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Biomedical subjects

A Vezzani

Publications and source records attributed to A Vezzani.

At least 73 records · Page 4Linked to original sources
PubMed1992

[Increasing the pressure of cerebral perfusion to control intracranial pressure].

ICP control can be achieved removing the surgical masses and manipulating the intracranial compartments; in the intensive care setting that can be attempted using CSF withdrawal or changing the cerebrovascular resistances, the intracranial blood content and the cerebral water content. The reduction of the ICP and the maintenance of a good cerebral perfusion pressure are the main aims of the therapy; when any standard treatment fails to control ICP a further attempt to preserve cerebral perfusion should be done by increasing the mean arterial pressure. In 10 patients with severe brain damage (GCS on admission ranging from 3 to 7, mean 5) from subarachnoid hemorrhage (3 cases) or trauma an infusion of dopamine (25-150 mg/h) and noradrenaline (0.4-2.4 mg/h) was started in case of intractable ICP. The ICP was defined intractable when the pressure was more than 40 mmHg for more than 5 m' after maximum therapy, as evaluated using the Therapy Intensity Level score. The infusion obtained a raise of the MAP of approximately 25% and a variable response on ICP. In 9 cases ICP dropped, in one case, instead, the ICP increased together with the arterial pressure. The reduction of ICP was 20-30%, with a good improvement of the CPP. The patients with a good response survived, the only patient without control of the ICP died. The physiopathologic mechanisms of this treatment are discussed; the most suitable explanation is indicated in an autoregulatory process. The infusion of cathecolamines can be harmful, and the patients eligible for this treatment must be carefully chosen. Notwithstanding this approach deserves further studies for the cases of intractable ICP.

Adult↗
PubMed1991

Increased preproneuropeptide Y mRNA in the rat hippocampus during the development of hippocampal kindling: comparison with the expression of preprosomatostatin mRNA.

The levels of preproneuropeptide Y (ppNPY) mRNA and preprosomatostatin (ppSOM) mRNA were analyzed in different brain regions during the development of hippocampal kindling in rats. ppNPY mRNA levels were markedly elevated in the dorsal hippocampus bilaterally, two days after stage 2 (preconvulsive stage) and stage 5 (full seizure expression). The contents of ppSOM mRNA were slightly, although not significantly, increased in the dorsal hippocampus at stage 2 whereas a significant increase was observed in the ipsilateral hippocampus of fully kindled rats. ppNPY and ppSOM mRNA levels were unchanged in the cortex and striatum at both stages of kindling. These results show that an increased synthesis of somatostatin and neuropeptide Y, with a greater effect for the latter, occurs during hippocampal kindling in rats. The relative role of the two peptides in the development and expression of kindling phenomenon remains to be elucidated.

Animals↗
PubMed1991

Changes in pre- and postsynaptic components of noradrenergic transmission in hippocampal kindling in rats.

We investigated whether modifications in noradrenergic neurotransmission occurred during the development of hippocampal kindling in rats. We measured the release of [3H]norepinephrine (NE) induced by field-electrical stimulation, NE-stimulation of inositol phosphates [( 3H]IP) accumulation in the presence of LiCl and isoproterenol-induced accumulation of cAMP in hippocampal slices taken from rats electrically kindled at stages 2 and 5 in the dorsal hippocampus. One week after the last of at least 3 consecutive stage 5 seizures or 48 h after the last stage 2 stimulation, 2 min electrical stimulation of stratum pyramidale CA1-CA3 or dentate gyrus (DG) slices from kindled and contralateral hippocampi induced frequency-dependent NE release (respectively 2, 4 and 8 times spontaneous release measured at 2, 5 and 10 Hz) which did not significantly differ from that observed in shams (implanted with electrodes but not stimulated). Basal release of NE from kindled and sham-treated rats did not differ either. Isoproterenol induced a dose-dependent increase above basal cAMP concentration ranging from 40% at 0.01 microM to 180% at 10 microM (P less than 0.01, Dunnett's test) which did not differ between stages 2 and 5 and sham-hippocampi. NE (1-1000 microM) induced a dose-dependent, prazosin-sensitive increase in [3H]IP accumulation in the hippocampal slices. A significantly higher increase was found at stages 2 (P less than 0.05, Tukey's test) and 5 (P less than 0.05 and P less than 0.01, Tukey's test) compared to shams at all doses studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

A peptidase-resistant cyclic octapeptide analogue of somatostatin (SMS 201-995) modulates seizures induced by quinolinic and kainic acids differently in the rat hippocampus.

Electroencephalographic (EEG) seizures were measured in rats after intrahippocampal injection of 120 nmol quinolinic acid into the stratum radiatum CA1 or 0.19 nmol kainic acid in the dentate gyrus or in the stratum radiatum. Injection of 5 micrograms SMS 201-995, a peptidase-resistant cyclic octapeptide analogue of somatostatin, into the stratum radiatum, 15 min before quinolinic acid, did not significantly modify the number of seizures and the total time in seizures. Five micrograms SMS 201-995 injected into the stratum radiatum reduced the number of seizures induced by kainic acid in the same area and the total time spent in seizures by 58% and 75%, respectively (Student's t-test; P less than 0.01). In both instances the latency to the first ictal episode was not significantly modified. Lesions of the medial septum, which reduced the activity of choline-o-acetyl-transferase (CAT) in the dorsal hippocampus by greater than 90% after one week did not significantly affect seizures induced by quinolinic acid. In rats lesioned in the medial septum, 5 micrograms SMS 201-995 reduced the total time spent in seizures by 43%, without changing the number of ictal episodes and raised the latency to the first quinolinic acid-induced seizure by 53% (ANOVA 2 x 2, P less than 0.05) but had no effect on these measures in the corresponding sham-operated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Functional and histological consequences of quinolinic and kainic acid-induced seizures on hippocampal somatostatin neurons.

