Estradiol differentially modulates the exocytotic proteins SNAP-25 and munc-18 in pituitary gonadotrophs

Long-term treatment with estradiol increases LH secretion from female gonadotrophs. The mechanisms are not fully clarified yet. Our previous data indicated that sexual steroids might affect late steps in GnRH signal transduction such as exocytosis. The secretion of hormones from neuroendocrine cells requires the merger of secretory vesicles with the plasma membrane. This regulated exocytosis is mediated by specific proteins, which are present in the pituitary gland. Here, we examined whether two of these crucial exocytotic proteins, SNAP-25 and munc-18, are affected by estradiol in female gonadotrophs. Female rat anterior pituitary cells and alphaT3-1 cells, derived from a murine immortalized gonadotroph cell line, were treated with 100 pM estradiol for 48 h. LH secretion of anterior pituitary cells, additionally stimulated with eight consecutive pulses of 1 nM GnRH for 15 min at an interval of 1 h, was determined by RIA. Gene expression was measured by quantitative RT-PCR and protein expression by immunoblotting. Additionally, quantitative RT-PCR was performed in single rat gonadotrophs to ascribe effects exclusively to intact gonadotrophs. Pulsatile GnRH enhanced the mRNA expression of SNAP-25 and munc-18 in accordance with the LH secretory response with the greatest increase at the third pulse of GnRH. Estradiol treatment further increased GnRH-induced LH secretion at all GnRH pulses. SNAP-25 gene expression was significantly decreased at the fifth GnRH pulse and unaffected at basal after 48 h of estradiol treatment. In contrast, munc-18 mRNA levels were not significantly affected by estradiol at different GnRH-pulses in mixed anterior pituitary cells, whereas munc-18 gene expression was significantly increased at basal. In alphaT3-1 cells and single gonadotrophs, long-term estradiol treatment significantly reduced SNAP-25 protein and gene expression. In contrast, the protein and gene expression of munc-18 was significantly enhanced in both alphaT3-1 cells and single gonadotrophs. In conclusion, munc-18 and SNAP-25 were oppositionally influenced by estradiol. The results suggest that estradiol modulates the expression of exocytotic proteins in gonadotrophs and thus affects LH secretion.     

Platelet and plasma BDNF in lower respiratory tract infections of the adult

Enhanced bronchial responsiveness during and following lower respiratory tract infections is a major clinical problem, but its pathogenesis is poorly understood. Brain-derived neurotrophic factor (BDNF), which can be released by platelets and leukocytes, has been identified as a mediator of bronchial hyperresponsiveness. It is unknown whether the release of BDNF is altered during lower respiratory tract infections of the adult. In this clinical pilot study, 16 patients (35-80 years old) with the diagnosis of an acute bacterial lower respiratory tract infection and elevated serum concentrations of c-reactive protein (>100 microg/ml) and procalcitonin (>0.1 ng/ml) were examined on admission to the hospital and 1 week after antibiotic treatment. Sixteen age- and sex-matched controls were examined in the same time period. BDNF concentrations in serum and platelets, but not in plasma, were markedly reduced in patients on the day of admission (median <25% of the controls). Analysis of the platelet marker serotonin (5-HT) suggested that the decrease of platelet BDNF is part of a non-specific release of platelet-derived mediators in this condition. Clinical improvement was accompanied by a restoration of serum and platelet BDNF concentrations which returned to control levels after 1 week of treatment. Cell culture experiments revealed that bacterial lipopolysaccharide (LPS) enhanced the release of BDNF by peripheral blood mononuclear cells of the patients at both time points. In conclusion, these data suggest that lower respiratory tract infections might be associated with an augmented release of BDNF by platelets and mononuclear cells.     

Enhanced poly(ADP-ribose) polymerase-1 activation contributes to recombinant tissue plasminogen activator-induced aggravation of ischemic brain injury in vivo

Recombinant tissue plasminogen activator (rt-PA) treatment improves functional outcome after acute ischemic stroke, inducing reperfusion by its thrombolytic activity. Conversely, there is evidence that rt-PA can mediate neuronal damage after ischemic brain injury in vivo. In addition to other mechanisms, enhancement of N-methyl-D-aspartate (NMDA) receptor signalling has been proposed to underlie rt-PA-mediated neurotoxicity. However, the role of poly(ADP-ribose) polymerase-1 (PARP-1) activation, which mediates postischemic excitotoxic cell death, in rt-PA-mediated aggravation of ischemic brain injury has not been established and was therefore addressed in this study. After permanent focal cerebral ischemia, intravenous rt-PA application significantly increased early postischemic PARP-1 activation within ischemic hemispheres and infarct volumes compared with control mice without affecting cerebral blood flow. Rt-PA induced increase in PARP-1 activation, and infarct volumes could be blocked by the PARP inhibitor 3-aminobenzamide. Moreover, the rt-PA-induced increase in PARP-1 activation was also prevented by the NMDA antagonist MK-801. In summary, we demonstrate that rt-PA treatment enhances postischemic PARP-1 activation, which contributes to rt-PA induced aggravation of ischemic brain injury in vivo. Furthermore, we provide evidence that NMDA receptor activation is required for rt-PA-mediated effects on postischemic PARP-1 activation.     

