Cardiac Biomarkers Release in Preadolescent Athletes After an High Intensity Exercise.

INTRODUCTION: An elevation of cardiac troponins has been described in healthy athletes after endurance exercises. The clinical significance of this increase is unclear and the lack of awareness of this phenomenon may lead to inappropriate management of these subjects. AIM: We sought to determine wether an intensive cycling training could determine a biomarkers elevation. METHODS: We evaluated serum high sensitivity cardiac troponin T, NH(2)-terminal pro-brain natriuretic peptide, CK-MB and CK in 21 healthy male preadolescent athletes (age 9.2 ± 1.7 years) after an intensive cycling training prolonged until muscular exhaustion (mean duration 16'41″). During exercise heart rhythm and rate were monitored with Holter. RESULTS: 62% of the group had an elevation of cardiac biomarkers: specifically, 6 children had an increase in troponin levels; 3 of them had an elevation of pro-brain natriuretic peptides as well. Pro-brain natriuretic peptides resulted increased in 9 subjects. There was no relation between troponin elevation and heart rate, age or exercise duration; subjects with increased pro-brain natriuretic peptides had mean and maximal heart rates lower than children with normal natriuretic peptides levels. Other sports were performed in 50% of subjects with normal troponins and only in 17% of those with increased values. CONCLUSIONS: A short, high-intensity exercise caused an elevation of cardiac biomarkers in 62% of our subjects. The grade of training may influence the release of troponin and this increase is probably related to a temporary discrepancy between O2 delivery and consumption. Increases in natriuretic peptides levels are possibly expression of different adaptations to exercise.

The role of comprehensive geriatric assessment and functional status in evaluating the patterns of antithrombotic use among older people with atrial fibrillation.

Aim of the study is to investigate the use of antithrombotic drugs in older patients with atrial fibrillation (AF) at the time of hospital discharge. We enrolled 399 ≥65 years old patients with AF consecutively admitted to our acute geriatric unit from September 2012 to February 2014. Utilization of antithrombotic drugs, comorbidities, functional, mental and nutritional status were evaluated through a comprehensive geriatric assessment (CGA). A Logistic regression model was used to assess variables associated with antithrombotic use. On admission, 198 patients (49.6%) used oral anticoagulants (OAC), 125 (21.3%) antiplatelets, 32 (8%) low weight molecular heparin (LMWH) and 44 (11%) none of them. At discharge the proportion of patients on OAC increased to 55.7%. Age>90years (OR=2.57, CI=1.28-5.16, p-value=0.008), severe functional impairment (OR=3.38, CI=1.63-7.01, p-value=0.001), polypharmacy (OR=2.07, CI=1.1-3.86, p-value=0.023), HAS-BLED score (OR=1.64, CI=1.09-2.47, p-value=0.019) and ≥1 OAC contraindication (OR=5.01, CI=2.68-9.34, p-value<0.001) were all associated with OAC underuse. In conclusion, OAC is underused in geriatric patients with AF, while antiplatelet, LMWH and no antithrombotic therapy are relatively overused. Factors associated with the decision to not prescribe OAC lie on a mix of clinical and geriatric variables, among which functional status is particularly relevant.

Under-detection of delirium and impact of neurocognitive deficits on in-hospital mortality among acute geriatric and medical wards.

