Aspirin and statin use and the subsequent development of depression in men and women: Results from a longitudinal population-based study.

OBJECTIVE: Low-grade chronic inflammation is one potential mechanism underlying the well-established association between major depressive disorder (MDD) and increased cardiovascular morbidity. Both aspirin and statins have anti-inflammatory properties, which may contribute to their preventive effect on cardiovascular diseases. Previous studies on the potentially preventive effect of these drugs on depression have provided inconsistent results. The aim of the present paper was to assess the prospective association between regular aspirin or statin use and the incidence of MDD. METHOD: This prospective cohort study included 1631 subjects (43.6% women, mean age 51.7 years), randomly selected from the general population of an urban area. Subjects underwent a thorough physical evaluation as well as semi-structured interviews investigating DSM-IV mental disorders at baseline and follow-up (mean duration 5.2 years). Analyses were adjusted for a wide array of potential confounders. RESULTS: Our main finding was that regular aspirin or statin use at baseline did not reduce the incidence of MDD during follow-up, regardless of sex or age (hazard ratios, aspirin: 1.19; 95%CI, 0.68-2.08; and statins: 1.25; 95%CI, 0.73-2.14; respectively). LIMITATIONS: Our study is not a randomized clinical trial and could not adjust for all potential confounding factors, information on aspirin or statin use was collected only for the 6 months prior to the evaluations, and the sample was restricted to subjects between 35 and 66 years of age. CONCLUSION: Our data do not support a large scale preventive treatment of depression using aspirin or statins in subjects aged from 35 to 66 years from the community.

LC-MS/MS based assay and reference intervals in children and adolescents for oxysterols elevated in Niemann-Pick diseases.

BACKGROUND: Niemann-Pick type C (NP-C) is a rare progressive neurodegenerative lipid storage disorder with heterogeneous clinical presentation and challenging diagnostic procedures. Recently oxysterols have been reported to be specific biomarkers for NP-C but knowledge on the intra-individual variation and on reference intervals in children and adolescents are lacking. METHODS: We established a LC-MS/MS assay to measure Cholestane-3β, 5α, 6β-triol (C-triol) and 7-Ketocholesterol (7-KC) following Steglich esterification. To assess reference intervals and intra-individual variation we determined oxysterols in 148 children and adolescents from 0 to 18 years and repeat measurements in 19 of them. RESULTS: The reported method is linear (r>0.99), sensitive (detection limit of 0.03 ng/mL [0.07 nM] for C-triol, and 0.54 ng/mL [1.35 nM] for 7-KC) and precise, with an intra-day imprecision of 4.8% and 4.1%, and an inter-day imprecision of 7.0% and 11.0% for C-triol (28 ng/ml, 67 nM) and 7-KC (32 ng/ml, 80 nM), respectively. Recoveries for 7-KC and C-triol range between 93% and 107%. The upper reference limit obtained for C-triol is 40.4 ng/mL (95% CI: 26.4-61.7 ng/mL, 96.0 nM, 95% CI: 62.8-146.7 nM) and 75.0 ng/mL for 7-KC (95% CI: 55.5-102.5 ng/mL, 187.2 nM, 95% CI: 138.53-255.8 nM), with no age or gender dependency. Both oxysterols have a broad intra-individual variation of 46%±23% for C-triol and 52%±29% for 7-KC. Nevertheless, all Niemann-Pick patients showed increased C-triol levels including Niemann-Pick type A and B patients. CONCLUSIONS: The LC-MS/MS assay is a robust assay to quantify C-triol and 7-KC in plasma with well documented reference intervals in children and adolescents to screen for NP-C in the pediatric population. In addition our results suggest that especially the C-triol is a biomarker for all three Niemann-Pick diseases.

Subclinical Hypothyroidism and the Risk of Stroke Events and Fatal Stroke: An Individual Participant Data Analysis.

