ACAT inhibition reduces the progression of preexisting, advanced atherosclerotic mouse lesions without plaque or systemic toxicity.

OBJECTIVE: Acyl-CoA:cholesterol acyltransferase (ACAT) converts cholesterol to cholesteryl esters in plaque foam cells. Complete deficiency of macrophage ACAT has been shown to increase atherosclerosis in hypercholesterolemic mice because of cytotoxicity from free cholesterol accumulation, whereas we previously showed that partial ACAT inhibition by Fujirebio compound F1394 decreased early atherosclerosis development. In this report, we tested F1394 effects on preestablished, advanced lesions of apolipoprotein-E-deficient mice. METHODS AND RESULTS: Apolipoprotein-E-deficient mice on Western diet for 14 weeks developed advanced plaques, and were either euthanized (Baseline), or continued on Western diet with or without F1394 and euthanized after 14 more weeks. F1394 was not associated with systemic toxicity. Compared with the baseline group, lesion size progressed in both groups; however, F1394 significantly retarded plaque progression and reduced plaque macrophage, free and esterified cholesterol, and tissue factor contents compared with the untreated group. Apoptosis of plaque cells was not increased, consistent with the decrease in lesional free cholesterol. There was no increase in plaque necrosis and unimpaired efferocytosis (phagocytic clearance of apoptotic cells). The effects of F1394 were independent of changes in plasma cholesterol levels. CONCLUSIONS: Partial ACAT inhibition by F1394 lowered plaque cholesterol content and had other antiatherogenic effects in advanced lesions in apolipoprotein-E-deficient mice without overt systemic or plaque toxicity, suggesting the continued potential of ACAT inhibition for the clinical treatment of atherosclerosis, in spite of recent trial data.

Cardiovascular risk factors and visiting nurse intervention--evaluation of a Croatian survey and intervention model: the CroHort study.

The aim of this study is to identify factors that influence the success of the implementation of the primary and secondary prevention programs in Croatia by the visiting/community services. Two main sources of information were used: reports about regular visiting nurse services in Croatia and research about visiting nurse participation in the Croatian Adult Health Cohort Study (CroHort) 2008. Out of the total number 9,070 respondents who participated in CAHS 2003 survey, during CroHort 2008 program 3,229 (35.6%) participants were re-interviewed. The qualitative analysis was done with a sample of 34 visiting nurses, which participated in the CroHort 2008. Results show that there are three key problems which limit preventive programs: inability of the health care system to recognize the importance of the primary prevention; visiting nurses' lack capacity to implement prevention and populations' lack of motivation and education.

Risk factors for cardiovascular disease in rural area of Croatia.

Rural areas, where 47.6% of the Croatian population lives are not generally the focus of research; yet there are challenges which affect the rural population that often go unreported. These communities often exhibit disadvantages in many areas of health. The aim of this study is to examine the specific health needs and related determinants of rural populations influenced by transition that were affected by the consequences of war. The focus of the research is rural lifestyle, behaviour and cardiovascular risk factors in three villages of Sisacko-moslavacka County. Results show that participants generally understand that their own lifestyles influence their health, but they often neglect to change their behaviour to improve their health. This can be explained through complex socio-economic conditions and traditional values of their heritage. These results suggest a need for further research on health status, attitude, and behaviour of Croatia's rural population. Specific public health intervention and services for rural populations must be promoted.

Ultra-high resolution, 3-dimensional magnetic resonance imaging of the atherosclerotic vessel wall at clinical 7T.

Accurate quantification and characterization of atherosclerotic plaques with MRI requires high spatial resolution acquisitions with excellent image quality. The intrinsically better signal-to-noise ratio (SNR) at high-field clinical 7T compared to the widely employed lower field strengths of 1.5 and 3T may yield significant improvements to vascular MRI. However, 7T atherosclerosis imaging also presents specific challenges, related to local transmit coils and B1 field inhomogeneities, which may overshadow these theoretical gains. We present the development and evaluation of 3D, black-blood, ultra-high resolution vascular MRI on clinical high-field 7T in comparison lower-field 3T. These protocols were applied for in vivo imaging of atherosclerotic rabbits, which are often used for development, testing, and validation of translatable cardiovascular MR protocols. Eight atherosclerotic New Zealand White rabbits were imaged on clinical 7T and 3T MRI scanners using 3D, isotropic, high (0.63 mm3) and ultra-high (0.43 mm3) spatial resolution, black-blood MR sequences with extensive spatial coverage. Following imaging, rabbits were sacrificed for validation using fluorescence imaging and histology. Image quality parameters such as SNR and contrast-to-noise ratio (CNR), as well as morphological and functional plaque measurements (plaque area and permeability) were evaluated at both field strengths. Using the same or comparable imaging parameters, SNR and CNR were in general higher at 7T compared to 3T, with a median (interquartiles) SNR gain of +40.3 (35.3-80.1)%, and a median CNR gain of +68.1 (38.5-95.2)%. Morphological and functional parameters, such as vessel wall area and permeability, were reliably acquired at 7T and correlated significantly with corresponding, widely validated 3T vessel wall MRI measurements. In conclusion, we successfully developed 3D, black-blood, ultra-high spatial resolution vessel wall MRI protocols on a 7T clinical scanner. 7T imaging was in general superior to 3T with respect to image quality, and comparable in terms of plaque area and permeability measurements.

