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G Nappi

Publications and source records attributed to G Nappi.

At least 19 recordsLinked to original sources
PubMed2006

Selective lesion of the substantia nigra pars reticulata reduces the cortical Fos expression induced by stimulation of striatal D1-like receptors, in the rat.

We investigated the effects of a selective lesion of the substantia nigra pars reticulata (SNr), obtained by stereotaxic injection of ibotenic acid, on the cortical expression of Fos protein induced by striatal infusion of dopamine, D1-like agonist SKF 38393, in Sprague-Dawley rats. The specific aim was to clarify the role of the basal ganglia output structures - SNr in particular - in the cortical activation that follows a D1-dependent activation of the striatofugal, direct pathway, in freely moving animals. The striatal, unilateral infusion of 30 mM SKF 38393 induced consistent Fos expression throughout the whole ipsilateral cerebral cortex, including motor, sensorimotor, associative, and limbic areas; such expression was dramatically reduced by excitotoxic lesion of the ipsilateral SNr. These findings confirm the prominent role of the SNr in the transmission of striatofugal signals to functionally different cortical areas.

Animals↗
PubMed2006

Peripheral proteasome and caspase activity in Parkinson disease and Alzheimer disease.

BACKGROUND: Defects of the ubiquitin-proteasome (UP) system, a multicatalytic complex degrading polyubiquitinated proteins, may intervene in the pathogenesis of neurodegenerative disorders characterized by intracellular formation of protein aggregates such as Parkinson disease (PD) and Alzheimer disease (AD) by inducing proapoptotic conditions. METHODS: The authors measured the activity of proteolytic UP core, proteasome 20S, and of proapoptotic caspase-3 and -9 in peripheral blood lymphocytes (PBLs) of PD and AD patients to establish whether changes in these systems are detectable peripherally. RESULTS: Proteasome 20S activity was reduced in PBLs of treated PD patients vs healthy controls (mean +/- SEM: 1.0 +/- 0.1 vs 2.3 +/- 0.2 nmol 7-amino-4-methylcoumarin (AMC)/10(6) cells, p < 0.001), whereas marked increases in caspase-3 activity (1370 +/- 153 vs 586 +/- 104 pmol AMC/10(6) cells, p < 0.001) and caspase-9 activity (873 +/- 86 vs 304 +/- 27 U/10(6) cells, p < 0.001) were found. Increased caspase-9 activity was also detected in PBLs of untreated PD patients (900 +/- 193 U/10(6) cells). PD duration and severity (Unified Parkinson's Disease Rating Scale score) were inversely correlated with proteasome 20S activity and directly correlated with caspase-3 activity. An inverse correlation was also observed in PD patients between caspase-3 activity and proteasome 20S activity. No significant changes in proteasome 20S or caspase activity or correlations between biochemical and clinical variables were found in patients with AD. CONCLUSIONS: A decrease in proteasome activity, possibly related to caspase activation, is detectable in peripheral blood lymphocytes of patients with Parkinson disease but not patients with Alzheimer disease, suggesting that these variables may be considered for the development of peripheral biomarkers of Parkinson disease.

Aged↗
PubMed2006

Peripheral levels of BDNF and NGF in primary headaches.

Neurotrophins, such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), have been implicated in the generation and modulation of pain. To investigate whether alterations in neurotrophin levels can be detected in subjects suffering from nociceptive disorders, such as primary headaches, we determined the peripheral (platelet and plasma) levels of BDNF and NGF in patients suffering from migraine, with or without aura, or cluster headache (CH), in the interictal phase, and in healthy volunteers. All primary headaches patients studied showed significantly decreased platelet levels of BDNF (migraine vs. controls P<0.001; CH vs. controls P<0.01), while a selective reduction of platelet NGF was observed in migraine sufferers and not in CH patients compared with control subjects (migraine vs. controls P<0.001). These changes were not accompanied by significant modifications of neurotrophin plasma levels. Our findings show for the first time that changes in peripheral levels of neurotrophines (BDNF and NGF) occur in patients suffering from different types of primary headaches, suggesting a potential involvement of BDNF and NGF in the pathophysiology of these disorders, and raising the possibility that differences in peripheral neurotrophins may help to distinguish migraine biologically from CH.

