Circadian rhythms are generated by a series of genes, collectively named
genes, which act as a self-sustained internal 24 h timing system in the body. Many physiological processes, including ...metabolism and the endocrine system, are regulated by
genes in coordination with environmental cues. Loss of the circadian rhythms has been reported to contribute to widespread obesity, particularly in the pediatric population, which is increasingly exposed to chronodisruptors in industrialized society. The aim of the present study was to evaluate the DNA methylation status of seven
genes, namely
,
,
and
, in a cohort of chronobiologically characterized obese adolescents (n: 45: F/M: 28/17; age ± SD: 15.8 ± 1.4 yrs; BMI SDS: 2.94 2.76; 3.12) hospitalized for a 3-week multidisciplinary body weight reduction program (BWRP), as well as a series of cardiometabolic outcomes and markers of hypothalamo-pituitary-adrenal (HPA) function. At the end of the intervention, an improvement in body composition was observed (decreases in BMI SDS and fat mass), as well as glucometabolic homeostasis (decreases in glucose, insulin, HOMA-IR and Hb1Ac), lipid profiling (decreases in total cholesterol, LDL-C, triglycerides and NEFA) and cardiovascular function (decreases in systolic and diastolic blood pressures and heart rate). Moreover, the BWRP reduced systemic inflammatory status (i.e., decrease in C-reactive protein) and HPA activity (i.e., decreases in plasma ACTH/cortisol and 24 h urinary-free cortisol excretion). Post-BWRP changes in the methylation levels of
,
and
genes occurred in the entire population, together with hypermethylation of
and
genes in males and in subjects with metabolic syndrome. In contrast to the pre-BWRP data, at the end of the intervention, cardiometabolic parameters, such as fat mass, systolic and diastolic blood pressures, triglycerides and HDL-C, were associated with the methylation status of some
genes. Finally, BWRP induced changes in
genes that were associated with markers of HPA function. In conclusion, when administered to a chronodisrupted pediatric obese population, a short-term BWRP is capable of producing beneficial cardiometabolic effects, as well as an epigenetic remodeling of specific
genes, suggesting the occurrence of a post-BWRP metabolic and endocrine chronoresynchronization, which might represent a "biomolecular" predictor of successful antiobesity intervention.
Abstract Background and objective Incidence and prevalence of Alzheimer's disease (AD) are higher in postmenopausal women than in age-matched men. Since at menopause the endocrine system and other ...biological paradigms undergo substantial changes, we thought to be of interest studying whether (and how) the balance between some biological parameters allegedly neuroprotective (e.g. related to estrogen, dehydroepiandrosterone and CD36 functions) and others considered pro-neurotoxic (e.g. related to glucocorticoid and interleukin-6 activities) vary during lifespan in either sex in either normalcy or neurodegenerative disorders. Subjects and methods Along with this aim, we evaluated the gene expression levels of estrogen receptors (ERs), glucocorticoid receptors (HGRs), interleukin-6 (IL-6) and CD36, a scavenger receptor of class B allegedly playing a key role in the proinflammatory events associated with AD, in a population of 209 healthy subjects (73M, 106F, 20–91-year old) and 85 AD patients (36M, 49F, 65–89-year old). Results obtained were related to plasma titers of estrogens, cortisol and dehydroepiandrosterone sulfate (DHEAS). Studies were performed in peripheral leukocytes, since these cells (1) are easily obtainable by a simple blood sampling, (2) express many molecules and multiple receptors which are under the same regulatory mechanisms as those operative in the brain and (3) some of them, e.g. monocytes, share many functions with microglial cells. Results In healthy men all the study parameters were quite stable during lifespan. In women, instead, at menopausal transition, some changes that may predispose to neurodegeneration occurred. In particular, there was (1) an up-regulation of ERs, and a concomitant increase of IL-6 gene expression, events likely due to the loss of the inhibitory control exerted by estradiol (E2 ); (2) an increase of HGRα:HGRβ ratio, indicative of an augmented cortisol activity on HGRα not sufficiently counteracted by the inhibitory HGRβ function; (3) a reduced CD36 expression, directly related to the increased cortisol activity; and (4) an augmented plasma cortisol:DHEAS ratio, widely recognized as an unfavorable prognostic index for the risk of neurodegeneration. In AD patients of both sexes, the expression of the study parameters was similar to that found in sex- and age-matched healthy subjects, thus indicating their unrelatedness to the disease, and rather a better correlation with biological events. Conclusions Menopausal transition is a critical phase of women's life where the occurrence of an unfavorable biological milieu would predispose to an increased risk of neurodegeneration. Collectively, the higher prevalence of AD in the female population would depend, at least in part, on the presence of favoring biological risk factors, whose contribution to the development of the disease occurs only in the presence of possible age-dependent triggers, such as beta-amyloid deposition.
