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Biomedical subjects

L Frattola

Publications and source records attributed to L Frattola.

At least 55 records · Page 3Linked to original sources
PubMed1995

Effect of anticonvulsant drugs on peripheral benzodiazepine receptors of human lymphocytes.

Anticonvulsant drugs, such as carbamazepine, may exert some of their effects through peripheral benzodiazepine receptors (PBR), which are present in glial cells and regulate the synthesis of neurosteroids. PBR have also been demonstrated in human lymphocytes, where they might be used as peripheral markers of anticonvulsant drug effects. In the present paper we investigated the interaction of various antiepileptic drugs with PBR of human lymphocytes and evaluated possible effects of acute and chronic treatment with these drugs. At normal therapeutic concentrations, diazepam, carbamazepine and phenobarbital occupy respectively 70, 30 and 10% of PBR sites in human lymphocytes. Although no change of receptor density or affinity was observed after acute in vitro treatment, in epileptic patients chronically treated with carbamazepine, phenobarbital and valproic acid, PBR Bmax was increased with respect to controls and untreated epileptics. Since PBR of human lymphocytes may be affected by anticonvulsant drug treatment, we suggest that they might be involved in the immunological alterations reported in these patients and might be used as peripheral markers of drug effects on the central nervous system.

Adolescent↗
PubMed1995

Listeria rhombencephalitis: report of two cases with early diagnosis and favourable outcome.

We present 2 cases of Listeria monocytogenes rhombencephalitis (L-RE), both affecting previously healthy adult men. Each of them developed a diphasic syndrome first characterized by fever, nausea and headache, followed, in a second phase, by severe brain stem dysfunction at the level of the pons, with meningism, multiple cranial nerve palsies, ataxia, and, in one case, seizures. The early examination of the cerebrospinal fluid (CSF) demonstrated the presence of Gram-positive bacilli whose typical characteristics were compatible with those of Listeria, allowing for immediate administration of a specific therapy. Neuroimaging techniques (either CT or MRI) did not provide any evidence of brain stem involvement, and they did not positively contribute to the diagnostic process. The immediate use of a specific antibiotic therapy led to a favourable clinical outcome for both patients.

Anti-Bacterial Agents↗
PubMed1995

Sensory impairments and mortality in an elderly community population: a six-year follow-up study.

Previous studies have shown that sensory impairments adversely affect the quality of life of elderly people, but have failed to demonstrate consistent results on mortality. We examined the predictive value of hearing and visual impairments on mortality in an urban population of 1140 non-institutionalized elderly subjects, aged 70-75 years. Baseline information was collected in 1986 through a door-to-door interview with a standardized questionnaire and the sensory assessment was performed using bedside tasks: the whispered voice test for hearing and the Snellen chart for vision. Overall mortality rate at 6 years was 25.5%, with a significant sex difference (males = 37.5%; females = 19.8%) and a significant interaction between sex and sensory impairment. Bivariate logistic regression showed that hearing deficit was associated with a significant increase in mortality risk only in the men. This increase remained significant even after control for the demographic variables and the global physical health status. Multivariate logistic regression showed that the effect of hearing deficit on mortality was mediated by psychosocial parameters (mood and social relationships level). Sensory assessment through simple bedside tests should become part of the routine clinical evaluation of elderly people.

Activities of Daily Living↗
PubMed1995

Proglumide, a cholecystokinin receptor antagonist, reduces neuroleptic action in Huntington's chorea.

In a pilot study, proglumide, a cholecystokinin receptor antagonist, was administered to 8 patients affected from Huntington's chorea under long-term haloperidol treatment. The effectiveness of haloperidol on chronic symptomatology was reduced by the concomitant administration of proglumide; the latter drug, when administered alone, did not modify the severity of chorea compared to placebo. Possible explanations of these results are discussed, stressing the modulatory role of CCK not only on the dopaminergic, but also on the GABAergic system.

Adolescent↗
PubMed1994

Comparison of the efficacy, safety and withdrawal of alpidem and alprazolam in anxious patients.

