Biomedical subjects

A Postiglione

Publications and source records attributed to A Postiglione.

At least 55 records · Page 3Linked to original sources

PubMed1993

Effect of acetyl-L-carnitine treatment on brain adenylate cyclase activity in young and aged rats.

The aim of the present study has been to evaluate the effect of acetyl-L-carnitine (ALCAR) on brain adenylate cyclase (AC) activity in adult and aged rats. In in vitro studies, ALCAR (1, 10 and 100 microM) did not exert any effect on frontal cortex basal AC activity. Acute and subchronic administrations of ALCAR were carried out in 4- and 25-month-old male Fisher rats and AC activity was determined in rat frontal cortex under both basal and stimulated conditions. The acute treatment of young rats with ALCAR (100 and 500 mg/kg s.c.) did not affect AC activity, whereas the subchronic administration of 250 mg/kg s.c. ALCAR enhanced the stimulation of AC by carbamylcholine (CCh), norepinephrine (NE) and dopamine (DA), without affecting the basal AC activity. Basal AC activity in old rats was lower than in young rats and was not modified by acute and subchronic ALCAR administration. Moreover, the response of the enzyme to CCh, NE and DA was potentiated by the subchronic administration of ALCAR. The concentration-response curve of CCh stimulation of AC activity in ALCAR-treated rats is shifted to the left in both young and aged rats. We conclude that ALCAR, subchronically administered, is able to enhance receptor-stimulated AC response in frontal cortex of both young and aged rats.

Acetylcarnitine↗

PubMed1993

Serum lipoprotein fatty acid profile in hereditary ataxias.

We investigated the serum fatty acid profiles of cholesterol esters, phospholipids and triglycerides in 24 patients with Friedreich's disease and 16 patients with other forms of spinocerebellar degeneration. In 8 patients with Friedreich's disease we also analyzed the fatty acid profile of the lipoprotein fractions. We found no major differences in fatty acid profiles between ataxic patients and sex and age-matched controls; in particular there was no decrease of linoleic acid in Friedreich's disease. The level of linoleic acid in serum cholesterol esters decreased with increasing disability of patients.

Adolescent↗

PubMed1993

Functionally abnormal monocytes in hypercholesterolemia.

We investigated some functions of monocytes from 20 type IIa hypercholesterolemic (HC) and five homozygous familial hypercholesterolemic (FH) patients. Monocytes from the HC patients contained as much cholesterol and formed as much thromboxane B2 in response to N-formyl-methionyl-leucyl-phenylalanine (fMLP) or calcium ionophore A23187 as those from normal individuals. In contrast, the generation of prostaglandin E2 and 6-ketoprostaglandin F1 alpha in response to these agonists was 1.5-3 times normal, and that of leukotriene B4 was 40-60% of the normal value (p < 0.05 for all). Studies in which the combination of fMLP or A23187 with sodium arachidonate were employed suggested that these abnormalities were independent of the availability of the endogenous substrate for the lipoxygenase or cyclooxygenase enzymes. Quantitatively and qualitatively comparable abnormalities were found in monocytes from the five FH patients, and these were little affected when the patients' plasma cholesterol levels were almost normalized by low density lipoprotein apheresis. In keeping with the abnormalities in the eicosanoid metabolism, monocytes from HC patients exhibited a defective ability (p < 0.05) to generate O2-, the extent of which was correlated with the impaired formation of leukotriene B4. On the other hand, adhesion studies indicated that patients' cells exhibited an abnormally high ability to adhere to glass (p < 0.01). These data indicate the presence of functionally abnormal monocytes in hypercholesterolemia and suggest a direction to be followed to understand the importance of such cells in the premature atherosclerosis that occurs in these patients.

Adolescent↗

PubMed1993

Cerebral blood flow velocity and systemic vascular resistance after acute reduction of low-density lipoprotein in familial hypercholesterolemia.

