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Biomedical subjects

R Fariello

Publications and source records attributed to R Fariello.

At least 19 recordsLinked to original sources
PubMed2002

The neuromelanin of human substantia nigra and its interaction with metals.

Neuromelanin (NM) is a peculiar biochemical component of several neurons in the Substantia Nigra (SN), the target area of the degenerative process in Parkinson Disease (PD). SN NM has peculiarities as to its composition and an impressive capacity of chelating metals, iron in particular, but not exclusively. Gaining insights into the structural and functional characteristics of NM should help understanding the reasons of selective vulnerability of nigral neurons in many parkinsonian conditions. From the present data a protective role of NM can be postulated until the buffering capability toward heavy metals are exhausted. The overloading of NM with iron and other metals in neurons may trigger inflammatory and degenerative processes aggravating the underlying pathological condition.

Drug Interactions↗
PubMed1998

Ventricular arrhythmias in normotensive subjects and in mild hypertensive patients.

Twenty-five normotensive subjects (14 men, 11 women) aged from 25 to 60 years (mean 36) and 30 untreated patients with mild hypertension (stages 1 and 2, JNC V) without target organ damage (16 men, 14 women), aged 26-59 years (mean 35.8) underwent continuous 24-hour ECG Holter monitoring with a Fukuda Denshi SM-40 ambulatory recorder and SCM-400 ECG analyzer. During 24-hour ambulatory ECG recording, mean heart rate was slightly but not significantly higher in hypertensive patients (73.3 +/- 10 beats per minute [bpm]) in comparison with normotensive subjects (71.2 +/- 12 bpm). The prevalence of premature atrial contractions was similar in the two groups. Total ventricular arrhythmias were more prevalent in the group of mild hypertensive patients (P < 0.05), who also had a higher prevalence in complex forms of ectopy (r = 0.81 for bigeminy; r = 0.83 for trigeminy; r = 0.83 for couplets). Holter recordings did not show abnormalities of ST-T wave or episodes of silent ischemia.

Adult↗
PubMed1997

Effects of nicergoline on age-related decrements in radial maze performance and acetylcholine levels.

The effects of chronic oral administration of nicergoline (5.0 mg/kg; bid) on locomotor activity, eight-arm radial maze performance plus striatal, cortical, and hippocampal acetylcholine (ACh) levels were examined in young and aged Wistar rats. Chronic nicergoline administration did not modify either the locomotor activity or radial maze learning in young rats. Young rats learned the radial maze procedure rapidly and improved their performance throughout the successive training sessions. Radial maze performance in young rats was characterised by very few arm reentries. Aged rats were hypoactive and did not explore or enter the radial maze arms, and consequently performed poorly in the radial maze throughout the training sessions. Nicergoline treatment did not significantly modify locomotor activity in aged rats. Aged rats treated with nicergoline also performed poorly initially but improved with repeated training in the radial maze. This improvement was associated with an increasing number of arms being entered and very few arm reentries. Reduced acetylcholine (ACh) levels were also associated with age. Aged rats had significantly reduced levels of ACh in the straitum and cortex, but not the hippocampus as compared to young rats. Nicergoline treatment did not change ACh levels in young rats, but substantially restored the reduced ACh levels in aged rats. These results indicate that nicergoline is an effective cognitive enhancer in a learning model of age-related deficits and that these results may be related to changes in the cholinergic system.

Acetylcholine↗
PubMed1997

Clinical and pharmacokinetic evaluation of L-dopa and cabergoline cotreatment in Parkinson's disease.

Previous investigations on the mutual pharmacokinetic influence of L-dopa and dopamine agonists in Parkinson's disease (PD) have shown controversial results. Two studies of the possible clinical and pharmacokinetic interaction between L-dopa and cabergoline were performed in 10 patients with de novo PD and 12 patients with fluctuating PD. In the first study (de novo patients), cabergoline was administered at increasing dosages until the maximum dosage of 2 mg/day once a day for 8 weeks; subsequently L-dopa (250 mg/day) was added. Blood levels of cabergoline were assayed in two different days, before starting L-dopa, and 1 week thereafter. In the second 8-week study (fluctuating patients), cabergoline was added to the current L-dopa therapy (maximum dosage 4 mg/day once a day). Blood levels of L-dopa were measured in two different days, before cabergoline was added, and at the end of the study. In both studies motor performance was evaluated by means of the Unified Parkinson's Disease Rating Scale (motor examination) and the Clinical Global Impression Scale; on-off diaries of daily motor condition also were filled by fluctuating patients. In patients with de novo PD, cabergoline pharmacokinetic parameters were unmodified by the adjunct of L-dopa, except that the time to reach the peak concentration (Tmax) significantly increased after L-dopa. In patients with fluctuating PD, no modification of L-dopa pharmacokinetics was observed before and after cabergoline coadministration. Clinical evaluations confirmed that cabergoline is effective in the treatment of advanced PD as well as in the management of de novo patients.