BACKGROUND: We investigated whether a new non-benzodiazepine anti-anxiety drug, alpidem, produces weaker withdrawal symptoms than alprazolam. METHOD: Under a double-blind procedure, 122 patients suffering from general anxiety disorders were randomly allocated to either alpidem (50 mg, three times a day) or alprazolam (0.5 mg, three times a day) for six weeks, followed by a two-week placebo withdrawal phase. The diagnosis of withdrawal syndrome (WS) was made, in blind conditions, on the basis of the Withdrawal Symptom Check List (WSCL), after one or two weeks of discontinuation of active treatment. RESULTS: The WS occurred significantly less frequently in the alpidem group (n = 10, 18%) than in the alprazolam group (n = 26, 48%). Typical withdrawal symptoms on the WSCL were also significantly less severe (P = 0.044) in the alpidem group compared with the alprazolam group. CONCLUSIONS: Alpidem may be a valid alternative to current benzodiazepine anxiolytic therapy because it produces fewer and weaker withdrawal symptoms than alprazolam and is better tolerated.

Adult↗
PubMed1993

Assessment of reliability and biological significance of glutamate levels in cerebrospinal fluid.

The published information on glutamate levels in cerebrospinal fluid (CSF) and modifications in neurological disorders is controversial. In the present study, we demonstrated a metabolic instability of glutamate in untreated CSF and a spurious elevation of its levels by the current methods of CSF acidification. These findings may explain the discrepancies observed with different methods of CSF processing and analysis. We suggest a method of inactivating CSF enzymes that yields stable glutamate levels under different storage conditions. Use of such a method may be necessary for clinical studies.

Acids↗
PubMed1993

Benzodiazepine receptors and diazepam binding inhibitor: a possible link between stress, anxiety and the immune system.

This review summarizes the evidence available on the involvement in stress of different classes of benzodiazepine receptors and their putative endogenous ligand, diazepam binding inhibitor (DBI), with particular reference to their role in modifications of the immune response. The presented data from in vitro, experimental, and clinical studies suggest that benzodiazepine receptors and DBI play a major role in regulating steroid production in both the adrenals and central nervous system, and may be involved in the activation of the hypothalamic-pituitary-adrenal axis in stress response.

Animals↗
PubMed1993

Sensory impairment and quality of life in a community elderly population.

OBJECTIVE: To determine the association between quality of life measures and sensory impairment in aged individuals living at home. DESIGN: Survey SETTING: A community survey, carried out in the historical center of a town in Northern Italy. PATIENTS: 1191 non-institutionalized elders (age 70-75 years). MEASUREMENTS: Comprehensive QOL questionnaire, free-field voice testing, and Snellen eye chart. RESULTS: Single sensory impairments (either visual or auditory) were significantly and independently associated with increased risk for depression (odds ratio: 2.3, 95% confidence interval: 1.5-3.4; OR:1.8, CI:1.1-2.7, respectively) and decreased self-sufficiency in daily living activities (OR:1.7, CI:1.1-2.6; OR:2.1, CI:1.4-3.2, respectively). Visual dysfunction, but not hearing dysfunction, was independently associated with lower social relationships (OR:2.0, CI:1.3-3.1). CONCLUSION: The quality of life of community-dwelling elderly people is significantly linked to sensory impairment, which can be detected through simple physical examination. Mood level and social relationships are particularly affected by visual impairment, whereas self-sufficiency in daily living is more strongly related to hearing impairment.

Activities of Daily Living↗
PubMed1992

Evaluation by somatosensory evoked potentials of the neurotoxicity of cisplatin alone or in combination with glutathione.

