Transcription factor GATA6 promotes migration of human coronary artery smooth muscle cells in vitro.

Vascular smooth muscle cell plasticity plays a pivotal role in the pathophysiology of vascular diseases. Despite compelling evidence demonstrating the importance of transcription factor GATA6 in vascular smooth muscle, the functional role of GATA6 remains poorly understood. The aim of this study was to elucidate the role of GATA6 on cell migration and to gain insight into GATA6-sensitive genes in smooth muscle. We found that overexpression of GATA6 promotes migration of human coronary artery smooth muscle cells in vitro, and that silencing of GATA6 in smooth muscle cells resulted in reduced cellular motility. Furthermore, a complete microarray screen of GATA6-sensitive gene transcription resulted in 739 upregulated and 248 downregulated genes. Pathways enrichment analysis showed involvement of transforming growth factor beta (TGF-ß) signaling which was validated by measuring mRNA expression level of several members. Furthermore, master regulators prediction based on microarray data revealed several members of (mitogen activated protein kinase) MAPK pathway as a master regulators, reflecting involvement of MAPK pathway also. Our findings provide further insights into the functional role of GATA6 in vascular smooth muscle and suggest that targeting GATA6 may constitute as a new approach to inhibit vascular smooth muscle migration.

YAP and TAZ in Vascular Smooth Muscle Confer Protection Against Hypertensive Vasculopathy.

BACKGROUND: Hypertension remains a major risk factor for cardiovascular diseases, but the underlying mechanisms are not well understood. We hypothesize that appropriate mechanotransduction and contractile function in vascular smooth muscle cells are crucial to maintain vascular wall integrity. The Hippo pathway effectors YAP (yes-associated protein 1) and TAZ (WW domain containing transcription regulator 1) have been identified as mechanosensitive transcriptional coactivators. However, their role in vascular smooth muscle cell mechanotransduction has not been investigated in vivo. METHODS: We performed physiological and molecular analyses utilizing an inducible smooth muscle-specific YAP/TAZ knockout mouse model. RESULTS: Arteries lacking YAP/TAZ have reduced agonist-mediated contraction, decreased myogenic response, and attenuated stretch-induced transcriptional regulation of smooth muscle markers. Moreover, in established hypertension, YAP/TAZ knockout results in severe vascular lesions in small mesenteric arteries characterized by neointimal hyperplasia, elastin degradation, and adventitial thickening. CONCLUSIONS: This study demonstrates a protective role of YAP/TAZ against hypertensive vasculopathy.

MRTFA overexpression promotes conversion of human coronary artery smooth muscle cells into lipid-laden foam cells.

OBJECTIVE: Smooth muscle cells contribute significantly to lipid-laden foam cells in atherosclerotic plaques. However, the underlying mechanisms transforming smooth muscle cells into foam cells are poorly understood. The purpose of this study was to gain insight into the molecular mechanisms regulating smooth muscle foam cell formation. APPROACH AND RESULTS: Using human coronary artery smooth muscle cells we found that the transcriptional co-activator MRTFA promotes lipid accumulation via several mechanisms, including direct transcriptional control of LDL receptor, enhanced fluid-phase pinocytosis and reduced lipid efflux. Inhibition of MRTF activity with CCG1423 and CCG203971 significantly reduced lipid accumulation. Furthermore, we demonstrate enhanced MRTFA expression in vascular remodeling of human vessels. CONCLUSIONS: This study demonstrates a novel role for MRTFA as an important regulator of lipid homeostasis in vascular smooth muscle cells. Thus, MRTFA could potentially be a new therapeutic target for inhibition of vascular lipid accumulation.

Inducible Deletion of YAP and TAZ in Adult Mouse Smooth Muscle Causes Rapid and Lethal Colonic Pseudo-Obstruction.