Aged↗
PubMed1996

Modulation of phosphoinositide turnover by chronic nicergoline in rat brain.

Basal and agonist-stimulated phosphoinositide (PI) turnover and inositol 1,4,5 -trisphospate (InsP3) content in rat brain were investigated after chronic nicergoline (SERMION) treatment. Oral administration of nicergoline (5 mg/kg b.i.d. for 7 weeks) enhanced the basal turnover of PI in the cerebral cortex compared to controls. This effect was paralleled by a significant rise of cortical InsP3 levels. No significant changes of noradrenaline- or carbachol-induced accumulation of [3H]-inositol-I-phophate ([3H]-InsP1) were found in cortices from nicergoline-treated rats. On the contrary, in the striatum nicergoline significantly potentiated the responsiveness of noradrenaline- and carbachol-stimulated PI turnover, leaving unchanged the basal production of [3H]-InsP1 and InsP3 levels. The results suggest that the interaction of nicergoline with PI transducing pathway might have relevance to the mechanisms of action of nicergoline.

Animals↗
PubMed1996

Ambulatory-determined 24-hour blood pressure in mild hypertensives and in normotensives.

Noninvasive ambulatory twenty-four-hour blood pressure (BP) monitoring was carried out in 30 normotensive subjects (16 women, 14 men), aged twenty-five to sixty years (mean thirty-eight) and in 29 mild essential hypertensive patients without target organ damage (14 women, 15 men), aged twenty-three to sixty-one years (mean thirty-nine). Hypertensive patients were not treated, and they discontinued any antihypertensive treatment at least four weeks before the study. During the daytime period (6 AM-10 PM) BP was monitored every fifteen minutes, and during the night (10 PM-6 AM), every thirty minutes. Obviously, mean twenty-four-hour systolic blood pressure (SBP) and diastolic blood pressure (DBP) were higher in hypertensive patients (P < 0.001). There was a persistent correlation in the group of mild hypertensives between successive BP hourly mean readings (r ranged from 0.61 to 0.93 for SBP and from 0.45 to 0.82 for DBP). In normotensive subjects these correlations failed in particular periods: 8 AM-9 AM, r = 0.30 for SBP and 0.45 for DBP; 1 PM-3 PM, r = 0.17-0.49 for SBP and 0.28-0.37 for DBP; 9 PM to midnight, r = 0.21-0.57 for SBP and 0.23-0.38 for DBP.

Adult↗
PubMed1995

[Ambulatory monitoring of blood pressure profiles in in hypertensive patients 26-65 years of age].

We evaluated blood pressure profile in a population of 380 untreated hypertensives (210 males, 170 females, stage 1 and 2 JNC 1993) observed consecutively. A 24-hour ambulatory blood pressure monitoring was performed using and A&D TM 2420 model 6 device programmed to measure systolic and diastolic blood pressure every 15 min from 7 am to 10 pm (daytime) and every 30 min from 10 pm to 7 am (night-time). Statistical analysis was carried out by dividing the patients into four groups on the basis of age: Group I, from 26 to 35 years (26 males, 14 females); Group II, from 36 to 45 years (48 males, 39 females); Group III, from 46 to 55 years (85 males, 72 females); Group IV, from 56 to 65 years (51 males, 45 females). Systolic blood pressure was higher in older male hypertensives (56 to 65 years) who also had a persistent systolic blood pressure elevation during night-time (non-dippers); diastolic blood pressure was significantly higher in male hypertensives aged 36 to 55 years.

Adult↗
PubMed1994

Motor expression of kainic acid seizures is attenuated by dopamine depletion in mice.

We studied the effect of striatal dopamine depletion induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice on kainic acid (KA) evoked seizures. MPTP, 36 mg/kgp i.p. for 3 days, caused an 80% drop of striatal dopamine. Animals pretreated with MPTP, plus controls treated with saline, were challenged with five different convulsant doses of KA (3, 6, 12, 18 and 36 mg/kg i.p.). The seizures were monitored by electrographic recording and behavioral observation. MPTP pretreatment greatly attenuated the severity of the convulsions and the mortality induced by KA. The effect was mostly evident at the intermediate and at the high doses of KA. Surprisingly, no differences between the MPTP and control groups were found on the intensity and time course of the electrical seizures. Increment doses of KA resulted in a more severe electrographic seizure pattern in both the saline and the MPTP pretreated groups. Our data suggest that the dopamine depletion induced by MPTP does not alter the genesis of KA induced seizures, but may alter the function of cerebral structures involved in the control of seizure motor expression.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1993

[Elevated cardiovascular mortality in subjects over 75 with low values of arterial pressure].

