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Biomedical subjects

G Serra

Publications and source records attributed to G Serra.

At least 19 recordsLinked to original sources

Cerebral blood-flow monitor for use in neonatal intensive care units.

The implementation of a real-time multichannel system for monitoring cerebral blood-flow is described. The instrument relies on a completely modular architecture and is based on the principle of measuring the electrical impedance between a number of periodically sensed electrode pairs positioned around the subject's head. The whole setup is controlled by a host computer that performs several functions, such as real-time acquisition, analysis, display and data logging. Two operating options can be chosen by the user: a normal mode that allows continuous monitoring and a triggered mode in which the measurement cycle is automatically started by the occurrence of a preset condition in some other circulatory signal, e.g. the permanently available ECG signal. The design is considerably user-friendly and embodies a number of special safety precautions to take account of the peculiar condition of patients, usually newborn infants hospitalized in intensive care units.

Cerebrovascular Circulation

Dizocilpine prevents the enhanced locomotor response to quinpirole induced by repeated electroconvulsive shock.

Repeated administration of electroconvulsive shock, as expected, potentiated the locomotor stimulant response to quinpirole (0.3 mg/kg s.c.), a dopamine D2-like receptor agonist. Chronic, but not acute, treatment with the NMDA receptor non-competitive antagonist dizocilpine (0.3 mg/kg i.p.) prevented electroconvulsive shock-induced potentiation of quinpirole locomotor response. These results suggest that NMDA receptor activation is necessary for the development of supersensitivity to dopamine receptor agonists produced by repeated electroconvulsive shock. The relevance of this observation in regard to the mechanism of electroconvulsive shock therapeutic effect is discussed.

Animals

Behavioural sensitization of mesolimbic dopamine D2 receptors in chronic fluoxetine-treated rats.

A common action of chronic antidepressant treatments is the potentiation of dopaminergic transmission in the limbic system. We now report that chronic, but not acute, treatment with fluoxetine (2.5 mg/kg by intragastric gavage once a day for 21 days) potentiates the locomotor stimulant effect of quinpirole, a selective dopamine D2/D3 receptor agonist. However, neither quinpirole-induced stereotypies nor the sedative effects elicited by low doses of this dopamine receptor agonist are influenced by chronic fluoxetine. These results suggest that fluoxetine, as well as classical antidepressants, sensitize postsynaptic dopamine D2/D3 receptors in the mesolimbic system.

Animals

Severe complex I deficiency in a case of neonatal-onset lactic acidosis and fatal liver failure.

We report a newborn admitted to our service on the 2nd day of life because of hypotonia and metabolic acidosis. A progressive hepatocellular dysfunction dominated the clinical picture and the patient died at 13 months of age because of severe hepatic failure. Persistent lactic acidosis, high ketone bodies levels and high-normal lactate/pyruvate and 3-hydroxybutyrate/acetoacetate molar ratios in plasma were found. Investigation of a liver biopsy revealed low activities of all the mitochondrial respiratory chain enzymes but in particular a marked decrease of complex I (NADH cytochrome c reductase) activity. All respiratory chain enzyme activities were normal in cultured skin fibroblasts. Mitochondrial DNA analysis failed to detect any major rearrangements. Although only a few cases have been reported so far, it is becoming clear that liver should be considered as one of the organs involved in oxidative phosphorylation disorders. The finding of unexplained progressive liver failure with poor neurological conditions, lactic acidaemia and ketonuria strongly warrants investigation for a respiratory chain disorder. Moreover, the finding of normal respiratory enzyme activities in a tissue other than liver does not rule out the existence of an oxidative phosphorylation disorder in patients with hepatocellular disease of unexplained origin.

Acidosis, Lactic

Fatty acid composition of human milk in Italy.

The fatty acid composition of breast milk from 20 Italian women, delivering at term and on ad libitum diets, was analyzed with high-resolution gas chromatography. Milk samples were collected twice a day, on the 1st, 4th, 7th, 14th, 21st and 28th day after colostrum appearance. No significant differences were detected between the two daily samples. During the maturation process a significant reduction in long-chain polyunsaturated fatty acids of the n-6 series (p = 0.002) and n-3 series (p = 0.005) was recorded, particularly in arachidonic acid (p = 0.035), docosatetraenoic acid (p = 0.035) and docosahexaenoic acid (p = 0.032). The linoleic acid/n-6 and alpha-linolenic acid/n-3 ratios increased (p = 0.024 and p = 0.037), while the docosatetraenoic/docosahexaenoic acid ratio decreased (p = 0.032). The fatty acid composition of mature milk was the following: saturated 45.50%; unsaturated 54.51%; monounsaturated 42.69%; polyunsaturated 11.82%; long-chain polyunsaturated 1.27%; linoleic acid 9.79%, and alpha-linolenic acid 0.36%. The fatty acid composition of milk collected from Italian women appears similar to that of women in other southern European countries and, therefore, could reflect dietary habits.

Adult

Role of D1 and alpha1 receptors in the enhanced locomotor response to dopamine D2-like receptor stimulation induced by repeated electroconvulsive shock.