Adult↗
PubMed2006

A novel ATP1A2 mutation in a family with FHM type II.

Familial hemiplegic migraine (FHM) is a rare subtype of migraine with aura with an autosomal dominant pattern of inheritance. Six FHM families underwent extensive clinical and genetic investigation. The authors identified a novel ATP1A2 mutation (E700K) in three patients from one family. In the patients, attacks were triggered by several factors including minor head trauma. In one subject a 3-day coma developed after a cerebral angiography. Overall, the phenotype of the patients closely resembles that of previously reported cases of FHM type II. The E700K variant might be regarded as the cause of the disease in this family, but this was not tested functionally.

Aged↗
PubMed2006

Abnormal modulatory influence of diffuse noxious inhibitory controls in migraine and chronic tension-type headache patients.

The aim of this study was to evaluate the function of pain modulating systems subserving diffuse noxious inhibitory controls (DNICs) in primary headaches. DNICs were examined in 24 migraineurs, 17 patients with chronic tension-type headache (CTTH) and 20 healthy subjects by means of nociceptive flexion RIII reflex and the cold pressor test (CPT) as heterotopic noxious conditioning stimulation (HNCS). The subjective pain thresholds (Tp) and the RIII reflex threshold (Tr) were significantly lower in CTTH vs. controls. In controls a significant inhibition of the RIII reflex was observed during the CPT (-30%, P < 0.05). Conversely, migraine and CTTH patients showed facilitation (+31%, P < 0.05 and +40%, P < 0.01, respectively) of the RIII reflex during the HNCS. This study demonstrates a dysfunction in systems subserving DNICs in both migraine and CTTH. Impairment of endogenous supraspinal pain modulation systems may contribute to the development and/or maintenance of central sensitization in primary headaches.

Adult↗
PubMed2006

Diaries and calendars for migraine. A review.

Headache is one of the most common types of pain and, in the absence of biological markers, headache diagnosis depends only on information obtained from clinical interviews and physical and neurological examinations. Headache diaries make it possible to record prospectively the characteristics of every attack and the use of headache calendars is indicated for evaluating the time pattern of headache, identifying aggravating factors and evaluating the efficacy of preventive treatment. This may reduce the recall bias and increase accuracy in the description. The use of diagnostic headache diaries does have some limitations because the patient's general acceptance is still limited and some subjects are not able to fill in a diary. In this review, we considered diaries and calendars especially designed for migraine and, in particular, we aimed at: (i) determining what instruments are available in clinical practice for diagnosis and follow-up of treatments; and (ii) describing the tools that have been developed for research and their main applications in the headache field. In addition to the literature review, we added two paragraphs concerning the authors' experience of the use of diaries and calendars in headache centres and their proposals for future areas of research.

Humans↗
PubMed2006

New appendix criteria open for a broader concept of chronic migraine.

After the introduction of chronic migraine and medication overuse headache as diagnostic entities in The International Classification of Headache Disorders, Second Edition, ICHD-2, it has been shown that very few patients fit into the diagnostic criteria for chronic migraine (CM). The system of being able to use CM and the medication overuse headache (MOH) diagnosis only after discontinuation of overuse has proven highly unpractical and new data have suggested a much more liberal use of these diagnoses. The International Headache Classification Committee has, therefore, worked out the more inclusive criteria for CM and MOH presented in this paper. These criteria are included in the appendix of ICHD-2 and are meant primarily for further scientific evaluation but may be used already now for inclusion into drug trials, etc. It is now recommended that the MOH diagnosis should no longer request improvement after discontinuation of medication overuse but should be given to patients if they have a primary headache plus ongoing medication overuse. The latter is defined as previously, i.e. 10 days or more of intake of triptans, ergot alkaloids mixed analgesics or opioids and 15 days or more of analgesics/NSAIDs or the combined use of more than one substance. If these new criteria for CM and MOH prove useful in future testing, the plan is to include them in a future revised version of ICHD-2.

Chronic Disease↗
PubMed2006

Advice alone vs. structured detoxification programmes for medication overuse headache: a prospective, randomized, open-label trial in transformed migraine patients with low medical needs.

