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Biomedical subjects

Giuseppe Nappi

Publications and source records attributed to Giuseppe Nappi.

At least 19 recordsLinked to original sources

Peripheral inflammation and neuroprotection: systemic pretreatment with complete Freund's adjuvant reduces 6-hydroxydopamine toxicity in a rodent model of Parkinson's disease.

Complete Freund's adjuvant (CFA), a pro-inflammatory agent, was inoculated, subcutaneously, to Sprague-Dawley rats prior to the intrastriatal injection of 6-hydroxydopamine (6-OHDA). Animals were sacrificed 7 and 28 days following 6-OHDA injection; neuronal damage, glial activation and cytokine levels, within the nigrostriatal system, were then investigated. Nigrostriatal degeneration induced by 6-OHDA was accompanied by early microglial and astroglial activation, which preceded the onset of dopaminergic cell loss, in the SNc, without significant changes in cytokine levels. CFA pretreatment markedly reduced the SNc neuronal loss and associated microglial activation, as well as the rotational response to apomorphine. These changes were associated with moderate, transient increases in the nigrostriatal levels of glial-cell-derived neurotrophic factor (GDNF) and pro-inflammatory cytokines, including interleukin (IL)-1alpha, IL-1beta and IL-6. Our results show that prior delivery of a peripheral, pro-inflammatory stimulus induces neuroprotection, in a rodent model of Parkinson's disease, possibly through the modulation of cytokine production at the nigrostriatal level.

Adjuvants, Immunologic↗

Unilateral lesion of the subthalamic nucleus enhances cortical fos expression associated with focally evoked seizures in the rat.

Reducing subthalamic nucleus (STN) activity has been proposed as an anti-epileptic procedure. Here we show that, on the contrary, a unilateral lesion of the STN causes slight (nonsignificant) increases in the severity of limbic seizures evoked by bicuculline infusion into the piriform cortex, associated with marked Fos expression throughout the cerebral cortex. Abolishing the STN control over the basal ganglia output may therefore play a facilitatory role on cortical activation associated with limbic seizures.

Animals↗

Evaluation of thermal water in patients with functional dyspepsia and irritable bowel syndrome accompanying constipation.

AIM: To evaluate the efficacy of water supplementation treatment in patients with functional dyspepsia or irritable bowel syndrome (IBS) accompanying predominant constipation. METHODS: A total of 3872 patients with functional dyspepsia and 3609 patients with irritable bowel syndrome were enrolled in the study by 18 Italina thermal centres. Patients underwent a first cycle of thermal therapy for 21 d. A year later patients were re-evaluated at the same centre and received another cycle of thermal therapy. A questionnaire to collect personal data on social and occupational status, family and pathological case history, life style, clinical records, utilisation of welfare and health structure and devices was administered to each patient at basal time and one year after each thermal treatment. Sixty patients with functional dyspepsia and 20 with IBS and 80 healthy controls received an evaluation of gastric output and oro-cecal transit time by breath test analysis. Breath test was performed at basal time and after water supplementation therapies. Gastrointestinal symptoms were evaluated at the same time points. Breath samples were analyzed with a mass spectometer and a gascromatograph. Results were expressed as T(1/2) and T-lag for octanoic acid breath test and as oro-cecal transit time for lactulose breath test. RESULTS: A significant reduction of prevalence of symptoms was observed at the end of the first and second cycles of thermal therapy in dyspeptic and IBS patients. The analysis of variance showed a real and persistant improvement of symptoms in all patients. After water supplementation for 3 wk a reduction of gastric output was observed in 49 (87.5%) of 56 dyspeptic patients. Both T(1/2) and T-lag were significantly reduced after the therapy compared to basal values [91 +/- 12 T(1/2) and 53 +/- 11 (T-lag), Tables 1 and 2] with results of octanoic acid breath test similar to healthy subjects. After water supplementation for 3 wk oro-cecal transit time was shorter than that at the beginning of the study. CONCLUSION: Mineral water supplementation treatment for functional dyspepsia or constipation accompanying IBS can improve gastric acid output and intestinal transit time.

Adult↗

Cardiovascular dysautonomia as a cause of falls in Parkinson's disease.

