Interleukin-1beta and interleukin-6 gene polymorphisms as risk factors for AD: a prospective study

Risk of incident dementia from any cause and Alzheimer's disease (AD) in relation to the IL-1beta-511 (C-->T) and IL-6-174 (G-->C) polymorphisms was investigated in an Italian elderly cohort (n=791) with 4 years of follow-up. Analyses were adjusted for socio-demographic confounders (age, gender, education), presence of the Apolipoprotein E-epsilon4 allele, and plasma total homocysteine (tHcy), a newly proposed AD risk factor. No significant association was found for the IL-1beta-511 and IL-6-174 polymorphisms with either dementia or AD. However, in the baseline dementia-free cohort considered as a whole, independently of other confounders, IL-1beta-511 T/T homozygotes had lower plasma tHcy than both heterozygotes (P=0.036) and wild-types (P=0.004). These data do not support the hypothesis that the IL-1-beta-511 and IL-6-174 polymorphisms affect dementia or AD risk. The relationship between the AD risk factor plasma tHcy and the IL-1beta-511 polymorphism was never reported before and might explain previous cross-sectional reports of an association between this polymorphism and AD.     

The benign cystic lymphoepithelial lesion of the parotid gland is a viral reservoir in HIV type 1-infected patients.

The presence of HIV-1 in cystic fluid aspirates from six cases of benign cystic lymphoepithelial lesion (BLL) of the parotid gland, a rare disorder affecting HIV-1-infected patients, has been investigated. HIV-1 p24 protein was present at a concentration ranging from 3 to 15 ng/ml, while it was undetectable in the peripheral blood of the same patients. The number of RNA copies of HIV-1 in the cystic fluids was high, ranging from 0.5 x 10(7) to 7.2 x 10(7) RNA copies/ml. BLL cystic fluid aspirates, despite the high level of HIV-1 RNA, were found to contain only a few infectious virions. The low infectivity correlated with the infrequent detection by electron microscopy of complete HIV-1 particles. The pathogenic mechanism leading to virus accumulation in the cystic fluid was studied by immunohistochemistry of tissue sections. p24 protein was associated with DRC-1+/S-100+ follicular dendritic reticulum cells, which were also present within the cystic cavities. Our findings are consistent with the possibility that the large amounts of virus present in the fluid derive from continuous shedding of HIV-1-infected cells from the surrounding lymphoid tissue.     

Effects of α-human atrial natriuretic peptide in guinea-pig isolated heart

The aim of the present investigation has been to ascertain whether or not atrial natriuretic peptides (ANP) can exert a direct effect on myocardial contractility. Alpha-human ANP (α-hANP) concentrations ranging from 1 pM to 50 nM have been used to perfuse guinea-pig isolated hearts in a non-recirculating Langendorff apparatus. A dual concentration-related effect has been induced by α-hANP on myocardial function. A maximal increase of +LV (+56%; P < 0.001) has been observed when guinea-pig hearts were perfused with 100 pM α-hANP, whereas a 25% decrease (P < 0.01) occurred with 50 nM α-hANP. Similar effects have also been induced by α-hANP on the coronary flow rate (CFR). A significant CFR increase (maximal at 10 pM α-hANP) was induced by picomolar concentrations of α-hANP, whereas a progressive decrease, which was maximal (−28%; P < 0.01) at 50 nM α-hANP, was observed with nanomolar concentrations of the peptide. No effects have been observed on heart rate. These results suggest that ANP has direct effects on both vascular and myocardial muscle cells. Coronary vasoconstriction induced by nanomolar concentrations of ANP can contribute to the cardiodepression, whereas ANP in picomolar concentrations can induce a coronary vasodilation which is not coupled with the enhanced myocardial contractility. The latter is the likely expression of a direct effect of the peptide on myocardial function.     

Levels of Circulating Pro-angiogenic Cells Predict Cardiovascular Outcomes in Patients With Chronic Heart Failure

BackgroundCirculating pro-angiogenic cells (PACs) contribute to vascular and myocardial regeneration. A low level of PACs is associated with worse outcome in patients with coronary heart disease. However, little is known about PACs in heart failure (HF).Methods and ResultsBlood was sampled at baseline in 111 patients with HF, 67 from 5 Italian Centers and 44 from Frankfurt, Germany. In cultured mononuclear cells from peripheral blood, PACs were counted as double-stained by tetramethylindocarbocyanine-labeled acetylated LDL and fluorescein-5-isothiocyanate–labeled lectin. Mean age of the patients was 62 years, 12 were females, 66 had ischemic etiology, 26 were in New York Heart Association Class >II. Cutoffs for PACs were assessed by receiver operating characteristic curves, to identify the optimal cutoffs for PAC level in predicting outcomes. Mean level of PACs was 35 ± 29 (mean ± SD) cells/mm², 2- to 3-fold lower than in age-matched healthy volunteers, but unrelated to severity of HF, age, or sex. Over 2.5 years, 12 cardiovascular deaths and 47 first hospitalizations for cardiovascular reasons were recorded. After adjustment for demographic and clinical variables, elevated creatinine and natriuretic peptides, and PACs ≤30.5/mm² were associated with a 2-fold higher risk of cardiovascular death and hospitalization, as shown by survival curves and by Cox multivariable.ConclusionsThe level of circulating PACs is an independent predictor of cardiovascular death and hospitalization in patients with chronic HF, it can be assessed in blood samples collected in a multicenter setting, and may offer an accessible tool to assess the role of vascular regeneration in patients with HF.     