BACKGROUND & AIMS: YAP (Yap1) and TAZ (Wwtr1) are transcriptional co-activators and downstream effectors of the Hippo pathway, which play crucial roles in organ size control and cancer pathogenesis. Genetic deletion of YAP/TAZ has shown their critical importance for embryonic development of the heart, vasculature, and gastrointestinal mesenchyme. The aim of this study was to determine the functional role of YAP/TAZ in adult smooth muscle cells in vivo. METHODS: Because YAP and TAZ are mutually redundant, we used YAP/TAZ double-floxed mice crossed with mice that express tamoxifen-inducible CreERT2 recombinase driven by the smooth muscle-specific myosin heavy chain promoter. RESULTS: Double-knockout of YAP/TAZ in adult smooth muscle causes lethality within 2 weeks, mainly owing to colonic pseudo-obstruction, characterized by severe distension and fecal impaction. RNA sequencing in colon and urinary bladder showed that smooth muscle markers and muscarinic receptors were down-regulated in the YAP/TAZ knockout. The same transcripts also correlated with YAP/TAZ in the human colon. Myograph experiments showed reduced contractility to depolarization by potassium chloride and a nearly abolished muscarinic contraction and spontaneous activity in colon rings of YAP/TAZ knockout. CONCLUSIONS: YAP and TAZ in smooth muscle are guardians of colonic contractility and control expression of contractile proteins and muscarinic receptors. The knockout model has features of human chronic intestinal pseudo-obstruction and may be useful for studying this disease.

Loss of Vascular Myogenic Tone in miR-143/145 Knockout Mice Is Associated With Hypertension-Induced Vascular Lesions in Small Mesenteric Arteries.

OBJECTIVE: Pressure-induced myogenic tone is involved in autoregulation of local blood flow and confers protection against excessive pressure levels in small arteries and capillaries. Myogenic tone is dependent on smooth muscle microRNAs (miRNAs), but the identity of these miRNAs is unclear. Furthermore, the consequences of altered myogenic tone for hypertension-induced damage to small arteries are not well understood. APPROACH AND RESULTS: The importance of smooth muscle-enriched microRNAs, miR-143/145, for myogenic tone was evaluated in miR-143/145 knockout mice. Furthermore, hypertension-induced vascular injury was evaluated in mesenteric arteries in vivo after angiotensin II infusion. Myogenic tone was abolished in miR-143/145 knockout mesenteric arteries, whereas contraction in response to calyculin A and potassium chloride was reduced by ≈30%. Furthermore, myogenic responsiveness was potentiated by angiotensin II in wild-type but not in knockout mice. Angiotensin II administration in vivo elevated systemic blood pressure in both genotypes. Hypertensive knockout mice developed severe vascular lesions characterized by vascular inflammation, adventitial fibrosis, and neointimal hyperplasia in small mesenteric arteries. This was associated with depolymerization of actin filaments and fragmentation of the elastic laminae at the sites of vascular lesions. CONCLUSIONS: This study demonstrates that miR-143/145 expression is essential for myogenic responsiveness. During hypertension, loss of myogenic tone results in potentially damaging levels of mechanical stress and detrimental effects on small arteries. The results presented herein provide novel insights into the pathogenesis of vascular disease and emphasize the importance of controlling mechanical factors to maintain structural integrity of the vascular wall.

Molecular Regulation of Arterial Aneurysms: Role of Actin Dynamics and microRNAs in Vascular Smooth Muscle.

Aortic aneurysms are defined as an irreversible increase in arterial diameter by more than 50% relative to the normal vessel diameter. The incidence of aneurysm rupture is about 10 in 100,000 persons per year and ruptured arterial aneurysms inevitably results in serious complications, which are fatal in about 40% of cases. There is also a hereditary component of the disease and dilation of the ascending thoracic aorta is often associated with congenital heart disease such as bicuspid aortic valves (BAV). Furthermore, specific mutations that have been linked to aneurysm affect polymerization of actin filaments. Polymerization of actin is important to maintain a contractile phenotype of smooth muscle cells enabling these cells to resist mechanical stress on the vascular wall caused by the blood pressure according to the law of Laplace. Interestingly, polymerization of actin also promotes smooth muscle specific gene expression via the transcriptional co-activator MRTF, which is translocated to the nucleus when released from monomeric actin. In addition to genes encoding for proteins involved in the contractile machinery, recent studies have revealed that several non-coding microRNAs (miRNAs) are regulated by this mechanism. The importance of these miRNAs for aneurysm development is only beginning to be understood. This review will summarize our current understanding about the influence of smooth muscle miRNAs and actin polymerization for the development of arterial aneurysms.

Patients with bicuspid and tricuspid aortic valve exhibit distinct regional microrna signatures in mildly dilated ascending aorta.