Parkinson's disease (PD) patients have a ninefold increased risk of recurring falls compared to healthy controls. The risk of falling due to cardiovascular dysautonomia (CVD) is not quantifiable. But, CVD is an integral part of the disease and at least 20% of PD patients suffer from orthostatic hypotension, an expression of CVD. One way to reduce falls due to CVD in PD patients could be to give adequate information on the relationship between falling risks and cardiovascular dysautonomia to patients and their caregivers. Moreover, drugs given for PD might contribute to OH and we propose that education and non-pharmacological strategies for its treatment might be preferable, especially because of the low efficacy of drugs available for the treatment of OH and the frailty of elderly PD patients.

Accidental Falls↗

Prostaglandins, glutamate and nitric oxide synthase mediate nitroglycerin-induced hyperalgesia in the formalin test.

Increasing evidence supports a possible role for nitric oxide (NO) in the transmission of pain signals and in the development of central mechanisms of hyperalgesia. Previously, we have shown that nitroglycerin, an NO donor, is able to induce a long-lasting hyperalgesic state in rats. Nitroglycerin-induced hyperalgesia can be detected as an increase in the nociceptive behavior evoked by the formalin test. In the present study we investigated the possible mediators in the nitroglycerin-induced hyperalgesic state. Male Sprague-Dawley rats were injected with nitroglycerin and pretreated with indomethacin, 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine hydrogen maleate (MK-801) or N(omega)-nitro-L-arginine methyl ester (L-NAME). The results obtained showed that inhibition of prostaglandins or NO synthesis prevents nitroglycerin-induced hyperalgesia in Phase II of the formalin test. A similar inhibitory effect was also observed following pretreatment with the glutamate antagonist MK801. The present findings point to the role of prostaglandins, NO synthesis and glutamate activity in the induction of nitroglycerin-induced hyperalgesia.

Animals↗

REM sleep behavior disorder, hallucinations, and cognitive impairment in Parkinson's disease.

The objective of this study was to evaluate the relationship between REM sleep behavior disorder (RBD), hallucinations, and cognitive impairment in Parkinson's disease (PD). One hundred and ten PD patients, divided into three groups (without RBD or hallucinations; with RBD but no hallucinations; with RBD and hallucinations), were submitted to neuropsychological evaluation. The group without RBD and hallucinations showed normal neuropsychological tests when compared to normal controls. The group with hallucinations was characterized by a more severe cognitive impairment affecting both short- and long-term memory, logical abilities, and frontal functions, while the RBD-only group presented frontal impairment. The hypothesis that RBD in PD can be considered a risk factor not only of the hallucinations but also of more severe and diffuse cognitive abnormalities needs to be strengthened through a longitudinal evaluation.

Aged↗

Botulinum toxin and neuromotor rehabilitation: An integrated approach to idiopathic cervical dystonia.

Currently, the best treatment option for idiopathic cervical dystonia (ICD) is injection of botulinum toxin (BTX) into the affected muscles, whereas rehabilitative approaches have given disappointing results. We evaluated whether the association of an ad hoc rehabilitative program may improve the clinical efficacy of BTX treatment in a single-center, cross-over, controlled study. Forty patients with ICD were randomly assigned to two different treatment groups: (1) BTX type A (BTX-A) plus a specific program of physical therapy (BTX-PT) or (2) BTX-A alone (BTX-0). Patients in the BTX-PT group showed a longer duration of the clinical benefit (118.8 vs. 99.1 days) and needed a lower dose of BTX at reinjection (284.5 vs. 325.5 units). In addition, they showed more marked reductions in their disability in activities of daily living (-9.7 vs. -4.85 points) and subjective pain (-13.35 vs. 6.95 points) scores. Association of BTX-A therapy with a specific program of physical therapy may improve ICD treatment outcome.

Activities of Daily Living↗

Uncommon primary headaches.

PURPOSE OF REVIEW: The new International Classification of Headache Disorders was recently published by the International Headache Society. Several uncommon primary headaches, including some new clinical entities (e.g. hypnic headache), were included in the section on 'Cluster headache and other trigeminal autonomic neuralgias' and 'Other primary headaches'. The recent classification offers an interesting opportunity to evaluate the clinical role and to discuss the mechanisms of some of the more relevant uncommon primary headaches. RECENT FINDINGS: Due to the low incidence of these uncommon headache forms, their diagnostic criteria, pathogenetic mechanisms and therapy are still debated. Differential diagnosis versus secondary headaches is also a crucial issue. In this review, some of the most important uncommon primary headaches are discussed in light of the most recent contributions to the literature. SUMMARY: The review focuses on the update of the main uncommon primary headaches, intending to clarify some controversial points and to indicate some headlines for further research.