The aim of this study was to compare the effectiveness of strong advice to withdraw the overused medication with the effectiveness of two structured pharmacological detoxification strategies in a cohort of patients diagnosed with probable migraine overuse headache (MOH) plus migraine and presenting low medical needs. One hundred and twenty patients participated in the study. Exclusion criteria included: previous detoxification treatments, coexistent medical or psychiatric illnesses and overuse of agents containing opioids, benzodiazepines and barbiturates. Group A received only intensive advice to withdraw the overused medication. Group B underwent a standard out-patient detoxification programme (advice+prednisone+preventive treatment). Group C underwent a standard in-patient withdrawal programme (as in group B + fluid replacement and antiemetics). Withdrawal therapy was considered successful if, after 2 months, the patient had reverted to an episodic pattern of headache and to an intake of symptomatic medication on fewer than 10 days/month. We were able to detoxify 75.4% of the whole cohort, 77.5% of patients in group A, 71.7% of patients in group B and 76.9% of those in group C (P>0.05). In patients with migraine plus MOH and low medical needs, effective drug withdrawal may be obtained through the imparting of advice alone.

Adolescent↗
PubMed2006

Headache attributed to infection: observations on the IHS classification (ICHD-II).

The aim of this study was to revise some topics in the chapter "Headache attributed to infections" in the last International Headache Society (IHS) classification. The authors searched for original studies and reviews about headache associated with infections. A checklist was submitted to 15 neurologists to quantify the relevance, comprehensibility and coherence between definitions, criteria and comments for each paragraph. The following paragraphs were fully discussed: (1) headache attributed to lymphocytic meningitis. This topic, being rather heterogeneous, should be divided into different subgroups; (2) headache attributed to HIV/AIDS. Distinctive features are not specified and diagnostic criteria are rather confusing; and (3) chronic post-infection headache. Diagnostic criteria should be reconsidered as the symptom "pain" is not the main diagnostic criterion. The authors propose the revision of three paragraphs of the new IHS classification to better define the most likely headache profile in specific CNS infections. The authors also underline the need to plan further ad hoc prospective studies.

Headache↗
PubMed2005

Two patients with COMT inhibitor-induced hepatic dysfunction and UGT1A9 genetic polymorphism.

The authors report two cases of catechol-O-methyltransferase (COMT) inhibitor-induced asymptomatic hepatic dysfunction in women with Parkinson disease. The patients were genotyped for the UDP-glucuronosyltransferase (UGT) 1A9 gene (which encodes the main COMT inhibitor-metabolizing enzyme), and found to carry mutations leading to defective glucuronidation activity. This suggests that UGT1A9 poor metabolizer genotype(s) may be a predisposing factor for COMT inhibitor-induced hepatotoxicity.

Adult↗
PubMed2005

Familial basilar migraine associated with a new mutation in the ATP1A2 gene.

Basilar migraine (BM), familial hemiplegic migraine (FHM), and sporadic hemiplegic migraine (SHM) are phenotypically similar subtypes of migraine with aura, differentiated only by motor symptoms, which are absent in BM. Mutations in CACNA1A and ATP1A2 have been found in FHM. The authors detected a novel mutation in the ATP1A2 gene (R548H) in members of a family with BM, suggesting that BM and FHM may be allelic disorders.

Adolescent↗
PubMed2005

Estradiol supplementation modulates neuroendocrine response to M-chlorophenylpiperazine in menstrual status migrainosus triggered by oral contraception-free interval.