BACKGROUND: Delirium is a neuropsychiatric disorder, triggered by medical precipitants causes. Study aims were to describe the prevalence and impact on in-hospital mortality of delirium identified through ICD-9 codes as well as evidence of neurocognitive deficits demonstrated in a population of older patients admitted to acute medical wards. METHODS: This was a prospective cohort multicenter study of 2521 older patients enrolled in the "Registro Politerapie SIMI (REPOSI)" during the years 2010 and 2012. The diagnosis of delirium was obtained by ICD-9 codes. Cognitive function was evaluated with the Short Blessed Test (SBT) and single SBT items were used as measures of deficits in attention, orientation and memory. Combination of deficits in SBT items was used as a proxy for delirium. Logistic regression was used to evaluate the association with in-hospital mortality of delirium and combined deficits in SBT items. RESULTS: Delirium was coded in 2.9%, while deficits in attention, orientation, and memory were found in 35.4%, 29.7% and 77.5% of patients. Inattention and either disorientation or memory deficits were found in 14.1%, while combination of the 3 deficits in 19.8%. Delirium, as per ICD-9 codes, was not a predictor of in-hospital mortality. In contrast, objective deficits of inattention, in combination with orientation and memory disorders, were stronger predictors after adjusting for covariates. CONCLUSIONS: The documentation of delirium is poor in medical wards of Italian acute hospitals. Neurocognitive deficits on objective testing (in a pattern suggestive of undiagnosed delirium) should be used to raise awareness of delirium, given their association with in-hospital mortality.

APOE and Alzheimer disease: a major gene with semi-dominant inheritance.

Apolipoprotein E (APOE) dependent lifetime risks (LTRs) for Alzheimer Disease (AD) are currently not accurately known and odds ratios alone are insufficient to assess these risks. We calculated AD LTR in 7351 cases and 10 132 controls from Caucasian ancestry using Rochester (USA) incidence data. At the age of 85 the LTR of AD without reference to APOE genotype was 11% in males and 14% in females. At the same age, this risk ranged from 51% for APOE44 male carriers to 60% for APOE44 female carriers, and from 23% for APOE34 male carriers to 30% for APOE34 female carriers, consistent with semi-dominant inheritance of a moderately penetrant gene. Using PAQUID (France) incidence data, estimates were globally similar except that at age 85 the LTRs reached 68 and 35% for APOE 44 and APOE 34 female carriers, respectively. These risks are more similar to those of major genes in Mendelian diseases, such as BRCA1 in breast cancer, than those of low-risk common alleles identified by recent GWAS in complex diseases. In addition, stratification of our data by age groups clearly demonstrates that APOE4 is a risk factor not only for late-onset but for early-onset AD as well. Together, these results urge a reappraisal of the impact of APOE in Alzheimer disease.

-308(G/A) TNF-alpha gene polymorphism and risk of depression late in the life.

The relationship between major depression (MD) and dementia in the elderly is still not clear, but it is certain that the immune system and in particular, pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-alpha, play a key role in the mechanisms underlying the two neuro-psychiatric disorders. In our experience, the -308(G/A) single nucleotide polymorphism (SNP) in the TNF-alpha gene is associated with earlier age at onset in patients affected by Alzheimer's disease (AD). The aim of this study was to investigate the association between the -308(G/A) SNP and late-life MD in elderly people without dementia. Blood samples were obtained from 50 subjects, after screening with the geriatric depression scale (GDS>or=15) and mini-mental state examination (MMSE>or=24). The -308 (G/A) SNP was genotyped by SSP-PCR amplification. Two-hundred-fourty age-matched healthy volunteers were taken as the control group. We identified different genotype and allele distributions of the SNP in old depressed patients and healthy controls (HC). Our results evidenced a significantly higher percentage of the GG genotype in depressed subjects (84.0% vs. 68.3%; p=0.007) and consequently of the G allele (92.0% vs. 81.9%; p=0.05). The presence of the GG genotype raised the risk of developing MD (odds ratio=OR=2.433, confidence interval=Cl=1.09-5.43). Our findings suggested that the investigated TNF-alpha SNP may: (1) affect MD susceptibility; (2) be involved both in AD and MD development, but probably with a distinct role in the two pathologies.

Clock drawing test (CDT) in the screening of mild cognitive impairment (MCI).

