Search PubMed⌕ Search

Biomedical subjects

P Cortelli

Publications and source records attributed to P Cortelli.

At least 109 records · Page 6Linked to original sources
PubMed1995

Defective brain and muscle energy metabolism shown by in vivo 31P magnetic resonance spectroscopy in nonaffected carriers of 11778 mtDNA mutation.

In vivo phosphorus magnetic resonance spectroscopy (31P-MRS) showed defective brain and muscle energy metabolism in three affected siblings in a family with Leber's hereditary optic neuropathy (LHON) with the 11778 mtDNA mutation. We studied 14 nonaffected members of the same pedigree by 31P-MRS and molecular genetics. Nine of 14 individuals studied had the 11778 mtDNA mutation, with various degrees of heteroplasmy. A decreased brain energy reserve, as shown by low phosphocreatine content and phosphorylation potential and high [ADP], was present in eight of these nine subjects with the 11778 mutation. A low rate of postexercise phosphocreatine recovery in muscle was present in six of the nine mutated individuals. Normal MRS findings in the brain of one and the muscle of three carriers were accompanied by a low percentage of mutated mtDNA. All subjects without mutation had normal brain and muscle MRS. 31P-MRS disclosed defective bioenergetics in the brain or muscle or both of all asymptomatic carriers studied from our pedigree.

Adenosine Diphosphate↗
PubMed1995

Tardive pain.

Explore the source record for details and available documents.

Aged↗
PubMed1994

Different classes of volume transmission signals exist in the central nervous system and are affected by metabolic signals, temperature gradients and pressure waves.

Volume transmission (VT) is the mode of intercellular communication involving the diffusion of transmitters, via extracellular fluid (ECF) pathways, from nerve cells selectively capable of producing the signal (signal source) to nerve and glial cells selectively capable of recognizing it (signal target). The proposal is now put forward that at least two classes of VT signals can be distinguished: (a) the private-code signals, exemplified by neurotransmitters, which are released by a limited group of nerve cells and recognized, via high affinity G-protein coupled receptors or by cytosolic enzymes such as guanylate cyclase in the case of nitric oxide, by a specific group of cells; and (b) the accessible-code signals, such as the electrical signals that are released by all neuronal cells and decoded by almost every CNS cell. In the present paper, it will be underlined that carbon dioxide, hydrogen ions, temperature gradients and pressure waves may be regulators of wiring transmission and VT.

Animals↗
PubMed1994

Functional alterations of the mitochondrially encoded ND4 subunit associated with Leber's hereditary optic neuropathy.

Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease associated with point mutations in mitochondrial DNA. The most frequent of these mutations is the G-to-A substitution at nucleotide position 11,778 which changes an evolutionarily conserved arginine with a histidine at position 340 in subunit ND4 of NADH:ubiquinone reductase (respiratory complex I). We report that this amino acid substitution alters the affinity of complex I for the ubiquinone substrate and induces resistance towards its potent inhibitor rotenone in mitochondria of LHON patients. Such changes could reflect a substantial loss in the energy conserving function of NADH:ubiquinone reductase and thus explain the pathological effect of the ND4/11,778 mutation.

Amino Acid Sequence↗
PubMed1994

Fatal familial insomnia and familial Creutzfeldt-Jakob disease: different prion proteins determined by a DNA polymorphism.

Fatal familial insomnia and a subtype of Creutzfeldt-Jakob disease, two clinically and pathologically distinct diseases, are linked to the same mutation at codon 178 (Asp-178-->Asn) but segregate with different genotypes determined by this mutation and the methionine-valine polymorphism at codon 129 of the prion protein gene. The abnormal isoforms of the prion protein in these two diseases were found to differ both in the relative abundance of glycosylated forms and in the size of the protease-resistant fragments. The size difference was consistent with a different protease cleavage site, suggesting a different conformation of the protease-resistant prion protein present in the two diseases. These differences are likely to be responsible for the type and location of the lesions that characterize these two diseases. Therefore, the combination of the mutation at codon 178 and the polymorphism at codon 129 determines the disease phenotype by producing two altered conformations of the prion protein.

Codon↗
PubMed1994

Cardiovascular autonomic dysfunction in normotensive awake subjects with obstructive sleep apnoea syndrome.

