Pieranna Arrighi

Microalbuminuria and renal haemodynamics in essential hypertension

The present study was designed to evaluate the renal haemodynamic pattern of never‐treated microalbuminuric and normoalbuminuric patients with essential hypertension. A total of 19 never‐treated essential hypertensive patients with microalbuminuria were selected and, as control subjects, 24 never‐treated essential hypertensive patients without microalbuminuria (determined on three 24‐h urine collections) were recruited. In the two groups, we compared blood pressure values, standing plasma noradrenaline, plasma renin activity, plasma aldosterone, urinary aldosterone, lipid profile, serum glucose and uric acid, glomerular filtration rate and renal plasma flow. In comparison with normoalbuminuric patients, microalbuminuric patients showed significantly higher systolic blood pressure values (P < 0.05), higher renal vascular resistances (P < 0.05) and lower plasma renin activity values (P < 0.01). Urinary albumin excretion showed a significant positive correlation with systolic (r = 0.46, P < 0.005) and mean blood pressure (r = 0.38, P < 0.05), serum uric acid (r = 0.43, P < 0.005) and triglyceride values (r = 0.36, P < 0.005), and a significant negative correlation with plasma renin activity (r =  − 0.34, P < 0.05). The present data are consistent with the occurrence of renal vasoconstriction in microalbuminuric never‐treated essential hypertensive patients.

Lack of correlation between microalbuminuria and endothelial function in essential hypertensive patients.

Objective: To evaluate whether microalbuminuria, defined as urinary albumin excretion between 30 and 300mg/24h, is associated with endothelial dysfunction in essential hypertensive patients. Design: We correlated urinary albumin excretion with vasodilatation in response to endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) agonists in the forearm vascular bed in essential hypertensive patients with (n=13) and without (n=23) microalbuminuria and matched normotensive controls (n=21). Method: We studied forearm vascular responses (strain-gauge plethysmography) to intrabrachial infusion of acetylcholine (0.15, 0.45, 1.5, 4.5 and 15 ng/100 ml forearm tissue/min) and of sodium nitroprusside (1, 2, 4 ng/100 ml forearm tissue per min). Minimal forearm vascular resistances (the ratio between mean arterial pressure and maximal forearm vasodilatation induced by 13 min of ischaemia + 1 min of exercise) were also evaluated. Results: Responses to acetylcholine, but not to sodium nitroprusside, were significantly blunted and minimal forearm vascular resistances were increased in hypertensive patients compared with controls. However, no correlation was found between urinary albumin excretion and vasodilatation in response to acetylcholine or to sodium nitroprusside or between urinary albumin excretion and minimal forearm vascular resistances. Conclusions: In hypertensive patients, increased urinary albumin excretion is associated neither with functional nor with structural dysfunction in the forearm vasculatur

Cortical source of blink-related delta oscillations and their correlation with levels of consciousness.

Recently, blink‐related delta oscillations (delta BROs) have been observed in healthy subjects during spontaneous blinking at rest. Delta BROs have been linked with continuous gathering of information from the surrounding environment, which is classically attributed to the precuneus. Furthermore, fMRI studies have shown that precuneal activity is reduced or missing when consciousness is low or absent. We therefore hypothesized that the source of delta BROs in healthy subjects could be located in the precuneus and that delta BROs could be absent or reduced in patients with disorders of consciousness (DOC). To test these hypotheses, electroencephalographic (EEG) activity at rest was recorded in 12 healthy controls and nine patients with DOC (four vegetative states, and five minimally conscious states). Three‐second‐lasting EEG epochs centred on each blink instance were analyzed in both time‐ (BROs) and frequency domains (event‐related spectral perturbation or ERSP and intertrial coherence or ITC). Cortical sources of the maximum blink‐related delta power, corresponding to the positive peak of the delta BROs, were estimated by standardized Low Resolution Electromagnetic Tomography. In control subjects, as expected, the source of delta BROs was located in the precuneus, whereas in DOC patients, delta BROs were not recognizable and no precuneal localization was possible. Furthermore, we observed a direct relationship between spectral indexes and levels of cognitive functioning in all subjects participating in the study. This reinforces the hypothesis that delta BROs reflect neural processes linked with awareness of the self and of the environment. Hum Brain Mapp 34:2178–2189, 2013.

Blink-related delta oscillations in the resting-state EEG: A wavelet analysis

Over the past decades, many studies have linked the variations in frequency of spontaneous blinking with certain aspects of information processing and in particular with attention and working memory functions. On the other hand, according to the theory postulated by Crick and Koch, the actual function of primary consciousness is based on the reciprocal interaction between attention and working memory in the automatic and serial mode. The purpose of this study was to investigate for electrophysiological correlates compatible with the cognitive nature of spontaneous blinking, by using the EEG recordings obtained in a group of seven healthy volunteers while they rested quietly though awake, with their eyes open, but not actively engaged in attention-demanding goal-directed behaviours. The global wavelet analysis - at total of 189 three-second EEG epochs time-locked to the blink - revealed an increase in the delta band signal corresponding to the blink. In particular, a reconstruction of the EEG signal by means of inverse-wavelet transform (IWT) showed a blink-related P300-like wave at mid-parietal site. We assumed this phenomenon to represent an electrophysiological sign of the automatic processing of contextual environmental information. This might play a role in maintaining perceptive awareness of the environment at a low level of processing, while the subject is not engaged in attention-demanding tasks but rather introspectively oriented mental activities or free association(s).