PURPOSE: The purpose of this study was to extend the observations from recent studies that have shown an increased mortality in elderly people with low blood pressure. METHODS: In 1982 we enrolled 88 subjects, 30 males, 58 females, aged 75-90 years, divided into 3 groups, according to their blood pressure and matched for sex, serum cholesterol, smoking and body mass index: Group I: 20 people with blood pressure equal or less than 120/75 mmHg; Group II: 46 subjects with blood pressure level ranging from 130/80 to 145/90 mmHg; Group III: 22 patients with hypertension (blood pressure equal or more than 160/95 mmHg). These three groups were followed for 6 years (1983-1988) to evaluate the mortality from cardiovascular diseases. During this period, no antihypertensive drugs were given, nor did any other treatment significantly modify the value of blood pressure. No patient changed starting group. RESULTS: Mortality from cardiovascular diseases was as follows: Group I: 14 deaths (mean age 82 +/- 5, 8 for heart failure, 2 for myocardial infarction, 4 for stroke); Group II: 8 (p < 0.001 versus Group I, mean age 81 +/- 3, 6 for heart failure, 1 for myocardial infarction, 1 for stroke); Group III: 4 (p < 0.001 versus Group I, mean age 80 +/- 2, 1 for heart failure, 1 for myocardial infarction, 1 for stroke and 1 for sudden death). CONCLUSIONS: This study adds further observations indicating an increase of mortality for cardiovascular diseases in subjects over 75 years with low levels of blood pressure, which could be more dangerous than moderately high levels in older people.

Aged↗
PubMed1991

The acute convulsant effect of MPTP is dependent on intracerebral MPP+.

The administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to C57 black mice causes an acute seizure syndrome the severity of which is dose dependent; there is also a good correlation between the seizure inducing potential of MPTP and the neostriatal dopamine (DA) depletion caused by MPTP. The simultaneous administration of MPTP and MAO B inhibitors attenuates both epileptiform phenomena and neostriatal DA depletion. On the contrary diethyldithiocarbamate (DDC) exacerbates both responses. All these pharmacological manipulations are known to affect the accumulation of 1-methyl-4-phenylpyridinium ion (MPP+) the main metabolite of MPTP. Thus the present data support the hypothesis of a strict dependence of the epileptiform phenomena on the presence of MPP+. Furthermore the tight correlation existing between the severity of epileptic events and DA depletion suggests that the acute excitotoxic syndrome may contribute to the long-term toxicity of MPTP. *On leave from the Department of Neurology, University of Pisa, Pisa, Italy.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1991

Nigral degeneration in acquired immune deficiency syndrome (AIDS).

Using stereological techniques we have estimated the volume density of melanin and counted the number of pigmented and non-pigmented neuronal cell bodies in the pars compacta of the substantia nigra of 12 autopsied patients with acquired immune deficiency syndrome (AIDS) who did not have inflammation or necrosis of the midbrain or clinical parkinsonism. The total number of neuronal cell bodies was 25% lower in AIDS (P less than 0.01) than in 12 age-matched controls, although the volume density of neuronal melanin did not differ from that of controls because the percentage of pigmented cell bodies was higher (P less than 0.01) and the cell bodies were more fully packed with melanin in AIDS. Also, the expected increase with age of the volume density of neuronal melanin (P less than 0.02) and the percentage of pigmented neurons (P less than 0.01) occurred in the controls but not in AIDS patients. Importantly, our histopathological examination showed unequivocal nigral degeneration with neuronal loss, small neuronal cell bodies packed with melanin, reactive astrocytosis and extra-cellular melanin in the AIDS patients but not in controls. Our study shows that a subclinical nigral degeneration is common in AIDS and could possibly explain the heightened susceptibility of some patients to drug-induced parkinsonism.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Snoring and risk of cardiovascular disease.

In order to evaluate the possible role played by snoring as a risk factor for cardiovascular disease, we studied 400 patients aged 30-80 years, divided into 4 groups matched for age, sex and body mass index. The first group consisted of 100 patients who snored, having risk factors (hypertension, diabetes, obesity, smoking, high serum cholesterol level) for cardiovascular disease. The second group consisted of 100 non-snoring patients with risk factors. The third and fourth groups were formed by 100 snoring and 100 non-snoring patients without risk factors. We investigated the morbidity and the mortality from cardiovascular disease over a period of five years (1982-1987). An increase in morbidity and mortality was found for snorers with risk factors (36 and 17 respectively) compared to non-snorers with risk factors (10 and 4, P less than 0.001), and also to both snorers and non-snorers without risk factors (7 and 3, P less than 0.001; 3 and 1, P less than 0.001 respectively). No difference was noted between snorers and non-snorers without risk factors. A higher morbidity and mortality for cardiovascular disease was found in snorers with risk factors as compared with non-snorers having risk factors. Furthermore, the morbidity and mortality in patients without risk factors was found to be lower compared with that found in snorers with risk factors. In conclusion, snoring worsened the prognosis of patients with risk factors for cardiovascular disease, but did not represent an independent or predictive risk factor in itself.