Lung MRI at 1.5 and 3 Tesla: observer preference study and lesion contrast using five different pulse sequences

OBJECTIVES: To compare the image quality and lesion contrast of lung MRI using 5 different pulse sequences at 1.5 T and 3 T. MATERIALS AND METHODS: Lung MRI was performed at 1.5 T and 3 T using 5 pulse sequences which have been previously proposed for lung MRI: 3D volumetric interpolated breath-hold examination (VIBE), true fast imaging with steady-state precession (TrueFISP), half-Fourier single-shot turbo spin-echo (HASTE), short tau inversion recovery (STIR), T2-weighted turbo spin-echo (TSE). In addition to 4 healthy volunteers, 5 porcine lungs were examined in a dedicated chest phantom. Lung pathology (nodules and infiltrates) was simulated in the phantom by intrapulmonary and intrabronchial injections of agarose. CT was performed in the phantom for correlation. Image quality of the sequences was ranked in a side-by-side comparison by 3 blinded radiologists regarding the delineation of pulmonary and mediastinal anatomy, conspicuity of pulmonary nodules and infiltrates, and presence of artifacts. The contrast of nodules and infiltrates (CNODULES and CINFILTRATES) defined by the ratio of the signal intensities of the lesion and adjacent normal lung parenchyma was determined. RESULTS: There were no relevant differences regarding the preference for the individual sequences between both field strengths. TSE was the preferred sequence for the visualization of the mediastinum at both field strengths. For the visualization of lung parenchyma the observers preferred TrueFISP in volunteers and TSE in the phantom studies. At both field strengths VIBE achieved the best rating for the depiction of nodules, whereas HASTE was rated best for the delineation of infiltrates. TrueFISP had the fewest artifacts in volunteers, whereas STIR showed the fewest artifacts in the phantom. For all but the TrueFISP sequence the lesion contrast increased from 1.5 T to 3 T. At both field strengths VIBE showed the highest CNODULES (6.6 and 7.1) and HASTE the highest CINFILTRATES (6.1 and 6.3). CONCLUSION: The imaging characteristics of different pulse sequences used for lung MRI do not substantially differ between 1.5 T and 3 T. A higher lesion contrast can be expected at 3 T.     

Experience-dependent plasticity of conceptual representations in human sensory-motor areas

Concepts are composed of features related to different sensory and motor modalities such as vision, sound, and action. It is a matter of controversy whether conceptual features are represented in sensory-motor areas reflecting the specific learning experience during acquisition. In order to address this issue, we assessed the plasticity of conceptual representations by training human participants with novel objects under different training conditions. These objects were assigned to categories such that for one class of categories, the overall shape was diagnostic for category membership, whereas for the other class, a detail feature affording a particular action was diagnostic. During training, participants were asked to either make an action pantomime toward the detail feature of the novel object or point to it. In a categorization task at test, we assessed the neural correlates of the acquired conceptual representations by measuring electrical brain activity. Here, we show that the same object is differentially processed depending on the sensory-motor interactions during knowledge acquisition. Only in the pantomime group did we find early activation in frontal motor regions and later activation in occipito-parietal visual-motor regions. In the pointing training group, these effects were absent. These results show that action information contributes to conceptual processing depending on the specific learning experience. In line with modality-specific theories of conceptual memory, our study suggests that conceptual representations are established by the learning-based formation of cell assemblies in sensory-motor areas.     

Syncope due to Brugada syndrome in a young athlete

A 30-year-old male athlete with exercise-related syncopal symptoms spontaneously exhibited a type 1 Brugada ECG and was inducible during electrophysiology study. He was diagnosed with symptomatic Brugada syndrome and deemed at high risk of sudden cardiac death. Thus, he received a cardioverter/defibrillator and was advised to abstain from further competitive sports activities. This case points to a role of the ECG in pre-participation screening. It also demonstrates that, in athletes with Brugada syndrome, repolarisation anomalies may be markedly attenuated during vigorous exercise and considerably increased immediately after exercise. The observed J-wave amplitude dynamics suggests enhancement of pre-existing autonomic dysfunction through heavy exertion.     

Evidence of subcortical and cortical aging of the acoustic pathway: a diffusion tensor imaging (DTI) study

RATIONALE AND OBJECTIVES: During aging, there is evidence of microstructural changes in certain cortical and subcortical brain regions. Diffusion tensor imaging (DTI) is used to study age related microstructural changes in the acoustic pathway. MATERIALS AND METHODS: Twenty healthy volunteers (mean age 28.5 years) and 15 healthy volunteers (mean age 61.3 years) were examined using a 1.5-T MR system with a high-resolution T1-weighted sequence and an integrated parallel imaging technique DTI Echo-planar-imaging (EPI) sequence. For reliability, 10 subjects underwent a second examination 2 days later. The fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) were measured in six brain regions of the auditory pathway. RESULTS: We found no left/right asymmetry in the selected brain structures. There were no significant differences (P < .05) in the ADC and FA in the lateral lemniscus and medial geniculate body of young and elderly subjects. However, FA was significantly increased (P < .05) in the inferior colliculus and decreased in the auditory radiation, the superficial temporal gyrus, and the transverse temporal gyrus in the elder subjects than in the younger ones. There were no significant differences in anisotropy in subsequent examinations in the younger individuals. CONCLUSIONS: These findings suggest evidence of age-related changes in the acoustic pathway. These changes are associated with a decrease in anisotropy mainly in the cortical grey and white matter rather than in the subcortical regions. Our DTI measurements were reproducible.     

LEARN 2 MOVE 7-12 years: a randomized controlled trial on the effects of a physical activity stimulation program in children with cerebral palsy

Background  

Regular participation in physical activities is important for all children to stay fit and healthy. Children with cerebral palsy have reduced levels of physical activity, compared to typically developing children. The aim of the LEARN 2 MOVE 7-12 study is to improve physical activity by means of a physical activity stimulation program, consisting of a lifestyle intervention and a fitness training program.