BACKGROUND AND PURPOSE: Low-density lipoprotein apheresis is currently used for the treatment of familial hypercholesterolemia, an inherited disorder of metabolism associated with premature development of cardiovascular disease. We wanted to evaluate cerebral blood flow velocity, cardiac output, and systemic vascular resistance in patients with familial hypercholesterolemia before and after low-density lipoprotein apheresis. METHODS: Ten patients (age range, 14 to 46 years; 4 males, 6 females) with familial hypercholesterolemia (8 homozygotes, 2 heterozygotes) and 10 healthy control subjects of comparable age and sex distribution participated in the study. Low-density lipoprotein apheresis by dextran sulfate was performed in 8 patients (7 homozygotes, 1 heterozygote). Six patients (4 homozygotes, 2 heterozygotes) underwent a procedure of extracorporeal erythrocyte filtration with the same extracorporeal volume as for low-density lipoprotein apheresis, but with the exclusion of the passage of plasma through the dextran sulfate column. Cerebral blood flow velocity (transcranial Doppler), cardiac output, and systemic vascular resistance (electric bioimpedance cardiography) were determined by noninvasive techniques before and 1 day and 7 days after low-density lipoprotein apheresis or extracorporeal erythrocyte filtration. Plasma and blood viscosities were measured at the same time. RESULTS: Before apheresis, mean and diastolic cerebral flow velocities were abnormally low in hypercholesterolemic patients (P < .01 and P < .02 vs healthy control subjects, respectively). After apheresis, low-density lipoprotein cholesterol was lowered by 40% to 60% from baseline, and cerebral blood flow velocities (mean, systolic, and diastolic velocities) were increased (P < .01). Cardiac output, systemic vascular resistance, and viscosity values were not significantly modified. Extracorporeal erythrocyte filtration (without passage of plasma through the dextran sulfate column) did not modify serum lipids, hemodynamic parameters, or viscosity values. CONCLUSIONS: Low-density lipoprotein apheresis produces potentially useful hemodynamic effects. They are not adequately explained by changes in blood viscosity alone and might reflect a restoration of endothelium-mediated vasodilation, which is inhibited by high concentrations of low-density lipoprotein.

Adolescent↗

PubMed1993

Direct effect of adenosine on prolactin secretion at the level of the single rat lactotroph: involvement of pertussis toxin-sensitive and -insensitive transducing mechanisms.

We studied the effect of adenosine on prolactin secretion by the anterior pituitary, and the transduction mechanisms whereby the purine exerts its action. Adenosine inhibited prolactin release in basal and in vasoactive intestinal peptide (VIP)- or TRH-stimulated conditions. Pertussis toxin pretreatment reduced the inhibition of VIP-stimulated prolactin secretion which was induced by adenosine, while it completely abolished the effect of the purine on TRH-evoked prolactin release. In membrane preparations of anterior pituitary cells, adenosine reduced the adenylate cyclase activity stimulated by VIP. Such an inhibition was not blocked by pertussis toxin pretreatment. Furthermore, the purine reduced TRH-stimulated inositol phosphate production in cultured anterior pituitary cells, an effect that was reversed by pretreatment with pertussis toxin. In addition, the nucleoside did not significantly affect the TRH-induced rise in intracellular calcium. In conclusion, our data show that adenosine inhibits prolactin secretion, acting on purinergic receptors coupled to the adenylate cyclase enzyme and phospholipase C. The effect of the nucleoside on adenylate cyclase seems to be achieved either by the involvement of an adenosine receptor coupled to the catalytic subunit of the enzyme via a pertussis toxin-sensitive G protein, or by the activation of a site directly coupled to the catalytic subunit of the adenylate cyclase (the P site). Its effect on phospholipase C seems to be mediated by a purinergic receptor coupled to the intracellular effector via a pertussis toxin-sensitive G protein.

Adenosine↗

PubMed1993

Transcranial Doppler evaluation of cerebrovascular reactivity to acetazolamide in normal subjects.

Acetazolamide (AZ), the selective inhibitor of carbonic anhydrase, was proved by intravenous Xenon 133 technique to increase cerebral blood flow (CBF). In this study cerebrovascular reactivity to AZ was evaluated in 10 normal subjects by transcranial Doppler (TCD) within the middle cerebral artery (MCA), since several reports have demonstrated that velocity of cerebral blood flow is well correlated to CBF. After 1 gr AZ injection blood flow velocity markedly increased in all subjects, with a peak in both systolic and diastolic velocity 20 min after drug administration. At that time systolic velocity increased by 35% and diastolic velocity by 50% in comparison to basal values. In contrast with Xenon 133 technique which gives one measurement only for each investigation, TCD allows a continuous monitoring of haemodynamic change following AZ infusion. MCA diastolic velocity at rest was inversely related to age (r = -.804, p < 0.01); baseline diastolic velocity was inversely related to the maximum percentage increment (r = -.745 p < .05). No change in blood pressure and heart rate was observed under experimental conditions. These results, confirm the usefulness of the AZ test in the evaluation of cerebrovascular reactivity and strongly support the use of TCD technique applied to AZ in order to investigate cerebrovascular haemodynamics in normal healthy subjects and in patients at risk of cerebrovascular insufficiency.

