Novel therapeutic approaches based on the pathological role of gut dysbiosis on the link between nonalcoholic fatty liver disease and insulin resistance.

The growing global epidemic of obesity and type 2 diabetes mellitus has determined an increased prevalence of NAFLD (non-alcoholic fatty liver disease), making it the most common chronic liver disease in the Western world and a leading cause of liver transplantation. In the last few years, a rising number of studies conducted both on animal and human models have shown the existence of a close association between insulin resistance (IR), dysbiosis, and steatosis. However, all the mechanisms that lead to impaired permeability, inflammation, and fibrosis have not been fully clarified. Recently, new possible treatment modalities have received much attention. To reach the review purpose, a broad-ranging literature search on multidisciplinary research databases was performed using the following terms alone or in combination: "NAFLD", "gut dysbiosis", "insulin resistance", "inflammation", "probiotics", "Chinese herbs". The use of probiotics, prebiotics, symbiotics, postbiotics, fecal microbiota transplant (FMT), Chinese herbal medicine, antibiotics, diet (polyphenols and fasting diets), and minor therapies such as carbon nanoparticles, the MCJ protein, water rich in molecular hydrogen, seems to be able to improve the phenotypic pattern in NAFLD patients. In this review, we provide an overview of how IR and dysbiosis contribute to the development and progression of NAFLD, as well as the therapeutic strategies currently in use.

Dynamic monitoring of restricted eating disorders by indirect calorimetry: a useful cognitive approach.

OBJECTIVE: Outpatient treatment in restricted eating disorder: indirect calorimetry during dynamic monitoring. DESIGN: A retrospective observational study. SUBJECTS: Twenty seven women affected by restricted eating disorder (essentially anorexia nervosa) with a body mass index [weight (kg)/height (m2)] of 17.29+/-2.47 were studied. The sample was compared as itself control during rehabilitative way. INTERVENTIONS: Fat mass (FM) and fat free mass (FFM) were determined by anthropometry technique. REE/day and respiratory quotient (RQ,VCO2/VO2) were measured by indirect calorimetry using a Calorimeter Vmax 29n-Sensor Medics-California. Skinfold thickness and circumferences were also measured. Arm muscle area (AMA) and fat area were calculated by formulas reported in Frisancho. RESULTS: The data indicated a positive correlation between AMA, VO2/ml/min and resting energy expenditure (REE)/day values examined during follow-up of patients. The increase of these parameters indicated a good monitoring index correlated to a FFM recovery during psychonutritional rehabilitation. CONCLUSION: Indirect calorimetry represents a useful approach for determining REE and prescribing diets in these patients. Moreover, the combined use of anthropometric techniques allows to accurately assess and adjust therapy according to the patient's progress. This study shows that restricted eating disorders are characterized by a recovery of FFM related to improvement of body weight and REE/day. On the contrary, the increase of AFA revealed a recovery of fat-metabolism (corresponding to RQ decrease) and lipid/carbohydrates oxidation improvement, only in the presence, at the same time, of O2 consumption increase.

The abnormality of N30 somatosensory evoked potential in idiopathic Parkinson's disease is unrelated to disease stage or clinical scores and insensitive to dopamine manipulations.

We recorded short latency somatosensory evoked potentials (SEPs) to median nerve stimuli in 40 patients affected by idiopathic Parkinson's disease (PD) classified from I to IV on the Hoehn and Yahr disability scale. SEPs were recorded before and after chronic administration of L-Dopa and bromocriptine, before and after acute administration of L-Dopa. Fourteen patients experiencing wearing off and dystonic-dyskinetic disturbances were recorded during the occurrence of these oscillations of their clinical status. Absent or reduced N30 components were found in 32.5% of patients. SEPs were not modified by acute or chronic administration of L-Dopa or bromocriptine or during off and dystonic or dyskinetic conditions. Multiple correlations of N30 with scores of the Unified Parkinson's Disease Rating Scale showed that N30 abnormality did not classify patients with prominent clinical features, nor did it predict the outcome of treatment.

Source model and scalp topography of pattern reversal visual evoked potentials to altitudinal stimuli suggest that infoldings of calcarine fissure are not part of VEP generators.