The use of high doses of cisplatin (DDP) in the treatment of different solid tumors is often prevented by the onset of a disabling sensory neuropathy. In an attempt to minimize DDP-induced neurotoxicity different schedules of DDP administration have been tested. Moreover, during the past few years some putative neuroprotective drugs have been reported as reducing DDP neurotoxicity. In this prospective, randomized study we evaluated in a series of 33 patients affected by relapsing ovarian cancer the effect on the sensory pathway of a non-conventional schedule of DDP administration as monochemiotherapy or in combination with one of the neuroprotective drugs (i.e. glutathione). The results of the neurophysiologic examinations performed before and immediately after chemotherapy suggest that these schedules besides being safe and effective in the treatment of the ovarian cancer, have an extremely low peripheral neurotoxicity.

Cisplatin↗
PubMed1992

Effects of alpidem in anxious elderly outpatients: a double-blind, placebo-controlled trial.

The efficacy and safety of alpidem, a new anxiolytic imidazopyridine, were compared with those of placebo in anxious elderly patients (65-80 years) by means of a randomized, double-blind, parallel group study. Following a 7-day "placebo run-in," 40 anxious patients were randomized to receive either alpidem or placebo. Daily doses ranging from 75 to 150 mg (25-50 mg t.i.d.) were administered for 3 weeks. Hamilton Rating Scale for Anxiety (HRSA), State Trait Anxiety Inventory (STAI-X1), Visual Analogue Scale (VAS), and Clinical Global Impression (CGI) were used on days 0, 3, 7, 14, and 21 for assessing efficacy. Psychomotor and mnesic performances were evaluated at the same time by means of the Digit Symbol Substitution Test (DSST), the Grünberger's test for fine motor coordination, and the Hawie's test for immediate memory. Possible adverse events were also recorded during the five visits. The anxiolytic efficacy of alpidem was significantly (p < 0.01) superior to that of placebo in all the rating scales adopted. The anxiolytic action was clearly evident from day 7. For most of the patients the active dose was 25 mg t.i.d. No relevant adverse effects were observed in both groups. No impairment of psychomotor and mnesic performances could be observed in the alpidem group. Alpidem is a new interesting anxiolytic drug for anxious elderly patients because it appears remarkably safe and, at effective doses, it does not impair psychomotor performances and cognitive functions.

Aged↗
PubMed1991

Acute noise stress in rats increases the levels of diazepam binding inhibitor (DBI) in hippocampus and adrenal gland.

We investigated the effect of acute noise-induced stress on the concentrations of diazepam binding inhibitor (DBI) and its processing products in brain regions and adrenal glands of rats. DBI levels in hippocampus began to increase at 15 and 30 min and became significantly higher (+100%) at 90 and 120 min after stress; they returned to normal values at 360 min. While basal DBI levels were similar in the left and right hippocampus, the stress-induced increase of DBI levels was significantly higher in the left compared to the right side. A significant increase was also detected in the adrenals; here, the time course of DBI increase paralleled that of previously reported plasma corticosterone in stressed rats, being significantly higher 30 min after stress, and recovering to normal values at 60 and 90 min. After acute noise-induced stress, no significant change of DBI levels was detectable in cerebral cortex, striatum, hypothalamus and cerebellum. The present study reports for the first time the occurrence of a modification of DBI and its processing products (ODN-like immunoreactivity) in an experimental model of stress, and suggests a role for these neuropeptides in emotional responses.

Adrenal Glands↗
PubMed1991

Effects of a MAO-B inhibitor in the treatment of Alzheimer disease.

119 patients were enrolled in a double-blind randomized parallel study versus placebo carried out to assess both the efficacy and tolerability of L-deprenyl (10 mg/day) for treatment of patients with organic mental disorders of the Alzheimer type (DAT). The treatments were given for 3 months, starting after a run-in period of 15 days to evaluate efficacy. A complete neuropsychological battery was administered monthly after the start of treatment whereas tolerability was assessed by checking, recording and classifying all the unfavorable experiences occurring. According to the results, L-deprenyl would seem to be a useful and reliable tool for the treatment of DAT patients in an attempt to improve their cognitive functions and reduce behavioral alterations, without frequent or severe side effects.

Activities of Daily Living↗
PubMed1990

Characterization of peripheral benzodiazepine receptors in human blood mononuclear cells.

