Biomedical subjects

E Martignoni

Publications and source records attributed to E Martignoni.

At least 19 recordsLinked to original sources

PubMed1992

Evidence of alpha-N-acetyl beta-endorphin in human cerebrospinal fluid.

Alpha-N-acetyl-beta-endorphin (Ac-beta-EP) is a post-translational product of beta-endorphin (beta-EP) with no analgesic properties. Ac beta-EP is present in human fetal and adult pituitary gland and cross-reacts in all available beta-EP assays. This study evaluates levels of Ac-beta-EP in the cerebrospinal fluid (CSF) of 22 normal subjects and 15 chronic headache sufferers. Since dopamine may play a role in the acetylation process, homovanillic acid levels were also determined. After extraction and high performance liquid chromatographic (HPLC) fractionation of CSF, an immunoreactive Ac-beta-EP peak was detected coeluting with reference peptide. Ac-beta-EP was detectable in all but 5 normal subjects. In headache sufferers, Ac-beta-EP levels were always detectable and their mean value was significantly higher than that of healthy subjects (11.6 +/- 11.8 vs 3.9 +/- 3.6 fmol/ml; P less than 0.01). Conversely, CSF beta-endorphin (beta-EP) concentrations were decreased in headache patients (9.8 +/- 9.4 vs 15.7 +/- 9.7 fmol/ml; P less than 0.05), and as a consequence the beta-EP/Ac-beta-EP ratio was also markedly reduced (P less than 0.005). No difference was observed for CSF homovanillic acid concentrations. These data demonstrate that HPLC coupled to radioimmunoassay allows the identification of low but significant amounts of Ac beta-EP in human CSF. This compound represents a confounding factor when beta-EP immunoreactivity is assessed by conventional methods. In headache sufferers, Ac-beta-EP levels were higher than normal, whereas beta-EP concentrations were lower.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Cerebrospinal fluid norepinephrine, 3-methoxy-4-hydroxyphenylglycol and neuropeptide Y levels in Parkinson's disease, multiple system atrophy and dementia of the Alzheimer type.

Neuropeptide Y, one of the most abundant polypeptides within the nervous system, is co-stored with catecholamines, especially norepinephrine (NE), thus suggesting its possible involvement in pathologies characterized by a noradrenergic impairment. In Parkinson's disease (PD), as well as in multiple system atrophy (MSA), a central noradrenergic deficit has been demonstrated, and in the dementia of Alzheimer type (DAT) an impaired noradrenergic transmission has been postulated. In this study we determined CSF NE and MHPG levels in 29 PD, 15 MSA, 22 DAT patients and in 36 controls, while CSF NPY-immunoreactivity (NPY-ir) levels were measured in 10 PD, 7 MSA, 10 DAT patients and 20 controls. PD, MSA, and DAT patients showed a significant reduction in CSF NPY-ir and NE levels compared with controls, while CSF MHPG levels resulted in a reduction in only the MSA group. Furthermore, an inverse correlation between either NE or MHPG levels and the duration of the orthostatic hypotension was found in MSA patients while for DAT patients the MHPG levels were directly correlated to the severity of cognitive impairment, and inversely to the duration of illness.

Adult↗

PubMed1992

The brain as a target for adrenocortical steroids: cognitive implications.

It is well established that a reciprocal control exists between the brain and glucocorticoid hormones. The brain regulates adrenocortical function via hypothalamic corticotrophin releasing hormone-41 (CRH-41), glucocorticoids act at specific receptors in the hippocampus, thus promoting negative feedback mechanisms. Because the hippocampus is a major site for memory processes, a role for excessive/long-lasting plasma glucocorticoid levels has been suggested in conditions of mental impairment. Major depression, Cushing's disease, and dementia of the Alzheimer type are disorders which share hyperactivity of the hypothalamo-pituitary-adrenal axis, as well as symptoms of cognitive decline. Although the mechanisms leading to hypercortisolemia appear to be different in each case, the neuropsychological features of these three disorders accord with the hypothesis of glucocorticoid-associated brain damage. It therefore is important to find pharmacological strategies that will avert or reduce these potential consequences on brain function.

Adrenocorticotropic Hormone↗

PubMed1992

Platelet catecholamines in cluster headache.

Platelet tyrosine and catecholamine (CA) content was measured in cluster headache sufferers during the different phases of the illness. Compared with controls, cluster headache sufferers had lower platelet levels of norepinephrine (NE) and epinephrine (E) in all phases of the syndrome. Tyrosine levels were increased significantly during the cluster headache attack. We suggest that these results provide biochemical evidence of sympathetic nervous system (SNS) hypofunction in cluster headache.

