Search PubMedSearch

Biomedical subjects

G Nappi

Publications and source records attributed to G Nappi.

At least 19 recordsLinked to original sources

Evidence of alpha-N-acetyl beta-endorphin in human cerebrospinal fluid.

Alpha-N-acetyl-beta-endorphin (Ac-beta-EP) is a post-translational product of beta-endorphin (beta-EP) with no analgesic properties. Ac beta-EP is present in human fetal and adult pituitary gland and cross-reacts in all available beta-EP assays. This study evaluates levels of Ac-beta-EP in the cerebrospinal fluid (CSF) of 22 normal subjects and 15 chronic headache sufferers. Since dopamine may play a role in the acetylation process, homovanillic acid levels were also determined. After extraction and high performance liquid chromatographic (HPLC) fractionation of CSF, an immunoreactive Ac-beta-EP peak was detected coeluting with reference peptide. Ac-beta-EP was detectable in all but 5 normal subjects. In headache sufferers, Ac-beta-EP levels were always detectable and their mean value was significantly higher than that of healthy subjects (11.6 +/- 11.8 vs 3.9 +/- 3.6 fmol/ml; P less than 0.01). Conversely, CSF beta-endorphin (beta-EP) concentrations were decreased in headache patients (9.8 +/- 9.4 vs 15.7 +/- 9.7 fmol/ml; P less than 0.05), and as a consequence the beta-EP/Ac-beta-EP ratio was also markedly reduced (P less than 0.005). No difference was observed for CSF homovanillic acid concentrations. These data demonstrate that HPLC coupled to radioimmunoassay allows the identification of low but significant amounts of Ac beta-EP in human CSF. This compound represents a confounding factor when beta-EP immunoreactivity is assessed by conventional methods. In headache sufferers, Ac-beta-EP levels were higher than normal, whereas beta-EP concentrations were lower.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Cerebrospinal fluid norepinephrine, 3-methoxy-4-hydroxyphenylglycol and neuropeptide Y levels in Parkinson's disease, multiple system atrophy and dementia of the Alzheimer type.

Neuropeptide Y, one of the most abundant polypeptides within the nervous system, is co-stored with catecholamines, especially norepinephrine (NE), thus suggesting its possible involvement in pathologies characterized by a noradrenergic impairment. In Parkinson's disease (PD), as well as in multiple system atrophy (MSA), a central noradrenergic deficit has been demonstrated, and in the dementia of Alzheimer type (DAT) an impaired noradrenergic transmission has been postulated. In this study we determined CSF NE and MHPG levels in 29 PD, 15 MSA, 22 DAT patients and in 36 controls, while CSF NPY-immunoreactivity (NPY-ir) levels were measured in 10 PD, 7 MSA, 10 DAT patients and 20 controls. PD, MSA, and DAT patients showed a significant reduction in CSF NPY-ir and NE levels compared with controls, while CSF MHPG levels resulted in a reduction in only the MSA group. Furthermore, an inverse correlation between either NE or MHPG levels and the duration of the orthostatic hypotension was found in MSA patients while for DAT patients the MHPG levels were directly correlated to the severity of cognitive impairment, and inversely to the duration of illness.

Adult

The trigemino-pupillary reflex: a model of sensory-vegetative integration.

Trigeminal stimulation can induce pupillary changes. In vivo and in vitro studies have demonstrated that electrical impulses applied at the trigeminal level can provoke a miotic response, whose nature has been ascribed to the anti-dromic release of neuropeptides (substance P in particular). In order to better define the pupil response to trigeminal stimulation, we investigated the human pupil response to quantified (painless and painful) corneal stimuli by means of a combined (neurophysiological and pharmacological) technique. The response to corneal stimulation was bilateral, direct and consensual. It had a biphasic progression with an initial mydriasis (which directly correlated with the stimulus intensity), followed by a miotic phase. The mydriatic phase disappeared after thymoxamine application, while homatropine pre-treatment prevented occurrence of the miotic phase. The data obtained indicate that the pupillary response to corneal stimulation (trigemino-pupillary reflex) is a multisynaptic reflex with an afferent branch involving the trigeminal system, and an afferent branch involving both the sympathetic and the parasympathetic system. Other pathways, such as the SP-mediated release of acetylcholine, cannot be excluded. Thus the reflex appears to be a potentially useful tool for investigating pain/vegetative interactions in various clinical conditions. In turn, the description of its changes in pathologies characterized by a sympathetic/parasympathetic deficit or by a SP-ergic imbalance will allow us to better describe its inner mechanisms.