Rare small bowel obstruction: Right paraduodenal hernia. Case report

INTRODUCTIONParaduodenal hernia (paramesocolic hernia), a rare congenital anomaly due to a midgut malrotation during fetal development, is recognized as the most frequent internal hernias. Two variants have been described: left and right, the latter less common than the first one.PRESENTATION OF CASEWe report a right paraduodenal hernia case in a 86 years old female patient who developed an acute bowel obstruction syndrome. Final diagnosis was achieved by imaging techniques as abdomen X-ray and CT and confirmed only after surgical operation.DISCUSSIONSurgical approach was via median laparotomy, consisting in hernia reduction, replacement and stitching of the bowel in its anatomical orientation, and fixing of the posterior wall defect. At 15 months follow-up from surgical procedure the patient is asymptomatic.CONCLUSIONParaduodenal hernia is a rare pathology but its involvement in bowel obstruction syndrome should be always taken into account during diagnostic process.     

Neural substrates for observing and imagining non-object-directed actions

The present fMRI study was aimed at assessing the cortical areas active when individuals observe non-object-directed actions (mimed, symbolic, and meaningless), and when they imagine performing those same actions. fMRI signal increases in common between action observation and motor imagery were found in the premotor cortex and in a large region of the inferior parietal lobule. While the premotor cortex activation overlapped that previously found during the observation and imagination of object-directed actions, in the parietal lobe the signal increase was not restricted to the intraparietal sulcus region, known to be active during the observation and imagination of object-directed actions, but extended into the supramarginal and angular gyri. When contrasting motor imagery with the observation of non-object-directed actions, signal increases were found in the mesial frontal and cingulate cortices, the supramarginal gyrus, and the inferior frontal gyrus. The opposite contrast showed activation virtually limited to visual areas. In conclusion, the present data define the common circuit for observing and imagining non-object-directed actions. In addition, they show that the representation of non-object-directed actions include parietal regions not found to be involved in coding object-directed actions.     

Edinburgh Cognitive and Behavioural ALS Screen (ECAS)-Italian version: regression based norms and equivalent scores

Cognitive assessment for individuals with Amyotrophic Lateral Sclerosis (ALS) can be difficult because of frequent occurrence of difficulties with speech, writing, and drawing. The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) is a recent multi-domain neuropsychological screening tool specifically devised for this purpose, and it assesses the following domains: executive functions, social cognition, verbal fluency and language (ALS-specific), but also memory and visuospatial abilities (Non-ALS specific). ECAS total score ranges from 0 (worst performance) to 136 (best performance). Moreover, a brief caregiver interview provides an assessment of behaviour changes and psychotic symptoms usually associated with ALS patients. The aim of the present study was to provide normative values for ECAS total score and sub-scores in a sample of Italian healthy subjects. Two hundred and seventy-seven Italian healthy subjects (151 women and 126 men; age range 30–79 years; educational level from primary school to university) underwent ECAS and Montreal Cognitive Assessment (MoCA). Multiple linear regression analysis revealed that age and education significantly influenced performance on ECAS total score and sub-scale scores. From the derived linear equation, a correction grid for raw scores was built. Inferential cut-off scores were estimated using a non-parametric technique and equivalent scores (ES) were computed. Correlation analysis showed a good significant correlation between adjusted ECAS total scores with adjusted MoCA total scores (r _rho = 0.669, p < 0.0001). The present study provided normative data for the ECAS in an Italian population useful for both clinical and research purposes.     

Effects of fenoterol on oxygen transport in patients with chronic airflow obstruction

A rise in cardiac output and a fall in arterial oxygen tension are well known side effects of bronchodilator drugs, particularly beta-adrenergic agonists. In recent years, fenoterol (Berotec), an effective beta-adrenergic agonist, has been used at increasing rates in asthmatic subjects, as well as in patients with chronic obstructive pulmonary disease (COPD). The effects of fenoterol on systemic hemodynamics or arterial oxygenation (or both) in patients with COPD have not been investigated; in these individuals, who often have increased sympathetic tone and hypoxemia even at rest, cardiovascular stimulation and a fall in arterial oxygen tension would be particularly undesirable side effects. In 14 patients with COPD (seven without a reversible component of airflow obstruction [group 1]; and seven with a reversible component of airflow obstruction [group 2]), we studied all of the important parameters of oxygen transport before and 60 minutes after administration of fenoterol. Studies were performed at rest and after exercise. At baseline, group 1 showed a faster heart rate, a lower cardiac output, a lower arterial oxygen flow, a wider arteriovenous oxygen content difference (C[a-v]O2), and a higher fraction of oxygen extracted by the tissues from a given arterial oxygen flow. In both groups, all measured parameters, including cardiac output and arterial oxygen pressure (PaO2) remained statistically unchanged one hour after administration of fenoterol; with exercise, the heart rate, blood pressure, minute ventilation, oxygen consumption, C(a-v)O2, and the percentage of oxygen extracted from arterial oxygen flow, as well as cardiac output and PaO2, increased in all instances; the exercise responses were not affected by the drug. These results suggest that at the time of its maximal effect on the airways (60 minutes), fenoterol has no untoward effect on the oxygen transport system, at rest or during exercise, in patients with COPD with or without a reversible component.