Can eccentric arterial plaques alone cause flow stagnation points and favour thrombus incorporation?

We have used an experimental model of aorta stenosis, with a Plexiglas plug, simulating a stable atheromatous plaque that promotes local turbulence and thrombosis. With animal survival of more than 24 h, we followed the partial fibrinolysis of the thrombus as well as its posterior organization and incorporation to the arterial wall as a neointima for up to 30 days. The mushroom plug form permitted the development of recirculation and stasis areas around it, favouring this evolution. Despite noted limitations, this study demonstrates that thrombus incorporation can contribute to plaque extension, as it can promote recirculation and stasis areas.

Consistent Alterations of Circulating Matrix Metalloproteinases Levels in Untreated Hypertensives and in Spontaneously Hypertensive Rats: A Relevant Pharmacological Target

Inconsistent matrix metalloproteinases (MMPs) levels have been reported in hypertension, with higher, similar and lower MMPs levels reported in hypertensives compared with normotensives. Differences between studies may reflect lack of control of drug effects, accompanying diseases and pre-analytical issues. We compared MMP-2, MMP-8 and MMP-9 levels in 38 untreated hypertensive patients (with no other diseases) with those found in 33 normotensive controls. We also studied endogenous MMPs inhibitors (TIMP-1, TIMP-2 and alpha-2-macroglobulin-A2M). Additionally, we assessed MMPs and A2M levels in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. We hypothesized that similar MMPs/endogenous inhibitors` profiles would be found in this animal model of hypertension and in clinical hypertension. MMPs, TIMPs and A2M were measured in plasma samples with commercially available ELISA and gelatin zymography. We found unaltered MMP-2, MMP-8, TIMP-1, TIMP-2 and A2M levels in hypertension. However, hypertensives had higher MMP-9 levels and MMP-9/A2M ratios than normotensives. Moreover, while we found similar MMP-2 and A2M levels in SHR and WKY rats, we found higher MMP-9 levels and MMP-9/A2M ratios in SHR versus WKY rats. These findings show consistent abnormal net plasma MMP-9 (but not MMP-2) activity in clinical and experimental hypertension. These parallel alterations in clinical hypertension and in SHR suggest an important role for MMPs in hypertension. While MMPs may be a relevant pharmacological target, antihypertensive drugs that down-regulate MMPs may offer advantages in the management of this disease.

Beyond the middle: A report about literacy and numeracy development of target group students in the middle years of schooling: Volume 1

The report was commissioned by the Department of Education, Science and Training to investigate the perceived efficacy of middle years programmes in all States and Territories in improving the quality of teaching, learning and student outcomes, especially in literacy and numeracy and for student members of particular target groups. These target groups included students from lower socio-economic communities, Aboriginal and Torres Strait Islander communities, students with a language background other than English, rural and remote students, and students struggling with the transition from middle/upper primary to the junior secondary years. The project involved large scale national and international literature reviews on Australian and international middle years approaches as well as an analysis of key literacy and numeracy teaching and learning strategies being used. In the report, there is emergent evidence of the relative efficacy of a combination of explicit state policy, dedicated funding and curriculum and professional development frameworks that are focused on the improvement of classroom pedagogy in the middle years. The programs that evidenced the greatest current and potential value for target group students tended to have developed in state policy environments that encouraged a structural rather than adjunct approach to middle years innovations. The authors conclude that in order to translate the gains made into sustainable improvement of educational results in literacy and numeracy for target groups, there is a need for a second generation of middle years theorising, research, development and practice.

Beyond the middle: A report about literacy and numeracy development of target group students in the middle years of schooling: Volume 2 (Appendices)

This research project was commissioned by the Commonwealth Department of Education, Science and Training to investigate the perceived efficacy of middle years programs in all States and Territories in improving the quality of teaching, learning and student outcomes - especially in literacy and numeracy and for student members of particular target groups. The latter groups included students from lower socio-economic communities, Aboriginal and Torres Strait Islander (Indigenous) communities, students with a Language Background Other than English (hereafter LBOTE), rural and remote students, and students struggling with the transition from middle/upper primary to the junior secondary years.

