Se, r = +0.64). These results suggest a balance between both. The parenteral alimentation was then supplemented with sodium selenite (3 μg/kg/d) and weekly with IM vitamin E (Protocol 1 : P1 : 30 to 60 mg according to age; Protocol 2 : P2 : twice these doses). The ratio VE/LT returned to normal faster in P2 than in P1 (P2 : 15–30 days; P1 : about 120 days). Selenium supplementation restores P-Se quickly (45–60 days) contrary to RBC-Se which is a slow process (120 d). High vitamin E intakes do not seem to have an effect upon selenium stores : no statistical differences were found between P1 and P2 during the same period. Such intakes may however be indicated during the first month of TPN to balance the time course for repletion of RBC-Se which is long (120 days).     

Pelvic Floor Muscle Assessment Outcomes in Women With and Without Provoked Vestibulodynia and the Impact of a Physical Therapy Program

IntroductionPhysical therapy (PT) may reduce the pain associated with provoked vestibulodynia (PVD) based on previous findings that pelvic floor muscle dysfunction (PFMD) is associated with PVD symptoms.AimsThe goals of this study were: (i) to determine whether women with and without PVD differ on measures of pelvic floor muscle (PFM) behavior; and (ii) to assess the impact of PT treatment for women with PVD on these measures.MethodsEleven women with PVD and 11 control women completed an assessment evaluating PFM behavior using surface electromyography (SEMG) recordings and a digital intravaginal assessment. Women with PVD repeated the assessment after they had undergone eight PT treatment sessions of manual therapy, biofeedback, electrical stimulation, dilator insertions, and home exercises.Main Outcome MeasuresSuperficial and deep PFM SEMG tonic activity and phasic activity in response to a painful pressure stimulus, PFM digital assessment variables (tone, flexibility, relaxation capacity, and strength).ResultsAt pretreatment, women with PVD had higher tonic SEMG activity in their superficial PFMs compared with the control group, whereas no differences were found in the deep PFMs. Both groups demonstrated contractile responses to the painful pressure stimulus that were significantly higher in the superficial as compared with the deep PFMs, with the responses in the PVD group being higher than those in control women. Women with PVD had higher PFM tone, decreased PFM flexibility and lower PFM relaxation capacity compared with control women. Posttreatment improvements included less PFM responsiveness to pain, less PFM tone, improved vaginal flexibility, and improved PFM relaxation capacity, such that women with PVD no longer differed from controls on these measures.ConclusionWomen with PVD demonstrated altered PFM behavior when compared with controls, providing empirical evidence of PFMD, especially at the superficial layer. A PT rehabilitation program specifically targeting PFMD normalized PFM behavior in women with PVD. Gentilcore-Saulnier, E, McLean L, Goldfinger C, Pukall CF, and Chamberlain S. Pelvic floor muscle assessment outcomes in women with and without provoked vestibulodynia and the impact of a physical therapy program.     

发展健康城市项目的20个步骤

健康城市项目是一个非常艰巨的项目。虽然 1 5年前世界卫生组织欧洲区就已启动健康城市项目 ,但时至今日这项目的实施还存在许多问题。把健康城市的理想转化为现实需要勇气、政治承诺和有志于革新与实验。建立公共卫生工作联盟 ,寻求健康促进新的资源 ,以及发展项目的策略和工作方法 ,并把其转化为具体方案和行动必须考虑不同的文化和传统 ,这是最具挑战性的任务之一[1] 。经过多年的欧洲健康城市项目实践 ,世界卫生组织概括总结了健康城市项目发展的基本步骤。一般而言 ,健康城市项目发展分为 3个阶段 :启动 ,组织 ,行动。这 3个阶段相互交…     

Pulsed-Field Gel Electrophoresis Is More Efficient than Ribotyping and Random Amplified Polymorphic DNA Analysis in Discrimination of Pasteurella haemolytica Strains

One hundred thirty-three strains of Pasteurella haemolytica of both biotypes (90 and 43 strains of biotypes A and T, respectively) and almost all the serotypes were subjected to ribotyping, random amplified polymorphic DNA (RAPD) analysis, and pulsed-field gel electrophoresis (PFGE) analysis for epidemiological purposes. A total of 15 patterns recorded as ribotypes HA to HO were found for the P. haemolytica biotype A strains, with ribotypes HA, HC, and HD being encountered most often (66 strains [74%]); and 20 ribotypes, designated HA′ to HT′, that were clearly distinct from those observed for biotype A strains were observed for strains of biotype T. RAPD analysis generated a total of 44 (designated Rp1 to Rp44) and 15 (designated Rp1′ to Rp 15′) unique RAPD patterns for biogroup A and biogroup T, respectively. Analysis of the data indicated that a given combined ribotype-RAPD pattern could be observed for biotype A strains of different serotypes, whatever the zoological or geographic origin, whereas this was not the case for biotype T strains. PFGE appeared to be more efficient in strain discrimination since selected strains from various zoological or geographical origins harboring the same ribotype-RAPD group were further separated into unique entities.