Seropositivity for Helicobacter pylori antibodies is associated with lower occurrence of venous bypass graft occlusion

Common chronic infections including those caused by cytomegalovirus (CMV), herpes simplex viruses (HSV), Helicobacter pylori and Chlamydia pneumoniae have previously been related to increased risk of coronary heart disease (CHD). We investigated the association between serology of these chronic infections and coronary bypass graft occlusions in 61 patients. As a result, IgG seropositivity rate against H. pylori was higher among patients without occlusion (82%) than in those with occlusion (45%) or apparently healthy controls (57%) (p = 0.004 and p = 0.008, respectively). In conclusion, H. pylori infection, as judged by IgG seropositivity, is associated with lower occurrence of venous bypass graft occlusion in patients with CHD and may thus be connected with better outcome and prognosis of CHD patients after bypass graft surgery.     

Developmental changes in cellular and extracellular structural macromolecules in the secondary palate and in the nasal cavity of the mouse

Vaziri Sani F, Kaartinen V, El Shahawy M, Linde A, Gritli‐Linde A. Developmental changes in cellular and extracellular structural macromolecules in the secondary palate and nasal cavity of the mouse. Eur J Oral Sci 2010; 118: 221–236. © 2010 The Authors. Journal compilation© 2010 Eur J Oral Sci The aim of this study was to analyse the hitherto largely unknown expression patterns of some specific cellular and extracellular molecules during palate and nasal cavity development. We showed that epithelia of the developing palate and the vomerine epithelium express similar sets of structural proteins. With the exception of keratin 15, which becomes barely detectable in the elevated palatal shelves, nearly all of these proteins become upregulated at the presumptive areas of fusion and in the adhering epithelia of the palate and nasal septum. In vivo and in vitro analyses indicated that reduction in the amount of keratin 15 protein is independent of Tgfβ–Alk5 signalling. Foxa1 expression also highlighted the regionalization of the palatal and nasal epithelia. Owing to the lack of reliable markers of the palatal periderm, the fate of peridermal cells has been controversial. We identified LewisX/stage‐specific embryonic antigen‐1 as a specific peridermal marker, and showed that numerous peridermal cells remain trapped in the medial epithelial seam (MES). The fate of these cells is probably apoptosis together with the rest of the MES cells, as we provided strong evidence for this event. Heparan sulphate, chondroitin‐6‐sulphate, and versican displayed dynamically changing distribution patterns. The hitherto‐unknown innervation pattern of the developing palate was revealed. These findings may be of value for unravelling the pathogenesis of palatal clefting.     

The effect of model order selection in group PICA

Independent component analysis (ICA) of functional MRI data is sensitive to model order selection. There is a lack of knowledge about the effect of increasing model order on independent components' (ICs) characteristics of resting state networks (RSNs). Probabilistic group ICA (group PICA) of 55 healthy control subjects resting state data was repeated 100 times using ICASSO repeatability software and after clustering of components, centrotype components were used for further analysis. Visual signal sources (VSS), default mode network (DMN), primary somatosensory (S₁), secondary somatosensory (S₂), primary motor cortex (M₁), striatum, and precuneus (preC) components were chosen as components of interest to be evaluated by varying group probabilistic independent component analysis (PICA) model order between 10 and 200. At model order 10, DMN and VSS components fuse several functionally separate sources that at higher model orders branch into multiple components. Both volume and mean z‐score of components of interest showed significant (P < 0.05) changes as a function of model order. In conclusion, model order has a significant effect on ICs characteristics. Our findings suggest that using model orders ≤20 provides a general picture of large scale brain networks. However, detection of some components (i.e., S₁, S₂, and striatum) requires higher model order estimation. Model orders 30–40 showed spatial overlapping of some IC sources. Model orders 70 ± 10 offer a more detailed evaluation of RSNs in a group PICA setting. Model orders > 100 showed a decrease in ICA repeatability, but added no significance to either volume or mean z‐score results. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Three-step tumor targeting of paclitaxel using biotinylated PLA-PEG nanoparticles and avidin-biotin technology: Formulation development and in vitro anticancer activity

