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Prominent Differences (prominent + difference)
Selected AbstractsUtilization of antiepileptic drugs during pregnancy: Comparative patterns in 38 countries based on data from the EURAP registryEPILEPSIA, Issue 10 2009The EURAP Study Group Summary We assessed the utilization of antiepileptic drugs (AEDs), 1999,2005, in 4,798 prospective epilepsy pregnancies from 38 countries participating in EURAP, an international AED and pregnancy registry. Prominent differences in utilization patterns were observed across the various countries. Exposure to second-generation AEDs ranged from 3.5% in India and 7.3% in Italy to 75% in Denmark. Even wider variation was recorded in exposure to individual AEDs. The utilization of second-generation AEDs increased over time (for lamotrigine, from 9.9% of all pregnancies before 2001 to 29.6% after 2003). The differences in use of individual AEDs across countries probably reflect lack of evidence concerning the optimal treatment of epilepsy in women of childbearing age, as well as variation in country-specific traditions, medication costs, and drug promotion. Our observations underscore the need for comparative studies to investigate the factors influencing the prescription of AEDs during pregnancy, as well as their influence on pregnancy outcome. [source] Comedication related to comorbidities: a study in 1203 hospitalized patients with severe psoriasisBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2008S. Gerdes Summary Background, Psoriasis is a common dermatological disorder characterized by an immune-mediated chronic inflammation which is associated with a variety of other diseases commonly referred to as comorbidities. The treatments for these diseases may interfere with the course and the treatment of psoriasis. Little is known on the general drug intake of patients with psoriasis. Objectives, To gain more insight into the general drug intake of patients with severe psoriasis. A correlation of comedication to respective diseases could lead to a better knowledge of comorbidities. Methods, Data on demographics, comedication and comorbidities from 1203 patients with severe psoriasis in Germany were analysed. As a control group data from 7099 subjects from the German National Health Survey 1998 were used. Results, Patients with severe psoriasis are receiving significantly more different systemic drugs on average than the general population, with the most prominent difference in multidrug treatment. Drugs used in the treatment of arterial hypertension, diabetes mellitus and other diseases of the metabolic syndrome as well as oral anticoagulants and anticonvulsant agents showed the greatest differences. Special characteristics of antihypertensive drug treatments could be determined. Conclusions, The data obtained in this study provide the basis for an improved management of patients with psoriasis. Knowledge of existing comedication and comorbidities may lead to the ability to treat psoriasis and comorbidities at the same time more safely and to use possible synergistic effects. [source] Electron microscopic study to compare preclinical Cushing's syndrome with overt Cushing's syndromeINTERNATIONAL JOURNAL OF UROLOGY, Issue 4 2002Daisaku Hirano Abstract Background: No significant differences in gross and light- microscopic features have been reported between preclinical and overt Cushing's adenomas. In this study, the ultrastructural differences between the two syndromes was attempted to be clarified. Methods: Two preclinical Cushing's syndrome adenomas and two overt Cushing's syndrome adenomas obtained from surgical extirpation were examined in an electron microscopic study. Results: Light microscopically, the adenomas of both syndromes were composed predominantly of clear cells, with few compact cells. Ultrastructurally, the prominent differences were of development in each organelle: the preclinical Cushing's adenomas had undeveloped mitochondria, which were smaller in size and had sparse cristae, lysosomes and polysomes, whereas the overt Cushing's adenomas contained well-developed mitochondria which were larger in size and were filled with abundant cristae, smooth endoplasmic reticulum (SER), lysosomes and polysomes. Conclusions: Preclinical Cushing's syndrome adenomas were ultrastructurally characterized by a reduced number of cellular organelles such as mitochondria and SER, which are necessary to synthesize glucocorticoid hormones. However, examination of a greater number of adenomas will be required to be able to draw conclusions on the ultrastructural differences between the two syndromes. [source] Defining the transcriptome of accelerated and replicatively senescent keratinocytes reveals