BACKGROUND: Migraine triggered by oral contraception (OC)-free interval is very common and may be extremely severe, long-lasting and poorly responsive to analgesics (status migrainosus). The serotoninergic (5-HT) system is crucially involved in pain threshold and it is sensitive to estradiol (E2). Therefore, we aimed to assess neuroendocrine correlates of OC status migrainosus in response to the direct central 5-HT agonist meta-chlorophenylpiperazine (m-CPP) and to test the effect of transdermal E2 supplementation of the OC-free interval. METHODS: Clinical investigative protocol, single-blinded placebo-controlled treatment. Oral m-CPP (0.5 mg/kg body weight) challenge test was performed in 10 patients with status migrainosus occurring within 48 h of the discontinuation of a monophasic pill (30 microg of ethinyl estradiol and 150 microg of desogestrel) and in six healthy women assuming the same OC as controls. In a consecutive menstrual cycle, patients with OC status migrainosus underwent to the same test after they were blindly treated with 2.0 g of percutaneous E2 gel or placebo daily during the pill-free interval. Plasma prolactin and cortisol levels and clinical characteristics of migraine attacks were evaluated. RESULTS: Women with OC-status migrainosus showed a derangement of prolactin release (F = 4.8; P < 0.01) and a lack of cortisol response (F = 5.8; P < 0.001) after m-CPP in comparison with controls. Transdermal E2 during the pill-free interval significantly restored prolactin (F = 2.8; P < 0.01) and cortisol responses (F = 18.9; P < 0.001) against placebo and positively affected the duration (P < 0.001), the number of hours in which pain intensity prohibits daily activity (P < 0.001), the episodes of vomiting (P < 0.001) and the consumption of analgesics (P < 0.001). CONCLUSIONS: Status migrainosus triggered by OC-free interval is associated with impaired prolactin and cortisol responses following m-CPP challenge. Transdermal E2 supplementation is able to restore neuroendocrine response to this specific 5-HT agent, exerting a positive clinical effect on the course of menstrually related migraine.

Administration, Cutaneous↗
PubMed2005

Effects of acute and chronic restraint stress on nitroglycerin-induced hyperalgesia in rats.

Nitric oxide (NO) plays an important role in initiation and maintenance of pain, and NO precursor nitroglycerin is able to activate spinal and brain structures involved in nociception. It is also known that acute and chronic stress induce biochemical changes affecting both pain threshold and behaviour, and that the biological pattern of depression can be mimicked in the laboratory using chronic unavoidable stress paradigms (learned helplessness). We, therefore, evaluated the effects of acute and chronic immobilization stress on pain response to nitroglycerin administration in the rat. Pain perception was expressed as the latency of response to a tail-flick test (hot stimulus). Measures were made 1, 2 and 4 h following nitroglycerin (10 mg/kg i.p.) or vehicle. Nitroglycerin caused hyperalgesia after 2 and 4 h (p < 0.05 versus baseline). Acute stress (90 min) induced a clear analgesic state (p < 0.01 versus non-stressed control animals), and nitroglycerin injection was unable to reverse stress-induced analgesia in this setting. By contrast, exposition to chronic immobilization stress (7 days) caused a significant increase in pain response (p < 0.05); in this case, hyperalgesia was shown to be further enhanced by nitroglycerin administration (p < 0.05 versus vehicle). These findings support the view that a condition of chronic stress used in the laboratory to reproduce the biological features of depression can enhance hyperalgesia induced by nitroglycerin administration. These observations may be relevant to pain disorders, and particularly to migraine, since nitroglycerin is able to induce spontaneous-like pain attacks in humans, and an unfavourable migraine outcome (transformation into a chronic daily headache) is associated with chronic stress and comorbid depression.

Animals↗
PubMed2005

A randomised, double-blind, dose-ranging study to evaluate efficacy and safety of three doses of botulinum toxin type A (Botox) for the treatment of spastic foot.

Botulinum toxin A (BTX) injections have been used successfully in the treatment of post-stroke foot spasticity, but the optimal dose-response relationship for selected muscles has yet to be established. The aim of this study was to outline beneficial and unwanted effects of three different doses of BTX in the treatment of spastic foot. In this randomised, double-blind, dose-ranging study, 45 spastic feet were randomly allocated to one of three groups, each of which was treated with a different dosage of BTX. The doses were decided on the basis of suggestions in the literature. Outcome measures (Modified Ashworth Scale, Medical Research Council Scale, gait assessment, presence of Achilles tendon clonus, Visual Analogue Scales for Gait Function and Pain, Adverse Effects scale) were applied at baseline, 4 weeks and 4 months after treatment. All the groups showed significant scales scores improvements after treatment with BTX. Group II (mean BTX total dose: 322 U) and Group III (mean BTX total dose: 540 U) showed a greater and more prolonged response than Group I (mean BTX total dose: 167 U). Group III showed the highest rate of adverse effects 4 weeks post-treatment. BTX injections constitute a useful and safe method of improving post-stroke foot spasticity, associated pain, gait speed and function. In particular, the medium BTX dosages (320 UI spread over 2-5 muscles) were found to be both safe and effective in producing long-lasting improvement of spastic foot dysfunction.