Despite recent advances in cancer therapy, many malignant tumors still lack effective treatment and the prognosis is very poor. Paclitaxel is a potential anticancer drug, but its use is limited by the facts that paclitaxel is a P-gp substrate and its aqueous solubility is poor. In this study, three-step tumor targeting of paclitaxel using biotinylated PLA-PEG nanoparticles and avidin-biotin technology was evaluated in vitro as a way of enhancing delivery of paclitaxel. Paclitaxel was incorporated both in biotinylated (BP) and non-biotinylated (LP) PEG-PLA nanoparticles by the interfacial deposition method. Small (mean size approximately 110nm), spherical and slightly negatively charged (-10mV) BP and LP nanoparticles achieving over 90% paclitaxel incorporation were obtained. The successful biotinylation of nanoparticles was confirmed in a novel streptavidin assay. BP nanoparticles were targeted in vitro to brain tumor (glioma) cells (BT4C) by three-step avidin-biotin technology using transferrin as the targeting ligand. The three-step targeting procedure increased the anti-tumoral activity of paclitaxel when compared to the commercial paclitaxel formulation Taxol((R)) and non-targeted BP and LP nanoparticles. These results indicate that the efficacy of paclitaxel against tumor cells can be increased by this three-step targeting method.     

Dysfibrinogenemia associated with thrombosis and third-trimester fetal loss. A case report

Dysfibrinogenemias are rare genetic disorders that are clinically silent, cause a mild bleeding tendency or have thromboembolic manifestations. During pregnancy they often cause hemorrhage and first-trimester abortions. A patient with a severe thrombotic tendency during pregnancy had a third-trimester fetal loss.     

Regional effects of donepezil and rivastigmine on cortical acetylcholinesterase activity in Alzheimer's disease

Donepezil and rivastigmine are acetylcholinesterase (AChE) inhibitors used to improve cholinergic neurotransmission and cognitive function in Alzheimer's disease (AD). This study examined direct effects of these drugs on AChE activity in the frontal, temporal, and parietal cortices in AD. Six AD patients were scanned with positron emission tomography before and after 3 months of treatment with donepezil (10 mg/day), and five AD patients were scanned before and after 3 to 5 months of treatment with rivastigmine (9 mg/day). Healthy unmedicated controls were imaged twice to evaluate the reproducibility of the method. A specific AChE tracer, [methyl-11C]N-methyl-piperidyl-4-acetate, and a 3D positron emission tomography system with MRI coregistration were used for imaging. Treatment with donepezil reduced the AChE activity (k3 values) in the AD brain by 39% in the frontal (p < 0.001, Bonferroni corrected), 29% in the temporal (p = 0.02, corrected) and 28% in the parietal cortex (p = 0.05, corrected). The corresponding levels of inhibition for rivastigmine were 37% (p = 0.003, corrected), 28% (p = 0.03, uncorrected) and 28% (p = 0.05, corrected). When the treatment groups were combined, the level of AChE inhibition was significantly greater in the frontal cortex compared to the temporal cortex (p = 0.03, corrected). The test-retest analysis with healthy subjects indicated good reproducibility for the method, with a nonsignificant 0% to 7% intrasubject variability between scans. The present study provides first evidence for the effect of rivastigmine on cortical AChE activity. Our results indicate that the pooled effects of donepezil and rivastigmine on brain AChE are greater in the frontal cortex compared to the temporal cortex in AD. This regional difference is probably related to the prominent temporoparietal reduction of AChE in AD. We hypothesize that the clinical improvement in behavioral and attentional symptoms of AD due to AChE inhibitors is associated with the frontal AChE inhibition.     

Functional and morphological effects of styrene on the auditory system of the rat

The effect of inhaled styrene on the structure and function of the auditory organ of the male Wistar rat was studied. The animals were exposed either to 600, 300 or 100 ppm styrene (12 h/day, 5 days/week, for 4 weeks). Auditory sensitivity was tested prior to and after the exposure by auditory brain stem audiometry (ABR) at frequencies of 1.0, 2.0, 4.0 and 8.0 kHz. Inner ear morphological changes were studied by light- and electron-microscopy. Exposure to 600 ppm styrene caused a 3 dB hearing loss only at the highest test frequency (8 kHz). Quantitative morphological analysis of cochlear hair cells (cytocochleograms) showed that 600 ppm styrene caused a severe outer hair cell (OHC) loss particularly in the third OHC row of the upper basal and lower middle coil. The inner hair cells were usually intact. Exposure to lower styrene concentrations (100 and 300 ppm) caused no unequivocal functional deficit or hair cell damage. We conclude that there appears to be a concentration threshold for styrene ototoxicity in rats (between 300 and 600 ppm).