Adult↗

PubMed1992

Free plasma catecholamine levels in healthy subjects: a basal and dynamic study. The influence of age.

We studied the levels of free plasma noradrenaline (norepinephrine, NE), adrenaline (epinephrine, E), and dopamine (DA) in 143 normal subjects, either basally or, in a part of them, in response to four tests stimulating the sympathoadrenomedullary activity: the tilt-table test (TTT), the cold-pressor test (CPT), the mental-arithmetic test (MAT), and the insulin tolerance test (ITT). In both cases we evaluated the influence of age, which is considered the main physiological variable affecting the peripheral sympathetic activity. A normal distribution of values was observed, in the basal study, only for NE, while E and particularly, DA levels were distributed in an non-homogeneous fashion; a direct correlation was observed between age of subjects and NE levels, while neither E, nor DA levels showed any correlation with the aging process; sex did not influence any of the catecholamines. In the dynamic study, CPT, ITT and, above all, TTT elicited a significant rise in NE levels, while the E release was greatly stimulated by the insulin-induced hypoglycaemia. Neither NE, nor E levels rose after the MAT stimulation. Also in this case, the elderly showed an increased noradrenergic responsiveness when compared with the young subjects, confirming the existence of an 'up-regulation' of the peripheral sympathetic tone in old people.

Adolescent↗

PubMed1991

Interobserver reliability between neurologists in training of Parkinson's disease rating scales. A multicenter study.

A multicenter study has been conducted to determine the interobserver reproducibility of four of the most frequently used rating scales for Parkinson's disease: the Columbia University Rating Scale (CURS) and the Webster Rating Scale (WRS), both for assessing clinical signs; the Northwestern University Disability Scale (NUDS); and the Hoehn and Yahr staging. Four resident neurologists, inexperienced in the use of the four scales, independently examined 48 parkinsonian patients. The extent to which their assessments agreed was determined by calculating the Cohen k index after the scores had been recodified. The physicians' scores agreed substantially for the CURS and the Hoehn and Yahr scale, while those for the NUDS and the WRS agreed only moderately. Analysis of individual item scores within the scales suggests improvements that would offer greater interobserver consistency.

Disability Evaluation↗

PubMed1991

Disordered pupil reactivity in Parkinson's disease.

Different varieties of pupillary abnormalities have been described in Parkinson's disease but it is not clear if this is due to the disease itself or to the pharmacological treatment. In this study, pupil reactivity to various stimuli (dark/light adaptation, light reflex, near vision reaction and electrical sural stimulation) was investigated in 23 de novo parkinsonian patients (not on drugs) to assess pupillary abnormalities and investigate their pathophysiological mechanisms. Parkinsonian patients exhibited larger pupil diameter after light adaptation, as well as a reduced amplitude of contraction and a prolonged contraction time at light reflex. The data obtained confirmed the existence in Parkinson's disease of a pupillary imbalance mainly involving the parasympathetic system.

Adaptation, Ocular↗

PubMed1991

Monoamines and related metabolite levels in the cerebrospinal fluid of patients with dementia of Alzheimer type. Influence of treatment with L-deprenyl.

An impairment of the monoaminergic systems has frequently been reported for Alzheimer's disease (AD) as well as an overactivity of cerebral monoamineoxidase B (MAO-B). L-deprenyl (LD), a selective and irreversible MAO-B inhibitor, has recently been proposed for the treatment of AD. The cerebrospinal fluid (CSF) levels of norepinephrine (NE), epinephrine (E), dopamine (DA), 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) were studied in 14 patients suffering from dementia of Alzheimer type (DAT) and in 14 controls. A three-month double-blind study comparing LD with placebo was carried out, in the DAT group, and the influence of the treatment on neurotransmitter levels and cognitive performance was evaluated. The basal study revealed a significant reduction in CSF NE and HVA levels in DAT patients when compared with controls; the treatment with LD determined a significant decrease in HVA levels only and, as to neuropsychological investigation, a global amelioration of cognitive performances.

Aged↗

PubMed1991

Dihydroergocryptine in the treatment of Parkinson's disease: a six months' double-blind clinical trial.

The short-term efficacy of dihydro-alpha-ergocryptine (DEK), a hydrogenate ergot derivative with dopamine (DA) agonist properties was evaluated in 20 L-dopa (LD) stable responder parkinsonian patients by a 6-month double-blind randomized, placebo-controlled study. A motor improvement was found only in DEK-treated patients at mean daily doses of approximately 40 mg, ranging from 15 to 60 mg. The side effects never required the withdrawal of the drug or changes in its schedule. The authors demonstrate the efficacy and the good tolerability of DEK as a new DA agonist drug that can be added to LD in the treatment of parkinsonian patients.

