Tarcisio Niglio

Obesity and the metabolic syndrome in a student cohort from Southern Italy

BACKGROUND AND AIM Cardiovascular (CV) risk factors present in childhood predict future CV events. Few data regarding the metabolic syndrome (MS) prevalence are available in adolescents from Mediterranean areas where obesity is becoming a social emergency. This study presents data of MS prevalence in a student cohort from southern Italy. METHODS AND RESULTS 1629 students between 7 and 14 years of age underwent anthropometric measurements and a blood sample was obtained to assess biochemical parameters. MS risk factors were calculated based on age and gender adjusted percentiles of parameter distributions. MS prevalence rate was 0.022 using paediatric, age-adjusted criteria; the rate increased to 0.029 using a 90th percentile criteria for fasting blood glucose instead of >100mg/dL. Using the criteria issued by the International Diabetes Federation the MS prevalence rate dropped to 0.005. The exploratory factor analysis identified four factors: age/fat related, lipids, blood pressure and blood glucose. Family history of type 2 diabetes mellitus was associated with triglyceride [OR=1.55 (1.0-2.3)] and BMI [OR=1.71 (1.2-2.4)] but not to blood glucose by logistic regression analysis. CONCLUSIONS In a student cohort from Southern Italy, obesity is associated with the features of MS.

Low dose chromium-polynicotinate or policosanol is effective in hypercholesterolemic children only in combination with glucomannan.

OBJECTIVE A low-fat, fiber-rich diet is the first step in the management for hypercholesterolemic children. Glucomannan (GM) is a natural fiber that has been demonstrated to lower total and LDL-cholesterol. The use of high-dose chromium-polynicotinate (CP) and policosanol (PC) has also shown cholesterol-lowering benefits. We aimed at investigating the effects of low-dose CP or PC and their GM combination in hypercholesterolemic children. METHODS A double-blind trial was conducted in 120 children (60 M, 60 F, 9 ± 4 years, median 9.6 years, range: 3-16 years) randomly assigned to 5 neutraceutical and 1 placebo (only resistant starch) 8-week treatment groups. Fasting blood glucose (FBG), total cholesterol (CholT), triglycerides (TG), HDL and LDL cholesterol were considered. RESULTS GM combination of low-dose CP or PC reduced CholT and LDL without changing HDL, TG and FBG. The highest post-treatment changes were seen after GM combination with CP (CholT 85 ± 3% and LDL 85 ± 5%, of pretreatment) which was significantly (p < 0.01) less than with low-dose CP or PC and starch. When GM was associated with starch, there was no lipid lowering effect, which was an unexpected finding as compared to previous data with GM and no starch. No adverse effects were reported. CONCLUSION This is the first report to show the cholesterol-lowering efficacy of GM combined treatment with low-dose CP or PC. Further studies are needed to investigate the best combinations and doses of nutraceutics to be added to the standard GM treatment. The potential negative association of GM and nutraceutics with starch is clearly shown.

Nucleus basalis magnocellularis lesions impair mossy fiber system in rat hippocampus: a quantitative histochemical and ultrastructural study

Lesions of the nucleus basalis magnocellularis (NBM) cause depletion of choline acetyltransferase (ChAT) in the cerebral cortex and behavioral changes consisting of impaired ability to learn avoidance tasks. Since hippocampal mossy fibers (MF) are involved in the elaboration of passive avoidance responses, we analyzed MF by means of Timms histochemical technique and electron microscopy, to find out whether monolateral lesions of NBM had any effect on MF system. NBM-lesioned rats, 3 weeks after lesioning, showed a significant and progressive decrease in the density of Timm staining as well as significant changes of the morphology of synapic boutons of the MF. These results suggest that, although NBM does not send direct projections to the hippocampus, lesions of this nucleus may have a neurodegenerative effect on the intrahippocampal pathway involved in avoidance responses.