Acetazolamide↗

PubMed1992

Molecular mechanisms mediating the effects of L-alpha-glycerylphosphorylcholine, a new cognition-enhancing drug, on behavioral and biochemical parameters in young and aged rats.

The behavioral effects of the acute and subchronic administration of L-alpha-glycerylphosphorylcholine (alpha-GPC) on passive and active avoidance behavioral tasks were investigated. When administered IP after training together with scopolamine 2 h before retest, alpha-GPC reverses the scopolamine-induced amnesia in the passive avoidance conditioning in young and old rats. Furthermore, the subchronic treatment with alpha-GPC positively and significantly influences the performance of both young and old animals in the active avoidance test. Moreover, in in vitro/ex vivo experiments alpha-GPC potentiates receptor-stimulated phosphatidylinositol hydrolysis in cortical synaptoneurosomes derived from young and old animals. In young but not old animals, alpha-GPC significantly potentiates potassium (40 mM)-stimulated intrasynaptosomal calcium oscillations in purified synaptosomes derived from the hippocampus. These results show that alpha-GPC improves the performance of animals in both active and passive conditioning tasks. Furthermore, subchronic treatment with the compound enhances in young and restores in aged animals the transduction of the signal, namely, the receptor-mediated production of inositol phosphate and the potassium-induced calcium mobilization. These modifications may represent at least part of the molecular mechanism of action of the compound.

Adenylyl Cyclases↗

PubMed1992

Prevalence of peripheral arterial disease and related risk factors in elderly institutionalized subjects.

Blood pressure was measured at the posterior tibial artery by Doppler ultrasonography in 124 elderly subjects (37 men and 87 women) living in two retirement homes in Naples (Italy). Ankle-to-arm systolic pressure ratios below 0.97 and 0.90 was considered as a probable and definite pathological sign of peripheral arterial disease, respectively. Half of the subjects (48% of men and 51% of women) gave a value below 0.97, while a third (35% of men and 33% of women) had a value below 0.90. By multiple regression analysis, mean blood pressure, plasma cholesterol levels and cigarette smoking were all negatively correlated with ankle systolic pressure values with a progressively lower significance. Most of the patients with pathological Doppler examination were asymptomatic at a questionnaire for intermittent claudication.

Age Factors↗

PubMed1991

Age-related alterations of somatostatin gene expression in different rat brain areas.

Numerous experimental and clinical studies have demonstrated that brain somatostatinergic neurotransmission plays an important role in the modulation of several brain functions, including learning and memory processes. Due to the gradual decline of cognitive performances occurring during aging, we evaluated whether an age-related modification of brain somatostatin gene activity occurred in discrete rat brain areas. Our study demonstrates that a significant reduction of pre-prosomatostatin mRNA levels occurred in aged animals (25 months) in the frontal cortex (-49%), in the parietal cortex (-80%) and in the striatum (-69%), despite the absence of changes in beta-actin gene expression. Conversely, no statistical differences were observed in the pre-prosomatostatin mRNA content of old animals in the hypothalamus. These results demonstrate that age-related alterations in somatostatin gene expression occur in the rat, and suggest that such alterations may be involved in the behavioral and cognitive impairments that occur during the aging process.

Aging↗

PubMed1991

Relative protection from cerebral atherosclerosis of young patients with homozygous familial hypercholesterolemia.

It is well known that hypercholesterolemia is correlated with coronary atherosclerosis, but no definite information is available on its association with cerebrovascular atherosclerosis. We studied 10 young patients (age 3-32 years) with homozygous familial hypercholesterolemia (FH), together with 3 normal relatives as healthy controls. Extra- and intracranial Doppler examination, MRI and cerebral blood flow by SPECT and 99mTc-HM-PAO were performed on all. Six out of 10 patients already had signs and symptoms of coronary heart disease, but all patients were free from ischemic brain lesions, as small as detectable at MRI, and had normal cerebral blood flow. Two patients presented significant stenosis of the carotid arteries at Doppler examination. Young patients with homozygous FH have early and clinically evident coronary atherosclerosis, while overt disease in the cerebral district is delayed despite the extremely elevated plasma cholesterol concentration. This was also confirmed by the autopsy of two patients, who died after the study and whose cerebral arteries were totally free from atherosclerotic lesions. The age, at which flow-reducing atherosclerotic lesions develop in hypercholesterolemic patients, differs with regard to the arterial district involved.

Adolescent↗

PubMed1991

Effect of acute administration of L-acetyl carnitine on cerebral blood flow in patients with chronic cerebral infarct.