Dihydroergotoxine↗

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

Lisuride plus selegiline in the treatment of early Parkinson's disease.

We treated 20 early Parkinson's disease subjects with the dopamine agonist lisuride in combination with the MAO-B inhibitor selegiline (L-deprenyl). We started with lisuride alone for one month, then we added selegiline versus placebo to lisuride in double-blind conditions for 3 months; finally all patients received lisuride and selegiline for another 3 months. Lisuride alone (1.43 +/- 0.10 mg) significantly improved PD. When selegiline (10 mg/day) was added in the double-blind phase the mean lisuride dosage could be reduced by 22.8% without deterioration of the clinical effects, and the same occurred in the former placebo group when selegiline was added. The combination of both drugs was well tolerated. These data are of interest for the interpretation of the effects of selegiline.

Adult↗

PubMed1990

Cerebrospinal fluid corticotropin-releasing factor levels and stimulation test in dementia of the Alzheimer type.

Experimental findings have recently suggested a toxic role for glucocorticoids in hippocampus, the main brain target for the adrenocortical hormones. In this study, we explored the activity of the hypothalamus-pituitary-adrenal (HPA) axis in a group of patients with dementia of the Alzheimer's type (DAT) and in a control group of age-matched subjects. We measured the corticotropin-releasing factor (CRF) levels in cerebrospinal fluid (CSF) and evaluated the plasma cortisol response to a CRF stimulation test. While no differences were observed in the results of the CRF test for two groups, CSF CRF values in DAT patients were found to be significantly higher than in controls. Bearing in mind the bidirectional relationships between the neuroendocrine and immune systems and the changes in some immunological parameters reported in DAT, the possible role of HPA axis hyperactivity in the pathogenesis of primary dementia is discussed.

Aged↗

PubMed1990

Neuroendocrine correlates of premenstrual syndrome: changes in the pulsatile pattern of plasma LH.

Some studies suggest that patients suffering from premenstrual syndrome (PMS) may be affected by an endogenous opioid dysfunction. Since opioids are the main modulators of the pulsatile LH secretion, we evaluated plasma LH pulsatility in 13 patients with PMS (aged 33.1 yr) and in six asymptomatic control volunteers (aged 31.5 yr), in the late luteal phase (-7, -5 days before their next menses). The patients were prospectively evaluated for two menstrual cycles with the Menstrual Distress Questionnaire; the main symptoms which worsened during the premenstrual period were mood swings and water retention. The pulsatility of plasma LH secretion was studied by collecting blood samples every 10 min for 12 hr, starting at 0800h. The presence of LH pulses was estimated using the program DETECT on the raw data. This program also allows the computation of the instantaneous secretory rate (ISR). Ovulation was ascertained in all the controls and in nine PMS patients by means of urinary LH assay and luteal progesterone (P) determination. The remaining four patients did not ovulate. Both the ovulatory and the anovulatory PMS patients had an increased number of LH pulses/12 hr (10.3 +/- 2.4 and 11.5 +/- 4.4, mean +/- SD, respectively) in comparison with the controls (7.0 +/- 1.3 pulses, p less than 0.01), together with a reduced amplitude and duration. Similar findings were obtained with the ISR computation. Plasma P levels were similar in both the ovulatory patients and controls. The increased frequency and reduced amplitude of LH pulses in the PMS patients most likely reflect a dysfunction of hypothalamic Gn-RH release, possibly linked to a reduction of opioid inhibition.

Adult↗

PubMed1990

Opioid control of the hypothalamus-pituitary-adrenal axis cyclically fails in menstrual migraine.

To assess the biological correlates of the precipitation of migraine attacks in the perimenstrual period, plasma beta-endorphin (beta-EP) and cortisol responses to naloxone (8 mg iv) and corticotropin releasing hormone (100 micrograms iv) were evaluated in both the follicular phase and the premenstrual period in 7 patients suffering from menstrual migraine and in 7 healthy, asymptomatic control volunteers. In the controls, naloxone evoked a significant release of both beta-EP (F = 5.86, p less than 0.002) and cortisol (F = 4.43, p less than 0.008), independently of the menstrual cycle phase (F = 0.31 and 1.04, for beta-EP and cortisol, respectively). Menstrual migraine patients, on the other hand, showed a significant hormone response only in the follicular phase, not in the premenstrual period. Corticotropin releasing hormone significantly increased beta-EP and cortisol in both the controls and the menstrual migraine patients, independently of the menstrual cycle phase. In both the naloxone and corticotropin releasing hormone testings, the basal beta-EP levels measured in the premenstrual period were lower than those observed in the follicular phase (p less than 0.02). These data demonstrate a cyclical, premenstrual dysfunction of the hypothalamic control exerted by opioids on the hypothalamus-pituitary-adrenal axis. Impairment of this fundamental adaptive mechanism (involved in stress responses and in pain control) could establish a causal relationship between menstrual-related migraine attacks and premenstrual opioid hyposensitivity.