An investigation on the mechanism of anticonvulsant action of ketamine and phencyclidine on convulsions due to cortical application of penicillin in rabbits

The intracortical injection of 500 units of penicillin in rabbits elicited intermittent bilateral spikes or spike-wave complexes followed by generalization of the epileptiform activity characterized by repeated ictal high-voltage, high frequency spikes paralleled by generalized convulsions. Administration of phencyclidine (PCP) (0.7-1.0 mg/Kg i.v.), ketamine (KT) (20-40 mg/Kg i.v.), pentobarbital (PB) (10 mg/Kg i.v.) and diazepam (3 mg/Kg i.v.) inhibited the generalization of the epileptiform activity induced by penicillin (500 units) counteracting the EEG and motor patterns of the ictal events, while did not influence the interictal spike-and-wave complexes. Physostigmine (0.1 mg/Kg i.v.), clonidine (0.1 mg/Kg i.v.), haloperidol (1 mg/Kg i.v.) and naloxone (10 mg/Kg i.v.) did not affect the inhibitory influence of PCP on epileptiform activity due to cortical application of penicillin. Thus, the mechanism of this anticonvulsant action of PCP seems not to depend on the neurotransmitter system related to the reported drugs. The mechanism of action of PCP and KT is discussed in connexion with the similarities of the effects of this drugs in respect to sigma opiate agonists and pentobarbital.

Absence of Right-Left Asymmetries in the Rat Hippocampus as Demonstrated by Timm Staining

Although biochemical and behavioural studies have shown right-left differences in several areas of the rat limbic system, some anatomical studies reported no significant right-left differences in several morphological parameters of the hippocampus. The purpose of the present study was to determine whether there are asymmetries in the micro-anatomy of the rat hippocampus by examining the intensity of Timm staining in various hippocampal fields and the area occupied by mossy fibres by the use of combined microdensitometric and quantitative image analysis techniques. Timm staining demonstrates the distribution of intrahippocampal association pathways because it is a histochemical marker of zinc and other heavy transition metals. There were no right-left differences in the density of Timm staining at the level of the dentate gyrus, in the dendritic layer of CA1 and CA2 fields, in the mossy fibre area or in the subiculum. These findings provide further evidence of a lack of morphological asymmetry in the rat hippocampus.

Muscarinic cholinoceptor subtypes in the rat frontoparietal cortex after ipsilateral lesions of the nucleus basalis magnocellularis.

Muscarinic cholinoceptor subtypes (M1 and M2) were studied in membrane particles of the rat frontoparietal cortex 72 h and 1, 2, 3, and 4 weeks after ipsilateral lesioning of the nucleus basalis magnocellularis (NBM). The affinity of the ligand used to characterize muscarinic cholinoceptors, 3H-quinuclidinyl benzilate did not significantly change in lesioned compared with sham-operated rats as well as the density of high affinity (M1) sites. Low affinity muscarinic cholinoceptors (M2 sites) were significantly decreased in NBM-lesioned rats 72 h and 1 week after lesioning. The density of M2 sites did not significantly differ in lesioned rats 2 or 3 weeks after NBM lesioning, but increased, in comparison with sham-operation 4 weeks after NBM lesioning. These findings suggest that frontoparietal M2 muscarinic cholinoceptors, which probably have a presynaptic localization, are sensitive to NBM lesions. Their changes at different times after NBM lesioning suggest the occurrence of loss, compensation and upregulation of cholinergic projections arising to the neocortex from the NBM.

Antiepileptic effects of N6-L-phenylisopropyladenosine (L-PIA) on penicillin-induced epileptogenic focus in rabbits.

In the present work the effects of a stable analog of adenosine (N-6-L-phenylisopropyladenosine, L-PIA) have been investigated against the epileptic focus induced by intracortical injection of penicillin. The intracortical (i.c.) injection of penicillin (300 units) in rabbits elicits an epileptiform EEG and motor activity. Pretreatment with L-PIA (1.5 mg/kg i.v.) prevents the motor component of the epileptic phenomenon, while the EEG seizures are unaffected. The i.c. injection of L-PIA (20 nMoles in the left cortex), 10 minutes before penicillin (300 units in the right cortex) prevents the spreading of the epileptic activity from the right to the left hemisphere. These results suggest that adenosine might regulate the spreading of seizures. The possible role played by adenosine in the spontaneous arrest of epilepsy has also been discussed.