The progressive increase of prevalence and incidence of dementia require growing attention in identifying subjects with early cognitive impairment. We have evaluated the results of mini mental state examination (MMSE) and CDT in elderly patients affected by MCI and mild dementia and in subjects without cognitive impairment, to measure whether combined use of two well-known cognitive screening tests (MMSE, CDT) is useful to identify precociously subjects with possible MCI. Using the statistical model of binomial logistic regression we have pointed out that CDT better differentiates healthy controls from MCI patients. MMSE, on the contrary of CDT, differentiates MCI patients from subjects affected by dementia. Finally, during screening, administration of both CDT and MMSE can be useful to identify precociously subjects with possible MCI.

Effects of aging and cyclosporin a on collagen turnover in human gingiva.

BACKGROUND: WE AIMED AT CHARACTERIZING THE AGING GINGIVA ANALYZING: i) collagen content and turnover in human gingival tissues and fibroblasts obtained from healthy young and aging subjects. ii) the effect of cyclosporin A administration in human cultured gingival fibroblasts obtained from aging compared to young subjects. METHODS: Morphological analysis was performed on haematoxylin-eosin and Sirius red stained paraffin-embedded gingival biopsies from young and aging healthy subjects. The expression of the main genes and proteins involved in collagen turnover were determined by real time PCR, dot blot and SDS-zymography on cultured young and aging gingival fibroblasts, and after cyclosporin A administration. RESULTS: Our results suggest that in healthy aged people, gingival connective tissue is characterized by a similar collagen content and turnover. Collagen turnover pathways are similarly affected by cyclosporin A treatment in young and aging gingival fibroblasts. CONCLUSIONS: Cyclosporin A administration affects gingival collagen turnover pathways in young and aging fibroblasts at the same extent, suggesting that during aging cyclosporin A administration is not related to relevant collagen turnover modifications.

Characterization of supraventricular tachycardia in infants: clinical and instrumental diagnosis.

Supraventricular tachycardia (SVT) is the most common symptomatic arrhythmias in children. Re-entry tachycardias are the most common form, on the contrary automatic tachycardias are relatively rare. There are four types or re-entry: along anomalous pathway with bi-directional (Wolff-Parkinson-White) or unidirectional conduction, intranodal re-entry, intra-atrial re-entry that is common after surgical procedure, and finally the uncommon sinus node re-entry. Automatic tachycardias may be atrial or junctional. The different types of tachycardia have a different incidence according to the age: in the first year of age re-entry along anomalous pathway is the dominant form, while intranodal reentry becomes common during adolescence. The age at the beginning of tachycardia is important for long term prognosis. When SVT starts in the first months of life it disappears in 80% of cases within the first year of life; on the contrary, if tachycardia starts later spontaneous remission is detected in only 15%-20% of patients. In infancy heart failure is the more common presenting symptom, thereafter palpitations become the principal cause of recognition of SVT. Syncope is reported in about 8% of cases and in another 15% usually neonates and infants, the SVT has an occasional detection. Electrocardiogram (ecg) usually allows the precise diagnosis of various types of SVT, and every effort should be made to record ecg during tachycardia. The parameters that should be evaluated are: heart rate, P wave axis, PR and RP interval, and finally presence or absence of AV block. Short lasting episodes should be difficult to be recorded; in these cases cardio-call and trans-telephonic transmission represent useful techniques to obtain SVT demonstration. Patients with SVT require a complete evaluation with others diagnostic techniques: echocardiogram, Holter monitoring, stress test, that should be chosen according the type of tachycardia. Electrophysiologic evaluation is now rarely performed for diagnostic purpose; trans-esophageal atrial stimulation being less invasive than intracardiac evaluation is more extensively employed when diagnosis of SVT is uncertain. Transesophageal stimulation is useful in the following situations: 1) evaluation of patients with symptoms suggestive of paroxistic tachycardia but without ecg documentation, 2) to assess the mechanism responsible for re-entry tachycardia: macro re-entry versus intranodal re-entry 3) to evaluate characteristics of anomalous pathway with bi-directional conduction, and 4)to terminate re-entrant SVT.

Prevalence of major depressive disorder and dementia in psychogeriatric outpatients.

