Gender differences in microRNA expression in levodopa-naive PD patients.

Gender is an important factor influencing epidemiological and clinical features of Parkinson's disease (PD). We aimed to evaluate gender differences in the expression of a panel of miRNAs (miR-34a-5p, miR-146a, miR-155, miR-29a, miR-106a) possibly involved in the pathophysiology or progression of disease. Serum samples were obtained from 104 PD patients (58 men and 46 women) never treated with levodopa. We measured levels of miRNAs using quantitative PCR. Correlations between miRNA expression and clinical data were assessed using the Spearman's correlation test. We used STRING to evaluate co-expression relationship among target genes. MiR-34a-5p was significantly upregulated in PD male patients compared to PD female patients (fc: 1.62; p < 0.0001). No correlation was found with age, BMI, and disease severity, assessed by UPDRS III scale, in male and female patients. MiR-146a-5p was significantly upregulated in female as compared to male patients (fc: 3.44; p < 0.0001) and a significant correlation was also observed between disease duration and mir-146a-5p. No differences were found in the expression of miR-29a, miR-106a-5p and miR-155 between genders. Predicted target genes for miR-34a-5p and miR-146-5p and protein interactions in biological processes were reported. Our study supports the hypothesis that there are gender-specific differences in serum miRNAs expression in PD patients. Follow-up of this cohort is needed to understand if these differences may affect disease progression and response to treatment.

Combined pulses of light and sound in the retina with nutraceuticals may enhance the recovery of foveal holes.

The present manuscript stems from evidence, which indicates that specific wavelength produce an activation of the autophagy pathway in the retina. These effects were recently reported to synergize with the autophagy-inducing properties of specific phytochemicals. The combined administration of photo-modulation and phytochemicals was recently shown to have a strong potential in eliciting the recovery in the course of retinal degeneration and it was suggested as a non-invasive approach named "Lugano protocol" to treat age-related macular degeneration (AMD). Recent translational findings indicate that the protective role of autophagy may extend also to acute neuronal injuries including traumatic neuronal damage. At the same time, very recent investigations indicate that autophagy activation and retinal anatomical recovery may benefit from sound exposure. Therefore, in the present study, the anatomical rescue of a traumatic neuronal loss at macular level was investigated in a patient with idiopathic macular hole by using a combined approach of physical and chemical non-invasive treatments. In detail, light exposure was administered in combination with sound pulses to the affected retina. This treatment was supplemented by phytochemicals known to act as autophagy inducers, which were administered orally for 6 months. This combined administration of light and sound with nutraceuticals reported here as Advanced Lugano's Protocol (ALP) produced a remarkable effect in the anatomical architecture of the retina affected by the macular hole. The anatomical recovery was almost complete at roughly one year after diagnosis and beginning of treatment. The structural healing of the macular hole was concomitant with a strong improvement of visual acuity and the disappearance of metamorphopsia. The present findings are discussed in the light of a synergism shown at neuronal level between light and sound in the presence of phytochemicals to stimulate autophagy and promote proliferation and neuronal differentiation of retinal stem cells.

Noradrenergic substrates sensing light within brainstem reticular formation as targets for light-induced behavioral and cardiovascular plasticity.

The occurrence of pure light exerts a variety of effects in the human body, which span from behavioral alterations, such as light-driven automatic motor activity, cognition and mood to more archaic vegetative functions, which encompass most organs of the body with remarkable effects on the cardiovascular system. Although empirical evidence clearly indicates occurrence of these widespread effects, the anatomical correlates and long-lasting changes within putatively specific neuronal circuitries remain largely unexplored. A specific role is supposed to take place for catecholamine containing neurons in the core of the brainstem reticular formation, which produces a widespread release of noradrenaline in the forebrain while controlling the vegetative nervous system. An indirect as well as a direct (mono-synaptic) retino-brainstem pathway is hypothesized to rise from a subtype of intrinsically photosensitive retinal ganglion cells (iPRGCs), subtype M1, which do stain for Brn3b, and project to the pre-tectal region (including the olivary pre-tectal nucleus). This pathway provides profuse axon collaterals, which spread to the periacqueductal gray and dorsal raphe nuclei. According to this evidence, a retino-reticular monosynaptic system occurs, which powerfully modulate the noradrenergic hub of reticular nuclei in the lateral column of the brainstem reticular formation. These nuclei, which are evidenced in the present study, provide the anatomical basis to induce behavioral and cardiovascular modulation. The occurrence of a highly interconnected network within these nuclei is responsible for light driven plastic effects, which may alter persistently behavior and vegetative functions as the consequence of long-lasting alterations in the environmental light stimulation of the retina. These changes, which occur within the core of an archaic circuitry such as the noradrenaline-containing neurons of the reticular formation, recapitulate, within the CNS, ancestral effects of light-driven changes, which can be detected already within the retina itself at the level of multipotent photic cells.

