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Biomedical subjects

C Pacchetti

Publications and source records attributed to C Pacchetti.

At least 19 recordsLinked to original sources
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↗
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.

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PubMed2004

Modifications of apoptosis-related protein levels in lymphocytes of patients with Parkinson's disease. The effect of dopaminergic treatment.

In this study, we investigated whether changes in the regulatory mechanisms of apoptosis and oxidative stress may be detected, peripherally, in patients with Parkinson's disease (PD). For this purpose, we measured caspase-3 activity, Bcl-2 concentrations, peripheral benzodiazepine receptor (PBR) expression and Cu/Zn superoxide dismutase (SOD) concentrations in lymphocytes of untreated PD patients, patients treated only with L-Dopa or with L-Dopa and dopamine agonists and healthy volunteers. Caspase-3 activity was significantly increased in all PD patient groups. Patients treated with L-Dopa and dopamine agonists showed the lowest values of Bcl-2, coupled with the highest density of PBRs, while increased levels of Cu/Zn SOD were found in the group under monotherapy with L-Dopa. We also found, in PD patients, clear, negative correlations between Bcl-2 levels and both duration and severity of the disease. Our findings point to the existence of changes in the regulatory mechanisms of apoptosis in PD patients -- observable outside the central nervous system -- which seem to be modulated by the pharmacological treatment with dopaminergic agents.

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PubMed2004

Comorbid disorders and hospitalisation in Parkinson's disease: a prospective study.

Parkinson's disease (PD) is often associated with other disorders, typical of the disease or of the age of PD patients, that can lead to hospitalisation, sometimes as emergencies. In this one-year prospective, longitudinal study, we investigated the comorbid events prompting the hospitalisation, or occurring during the planned hospitalisation, of an unselected group of 180 PD patients, admitted to 9 general hospitals in the course of the study. The most frequent acute comorbid events were trauma (30.5%), mostly due to falls, and vascular disorders (29.3%). Comorbidities were closely related to PD in 50% of cases. More than 50% of patients did not require (in addition to PD therapy) specific treatment for the acute comorbid event. Older age was associated with increased risk of complications. The setting up of multidisciplinary networks covering entire territories could help to improve the way in which we tackle the clinical and social problems generated by PD and its comorbidities.

Accidental Falls↗
PubMed2004

Cognitive rehabilitation in Parkinson's disease.

A rehabilitation program of 6 weeks, including both motor and cognitive training, was applied to 20 patients affected by Parkinson's disease (PD) in the early stages, presenting with mild cognitive deficits, but no dementia. Cognitive rehabilitation has been performed by utilizing a software elaborated for neuropsychological training (TNP). At the end of the scheduled sessions, the patients showed a significant improvement at verbal fluency, logic memory and Raven's matrices tests, as compared to baseline. These results remained stable over the time. We hypothesize that rehabilitative training exerts its positive effects by reinforcing cognitive strategies, in particular, by enhancing frontal function, which are typically impaired in PD, and suggests that this instrument could be implemented in nonpharmacological treatment of this pathology.

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PubMed2003

Modifications of plasma and platelet levels of L-DOPA and its direct metabolites during treatment with tolcapone or entacapone in patients with Parkinson's disease.

We compared--retrospectively--the effects of a 3-month therapy with catechol- O-methyltransferase (COMT) inhibitors tolcapone (100 mg, t.i.d.) and entacapone (200 mg, t.i.d.), on L-DOPA metabolism in two groups of parkinsonian patients with motor fluctuations. Plasma and platelets concentrations of L-DOPA and its direct metabolites, dopamine and 3- O-methyldopa (3-OMD), were measured before starting treatment, after two weeks and at the end of treatment. Patients treated with tolcapone showed significant increases in plasma and platelet L-DOPA levels and marked reduction of plasma and platelet 3-OMD levels, both at short- and long-term. Entacapone did not modify L-DOPA levels, while inducing a less marked reduction of plasma and platelet 3-OMD concentrations, with respect to tolcapone, at both time points. Both drugs were similarly effective in increasing plasma and platelet levels of dopamine. These results confirm the different profiles of activity of the two drugs, with tolcapone proving more effective on both the intra- and extra-cellular levels of L-DOPA and 3-OMD.

Age Factors↗
PubMed2003

Sleep attacks in Parkinson's disease: a clinical and polysomnographic study.

The objective of the study was to evaluate daytime sleepiness, (the features of episodes of sudden sleep onset), i. e., so-called sleep attacks (SAs), in three male Parkinson's disease (PD) patients (mean age 66 years) on chronic therapy with ropirinole or pramipexole. A structured clinical interview, the Epworth Sleepiness Scale, and continuous 24-h ambulatory polysomnography were used to assess the features of SAs occurring in the patients in their normal home environments. The polysomnographic patterns characterizing SAs (sleep occurring against a background of wakefulness, and not preceded by a feeling of sleepiness or by other heralding symptoms) were analyzed. The results showed that SAs can be clearly documented through polysomnographic monitoring and really, but rarely, occur in PD. SAs seem to represent the extreme of the continuum of daytime sleepiness observed in PD patients.