Cardiovascular autonomic function in normotensive awake patients with obstructive sleep apnoea syndrome was studied in 21 normotensive (mean age 48 +/- 14 years), drug-free men with obstructive sleep apnoea syndrome. Cardiovascular reflex tests with continuous blood pressure monitoring and biochemical indices were performed the morning after a standard polygraphic sleep recording. A group of 20 age-matched (mean age 49 +/- 19 years) normal subjects was used as controls. The obstructive sleep apnoea syndrome patients showed higher heart rate and noradrenaline plasma levels (p < 0.05) at rest and a higher blood pressure response to head-up tilt (p < 0.01), suggesting sympathetic overactivity. Respiratory arrhythmia, baroreflex sensitivity index and Valsalva ratio were significantly lower in the obstructive sleep apnoea syndrome group (p < 0.01) whereas the decrease in heart rate induced by the cold face test was significantly higher (p < 0.05) showing a blunting of reflexes dependent on baroreceptor or pulmonary afferents with normal or increased cardiac vagal efferent activity. These abnormalities in autonomic regulation may predispose obstructive sleep apnoea syndrome patients to cardiovascular complications like hypertension and cardiac arrhythmias.

Adult↗
PubMed1994

Magnetic resonance spectroscopy studies in migraine.

We describe the method of 31phosphorous magnetic resonance spectroscopy and review the results when it is applied to the study of brain and muscle energy metabolism in migraine subjects. Brain energy metabolism appears to be abnormal in all major subtypes of migraine when measured both during and between attacks. Impaired energy metabolism is also documented in skeletal muscle. We suggest that migraine is associated with a generalized disorder of mitochondrial oxidative phosphorylation and that this may constitute a threshold for the triggering of migraine attacks.

Brain↗
PubMed1994

Abnormal platelet mitochondrial function in patients affected by migraine with and without aura.

To investigate energy metabolism in migraine, we determined platelet mitochondrial enzyme activities in 40 patients with migraine with aura and in 40 patients with migraine without aura during attack-free intervals and in 24 healthy control subjects. NADH-dehydrogenase, citrate synthase and cytochrome-c-oxidase activities in both patient groups were significantly lower than in controls (p < 0.01), while NADH-cytochrome-c-reductase activity was reduced only in migraine with aura (p < 0.01). No alteration in succinate-dehydrogenase was observed. Monoamine-oxidase activity differed between sexes (p < 0.05) but within each sex group no difference was observed between patients and controls. We hypothesize that the defect in mitochondrial enzymes observed indicates a systemic impairment of mitochondrial function in migraine patients.

Adolescent↗
PubMed1994

Diurnal blood pressure variation and hormonal correlates in fatal familial insomnia.

Fatal familial insomnia is a prion disease in which a selective thalamic degeneration leads to total sleep deprivation, hypertension, dysautonomia, adrenal overactivity, and impaired motor functions. With patients under continuous recumbency and polysomnographic control, we assessed the changes in the 24-hour patterns of blood pressure, heart rate, plasma catecholamines, corticotropin, and serum cortisol in three patients at different stages of the disease. Six healthy volunteers were used as control subjects. A dominant 24-hour component was detected at rhythm analysis of all variables, both in patients and control subjects. In the patients, the amplitudes gradually decreased as the disease progressed, leading to the obliteration of any significant dirunal variation only in the preterminal stage. A shift in phase corresponded to the loss of the nocturnal fall in blood pressure in an early stage of the disease, when nocturnal bradycardia was still preserved. Plasma cortisol was high and became increasingly elevated, whereas corticotropin remained within normal levels; abnormal nocturnal peaks appeared in their circadian patterns. The disrupted patterns of cortisol and blood pressure preceded the development of hypertension and severe dysautonomia, which in turn were paralleled by increasing catecholamine and heart rate levels. Our data demonstrate that in patients with fatal familial insomnia the changes detectable in the rhythmic component of diurnal blood pressure variability result in a pattern of secondary hypertension. Disturbances in thalamic, pituitary-adrenal, and autonomic functions seem to be involved in mediating these changes.

Adrenocorticotropic Hormone↗
PubMed1994

Progressive disruption of the circadian rhythm of melatonin in fatal familial insomnia.

Fatal familial insomnia (FFI) is a disease characterized by loss of sleep activity due to selective thalamic degeneration. To assess the secretory pattern of melatonin (MT) in FFI, we studied two cases of overt disease under standardized conditions and polysomnographic control. Each patient underwent repeated 24-h study sessions, and MT was assayed at 30-min intervals. Six healthy volunteers were used as controls. Slow wave sleep was never recorded, whereas occasional episodes of enacted dreaming accompanied by rapid ocular movements and complex muscular activities were documented, with no detectable rhythm. Plasma MT concentrations gradually decreased as the disease progressed. A significant circadian rhythm was detected in the earlier recordings, with decreasing amplitudes with disease progression. Complete rhythm obliteration was achieved in the most advanced stage. Normally placed nocturnal acrophases were detected in the earlier stages, but then a shift toward the daytime hours was observed. Thalamic lesions of FFI appear to determine a progressive disruption of the sleep/wake cycle accompanied by decreased circulating levels of MT, with progressive alterations in the circadian rhythm of this hormone. On the other hand, decreased secretion of MT may contribute to the sleep disturbances of FFI.

