Linking the synapse to the cytoskeleton: a breath-taking role for microfilaments

Cytoskeletal elements, in particular microtubules and microfilaments, are essential players in a large variety of phenomena requiring cellular and intracellular motility. To name but a few, they are intimately involved in determining cell shape and adhesion, establishment and maintenance of polarity, locomotion and organelle transport in all eukaryotic cells, including neurons. Here, we would like to focus on the synapse in the vertebrate central nervous system, proposing a model for a specific dialogue between neuronal microfilaments and other protein components in neurotransmission and synaptic plasticity.     

Temporal patterns of the cerebral inflammatory response in the rat lithium-pilocarpine model of temporal lobe epilepsy

To better understand the role of inflammatory responses in temporal lobe epilepsy, we characterized Interleukin1-beta (IL1-beta), Nuclear Factor-kappaB (NF-kappaB), and Cyclooxygenase-2 (COX-2) expression together with neurodegeneration in the rat lithium-pilocarpine model. The immunohistochemical expression of IL1-beta, NF-kappaB, and COX-2 started by 12 h post-injection, persisted for 24 h (status epilepticus period), and returned to basal levels by 3 and 6 days (latent period). The regional distribution of IL1-beta, NF-kappaB, and COX-2 occurred mainly in structures prone to develop neuronal damage. Using double-staining protocols, we detected IL1-beta expression in glial cells, COX-2 expression in neurons, and NF-kappaB in both cell types. The presence of Fluoro-Jade-B-positive degenerating neurons was associated with IL1-beta, NF-kappaB, and COX-2 proteins expression during status epilepticus but not during the latent period while neurons were still degenerating. These data suggest that seizure-related IL1-beta, NF-kappaB, and COX-2 expression may contribute to the pathophysiology of epilepsy by inducing neuronal death and astrocytic activation.     

Negative and positive childhood experiences across developmental periods in psychiatric patients with different diagnoses – an explorative study

Background  

A high frequency of childhood abuse has often been reported in adult psychiatric patients. The present survey explores the relationship between psychiatric diagnoses and positive and negative life events during childhood and adulthood in psychiatric samples.     

The usefulness of 99mTc sulfur colloid bone marrow scintigraphy combined with 111In leucocyte scintigraphy in prosthetic joint infection

AIM: To assess the extent to which bone marrow scintigraphy (BMS) makes the interpretation of leucocyte scintigraphy (LS) easier and improves its diagnostic value. METHODS: Seventy-three 111In LSs, 99mTc hydroxymethylene diphosphonate bone scintigraphies (BSs) and 99mTc sulfur colloid BMSs were performed in 60 patients with suspected infection related to a hip prosthesis or knee prosthesis, either in situ (+group, n = 43) or after removal for septic loosening (-group, n = 30). Bacteriological samples were obtained from all patients. LS was interpreted together with BS (LS-BS) or with BMS (LS-BMS) by three independent readers. RESULTS: The concordance among readers, estimated by the kappa test, was average with LS-BS (kappa/kappam coefficients = 0.58, 0.58 and 0.46, respectively, for the three pairs of readers) and excellent with LS-BMS (kappa/kappam coefficients = 1.00 for the three pairs of readers). With LS-BS, 64/219 interpretations were equivocal whereas only one was equivocal with LS-BMS. Sensitivity, specificity and accuracy of LS-BMS were, respectively, 80%, 94% and 91% in the +group, and 33%, 100% and 93% in the -group. CONCLUSION: We conclude that (1) the interpretation of the results for LS-BMS is very easy, in contrast to LS-BS; (2) the diagnostic value of LS-BMS for detecting infected joint prostheses is good; and (3) additional data are needed to assess the accuracy of LS-BMS when the prosthesis has been removed.     

Sentinel node scintigraphy in breast cancer using a dual tracer technique

AIM: In order to depict the anatomy and improve the localization, sentinel node scintigraphy in breast cancer was combined with intravenous administration of pertechnetate. As this may reduce the detectability of weak 'hot spots', the number of lymph nodes detected at scintigraphy and at surgery in one group of patients was compared with that obtained in another group that had not received pertechnetate. PATIENTS AND METHODS: The number of 'hot spots' at frontal and lateral views in 47 female patients at scintigraphy performed 2-3 h after subcutaneous injection of radiocolloid together with 25 MBq pertechnetate i.v. was compared in retrospect with that of 41 female patients who had not received pertechnetate. The number of lymph nodes detected at surgery using a hand-held gamma probe together with blue dye in the two groups was also compared. The washout kinetics of pertechnetate was studied in 10 patients. RESULTS: There was no difference in the number of detected lymph nodes at any comparison. The kinetics study revealed a decreasing activity with time after correction for physical decay. CONCLUSION: Administration of a 25 MBq pertechnetate i.v. in order to improve the anatomical localization at sentinel node scintigraphy in breast cancer does not reduce the detectability of radioactive lymph nodes.     