The potential effects of nutrients and light on autophagy-mediated visual function and clearance of retinal aggregates.

Increasing findings indicate that a dysfunction in the autophagy machinery is common during retinal degeneration. The present article provides evidence showing that an autophagy defect in the outer retinal layers is commonly described at the onset of retinal degeneration. These findings involve a number of structures placed at the border between the inner choroid and the outer retina encompassing the choriocapillaris, the Bruch's membrane, photoreceptors and Mueller cells. At the center of these anatomical substrates are placed cells forming the retinal pigment epithelium (RPE), where autophagy seems to play most of its effects. In fact, a failure of the autophagy flux is mostly severe at the level of RPE. Among various retinal degenerative disorders, age-related macular degeneration (AMD) is mostly affected by a damage to RPE, which can be reproduced by inhibiting the autophagy machinery and it can be counteracted by the activation of the autophagy pathway. In the present manuscript evidence is provided that such a severe impairment of retinal autophagy may be counteracted by administration of a number of phytochemicals, which possess a strong stimulatory activity on autophagy. Likewise, natural light stimulation administered in the form of pulsatile specific wavelengths is capable of inducing autophagy within the retina. This dual approach to stimulate autophagy is further strengthened by the interaction of light with phytochemicals which is shown to activate the chemical properties of these natural molecules in sustaining retinal integrity. The beneficial effects of photo-biomodulation combined with phytochemicals is based on the removal of toxic lipid, sugar and protein species along with the stimulation of mitochondrial turn-over. Additional effects of autophagy stimulation under the combined effects of nutraceuticals and light pulses are discussed concerning stimulation of retinal stem cells which partly correspond to a subpopulation of RPE cells.

The Workplace Health Promotion (WHP) programme in an Italian University Hospital.

INTRODUCTION: Description of the lifestyles of employees of the Siena University Hospital (Azienda Ospedaliera Universitaria Senese: AOUS), as assessed through a Workplace Health Promotion (WHP) project in the two-year period 2017-18; assessment of possible short-term effects of integrated health promotion interventions in the workplace, within the framework of the Tuscany WHP network, as applied in the AOUS and involving about 1,000 workers. METHODS: A cross-sectional study and a pre-post evaluation of data collected by means of anonymous questionnaires in two phases: before the beginning of the programme and after 12 months. RESULTS: Twelve months after the start of the programme regarding diet (consumption of fruit and vegetables) and physical activity, the positive effects that emerged were not statistically significant. No differences were observed between gender or professional categories. The employees' perception of the programme was satisfactory. CONCLUSIONS: Albeit within the methodological limits of the assessment, the results showed that the diffusion of some major risk factors for chronic diseases had not decreased after 12 months' exposure to the programme. However, monitoring of these risk factors needs to be continued over a longer period, in order to detect the appearance of the expected changes in the long term. Moreover, it is essential to continue monitoring by sex and professional category, in order to pick out any differences and, if possible, take remedial actions. Further studies, in collaboration with the pertinent physicians, are desirable, since integrating data collected during health surveillance with a limited set of indicators of general risk factors may help to promptly identify possible health needs among employees.

Self-reported recurrent pain and medicine use among 15-year-olds: results from the HBSC Italian study.