Adult↗
PubMed1994

Idiopathic recurring stupor.

Idiopathic recurring stupor (IRS) is a disease of unknown pathogenesis presenting with recurrent stuporous states. We describe three IRS patients in whom there were no metabolic, toxic, or structural brain dysfunctions. Ictal EEGs were characterized by fast (14- to 16-Hz), unreactive background activity. Flumazenil, a benzodiazepine receptor antagonist, promptly resolved the clinical and EEG picture. In all patients, ictal plasma determination showed a marked increase in benzodiazepine-like activity identified as endozepine-4. IRS may be due to an unexplained excess of endozepine-4.

Adult↗
PubMed1994

31P-magnetic resonance spectroscopy in migraine without aura.

We investigated 22 patients with migraine without aura, all drug-free and in headache-free periods, by means of 31P-magnetic resonance spectroscopy (MRS) of brain and muscle. Brain 31P-MRS showed significantly low phosphocreatine, increased adenosine diphosphate, and decreased phosphorylation potential. There was a slow rate of phosphocreatine recovery after exercise in the muscle of 12 of 22 patients. Energy metabolism is abnormal in migraine without aura, as previously demonstrated in patients with migraine stroke and migraine with aura.

Adolescent↗
PubMed1994

Longitudinal monitoring of the levodopa concentration-effect relationship in Parkinson's disease.

We prospectively evaluated over 4 years the intrasubject relationship between levodopa plasma concentration and the tapping effect after a standard oral levodopa test in 28 patients with mild-to-moderate idiopathic Parkinson's disease. The onset and duration of the tapping effect significantly shortened over years; response amplitude did not vary. Levodopa plasma kinetics remained unchanged. Pharmacodynamic modeling indicated a progressive decrease in the equilibration half-life between plasma drug concentration and effect, which correlated with the shorter motor response. No clear-cut change in maximum response (Emax) emerged, but levodopa concentration needed to yield 50% of maximum effect (EC50) significantly increased. These data indicate that the duration of motor response becomes a major determinant of drug efficacy over years. The modifications in levodopa effect-compartment equilibration half-life and EC50 further support the suggestion that alterations in cerebral levodopa kinetics have an important role in the development of response fluctuations.

Adult↗
PubMed1994

Do autonomic cardiovascular reflexes predict the nocturnal rise in blood pressure in obstructive sleep apnea syndrome?

To investigate the relationship between nocturnal changes in blood pressure (BP) and diurnal cardiovascular reflexes we examined a group of 19 male normotensive obstructive sleep apnea syndrome (OSAS) patients. All patients underwent a full polysomnographic examination including BP monitoring by a finger arterial pressure device (Finapres) and a battery of cardiovascular reflex tests; plasma catecholamine levels at rest were also measured. During sleep, BP increased with an average difference of 15.4 +/- 7.5 mmHg for systolic and 8.3 +/- 4.6 mmHg for diastolic pressure. Compared with control subjects, OSAS patients had lower values of Valsalva ratio (VR) (1.75 +/- 0.4 vs 1.34 +/- 0.2, p = 0.0004), E/I ratio (1.35 +/- 0.2 vs 1.13 +/- 0.9, p = 0.0004) and baroreflex sensitivity index (BRSI) (5.4 +/- 2.1 vs 2.7 +/- 1.9 mms/mmg, p = 0.0006) and a higher systolic (p = 0.02) and diastolic (p = 0.002) pressure response to tilting-up test. Noradrenaline plasma levels were also significantly higher (345 +/- 125 vs 224 +/- 92 pg/ml, p = 0.001). No significant correlations were found between the nocturnal rise in BP and the pressure responses during sympathetic manoeuvres or rest levels of noradrenaline. The nocturnal changes in systolic blood pressure during the night were negatively dependent on the diurnal BRSI (r = -0.91, p = 0.0007) and VR (r = -0.70, p = 0.006). We conclude that the high levels of noradrenaline at rest and the altered sympathetic cardiovascular reflexes alone do not account for the nocturnal variation in blood pressure in OSAS.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