OBJECTIVE: The objective was to determine the risk of stroke associated with subclinical hypothyroidism. DATA SOURCES AND STUDY SELECTION: Published prospective cohort studies were identified through a systematic search through November 2013 without restrictions in several databases. Unpublished studies were identified through the Thyroid Studies Collaboration. We collected individual participant data on thyroid function and stroke outcome. Euthyroidism was defined as TSH levels of 0.45-4.49 mIU/L, and subclinical hypothyroidism was defined as TSH levels of 4.5-19.9 mIU/L with normal T4 levels. DATA EXTRACTION AND SYNTHESIS: We collected individual participant data on 47 573 adults (3451 subclinical hypothyroidism) from 17 cohorts and followed up from 1972-2014 (489 192 person-years). Age- and sex-adjusted pooled hazard ratios (HRs) for participants with subclinical hypothyroidism compared to euthyroidism were 1.05 (95% confidence interval [CI], 0.91-1.21) for stroke events (combined fatal and nonfatal stroke) and 1.07 (95% CI, 0.80-1.42) for fatal stroke. Stratified by age, the HR for stroke events was 3.32 (95% CI, 1.25-8.80) for individuals aged 18-49 years. There was an increased risk of fatal stroke in the age groups 18-49 and 50-64 years, with a HR of 4.22 (95% CI, 1.08-16.55) and 2.86 (95% CI, 1.31-6.26), respectively (p trend 0.04). We found no increased risk for those 65-79 years old (HR, 1.00; 95% CI, 0.86-1.18) or ≥ 80 years old (HR, 1.31; 95% CI, 0.79-2.18). There was a pattern of increased risk of fatal stroke with higher TSH concentrations. CONCLUSIONS: Although no overall effect of subclinical hypothyroidism on stroke could be demonstrated, an increased risk in subjects younger than 65 years and those with higher TSH concentrations was observed.

External urethral sphincter electromyography in asymptomatic women and the influence of the menstrual cycle.

OBJECTIVE: To investigate by electromyography (EMG), the presence of complex repetitive discharges (CRDs) and decelerating bursts (DBs) in the striated external urethral sphincter during the menstrual cycle in female volunteers with no urinary symptoms and complete bladder emptying. SUBJECTS AND METHODS: Healthy female volunteers aged 20-40 years, with regular menstrual cycles and no urinary symptoms were recruited. Volunteers completed a menstruation chart, urinary symptom questionnaires, pregnancy test, urine dipstick, urinary free flow and post-void ultrasound bladder scan. Exclusion criteria included current pregnancy, use of hormonal medication or contraception, body mass index of >35 kg/m(2) , incomplete voiding and a history of pelvic surgery. Eligible participants underwent an external urethral sphincter EMG, using a needle electrode in the early follicular phase and the mid-luteal phase of their menstrual cycles. Serum oestradiol and progesterone were measured at each EMG test. RESULTS: In all, 119 women enquired about the research and following screening, 18 were eligible to enter the study phase. Complete results were obtained in 15 women. In all, 30 EMG tests were undertaken in the 15 asymptomatic women. Sphincter EMG was positive for CRDs and DBs at one or both phases of the menstrual cycle in eight (53%) of the women. Three had CRDs and DBs in both early follicular and mid-luteal phases. Five had normal EMG activity in the early follicular phase and CRDs and DBs in the mid-luteal phase. No woman had abnormal EMG activity in the early follicular phase and normal activity in the luteal phase. There was no relationship between EMG activity and age, parity or serum levels of oestradiol and progesterone. CONCLUSIONS: CRDs and DB activity in the external striated urethral sphincter is present in a high proportion of asymptomatic young women. This abnormal EMG activity has been shown for the first time to change during the menstrual cycle in individual women. CRDs and DBs are more commonly found in the luteal phase of the menstrual cycle. The importance of CRDs and DBs in the aetiology of urinary retention in young women remains uncertain. The distribution and or quantity of abnormal EMG activity in the external urethral sphincter may be important. In a woman with urinary retention the finding of CRDs and DBs by needle EMG does not automatically establish Fowler's syndrome as the explanation for the bladder dysfunction. Urethral pressure profilometry may be helpful in establishing a diagnosis. Opiate use and psychological stress should be considered in young women with urinary retention.

Commotion cérébrale chez l'enfant et l'adolescent sportif [Concussion in children and adolescents during sports].

Concussion, a frequent injury in sports, is rarely evoked and often trivialized in children and teenagers. Knowledge of the diverse symptoms and signs to seek for is essential to an appropriate and secure management. The initial treatment relies on cognitive and physical rest followed by a progressive return to school and subsequently sport activities. The aim of this article is to review an injury whose prognosis is generally favourable, but whose rare complications can prove dramatic.

Relationship between obesity and the risk of clinically significant depression: Mendelian randomisation study.