BACKGROUND: The prevalence of adolescent pain varies considerably across epidemiological studies, and little information is available on pain-related behaviours among adolescents, including medicine use. The aims of this study were: [1] to examine the prevalence of recurrent pain among 15-year-old adolescents in Italy; [2] to investigate the association between recurrent pain and medicine use among boys and girls; and [3] to evaluate the consistency of these associations across Regions. METHODS: The World Health Organization (WHO) collaborative International Health Behaviour in School-aged Children 2013/2014 study collected self-reported data on pain and medicine use from 13611 15-year-old adolescents in 21 Italian Regions. We used multi-level multivariate logistic regression, stratified by gender, to analyse the association between recurrent pain and medicine use for headache, stomachache, nervousness and difficulties in getting to sleep. RESULTS: On average, across all Regions, almost 45% of adolescents reported recurrent headache, more than 30% reported recurrent backache and approximately 30% reported recurrent stomachache. Although the prevalence of both pain and medicine use was much higher among girls, the association between pain and medicine use was similarly strong in adolescents of both genders. Adolescents with recurrent pain proved more likely to use medicines also for non-corresponding pain, nervousness and difficulties in getting to sleep. The association between recurrent pain and medicine use was consistent across Regions despite large inter-regional differences in the prevalence of both phenomena. CONCLUSIONS: Recurrent pain in adolescence is common nationwide. Adolescents with recurrent pain are more likely to use medicines in general. Recurrent pain and medicine use should be addressed by adolescent health policies.

"OKKIO alla salute 2014" results from the Tuscan sample.

BACKGROUND: The prevalence of overweight and obesity among children is rapidly increasing in many countries. For this reason we decided to investigate the eating habits of 8-9 years old Tuscany children, by paying attention to the frequency of their meals per day and to their food choices, also in relation to children's Body Mass Index (BMI) classes. In addition, we considered some environmental factors that could affect children eating behaviors, such as parents' BMI. METHODS: Data from the 2014 Tuscany nutritional surveillance system (part of the national periodical survey) and collected from children, parents and teachers, have been linked to study of children's eating habits. Logistic regression analyses were used to investigate the association between incorrect dietary habits and the potential predictors of overweight and obesity. RESULTS: More than half of the 2,163 children (68.64% overall, 67.61% females, 69.56% males) reported to have eaten an appropriate breakfast in the morning, while 5.9% skipped breakfast and only 33.5% of children ate an appropriate mid-morning snack. Logistic regression showed that having breakfast and especially an adequate breakfast are protective factors against obesity (OR 0.57, p<0.01; OR 0.84; p=0.03 respectively). CONCLUSION: In Tuscany Region, unhealthy dietary habits are common among children. The identified deficiencies may be a harbinger of future public health problems.

Methamphetamine increases Prion Protein and induces dopamine-dependent expression of protease resistant PrPsc.

The cellular prion protein (PrPc) is physiologically expressed within selective brain areas of mammals. Alterations in the secondary structure of this protein lead to scrapie-like prion protein (PrPsc), which precipitates in the cell. PrPsc has been detected in infectious, inherited or sporadic neurodegenerative disorders. Prion protein metabolism is dependent on autophagy and ubiquitin proteasome. Despite not being fully elucidated, the physiological role of prion protein relates to chaperones which rescue cells under stressful conditions.Methamphetamine (METH) is a widely abused drug which produces oxidative stress in various brain areas causing mitochondrial alterations and protein misfolding. These effects produce a compensatory increase of chaperones while clogging cell clearing pathways. In the present study, we explored whether METH administration modifies the amount of PrPc. Since high levels of PrPc when the clearing systems are clogged may lead to its misfolding into PrPsc, we further tested whether METH exposure triggers the appearance of PrPsc. We analysed the effects of METH and dopamine administration in PC12 and striatal cells by using SDS-PAGE Coomassie blue, immune- histochemistry and immune-gold electron microscopy. To analyze whether METH administration produces PrPsc aggregates we used antibodies directed against PrP following exposure to proteinase K or sarkosyl which digest folded PrPc but misfolded PrPsc. We fond that METH triggers PrPsc aggregates in DA-containing cells while METH is not effective in primary striatal neurons which do not produce DA. In the latter cells exogenous DA is needed to trigger PrPsc accumulation similarly to what happens in DA containing cells under the effects of METH. The present findings, while fostering novel molecular mechanisms involving prion proteins, indicate that, cell pathology similar to prion disorders can be mimicked via a DA-dependent mechanism by a drug of abuse.

Severe obesity prevalence in 8- to 9-year-old Italian children: a large population-based study.