MicroRNAs are able to modulate gene expression in a range of diseases. We focused on microRNAs as potential contributors to the pathogenesis of ascending aorta (AA) dilatation in patients with stenotic tricuspid (TAV) or bicuspid aortic valve (BAV). Aortic specimens were collected from the 'concavity' and the 'convexity' of mildly dilated AAs and of normal AAs from heart transplant donors. Aortic RNA was analyzed through PCR arrays, profiling the expression of 84 microRNAs involved in cardiovascular disease. An in silico analysis identified the potential microRNA-mRNA interactions and the enriched KEGG pathways potentially affected by microRNA changes in dilated AAs. Distinct signatures of differentially expressed microRNAs are evident in TAV and BAV patients vs. donors, as well as differences between aortic concavity and convexity in patients only. MicroRNA changes suggest a switch of SMC phenotype, with particular reference to TAV concavity. MicroRNA changes potentially affecting mechanotransduction pathways exhibit a higher prevalence in BAV convexity and in TAV concavity, with particular reference to TGF-ß1, Hippo, and PI3K/Akt/FoxO pathways. Actin cytoskeleton emerges as potentially affected by microRNA changes in BAV convexity only. MicroRNAs could play distinct roles in BAV and TAV aortopathy, with possible implications in diagnosis and therapy.

Regulation of microRNA expression in vascular smooth muscle by MRTF-A and actin polymerization.

The dynamic properties of the actin cytoskeleton in smooth muscle cells play an important role in a number of cardiovascular disease states. The state of actin does not only mediate mechanical stability and contractile function but can also regulate gene expression via myocardin related transcription factors (MRTFs). These transcriptional co-activators regulate genes encoding contractile and cytoskeletal proteins in smooth muscle. Regulation of small non-coding microRNAs (miRNAs) by actin polymerization may mediate some of these effects. MiRNAs are short non-coding RNAs that modulate gene expression by post-transcriptional regulation of target messenger RNA. In this study we aimed to determine a profile of miRNAs that were 1) regulated by actin/MRTF-A, 2) associated with the contractile smooth muscle phenotype and 3) enriched in muscle cells. This analysis was performed using cardiovascular disease-focused miRNA arrays in both mouse and human cells. The potential clinical importance of actin polymerization in aortic aneurysm was evaluated using biopsies from mildly dilated human thoracic aorta in patients with stenotic tricuspid or bicuspid aortic valve. By integrating information from multiple qPCR based miRNA arrays we identified a group of five miRNAs (miR-1, miR-22, miR-143, miR-145 and miR-378a) that were sensitive to actin polymerization and MRTF-A overexpression in both mouse and human vascular smooth muscle. With the exception of miR-22, these miRNAs were also relatively enriched in striated and/or smooth muscle containing tissues. Actin polymerization was found to be dramatically reduced in the aorta from patients with mild aortic dilations. This was associated with a decrease in actin/MRTF-regulated miRNAs. In conclusion, the transcriptional co-activator MRTF-A and actin polymerization regulated a subset of miRNAs in vascular smooth muscle. Identification of novel miRNAs regulated by actin/MRTF-A may provide further insight into the mechanisms underlying vascular disease states, such as aortic aneurysm, as well as novel ideas regarding therapeutic strategies. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech.

Emerging roles of the myocardin family of proteins in lipid and glucose metabolism.

Members of the myocardin family bind to the transcription factor serum response factor (SRF) and act as coactivators controlling genes of relevance for myogenic differentiation and motile function. Binding of SRF to DNA is mediated by genetic elements called CArG boxes, found often but not exclusively in muscle and growth controlling genes. Studies aimed at defining the full spectrum of these CArG elements in the genome (i.e. the CArGome) have in recent years, unveiled unexpected roles of the myocardin family proteins in lipid and glucose homeostasis. This coactivator family includes the protein myocardin (MYOCD), the myocardin-related transcription factors A and B (MRTF-A/MKL1 and MRTF-B/MKL2) and MASTR (MAMSTR). Here we discuss growing evidence that SRF-driven transcription is controlled by extracellular glucose through activation of the Rho-kinase pathway and actin polymerization. We also describe data showing that adipogenesis is influenced by MLK activity through actions upstream of peroxisome proliferator-activated receptor γ with consequences for whole body fat mass and insulin sensitivity. The recently demonstrated involvement of myocardin coactivators in the biogenesis of caveolae, Ω-shaped membrane invaginations of importance for lipid and glucose metabolism, is finally discussed. These novel roles of myocardin proteins may open the way for new unexplored strategies to combat metabolic diseases such as diabetes, which, at the current incidence, is expected to reach 333 million people worldwide by 2025. This review highlights newly discovered roles of myocardin-related transcription factors in lipid and glucose metabolism as well as novel insights into their well-established role as mediators of stretch-dependent effects in smooth muscle. As co-factors for serum response factor (SRF), MKLs regulates transcription of genes involved in the contractile function of smooth muscle cells. In addition to mechanical stimuli, this regulation has now been found to be promoted by extracellular glucose levels in smooth muscle. Recent reports also suggest that MKLs can regulate a subset of genes involved in the formation of lipid-rich invaginations in the cell membrane called caveolae. Finally, a potential role of MKLs in non-muscle cells has been discovered as they negatively influence adipocyte differentiation.