Spectral Parameters Modulation and Source Localization of Blink-Related Alpha and Low-Beta Oscillations Differentiate Minimally Conscious State from Vegetative State/Unresponsive Wakefulness Syndrome

Recently, the cortical source of blink-related delta oscillations (delta BROs) in resting healthy subjects has been localized in the posterior cingulate cortex/precuneus (PCC/PCu), one of the main core-hubs of the default-mode network. This has been interpreted as the electrophysiological signature of the automatic monitoring of the surrounding environment while subjects are immersed in self-reflecting mental activities. Although delta BROs were directly correlated to the degree of consciousness impairment in patients with disorders of consciousness, they failed to differentiate vegetative state/unresponsive wakefulness syndrome (VS/UWS) from minimally conscious state (MCS). In the present study, we have extended the analysis of BROs to frequency bands other than delta in the attempt to find a biological marker that could support the differential diagnosis between VS/UWS and MCS. Four patients with VS/UWS, 5 patients with MCS, and 12 healthy matched controls (CTRL) underwent standard 19-channels EEG recordings during resting conditions. Three-second-lasting EEG epochs centred on each blink instance were submitted to time-frequency analyses in order to extract the normalized Blink-Related Synchronization/Desynchronization (nBRS/BRD) of three bands of interest (low-alpha, high-alpha and low-beta) in the time-window of 50–550 ms after the blink-peak and to estimate the corresponding cortical sources of electrical activity. VS/UWS nBRS/BRD levels of all three bands were lower than those related to both CTRL and MCS, thus enabling the differential diagnosis between MCS and VS/UWS. Furthermore, MCS showed an intermediate signal intensity on PCC/PCu between CTRL and VS/UWS and a higher signal intensity on the left temporo-parieto-occipital junction and inferior occipito-temporal regions when compared to VS/UWS. This peculiar pattern of activation leads us to hypothesize that resting MCS patients have a bottom-up driven activation of the task positive network and thus are tendentially prone to respond to environmental stimuli, even though in an almost unintentional way.

Reciprocal dynamics of EEG alpha and delta oscillations during spontaneous blinking at rest: A survey on a default mode-based visuo-spatial awareness

By means of a narrowband wavelet analysis (0.5-6Hz), EEG delta event-related oscillations (EROs), both time- and phase-locked to spontaneous blinking (delta blink-related oscillations or delta BROs), have recently been demonstrated. On the basis of their spatiotemporal characteristics, delta BROs have been proposed as being involved in an automatic mechanism of maintaining awareness in a visuo-spatial context. The aim of the present study was: a) to investigate whether spontaneous blinking was also able to modulate alpha oscillations and, if so, b) whether this modulation was consistent with delta BROs, in order c) to acquire additional information for a better understanding of the cognitive phenomena underlying blinking. Using a broadband (0.5-100 Hz) continuous wavelet transform (CWT), we analysed a total of 189 three-second EEG epochs time-locked to the blinks of seven healthy volunteers. The EEG signals were submitted both to band-pass filtered cross-trial averaging (to obtain frequency-specific BROs) and to alpha event-related synchronization/desynchronization (i.e., blink-related synchronization/desynchronization, BRS/BRD). The alpha oscillations showed: a) an early BRS; b) a BRD in the same temporal window of the delta BROs and, c) a late BRS. We postulate that: a) the early BRS represents the short-term memory maintenance of the last visually perceived trace of the surroundings; b) the alpha BRD is associated with the comparison between the newly perceived image of the environment and its mnestic representation, and, lastly, c) the late BRS is connected with neuronal recovery phenomena.

Hipnic modulation of cerebellar information processing: implications for the cerebro-cerebellar dialogue

Recent evidence indicates that during the sleep-waking cycle the forebrain and the cerebellum show parallel changes of their operating capabilities and suggest that cooperation between these two structures plays a different role in the different behavioral states. In particular, a high degree of cerebro-cerebellar cooperation is expected in waking and in paradoxical sleep when enhanced information processing within the cerebellum and the cortex is associated with effective reciprocal cerebrocerebellar signal transmission. We first speculate that during waking, a state in which a wide range of behaviors is produced by the interaction with the external world, the cerebellum might assist the cortex to develop the neural dynamic patterns which underlie behaviors and that this could be accomplished via cerebellar modulation of both short- and long-range cortical synchronization. In particular, we propose that the cerebellum might favour the automatic triggering of the patterns already acquired, when requested by the context, as well as the acquisition of novel patterns, when found to be of adaptive value, and might even modulate the access to consciousness of brain operations, if producing unpredicted results, by regulating pattern complexity. This proposal is based on the experimental evidence that oscillatory activity may flow within the cerebro-cerebellar loops and that stimulation or lesion of the cerebellar structures affects cortical synchronization. Then we report evidence indicating that during paradoxical sleep, when brain activation occurs in the absence of sensory inflow and motor output, cerebro-cerebellar cooperation mainly favours consolidation of newly acquired waking patterns and/or savings of old patterns from disruption possibly through a non-utilitarian replay process. Finally, we propose that cerebro-cerebellar cooperation weakens during slow wave sleep, given that in this sleep state neuronal activity and excitability decrease both in the cerebellum and in the forebrain and cerebello-cortical signal transmission is at least partially gated at the thalamic level.