Adult

The brain as a target for adrenocortical steroids: cognitive implications.

It is well established that a reciprocal control exists between the brain and glucocorticoid hormones. The brain regulates adrenocortical function via hypothalamic corticotrophin releasing hormone-41 (CRH-41), glucocorticoids act at specific receptors in the hippocampus, thus promoting negative feedback mechanisms. Because the hippocampus is a major site for memory processes, a role for excessive/long-lasting plasma glucocorticoid levels has been suggested in conditions of mental impairment. Major depression, Cushing's disease, and dementia of the Alzheimer type are disorders which share hyperactivity of the hypothalamo-pituitary-adrenal axis, as well as symptoms of cognitive decline. Although the mechanisms leading to hypercortisolemia appear to be different in each case, the neuropsychological features of these three disorders accord with the hypothesis of glucocorticoid-associated brain damage. It therefore is important to find pharmacological strategies that will avert or reduce these potential consequences on brain function.

Adrenocorticotropic Hormone

Accompanying symptoms of cluster attacks: their relevance to the diagnostic criteria.

Two-hundred-and-fifty-one consecutive cluster headache (CH) patients referred to the Pavia and Parma Headache Centers were evaluated in order to verify the presence and recurrence of one or more autonomic symptoms. Data obtained show that in 2.8% of patients cluster attacks were not accompanied by localized autonomic symptoms, thus confirming the report of Ekbom. We observed a high prevalence of photophobia, nausea and vomiting. The IHS diagnostic criteria for CH may need to be modified. The high frequency of "general" autonomic symptoms seems to suggest a component of "central" drive in the physiopathology of cluster headache.

Adult

Free plasma catecholamine levels in healthy subjects: a basal and dynamic study. The influence of age.

We studied the levels of free plasma noradrenaline (norepinephrine, NE), adrenaline (epinephrine, E), and dopamine (DA) in 143 normal subjects, either basally or, in a part of them, in response to four tests stimulating the sympathoadrenomedullary activity: the tilt-table test (TTT), the cold-pressor test (CPT), the mental-arithmetic test (MAT), and the insulin tolerance test (ITT). In both cases we evaluated the influence of age, which is considered the main physiological variable affecting the peripheral sympathetic activity. A normal distribution of values was observed, in the basal study, only for NE, while E and particularly, DA levels were distributed in an non-homogeneous fashion; a direct correlation was observed between age of subjects and NE levels, while neither E, nor DA levels showed any correlation with the aging process; sex did not influence any of the catecholamines. In the dynamic study, CPT, ITT and, above all, TTT elicited a significant rise in NE levels, while the E release was greatly stimulated by the insulin-induced hypoglycaemia. Neither NE, nor E levels rose after the MAT stimulation. Also in this case, the elderly showed an increased noradrenergic responsiveness when compared with the young subjects, confirming the existence of an 'up-regulation' of the peripheral sympathetic tone in old people.

Adolescent

Central analgesic activity of ibuprofen. A neurophysiological study in humans.

Ibuprofen is a widely used non-steroidal anti-inflammatory drug (NSAID). Inhibition of prostaglandin biosynthesis is considered to be the main mechanism of action of this substance. Recently, a central analgesic activity was described in an experimental study. In order to explore the possibility that ibuprofen induces analgesia at central level in humans, we investigated, in a double-blind design, the effects of orally-given 600 mg granular ibuprofen or placebo on nociceptive flexion reflex in normal volunteers. Ibuprofen produced a significant increase, as compared to placebo, in the threshold of the nociceptive reflex. The ratio between subjective pain threshold (Tp) and reflex threshold (Tr) was unchanged after either ibuprofen or placebo administration, indicating that Tp strictly paralleled Tr. These results indicate that ibuprofen displays a central antalgic activity in humans. Different supraspinal structures are probably involved, but the exact mechanisms are still to be clarified.

Administration, Oral

Haemodynamic and neurohormonal responsiveness to different stress tests in mitral valve prolapse.