BACKGROUND AND OBJECTIVES: Little information is available on severe obesity in childhood. This study estimates the prevalence of severe obesity in 8- to 9-year-old children resident in Italy and its association with gender, age, geographical area and parents' nutritional status and education using the World Health Organization (WHO) and International Obesity Task Force (IOTF) criteria. SUBJECTS/METHODS: A nationally representative sample of grade 3 Italian students was measured in 2010 (N=42,431) using standardized instruments and methodology. Severe obesity in children was assessed using definitions provided by the WHO and by the IOTF. Prevalence was estimated within categories of sociodemographic variables and their independent effects were estimated using multivariate logistic regression. RESULTS: The estimated prevalence of severe obesity in 2010 was 4.5% (95% confidence interval (CI): 4.2-4.7) according to the WHO definition and 2.7% (95% CI: 2.5-2.9) with IOTF cutoffs. These values were slightly lower than those observed in 2008. The prevalence was higher in males, in 8-year-old children and in the South. Parental low education and high body mass index were strongly associated with childhood severe obesity. CONCLUSION: According to the definition used, between 30,000 and 50,000 children aged 8-9 years suffer severe obesity in Italy.

The methodology of the Italian HBSC 2010 study (Health Behaviour in School-aged Children).

Italy has participated in the Health Behaviour in School-aged Children (HBSC) study since 2000. These surveys collect data every four years on the well-being and health behaviour of boys and girls aged 11, 13 and 15. Until 2007, the coordination group of the University of Turin, Siena and Padua directly sent the questionnaires to each sampled school to collect the data. The sample of about 4500 students was nationally representative. In 2008 the HBSC became part of the project "Surveys on behavioral risks in children aged 6-17 years", coordinated by the National Institute of Health (ISS) and promoted by the Ministry of Health, in collaboration with the Ministry of Education, University and Research. For the first time, in 2010, the survey was conducted by health workers in collaboration with teachers in all regions with a representative sample, not just at the national level, but also at regional level. In the 2,504 sampled schools, 77,113 students (25,079 eleven-year-old, 26,048 thirteen-year-old and 25,986 fifteen-year-old) completed an anonymous questionnaire. Knowledge of the health-related behaviour of school-aged adolescents may help monitoring and enable policies for young people to be formulated and implemented.

Correlation between physical activity and sedentary behavior with healthy and unhealthy behaviors in Italy and Tuscan region: a cross sectional study.

INTRODUCTION: Regular physical activity (PA) has associated with various positive health aspects such as a decreased risk of chronic or generic illnesses, furthermore, a sedentary lifestyle has been associated with health problems such as obesity. To examine the relationship between patterns of PA, screen-based media use (SBM) and social health indicators within a specific demographic group and highlight the regional vs. national differences in these relationships. METHODS: The data is drawn from the Health Behaviour in School-Aged Children (HBSC) database, a national cross-sectional survey in a representative sample (N = 3920) of students aged 11-13-15 years and compared to those of the Tuscan region (N = 3381). Variables considered other than PA and SBM use includes positive health indicators such as physical health status, quality of family and peer relationships, fruit consumption, breakfast consumption as well as negative health indicators, such as health complaints, smoking and alcohol use. RESULTS: Some positive health indicators showed a positive correlation with PA. Students adopting healthy behaviours often met the Physical Activity Guide Line (PAGL). On the contrary, negative health indicators were associated with PAGL in a negative way. In general SBM was positively related to several of the negative health indicators and vice versa. SBM was related in a positive fashion to tobacco use that represents a protective factor. DISCUSSION: The results show that met PAGL is associated with positive health indicators and that high levels of SBM use is associated with negative health indicators. The study also emphasizes the relationship between PA, SBM use and socialfactors. Increasing PA and decreasing SBM use should be an aim in general health behaviour promotion.

High-intensity exercise training induces morphological and biochemical changes in skeletal muscles.