The relationship between depression and dementia in the elderly has been widely investigated, but the real interplay between these variables is still not clear. This observational study highlights the influence of some basic variables, such as sex and age, in the development of dementia and major depression. It shows (i) the importance of sex in the age of onset of depression and dementia, (ii) the presence of two types of depressive syndrome, the first linked to the development of dementia, the second as reactive depression; (iii) the need for more attention to depressive symptoms in young-elderly men.

Affectivity and sexuality in the elderly: often neglected aspects.

Sexuality and affectivity constitute a complex phenomenon involving many spheres: biological, psychological and social. To investigate these aspects, we distributed a dedicated questionnaire, followed by an interview, to 130 elderly residents in Milan and 100 in Monza. The answers indicated that the elderly communicate their emotions regarding the affective and sexual sphere, with different levels of desire for physical contact. The main variables were sex, age, marital status, co-morbidity and poly-pharmacotherapy, the perception of health status and of oneself, past experiences, cultural conditioning and social factors.

PIN1 promoter polymorphisms are associated with Alzheimer's disease.

In our study, we analyzed the coding and promoter regions of the PIN1 gene in a group of 111 Alzheimer's disease (AD) patients looking for a possible genotype-phenotype correlation. The presence of SNPs - which could affect and modify the clinical phenotype of AD patients was also investigated. We identified two single nucleotide polymorphisms (SNPs) at positions -842 (G-->C) and -667 (C-->T) in the promoter region of the PIN1 gene. Our results evidenced a significantly higher percentage of -842C allele carriers in AD subjects with respect to healthy controls. We found that this allele significantly raised the risk of developing AD (OR 3.044, CI 1.42-6.52). The -842 and -667 SNPs were in linkage disequilibrium and combined to form haplotypes. The CC haplotype conferred a higher risk of developing AD (OR 2.95, confidence interval 1.31-6.82). Finally, protein expression analyses revealed that subjects carrying the -842 CC genotype or the CC haplotype showed reduced levels of the PIN1 protein in peripheral mononuclear cells.

Assessment of selective homing and contribution to vessel formation of cryopreserved peripherally injected bone marrow mononuclear cells following experimental myocardial damage.

In view of a potential clinical use we aimed this study to assess the selective homing to the injured myocardium and the definitive fate of peripherally injected labeled and previously cryopreserved Bone Marrow Mononuclear cells (BMMNCs). The myocardial damage (cryoinjury) was produced in 59 rats (45 treated, 14 controls). From 51 donor rats 4.4 x 10(9) BMMNCs were isolated and cryopreserved (slow-cooling protocols); the number of CD34+ and the viability of pooled cells was assessed by flow-cytometry analysis before and after cryopreservation and simulated delivery through a 23G needle. Seven days after injury, BMMNCs were thawed, labeled with PKH26 dye and peripherally injected (20 x 10(6) cells in 500 microl) in recipient rats. Two weeks after experimental injury, the heart, lungs, liver, kidneys, spleen and thymus were harvested to track transplanted cells. Except a small amount in the spleen, PKH26+ cells were found only in the infarcted myocardium of the treated animals. Typical vascular structures CD34+ were found in the infarcted areas of all animals; treated rats showed a significantly higher number of these structures if compared with untreated. Morphological ultra-structural examination of infarcted areas confirmed in treated rats the presence of early-stage PKH26+ vascular structures derived from injected BMMNCs. The estimated mean CD34+ cells loss due to the cryopreservation procedure and to the system of delivery was 0.24% and 0.1%, respectively, confirming the feasibility of the procedure. This study supports the possible therapeutic use of cryopreserved peripherally injecetd BMMNCs as a source of CD34+ independent vascular structures following myocardial damage.

High-altitude trekking in the Himalayas increases the activity of circulating endothelial cells.