Diagnosis, Differential↗

Use of complementary and alternative medicine by patients with chronic tension-type headache: results of a headache clinic survey.

OBJECTIVES: This study was undertaken to evaluate the rates, pattern, and presence of predictors of complementary and alternative medicine use in a clinical population of patients with chronic tension-type headache. BACKGROUND: The use of complementary and alternative medicine in the treatment of headaches is a growing phenomenon about which little is known. METHODS: A total of 110 chronic tension-type headache patients attending a headache clinic participated in a physician-administered structured interview designed to gather information on complementary and alternative medicine use. RESULTS: Past use of complementary and alternative therapies was reported by 40% of the patients surveyed (22.7% in the previous year). Chronic tension-type headache patients prefer complementary and alternative practitioner-administered physical treatments to self-treatments, the most frequently used being chiropractic (21.9%), acupuncture (17.8%), and massage (17.8%). Only 41.1% of the patients perceived complementary and alternative therapies to be beneficial. The most common source of recommendation of complementary and alternative medicine was a friend or relative (41.1%). Most of the chronic tension-type headache patients used complementary and alternative treatment as a specific intervention for their headache (77.3%). Almost 60% of complementary and alternative medicine users had not informed their medical doctors of their use of complementary and alternative medicine. The most common reasons given for choosing to use a complementary or alternative therapy was the "potential improvement of headache" it offered (45.4%). The patients who had used more complementary and alternative treatments were found to be those recording a higher lifetime number of visits to conventional medical doctors, those with a comorbid psychiatric disorder, those enjoying a higher (household) income, and those who had never tried a preventive pharmacological treatment. CONCLUSIONS: Our findings suggest that headache-clinic chronic tension-type headache patients, in their need of and quest for care, seek and explore both conventional and complementary and alternative therapies, even if only 41.1% of them perceived complementary treatments as effective. Physicians should be made aware of this patient-driven change in the medical climate in order to prevent misuse of health care resources and to be better equipped to meet patients' care requirements.

Adolescent↗

Eletriptan: a review and new perspectives.

Eletriptan is a second-generation 5-hydroxytryptamine(1B/1D) receptor agonist, or triptan, indicated for the acute treatment of migraine. Eletriptan has a favorable pharmacokinetic and pharmacodynamic profile expressed by bioavailability, half-life and high selectivity for cranial arteries. It has been shown to be effective and well tolerated in a wide preapproval development program, which included over 11,000 patients and treated more than 74,000 migraine attacks. In clinical trials, eletriptan has been demonstrated to be one of the most effective oral therapies for the acute treatment of migraine and has shown a very high safety and tolerability profile across the studies performed. Eletriptan showed the most favorable cost-effectiveness profile when compared with other agents in its class.

Animals↗

Prolonged blockade of NMDA or mGluR5 glutamate receptors reduces nigrostriatal degeneration while inducing selective metabolic changes in the basal ganglia circuitry in a rodent model of Parkinson's disease.

We compared the neuroprotective and metabolic effects of chronic treatment with ionotropic or metabotropic glutamate receptor antagonists, in rats bearing a unilateral nigrostriatal lesion induced by 6-hydroxydopamine (6-OHDA). The ionotropic, N-methyl-D-aspartate receptor antagonist MK-801 increased cell survival in the substantia nigra pars compacta (SNc) and corrected the metabolic hyperactivity (increased cytochrome oxidase activity) of the ipsilateral substantia nigra pars reticulata (SNr) associated with the lesion, but showed no effects on the 6-OHDA-induced hyperactivity of the subthalamic nucleus (STN). Significant-although less pronounced-protection of SNc neurons was also observed following treatment with the metabotropic glutamate receptor (mGluR5) antagonist 2-methyl-6-(phenylehtynyl)-pyridine (MPEP). As opposed to MK-801, MPEP abolished the STN metabolic hyperactivity associated with the nigrostriatal lesion, without affecting SNr activity. Specific modulation of STN hyperactivity obtained with mGluR5 blockade may, therefore, open interesting perspectives for the use of this class of compounds in the treatment of Parkinson's disease.