Aged↗
PubMed2002

Hallucinations and sleep-wake cycle in PD: a 24-hour continuous polysomnographic study.

Twenty-four-hour ambulatory polysomnography was performed in 20 patients with PD who were having visual hallucinations (12 men and 8 women, mean age 70 +/- 6 years). Visual hallucinations were clearly related to daytime NREM sleep or nocturnal REM sleep in 33% of the instances. The data reinforce the hypothesis that neural mechanisms implicated in generating sleep and, in particular, in dream imagery play a role in the occurrence of visual hallucinations in PD.

Aged↗
PubMed2002

Parkinson's disease and reproductive life events.

Onset, progression and duration of Parkinson's disease (PD) seem to be similar in men and women but gender differences have been suggested concerning clinical aspects, such as more severe disease in men and more dyskinesia in women. Taking into account the multiple influences of sex hormones, estrogens in particular, on basal ganglia function, the present work compared the characteristics of reproductive events in PD subjects and in healthy women, with regard to onset and clinical aspects of the disease with respect to the milestones of reproductive life. A total of 150 PD women and 200 healthy women matched for age were interviewed about reproductive life and disease characteristics (if patients). As a group, the women with PD had menarche later than the controls, but in the normal range. Menopause was similar to the controls for time, type (natural) and onset (slow), but with less hormonal therapies. Women with PD had fewer children, while breast feeding and gynecological diseases were comparable to controls. The characteristics of menses were similar as far as dysmenorrhea and premenstrual syndrome (PMS). The women with PD onset before menopause had a longer disease duration, with a more frequent fluctuating stage, and longer treatment with both levodopa and dopamine agonists. They had more dysmenorrhea and PMS when compared with women with PD onset after menopause and controls.

Adult↗
PubMed2000

Botulinum toxin treatment for functional disability induced by essential tremor.

This study aimed to improve botulinum toxin's (BTX) efficacy and to reduce its unwanted effects in the treatment of functional disability due to essential tremor (ET) of the hand. Twenty patients with disabling ET, not responding to conventional pharmacological therapy, were enrolled in this open-label study. Activities of daily living self-questionnaire (ADLS) and severity tremor scale (STS) were used to establish patients' functional disability and tremor severity. Accelerometry and surface electromyography were used to identify the arm muscles with tremorogenic activity during impaired positions. Global rating was used to measure treatment efficacy and unwanted effects. BTX type A was injected into the muscles principally responsible for impaired positions. After BTX treatment, there was a significant reduction in both severity and functional rating scales scores (ADLS and STS) and of tremor amplitude as measured with accelerometry and EMG. Adverse effects were limited to a slight third finger extension weakness in 15% of patients. BTX injections are effective and safe in reducing disability due to ET, if based on the criterion of functional selection.

Aged↗
PubMed1999

Peripheral markers of oxidative stress in Parkinson's disease. The role of L-DOPA.

Oxidative stress plays a central role in the pathogenesis of Parkinson's disease (PD). L-DOPA, the gold standard in PD therapy, may paradoxically contribute to the progression of the disease because of its pro-oxidant properties. The issue, however, is controversial. In this study, we evaluated peripheral markers of oxidative stress in normal subjects, untreated PD patients and PD patients treated only with L-DOPA. We also measured platelet and plasma levels of L-DOPA, 3-O-methyldopa (the long-lasting metabolite of the drug), and dopamine. We found that isolated platelets of treated PD patients form higher amounts of 2,3-dihydroxybenzoate, an index of hydroxyl radical generation, than platelets of controls or untreated patients. In treated patients, platelet levels of 2,3-dihydroxybenzoate were positively correlated with platelet levels of L-DOPA, 3-O-methyldopa, and with the score of disease severity. Disease severity was correlated with platelet and plasma levels of L-DOPA, as well as with the daily intake of the drug. No significant differences in platelet levels of cytosolic and mitochondrial isoforms of the antioxidant enzyme superoxide dismutase were found between PD patients, either treated or untreated, and controls. Our findings lend further support to the hypothesis that L-DOPA might promote free radical formation in PD patients.

Antiparkinson Agents↗
PubMed1997

Simultaneous determination of L-dopa and 3-O-methyldopa in human platelets and plasma using high-performance liquid chromatography with electrochemical detection.