IN THE PRESENT STUDY WE INVESTIGATED THE EFFECT OF TWO DIFFERENT EXERCISE PROTOCOLS ON FIBRE COMPOSITION AND METABOLISM OF TWO SPECIFIC MUSCLES OF MICE: the quadriceps and the gastrocnemius. Mice were run daily on a motorized treadmill, at a velocity corresponding to 60% or 90% of the maximal running velocity. Blood lactate and body weight were measured during exercise training. We found that at the end of training the body weight significantly increased in high-intensity exercise mice compared to the control group (P=0.0268), whereas it decreased in low-intensity exercise mice compared to controls (P=0.30). In contrast, the food intake was greater in both trained mice compared to controls (P < 0.0001 and P < 0.0001 for low-intensity and high-intensity exercise mice, respectively). These effects were accompanied by a progressive reduction in blood lactate levels at the end of training in both the exercised mice compared with controls (P=0.03 and P < 0.0001 for low-intensity and high-intensity exercise mice, respectively); in particular, blood lactate levels after high-intensity exercise were significantly lower than those measured in low-intensity exercise mice (P=0.0044). Immunoblotting analysis demonstrated that high-intensity exercise training produced a significant increase in the expression of mitochondrial enzymes contained within gastrocnemius and quadriceps muscles. These changes were associated with an increase in the amount of slow fibres in both these muscles of high-intensity exercise mice, as revealed by the counts of slow fibres stained with specific antibodies (P < 0.0001 for the gastrocnemius; P=0.0002 for the quadriceps). Our results demonstrate that high-intensity exercise, in addition to metabolic changes consisting of a decrease in blood lactate and body weight, induces an increase in the mitochondrial enzymes and slow fibres in different skeletal muscles of mice, which indicates an exercise-induced increase in the aerobic metabolism.

High-intensity exercise training produces morphological and biochemical changes in adrenal gland of mice.

The effects of training are dependent on complex, adaptive changes which are induced by acute physical exercise at different levels. In particular, evidence shows that the hypothalamus-pituitary-adrenocortical axis, as well as the sympatho-adrenomedullary system, is mainly involved in mediating the physiological effects of physical exercise. The aim of the present study was to investigate, through a morphological and biochemical approach, the effects of training on the adrenal gland of mice, following two different protocols consisting of either low- or high-intensity training. Mice were run daily on a motorised treadmill for 8 weeks, at a velocity corresponding to 60% (low-intensity exercise) or 90% (high-intensity exercise) of the maximal running velocity previously determined by an incremental exercise test. We found that physical exercise produced an increase in the adrenal gland size compared with the control (sedentary) mice. The increase was 31.04% for mice that underwent high-intensity exercise and 10.08% for mice that underwent low intensity exercise, and this appeared to be the result of an increase in the area of both the adrenal cortex and adrenal medulla. Morphological analysis of the adrenal cortex showed that both types of exercise produced an increase in cytoplasmic vacuoles in steroidogenic cells, appearing more abundant after high-intensity exercise. No change was found in the reticulate zone. In the adrenal medulla, despite the absence of morphological changes, immunohistochemistry for tyrosine hydroxylase, dopamine ß-hydroxylase and phenyl-ethanolamine-N-methyltransferase demonstrated an increased immunopositivity for these cathecolamine-synthesizing enzymes after intense exercise. These results were confirmed by immunoblot accompanied by densitometric analysis.

BMI from nutritional surveillance of 8-9 years old children in Tuscany (Italy).

INTRODUCTION: The latest increase in childhood obesity focused attention on the important consequences that this phenomenon may have on public health in relationship to the increasing risk that an obese child may become an obese adult. To deal with this problem, there is necessary to assess systematically the distribution of childhood nutritional status at different levels: international, regional and local. In this paper are presented data on underweight, overweight and obesity prevalence in third grade primary school children, aged 8/9 years in Tuscany (2008) and its distribution in relationship to the demographic breadth of their place of residence. METHODS: Data from statistic sample of 2109 (1.091 males, 1.018 females), 8/9 years school-children were collected; weight and height were measured using standardised personnel and instruments. Exact month age was calculated between the data of measurement and that of birth. Body Mass Index (BMI) classes were calculated using Cole et al.'s epidemiologic cut-off for children and adolescents. Residence areas were divided into four classes based on the number of inhabitants (< 10.000; 10.000-50.000; > 50.000; > 50.000 metropolitan). RESULTS: The prevalence of underweight was 0.88% (0.76% in males and 1.01% in females), the prevalence of overweight was 23.43% (22.33% in males and 24.65% in females), the prevalence of obese was 7.95% (9.08% in males, 6.70% in females). The lowest prevalence of obese (6.46%) was found in towns with over 50.000 residents (metropolitan). CONCLUSION: The obesity prevalence in Tuscany children is still lower than that of the Italian National Survey, while the overweight prevalence it's the same. Obesity prevalence (10.71%) is higher in municipalities with low residents number (< 10.000).

Accuracy of different reduced versions of a validated food-frequency questionnaire in italian men and women.