Animals↗

Oxidative stress and pro-apoptotic conditions in a rodent model of Wilson's disease.

Wilson's disease (WD) is an inherited disorder, characterized by selective copper deposition in liver and brain, chronic hepatitis and extra-pyramidal signs. In this study, we investigated changes of biochemical markers of oxidative stress and apoptosis in liver, striatum and cerebral cortex homogenates from Long-Evans Cinnamon (LEC) rats, a mutant strain isolated from Long Evans (LE) rats, in whom spontaneous hepatitis develops shortly after birth. LEC and control (LE) rats at 11 and 14 weeks of age were used. We determined tissue levels of glutathione (GSH/GSSG ratio), lipid peroxides, protein-thiols (P-SH), nitric oxide metabolites, activities of caspase-3 and total superoxide-dismutase (SOD), striatal levels of monoamines and serum levels of hepatic amino-transferases. We observed a decrease of protein-thiols, GSH/GSSG ratio and nitrogen species associated to increased lipid peroxidation in the liver and striatum - but not in the cerebral cortex - of LEC rats, accompanied by dramatic increase in serum amino-transferases and decrease of striatal catecholamines. Conversely, SOD and caspase-3 activity increased consistently only in the cortex of LEC rats. Hence, we assume that enhanced oxidative stress may play a central role in the cell degeneration in WD, at the main sites of copper deposition, with discrete pro-apoptotic conditions developing in distal areas.

Analysis of Variance↗

Comparative analysis of the neuronal activation and cardiovascular effects of nitroglycerin, sodium nitroprusside and L-arginine.

In this study, we compare the biological effects, Fos expression and cardiovascular responses induced in the rat, of different nitric oxide modulators (nitroglycerin, sodium nitroprusside and L-arginine). Nitroglycerin and sodium nitroprusside induced a similar pattern of neuronal activation in several areas, which include the paraventricular and supraoptic nuclei of the hypothalamus, central nucleus of the amygdala, parabrachial nucleus, locus coeruleus, ventrolateral medulla and nucleus tractus solitarius. However, only nitroglycerin activated the periaqueductal grey and nucleus trigeminalis caudalis. L-arginine-induced neuronal activation was restricted to the paraventricular and supraoptic nuclei of the hypothalamus. As regards cardiovascular effect, both nitroglycerin and sodium nitroprusside induced moderate hypotension (nitroglycerin: -23.3%, sodium nitroprusside: -24.3%) that lasted 40 min in the case of sodium nitroprusside and 80 min in the case of nitroglycerin. L-arginine did not significantly influence blood pressure. These data suggest that nitroglycerin, sodium nitroprusside and L-arginine are associated with different biological effects on both the central nervous system and the cardiovascular system. Of the NO-related drugs tested in this study, only nitroglycerin confirmed its ability to activate brainstem areas implicated in nociception.

Analysis of Variance↗

Activation of the transcription factor NF-kappaB in the nucleus trigeminalis caudalis in an animal model of migraine.

The infusion of nitroglycerin (NTG) induces an inflammatory state in perivascular meningeal tissues of rat via the activation, inter alia, of nuclear factor kappa B (NF-kappaB). This phenomenon has been related to the mechanisms involved in the pathophysiology of migraine, a common neurovascular disorder. In the present study, we sought to elucidate whether NF-kappaB activation might have a role in the determinism of migraine attacks also at the neuronal level. Therefore, we investigated the transcriptional activity of NF-kappaB in the brainstem of rats systemically injected with NTG and killed 4h later. Activation of NF-kappaB in brain areas was detected by means of both the immunohistochemical technique and the Western blot analysis. A significant increase of nuclear immunostaining of p65, an indicator of NF-kappaB activation, was detected in lamina I and II of nucleus trigeminalis caudalis in rats injected with NTG when compared with the control group. Western blot analysis confirmed the activation of the NF-kappaB pathway showing an increase in the optical density of p65 in nuclear extracts of lower brainstem of rats injected with the nitric oxide (NO) donor. The present study contributes to expand on our understanding of the complex mechanisms by which NTG may trigger migraine-like headaches in migraineurs. Furthermore, these findings pave the way to new bio-molecular and pharmacological avenues for the development of innovative migraine therapies.

Animals↗

Medical healthcare use in Parkinson's disease: survey in a cohort of ambulatory patients in Italy.