ObjectiveChanges in many gastrointestinal peptides, including the anorexigenic peptide YY (PYY), which is produced by L cells, occur in both anorexia nervosa (AN) and obesity (OB). High PYY levels ...are present in AN, whereas in morbid OB fasting and postprandial PYY secretion is blunted. Somatostatin (somatotropin release-inhibiting factor (SRIF)) reportedly inhibits plasma PYY concentrations in animals and healthy humans, but the effect of a SRIF infusion on spontaneous PYY secretion in AN and OB is unknown.MethodsA total of 18 young women, seven with acute AN (A-AN), four with AN in the recovery phase (R-AN), and seven with morbid OB, were studied. All subjects underwent an infusion of SRIF (9 μg/kg i.v./h, over 60 min), with blood samples drawn before and at different time intervals after SRIF administration. Plasma PYY levels were measured at each time point.ResultsSRIF significantly inhibited plasma PYY concentrations in R-AN and OB, without affecting PYY titers in A-AN. In OB, the inhibitory effect of SRIF also persisted at 90 min. Withdrawal of SRIF infusion in R-AN resulted in a prompt restoration of basal plasma PYY levels, whereas termination of SRIF infusion in OB was followed by a slower increase of PYY titers toward baseline levels. After infusion, PYY Δ area under the curve (ΔAUC) in R-AN was significantly higher than those in A-AN and OB patients. A significant difference in PYY ΔAUC between A-AN and OB was present.ConclusionsThese results suggest the existence of a hypo- and hyper-sensitivity of L cells to the inhibitory effect of SRIF in A-AN and OB respectively.
The effects of the 5-HT1A receptor antagonist WAY 100635 on recognition memory were investigated in two different amnestic models in the rat by using the object recognition task. WAY 100635 at 1 ...mg/kg, but not at 0.3 mg/kg, counteracted scopolamine-induced performance deficits in the acquisition version of this behavioral paradigm. At the same dose, WAY 100635 antagonized extinction of recognition memory in the normal rat, suggesting that it affected acquisition, storage and retrieval of information. These results support and extend prior findings that interactions between the serotonergic and cholinergic systems are relevant to cognition and indicate that WAY 100635 modulates different aspects of recognition memory.
Abstract
Background
Undocumented migrants experience many health problems; a comparison with a suitable control group of natives living in the same socio-economic conditions is still lacking.
Methods
...Demographic data and data on risk factors, chronic conditions and dietary habits were obtained for 6933 adults (2950 Italians and 3983 undocumented migrants) receiving medical assistance from 40 non-governmental organizations all over the country.
Results
Attributed to the fact that these were unselected groups, differences were found in their demographic features, the main ones being their marital status (singles: 50.5% among Italians and 42.8% among migrants; P < 0.001). Smokers were more frequent among Italians (45.3% versus 42.7% P = 0.03); the same happened with hypertension (40.5% versus 34.5% P < 0.001). Migrants were more often overweight (44.1% versus 40.5% P < 0.001) and reporting a chronic condition (20.2% versus 14.4% P < 0.001). Among those on medications (n = 1354), Italians were fewer (n = 425) and on different medications. Differences emerged also in dietary habits.
Conclusions
Differences in health conditions exist between native-borns and undocumented migrants, not because of a bias related to socio-economic conditions. Further studies are needed to design sustainable health policies and tailored prevention plans.
We designed and tested a 10-kW solar rotary kiln reactor to effect the calcination reaction: CaCO
3 → CaO+CO
2. The reactor processes 1–5 mm limestone particles, producing 95% or higher purity lime ...with a
t
60 reactivity ranging from 14 s to 38 min. The degree of calcination and the reactivity both depend on the reactant’s decomposition temperature (1323–1423 K), residence time (3–7 min), and feed rate (10–50 g/min). The reactor’s efficiency, defined as the enthalpy of the calcination reaction at a specified temperature divided by the solar energy input, reached 20% for solar flux inputs of about 1200 kW m
−2 and for quicklime production rates of about 1.3 kg/h. The solar lime reactor operated reliably for more than 100 h for a total of 24 sunny days, withstanding the thermal shocks that occur in solar applications.