This study aimed to explore how possible it would be to reduce the length of a food-frequency questionnaire (FFQ) while maintaining adequate accuracy. This FFQ was validated in women in a previous study by our group, whereas the validation in men was one of the aims of the present study. A 15-item FFQ was administered to 136 men and 211 women (age range 25-75 years) recruited by proportional age-stratified sampling, who agreed to fill in a 14-day diet diary. For the intermediate version of the FFQ we considered only eight items in women and 10 in men. For the very short version we considered only three items. The positive likelihood ratio was markedly lower for the very short version (men = 1.2 and women = 1.5) with respect to the intermediate version (men = 6 and women = 6.3) and the 15-item version (men = 19.6 and women = 19.9). The specificity of the very short version was low (22.2% for men and 35.2% for women). The area under ROC curve of the three-item FFQ was significantly lower with respect to the other two versions. In conclusion, our study suggests that the shortest version of the FFQ could be usefully employed only in those clinical settings where the main objective is the identification of individuals who do not have a low calcium intake. ROC analysis and posttest probability calculated by positive likelihood ratio may represent an optimal method for assessing the accuracy of FFQs.

Underweight and overweight among children and adolescents in Tuscany (Italy). Prevalence and short-term trends.

INTRODUCTION: The recent increase in both childhood obesity and adolescent anorexia nervosa in developed countries has underlined the important consequences that these trends may have on public health, as there is an increased risk that these conditions may become chronic diseases in adulthood. Therefore, it is necessary to monitor prevalence rates and trends in thinness and overweight (including obesity) among children and adolescents at different levels: international, national and sub-national. Since 2001/2002, a nutritional surveillance system has been implemented in the Tuscany Region to estimate the nutritional status and lifestyles of children and adolescents. The main objectives were to assess the prevalence of thinness, overweight and obesity among Tuscan children and adolescents and to provide baseline information on the prevalence of thinness, for the first time calculated according to the new international definitions, for geographical comparisons and descriptions of time trends. METHODS: Independent cross-sectional sample surveys were conducted in 2002, 2004 and 2006 in Tuscany, North-Central Italy. Data were collected from stratified two-stage cluster samples of children aged 9 years (n = 3,048 in 2002 and n = 1,430 in 2006) and of adolescents aged 11-13-15 years (n = 1,066, n = 1185 and n = 1,160 in 2004 and n = 1,189, n = 1,211 and n = 1,178 in 2006, respectively). Weights and heights of primary school children were measured by means of standardized methods, while those of adolescents were self-reported. Decimal age was calculated from the date of birth to the date of measurement. Body Mass Index classes were calculated according to the International Obesity Task Force standards. Instead of the term underweight in children, we used the term thinness, which the World Health Organization uses to mean low Body Mass Index for age in adults and adolescents. According to Cole's recently published cut-offs for thinness, we divided our Body Mass Index values below 18.5 into three grades. RESULTS: This study presents data on the prevalence of different grades of nutritional status (thinness, normal weight, overweight and obesity) among Tuscan school-aged children from primary to high school (9-11-13-15-y-old), assessed by means of Body Mass Index, according to international definitions. From 2002 to 2006 the prevalence of thinness among children aged 9 years decreased from 4.6% to 4.2%, and the prevalence of normal weight from 63.7% to 62.4%; the prevalence of overweight (including obesity) rose from 31.7% to 33.4%. From 2004 to 2006, among pre-adolescents aged 11 years, the prevalence of thinness declined from 11.0% to 10.1%; the prevalence of normal weight rose from 68.4% to 70.2%, and the prevalence of overweight declined from 20.7% to 19.6%. Among adolescents aged 13 years, the prevalence of thinness declined from 9.8% to 8.0%; the prevalence of normal weight rose from 73.5% to 74.0%, and the prevalence of overweight from 16.8% to 17.9%. Among adolescents aged 15 years, the prevalence of thinness declined from 9.8% to 8.7%, and the prevalence of normal weight from 77.0% to 71.6%, while the prevalence of overweight rose from 13.3% to 19.7%. The 2006 data showed that the trend in the prevalence of overweight (including obesity) tended to decrease with age for both sexes, though more markedly in girls (from 34.0% at 9-y of age to 12.2% at 15-y of age) than in boys (from 32.8% at 9-y of age to 22.8% at 13-y of age to 27.5% at 15-y of age). By contrast, the prevalence of thinness increased with age in girls (from 4.9% at 9-y of age to 14,1% at 15-y of age), while boys presented a similar low prevalence at 9 and 15-y of age (3.3% and 3.1%), doubling the values at 11 and 13-y of age (7.5% and 6.5%). The trend in the prevalence of normal weight increased with age from 62.4% at 9-y of age to 74.0% at 13-y of age and to 71.6% at 15-y of age. Boys displayed a higher prevalence than girls only at 9-y of age (63.9% vs. 61.0%). DISCUSSION: The results of this study allow us to analyze data from the nutritional surveillance system in Tuscany using recent definitions of Body Mass Index cut-off points among children, pre-adolescents and adolescents. As a rule, the trend in the prevalence of overweight (including obesity) among girls from 9-y to 15-y-old strongly decreased, while the prevalence of thinness increased. In boys, this decrease was less marked and the prevalence of thinness displayed an irregular trend, with an increment from 9-y to 11-y-old and a decrease from 13-y to 15-y old. The trend in the prevalence of normal weight increased with age, with a higher prevalence among boys than girls.