In the present study, peripheral-type benzodiazepine receptors in human circulating mononuclear cells were characterized, using [3H]PK 11195 as specific ligand. The specific binding was saturable, with a Bmax of 14 pmol/mg protein and a Kd of 7 nM. The pharmacological characterization, using different displacing drugs, indicated a mitochondrial type of peripheral benzodiazepine receptor since it was not coupled to the GABA receptor and was displaced by protoporphyrin IX. These data indicate that human circulating mononuclear cells possess benzodiazepine recognition sites, similar to non-neuronal receptors. The role of these receptors and possible modifications in different diseases need to be investigated.

Adult↗
PubMed1990

Decreased density of benzodiazepine receptors in lymphocytes of anxious patients: reversal after chronic diazepam treatment.

Peripheral-type benzodiazepine receptors were measured in human circulating lymphocytes using 3H-PK 11195 as specific ligand. In a group of outpatients with anxiety disorders a significant decrease of receptor density (-37%) was found compared with age-matched controls. In these patients long-term diazepam treatment restored binding density to normal levels: the effect persisted after drug withdrawal. Acute i.v. diazepam administration did not change receptor density. The observed receptor changes could reflect a down-regulation phenomenon and indicate that lymphocyte function reflect central nervous events.

Anxiety Disorders↗
PubMed1990

Decrease in phorbol ester receptors in human brain tumors.

We have characterized the specific binding of [3H]-phorbol-12,13-dibutyrate in the white and gray matter of normal human brain and in cerebral tumors as an index of the availability of protein kinase C enzyme molecules. White matter has less than 50% phorbol-ester-binding capacity in comparison to gray matter. The binding is lower in tumors of glial origin when compared with normal white matter. Tumors of nonglial origin such as neurinoma and meningioma have a lower binding capacity than glial tumors. Metastatic tissues have the lowest binding capacity. The analysis of binding parameters in tumors and in the corresponding normal peritumoral tissues confirms the decreased binding capacity of neoplastic tissues in comparison to tissues not undergoing malignant transformation. These data suggest that brain glial tumors have a low availability of protein kinase C enzyme molecules and point to the potential involvement of this system in malignant transformation of human brain cells.

Adult↗
PubMed1990

Cerebrospinal fluid levels of diazepam-binding inhibitor in neurodegenerative disorders with dementia.

We investigated CSF levels of diazepam-binding inhibitor (DBI), a recently discovered neuropeptide that allosterically modulates GABAergic transmission, in various neurodegenerative disorders with dementia (28 patients with Parkinson's disease, 10 with Alzheimer's disease, 7 with Huntington's chorea). We applied a battery of neuropsychological tests to determine the degree of dementia and to exclude the presence of mood alterations. CSF DBI levels were elevated in parkinsonian subjects with dementia and in patients with Alzheimer's disease, but decreased in Huntington's chorea patients. We hypothesize that modifications of CSF DBI levels may be related to a functional or structural alteration of the GABAergic system.

Adult↗
PubMed1990

Double blind comparison of zolpidem 20 mg versus flunitrazepam 2 mg in insomniac in-patients.

The efficacy of zolpidem 20 mg was compared to that of flunitrazepam 2 mg. Forty-two insomniac female in-patients between 30 and 65 years of age were included in a double blind, parallel group trial and were randomly allocated to the two treatments. Study duration was 9 days with 2 days of placebo run-in, 5 days of active medication and 2 days of placebo withdrawal. Sleep latency, sleep duration, number of awakenings and time spent asleep during the night were given an ordinal score; condition in the morning was evaluated by Visual Analogue Scales and the psychomotor performance was evaluated by the tests: night-day for anterograde amnesia, digit span for verbal recall and Grünberger's fine motor function test. There was no significant difference between zolpidem and flunitrazepam for any of the variables; the drugs were significantly better than placebo baseline for all the sleep efficacy variables. The results of this study indicate that zolpidem is as effective as flunitrazepam in inducing and maintaining sleep but it does not induce a sense of weakness in the morning and does not impair memory.

Adult↗