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Biomedical subjects

L Pinessi

Publications and source records attributed to L Pinessi.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effects of subcutaneous sumatriptan on plasma growth hormone concentrations in migraine patients.

The purpose of this study was to assess the sensitivity of 5-HT1D receptors in migraine using sumatriptan as a pharmacological probe. The drug stimulates the release of growth hormone (GH) and this effect may be used to explore the function of cerebral serotonergic systems in vivo. We administered sumatriptan and placebo to 15 migraineurs and to 10 controls. Blood samples were collected -15, 0, 15, 30, 45, 60 and 90 min after injection. Placebo had no effect on hormone concentrations. Sumatriptan induced a significant (P<0.01) increase in GH concentrations both in migraine patients and healthy controls. The GH increase was not significantly different in the two groups. Our results suggest that cerebral serotonergic functions mediated by 5-HT1D receptors are not altered in migraine. Sumatriptan overuse could lead to adverse effects mediated by its neuroendocrine activity.

Adult↗
PubMed2000

Autonomic responses and pain perception in Alzheimer's disease.

We analysed the effects of electrical noxious stimulation on the autonomic nervous system of Alzheimer's disease (AD) patients who were assessed by means of the Mini Mental State Examination test (MMSE). To do this, we used electrical stimuli at two different intensities: just above pain threshold and twice pain threshold. We recorded heart rate and systolic blood pressure by using conventional electrocardiography and finger photo-plethysmography. When a pain stimulus just above threshold was delivered, AD patients were found to have blunted autonomic responses compared to controls of the same age. Similarly, prestimulus expectation produced a less pronounced increase of the responses in AD patients compared to the controls. However, when the painful stimulus was increased to twice the pain threshold, the systolic blood pressure increase of AD patients did not differ from the controls, whereas heart rate increase was still slightly diminished. By contrast, pain perception was similar in the two groups when the stimulus was at pain threshold, whereas it was blunted in AD patients when the stimulus was twice the pain threshold. These findings show that in AD mild noxious stimulation produces blunted autonomic responses and normal pain perception, whereas strong noxious stimulation produces quasi-normal autonomic responses and blunted pain perception. These results indicate that AD patients have an increased threshold for both autonomic activation and pain tolerance.

Aged↗
PubMed1999

Pain threshold and tolerance in Alzheimer's disease.

We tested both pain thresholds and pain tolerance in patients with Alzheimer's disease (AD) by means of phasic and tonic noxious stimuli. In the first case, electrical stimulation was used, whereas in the second case arm ischemia was studied. By comparing AD patients with normal subjects of the same age, we found no differences in stimulus detection and pain thresholds, whereas a clearcut increase in pain tolerance was present in AD patients. The severity of AD was assessed by means of the Mini Mental State Examination test (MMSE) and the spectral analysis of the electroencephalogram (EEG). There was a straightforward correlation between MMSE scores and pain tolerance such that the more severe the cognitive impairment the higher the tolerance to pain. In addition, analysis of the EEG power spectra indicated that patients with low alpha and high delta peaks showed an increase in pain tolerance to both electrical stimulation and ischemia. These findings show that, whereas the sensory-discriminative component of pain is maintained in AD patients, pain tolerance is altered and depends on cognitive and affective factors. Thus, pain tolerance is tightly related to the severity of the disease according to the rule, 'the more severe the MMSE and EEG changes, the higher the tolerance to pain'.

Aged↗
PubMed1995

Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease.

Some cases of Alzheimer's disease are inherited as an autosomal dominant trait. Genetic linkage studies have mapped a locus (AD3) associated with susceptibility to a very aggressive form of Alzheimer's disease to chromosome 14q24.3. We have defined a minimal cosegregating region containing the AD3 gene, and isolated at least 19 different transcripts encoded within this region. One of these transcripts (S182) corresponds to a novel gene whose product is predicted to contain multiple transmembrane domains and resembles an integral membrane protein. Five different missense mutations have been found that cosegregate with early-onset familial Alzheimer's disease. Because these changes occurred in conserved domains of this gene, and are not present in normal controls, they are likely to be causative of AD3.