Inhibition of Polyamine Uptake Potentiates the Anti-Proliferative Effect of Polyamine Synthesis Inhibition and Preserves the Contractile Phenotype of Vascular Smooth Muscle Cells.

Increased vascular smooth muscle cell (VSMC) proliferation is a factor in atherosclerosis and injury-induced arterial (re) stenosis. Inhibition of polyamine synthesis by α-difluoro-methylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, attenuates VSMC proliferation with high sensitivity and specificity. However, cells can escape polyamine synthesis blockade by importing polyamines from the environment. To address this issue, polyamine transport inhibitors (PTIs) have been developed. We investigated the effects of the novel trimer44NMe (PTI-1) alone and in combination with DFMO on VSMC polyamine uptake, proliferation and phenotype regulation. PTI-1 efficiently inhibited polyamine uptake in primary mouse aortic and human coronary VSMCs in the absence as well as in the presence of DFMO. Interestingly, culture with DFMO for 2 days substantially (>95%) reduced putrescine (Put) and spermidine (Spd) contents without any effect on proliferation. Culture with PTI-1 alone had no effect on either polyamine levels or proliferation rate, but the combination of both treatments reduced Put and Spd levels below the detection limit and inhibited proliferation. Treatment with DFMO for a longer time period (4 days) reduced Put and Spd below their detection limits and reduced proliferation, showing that only a small pool of polyamines is needed to sustain VSMC proliferation. Inhibited proliferation by polyamine depletion was associated with maintained expression of contractile smooth marker genes. In cultured intact mouse aorta, PTI-1 potentiated the DFMO-induced inhibition of cell proliferation. The combination of endogenous polyamine synthesis inhibition with uptake blockade is thus a viable approach for targeting unwanted vascular cell proliferation in vivo, including vascular restenosis.

NSAIDs and Cardiovascular Diseases: Role of Reactive Oxygen Species.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used drugs worldwide. NSAIDs are used for a variety of conditions including pain, rheumatoid arthritis, and musculoskeletal disorders. The beneficial effects of NSAIDs in reducing or relieving pain are well established, and other benefits such as reducing inflammation and anticancer effects are also documented. The undesirable side effects of NSAIDs include ulcers, internal bleeding, kidney failure, and increased risk of heart attack and stroke. Some of these side effects may be due to the oxidative stress induced by NSAIDs in different tissues. NSAIDs have been shown to induce reactive oxygen species (ROS) in different cell types including cardiac and cardiovascular related cells. Increases in ROS result in increased levels of oxidized proteins which alters key intracellular signaling pathways. One of these key pathways is apoptosis which causes cell death when significantly activated. This review discusses the relationship between NSAIDs and cardiovascular diseases (CVD) and the role of NSAID-induced ROS in CVD.

Impacts of education level and employment status on health-related quality of life in multiple sclerosis patients.