links to differentiation, interferon signaling, and Notch related pathways,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2006Ranjan J. Perera Abstract Epidermal keratinocytes (KCs) undergo highly orchestrated morphological and molecular changes during transition from proliferative compartment into growth arrested early and late differentiation layers, prior to dying in outermost cornified layers of normal skin. Creation of stratum corneum is vital to barrier function protecting against infection. Transcriptional events in KCs regulating complex processes of differentiation and host defense required to maintain constant epidermal thickness and resistance to infection in either young or aged skin are largely unknown. Furthermore, as terminal differentiation is characterized by irreversible loss of replicative potential culminating in dead layers at the skin surface, this process may be viewed as a form of senescence. However, a complete transcriptional profile of senescent (SN) human KCs has not been previously defined to permit delineation of molecular boundaries involving differentiation and senescence. To fill this void, we utilized global transcriptional analysis of KCs maintained in vitro as either cultures of proliferating (PR) cells, early and late confluent (LC) (accelerated senescence) cultures, or KCs undergoing replicative senescence. Global gene expression profiling revealed early confluent (EC) KCs were somewhat similar to PR KCs, while prominent differences were evident when compared to LC KCs; which were also distinct from replicatively SN KCs. While confluent KCs have in common several genes regulating differentiation with replicatively SN KCs, the latter cells expressed elevated levels of genes involved in interferon signaling and inflammatory pathways. These results provide new insights into cell autonomous transcriptional-based programs operative within KCs contributing to replicative senescence, with partial sharing of genes involved in differentiation. In addition, regulation of KC senescence may involve participation of interferon signaling pathways derived from the important role of KCs in protecting skin from infection. Integrating all of the transcriptional data revealed a key role for Notch receptor mediated signaling in the confluency induced differentiation phenotype using this model system. J. Cell. Biochem. 98: 394,408, 2006. © 2006 Wiley-Liss, Inc. [source] Comparison of 17,-estradiol structures from x-ray diffraction and solution NMRMAGNETIC RESONANCE IN CHEMISTRY, Issue 6 2005Fernando Commodari Abstract The NMR-derived structure of estrogen (17,-estradiol, E2), the drug of choice for postmenopausal women, was compared with a recent literature crystal x-ray structure of Fab-bound E2. 1H and 13C NMR spectra of E2 were acquired in DMSO- d6. Assignments were obtained from an analysis of DQF-COSY, TOCSY, HETCOR, HMQC and HMBC 2D NMR spectra. The 1H and 13C NMR assignments are the first reported for E2 in DMSO- d6. Two solution structures, S1 and S2, were obtained with molecular modeling using NOE constraints. S1 overlaps with the crystal structure for all rings. S2 shows prominent differences in the C-ring (C9C11C12C13) segment, which deviates from a chair conformation, and excellent overlap in the A-, B- and D-rings of E2. The C-ring in S2 adopts a boat conformation as opposed to a chair conformation in the x-ray and S1 structures. The S2 structure is about 6° more twisted than the bound x-ray and S1 models. The S1, S2 and x-ray structures had ring bowing values of 10.1 ± 0.3, 11 ± 1 and 10.37°, respectively. Of the 100 solution conformers generated, 83 had S1 conformation and 17 had S2 conformation, with average internal energies of 112 ± 2 and 141 ± 2 kcal mol,1, respectively. The 100 S1 - and S2 - derived conformers showed a r.m.s.d. of 0.72 Å for all atoms. The x-ray, S1 and S2 C18O17 distances were 2.93, 2.92 ± 0.01 and 2.93 ± 0.01 Å, respectively, and the O3O17 distances were 11.06, 11.18 ± 0.12, and 10.89 ± 0.05 Å, respectively. Copyright © 2005 John Wiley & Sons, Ltd. [source] Inhibition of Canonical Wnt Signaling Increases Microvascular Hemorrhaging and Venular Remodeling in Adult RatsMICROCIRCULATION, Issue 5 2010JASON T. GLAW Microcirculation (2010) 17, 348,357. doi: 10.1111/j.1549-8719.2010.00036.x Abstract Objective:, The canonical Wnt signaling pathway, heavily studied in development and cancer, has recently been implicated in microvascular growth with the use of developmental and in vitro models. To date, however, no study exists showing the effects of perturbing the canonical Wnt pathway in a complete microvascular network undergoing physiological remodeling in vivo. Our objective was to investigate the effects of canonical