Circulating endothelial progenitor cells (EPCs) are believed to contribute to vascular homeostasis; unfortunately, the response of EPCs in physiological conditions remains largely unknown. Herein we report our observations of a 44-year-old healthy subject after a trek in the Himalayas that support high-altitude hypoxia and exercise oxygen demands are strong stimuli for clonogenic endothelial cell activation and activity, as shown by the increase in the number of mature EPCs and in the endothelial colony-forming unit capacity. Both of these effects were completely reverted at sea level, 45 days after the subject's trek.

Mast cell density, hepatic stellate cell activation and TGF-beta1 transcripts in the aging Sprague-Dawley rat during early acute liver injury.

Mast cells (MCs) have been indicated as a source of various inflammatory cytokines, chemokines and growth factors. This study evaluates liver tissue MC density as a quantitative marker of acute liver inflammation in 2- and 19-month old rats treated with carbon tetrachloride (CCl4) toassess the relationships between MC density, hepatocellular damage, mRNA encoding TGF-beta1, hepatic stellate cell (HSC) activation and collagen levels. Consecutive histological sections from each age group were stained with toluidine blue to identify granulated MCs, Direct Red 80 to recognize collagen matrix, and by immunohistochemistry to identify activated hepatic stellate cells (HSCs), which were subsequently counted by means of a computer-aided image analysis. Histology showed hepatocellular necrosis with inflammatory cell infiltration and collagen matrix deposition. Two and 24 hours after intoxication, MC density had considerably increased in the younger rats, but less in those aged 19 months. Although the untreated older rats had a larger area occupied by activated HSCs than the untreated younger rats, the increase in the number of HSCs was greater in the younger rats both two and 24 hours after intoxication. The greater MC density in younger rats suggests that older rats have a reduced immune response or recruit fewer MCs. The activated HSCs and TGF-beta1 transcripts did not increase significantly during the study period, thus indicating that these are later events in chemically induced hepatic toxicity. In conclusion. MC density may be an index of acute liver inflammation after CCl4 intoxication.

CHF-1024, a DA2/alpha2 agonist, blunts norepinephrine excretion and cardiac fibrosis in pressure overload.

We compared the effects of an ACE inhibitor, captopril, with those of a DA2-dopaminergic/alpha2-adrenergic receptor agonist (CHF-1024) on neuroendocrine activation and cardiac fibrosis in a model of pressure-overload hypertrophy. Interrenal aortic stenosis was performed in 89 rats, treated with CHF-1024 (0.33, 2 or 6 mg kg(-1) day(-1)), or captopril (1 g/L). Hemodynamic variables were recorded. Cardiac and renal weights, plasma aldosterone, renin activity and urinary catecholamine excretion were measured, as well as cardiac collagen. Blood pressure was lower in stenotic animals treated with CHF-1024 compared to vehicle (161 +/- 10 vs 219 +/- 10 mmHg, p < 0.01), but LV weight was similar. CHF-1024 elicited a marked dose-dependent attenuation of urinary norepinephrine excretion (1.80 +/- 0.18 in controls compared to 0.40 +/- 0.14 microg/24 h at the highest dose, p < 0.01) and of LV perivascular fibrosis. Captopril provoked a marked hypotension, reduced cardiac and body weights, plasma aldosterone concentration, dopamine excretion and perivascular collagen. The DA2/alpha2 agonist CHF-1024 effectively blunts adrenergic drive and cardiac fibrosis in a rat model of pressure overload.

The hemochromatosis gene affects the age of onset of sporadic Alzheimer's disease.

In the present study we analysed the genotype of HFE, the gene involved in hemochromatosis, in 107 patients with sporadic late-onset AD and in 99 age-matched non-demented controls. We observed that patients carrying the mutant HFE-H63D allele had a mean age at onset of 71.7 +/- 6.0 years versus 76.6 +/- 5.8 years of those who were homozygous for the wild-type allele (p = 0.001). The frequency of the HFE-H63D mutation was highest (0.22) in the patients aged <70 years at the time of disease onset, whereas it was 0.12 in those with disease onset at an age of 70-80 years, and 0.04 in those aged more than 80 years. The APOE genotype did not significantly modify the effect of HFE on age at onset. We conclude that mild disturbances of iron homeostasis associated with a common genetic determinant may interact with other pathogenic mechanisms involved in AD. HFE mutations may anticipate AD clinical presentation in susceptible individuals.