AIM: To evaluate the impacts of education level and employment status on health-related quality of life (HRQoL) in multiple sclerosis patients. METHODS: This study included 100 multiple sclerosis patients treated at the Department of Neurology, Clinical Center of the University of Sarajevo. Inclusion criteria were the Expanded Disability Status Scale (EDSS) score between 1.0 and 6.5, age between 18 and 65 years, stable disease on enrollment. Quality of life (QoL) was evaluated by the Multiple Sclerosis Quality of Life-54 questionnaire (MSQoL-54). Mann-Whitney and Kruskal-Wallis test were used for comparisons. Linear regression analyses were performed to evaluate prediction value of educational level and employment status in predicting MSQOL-54 physical and mental composite scores. RESULTS: Full employment status had positive impact on physical health (54.85 vs. 37.90; p les than 0.001) and mental health (59.55 vs. 45.90; p les than 0.001) composite scores. Employment status retained its independent predictability for both physical (r(2)=0.105) and mental (r(2)=0.076) composite scores in linear regression analysis. Patients with college degree had slightly higher median value of physical (49.36 vs. 45.30) and mental health composite score (66.74 vs. 55.62) comparing to others, without statistically significant difference. CONCLUSION: Employment proved to be an important factor in predicting quality of life in multiple sclerosis patients. Higher education level may determine better QOL but without significant predictive value. Sustained employment and development of vocational rehabilitation programs for MS patients living in the country with high unemployment level is an important factor in improving both physical and mental health outcomes in MS patients.

Gender Differences in Biochemical and Electroneurographic Parameters of Median and Ulnar Nerve.

INTRODUCTION: In this article are demonstrated differences in the aspects of the metabolic syndrome (MSy) between genders, as well as the association of MSy and neuropathy. THE AIM: The aim of our study was that in patients with newly discovered metabolic syndrome of both sexes make comparison of fasting blood glucose levels and after oral glucose tolerance test, as well as neurophysiological parameters of n.medianus and n.ulnaris. PATIENTS AND METHODS: All participants were examined dermatologically. The analysis included the 36 male and 36 female respondents with a newly discovered MSy. RESULTS: The average age of men was 52.75±7.5 (40-65) years and women 52.1±7.7 (38-67) years. The average value of fasting blood glucose in women was 5.86±0.87 (4.5-8) mmol/L, and non significantly higher in men (p=0.0969) as 6.19±0.8 (4.7-8) mmol/L. Average values of blood sugar 120 minutes after oral glucose tolerance test were not significantly different (p=0.7052), and was 5.41±1.63 (3.3-9.7) mmol/L in women and 5.27±1.52 (2.7-9.8) mmol/L in men. Median motor velocity were significantly higher in women for n.medianus on the left (p=0.0024), n.ulnaris on the left (p=0.0081) and n.ulnaris on the right side (p=0.0293), and the median motor terminal latency were significantly longer in n.ulnaris on the left (p=0.0349) and n.ulnaris on the right side (p=0.011). There was no significant difference in the sensory conductivity velocity in n.medianus and n.ulnaris between the groups, but the amplitude with the highest peak of the sensory response was significantly higher in n.medianus on the left (p=0.0269) and n.ulnaris on the left side (p=0.0009) in female patients. CONCLUSION: The results indicate that there are differences in neurophysiological parameters of the investigated nerves between the genders, and that tested nerve structures in the course of MSy are affected slightly more in men. There were no significant differences in skin changes between genders.

Cutaneous silent period in the assessment of small nerve fibers in patients on hemodialysis.

AIM: In hemodialysis patients renal disease may cause an impairment of central and peripheral nervous system. In most cases of the peripheral nervous system polyneuropathy is reported. The aim of this study was to evaluate the function of small A-delta nerve fibres, whose function is often overlooked. METHODS: The function of large diameter nerve fibers was performed by standard routine neurophysiological examination. Cutaneous silent period (CSP) was elicited by single electrical stimulations at the tip of digit II by the bipolar electrodes. The superficial electrodes were placed on the muscle belly of m. abductor pollicis brevis. The onset latency (L1) was recorded at the beginning of voluntary muscle activity suppression, the late latency (L2) at the start of new muscle activity. The difference between two latencies indicates the duration of CSP. RESULTS: The study included 38 consecutive patients (male/female - 21/17, median age 56.6±10.9 years) treated with hemodialysis (one month to 30 years) and 35 healthy subjects (male/female 23/17, age 47.4±10.1 years). The results of the conduction study demonstrated a significant prolongation of F-waves of the median and ulnar nerves, decreased motor and sensory velocities of both nervesin patients on hemodialysis (p less than 0.001). In patients with A-V fistulas a significant prolongation of the onset CSP latency L1 was obtained (p less than 0.001), whereas duration of CSP was not changed. CONCLUSION: In hemodialysis patients the significant impairment of small nerve fibers was recorded. The evaluation of small nerve fibers contributes to the assessment of the whole peripheral nerve function.