BACKGROUND: Parkinson's disease (PD) is a chronic neurodegenerative disease which at present has no cure, and it usually results in severe disability. The burden of PD increases as the illness progresses, resulting in the extensive utilisation of both health and community services. Knowledge of healthcare use patterns and of their determinants may greatly contribute to improve patient care, however few studies have examined this issue in PD. The present study was devised to describe the type of and reasons for medical healthcare resource use in persons with PD attending a Centre for PD and Movement Disorders, and to examine drug prescriptions issued on such occasions. METHODS: The study was a retrospective, cross-sectional survey in a cohort of ambulatory patients with PD, conducted by means of standard interviews. RESULTS: In the year before the study, 92 (70.8%) of 130 patients used medical healthcare resources: 1/5 of the patients was admitted to hospital, 1/5 to emergency room, 2/5 were visited by a non-neurology specialist, and 1/4 by the GP. Reasons were: nearly 20% programmed hospital admissions and visits, and more than 25% injuries and musculo-skeletal diseases. Other conditions typically occurring in PD (e.g. dementia, diabetes and cardio- and cerebro-vascular disease) were less frequently involved. On such occasions, drugs for PD were occasionally changed, however drug prescriptions for other indications were issued to more than 66% of the patients. CONCLUSION: Several physicians other than the neurologist may take care of PD patients on different occasions, thus emphasising the need for communication between the reference neurologist and other physicians who from time to time may visit the patient.

Adult↗

Relationship between hallucinations, delusions, and rapid eye movement sleep behavior disorder in Parkinson's disease.

Psychotic symptoms are the main and the most disabling "nonmotor" complications of Parkinson's disease (PD), the pathophysiology of which is poorly recognized. Polysomnographic studies have shown a relationship between visual hallucinations and rapid eye movement (REM) sleep. The objective of this study is to clarify the relationship between psychotic symptoms and REM sleep behavior disorder (RBD) in PD. In a Parkinson's disease outpatient unit, 289 consecutive subjects with idiopathic PD were administered (in the period from January to December 2002) a multiple-choice questionnaire and structured interview on sleep and mental disorders. RBD was diagnosed in accordance with the minimal diagnostic criteria of the International Classification of Sleep Disorders. Hallucinations and delusional disorders were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders-IV criteria. The presence or absence of psychotic symptoms, of RBD, and of daytime sleepiness, as well as motor status, cognitive status, and mood were assessed. Approximately 32% (n = 92) of the subjects presented with psychotic disorders; 30% (n = 86) had experienced hallucinations; 2% (n = 6) had delusions without hallucinations. Sixty-two (72%) hallucinators reported nocturnal hallucinations. A total of 6.6% (n = 19) of the subjects complained of a delusional disorder. There were 26.6% (n = 77) of subjects who presented with RBD: 28 (36%) with onset before and 49 (63%) with onset after PD diagnosis. The presence of RBD was associated with an increased risk of manifesting hallucinations and delusions (odds ratio [OR], 2.73). Other independent clinical factors found to have an effect on psychotic disorders were cognitive impairment (OR, 3.92), disease duration (OR, 2.46), advanced age (OR, 2.34), and severity of motor symptoms (OR, 2.06). These results suggest that RBD is widely associated with psychosis in PD.

Aged↗

Neurophysiological approach to central pain modulation in primary headaches.

The study of CNS pain-modulating pathways has led to important discoveries about the role of central nociceptive structures such as PAG and hypothalamus in the pathophysiology of episodic and chronic primary headaches. Functional neuroimaging studies have revealed that primary headaches are characterised by different patterns of activation of central pain modulatory structures. A future model of headache pathophysiology investigating the contribution of CNS pain-modulating pathways will probably increase our understanding of pain processing in primary headaches. Herein we review the neurophysiological approaches to assess central pain modulation in primary headaches with emphasis on the diffuse noxious inhibitory control, a form of endogenous pain inhibition. In addition, patients' data will be presented that highlights the utility of such methods for primary headache's pathophysiology and clinical monitoring.

Headache↗

Introduction to the new International Classification of Headache Disorders.

Based on the first edition of the classification (already validated), the ICHD-II is intended for not only the researcher and clinician but also the neurologist and general practitioner. All the headaches are classified into groups and subgroups to provide the level of diagnosis necessary for each user.

Headache Disorders↗