Effect of choline alfoscerate treatment on changes in rat hippocampus mossy fibres induced by monolateral lesioning of the nucleus basalis magnocellularis

We have recently demonstrated that monolateral lesions of the Nucleus Basalis Magnocellularis (NBM), which is a nucleus sending cholinergic projections to the fronto-parietal cortex, cause a loss in the intensity of Timm staining in the intrahippocampal pathway of mossy fibres (MF). Moreover, these lesions induce ultrastructural changes consistent with the occurrence of degeneration of presynaptic buttons of MF. The present study was designed to quantify the effects of NBM lesioning on the morphology of the presynaptic buttons of MF. Moreover the effects of 4-week choline alfoscerate (alphaGFC) treatment on the density of Timm staining and on the ultrastructure of presynaptic buttons of MF were assessed, alphaGFC, which was given at an oral daily dose of 100 mg/kg, is a precursor in the biosynthesis of several brain phospholipids which increases the availability of choline in the nervous tissue. Monolateral lesions of NBM cause, 4 weeks after lesioning, a significant decrease in the intensity of Timm staining in the MF area accompanied by a loss of about 23% of presynaptic buttons of MF. Moreover about 40% of presynaptic buttons of MF show an impaired morphology. alphaGFC administration restored the intensity of Timm staining in the MF area. In alphaGFC-treated rats, the loss of presynaptic buttons and the number of impaired buttons were reduced to about 12% and 27%, respectively in comparison with non-treated animals. These results confirm and extend our previous observations indicative of the occurrence of transneuronal degenerations in the MF of the hippocampus after monolateral NBM lesioning. Moreover these findings show that alphaGFC treatment is able to counter in part these degenerative changes.

Changes in the intensity of sulfide staining in fronto-parietal cortex of the rat following nucleus basalis magnocellularis lesions: possible relevance to Alzheimer's disease.

The sulfide staining technique, known also as neo-Timm staining, predominantly stains associational fibres arising from cortical interneurons located primarily in the neuropil of layers I-III of the rat cerebral cortex. The density of these fibres, considered to have a possible role in cognitive and mnemonic processes, has been demonstrated to be related to the density of zinc-containing presynaptic buttons in the cerebral cortex. The unilateral injection of ibotenic acid into the nucleus basalis magnocellularis (NBM) resulted in no changes in the density of sulfide staining in the first 3 weeks after neurotoxin injection and in a significant loss of sulfide staining in the neuropil of cortical layers I-III 4 weeks after NBM lesion in the fronto-parietal cortex ipsilaterally to the lesion. These data suggest that unilateral lesioning of the NMB may cause changes of chemo-specific zinc-containing intracortical pathways. Moreover, they indicate that, in a manner similar to that described in the brain of Alzheimers disease patients, NBM-lesioned rats show a decrease of zinc tissue stores in the fronto-parietal cortex.

increased size of third ventricle in patients with multiple sclerosis and chronic cerebrospinal venous insufficiency

Objective: The aim of the present study was to assess the size of the third ventricle in a sample of patients with multiple sclerosis (MS) affected by chronic cerebrospinal venous insufficiency (CCSVI), versus size of the third ventricle in a healthy control group. Background: CCSVI, a new nosological vascular pattern, has recently been associated with MS. Methods: We enrolled 33 patients affected by MS (three in the primary progressive clinical course, 23 in the relapsing–remitting clinical course, and seven in the secondary–progressive clinical course). All patients had been affected by CCSVI and were tested using an echo color Doppler (ECD) imaging unit. The group of 33 affected by both MS and CCSVI (MS–CCSVI) was composed of 19 females and 14 males with a mean age of 40±10 years, from a minimum age of 20 years to a maximum age of 66 years, with a median of 40 years and a mode of 32 years. We compared the 33 MS–CCSVI patients with 33 healthy control subjects of similar sex and age. In the MS–CCSVI group, the MS clinical severity was expressed by expanded disability status scale (EDSS) score: light (19 patients, scoring 1, 2, or 3); medium (ten patients with a score of 4, 5, or 6), and severe (four patients with a score of 7, 8, or 9). The average duration of the MS was 10±7 years (from a minimum of 1 to a maximum of 26 years, with a median of 10 years and a mode of 1 year). Results: In the MS–CCSVI group, the third ventricle diameter was 6.2±1.7 mm (from a minimum of 2.5 mm to a maximum of 9.2 mm, with a median of 6.3 mm, and a mode of 6.0 mm). Our data showed that 29 patients (88%) had an increase in third ventricle diameter, whereas only four patients (12%) had physiological size (less than 4 mm) comparable to all healthy control group subjects (27.28%). These results show that the increase in the third ventricle diameter could represent a criterion of positivity of neurological disease in patients with CCSVI.