Adult↗

PubMed1990

Naproxen sodium in menstrual migraine prophylaxis: a double-blind placebo controlled study.

In this study, the efficacy of Naproxen sodium (Nxs) in the prophylaxis of Menstrual Migraine (MM) was tested, versus Placebo (PL). Forty women suffering from MM were admitted to a double-blind treatment protocol with Nxs 550 mg twice each day by mouth or Placebo (PL), for 3 months; in the next 3 months all the women were treated with the active drug in an open study. The headache intensity and duration, as well as the number of days of headache and the analgesic consumption, were significantly reduced with Nxs compared to PL. The efficacy of Nxs, shown also in improving premenstrual pain, and its good tolerability, support the use of this drug in the prophylactic therapy of MM.

Adult↗

PubMed1990

Dementia of the Alzheimer type and hypothalamus-pituitary-adrenocortical axis: changes in cerebrospinal fluid corticotropin releasing factor and plasma cortisol levels.

The activity of the hypothalamus-pituitary-adrenocortical (HPA) axis was explored in 10 patients with dementia of the Alzheimer type (DAT) and in 11 age-matched controls, by measuring 1) corticotropin-releasing factor (CRF) levels in cerebrospinal fluid (CSF), 2) the circadian changes of plasma cortisol, 3) and 4) the plasma cortisol response to dexamethasone suppression test (DST) and to CRF stimulation test. CSF CRF levels in DAT were significantly higher than in controls and inversely related to the Mini Mental State (MMS) score. The patients also displayed increased morning (0800 h) plasma cortisol values, with higher mesor and amplitude in the circadian pattern. Dexamethasone resistance was shown by 6 of the 10 DAT subjects. Plasma cortisol response to CRF administration was similar in the two groups, except for the peak values, which in DAT patients were reached earlier than in controls. The present data suggest an overactivity of HPA axis in DAT; its possible role in the evolution of the disease is discussed.

Aged↗

PubMed1990

Effectiveness of Madopar HBS plus Madopar standard in patients with fluctuating Parkinson's disease: two years of follow-up.

Clinical response to a new galenic formulation of levodopa plus benserazide, Madopar HBS, was studied in 25 fluctuating parkinsonians. This open study was planned in two phases. In the first phase, the administering of HBS alone resulted in a surprisingly high number of dropouts. In the second phase, Madopar standard in association with Madopar HBS, the follow-up period was 24 months. A stable long-lasting improvement in predictable fluctuations and their severity was maintained for the whole period without any change in drug dose. Nocturnal and early morning akinesia improved too. The study shows that Madopar HBS plus Madopar standard is effective in producing a prolonged and stable response in parkinsonian fluctuating patients.

Adult↗

PubMed1989

Neuroendocrine evidence of deranged noradrenergic activity in chronic migraine.

Migraine is a psychobiological disorder in which a recurrent failure of opioid and adrenergic systems might occur, as plasma and CSF studies suggest. In order to elucidate the relationship between noradrenergic and opioidergic functions, the plasma beta-endorphin (beta-EP) response to clonidine and the cortisol response to dexamethasone were evaluated together in 25 patients suffering from migraine without aura, and with chronic tension headache (MTH). Baseline beta-EP plasma levels and beta-EP response to clonidine were significantly lower in MTH subjects than in controls, suggesting a postsynaptic hypothalamo-pituitary impairment. Forty-four percent of the MTH subjects showed either a lack of suppression of plasma cortisol following dexamethasone administration, or basal cortisol concentrations higher than controls and suppressors, suggesting a disinhibition of the hypothalamopituitary-adrenal (HPA) axis. An inverse correlation was found between pain severity and beta-EP secretion induced by clonidine (delta max), and no relationship was found between beta-EP and mood. These data suggest a failure of central noradrenergic activity, or perhaps an impaired secretion of beta-EP not related to HPA axis hyperactivity or to affective state.

Adult↗