Visual evoked potentials (VEPs) to pattern reversal vertical bar stimuli were recorded from 19 scalp, 2 zygomatic and 3 inion derivations referenced to digitally linked earlobes in 50 controls. 1, 2 and 4 cycles per degree (cpd) patterns were presented as full field (FF) stimuli, on upper and lower hemifields (UHF-LHF), upper and lower quadrants and with the occlusion of central and peripheral UHF and LHF. VEPs to octant stimuli were also recorded with 2 cpd patterns. N1, P1 and N2 components were recorded from posterior and inion derivations with FF stimuli, from posterior derivations with LHF stimuli, only from inion leads with UHF stimuli, from derivations ipsilateral to stimuli with quadrants and octants, and from midline derivations only with lower quadrants. Polarity inverted sequences (iP1-iN1-iP2) were recorded from the other scalp derivations, with similar latency and spatial frequency sensitivity as N1-P1-N2. The orientation of Equivalent Dipoles (ED) was orthogonal with surface coordinates of mesial and occipito-polar calcarine cortex, measured on Magnetic Resonance Imaging. A model of VEP generators is proposed, suggesting that the VEP sequence is elicited only in mesial and occipito-polar surfaces of calcarine cortex.

Effects of drug manipulations on anterior components of somatosensory evoked potentials in a parkinsonian animal model.

Somatosensory Evoked Potentials (SEPs) to median nerve stimuli were recorded in seven Cynomolgus monkeys before and after the induction of the MPTP-parkinsonian syndrome. SEPs recorded after the onset of parkinsonism showed a significant amplitude reduction of an anterior negative component peaking at about 15 ms (N15), independent of the severity of symptoms. The amplitude decrease was not reversed by the administration of I-dopa, despite clinical improvement, or cholinergic, noradrenergic and gabaergic agents. Amplitudes of N15 and of parietal P15 components were increased by the administration of the N-MDA antagonists ketamine and MK 801, and markedly increased when monkeys were given the anaesthetic agent etomidate. The present study shows that the reduced N15 SEP component of parkinsonian monkeys is similar to the reduced frontal N30 SEP component evidenced by other authors in patients affected by Parkinson's disease. The attenuation of N15 is not related to deficitary dopaminergic, noradrenergic, cholinergic and gabaergic systems. The implications of this finding and the role of glutamate toxicity are discussed.

Focal abnormalities of P3 ERPs unveiled in patients with cortical lesions and primary progressive aphasia by average reference recordings.

Event related potentials (ERPs) to an auditory odd-ball paradigm were recorded with the linked earlobe reference (LER) and with a computer calculated average reference (AR), excluding the two linked earlobe derivations. The study was performed in 30 patients with lesions of frontal, parietal, occipital cortex, unilateral and bilateral lesions of the medial temporal lobe (MTL), in four patients affected by Primary Progressive Aphasia (PPA) and in 56 age matched controls. Latencies, amplitudes and scalp distribution of the earlier ERP components (P1, N1, P2, N2) were within normal limits for both LER and AR recordings. P3 scalp distribution in patients was normal when LER was used, with the exception of two patients affected by bilateral MTL lesions. When P3 was recorded using AR, the scalp distribution was statistically different from normal distributions in all patients. A negativity, instead of the positive P3 observed in controls, was recorded in patients from leads corresponding to the affected areas. This finding might have clinical applications, and confirms earlier studies suggesting that P3 is generated simultaneously from different cortical areas.

Comparison of event related potentials (ERPs) distributions obtained with three reference systems: linked binaural, mean reference, extracephalic.

Event related potentials (ERPs) to auditory and visual oddball paradigms were recorded from 19 scalp derivations in 10 controls. Three different reference systems were used: the linked earlobes (LE), the computer calculated mean reference (MR), and a calibrated sterno-vertebral extracephalic reference (EC). The distribution of ERPs was represented on single plane maps (quadratic interpolation, 4-NN method). With LE reference N2, P3a-P3b had no polarity reverted counterparts on the scalp. With EC reference a negativity was recorded on T3-T4 (and partly T5-T5) derivations with the same latency as P3a-P3b vertex component. With MR the N2, P3a-P3b components at vertex were paralleled by polarity reverted counterparts on anterior frontal, temporal and occipital derivations.

Memory and naive CD4+ lymphocytes in multiple sclerosis.

Helper-inducer (CD29+CD4+) and suppressor-inducer (CD45RACD4+) T-cells have been recently renamed as memory and naive T-cells, respectively. We measured cells expressing these phenotypes in peripheral blood of 46 definite multiple sclerosis (MS) patients [32 relapsing-remitting (RR-MS), 14 secondary progressive (P-MS)] and controls. CD25+ (interleukin-2-receptor-positive) cells were also evaluated in the same groups of patients. RR-MS patients showed increased levels of CD29+CD4+ and CD25+ cells compared with controls. This finding was more evident in RR-MS patients during the attack than during the stable phase of the disease. In P-MS patients we found a reduction of CD45+CD4+ cells compared with either RR-MS patients or control subjects. Our results show that RR-MS and P-MS are characterized by two different T-cell subpopulations. This finding supports the hypothesis that during the evolution from RR-MS and P-MS changes occur in the immunological status of the patients.

