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Biomedical subjects

L Rampello

Publications and source records attributed to L Rampello.

At least 37 records · Page 2Linked to original sources

Neuropsychiatric effects and type of IFN-alpha in chronic hepatitis C.

Chronic hepatitis is often associated with neuropsychiatric disorders. Interferon (IFN) is the drug most widely used to treat this disease, and its side effects, such as depression, often involve the central nervous system (CNS). Symptoms include a slowing down of psychomotor functions, loss of interest, frontal lobe dysfunction, parkinsonism, and delirium. The occurrence of these complications calls for dropping out of IFN treatment or for a significant dose reduction and administration of antidepressants. Efficacy and side effects vary on the basis of the IFN type employed. The aim of our study was to evaluate if the frequency, form, and degree of depression induced are related to the type of IFN employed. We studied 96 patients with chronic hepatitis C. Our study series was divided into four groups according to the type of IFN-alpha administered. Depression degree was clinically evaluated using the Hamilton Depression Rating Scale (HAM-D). All patients were tested before treatment and 1, 3, and 6 months (15 days after the end of treatment) later. Our results showed that the type of IFN used seemed to influence the depression onset rate, with the leukocyte type inducing the lowest level of depression. However, when a number of symptoms associated with the depression were considered, the results of other types of IFN-alpha were found to be better. Use of the most suitable type of IFN-alpha could thus lead to more personalized treatment, with fewer side effects. The type of IFN used seems to influence the psychological side effects and the adaptation rate to therapy. It would be appropriate to choose the type of IFN on the basis of a neuropsychiatric assessment carried out before treatment.

Adult↗

Nicergoline facilitates vestibular compensation in aged male rats with unilateral labyrinthectomy.

The ergoline derivatives, nicergoline (NIC) or dihydroergocristine (DHE) were administered at various doses (0.1, 0.5 and 1 mg/kg) to aged male rats subjected to labyrinth unilateral lesion (LBX). The nystagmus rate appeared to be lower in animals treated with DHE or NIC 1mg/kg than in saline-injected rats, when observed on day 1 and 2 after operation. The number of falls in the rotorod test of LBX animals was decreased by NIC 0.5 or 1 mg/kg at all observation times. This parameter was affected by DHE only at the higher dose. These results suggest that NIC facilitates vestibular compensation of LBX rats. DHE appeared to be less potent in this respect. Since both drugs act on central dopaminergic neurotransmission, it is possible that this neurotransmission may be involved in their mechanism of action.

Age Factors↗

Modulatory action of noradrenergic system on spinal motoneurons in humans.

Previous findings in animals demonstrated that the noradrenergic coeruleospinal system exerts a tonic facilitation on spinal reflexes and that activation of alpha2-autoinhibitory receptors can be responsible for a disfacilitation of the spinal activity. To investigate this issue further, we examined whether this system is also involved in descending facilitatory control of spinal motoneurons in healthy humans. The H-reflex technique was utilized to assay the motoneuronal excitability. The ratio between the maximal reflex response (H) and maximal direct response (M) was determined in each subject and was calculated at 10 min intervals before and after i.v. administration of the alpha2-agonist clonidine (0.5 microg/kg). In all subjects a marked decrease of the H/M ratio, due to depression of the H response, occurred 10 min following the clonidine injection and reached its maximum within 30 min. No significant changes of blood pressure values were provoked by drug injections. These results suggest that an autoinhibitory action may be induced by alpha2-receptor activation of locus coeruleus neurons in humans, and that this device may serve as a mechanism for a myotonolytic action on spinal motoneurons.

Adrenergic alpha-2 Receptor Agonists↗

Interferon alpha-induced depression in chronic hepatitis C patients: comparison between different types of interferon alpha.

IFN alpha treatment is able to produce dose-related side effects, such as depression, in the central nervous system. We assessed the effects on depression of four different types of IFN alpha (recombinant IFN alpha 2a, recombinant IFN alpha 2b, lymphoblastoid IFN alpha, leukocyte IFN alpha), administered at the same doses in four homogeneous groups of chronic hepatitis C patients (96 patients; 24 patients for each group). A group of 18 untreated hepatitis C patients was considered as a control group. Depression was measured using Zung's self-rating depression scale (SDS scale) before starting IFN alpha therapy and at the 1st, 3rd and 6th month of treatment. In all patients evaluated, mean SDS values increased from mild to moderate depression, but never attained severe depression (SDS > 70). More elevated SDS values were observed in the 1st month of treatment, with a progressive decrease during the end points above-mentioned. The recombinant IFN alpha 2a and lymphoblastoid IFN alpha arms presented higher SDS mean scores compared to the recombinant IFN alpha 2b and leukocyte IFN alpha arm. Only in the leukocyte IFN alpha arm SDS values returned to basal values at the 6-month end point. Leukocyte IFN alpha seemed to present a more elevated tolerability than other IFN alpha types available for clinical practice. A very careful selection of hepatitis C patients is required before starting IFN alpha therapy.