Laminin α2 Chain-Deficiency is Associated with microRNA Deregulation in Skeletal Muscle and Plasma.

microRNAs (miRNAs) are widespread regulators of gene expression, but little is known of their potential roles in congenital muscular dystrophy type 1A (MDC1A). MDC1A is a severe form of muscular dystrophy caused by mutations in the gene encoding laminin α2 chain. To gain insight into the pathophysiological roles of miRNAs associated with MDC1A pathology, laminin α2 chain-deficient mice were evaluated by quantitative PCR. We demonstrate that expression of muscle-specific miR-1, miR-133a, and miR-206 is deregulated in laminin α2 chain-deficient muscle. Furthermore, expression of miR-223 and miR-21, associated with immune cell infiltration and fibrosis, respectively, is altered. Finally, we show that plasma levels of muscle-specific miRNAs are markedly elevated in laminin α2 chain-deficient mice and partially normalized in response to proteasome inhibition therapy. Altogether, our data suggest important roles for miRNAs in MDC1A pathology and we propose plasma levels of muscle-specific miRNAs as promising biomarkers for the progression of MDC1A.

Cutaneous silent period in the evaluation of small nerve fibres.

INTRODUCTION: High intensity cutaneous stimulus transiently suppresses tonic voluntary muscle activity resulting in cutaneous silent period (CSP). AIM: The aim of our study was to evaluate the normal values of an onset latency L1, a late latency L2 and a duration of CSP after stimulating sensory fibres of the median nerve. MATERIAL AND METHODS: This prospective study was performed at the Neurology Department, Clinical Center of Sarajevo University in period from January 1st 2013 to December 1st 2013. In our study we examined 61 subjects. The group included our relatives, coworkers and friends. The informed consent from testing subjects was obtained. RESULTS: The origin of silent period is stimulation of small A-delta nerve fibres. The pre-synaptic or post-synaptic interruption of the electrical volley to motor neurons is discussed. Median values of muscle activity suppression in healthy female is 55.0 ms (45.0-74.0) and 59.0 ms (52.0-67) male subjects. There is a correlation between the onset latency L1 and the late L2 latency (p < 0.03). In the on-going study it seems that delay of L1 and shorter muscle activity suppression might provide a sign of small nerve fibres involvement. CONCLUSION: The use of CSP improves the value of neurophysiology examination.

Post stroke depression.

INTRODUCTION: Comorbidity of depression and stroke significantly reduces the quality of life of patients after the stroke. Squeal after stroke also determines the quality of life and have impact on the occurrence of depression after the stroke. In our study we investigated the occurrence of depression in patients after different types and subtypes of stroke measured by the Hamilton scale compared to the level of disability measured by NIHSS scale. GOAL: The goal was to make a comparative analysis of depression after stroke, according to gender and age, side of the lesion and the severity of neurological deficit. MATERIAL AND METHODS: Material for our work are 210 patients with stroke treated at the Neurology Clinic, Clinical Center of Sarajevo University in 2012, 105 male and 105 female. The mean age of the patients was 67.12 +/- 9.5 years. Ischemic stroke was present in 65% cases. There was no statistically significant difference between ischemic and hemorrhagic stroke among genders. In case of hemorrhagic M-56.7%, F-43.3%; ischemic M-48.3%, F-51.7% (chi-square = 6.563, p = 0.082). Depression was more prevalent among younger patients (52-60 years) with 39.2% then in the group of older patients (61-70 years) with 32% of depressed. In relation to gender there was significantly more patients with depression among women compared to men (63.8:27.2%, chi-square = 14.38, p = 0.00019). Depression was more frequent in patients with stroke in the left hemisphere medial localization (63%). NIHSS scale average was 16.07 with the minimum of 11 and maximum of 22, F = 52.56, p = 0.001. CONCLUSIONS: We can conclude that depression after stroke is more frequent in younger patients, female patients, patients with localized stroke in the medial left hemisphere and with higher disability score.

Hyperlipidemia as a risk factor for persons in specific professions.