P3 recordings in patients with bilateral temporal lobe lesions.

We recorded event-related potentials to an acoustic "oddball" paradigm from 19 scalp derivations in five patients (three women and two men; age range, 44 to 56) who had global amnesia following encephalitis. CT and MRI showed severe bilateral lesions of anterior and midtemporal lobes. A P3 component, with a peak latency within the normal limits for age-matched controls, was recorded to "target" stimuli in four patients from all leads except Fp1, Fp2, F7, F8, T3, and T4. In the fifth patient, the P3 peak was delayed.

Delayed P3 event-related potentials (ERPs) in thalamic hemorrhage.

Delayed P3 ERPs were recorded with an acoustic oddball paradigm in 5 patients affected by unilateral thalamic hemorrhage. P3 latencies in these 5 patients were above the normal mean latency of age-matched controls +2/+3 S.D.s. The P3 delay was persistent in serial follow-ups at 6 months from stroke. Normal P3 latencies were instead recorded in 4 patients with paramedian hemorrhage not involving or only partially involving the thalamus.

Evoked potentials (EPs) in experimental allergic encephalomyelitis: a study of EP modifications during the course of a controlled disease.

24 juvenile strain 13 guinea pigs were sensitized with homologous spinal cord homogenate in complete Freund's adjuvant in order to obtain Experimental Allergic Encephalomyelitis (EAE) in the Chronic Relapsing (CR-EAE), Chronic Progressive (CP-EAE) and Acute (A-EAE) forms. Visual, Brain-Stem Acoustic, Somatosensory Evoked Potentials were recorded in these animals, prior to the sensitizing injection and during the course of the disease. The aim of our study was to observe modifications of Evoked Potentials during progression of a demyelinating disease. Latency delays of Evoked Potentials appeared 15 days after the sensitizing injection, preceding or simultaneously with clinical alterations and when demyelinated plaques were not detected in anatomical specimens.

Three-dimensional transcranial Doppler in acute ischemic stroke in the territory of the middle cerebral artery: clinical and CT correlation.

We studied 34 patients with acute ischemic stroke in the territory of the middle cerebral artery (MCA) by three-dimensional transcranial Doppler (TCD-3D). The parameters analyzed were: mean blood flow velocity, systolic and diastolic velocities; indices of pulsatility, hemisphere asymmetry and pulsatility transmission. Of the 34 patients 11 presented marked slowing of flow velocity in the MCA on the infarct side with an asymmetry index (AI) of over 40%, 8 patients with slightly reduced flow velocity in the MCA and an AI of 25-40%, 2 patients in whom there was indirect evidence of collateral circulations in the anterior cerebral artery distribution together with slowing of MCA flow; 5 patients had stenosis of the MCA, 9 patients showed no alterations of the Doppler parameters. The correlation between neurological symptom pattern and AI was significant (r = 0.76). Noninvasive, easy to perform, performable at once and reliable, TCD-3D is a great improvement on traditional transcranial Doppler and is especially useful in assessing the hemodynamics of the cerebral circulation in ischemic stroke.

Multiple sclerosis: an immune system activation disease.

Two-color flow-cytometric analysis on peripheral blood lymphocytes of 46 untreated multiple sclerosis patients (MS), 36 other medical disease patients (OMD) and 19 healthy control subjects (HC) was performed to know the relationships between T and B cell subpopulations. In MS patients we observed an increase of total lymphocyte count and an increase of CD4+CD29+ cells, which are adjuvant to B cell in antibody production. We hypothesized this change is related to the reduction of CD21+ cells, expressing B2 antigen which disappears after B cell activation. The unperfect balance of immune system in MS was also demonstrated by the increased level of CD25+ cells in relapsing-remitting patients and by the decreased level of CD4+ CD45RA+ (suppressor inducer) cells in progressive patients.

Reduction of P3 latency during outcome from post-traumatic amnesia.

We studied 10 patients with post-traumatic amnesia (PTA) and normal CTscans. P3 with an oddball paradigm, several neuropsychological tests and EEG were performed the day after the trauma and several times later until full recovery. In all patients, P3 latencies at admission were above normal limits (mean + 2 SDs) and decreased progressively during recovery from PTA. The latency reductions correlated significantly with improvement of neuropsychological tests.

Mapped distribution of pattern reversal VEPs to central field and lateral half-field stimuli of different spatial frequencies.