Alzheimer Disease↗
PubMed1994

Analysis of the functional effects of a mutation in SOD1 associated with familial amyotrophic lateral sclerosis.

Mutations in the Cu, Zn superoxide dismutase (SOD1) gene have been reported in some pedigrees with Familial Amyotrophic Lateral Sclerosis (FALS). We have investigated the functional and structural effects of a Gly-->Ser mutation at codon 41 of SOD1 in a pedigree with FALS and the topography of SOD1 expression in the mammalian CNS. These analyses show that the 41Gly-->Ser mutation causes a 27% reduction in Cu, Zn SOD activity. SOD1 is transcribed at high levels in rat motoneurons and four other types of neurons homologous to upper motoneurons that degenerate in human ALS. However, SOD1 is transcribed at lower levels in other types of neurons, such as cerebellar Purkinje cells, which are not usually involved significantly in human ALS. On the other hand, immunocytochemical studies indicate that most types of rat neurons contain similar levels of Cu, Zn SOD immunoreactive protein. Nevertheless, these results suggest that the essential feature causing this subtype of ALS is either a reduction in Cu, Zn SOD activity in cell types that presumably critically require Cu, Zn SOD for protection against oxidative damage or the fact that the mutation in SOD1 associated with FALS results in a novel gain of function that is particularly deleterious to those cell types expressing SOD1 at high levels.

Amino Acid Sequence↗
PubMed1994

SOD1 missense mutation in an Italian family with ALS.

We have discovered a new Italian pedigree with autosomal-dominant ALS. The pedigree, at present, comprises 75 members distributed in five generations. ALS was diagnosed in eight patients. The mean +/- SD age of onset of the disease was 46.8 +/- 13.5 years, with a range of 29 to 63 years. The mean +/- SD duration of the disease was 11.6 +/- 1.7 months. Molecular genetic studies showed a missense mutation (Gly-->Ser, codon 41) in exon 2 of the Cu/Zn superoxide dismutase gene (SOD1) on chromosome 21 in the available affected member and in 45% of the at-risk subjects of the pedigree. This study confirms the presence of SOD1 point mutations in families with autosomal-dominant ALS and suggests that additional genetic or environmental factors may be involved in the full expression of the disease.

Adult↗
PubMed1993

The power of systematic genealogical study in familial Alzheimer disease.

Several kindreds (N, C, To and RB) with familial Alzheimer disease (FAD) from the same small area of Calabria are currently under study. Recently two of us (F.M. and L.F-S.) identified a family in Milan (FJ01) made up of 3 siblings whose parents were of Calabrian origin. Through a subsequent systematic or blanket genealogical study a link has been traced between kindreds To and FJ01. We discuss the relevance of these results to genetic studies.

Adult↗
PubMed1993

Clonidine lowers alpha-MSH-like immunoreactivity in human plasma.

In a group of seven healthy subjects, the effects of acute intravenous administration of clonidine, a selective alpha 2 receptor stimulator, on plasma alpha-MSH-LI concentrations were measured. In comparison with saline, clonidine (0.075 mg) significantly reduced alpha-MSH-LI concentrations, with a maximum fall between 30 and 60 min., followed by a return to basal concentrations at 120 min.; no significant variations in plasma ACTH and cortisol were seen. The precise mechanism of this effect is unclear. Our study suggests that separate regulatory mechanisms exist for the secretion of POMC related peptides in the corticotroph and melanotroph cells of the human pituitary gland.

Adrenocorticotropic Hormone↗
PubMed1993

Analysis of the c-FOS gene on chromosome 14 and the promoter of the amyloid precursor protein gene in familial Alzheimer's disease.

The c-FOS gene product, a putative transacting transcriptional regulator of the amyloid precursor protein (APP) gene, is a candidate locus for the familial Alzheimer's disease (FAD) mutation on chromosome 14 (FAD14). In light of this functional relationship, we investigated the nucleotide sequence and segregation of c-FOS and the nucleotide sequence of the 5' APP promoter. Single-stranded conformational polymorphisms (SSCPs) in the c-FOS gene revealed that c-FOS closely cosegregates with the FAD14 gene but does not show allelic association with FAD. A conservative third-position T-->C mutation was demonstrated in exon 2 (codon 84) of c-FOS, and a C-->G substitution was detected at -209 bp in the 5' promoter of APP. Neither were unique to FAD and are unlikely to be pathogenic or secondary modifiers of the FAD phenotype. We conclude that the c-FOS open reading frame is probably not the site of the FAD14 locus, but we cannot exclude the existence of modifier loci on chromosome 21.