Aged↗
PubMed2005

17beta-estradiol reduces neuronal apoptosis induced by HIV-1 gp120 in the neocortex of rat.

The human immunodeficiency virus type 1 (HIV-1) coat glycoprotein gp120 represents a likely contributor to the development of HIV-1 associated dementia (HAD), a neurological syndrome often observed in AIDS patients and characterised by significant neuronal loss in the neocortex. Since recent studies have highlighted that female sex hormones represent potential neuroprotective agents against damage produced by acute and chronic injuries in the adult brain, we have investigated whether estrogens exert protection in a rat model of gp120 neurotoxicity. Our results demonstrate that systemic administration of 17beta-estradiol (E2, 0.02-0.2 mg/kg) significantly reduces apoptotic cell death observed in the neocortex of rat following subchronic i.c.v. administration of gp120 (100 ng/rat/day). Furthermore, both tamoxifen and ICI182,780, two selective antagonists of estrogen receptors (ER) in the brain, reverted the neuroprotective effect of E2. The molecular mechanism of estrogenic neuroprotection does not appear to involve modulation of the antiapoptotic Bcl-2 or the proapoptotic Bax since we failed to observe changes in the levels of the two proteins in the neocortical tissue after gp120 and/or E2 treatment. However, we detected increased levels of IL-1beta in the neocortex of rats injected with gp120, as early as 6h after drug administration, and this effect was potentiated following pretreatment with E2. Taken together, our results demonstrate that E2 exerts neuroprotection against gp120 neurotoxicity in vivo through a mechanism involving ER activation and, possibly, via modulation of neocortical levels of IL-1beta.

Animals↗
PubMed2005

Focus on trial endpoints of clinical relevance and the use of almotriptan for the acute treatment of migraine.

Almotriptan is a 5-HT(1B/1D) receptor agonist, or triptan, indicated for the acute treatment of migraine. It has been shown to be effective and well tolerated for the treatment of acute migraine in approximately 5000 patients enrolled in short-term placebo- and active-controlled trials and long-term open-label trials. A recent meta-analysis reported that almotriptan has the highest sustained pain-free (SPF) rate and lowest adverse-event (AE) rate of all oral triptans. Sustained pain free is a composite endpoint of pain freedom at 2 h, no recurrence of moderate-to-severe headache and no use of rescue medication from 2 to 24 h after dosing. Patient surveys have indicated that migraine sufferers consider complete pain relief, no recurrence, rapid onset and no side-effects to be the most important attributes of their acute treatment. Composite endpoints such as SPF and SPF with no AEs (SNAE) contain the attributes that migraine sufferers express as being the most important elements of an acute migraine therapy, and their use in future clinical trials should aid in the selection of agents that can offer patients the highest likelihood of consistent treatment success.

Acute Disease↗
PubMed2005

Single high-dose steroid treatment in episodic cluster headache.

Corticosteroids appear to be the most rapid-acting of the prophylactic drugs used in the treatment of cluster headache (CH). These agents are frequently employed as a short-term regimen to induce clinical remission. In this study, we assessed in an open fashion the effect of high dose methylprednisolone (MPD) in a group of 13 patients with episodic CH (3 females and 10 males). On the 8th day of the active period, MPD was administered intravenously at the dose of 30 mg/kg body weight, as a 3-h infusion in saline. The attack frequency was followed for 7 days. The mean daily attack frequency before MPD administration was statistically different from that reported after treatment (respectively: 1.38 +/- 0.42 and 0.83 +/- 0.78; P = 0.05 Student's t-test). The mean interval between MPD administration and the occurrence of the first subsequent attack was 3.8 +/- 2.2 days (range: 2-7 days). Only 3 (23%) of 13 patients experienced a complete headache remission. No significant side-effects were noted after MPD administration. These data further demonstrate that in most patients with episodic CH, high-dose systemic steroid administration may invariably interrupt attack recurrence for a few days, but is ineffective in maintaining complete clinical remission. This study also suggests that MPD administered as a solitary dose does not provide any advantage above prednisone in CH treatment.

Cluster Headache↗