BACKGROUND: Obesity has been shown to be associated with depression and it has been suggested that higher body mass index (BMI) increases the risk of depression and other common mental disorders. However, the causal relationship remains unclear and Mendelian randomisation, a form of instrumental variable analysis, has recently been employed to attempt to resolve this issue. AIMS: To investigate whether higher BMI increases the risk of major depression. METHOD: Two instrumental variable analyses were conducted to test the causal relationship between obesity and major depression in RADIANT, a large case-control study of major depression. We used a single nucleotide polymorphism (SNP) in FTO and a genetic risk score (GRS) based on 32 SNPs with well-established associations with BMI. RESULTS: Linear regression analysis, as expected, showed that individuals carrying more risk alleles of FTO or having higher score of GRS had a higher BMI. Probit regression suggested that higher BMI is associated with increased risk of major depression. However, our two instrumental variable analyses did not support a causal relationship between higher BMI and major depression (FTO genotype: coefficient -0.03, 95% CI -0.18 to 0.13, P = 0.73; GRS: coefficient -0.02, 95% CI -0.11 to 0.07, P = 0.62). CONCLUSIONS: Our instrumental variable analyses did not support a causal relationship between higher BMI and major depression. The positive associations of higher BMI with major depression in probit regression analyses might be explained by reverse causality and/or residual confounding.

Families in the Shadow of Cancer

The aims of this study were 1) to clarify the factors associated with family functioning in cancer patient’s families with dependant children, 2) to examine children’ mental health when they are exposed to parental cancer, 3) to explore the subjective experience of having cancer during pregnancy, and finally, 4) to describe the implementation of a childcentred family intervention for cancer patients’ families with dependant children in an adult oncology setting. The study groups were collected between May 1st 2002 and April 30th 2004. They consisted of one European group collected from six different countries (N = 381) and two Finnish clinical groups (N = 85 and N = 2). The first Finnish clinical group of 85 cancer patient families with dependant children included a sub-sample of 54 families with children aged 11-17 years. The second Finnish clinical group consisted of two pregnant cancer patients. Additionally, a control group (N = 59) consisting of a sub-sample of 49 families with children aged 11-17 years was used. Quantitative methods (FAD, BDI, YSR, SOC, SF-8) and qualitative methods (observation, interviews, diaries, videotapes) were used exclusively and/or in combination. The results can be summarised as follows: 1) cancer “per se “ did not impair family functioning, children’s mental health, early interaction between ill mothers and their infant, 2) maternal depression or the ill parent’s depression were significantly associated with impairment in family functioning, 3) the individual’s good sense of coherence was associated with improvement in family functioning, and 4) a child-centred family intervention, which aims to give space for elaborating on cancer in the family, validates the sense of coherence and children’s feelings, and promotes open communication was welcomed. It is important to note that in the European study group, the prevalence of depression was 35 % (BDI > 16) among ill mothers, and 28% among healthy mothers, 28% among ill fathers, and 13% among healthy fathers. Early screening and effective treatment of depression in cancer patients and their partners is of paramount importance for the mental health of children and the well-being of the family. Pregnant cancer patients are in need of psychosocial support.

Estimation of reference curves for the urinary steroid metabolome in the first year of life in healthy children : Tracing the complexity of human postnatal steroidogenesis.

CONTEXT: Complex steroid disorders such as P450 oxidoreductase deficiency or apparent cortisone reductase deficiency may be recognized by steroid profiling using chromatographic mass spectrometric methods. These methods are highly specific and sensitive, and provide a complete spectrum of steroid metabolites in a single measurement of one sample which makes them superior to immunoassays. The steroid metabolome during the fetal-neonatal transition is characterized by (a) the metabolites of the fetal-placental unit at birth, (b) the fetal adrenal androgens until its involution 3-6 months postnatally, and (c) the steroid metabolites produced by the developing endocrine organs. All these developmental events change the steroid metabolome in an age- and sex-dependent manner during the first year of life. OBJECTIVE: The aim of this study was to provide normative values for the urinary steroid metabolome of healthy newborns at short time intervals in the first year of life. METHODS: We conducted a prospective, longitudinal study to measure 67 urinary steroid metabolites in 21 male and 22 female term healthy newborn infants at 13 time-points from week 1 to week 49 of life. Urine samples were collected from newborn infants before discharge from hospital and from healthy infants at home. Steroid metabolites were measured by gas chromatography-mass spectrometry (GC-MS) and steroid concentrations corrected for urinary creatinine excretion were calculated. RESULTS: 61 steroids showed age and 15 steroids sex specificity. Highest urinary steroid concentrations were found in both sexes for progesterone derivatives, in particular 20α-DH-5α-DH-progesterone, and for highly polar 6α-hydroxylated glucocorticoids. The steroids peaked at week 3 and decreased by ∼80% at week 25 in both sexes. The decline of progestins, androgens and estrogens was more pronounced than of glucocorticoids whereas the excretion of corticosterone and its metabolites and of mineralocorticoids remained constant during the first year of life. CONCLUSION: The urinary steroid profile changes dramatically during the first year of life and correlates with the physiologic developmental changes during the fetal-neonatal transition. Thus detailed normative data during this time period permit the use of steroid profiling as a powerful diagnostic tool.