The effect of L-acetyl carnitine (L-AC) on cerebral blood flow (CBF) was evaluated in 20 patients with chronic cerebrovascular disease, who suffered an ischaemic stroke at least 6 months before the study. All patients performed a CT scan and were investigated with xenon-133 by brain dedicated single photon emission computed tomography (SPECT, Tomomatic 32, Medimatic Inc., Copenhagen). A single high dose (1.5 g) of L-acetyl carnitine was intravenously administered to 10 patients, while sodium acetate as placebo was injected to 10 other subjects. Cerebral blood flow (ml/min x 100 g) was evaluated before and 45 min after the injection. No changes were observed after placebo injection (43 +/- 12 ml/min x 100 g versus 43 +/- 10 ml/min x 100 g). CBF increased (from 42 +/- 9 ml/min x 100 g to 46 +/- 9, P less than 0.05) in both ipsilateral and contralateral hemisphere, the ischaemic area, but not in the stroke corresponding zone. It was concluded that L-acetyl carnitine at the i.v. dosage of 1.5 g acutely enhanced CBF in patients with chronic cerebral infarct.

Acetylcarnitine↗

PubMed1991

Mixed transcortical aphasia: clinical features and neuroanatomical correlates. A possible role of the right hemisphere.

This paper reports the clinical features of 2 patients affected by mixed transcortical aphasia. Both of them had extensive damage of the left hemisphere. Cerebral blood flow measurement showed a marked decrease in left-hemisphere flow. In particular, speech areas were found to be morphologically and functionally damaged. The present findings, together with a critical review of the literature, served as a starting point for a discussion of linguistic features, diagnostic criteria and classical neuroanatomical interpretation of mixed transcortical aphasia. The possible contribution of the right hemisphere in determining this aphasic syndrome is suggested.

Aged↗

PubMed1991

Cerebrovascular effects of angiotensin converting enzyme inhibition involve large artery dilatation in rats.

BACKGROUND AND PURPOSE: The aim of the study was to selectively examine the effects of converting enzyme inhibition on the large brain arteries by using concomitant inhibition of carbonic anhydrase to cause severe dilatation of mainly parenchymal resistance vessels. METHODS: Cerebral blood flow was measured using the xenon-133 injection technique in three groups of Wistar rats either during carbonic anhydrase inhibition with acetazolamide (treatment A, n = 8), during carbonic anhydrase inhibition followed by converting enzyme inhibition with captopril 40 minutes later (treatment B, n = 10), or during carbonic anhydrase inhibition preceded by converting enzyme inhibition 20 minutes earlier (treatment C, n = 7). RESULTS: After treatment A, cerebral blood flow rose rapidly and stabilized within 20 minutes at an average of 220 ml/100 g.min; flow remained stable until at least 60 minutes. After treatment B, cerebral blood flow increased by a further 17.4%, from an average of 219 ml/100 g.min to an average of 257 ml/100 g.min (p less than 0.01). After treatment C, cerebral blood flow stabilized at an average of 238 ml/100 g.min, with flow from 20 to 60 minutes always being higher (from 5% to 17%) than during carbonic anhydrase inhibition alone (p less than 0.02). Thus the additional inhibition of converting enzyme resulted in higher cerebral blood flow than during inhibition of carbonic anhydrase alone. CONCLUSIONS: These results suggest that converting enzyme inhibition reduced resistance of large brain arteries and support the hypothesis that there is some angiotensin II-induced tone in large cerebral arteries.

Acetazolamide↗

PubMed1991

Changes in middle cerebral artery blood velocity in uremic patients after hemodialysis.

BACKGROUND AND PURPOSE: Strokes are a frequent complication in uremic patients on dialysis. We wanted to evaluate the effect of this treatment on cerebral hemodynamic parameters, particularly those of patients with carotid stenosis, who are at higher risk for atherothrombotic ischemic events. METHODS: We used transcranial Doppler ultrasonography to evaluate blood velocity of the middle cerebral artery in 18 uremic patients before and after hemodialysis. Carotid stenosis was evaluated by echo-Doppler investigation. Six patients were also studied before and after recombinant human erythropoietin treatment. RESULTS: Dialysis treatment decreased mean blood velocity in all patients (p less than 0.001). Eight of 18 patients (44%) with mild (16-50%), moderate (51-80%), or severe (greater than 80%) carotid stenosis had lower velocity than patients with normal carotid arteries (p less than 0.01), and they experienced a further decrease to even lower levels after hemodialysis (p less than 0.05). In patients treated with recombinant human erythropoietin, hematocrit increased from 28 +/- 8% to 37 +/- 5% (p less than 0.001), and blood velocity had a further decrease by 11%. All changes were associated with modifications toward normality of pH, PaCO2, and hematocrit. CONCLUSIONS: Transcranial Doppler ultrasonography represents a useful method for monitoring cerebral circulation of uremic patients, especially of those at possible risk for ischemia.