The effects of the nitric oxide (NO) donor molsidomine on aged rats’ cognition were evaluated in two different behavioral tasks: the step-through passive avoidance paradigm and the object recognition ...test. Post-training injection of molsidomine (at 4 but not at 2
mg/kg) significantly counteracted the performance deficits displayed by old rats in both the behavioral paradigms. These results support and extend prior findings about the implication of NO in learning and memory mechanisms. In addition, for the first time, a NO donor was found to antagonize age-related memory impairments, suggesting that the integrity of the NO-ergic system may be important in brain aging processes.
Nitric oxide (NO) is hypothesized to be a novel intracellular messenger in the central nervous system. Recently, NO involvement in learning and memory processes has been proposed. Compounds that ...inhibit nitric oxide synthase, the key synthesizing enzyme, may block cognition, while NO donors may facilitate it. The aim of this study was to assess in the rat the effects of the NO donor molsidomine (2 and 4 mg/kg, i.p.) on memory deficits caused by scopolamine. For this purpose, the object recognition task and the step-through passive avoidance procedure were chosen. In addition, the effects of molsidomine in antagonizing the scopolamine-induced hypermotility were also examined. Scopolamine at 0.2 mg/kg (object recognition) and 0.75 mg/kg (passive avoidance) disrupted acquisition in both the tasks and induced locomotor hyperactivity at the dose of 0.2 mg/kg. Molsidomine at either dose reversed the scopolamine-induced deficits in the object recognition paradigm but did not counteract the hypermotility and the deficits occurred in the passive avoidance test. These results suggest that to some extent, the NO donor molsidomine is involved in memory processing.
Endothelial dysfunction in haemophilia patients SARTORI, M. T.; BILORA, F.; ZANON, E. ...
Haemophilia : the official journal of the World Federation of Hemophilia,
September 2008, Letnik:
14, Številka:
5
Journal Article
Recenzirano
Haemophilia patients may develop cardiovascular diseases, suggesting that their clotting defect does not protect them completely from atherosclerosis and its complications. We aimed to evaluate ...cardiovascular risk factors and, for the first time, the presence of endothelial dysfunction in middle‐aged haemophilia patients. We studied 40 patients with haemophilia A and B (24 with moderate–severe disease and 16 with mild disease), and 40 healthy controls. Flow‐mediated dilation (FMD), carotid ultrasound (US) intima media thickness (IMT), arterial blood pressure, body mass index (BMI), cholesterol, triglycerides, glucose, insulin, lipoprotein(a) and homocysteine levels were measured, and PAI‐1 and t‐PA levels before and after venous occlusion (VO), and antibodies to HIV, HBV and HCV were assayed. At least one cardiovascular risk factor was detected in 87.5% of patients, and 2 or more in 47.5% of cases. At US exam, none of the patients had significant carotid stenosis or significant differences in IMT compared to controls. In contrast, all the patients had a significant FMD impairment, associated with a reduced t‐PA release after VO in 70% of cases. PAI‐1 levels significantly correlated with BMI, triglycerides and insulin values. Fifteen haemophilia patients with chronic viral hepatitis and/or HIV infection showed a significantly lower FMD than patients without active infection. We found an endothelial dysfunction with impaired FMD and t‐PA release in our haemophilia patients, usually associated with cardiovascular risk factors. Other pathogenic mechanisms, such as chronic viral infections, are likely to be involved in this endothelial damage, however.
We analysed drug dispensation by charitable organisations in a year time. Drugs were grouped according to the Anatomic Therapeutic Chemical classification and the amount dispensed was calculated with ...the system of the Daily Defined Dose (DDD) and expressed as DDD/1000 subjects/day. A number of 87,550 subjects were studied (13,308 Italians; 74,242 Immigrants). Though we noticed a great sesonal variability, the drugs most frequently dispensed were those for the respiratory, cardiovascular and gastrointestinal system and antibiotics, which is different from the rest of the Italian population and the immigrant population assisted by our National Health Service (NHS). We also found that chronic diseases are increasing in these subjects. We conclude that the subjects not receiving NHS assitance have, at least in part, different health patterns and requirements. This should be considered when planning tailored interventions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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