Unilateral hearing loss: benefits and satisfaction from the use of hearing aids

A unilateral hearing loss is characterized by reduced hearing in one ear. The problems caused by sensory deprivation can be minimized with the use of hearing aids (HA). Aim: To analyze the correlation between the prescribed grain and the insertion gain difference and with the results obtained regarding the benefit and satisfaction with the use of hearing aids in unilateral hearing impaired patients. Materials and Methods: Prospective study with 15 subjects, mean age of 41.6 years, of both genders, users of hearing aids effectively. We used the International Questionnaire Results for hearing aids (International Outcome Inventory for Hearing Aids - IOI-HA), measured with a probe microphone. Results: The mean values in the analyses of the IOI-HA per item were positive and higher than four points. In relation to the objective measures, the frequencies in which we obtained the gain values which were closer to the target were: 1K Hz, 2K Hz and 500 Hz, respectively. Conclusion: The satisfaction of individuals using hearing aid unilaterally is not completely correlated to the prescribed gain, because even if the target is not being reached in some frequencies, the individuals were pleased as to the use of their hearing aids.

Effect of image compression of digital lateral cephalograms on the reproducibility of cephalometric points

Objectives: To evaluate the influence of JPEG quality factors 100, 80 and 60 on the reproducibility of identification of cephalometric points on images of lateral cephalograms, compared with the Digital Imaging and Communications in Medicine (DICOM) format. Methods: The sample was composed of 30 images of digital lateral cephalograms obtained from 30 individuals (15 males and 15 females) on a phosphor plate system in DICOM format. The images were converted to JPEG with quality factors 100, 80 and 60 with the aid of software, adding up to 90 images. The 120 images (DICOM, JPEG 100, 80 and 60) were blinded and 12 cephalometric points were identified on each image by three calibrated orthodontists, using the x-y coordinate system, on a cephalometric software. Results: The results revealed that identification of cephalometric points was highly reproducible, except for the point Orbitale (Or) on the x-axis. The different file formats did not present a statistically significant difference. Conclusions: JPEG images of lateral cephalograms with quality factors 100, 80 and 60 did not present alterations in the reproducibility of identification of cephalometric points compared with the DICOM format. Good reproducibility was achieved for the 12 points, except for point Or on the x-axis. Dentomaxillofacial Radiology (2009) 38, 393-400. doi: 10.1259/dmfr/40996636

CDKN2A is not the principal target of deletions on the short arm of chromosome 9 in neuroendocrine (Merkel cell) carcinoma of the skin

The majority of small-cell lung cancers (SCLCs) express p16 but not pRb, Given our previous study showing loss of pRb in Merkel cell carcinoma (MCC)/neuroendocrine carcinoma of the skin and the clinicopathological similarities between SCLC acid MCC, we wished to determine if this was also the case in MCC, Twenty-nine MCC specimens from 23 patients were examined for deletions at 10 loci on 9p and I on 9p. No loss of heterozygosity (LO H) was peen in 9 patients including 2 for which tumour and cell line DNAs were examined. Four patients had LOH for all informative loci on 9p, Ten tumours showed more limited regions of loss on 9p, and from these 2 common regions of deletion were determined, Half of all informative cases had LOH at D95168, the most telomeric marker examined, and 3 specimens showed loss of only D9S168, A second region (InFNA-D9S126) showed L0H in 10(44%) cases, and case MCC26 showed LOH for only D9S126, implicating genes centromeric of the CDKN2A locus. No mutations in the coding regions of p16 were seen in 7 cell lines tested, and reactivity to anti-p16 antibody was seen in all Il tumour specimens examined and in 6 of 7 cell lines from 6 patients. Furthermore, all cell lines examined reacted with anti-p 14' antibody, These results suggest that neither transcript of the CDKN2A locus is the target of deletions on 9p in MCC and imply the existence of tumour-suppressor genes mapping both centromeric and telomeric of this locus. (C) 2001 Wiley-Liss, Inc.