In this study the blood pressure, heart rate, plasma noradrenaline and plasma adrenaline responses to various forms of sympatho-neural stress were evaluated in patients with mitral valve prolapse (MVP). Sympathetic reactivity in different subgroups of MVP were related to the degree of ventricular arrhythmia. Thirty-eight patients with mitral valve prolapse and 17 healthy controls were studied. All underwent 24-h ECG recording, 2-D echocardiography, head-up tilt to 60 degrees, pressor tests (sustained handgrip, mental arithmetic, cold pressor) and psychological assessment. The blood pressure, noradrenaline and adrenaline response to stress in patients without premature ventricular contraction were similar to those of the controls. In patients with unifocal premature ventricular contraction (PVC) less than 300/h, responses were similar to normal but were associated with higher plasma noradrenaline levels in the basal state and a diminished response to isometric stress. In patients with more than 300/h unifocal premature ventricular contraction, pairs of premature ventricular contraction, or runs of ventricular tachycardia there were lower blood pressure values in the basal state with reduced blood pressure, heart rate and plasma noradrenaline and adrenaline responses to head-up tilt and sustained handgrip, but marked increases in blood pressure, heart rate and plasma noradrenaline levels during the cold pressor test. Our data suggest different degrees of autonomic involvement in mitral valve prolapse which may be related to the various degrees of arrhythmia which seem to contribute to their symptoms.

Adolescent

Disordered pupil reactivity in Parkinson's disease.

Different varieties of pupillary abnormalities have been described in Parkinson's disease but it is not clear if this is due to the disease itself or to the pharmacological treatment. In this study, pupil reactivity to various stimuli (dark/light adaptation, light reflex, near vision reaction and electrical sural stimulation) was investigated in 23 de novo parkinsonian patients (not on drugs) to assess pupillary abnormalities and investigate their pathophysiological mechanisms. Parkinsonian patients exhibited larger pupil diameter after light adaptation, as well as a reduced amplitude of contraction and a prolonged contraction time at light reflex. The data obtained confirmed the existence in Parkinson's disease of a pupillary imbalance mainly involving the parasympathetic system.

Adaptation, Ocular

Monoamines and related metabolite levels in the cerebrospinal fluid of patients with dementia of Alzheimer type. Influence of treatment with L-deprenyl.

An impairment of the monoaminergic systems has frequently been reported for Alzheimer's disease (AD) as well as an overactivity of cerebral monoamineoxidase B (MAO-B). L-deprenyl (LD), a selective and irreversible MAO-B inhibitor, has recently been proposed for the treatment of AD. The cerebrospinal fluid (CSF) levels of norepinephrine (NE), epinephrine (E), dopamine (DA), 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) were studied in 14 patients suffering from dementia of Alzheimer type (DAT) and in 14 controls. A three-month double-blind study comparing LD with placebo was carried out, in the DAT group, and the influence of the treatment on neurotransmitter levels and cognitive performance was evaluated. The basal study revealed a significant reduction in CSF NE and HVA levels in DAT patients when compared with controls; the treatment with LD determined a significant decrease in HVA levels only and, as to neuropsychological investigation, a global amelioration of cognitive performances.

Aged

Dihydroergocryptine in the treatment of Parkinson's disease: a six months' double-blind clinical trial.

The short-term efficacy of dihydro-alpha-ergocryptine (DEK), a hydrogenate ergot derivative with dopamine (DA) agonist properties was evaluated in 20 L-dopa (LD) stable responder parkinsonian patients by a 6-month double-blind randomized, placebo-controlled study. A motor improvement was found only in DEK-treated patients at mean daily doses of approximately 40 mg, ranging from 15 to 60 mg. The side effects never required the withdrawal of the drug or changes in its schedule. The authors demonstrate the efficacy and the good tolerability of DEK as a new DA agonist drug that can be added to LD in the treatment of parkinsonian patients.

Dihydroergotoxine

Cardiopressor effects of short-term treatment with cabergoline in L-dopa stable responder parkinsonian patients: relevance of postprandial hypotension.

The hemodynamic and biochemical effects of cabergoline, a new ergoline derivative with selective, potent, and long-lasting dopamine (DA) agonistic properties, were evaluated in 19 parkinsonian patients, all previously identified as stable responders to levodopa plus L-Dopa decarboxylase inhibitor. The purpose of the study was to find markers capable of predicting the development of cardiopressor side effects during DA-agonistic therapy. Blood pressure (BP), heart rate, and plasma catecholamine responses to a standard meal and a tilt table test were evaluated before and during cabergoline therapy. Cabergoline (1.0 mg/day x os) in this open study significantly reduced the BP response to standing exclusively in the subgroup of patients who exhibited marked postprandial hypotension in baseline conditions. The patients subsequently experienced a partial recovery at day 7 of treatment. This finding indicates that postprandial hypotension is an early marker of autonomic failure in patients with Parkinson's disease (PD) and suggests the usefulness of evaluating cardiopressor response to a standard meal before starting new DA-agonist therapy in PD.

Aged

Magnesium prophylaxis of menstrual migraine: effects on intracellular magnesium.