'And the best essay is...' : Extended contact and cross-group friendships at school

We conducted one experimental intervention based on extended contact principles aimed at fostering the formation of cross-group friendships within educational settings. Italian school children took part in a school competition for the best essay on personal experiences of cross-group friendships with immigrants, to be written in small groups. This manipulation was intended to favour the exchange of personal positive cross-group experiences, thus capitalizing on the benefits of extended contact. In the control condition, participants wrote an essay on friendship, without reference to cross-group relations. Results revealed that children who took part in the intervention reported a higher number of outgroup friends 3 months later. This indirect effect was sequentially mediated by pro-contact ingroup and outgroup norms and by outgroup contact behavioural intentions. This study provides experimental evidence that interventions based on extended contact can foster cross-group friendship formation. Theoretical and practical implications of the findings are discussed.

Grande fréquence des prescriptions médicamenteuses à visée cardiovasculaire potentiellement inappropriées dans la population âgée [Potentially inappropriate prescribing cardiovascular medications in the aged population: prospective study in a district hospital centre (France)].

OBJECTIVES: Cardiovascular disease is a leading cause of morbidity and mortality in the elderly population. We evaluated the adequacy of prescribing (miss and under used) with respect to STOPP-START criteria. METHODS: A sample of 100 patients hospitalized in cardiovascular specialty divisions (medicine or surgery) or in the different sectors making up the geriatric network (day-care hospital, short or rehabilitation ward, nursing home) has been considered. Drug prescriptions at the admission time were analysed. RESULTS: Eight hundred and seventy-four prescriptions were analysed. In 65% of patients, from 5 to 10 medications were prescribed and in 28% over 10. Fifty-four percent of patients had, at least, one potentially inappropriate prescription (PIP) by STOPP. Among them, 48% of PIP prescriptions contained 1, 41% 2 and 11% 3 or more. The omission of one medication according to START criteria concerned 57% of the sample. Among them, 46% had one omission, 44% 2 to 3 and 10% 4 omissions or over. The cardiovascular system is the one most concerned by the PIP. Whether 28.1% of the PIP by STOPP criteria concerned cardiovascular drugs, the omission of prescription, according to START criteria, was 41.8%. There was no significant difference between the different settings studied. There was no effect of age or sex on the impact of PIP (P>0.20) or being polymédiqué (P=0.44). According to the criteria STOPP-A, the prescription of antiplatelet (indication and dose) was highlighted. Prescribing omission also concerned antiplatelet agents but also statins in patients with atherosclerosis as well as antiplatelet and anticoagulant in patients with permanent atrial fibrillation and inhibitor of angiotensin converting enzyme (ACE) after myocardial infarction or with chronic heart failure. CONCLUSION: Potentially inappropriate prescribing medications were very common in elderly patients with cardiovascular conditions. They concerned as much as underusing of important drugs with potential benefits and prescribing commission of treatment that did not fit with patients' comorbidities and/or characteristics.

Smoking cessation and the incidence of pre-diabetes and type 2 diabetes: a cohort study.