Adult↗

PubMed1991

Treatment of severe hypercholesterolaemia by LDL-apheresis.

The most severe forms of hypercholesterolaemia scarcely respond to diet and conventional drugs administration and need, therefore, alternative treatments. Terapeutic Plasma Exchange demonstrated an improved survival of subjects with Familial Hypercholesterolaemia (FH) in spite of its limitations. Semi-selective and selective techniques have been developed in order to remove LDL cholesterol alone. We studied the efficiency in LDL removal both of membrane filtration as of dextrane sulphate adsorption on 14 FH patients, performing 302 procedures. Cholesterol extraction with the different methods was in the range of 40-65%. Mean cholesterol level was reduced from 7% to 64% depending on the protocol used. The procedures were all performed on an outpatient basis. Side effects occurred rarely and were always of not serious degree. The short and the middle term clinical effects of LDL-Apheresis are then evaluated.

Adolescent↗

PubMed1990

Cerebral blood flow in progressive aphasia without dementia. Case report, using 133xenon inhalation, technetium 99m hexamethylpropyleneamine oxime and single photon emission computerized tomography.

We report a case of progressive aphasia without clinical signs of intellectual or behavioral impairment, satisfying Mesulam's clinical criteria of primary progressive aphasia, as 4 yrs of extensive psychometric testing and radiological imaging, comprising CT and MRI, failed to detect evidence of relevant involvement outside the left perisylvian regions. Cranial CT was normal but MRI showed multiple bilateral lesions in the deep white matter. Cerebral blood flow (CBF) studies by single photon emission computerized tomography, however, showed an initial frontotemporal focus of hypoperfusion that progressively extended to include most of the ipsilateral hemisphere and the contralateral frontal lobe. This suggests that CBF imaging may yet be the most sensitive technique in revealing subclinical injury in the degenerative brain diseases of focal onset.

Administration, Inhalation↗

PubMed1990

Hemodynamic changes in the peripheral circulation after repeat low density lipoprotein apheresis in familial hypercholesterolemia.

Repeat low density lipoprotein (LDL) apheresis and blood flow determinations in the forearm and leg were performed in 10 patients (age range, 13-49 years; four male, six female) with familial hypercholesterolemia (eight homozygous, two heterozygous). To perform LDL apheresis, plasma was first separated by a polysulphone hollow fiber filter; then, LDL was selectively removed from plasma by dextran sulphate cellulose beads packed in columns. Blood flows in the forearm and leg were determined at rest and during a reactive hyperemia test (peak flow). This test was performed noninvasively by a strain-gauge plethysmograph with semicontinuous registration of arterial blood flow variables before the first apheresis and 3 weeks after the last of six procedures for apheresis. Resting arterial blood flows in the forearm and leg were slightly increased after repeat LDL apheresis (p less than 0.05). Peak blood flow in the leg significantly increased (+34%, p less than 0.01). No change in peak blood flow in the forearm was observed. Systolic blood pressures were slightly but significantly reduced (p less than 0.05); forearm peripheral resistances were also reduced (p less than 0.05). Flow response was not related to LDL receptor status. Blood and plasma viscosities were determined before and 7 days after the last apheresis. Blood viscosity was significantly reduced after LDL apheresis at shear rates of 11.25-450 sec-1. Plasma viscosity did not change.

Adolescent↗

PubMed1990

Cerebral blood flow in patients with chronic cerebrovascular disease: effect of acetyl L-carnitine.

The effect of acetyl-L-carnitine on cerebral blood flow was evaluated in ten patients with cerebrovascular disease, who suffered an ischaemic stroke at least six months before the study. All patients performed a computerized tomograph scan and were investigated by Xenon 133 using a brain dedicated Single Photon Emission Computerized Tomography. Acetyl-L-carnitine was administered intravenously (i.v.) at a dosage of 1.5 g. Cerebral blood flow (ml/min. 100 g) was evaluated before and 45 min after the injection. Cerebral blood flow improved in both the ispilateral and controlateral hemisphere of the ischaemic area, but not in the stroke corresponding zone. It is concluded that acetyl-L-carnitine at a dosage of 1.5 g i.v. improves cerebral blood flow in patients with cerebrovascular disease.

Acetylcarnitine↗