PET with [18F]fluorothymidine for imaging of primary breast cancer: a pilot study

The aim of this study was to evaluate the use of [¹⁸F]fluorothymidine (FLT) as a positron emission tomography (PET) tracer for the diagnosis of breast cancer. To this end, 12 patients with 14 primary breast cancer lesions (T2–T4) were studied by FLT-PET. For comparison, [¹⁸F]fluorodeoxyglucose (FDG) PET scans were performed in six patients. Thirteen of the 14 primary tumours demonstrated focally increased FLT uptake (SUV_mean=3.4±1.1). Seven out of eight patients with histologically proven axillary lymph node metastases showed focally increased FLT uptake in the corresponding areas (SUV_mean=2.4±1.2). The lowest SUV (mean =0.7) was observed in one of two inflammatory cancers. The contrast between primary tumours or metastases and surrounding tissue was high in most cases. In direct comparison to FDG-PET, the SUVs of primary tumours (5/6) and axillary lymph node metastases (3/4) were lower in FLT-PET (SUV_FLT: 3.2 vs SUV_FDG: 4.7 in primary tumours and SUV_FLT: 2.9 vs SUV_FDG: 4.6 in lymph node metastases). Since FLT uptake in surrounding breast tissue was also lower, tumour contrast was comparable to that with FDG. It is of note that normal FLT uptake was very low in the mediastinum, resulting in a higher tumour-to-mediastinum ratio as compared to FDG (P=0.03). FLT-PET is suitable for the diagnosis of primary breast cancer and locoregional metastases. High image contrast may facilitate the detection of small foci, especially in the mediastinum.     

The cross-cultural adaptation of the Work Role Functioning Questionnaire in Canadian French

The Work Role Functioning Questionnaire (WRFQ) is a new work disability measurement tool assessing the perceived impact of a health problem on the worker's ability to perform his job. The objective of this study was to make the cross-cultural adaptation of the WRFQ for the French Canadian population. The methodology was composed of five steps: forward translation, synthesis of the translations, back translation, revision by an expert committee and test of the pre-final version. The psychometric properties of the translated version were evaluated by administering the questionnaire to forty workers with a musculoskeletal disorder (MSD). Results indicated good content validity and internal consistency (Cronbach alpha > 0.80 for each scale). Construct validity was tested and confirmed through three hypotheses: (1) subjects with MSD scored higher for the Physical, Work Scheduling and Output demands scales than for the Mental and Social demands scales, (2) subjects having back pain had lower scores than subjects having pain at other body sites and (3) subjects with an MSD had lower scores than healthy workers working full time. This study confirmed that the process used for the adaptation of the Canadian French version of the WRFQ was successful and that this version had good psychometric properties.     

The effect of natural habituation on coagulation responses to acute mental stress and recovery in men

Blood coagulation activation might be one mechanism linking acute mental stress with coronary events.We investigated the natural habituation of coagulation responses and recovery to short-term mental stress. Three times with one-week intervals, 24 men (mean age 47 +/- 7 years) underwent the same 13-min stressor (preparation, job interview, mental arithmetic). During each visit venous blood was obtained four times (baseline, immediately post-stress, 45 min of recovery, 105 min of recovery). Eight blood coagulation parameters were measured at weeks one and three. Acute stress provoked increases in von Willebrand factor antigen, fibrinogen, clotting factor FVII activity (FVII:C), FVIII:C, FXII:C (p's < or = 0.019), and D-dimer (N.S.). All coagulation parameters experienced full recovery except FVIII:C (p = 0.022). Stress did not significantly affect activated partial thromboplastin time and prothrombin time. At all time points FVIII:C and FXII:C levels were significantly higher at week one compared to week three (p's < or = 0.041). Before catheter insertion, systolic blood pressure (p = 0.001) and heart rate (p = 0.026) were relatively higher at week one. Unlike the magnitude of systolic blood pressure response to stress (p = 0.007) and of cortisol recovery from stress (p = 0.002), the magnitude of all coagulation responses to stress and the recovery from stress were similar in week one and week three. Sympathetic activation with anticipatory stress best explained increased baseline activity in FVIII and FXII at week one. An incapacity of the coagulation system to adapt to stress repeats is perhaps a consequence of evolution, but might also contribute to increased coronary risk in some individuals, particularly in those with cardiovascular diseases.