AIMS: Smoking cessation has been suggested to increase the short-term risk of type 2 diabetes mellitus (T2DM). This study aimed at assessing the association between smoking cessation and incidence of T2DM and impaired fasting glucose (IFG). METHODS: Data from participants in the CoLaus study, Switzerland, aged 35-75 at baseline and followed for 5.5years were used. Participants were classified as smokers, recent (≤5years), long-term (>5years) quitters, and non-smokers at baseline. Outcomes were IFG (fasting serum glucose (FSG) 5.6-6.99mmol/l) and T2DM (FSG ≥7.0mmol/l and/or treatment) at follow up. RESULTS: 3,166 participants (63% women) had normal baseline FSG, of whom 26.7% were smokers, 6.5% recent quitters, and 23.5% long-term quitters. During follow-up 1,311 participants (41.4%) developed IFG (33.6% women, 54.7% men) and 47 (1.5%) developed T2DM (1.1% women, 2.1% men). Former smokers did not have statistically significant increased odds of IFG compared with smokers after adjustment for age, education, physical activity, hypercholesterolemia, hypertension and alcohol intake, with OR of 1.29 [95% confidence interval 0.94-1.76] for recent quitters and 1.03 [0.84-1.27] for long-term quitters. Former smokers did not have significant increased odds of T2DM compared with smokers with multivariable-adjusted OR of 1.53 [0.58-4.00] for recent quitters and 0.64 [0.27-1.48] for long-term quitters. Adjustment for body-mass index and waist circumference attenuated the association between recent quitting and IFG (OR 1.07 [0.78-1.48]) and T2DM (OR 1.28 [0.48-3.40]. CONCLUSION: In this middle-aged population, smoking cessation was not associated with an increased risk of IFG or T2DM.

A comparison of injuries among children and adult football (soccer) players

Football is a universal and an affordable game but we need to minimize the incidence of accidents among the increasing number of young football players. Our 11 year retrospective epidemiological study (1990-2000) of football injuries in children (N= 1000) was compared with those of adult players in the 2006 European Championship. This comparative study confirmed that the anatomical, biomechanical and biological conditions differ between adults and children and that they warrant particular attention to protect the latter vulnerable group against bone avulsions, overuse pathologies and fatigue-fractures. Injuries were shown to increase significantly with age up to 16 years (P=0.005). Children suffer mainly from contusions, fractures and sprain injuries. Head injuries were more common in boys (P=0.070), while girls were more prone to sprains. The types of injuries differ between adults and children (sprain versus fractures), the anatomical location of injuries is different (lower limbs in adults, lower and upper limbs in children), the circumstances of the injuries are different (contact in adults versus non-contact in children), and teenage girls have different types of injuries than teenage boys. An increased incidence of injuries is due to changes in the position of the center of gravity and in the morphotype during rapid growth. For these reasons it is mandatory to adapt the training to the age and sex of the players. It is unsafe to train children the same way as adults. The height, the weight and the speed of growth must be taken into account by the multidisciplinary team when organising the training programmes. -- Le football fait partie des sports les plus pratiqués au monde en raison de sa popularité et de son accessibilité économ ique. L'incidence des blessures liées à cette pratique doit être diminuée surtout chez les jeunes joueurs en raison de la croissance exponentielle du nombre de joueurs féminins et masculins. Une étude épidémiologique rétrospective sur 11 ans (1990-2000) a été réalisée chez les enfants victimes de blessures liées au football (N==1000), puis a été comparée aux données recueillies de l'UEFA lors d'un Championnat Européen en 2006 sur les lésions des joueurs adultes. Cette étude comparative confirme que les structures anatomiques, biologiques et les tensions biomécaniques chez l'enfant diffèrent de celles de l'adulte. Les enfants ont un risque plus élevé de souffrir d'avulsion osseuse et de fractures de fatigue que les adultes. Les blessures augmentent significativement avec l'âge jusqu'à 16 ans (P==0,005). Les traumatismes crâniens sont plus fréquents chez les garçons tandis que les entorses sont plus à risque chez les filles. Les adultes font plus souvent des entorses tandis que les enfants font plus de fractures. La localisation anatomique diffère également entre ces deux groupes (les membres inférieurs chez l'adulte et les membres inférieurs et supérieurs chez l'enfant). La circonstance des blessures diffère également (choc avec un autre joueur chez l'adulte et des blessures sans contact chez l'enfant). Chez les adolescents, les blessures des filles diffèrent de celles des garçons. L'augmentation chez les enfants de cette incidence est liée au déplacement lors de la croissance du centre de gravité, avec une maladresse accrue lors des phases de croissance. Pour toutes ces raisons, il est justifié d'adapter les entraînements de football en fonction de l'âge, du sexe et du morphotype. L'entrainement des enfants doit être différent de celui des adultes. Le poids, la taille et la vitesse de croissance doit être prise en compte dans des structures multidisciplinaires afin de permettre une meilleure longévité sportive des jeunes joueurs de football.