Aged↗

Tacrine treatment of Alzheimer's disease: many expectations, few certainties.

Quality of life and behavioral functions are severely reduced in patients affected by Alzheimer's disease (AD). Among the drugs employed in the treatment of this invalidating degenerative dementia, tacrine (THA) seemed to play a possible therapeutic role. Our study was aimed to evaluate the efficacy of THA in the treatment of AD, performing a comparison with lecithin and/or placebo treatment. Five randomized controlled trials on tacrine versus lecithin and/or placebo treatment were randomly selected. Mantel-Haenszel-Peto method was applied. Patients treated with tacrine achieved better results than control subjects (overall OR = 2.34; 95% CI 1.42-3.85); but long-term treatment with tacrine was not significantly more efficacious than placebo. Statistical significance in favor of THA versus other drugs employed was obtained in MMSE and ADAS-Cog tests in the studies carried out by Eagger et al. and Knapp et al. Moreover, Fitten et al. administered the highest tolerated THA dose to only a few patients enrolled in the study. The presence of broad CIs observed in the 5 meta-analytic studies infer non homogeneity of effects of treatment. Solely few patients improved, whereas the clinical conditions of the majority remained stationary. Between 5 and 10% of the outpatients in each single study presented reversible side effects calling for suspension of THA treatment. The optimal dose ranged between 80 and 160 mg THA, but often produced side effects. Comparative trials revealed the reduced efficacy and elevated toxicity of THA treatment, dampening the initial enthusiasm concerning the usefulness of this drug in AD. Furtermore, tacrine-induced side effects provoked many dropouts in all studies investigated. The effectiveness of tacrine treatment in AD disease was not fully confirmed. Other studies are required to identify doses and modalities of administration of this drug in AD.

Aged↗

Effects of acute or chronic administration of risperidone on motor and sexual behavior of male rats.

A number of experiments were carried out to explore the behavioral profile of a novel antipsychotic, risperidone, after acute or chronic administration, in a dose range of 0.1-10 mg kg-1. This drug did not affect the acquisition and retention of avoidance behaviors in a dose of 0.1 mg kg-1, either after acute or chronic administration. Higher doses induced a inhibited acquisition and a facilitated extinction (only after chronic treatment) of active avoidance behavior, but no significant effect on the retention of passive avoidance responses. In contrast, haloperidol inhibited the acquisition and facilitated the extinction of active avoidance behavior, and reduced the retention of passive avoidance reaction at the dose of 0.1 mg kg-1 injected either acutely or chronically. Ambulation and rearing of rats rated in an open field was increased by risperidone injected acutely at the dose of 1 mg kg-1. Under the same experimental conditions, grooming appeared to be reduced. In the same test, acute or chronic haloperidol 1 or 10 mg kg-1 inhibited all behavioral items. Furthermore, in contrast to haloperidol, the acute or chronic administration of risperidone in a dose range of 0.1-10 mg kg-1 did not substantially induce catalepsy and did not affect apomorphine-induced stereotypies. Also, the dose of 0.1 mg kg-1 induced a facilitation of male sexual behavior by increasing the frequency and reducing the latency of mountings, intromissions and ejaculations, while haloperidol 1 or 10 mg kg-1 inhibited this behavior. These findings suggest that the pharmacological profile of risperidone differs from that of classical neuroleptics, like haloperidol, probably due to different mechanism or site of action.

Analysis of Variance↗

Neurobehavioral syndrome induced by H2-receptor blocker withdrawal: possible role of prolactin.

Cimetidine and ranitine are histamine H2-receptor blockers widely used for the treatment of gastric hypersecretion and duodenal pathologies. They are known to induce hyperprolactinemia in humans. Forty-six patients treated with cimetidine or ranitidine who were exhibiting a neurobehavioral syndrome after withdrawal of the drugs were selected. This syndrome was associated with a drop in plasma prolactin levels. The symptoms of this syndrome were greatly improved by restoration of treatment with the same drugs and reappeared when the treatment was again suspended. This syndrome was inhibited in 36 patients by administration of domperidone (30 mg/day), a drug inducing hyperprolactinemia without crossing the blood-brain barrier, as compared with 10 control patients treated with placebo. These results suggest that the drop in prolactin levels occurring when cimetidine and ranitidine are suspended may contribute to the development of this syndrome. Also, the withdrawal of H2-receptor blockers could be included among the possible causes of some neurotic syndromes.