INTRODUCTION: The increase in lipid levels associated with other risk factors for the occurrence of ischemic heart disease and stroke is one of the most important health problems in the world. Risk for development of changes is greater for people of specific occupations such as police officers. MATERIAL AND METHODS: This prospective study included 300 police officers, 150 as experimental and 150 respondents as a control group. To both groups same methods have been applied: A detailed history, physical examination, complete laboratory evaluation, lipid electrophoresis targeted to hypercholesterolemia, ultrasound of the abdomen and Color Doppler of the neck vascular structures. The results obtained by statistical analysis of the data showed that there was a significant increase in levels of cholesterol and triglyceride levels in experimental compared to the control group. Ultrasound of the abdomen showed fatty infiltrated liver in 16% of respondents from the experimental and 2% of the respondents in the control group 2%. Color Doppler of the neck blood vessels in 14% of respondents from experimental group showed changes in blood vessels, which ranged from mild thickening of the intima of the vessel to a 50% decrease in circulation. For the control group, this percentage was 0.66%. Considering that this study involved young, active working population, hyperlipidemia becomes a bigger problem.

Suicidal ideation and thoughts of death in epilepsy patients.

BACKGROUND: Suicidal behavior is an important worldwide health problem. Psychiatric disorders, especially mood disorders, are the main risk factors for suicidal behavior. Suicide is an important cause of death in patients with epilepsy. The aim of this study was to analyze the presence of suicidal ideation in patients with epilepsy. SUBJECTS AND METHODS: The study included 50 epilepsy inpatients and outpatients of both genders, aged 18 years and older, treated at the Department of Neurology, Clinical Center University of Sarajevo in the period from 1(st) of April - October 1(st) 2007. The sample was selected randomly. Applied research instruments were general questionnaire, HAM-D-17, BHS and BSS. RESULTS: Suicidal ideation and thoughts of death were present in 38% epilepsy patients. Symptoms of depression as well as feelings of hopelessness were found in half of the participants (52% and 48%), and were significantly more common in epilepsy patients with suicidal ideation. There was a significant relation of suicidal ideation with the presence of chronic pain (3.86; p=0.49), sexual/physical abuse history (5.95, p=0.015), level of hopelessness (20.7; p=0.000) and severity of depression (14.48; p=0.000) in epilepsy patients. Multiple logistic regression analysis showed that unemployment (Exp(B) 33.9; p=0.007) and the level of hopelessness (Exp(B) 14.9; p=0.001) were independently related to suicidal ideation in these patients. CONCLUSIONS: The study has shown that the level of hopelessness and unemployment have a predictive value for appearance of suicidal ideation in epilepsy patients. In the prediction of suicidal ideation in this population of patients, there is no single variable that should be considered as specific and separate.

Predilection role diabetes mellitus and dyslipidemia in the onset of ischemic stroke.

INTRODUCTION: Stroke is the third leading cause of mortality, disability and dementia, but leading cause of epileptic manifestations in the elderly. Diabetes mellitus as permanently elevated blood glucose, often accompanied by dyslipidemia, is among the leading causes of atherosclerotic alteration in blood vessels and is also increasing in the world. GOAL: To determine the existence and predilection of diabetes mellitus and dyslipidemia, in the development of ischemic stroke. MATERIAL AND METHODS: During the 2011 are analyzed all people with stroke admitted at the Neurology Clinic. All patients underwent neurological tests and the laboratory test with special emphasis on the value of blood glucose and lipid levels, with brain CT which confirmed the existence of a stroke, EEG and internist examination. RESULTS: During the one-year period the stroke was confirmed in 1184 patients, aged 33-81 years and 37% in the younger age group (up to 50 yrs.). There was 50.67% male and 49.33% female patients. Ischemic stroke was confirmed in 78.0% (56% with thrombotic and 22% with embolic genesis), of which the 32% was lacunar infarcts (up to 1.5 cm) and hemorrhagic in 22% (SAH in 4.8%, and intracerebral hemorrhage in 17.2%). The most frequent risk factors were hypertension 85%, then smoking in 65%, diabetes mellitus in 39.0%, in 27.38% dyslipidemia, previous stroke in 26.69%, in 23.57% arrhythmia In the baseline sample 30.06% of patients had previously diabetes mellitus and in 8.94% the diabetes was diagnosed during hospitalization, while dyslipidemia was known from earlier in 22.0% and in 5.38% cases was detected during the hospitalization. Among treated patients 79.01% survived, while 20.09% have a fatal outcome. CONCLUSIONS: Diabetes mellitus and dyslipidemia, along with hypertension and smoking are the leading risk factors for the occurrence of stroke. By timely detection and treatment can be controlled slow atherosclerotic changes in blood vessels and thus prevent stroke.