The influence of dopamine-1 receptor blockade on the humoral and renal effects of low-dose atrial natriuretic factor in human hypertensives

To test whether dopaminergic mechanisms can modulate the humoral and renal effects of atrial natriuretic factor (ANF), seven untreated, mildly hypertensive patients without complications were given a placebo (saline for 60 min) followed by a low dose of ANF (0.005 microgram/kg per min), or D-sulpiride (0.05 mg/kg per min), a specific dopamine-1 antagonist, or ANF + D-sulpiride at the same doses, for 60 min. The sequence of the three treatments was random, with a 72-h interval between treatments. The ANF infusion, which increased plasma ANF within the physiological range, significantly increased urinary sodium excretion, fractional sodium excretion and haematocrit; it reduced plasma aldosterone and tended to reduce plasma renin activity without changing blood pressure, the heart rate, renal plasma flow or the glomerular filtration rate. D-Sulpiride, when given alone, significantly increased mean blood pressure and reduced absolute and fractional sodium excretion without changing the heart rate, glomerular filtration rate, renal plasma flow, haematocrit, plasma renin activity or plasma aldosterone. When infused with D-sulpiride, ANF did not change absolute or fractional sodium excretion or haematocrit. This study provides evidence that dopaminergic mechanisms play a role in the natriuretic and plasma volume effects of a synthetic human ANF analogue infused at a low dose in patients with essential hypertension.

What Effect Does Blood Pressure Control Have on the Progression Toward Renal Failure

Since hypertension is associated with nephrosclerosis and an increased progression toward end-stage renal failure, the therapeutic approach to the treatment of hypertension should aim to protect the kidney against damage or to halt the progression toward end-stage renal failure. It appears that compared with systolic and mean blood pressure, the level of diastolic blood pressure is particularly associated with renal damage. In the presence of kidney failure the choice of antihypertensive drug should be made according to pharmacokinetic and pharmacodynamic properties. From the pharmacokinetic point of view, drugs that are eliminated via the biliary route are preferable since no dosage adjustment is required, and those with a favorable trough to peak effect can achieve better blood pressure control by reducing blood pressure variability. Pharmacodynamic properties should include efficacy in lowering blood pressure, beneficial renal effects, and good tolerability. Hence, the dihydropyridine calcium antagonists, which are effective during volume repletion and which counteract vasoconstrictor mechanisms, seem to be particularly effective. There is some suggestion, but no definitive proof, that blood pressure should be lowered well below 140/90 mm Hg; to achieve this, combination therapy frequently must be used. The rationale for combining two or more antihypertensive drugs is based on the knowledge that this combination can exert an additive antihypertensive action while reducing side effects. The combination of an angiotensin converting enzyme inhibitor with a dihydropyridine calcium antagonist may well fulfill these criteria since this combination could enhance both antihypertensive and renal hemodynamic effects in comparison to single-drug treatment and could reduce the side effects of both drugs.

Corrigendum to "Blink-related delta oscillations in the resting-state EEG: A wavelet analysis" (Neurosci. Lett. 449 (2009) 57-60)

Subsequent recordings collected during a follow-up of our studieson blink-related EEG have not produced results overlapping thosereported in the previous paper [3]. In particular, the blink-relateddelta oscillation, that was a biphasic negative-positive waveformin the above-mentioned paper, has turned out to be reversed inpolarity (i.e., positive-negative) in the recent recordings.The only difference in the EEG data processing with respect tothe previous recordings was in the export file format: EDF (recent)vs ASCII (previous). We believe that the polarity originating fromthe EDF files (i.e., positive-negative) should be considered correct,because EEG data exported in the form of EDF files, according tothe specifications of the format itself, faithfully represent originalraw data [6,7]. On the contrary, data exported in the form of filetext (with an ASCII code) only allow reproducing signals visual-izedontherecordingdevicescreen.But,indoingso,thewaveformis reconstructed referring to an internal code, according to whichnegative values are assigned to the points situated in the inferiorpart of the picture (with respect to an equatorial line of symme-try). This poses a serious problem when the reference coordinatesof the recording device, concerning vice versa the polarity of thedeflections with respect to the isoelectric line, are such that posi-tive deflections are downward. In this case, in fact, the procedureof exporting data as ASCII files, by assigning negative values to thesamedeflections(becausetheyarereallydownwardfromaspatialpoint of view), gives rise to an error of inverted polarity. In otherwords, such a procedure preserves the graphic representation ofthe data without considering the true polarity.This would not be a problem when on-line averaged evokedpotentials with known waveform and polarity are exported (pro-vided that one reverses the polarity off-line so they match with