Adult↗

Behavioral and neurochemical alterations induced by reversible conductive hearing loss in aged male rats.

Eighteen months old male rats of the Sprague-Dawley strain were subjected to a reversible conductive hearing loss (HL) or a sham operation. A series of behavioral tests performed 3 months after surgery, revealed a sustained deficit in learning and memory capacity and a marked depressive attitude of rats with HL. At this time, a group of these animals were allowed to recover from HL for 1 month and were again tested behaviorally compared to those with persistent auditory deficit. A better performance at the active and passive avoidance tests and normal responsiveness to the despair test was found in animals with recovered hearing capacity as compared to those with persistent HL. A biochemical analysis revealed a decrease of dopamine and homovanillic acid content and of choline-acetyltransferase and acetylcholinesterase activity in the striatum and hippocampus of animals with persistent HL as compared to those with recovered auditory deficit. These data suggest that persistent auditory deafferentation affects cognitive mechanism in old rats in a reversible manner.

Aging↗

Vestibular compensation in aged rats with unilateral labyrinthectomy treated with dopaminergic drugs.

Drugs acting as agonists (SKF38393 and quinpirol) or antagonists (SCH23390 and sulpiride) on dopamine receptors were administered at various doses (1, 2 or 4 mg kg-1 day-1) to aged male rats of the Sprague-Dawley strain subjected to labyrinth unilateral lesion. The time course of vestibular compensation was evaluated by recording spontaneous eye nystagmus and by scoring ambulation and rearing with the open field test and motor ability and coordination with the rotorod test. Treatment started 3 days prior to surgery and continued until day 7 after surgery. The vestibular compensation of untreated young male rats was also studied with the same methods. The decline of spontaneous nystagmus in aged animals was slower than that of young rats and was facilitated by the large doses of quinpirol (D2 receptor agonist) and inhibited by sulpiride (D2 receptor antagonist) 4 mg kg-1 day-1, while the other drugs did not affect this parameter. After operation, ambulation and rearing of aged rats increased more slowly as compared to that of young animals. Moreover, motor performance and coordination in aged rats improved less rapidly than those of young controls. Dopamine receptor agonists increased ambulation and improved motor performance and coordination in aged rats, while dopamine receptor antagonists exerted opposite effects. Rearing was not affected by any kind of drug treatment. These results suggest that dopamine neurotransmission plays a role in vestibular compensation process following unilateral labyrinthectomy in aged animals, and this may have clinical relevance in vestibular pathologies of peripheral origin that are associated to brain ageing.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Hysterical neurosis of the conversion type: therapeutic activity of neuroleptics with different hyperprolactinemic potency.

To show a possible correlation between drug-induced hyperprolactinemia and improvement of hysterical neurosis of the conversion type, we followed 18 patients monitoring clinical somatic and psychic symptoms as well as serum prolactin levels. Six patients were treated with haloperidol and 12 with sulpiride; after 2 months sulpiride was administered at half the daily dose to 6 patients previously treated with the same drug. Clinical evaluation showed that sulpiride treatment led to a greater improvement compared to the haloperidol group. The different effectiveness of treatment could be explained by the different hyperprolactinemic potency. The therapeutic efficacy of neuroleptics suggests also that hyperactivity of dopaminergic transmission is involved in the pathophysiology of hysterical neurotic symptoms.

Adult↗

Comparative effects of amitriptyline and amineptine in patients affected by anxious depression.

In a double-blind, placebo-controlled study, the therapeutic efficacy of two antidepressants with different neurochemical mechanisms of action, amitriptyline and amineptine, was investigated in patients affected by anxious depression. Sixty-six patients with the primary diagnosis of major depression or bipolar affective disorder (DSM-III-R) and meeting additional operational clinical criteria such as anxiety, trepidation, restlessness, early and/or late insomnia, impulsivity, hostility, dysphoria, compulsivity, hyperperspiration, palpitation, pollakiuria and phobias were included. They were randomly assigned to three groups (n = 22) and treated either with placebo, amitriptyline (up to 100 mg/day) or amineptine (up to 200 mg/day) for 6 weeks. Patients showed better response to amitriptyline, a preferential inhibitor of serotonin reuptake, than to amineptine, a selective inhibitor of dopamine reuptake. The present results suggest that alterations in serotonergic rather than dopaminergic transmission contribute to the pathophysiology of anxious depression.

Adolescent↗

Behavioral effects of L-alpha-glycerylphosphorylcholine: influence on cognitive mechanisms in the rat.