We previously reported that, in rats chronically treated with the antidepressant drug imipramine, the enhanced locomotor response to the D2-like receptor agonist quinpirole became less sensitive to the inhibitory effect of the D1 receptor antagonist SCH 23390 and more sensitive to the inhibitory effect of the alpha1 receptor antagonist prazosin. In this study, we show that in electroconvulsive shock-treated rats these antagonists behave in the opposite manner to that observed in imipramine-treated rats, with SCH 23390 being highly effective and prazosin ineffective in antagonizing the locomotor response to quinpirole. The possibility that these differences may reflect some of the clinical characteristics of these antidepressant treatments is discussed.

Animals

Biochemical and electrophysiological effects of 7-OH-DPAT on the mesolimbic dopaminergic system.

Systemic administration of the putative selective D3 receptor agonist 7-hydroxy-2-(N,N-di-n-propylamino)tetralin (7-OH-DPAT) consistently decreased extracellular dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the nucleus accumbens and dopaminergic neuronal activity in the ventral tegmental area. 7-OH-DPAT inhibited dopamine release in the nucleus accumbens also when locally perfused through the dialysis probe. The results suggest the possibility that stimulation of dopamine D3 receptors with 7-OH-DPAT mimic biochemical and electrophysiological actions previously ascribed to D2 autoreceptor stimulation; however the lack of selective D3 antagonist precludes any firm conclusion in this sense.

Animals

An AT-deletion causing a frameshift in the arylsulfatase A gene of a late infantile metachromatic leukodystrophy patient.

A metachromatic leukodystrophy (MLD) patient affected with the late infantile form was found to be homozygous for an AT-deletion (2324delAT) in the arylsulfatase A gene. The mutation causes a frameshift at the beginning of exon 8 leading to an early termination codon. The parents and unaffected brother of the patient were heterozygous for the microdeletion. The mutation was not detected in another 31 MLD Italian patients. No aberrant transcript caused by the mutation was revealed by the reverse transcription-polymerase chain reaction method.

Amino Acid Sequence

Reduced serum levels of dehydroepiandrosterone sulphate in adrenal incidentalomas: a marker of adrenocortical tumour.

BACKGROUND AND OBJECTIVE: Reduced serum levels of dehydroepiandrosterone sulphate (DHEAS) have been shown in patients with Cushing's syndrome resulting from adrenocortical adenoma, in contrast with normal DHEAS levels in patients with Cushing's disease. The aim of this study was to verify whether patients with incidentally discovered adrenocortical adenomas also have reduced levels of DHEAS. DESIGN: Evaluation of serum DHEAS, serum and urinary cortisol, plasma ACTH and low dose dexamethasone suppression test in patients with adrenal incidentaloma and Cushing's syndrome. PATIENTS: Thirty-two patients with adrenal incidentaloma and, as controls, 17 patients with overt Cushing's syndrome, were studied. RESULTS: Serum DHEAS levels lower than normal were found in 21/24 (87.5%) patients with adrenocortical incidentaloma, but in only 1/8 patients with a mass of non-adrenocortical origin. This patient had massive bilateral metastatic infiltration of both adrenal glands and primary adrenal failure. The prevalence of low DHEAS levels in the two groups was significantly different (P = 0.0001). In patients with adrenocortical incidentaloma, the prevalence of low DHEAS levels was significantly higher (P = 0.0001) than that found for some hormonal alterations indicating pre-clinical hypercortisolism (high urinary cortisol, unsuppressed serum cortisol after low dose dexamethasone administration and low plasma ACTH). Low DHEAS levels were found in all patients with Cushing's syndrome due to adrenocortical adenoma but in none of those with Cushing's disease. CONCLUSIONS: Our results indicate that the finding of low DHEAS levels can be considered a marker of the adrenocortical origin of an adrenal incidentaloma, provided adrenal failure has been excluded.

17-alpha-Hydroxyprogesterone

[Anxious-excited depression: a mixed affective syndrome].

A mixed affective syndrome is described which meets the criteria for major depression but not those of the DSM III-R for a mixed state. The clinical picture is characterized by lack of motor retardation and fluent verbalization; the facial expression is animated and sometimes dramatic. Patients suffer considerably and are often tearful. They complain of inner tension and restlessness, racing thoughts and despair. Emotional lability and momentary irritability are observed. Insomnia occurs initially or with frequent early waking. Suicidal ideation occurs and makes the syndrome of concern in view of its impulsive nature. Antidepressants increase restlessness, insomnia, aggressiveness and the impulsiveness of suicidal ideation. Low-dose neuroleptics, lithium and anticonvulsivants are highly effective. A few sessions of ECT offer rapid improvement.

Anxiety Disorders

Antidepressant-like effect of selective dopamine D1 receptor agonists in the behavioural despair animal model of depression.

We compared the effect of two selective dopamine D1 receptor agonists, SKF 38393 ((+/-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol.HCl) and A68930 ((1R,3S)-1-aminomethyl-5,6-dihydroxy-3-phenylisochroman.HCl), and that of imipramine in the behavioural despair model of depression. The dopamine D1 receptor agonists and imipramine showed an anti-immobility effect. Moreover we found that the 'antidepressant' effect of imipramine in the behavioural despair test was antagonized by SCH 23390, a selective dopamine D1 receptor blocker. The results further support the hypothesis that dopamine D1 receptor stimulation plays an important role in the mechanism of action of antidepressants and suggest that dopamine D1 receptor agonists might be considered as potential antidepressant drugs.

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