The effects of oral Magnesium (Mg) pyrrolidone carboxylic acid were evaluated in 20 patients affected by menstrual migraine, in a double-blind, placebo controlled study. After a two cycles run-in period, the treatment (360 mg/day of Mg or placebo) started on the 15th day of the cycle and continued till the next menses, for two months. Oral Mg was then supplemented in an open design for the next two months. At the 2nd month, the Pain Total Index was decreased by both Placebo and Mg, with patients receiving active drug showing the lowest values (P less than 0.03). The number of days with headache was reduced only in the patients on active drug. Mg treatment also improved premenstrual complaints, as demonstrated by the significant reduction of Menstrual Distress Questionnaire (MDQ) scores. The reduction of PTI and MDQ scores was observed also at the 4th month of treatment, when Mg was supplemented in all the patients. Intracellular Mg++ levels in patients with menstrual migraine were reduced compared to controls. During oral Mg treatment, the Mg++ content of Lymphocytes (LC) and Polymorphonucleated cells (PMN) significantly increased, while no changes in plasma or Red Blood Cells were found. An inverse correlation between PTI and Mg++ content in PMN was demonstrated. These data point to magnesium supplementation as a further means for menstrual migraine prophylaxis, and support the possibility that a lower migraine threshold could be related to magnesium deficiency.

Administration, Oral

Lisuride plus selegiline in the treatment of early Parkinson's disease.

We treated 20 early Parkinson's disease subjects with the dopamine agonist lisuride in combination with the MAO-B inhibitor selegiline (L-deprenyl). We started with lisuride alone for one month, then we added selegiline versus placebo to lisuride in double-blind conditions for 3 months; finally all patients received lisuride and selegiline for another 3 months. Lisuride alone (1.43 +/- 0.10 mg) significantly improved PD. When selegiline (10 mg/day) was added in the double-blind phase the mean lisuride dosage could be reduced by 22.8% without deterioration of the clinical effects, and the same occurred in the former placebo group when selegiline was added. The combination of both drugs was well tolerated. These data are of interest for the interpretation of the effects of selegiline.

Adult

Neurophysiological markers of central and peripheral involvement of the nervous system in HIV-infection.

Peroneal motor and sural sensory conduction velocities (MNCVs/SNCVs), somatosensory evoked potentials to median nerve stimulation (MN-SEPs) and motor evoked potentials (MEPs) to transcranial stimulation were examined in 138 HIV-infected patients (in the different stages of the disease), 20 seronegative intravenous drug abusers (IVDAs), and 20 healthy subjects. Findings of peroneal MNCV slowing in patients ranged from 16% (asymptomatic HIV patients) to 63% (AIDS) and of sural SNCV slowing from 13% to 40%. Altered MN-SEPs ranged from 10% to 30%, and MEPs ranged from 44% to 72%, mostly due to a prolongation of the central motor conduction time (CMCT). All seronegative IVDAs showed patterns within the normal range. Electrophysiological techniques were helpful in demonstrating early and subclinical alterations in HIV patients.

Adult

Treatment of severe hypercholesterolaemia by LDL-apheresis.

The most severe forms of hypercholesterolaemia scarcely respond to diet and conventional drugs administration and need, therefore, alternative treatments. Terapeutic Plasma Exchange demonstrated an improved survival of subjects with Familial Hypercholesterolaemia (FH) in spite of its limitations. Semi-selective and selective techniques have been developed in order to remove LDL cholesterol alone. We studied the efficiency in LDL removal both of membrane filtration as of dextrane sulphate adsorption on 14 FH patients, performing 302 procedures. Cholesterol extraction with the different methods was in the range of 40-65%. Mean cholesterol level was reduced from 7% to 64% depending on the protocol used. The procedures were all performed on an outpatient basis. Side effects occurred rarely and were always of not serious degree. The short and the middle term clinical effects of LDL-Apheresis are then evaluated.

Adolescent

Cluster headache. Recent developments in clinical characterization and pathogenesis.

The preliminary results of some new studies on cluster headache (CH) point to: (a) the existence of a form, secondary episodic CH, which should be included in the classification of headache; (b) the significant role played by air temperature variations and the number of daylight hours on the onset of CH active periods. Data from the evaluation of pupil response to corneal stimuli suggest a widespread alteration of the pain/autonomic integrative processes at the level of the central nervous system. Finally, data on new preventive (i.e., verapamil and ozone) and symptomatic (i.e., hyperbaric oxygen and sumatriptan) treatments are reported.

Autonomic Nervous System