Wnt inhibition on the microvascular remodeling of adult rats. Methods:, Canonical Wnt inhibitor DKK-1, Wnt inhibitor sFRP-1, BSA or saline was superfused onto the exteriorized mesenteric windows of 300 g adult female Sprague-Dawley rats for 20 minutes. Three days following surgery, mesenteric windows were imaged intravitally and harvested for immunofluorescence staining with smooth muscle alpha-actin and BRDU. Results:, We observed prominent differences in the response of the mesenteric microvasculature amongst the various treatment groups. Significant increases in hemorrhage area, vascular density, and draining vessel diameter were observed in windows treated with Wnt inhibitors as compared to control-treated windows. Additionally, confocal imaging analysis showed significant increases in proliferating cells as well as evidence of proliferating smooth muscle cells along venules. Conclusions:, Together, our results suggest that canonical Wnt inhibition plays an important role in microvascular remodeling, specifically venular remodeling. [source] Genome-wide profiling of oral squamous cell carcinomaTHE JOURNAL OF PATHOLOGY, Issue 3 2004Yann-Jang Chen Abstract Oral squamous cell carcinoma (OSCC) is a common malignancy, the incidence of which is particularly high in some Asian countries due to the geographically linked areca quid (AQ) chewing habit. In this study, array-based comparative genomic hybridization was used to screen microdissected OSCCs for genome-wide alterations. The highest frequencies of gene gain were detected for TP63, Serpine1, FGF4/FGF3, c- Myc and DMD. The highest frequencies of deletion were detected for Caspase8 and MTAP. Gained genes, classified by hierarchical clustering, were mainly on 17q21,tel; 20q; 11q13; 3q27,29 and the X chromosome. Among these, gains of EGFR at 7p, FGF4/FGF3, CCND1 and EMS1 at 11q13, and AIB1 at 20q were significantly associated with lymph node metastasis. The genomic profiles of FHIT and EXT1 in AQ-associated and non-AQ-associated OSCCs exhibited the most prominent differences. RT-PCR confirmed the significant increase of TP63 and Serpine1 mRNA expression in OSCC relative to non-malignant matched tissue. A significant increase in Serpine1 immunoreactivity was observed from non-malignant matched tissue to OSCC. However, there was no correlation between the frequent genomic loss of Caspase 8 and a significant decrease in Caspase8 expression. These data demonstrate that genomic profiling can be useful in analysing pathogenetic events involved in the genesis or progression of OSCC. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Inflammatory and oxidative stress biomarkers in allergic rhinitis: the effect of smokingCLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2009K. Tanou Summary Background Accumulating evidence confirms the presence of pan-airway inflammation in allergic rhinitis patients. Smoking is known to affect the asthmatic airway inflammation. However, no study has evaluated the impact of smoking on airway inflammation of allergic rhinitis patients. Objective The aim of the present study was to evaluate the impact of smoking on inflammatory and oxidative stress biomarkers in patients with seasonal allergic rhinitis, using non-invasive methods for sample collection. Methods Forty patients with seasonal allergic rhinitis (20 smokers and 20 non-smokers) and 30 healthy subjects (15 smokers and 15 non-smokers) were recruited for the study during pollen season. All subjects were submitted to measurement of the fraction of exhaled NO (FeNO), exhaled breath condensate (EBC) collection, nasal lavage collection, pre- and post- bronchodilation spirometry and metacholine bronchial challenge testing. pH, leukotriene B4 (LTB4) and 8-isoprostane were determined in EBC and nasal lavage samples. Results Patients with allergic rhinitis presented higher LTB4 and 8-isoprostane levels in nasal lavage (P<0.0001 for both comparisons), with no significant differences between smokers and non-smokers. Patients with allergic rhinitis also presented higher LTB4 levels and lower pH in EBC (P<0.001 and P=0.004, respectively), with prominent differences between smokers and non-smokers (P<0.0001 and P=0.003, for LTB4 and pH, respectively). A significant correlation between nasal lavage and EBC LTB4 values was observed (rs=0.313, P=0.048). Conclusions Patients with allergic rhinitis present increased LTB4 and 8-isoprostane in their nasal cavity, however, with no significant differences between smokers and non-smokers. In contrast, smokers with allergic rhinitis present higher LTB4 levels and lower pH in EBC, suggesting that these patients may be more susceptible to the deleterious effects of smoking, compared with non-smokers. [source] | ||||||||||