Various high-performance liquid chromatographic (HPLC) methods for the determination of plasma levels of L-dopa and of its metabolite, 3-O-methyldopa (3-OMD), have been previously described. In this study, we report a modification of these methods, that enables the assay of these two compounds in platelets and plasma obtained from the same sample of whole blood. Reversed-phase (RP) HPLC with electrochemical (coulometric) detection was used. The within-run and between-run coefficients of variations, for the two compounds, were less than 10%, in both platelets and plasma; the detection limits for platelet levels of L-dopa and 3-OMD were 2 and 6 ng/10(9) platelets, respectively. In plasma, the detection limits for L-dopa and 3-OMD were 1 and 3 ng/ml, respectively. The method is rapid and simple. When applied to a population of patients with Parkinson's disease under treatment with L-dopa, this method revealed detectable levels of L-dopa and 3-OMD in the platelets of all patients. The application of this technique may provide new insights into the pharmacokinetics of L-dopa in patients with Parkinson's disease.

Adult↗
PubMed1997

Is seborrhea a sign of autonomic impairment in Parkinson's disease?

An increase of sebum excretion rate (SER) is frequently observed in patients suffering from Parkinson's disease (PD). Some authors attribute it to the hyperactivity of the parasympathetic system, while others consider the possible action of androgens or of MSH-hormone. The aim of our study was to verify and quantify SER in 70 parkinsonian patients and compare it with SER in 60 normal subjects. We found higher values of SER in male subjects, both in normal and in parkinsonian patients. The highest rate of excretion was observed in parkinsonian males, in agreement with the possible main role of androgens or testosterone in sebum excretion, while the phenomenon did not appear to be related to abnormalities of the autonomic nervous system. The association of PD and sex hormones might therefore be crucial for the developing of seborrhea.

Aged↗
PubMed1995

"Off" painful dystonia in Parkinson's disease treated with botulinum toxin.

The "off" painful dystonia (OPD), usually concerning the feet, is a type of abnormal involuntary movement, induced by the chronic use of levodopa. It is mostly observed in the advanced stage of Parkinson's disease (PD), particularly in the early morning, in the evening, and late at night. Indeed, some patients have experienced OPD also during "on" periods when dystonic posture of the foot alternates with dyskinesia. The pain probably is due to sustained muscle contraction, which causes prolonged muscle spasm, as in primary dystonia or torticollis. Dopaminergic drugs like bromocriptine, pergolide, and especially apomorphine (s.c. infusions, or bolus), can dramatically improve the OPD. Anticholinergics baclofen and lithium are alos used in the management of OPD with some benefit. On the other hand, clinical experience shows that in many cases, these therapeutic procedures are not always enough to produce the expected results. Thirty PD patients (22 men and eight women) with OPD of the foot were treated with botulinum toxin (Botox, Btx) using electromyograms to guide injections. Dystonia was evaluated using a quantitative rating scale. The selection of the muscles for Btx treatment was carried out on the basis of foot posture. We injected Btx into tibialis posterior, tibialis anterior, gastrocnemius, flexor digitorum longus, and extensores hallucis longus with a median dose 40 IU for each muscle, distributed in two sites. In all patients, the pain improved within 10 days, whereas in 21 patients, the pain disappeared completely for 4 months (range, 3-7 months); a concomitant improvement in intensity of the dystonic spasm was also observed. No side effects were reported. Seven patients with associated "on" foot dystonia described an improvement of foot posture on walking. In conclusion, in this uncontrolled study, the use of Btx in OPD seemed a promising tool to improve pain linked to foot dystonia; however, because of the well-known underlying dopaminergic defect in OPD, the Btx therapy should be considered only if the dopaminergic treatment established for the management of OPD has failed.

Aged↗
PubMed1995

A crossover, controlled study comparing pergolide with bromocriptine as an adjunct to levodopa for the treatment of Parkinson's disease.

A single-blind, crossover study was carried out to compare the efficacy and safety of pergolide against that of bromocriptine in 57 patients with Parkinson's disease who showed a declining response to levodopa therapy. Patients were randomly assigned to receive either bromocriptine followed by pergolide, or pergolide followed by bromocriptine. Both drugs were administered for 12 weeks. Patients were assessed by a clinician blinded to treatment assignment using the New York University Parkinson's Disease Scale. The average daily dose of pergolide was 2.3 +/- 0.8 mg and of bromocriptine 24.2 +/- 8.4 mg. Addition of pergolide or bromocriptine resulted in a significant improvement in total scores when compared with the previous treatment of levodopa alone (pergolide, p = 0.0001; bromocriptine, p = 0.0005). Pergolide was more effective than bromocriptine in daily living scores (p = 0.02) and motor scores (p = 0.038). No differences in the incidence of dyskinesias, dystonias, or psychosis were observed between groups. Fewer adverse events were recorded in the pergolide group, and most patients and physicians preferred pergolide to bromocriptine. Pergolide as adjunctive therapy to levodopa was more effective than bromocriptine in this short-term trial.

Aged↗