Adult↗
PubMed1993

Adrenergic regulation of alpha-MSH secretion in man: evidence for a stimulatory role of beta-receptors.

In several animal species the catecholamines stimulate the release of alpha-MSH from the melanotrope cells of the pituitary neurointermediate lobe through beta-receptors. The human hypophysis does not include a well-defined intermediate lobe and the methods for measuring alpha-MSH are often poorly sensitive. Neuroregulation of this hormone in man has thus received little attention. To see whether the adrenergic system is involved in the control of alpha-MSH secretion and whether the latter is independent of that of other peptides derived from proopiomelanocortin, such as ACTH, we studied the effects on plasma alpha-MSH-like immunoreactivity (alpha-MSH-LI), ACTH, and cortisol of some adrenergic drugs active on the beta-receptors. Six normal volunteers underwent the infusion of the following drugs: isoproterenol (0.03 microgram.kg-1.min-1 for 60 min), propranolol (1 mg.min-1 for 5 min followed by 0.1 mg.min-1 for 115 min), propranolol+isoproterenol (infused between 30 and 90 min of propranolol infusion), placebo (saline solution). Isoproterenol increased alpha-MSH-LI at 15 min (p < 0.001). Propranolol induced a fall of alpha-MSH-LI between 30 and 60 min (p < 0.001), followed by a return to preinfusion concentrations beginning at 75 min, and completely prevented the stimulatory effect of isoproterenol. Plasma ACTH and serum cortisol were always unaffected. These results indicate that in man the adrenergic system stimulates alpha-MSH-LI release through beta-receptors, and that alpha-MSH-LI secretion is dissociated from that of ACTH and cortisol. This in turn suggests that separate neuroregulatory mechanisms exist for the melanotrope and corticotrope cells.

Adrenocorticotropic Hormone↗
PubMed1992

Genetic evidence for a novel familial Alzheimer's disease locus on chromosome 14.

Familial Alzheimer's disease (FAD) has been shown to be genetically heterogeneous, with a very small proportion of early onset pedigrees being associated with mutations in the amyloid precursor protein (APP) gene on chromosome 21, and some late onset pedigrees showing associations with markers on chromosome 19. We now provide evidence for a major early onset FAD locus on the long arm of chromosome 14 near the markers D14S43 and D14S53 (multipoint lod score z = 23.4) and suggest that the inheritance of FAD may be more complex than had initially been suspected.

Aged↗
PubMed1991

Familial Alzheimer's disease. Evidences for clinical and genetic heterogeneity.

We report the genealogical, clinical and molecular genetic findings of a new family with autosomal dominant early-onset Alzheimer's disease (FAD) discovered in Torino (Italy). Up to now, the pedigree comprises 1500 members, distributed in 8 generations. 22 patients affected with Alzheimer's disease have been identified. The clinical course of the disease was fairly uniform in all the patients. An high incidence of myoclonic jerks and epileptic seizures was found. Molecular genetic studies showed the presence of positive but nonsignificant lod scores between chromosome 21 anonymous DNA markers and the disease. The data obtained from the Torino family were computed together with those of additional 47 pedigrees, with both early-onset and late-onset Alzheimer's disease. A predisposing locus for the disease was found on the pericentromeric region of chromosome 21 only in early-onset FAD pedigrees.

Adult↗
PubMed1991

[Pharmacologic treatment of migraine. Critical review of the literature].

The current aim of migraine treatment is to control attacks and reduce their frequency and intensity. Numerous drugs have been experimented in the pharmacological treatment of migraine, often with positive results. Almost always, only the main action mechanism can be hypothesised and sometimes drugs seem to act with very different mechanisms. Here mention is made of the principles, symptomatic and preventive, on which the pharmacological treatment of migraine is based. The drugs used in the two types of treatment are examined in terms of their action mechanism and their pharmacological group. Particular attention is paid to indications, contraindications and limitations of each treatment and the results reported in the literature are reviewed. For optimal treatment, prevention is considered indispensable for controlling symptomatology and preventing the pain becoming chronic. Correct preventive action also serves to avoid constant resort to symptomatic drugs, particularly analgesics, for which the risk of developing dependence or headache upon suspension of treatment is described.