The phosphorylcholine precursor, L-alpha-glycerylphosphorylcholine (alpha-GPC), was injected at the dose of 100 mg/kg/day for 20 days to aged male rats of the Sprague-Dawley strain, 24 months old, showing a deficit of learning and memory capacity. The drug was also administered to rats with amnesia induced pharmacologically with bilateral injections of kainic acid into the nucleus basalis magnocellularis (NBM). Learning and memory capacity of the animals, studied with tests of active and passive avoidance behavior, was improved after treatment with alpha-GPC in all experimental groups. These results indicate that this drug affects cognitive mechanisms in the rat through an involvement of central neurotransmission.

Animals↗

Effects of TRH-T on spinal motoneurones in man.

The effect of thyrotropin-releasing hormone tartrate (TRH-T) on the decrease in H Max/M Max ratio, an index of the spinal motoneurone pool, induced by haloperidol, was studied in 15 healthy volunteers. In all subjects, the H response was examined by an electromyographic apparatus. The values were expressed as H Max/M Max ratio, that gives an index of excitability of the spinal motoneurone pool. It was found that the mean H Max/M Max ratio value significantly decreased after haloperidol administration, but this effect was completely reversed by the injection of TRH-T. This finding suggests that the peptide may modulate motoneurone functions.

Adult↗

Trophic action of acetyl-L-carnitine in neuronal cultures.

Daily addition of acetyl-L-carnitine (100 microM) to cultured cerebellar granule cells since the first day of maturation led to an increased rate of expression of D-[3H]aspartate uptake (an established marker of maturation of glutamatergic neurons) and of N-methyl-D-aspartate (NMDA) receptors linked to large conductance ion channels permeable to Ca2+. Acetyl-L-carnitine treatment also increased neuronal survival, as reflected by a greater percentage of cultures retaining functional NMDA receptors after 15 days of maturation. These results support the view that acetyl-L-carnitine exerts neuronotrophic activity and prevents age-dependent neuronal degeneration.

Acetylcarnitine↗

Adenosine deaminase increases release of excitatory amino acids through a mechanism independent of adenosine depletion.

Addition of adenosine deaminase to cultured cerebellar neurones, led to large increases in the influx of 45Ca2+ and hydrolysis of polyphosphoinositide. These effects were inhibited or attenuated by glutamate receptor antagonists (AP5 or MK-801) and were not observed in cells stimulated by maximum concentrations of glutamate or quisqualate. Stimulation of the influx of 45Ca2+ and hydrolysis of phosphoinositide by adenosine deaminase may be secondary to an enhanced release of endogenous glutamate that in turn activates specific excitatory amino acid receptors. Accordingly, adenosine deaminase potently increased release of D-[3H]aspartate, an effect that requires the presence of extracellular Na+ and is insensitive to inhibition by MK-801. None of the effects of adenosine deaminase may be simply related to a fall in endogenous adenosine. In fact, the action of adenosine deaminase was neither reversed by agonists (L-PIA or NECA), nor mimicked by antagonists (IBMX or theophylline) of adenosine receptors. It is speculated that adenosine deaminase stimulates release of neurotransmitter through a mechanism independent of depletion of adenosine. A possible direct action of adenosine deaminase should be taken into account when the enzyme is used to unmask the effects of endogenous adenosine.

1-Methyl-3-isobutylxanthine↗

Dopaminergic hypothesis for retarded depression: a symptom profile for predicting therapeutical responses.

We assessed the therapeutical efficacy of various antidepressants (amineptine, minaprine and clomipramine) in patients affected by retarded depression. All patients exhibited symptoms of retardation, including hypokinesia, anergia, reduction of speech, increased salivation, hypersomnia, Parinaud's syndrome, reduced sexual activity, slowness, hypomimia, orthostatic hypotension, dysphagia and drowsiness. Antidepressant drugs were administered for a 6-week period in a randomized double-blind vs placebo design. The rank order of clinical effectiveness (amineptine much greater than minaprine greater than clomipramine greater than placebo) paralleled the specificity of antidepressants as dopaminomimetic agents. These results support the view that a reduced dopaminergic transmission contributes to the pathophysiology of retarded depression.

Adult↗

L-acetylcarnitine attenuates the age-dependent decrease of NMDA-sensitive glutamate receptors in rat hippocampus.

NMDA-sensitive glutamate receptors are involved in the regulation of neuronal plasticity, and contribute to the synaptic mechanisms underlying the learning process. Aging is associated with a reduction in the maximal density of NMDA-sensitive glutamate binding sites in rat hippocampus. This reduction is attenuated after long-term administration with L-acetylcarnitine (10 mg/Kg i.p. once a day for 4 months). These results support a neuroprotective and neurotrophic role for L-acetylcarnitine during aging.

Acetylcarnitine↗