Adult↗
PubMed1991

Extended release felodipine in essential hypertension. Variations in blood pressure during whole-day continuous ambulatory recording.

Intraarterial blood pressure (BP) monitoring during free ambulation (Oxford technique) was carried out in 12 essential mild-to-moderate hypertensive patients undergoing 4 weeks treatment with felodipine, 10 mg given once daily in an extended release formulation. Compared to placebo, felodipine significantly reduced systolic and diastolic blood pressure throughout 24 h. The greatest reduction was observed at 10 AM, 3 h after drug administration (-32 +/- 6/-24 +/- 5 mm Hg for systolic and diastolic BP, respectively, P less than .001). Hourly BP values remained significantly lower up to and including the 24th hour during felodipine extended release treatment (-18 +/- 5/-11 +/- 3 mm Hg, P less than .001). Felodipine extended release also reduced 24 h blood pressure variability, evaluated on the standard deviation of each hourly mean (from 16.3 +/- 0.9/12.6 +/- 0.6 to 13.4 +/- 0.6/10.4 +/- 0.6 mm Hg, P less than .01). Furthermore, absolute BP values dropped significantly at the peaks of dynamic exercise (bicycle ergometer: from 248 +/- 13/123 +/- 11 to 204 +/- 24/102 +/- 13 mm Hg, P less than .001), isometric exercise (hand grip: from 232 +/- 18/133 +/- 16 to 180 +/- 20/101 +/- 16 mm Hg, P less than .001), and cold pressor test (from 229 +/- 20/127 +/- 14 to 178 +/- 22/99 +/- 15 mm Hg, P less than .001). In conclusion, felodipine extended release exerts a good antihypertensive effect which is maintained for 24 h and reduces the level of blood pressure peaks reached under different physical stresses.

Adult↗
PubMed1991

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↗
PubMed1991

Exercise-induced modifications in cardiorespiratory parameters of hypertensive patients treated with calcium antagonists.

The effects of calcium antagonists in reducing blood pressure at rest and during exercise were examined in patients with mild-to-moderate essential hypertension. The haemodynamic effects of calcium antagonists were evaluated at rest and during exercise. We also examined 10 patients with mild-to-moderate essential hypertension taking lacidipine, a new dihydropyridine calcium antagonist (4 mg once a day, at 0700 h). Compared with placebo, lacidipine induced significant mean reductions in 24-h blood pressure (P less than 0.001 for systolic blood pressure; P less than 0.002 for diastolic blood pressure). After 24 h, the blood pressure reductions were still significant (P less than 0.02 for systolic blood pressure; P less than 0.04 for diastolic blood pressure). The heart rate did not change. During dynamic exercise, blood pressure at maximal effort was reduced (P less than 0.01 for systolic and diastolic blood pressure) and the external workload reached at the anaerobic threshold was significantly increased (P less than 0.001), but not at maximum effort. Ventilation and tidal volume were similar at both the anaerobic threshold and peak exercise, while oxygen uptake and carbon dioxide production were increased at the anaerobic threshold (P less than 0.02 for carbon dioxide production) but were similar at peak exercise.

Adrenergic alpha-Antagonists↗
PubMed1990

Effect of enalapril on parasympathetic activity.

To evaluate the effect of converting enzyme inhibition induced by enalapril on parasympathetic activity, we studied ten essential hypertensive patients, age range 38-58 years, WHO I-II. Parasympathetic evaluation was obtained by measuring the variation of heart period (VHP) during at least 1 minute of steady-state, regular respiration. VHP was derived from the difference between the mean of all maximum and the mean of all minimum heart periods. The higher the VHP, the higher the parasympathetic control of heart rate and vice versa. VHP was measured supine and with tilting (30 degrees, 60 degrees, 85 degrees). Blood pressure was reduced after 1 month of enalapril treatment, while the heart rate did not change. VHP increased at the end of enalapril treatment compared with placebo: in the supine position it increased from 36 +/- 3.2 ms to 44 +/- 3.5 ms, p less than 0.01. VHP was also increased by enalapril at 30 degrees (p less than 0.05) and 60 degrees (p less than 0.05), while no difference was observed at 85 degrees between placebo and enalapril. A positive correlation was found between supine enalapril changes of VHP and those of systolic and diastolic BP. In conclusion, enalapril seems to increase parasympathetic cardiovascular control in essential hypertensive patients. This result might explain the lack of increase in heart rate that would be expected as a result of the vasodilating effect of enalapril.

Adult↗