Humans↗
PubMed1990

Beta-endorphin-like and alpha-MSH-like immunoreactivities in human milk.

We measured with radioimmunoassay the beta-endorphin-like and alpha-MSH-like immunoreactivities in milk and plasma of 8 lactating women. Mean beta-endorphin concentrations ( +/- SD) were 16.6 +/- 6.7 fmol/ml in milk and 9.9 +/- 4.1 fmol/ml in plasma. alpha-MSH concentrations (mean +/- SD) were 39.4 +/- 15.5 pg/ml in milk and 18.2 +/- 8.4 pg/ml in plasma. The concentrations of both peptides in milk were significantly (p less than 0.05) higher than in plasma. No significant correlation between milk and plasma concentrations of these peptides was found.

Adult↗
PubMed1990

Effects of chronic ethanol treatment on alpha-MSH concentrations in rat brain and pituitary.

Male Sprague-Dawley rats were chronically treated with a liquid diet containing 6.5% (v/v) ethanol or equicaloric sucrose. Rats were killed after 21 days of treatment. alpha-MSH-like immunoreactivity was measured in the intermediate lobe of the pituitary gland and in several brain regions. Chronic ethanol treatment significantly reduced alpha-MSH-like immunoreactivity in the pituitary gland; in the arcuate nucleus of the hypothalamus and in the substantia nigra. The results of this study confirm the earlier findings that chronic ethanol treatment reduces POMC biosynthesis in the pituitary gland and in the central nervous system.

Alcoholism↗
PubMed1990

[Plasma beta-endorphin and caffeine consumption in chronic hemicrania].

Thanks to recent biochemical and neuroendocrine findings, migraine belonging to the group of primary headaches appears as a pathology of the antinociceptive system with evolutive character. It has been demonstrated, in fact, that right at the early stage of migraine, there is a significant reduction in liquoral concentrations of beta-endorphin (beta-E), endogenous opioid peptide followed by a similar change in the plasma opioid system. The opioid system deficiency is even more evident after stimulation tests that point to reduced reactivity of the hypothalamo-hypophyseal system with respect to stimuli that in normal subjects trigger hypophyseal beta-E incretion. Caffeine, a member of the methyl-xanthine group, is an interesting molecule in the study of migraine patients because the chronic intake of this substance, contained in numerous analgesics, has been related to the chronic nature of the pain. The purpose of the present study is to assess the relationship between caffeine consumption and plasma opioid system. With the administration of a single oral dose of caffeine, normal subjects present an increase in plasma concentrations of beta-E, while in patients with chronic migraine, the response is significantly lower. These data confirm the poor reactivity of the plasma opioid system to pharmacological stimuli in migraine. Average daily consumption of caffeine has also been determined. It was not possible to establish a correlation between consumption of caffeine and plasma concentrations of beta-E whether basal or after stimulus with caffeine.

Administration, Oral↗
PubMed1988

Alpha-melanocyte-stimulating hormonelike immunoreactivity is increased in cerebrospinal fluid of patients with Parkinson's disease.

We measured alpha-melanocyte-stimulating hormonelike immunoreactivity in cerebrospinal fluid of 12 healthy control subjects and nine patients with Parkinson's disease, four of whom had never been treated. Mean cerebrospinal fluid alpha-melanocyte-stimulating hormonelike immunoreactivity concentration was two-fold greater in parkinsonian patients (44.1 +/- 9.3 [SD] pg/mL) as compared with control subjects (21.8 +/- 10.0 pg/mL). No significant correlation was found between cerebrospinal fluid alpha-melanocyte-stimulating hormonelike immunoreactivity concentrations and patient age, disease severity, or duration of disease. These results suggest a functional relation between dopaminergic and melanotropinergic systems in the human brain.

Aged↗