Post-ischemic administration of diazoxide attenuates long-term microglial activation in the rat brain after permanent carotid artery occlusion

Diazoxide is a putative mitochondrial, ATP-sensitive potassium channel opener that has been implicated in neuroprotection in cerebral ischemia. Administered as pretreatment, diazoxide can attenuate ischemia-related neuronal injury, but little is known about the potential neuroprotective properties of the drug when it is given after the onset of an ischemic insult. In a previous study, we applied diazoxide after imposing chronic cerebral hypoperfusion by means of permanent, bilateral occlusion of the common carotid arteries (2VO) in rats. We observed that ischemia-induced learning impairment assessed in the Morris water maze, and microglial activation visualized by immunocytochemistry, were prevented by diazoxide as determined at 13 weeks after 2VO. However, dimethyl sulfoxide, the organic solvent of diazoxide also prevented memory deficits, without any effect on microglial activity. Therefore, we have repeated our experiments with the use of an inorganic solvent, aqueous NaOH solution in order to clarify the effect of diazoxide independent of dimethyl sulfoxide. The present results demonstrated that diazoxide alone did not improve learning performance, but it prevented microglial activation in the hippocampus 13 weeks after the onset of 2VO. These data provide evidence that post-treatment with diazoxide is not effective in impeding a long-term memory deficiency, but it can attenuate ischemia-induced microglial activation, independently of the solvent used.     

In vitro degradation of polymeric networks of poly(propylene fumarate) and the crosslinking macromer poly(propylene fumarate)-diacrylate

Polymeric networks of poly(propylene fumarate) (PPF) crosslinked with poly(propylene fumarate)-diacrylate (PPF-DA) are currently being investigated as an injectable, biodegradable bone cement. This study examined the effect of crosslinking density, medium pH, and the incorporation of a beta-tricalcium phosphate (beta-TCP) filler on the in vitro degradation of PPF/PPF-DA. Cylindrical specimens were submerged in buffered saline at 37 degrees C and the change in weight, geometry, and compressive mechanical properties were monitored over a 52-week period. All formulations showed an initial increase in modulus and yield strength over the first 12 weeks, achieving maxima of 1307+/-101 and 51+/-3MPa, respectively, for the beta-TCP composite. PPF/PPF-DA networks with the lower crosslinking density demonstrated the greatest degradation with a 17% mass loss. Samples in the lower buffer pH 5.0 compared to physiological pH 7.4 did not show any differences in mass loss, but exhibited a faster decrease in the compressive strength over time. The beta-TCP composites maintained their mechanical properties at the level following their initial increase. These results show that the degradation of PPF/PPF-DA networks can be controlled by the crosslinking density, accelerated at a lower pH, and prolonged with the incorporation of the beta-TCP filler.     

Selecting relevant electrode positions for classification tasks based on the electro-encephalogram

The aim is to describe a general approach to determining important electrode positions when measured electro-encephalogram signals are used for classification. The approach is exemplified in the frame of the brain-computer interface, which crucially depends on the classification of different brain states. To classify two brain states, e.g. planning of movement of right and left index fingers, three different approaches are compared: classification using a physiologically motivated set of four electrodes, a set determined by principal component analysis and electrodes determined by spatial pattern analysis. Spatial pattern analysis enhances the classification rate significantly from 61.3±1.8% (with four electrodes) to 71.8±1.4%, whereas the classification rate using principal component analysis is significantly lower (65.2±1.4%). Most of the 61 electrodes used have no influence on the classification rate, so that, in future experiments, the setup can be simplified drastically to six to eight electrodes without loss of information.     

How to Optimize Radiological Images Captured from Digital Cameras, Using the Adobe Photoshop 6.0 Program

Over the past decade, the technology that permits images to be digitized and the reduction in the cost of digital equipment allows quick digital transfer of any conventional radiological film. Images then can be transferred to a personal computer, and several software programs are available that can manipulate their digital appearance. In this article, the fundamentals of digital imaging are discussed, as well as the wide variety of optional adjustments that the Adobe Photoshop 6.0 (Adobe Systems, San Jose, CA) program can offer to present radiological images with satisfactory digital imaging quality.     

Defects in neurofibromatosis 2 protein function can arise at multiple levels

Neurofibromatosis 2 (NF2) is an inherited cancer syndrome resulting from mutations in the NF2 tumor suppressor gene. Analysis of NF2 mutations has revealed some general genotype-phenotype correlations. Severe disease has been associated with mutations that produce a premature termination while more mild disease has been associated with missense mutations. Here, we provide experimental proof for these genotype-phenotype correlations by demonstrating that nonsense mutations fail to produce stable merlin protein while missense mutations result in the generation of merlin proteins defective in negative growth regulation. This inability to suppress cell growth may result from defects in the function of merlin at several levels, including failure to form an intramolecular complex. Based on these findings, we propose a model for merlin growth suppression that provides a framework for analyzing NF2 patient mutations and merlin function.      