Nationalist neoliberalism? Minority Nationalism, competitiveness and the urban question

Presentation at: II IAS Annual Research Programme International ConferenceSession: Governing Regions, Lancaster Setember 17-19 2007

Mycobacterium tuberculosis Infection in Young Children: Analyzing the Performance of the Diagnostic Tests

This study evaluated the performance of the Tuberculin Skin Test (TST) and Quantiferon-TB Gold in-Tube (QFT) and the possible association of factors which may modify their results in young children (0-6 years) with recent contact with an index tuberculosis case. Materials and Methods: A cross-sectional study including 135 children was conducted in Manaus, Amazonas-Brazil. The TST and QFT were performed and the tests results were analyzed in relation to the personal characteristics of the children studied and their relationship with the index case. Results: The rates of positivity were 34.8% (TST) and 26.7% (QFT), with 14.1% of indeterminations by the QFT. Concordance between tests was fair (Kappa = 0.35 P<0.001). Both the TST and QFT were associated with the intensity of exposure (Linear OR = 1.286, P = 0.005; Linear OR = 1.161, P = 0.035 respectively) with only the TST being associated with the time of exposure (Linear OR = 1.149, P = 0.009). The presence of intestinal helminths in the TST+ group was associated with negative QFT results (OR = 0.064, P = 0.049). In the TST- group lower levels of ferritin were associated with QFT+ results (Linear OR = 0.956, P = 0.036). Conclusions: Concordance between the TST and QFT was lower than expected. The factors associated with the discordant results were intestinal helminths, ferritin levels and exposure time to the index tuberculosis case. In TST+ group, helminths were associated with negative QFT results suggesting impaired cell-mediated immunity. The TST-&QFT+ group had a shorter exposure time and lower ferritin levels, suggesting that QFT is faster and ferritin may be a potential biomarker of early stages of tuberculosis infection.

Neuropeptide Y at the cellular level – Studies on PreproNPY L7P Polymorphism and the Mitochondrial Form of NPY

Neuropeptide Y (NPY) is a widely expressed neurotransmitter in the central and peripheral nervous systems. Thymidine 1128 to cytocine substitution in the signal sequence of the preproNPY results in a single amino acid change where leucine is changed to proline. This L7P change leads to a conformational change of the signal sequence which can have an effect on the intracellular processing of NPY. The L7P polymorphism was originally associated with higher total and LDL cholesterol levels in obese subjects. It has also been associated with several other physiological and pathophysiological responses such as atherosclerosis and T2 diabetes. However, the changes on the cellular level due to the preproNPY signal sequence L7P polymorphism were not known. The aims of the current thesis were to study the effects of the [p.L7]+[p.L7] and the [p.L7]+[p.P7] genotypes in primary cultured and genotyped human umbilical vein endothelial cells (HUVEC), in neuroblastoma (SK-N-BE(2)) cells and in fibroblast (CHO-K1) cells. Also, the putative effects of the L7P polymorphism on proliferation, apoptosis and LDL and nitric oxide metabolism were investigated. In the course of the studies a fragment of NPY targeted to mitochondria was found. With the putative mitochondrial NPY fragment the aim was to study the translational preferences and the mobility of the protein. The intracellular distribution of NPY between the [p.L7]+[p.L7] and the [p.L7]+[p.P7] genotypes was found to be different. NPY immunoreactivity was prominent in the [p.L7]+[p.P7] cells while the proNPY immunoreactivity was prominent in the [p.L7]+[p.L7] genotype cells. In the proliferation experiments there was a difference in the [p.L7]+[p.L7] genotype cells between early and late passage (aged) cells; the proliferation was raised in the aged cells. NPY increased the growth of the cells with the [p.L7]+[p.P7] genotype. Apoptosis did not seem to differ between the genotypes, but in the aged cells with the [p.L7]+[p.L7] genotype, LDL uptake was found to be elevated. Furthermore, the genotype seemed to have a strong effect on the nitric oxide metabolism. The results indicated that the mobility of NPY protein inside the cells was increased within the P7 containing constructs. The existence of the mitochondria targeted NPY fragment was verified, and translational preferences were proved to be due to the origin of the cells. Cell of neuronal origin preferred the translation of mature NPY (NPY1-36) when compared to the non neuronal cells that translated both, NPY and the mitochondrial fragment of NPY. The mobility of the mitochondrial fragment was found to be minimal. The functionality of the mitochondrial NPY fragment remains to be investigated. L7P polymorphism in the preproNPY causes a series of intracellular changes. These changes may contribute to the state of cellular senescence, vascular tone and lead to endothelial dysfunction and even to increased susceptibility to diseases, like atherosclerosis and T2 diabetes.