Alpha-1-antichymotrypsin and oxidative stress in the peripheral blood from patients with probable Alzheimer disease: a short-term longitudinal study.

To evaluate the stability and reproducibility of selected peripheral oxidative stress markers and their possible relation to cognitive performance, three different blood samples were taken at 7- to 10-day intervals from 11 patients with probable Alzheimer disease (AD) and 11 nondemented controls. Blood samples were also collected once from 6 patients with vascular dementia (VD). Alpha-1-antichymotrypsin (ACT), C-reactive protein (CRP), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), lactoferrin (LTF), and total lipid peroxidation (LPO) were then measured. Blood levels of ACT and GSH-Px were increased in AD patients but not in patients with VD. Levels of LTF, CRP, and LPO were comparable between AD patients and controls. Erythrocyte SOD activity was increased in AD patients. Blood levels of ACT negatively correlated with LPO levels and positively correlated with scores of the Global Deterioration Scale of AD patients. ACT might be implicated in controlling oxidative damage of blood lipids and their turnover during the progression of AD.

Aloe-Emodin quinone pretreatment reduces acute liver injury induced by carbon tetrachloride.

Aloe contains several active compounds including aloin, a C-glycoside that can be hydrolyzed in the gut to form aloe-emodin anthrone which, in turn, is auto-oxidized to the quinone aloe-emodin. On the basis of the claimed hepatoprotective activity of some antraquinones, we studied aloe-emodin in a rat model of carbon tetrachloride (CCl4) intoxication, since this xenobiotic induces acute liver damage by lipid peroxidation subsequent to free radical production. Twelve rats were treated with CCl4 (3 mg/kg) intraperitoneally and six were protected with two intraperitoneally injections of aloe-emodin (50 mg/kg; CCl4+aloe-emodin); six other rats were only aloe-emodin injected (aloe-emodin) and six were untreated (control). Histological examination of the livers showed less marked lesions in the CCl4+aloe-emodin rats than in those treated with CCl4 alone, and this was confirmed by the serum levels of L-aspartate-2-oxoglutate-aminotransferase (394+/-38.6 UI/l in CCl4, 280+/-24.47 UI/l in CCl4+aloe-emodin rats; P<0.05). We also quantified changes in hepatic albumin and tumour necrosis factor-alpha mRNAs. Albumin mRNA expression was significantly lower only in the liver of CCl4 rats (P<0.05 versus control) and was only slightly reduced in the CCl4+aloe-emodin rats. In contrast tumour necrosis factor-alpha mRNA was significantly higher (P<0.05) in the CCl4 than the control rats and almost equal in the CCl4+aloe-emodin, aloe-emodin and control groups. In conclusion, aloe-emodin appears to have some protective effect not only against hepatocyte death but also on the inflammatory response subsequent to lipid peroxidation.

Gene polymorphism affecting alpha1-antichymotrypsin and interleukin-1 plasma levels increases Alzheimer's disease risk.

Plasma levels of alpha1-antichymotrypsin (ACT) and interleukin-1beta (IL-1beta) were increased in patients with probable Alzheimer's disease (AD). A common polymorphism within ACT and IL-1beta genes affected plasma levels of ACT or IL-1beta, and AD patients with the ACT T,T or IL-1beta T,T genotype showed the highest levels of plasma ACT or IL-1beta, respectively. The concomitant presence of the ACT T,T and IL-1beta T,T genotypes increased the risk of AD (odds ratio: 5.606, confidence interval: 1.654-18.996) and decreased the age at onset of the disease.