Visual evoked potentials (VEPs) to pattern reversal vertical bar stimuli of 3 different sizes (1, 2, 4 c/deg) were recorded from 19 scalp derivations in 50 controls. The stimuli were presented on a full-field (FF) screen of 24 degrees visual angle, and on left and right half-fields (HF) of 12 degrees radius. In 15 controls partial HF stimuli were presented on the central 3 and 6 degrees and as hemiannular stimuli of 12 degrees with occlusion of the central 3 and 6 degrees. An antero-posterior polarity reversal of the N1-P1-N2 sequence was observed for FF VEPs. A tangential polarity reversal was observed for HF VEPs. Also with central or hemiannular stimuli polarity reversals of all VEP components were observed within the scalp. Variants of VEP distribution, absence or prominence of some of the ipsi- or contralateral VEP components were observed in 8-40% of controls. The FF and HF VEP distribution, and the variant VEP asymmetries were partly dependent on the pattern spatial frequency.

Mapping of event-related potentials to auditory and visual odd-ball paradigms in patients affected by different forms of dementia.

The paper reports the results of recordings and maps of event-related potentials (ERPs) in patients with Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and in subjects affected by dementia in multiple sclerosis (MS). ERPs were recorded from 19 scalp electrode derivations using both visual and acoustic paradigms. In 43% of AD patients, ERPs were normal; in 20%, although present, ERP components were delayed, while in the other 37% none of the N2 and P3 peaks could be recorded, because of abnormal topography of potentials on the scalp. In patients with PSP, the normal ERP sequence was not identified. In patients with MS delayed ERPs (50%), abnormal topography of ERPs (30%) and absence of ERPs (20%) were observed. The follow-up of AD patients showed a progressive alteration of ERPs. ERP topography alterations were observed in AD, PSP and MS patients with poorest cognitive performances.

Maps of somatosensory evoked potentials (SEPs) to mechanical (tapping) stimuli: comparison with P14, N20, P22, N30 of electrically elicited SEPs.

Bit mapped color imaging of SEPs was recorded from 19 derivations in 11 healthy volunteers after electrical stimulation of the median nerve at the wrist, index finger digital nerve stimulation, and mechanical stimulation of the index fingertips by an electromechanically driven vibrating thin metallic plate. The latencies of SEP components increased for the various stimulation modalities, being shortest after median nerve stimulation at the wrist and longest after mechanical stimulation of the index fingertips. The scalp distribution of SEPs to mechanical stimuli was, however, the same as other SEPs, independently of the stimulation employed, and components corresponding to N20 and P22 were recorded only contralaterally to the stimulated side.

Mapping of event-related potentials to auditory and visual odd-ball paradigms.

This paper reports the results of recordings and maps of event-related potentials (ERPs) obtained in normal subjects, patients with Alzheimer's disease (AD), progressive supranuclear palsy, confusional states, and in subjects with homonymous hemianopsia. ERPs were recorded from 19 scalp electrode derivations using both visual and acoustic paradigms. In normal subjects, the topographical distribution of all ERP components is described in detail. In 45% of AD patients, ERPs were normal; in 35%, although present, ERP components were delayed, while in the other 20% the N2 and P3 peaks could not be recorded. In patients with progressive supranuclear palsy, the normal ERP sequence was not identified. Our findings in normals and in hemianopic patients suggest that the early modulation of stimulus-related potentials could be located in primary associative areas, and that N2, P3a, P3b, SW should have different origins.

[The sympathetic skin response: neurophysiological basis, normal values, clinical applications]. / La riposta simpatica cutanea: basi neurofisiologiche, valori normativi, applicazioni cliniche.

The sympathetic skin response (SSR) represents the momentary change in skin potential reflexively evoked by a variety of arousal stimuli. Although sudomotor unmyelinated fibres are the final efferent pathway of SSR, little is known about the afferent and central components. SSR was recorded using different classes of stimuli in 20 controls, 15 peripheral neuropathy and 13 stroke patients. In controls SSR latencies changed significantly with different recording sites but not with different stimulation sites. Additionally, ischemic conduction block of the arm abolished SSR recorded at the hand after median nerve stimulation. In 1 patient with subacute ganglionitis and in 3 with demyelinating neuropathies the SSR could be elicited with deep inspiration but not by electric stimulation. These results suggest that myelinated fibres serve as afferents for SSR. In stroke patients SSR was absent bilaterally after stimulation of the paralyzed side but present after stimulation of the normal one. Therefore in humans the cortex seems to have a suprasegmental excitatory influence on SSR. The above findings imply that an unobtainable SSR by electric stimulation may be due not only to dysfunction of the autonomic efferent nerve fibers, but also to involvement of sensory afferents or suprasegmental structures.