Methamphetamine induces ectopic expression of tyrosine hydroxylase and increases noradrenaline levels within the cerebellar cortex.

Methamphetamine produces locomotor activation and typical stereotyped motor patterns, which are commonly related with increased catecholamine activity within the basal ganglia, including the dorsal and ventral striatum. Since the cerebellum is critical for movement control, and for learning of motor patterns, we hypothesized that cerebellar catecholamines might be a target of methamphetamine. To test this experimental hypothesis we injected methamphetamine into C57 Black mice at the doses of 5 mg/kg two or three times, 2 h apart. This dosing regimen is known to be toxic for striatal dopamine terminals. However, we found that in the cerebellum, methamphetamine increased the expression of the primary transcript of the tyrosine hydroxylase (TH) gene, followed by an increased expression of the TH protein. Increased TH was localized within Purkinje cells, where methamphetamine increased the number of TH-immunogold particles, and produced a change in the distribution of the enzyme by increasing the cytoplasmic percentage. Increased TH expression was accompanied by a slight increase in noradrenaline content. This effect was highly site-specific for the cortex of posterior vermal lobules, while only slight effects were detectable in the hemispheres. The present data indicate that the cerebellum does represent a target of methamphetamine, which produces specific and fine alterations of the catecholamine system involving synthesis, amount, and compartmentalization of TH as well as increased noradrenaline levels. This may be relevant for motor alterations induced by methamphetamine. In line with this, inherited cerebellar movement disorders in various animal species including humans are associated with increased TH immunoreactivity within intrinsic neurons of the same lobules of the cerebellar cortex.

Abnormal involuntary movements (AIMs) following pulsatile dopaminergic stimulation: severe deterioration and morphological correlates following the loss of locus coeruleus neurons.

Parkinsonian patients are treated with dopamine replacement therapy (typically, intermittent administration of the dopamine precursor L-DOPA); however, this is associated with the onset of abnormal involuntary movements, which seriously impair the quality of life. The molecular mechanisms underlying abnormal involuntary movements represent an intense field of investigation in the area of neurobiology of disease, although their aetiology remains unclear. Apart from the fine cellular mechanisms, the pathways responsible for the generation of abnormal involuntary movements may involve changes in neurotransmitter systems. A potential candidate is noradrenaline, since a severe loss of this neurotransmitter characterizes Parkinson's disease, and noradrenergic drugs produce a symptomatic relief of L-DOPA-induced dyskinesia. In previous studies we found that pulsatile dopamine release, in the absence of the physiological noradrenaline innervation, produces motor alterations and ultrastructural changes within striatal neurons. In the present study we demonstrate that a unilateral damage to the noradrenaline system anticipates the onset and worsens the severity of L-DOPA-induced contralateral abnormal involuntary movements in hemi-parkinsonian rats. Similarly, ubiquitin-positive striatal ultrastructural changes occur in unilaterally dopamine-depleted, noradrenaline-deficient rats following chronic L-DOPA administration. This study confirms a significant impact of the noradrenergic system in the natural history of Parkinson's disease and extends its role to the behavioural and morphological effects taking place during pulsatile dopamine replacement therapy.