Pulmonary vascular remodeling: a target for therapeutic intervention in pulmonary hypertension

Pulmonary vascular remodeling is an important pathological feature of pulmonary hypertension, leading to increased pulmonary vascular resistance and reduced compliance. It involves thickening of all three layers of the blood vessel wall (due to hypertrophy and/or hyperplasia of the predominant cell type within each layer), as well as extracellular matrix deposition. Neomuscularisation of non-muscular arteries and formation of plexiform and neointimal lesions also occur. Stimuli responsible for remodeling involve transmural pressure, stretch, shear stress, hypoxia, various mediators [angiotensin II, endothelin (ET)-1, 5-hydroxytryptamine, growth factors, and inflammatory cytokines], increased serine elastase activity, and tenascin-C. In addition, there are reductions in the endothelium-derived antimitogenic substances, nitric oxide, and prostacyclin. Intracellular signalling mechanisms involved in pulmonary vascular remodeling include elevations in intracellular Ca2+ and activation of the phosphatidylinositol pathway, protein kinase C, and mitogen-activated protein kinase. In animal models of pulmonary hypertension, various drugs have been shown to attenuate pulmonary vascular remodeling. These include angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, ET receptor antagonists, ET-converting enzyme inhibitors, nitric oxide, phosphodiesterase 5 inhibitors, prostacyclin, Ca2+-channel antagonists, heparin, and serine elastase inhibitors. Inhibition of remodeling is generally accompanied by reductions in pulmonary artery pressure. The efficacy of some of the drugs varies, depending on the animal model of the disease. In view of the complexity of the remodeling process and the diverse aetiology of pulmonary hypertension in humans, it is to be anticipated that successful anti-remodeling therapy in the clinic will require a range of different drug options. (C) 2001 Elsevier Science Inc. All rights reserved.

Dipeptidyl peptidase IV is a target for covalent adduct formation with the acyl glucuronide metabolite of the anti-inflammatory drug zomepirac

The nonsteroidal anti-inflammatory drug zomepirac (ZP) is metabolised to a chemically reactive acyl glucuronide conjugate (ZAG) which can form covalent adducts with proteins. In vivo, such adducts could initiate immune or toxic responses. In rats given ZP, the major band detected in liver homogenates by immunoblotting with a polyclonal ZP antiserum was at 110 kDa. This adduct was identified as ZP-modified dipeptidyl peptidase IV (DPP IV) by immunoblotting using the polyclonal ZP antiserum and monoclonal DPP IV antibodies OX-61 and 236.3. In vitro, ZAG, but not ZP itself, covalently modified recombinant human and rat DPP IV. Both monoclonal antibodies recognized DPP IV in livers from ZP- and vehicle-dosed rats. Confirmation that the 110 kDa bands which were immunoreactive with the ZP and DPP IV antibodies represented the same molecule was obtained from a rat liver extract reciprocally immunodepleted of antigens reactive with these two antibodies. Furthermore, immunoprecipitations with OX-61 antibody followed by immunolotting with ZP antiserum, and the reciprocal experiment, showed that both these antibodies recognised the same 110 kDa molecule in extracts of ZP-dosed rat liver. The results verify that DPP IV is one of the protein targets for covalent modification during hepatic transport and biliary excretion of ZAG in rats. (C) 2001 Elsevier Science Inc. All rights reserved.

Inhibitors of human immunodeficiency virus type 1 reverse transcriptase target distinct phases of early reverse transcription

Early HIV-1 reverse transcription can be separated into initiation and elongation phases. Here we show, using PCR analysis of negative-strand strong-stop DNA [(-)ssDNA] synthesis in intact virus, that different reverse transcriptase (RT) inhibitors affect distinct phases of early natural endogenous reverse transcription (NERT), The effects of nevirapine on NERT were consistent with a mechanism of action including both specific and nonspecific binding events. The nonspecific component of this inhibition targeted the elongation reaction, whereas the specific effect seemed principally to be directed at very early events (initiation or the initiation-elongation switch), In contrast, foscarnet and the nucleoside analog ddATP inhibited both early and late (-)ssDNA synthesis in a similar manner. We also examined compounds that targeted other viral proteins and found that Ro24-7429 (a Tat antagonist) and rosmarinic acid (an integrase inhibitor) also directly inhibited RT, Our results indicate that NERT can be used to identify and evaluate compounds that directly target the reverse transcription complex.