Uterine myomata and outcome of assisted reproduction

The aim of this work was to study the effect of uterine myomata on the implantation rate and outcome in in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Among 406 patients, 51 (12.6%) were found to have uterine corporeal myomata. Twelve patients were excluded from the study as they had large myomata, submucous myomata or intramural myomata encroaching on the cavity. These patients were advised to have myomectomy before being enrolled in the IVF/ICSI programme. The remaining patients (n = 39) were sorted according to the number, site and size of the myomata as assessed by transvaginal sonography. Three patients had more than one myoma. Most of the myomata were subserous (72.7%) and the mean diameter of the myomata was 3.5 +/- 0.9 cm. A control group (n = 367) was chosen with normal uteri and no history of uterine reconstruction surgery. The mean age of myoma patients was 34.7 +/- 3.6 years as compared to 34.0 +/- 4.4 years in the control group. The age, period of infertility, body mass index, duration and number of human menopausal gonadotrophin ampoules needed for stimulation, oestradiol levels, number of oocytes retrieved and the fertilization rate were not significantly different in the myoma patients compared to the control group. Fifteen myoma patients (38.5%) subsequently showed one or more pregnancy sacs on ultrasonography of which three (20%) spontaneously aborted during the first trimester and two (13.3%) had preterm labour, as compared to 123 (33.5%), 19 (15.5%) and nine (7.3%) respectively, among the control group (P = 0.27, 0.33 and 0.21). In conclusion, uterine corporeal myomata, not encroaching on the cavity and <7 cm in mean diameter, do not affect the implantation or miscarriage rates in IVF or ICSI.      

Covariances of Mitogenic Responses in Leukaemic Blood Lymphocytes: a Functional Marker System for the Human B Lymphocyte Differentiation

Various polyclonal activating substances have been shown to stimulate human chronic lymphatic leukaemic (CLL) cells to undergo blast transformation, to divide and to secrete monoclonal immunglobulin. CLL cells from different patients show distinct response patterns to these ligands. We have statistically analysed these response patterns and found that responses to certain ligands demonstrate covariance; that is, a high response to one ligand is statistically associated with a high response to another ligand. A factor analysis of these data on the basis of responses of CLL cells from twenty-one patients and from the use of five different ligands in three different concentrations has shown that as few as two factors can account for as much as 63% of the total variance of these responses. On the assumption that these two factors were T-cell dependency of CLL responses and stage of maturity of the responding CLL cell, we have formulated a theory that explains the basis for this functional marker system for CLL cells. It is possible application to the characterization of individual CLL clones has been discussed.     

Artifact analysis of approximate helical cone-beam CT reconstruction algorithms

In this paper, four approximate cone-beam CT reconstruction algorithms are compared: Advanced single slice rebinning (ASSR) as a representative of algorithms employing a two dimensional approximation, PI, PI-SLANT, and 3-PI which all use a proper three dimensional back-projection. A detailed analysis of the image artifacts produced by these techniques shows that aliasing in the z-direction is the predominant source of artifacts for a 16-row scanner with 1.25 mm nominal slice thickness. For a detector with isotropic resolution of 0.5 mm, we found that ASSR and PI produce different kinds of artifacts which are almost at the same level, while PI-SLANT produces none of these artifacts. It is shown that the use of redundant data in the 3-PI method suppresses aliasing artifacts efficiently for both scanners.     

THE EFFECT OF PROSTAGLANDIN E1 ON PULMONARYBLOOD FLOW AFTER RETROGRADE FLUSH ANDCOLD STORAGE OF LUNGS

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Identification of COL4A5 defects in Alport's syndrome by immunohistochemistry of skin

BACKGROUND: The COL4A3-COL4A4-COL4A5 network in the glomerular basement membrane is affected in the inherited renal disorder Alport's syndrome (AS). Approximately 85% of the AS patients are expected to carry a mutation in the X-chromosomal COL4A5 gene and 15% in the autosomal COL4A3 and COL4A4 genes. The COL4A5 chain is also present in the epidermal basement membrane (EBM). It is predicted that approximately 70% of the COL4A5 mutations prevent incorporation of this chain in basement membranes. METHODS: We investigated whether or not COL4A5 defects could be detected by immunohistochemical analysis of the EBM. Punch skin biopsies were obtained from 22 patients out of 17 families and two biopsy specimens from healthy males were used as controls. RESULTS: In four cases with the COL4A5 frameshift or missense mutations, the COL4A5 chain was either lacking from the EBM (male) or showed a focally negative pattern (female). In three other patients with a COL4A5 missense mutation, a COL4A3 and a COL4A4 mutation, respectively, the COL4A5 staining was normal. A (focally) negative EBM-COL4A5 staining was found in three patients of six families with a diagnosis of AS and in one family of a group of four families with possible AS. CONCLUSIONS: The (focal) absence of COL4A5 in the EBM of skin biopsy specimens can be used for fast identification of COL4A5 defects. Combined with polymorphic COL4A5 markers, both postnatal and prenatal DNA diagnosis are possible in the family of the patient.