Combined PET/DCE-MRI in a Rabbit Model of Atherosclerosis: Integrated Quantification of Plaque Inflammation, Permeability, and Burden During Treatment With a Leukotriene A4 Hydrolase Inhibitor.

OBJECTIVES: The authors sought to develop combined positron emission tomography (PET) dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) to quantify plaque inflammation, permeability, and burden to evaluate the efficacy of a leukotriene A4 hydrolase (LTA4H) inhibitor in a rabbit model of atherosclerosis. BACKGROUND: Multimodality PET/MRI allows combining the quantification of atherosclerotic plaque inflammation, neovascularization, permeability, and burden by combined 18F-fluorodeoxyglucose (18F-FDG) PET, DCE-MRI, and morphological MRI. The authors describe a novel, integrated PET-DCE/MRI protocol to noninvasively quantify these parameters in aortic plaques of a rabbit model of atherosclerosis. As proof-of-concept, the authors apply this protocol to assess the efficacy of the novel LTA4H inhibitor BI691751. METHODS: New Zealand White male rabbits (N = 49) were imaged with integrated PET-DCE/MRI after atherosclerosis induction and 1 and 3 months after randomization into 3 groups: 1) placebo; 2) high-dose BI691751; and 3) low-dose BI691751. All animals were euthanized at the end of the study. RESULTS: Among the several metrics that were quantified, only maximum standardized uptake value and target-to-background ratio by 18F-FDG PET showed a modest, but significant, reduction in plaque inflammation in rabbits treated with low-dose BI691751 (p = 0.03), whereas no difference was detected in the high-fat diet and in the high-dose BI691751 groups. No differences in vessel wall area by MRI and area under the curve by DCE-MRI were detected in any of the groups. No differences in neovessel and macrophage density were found at the end of study among groups. CONCLUSIONS: The authors present a comprehensive, integrated 18F-FDG PET and DCE-MRI imaging protocol to noninvasively quantify plaque inflammation, neovasculature, permeability, and burden in a rabbit model of atherosclerosis on a simultaneous PET/MRI scanner. A modest reduction was found in plaque inflammation by 18F-FDG PET in the group treated with a low dose of the LTA4H inhibitor BI691751.

[Possibilities of application of distance learning in medical curriculum]. / Mogucnosti uvodenja ucenja na daljinu u medicinski curriculum.

Possibilities of introduction of distance learning in medical curriculum is the title of project which commenced in 2002 at Cathedra for Medical Informatics of the Medical faculty in Sarajevo. Project is approved by Federal and Cantonal ministries of science and education. The purpose of this project is to support improvement of the educational process at biomedical faculties using contemporary methods, methodologies and information technologies in accordance with strategies and objectives given by Bologna declaration. Pilot project is attained after three years, theoretical and practical part of subject Medical Informatics are adapted to modern concepts of education using world trends of distance learning. One group of students from Medical faculty was involved in this project, which was finalized by electronic registration of exam and electronic testing on June 20, 2005 in public, in Physiological amphitheatre of Medical faculty in Sarajevo. In this article we have given complete description of this project as well as its basic adventages and disadvantages.

Distance learning at biomedical faculties in bosnia & herzegovina.

Increase and development of distance learning technologies over the past decade has exposed the potential and the efficiency of new technologies. Benefit and use of contemporary information technologies is the area where medical informatics got the most on understanding and importance. Definition of distance learning as "use of technologies based on health care delivered on distance" covers areas such as electronic health, tele-health (e-health), telematics, telemedicine, tele-education, etc. For the need of e-health, telemedicine, tele-education and distance learning there are various technologies and communication systems from standard telephone lines to the system of transmission digitalized signals with modem, optical fiber, satellite links, wireless technologies, etc. Tele-education represents health education on distance, using Information Communication Technologies(ICT), as well as continuous education of a health system beneficiaries and use of electronic libraries, data bases or electronic data with data bases of knowledge. In this paper authors described activities on introduction of distance learning in teaching process at Medical faculty, University of Sarajevo, Bosnia and Herzegovina. Internet was not really meant to be a means of human communication at first; but the clearly the Net become a main piece of human communication.