Changes in endogenous somatostatin after quinolinic and kainic acids were investigated by measuring somatostatin-like peaks by in vivo voltammetry and by assessing the distribution of somatostatin-positive neurons by immunocytochemistry. Kainic acid (0.19 nmol/0.5 microliter) or quinolinic acid (120 nmol/0.5 microliter) in doses inducing comparable electroencephalographic seizure patterns, were injected into the hippocampus of freely moving rats. Somatostatin-like peaks were measured every 6 min for 3 h by a carbon fiber electrode implanted in the proximity of the injection needle. Kainic acid kept somatostatin-like peaks significantly higher than saline from 48 min after the injection till the end of the recording. Somatostatin-like peaks were dramatically elevated by quinolinic acid, reaching a maximum of 482% 60 min after the injection. Three days later, administration of kainic acid resulted in selective degeneration of CA3 pyramidal neurons but did not affect the number of somatostatin-positive cells, while quinolinic acid induced cell loss in all pyramidal layers and complete degeneration of somatostatin-positive cells in the whole hippocampus. Thus, the quantitative difference in somatostatin release in response to doses of kainic and quinolinic acids inducing comparable electroencephalographic seizure patterns was reflected in a substantial difference in the neurodegenerative consequences. In both models, the release of somatostatin in response to seizures may be interpreted as a "defense" mechanism aimed at reducing the spread of excitation in the tissue.

Animals↗
PubMed1991

[Arterio-jugular difference of oxygen and intracranial pressure in comatose, head injured patients. II. Clinical correlations].

The ICP monitoring is currently used in the treatment of the head injured patients in order to avoid dangerous increases of the pressure and critical reduction of cerebral perfusion pressure (CPP). The cerebral blood flow is dependent on the CPP and is kept constant, under normal circumstances, by autoregulation. When autoregulation is impaired or overwhelmed oxygen delivery becomes uncoupled to the metabolic needs of cerebral tissue: in such a condition the rate of oxygen extraction changes and the artero-jugular difference for O2 (AVDO2) reflects this change. The AVDO2 can be used as an estimate of the CBF and can detect a situation of hyperemia (low AVDO2) or ischemia (high AVDO2). In 224 comatose head injured patients the ICP was measured using ventricular or subarachnoid catheters: the CPP was continuously assessed and the outcome was evaluated six months after the trauma. In 45 patients the AVDO2 was studied and the data were corrected for a PaCO2 of 40 mmHg and investigated. The severity of the ICP is decisive for the prognosis and, accordingly, the number of times the CPP is below 60 mmHg plays a major role in the outcome. The mortality rate was 21% for the patients without ICP greater than 20 mmHg and 54% for the patients with severe increases in ICP. The mean values of AVDO2 were low, ranging around 4.6 vol%; only 4 patients showed some temporary evidence of ischemia, as assessed by an AVDO2 greater than 8 vol%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Autoradiographical analysis of excitatory amino acid binding sites in rat hippocampus during the development of hippocampal kindling.

Binding sites for excitatory amino acids have been determined by autoradiographical procedures in the rat hippocampus and striatum during hippocampal kindling. The binding sites measured were the N-methyl-D-aspartate (NMDA)-sensitive sites for L-[3H]glutamate and [3H]MK-801 sites (transmitter recognition site and ion channel of the NMDA receptor, respectively), [3H]alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) sites (quisqualate receptor), [3H]kainate sites (kainate receptor) and NMDA-insensitive sites for L-[3H]glutamate. In general, little change was apparent in the hippocampus or striatum for any of these binding sites when assessed 48 h after attaining stages 1/2, 3 or 5 of kindling. These results suggest that hippocampal kindling does not bring about a change in the excitatory amino acid receptor binding sites examined, and that the appearance of an NMDA receptor-mediated component to synaptic responses in the hippocampus produced by kindling, cannot be explained on this basis.

Amino Acids↗
PubMed1990

Kynurenic acid synthesis by human glioma.

Biopsy material from human gliomas obtained during neurosurgery was used to investigate whether pathological human brain tissue is capable of producing kynurenic acid (KYNA), a natural brain metabolite which can act as an antagonist at excitatory amino acid receptors. Upon in vitro exposure to 40, 200 or 1000 microM L-kynurenine, the immediate bioprecursor of KYNA, freshly prepared tissue slices in a dose-dependent fashion produced KYNA which was detected in the incubation medium. De novo synthesized KYNA was identified by several chromatographic procedures. Astrocytomas produced significantly more KYNA than glioblastomas.

Adult↗
PubMed1990

Hypophosphatemia in course of chronic obstructive pulmonary disease. Prevalence, mechanisms, and relationships with skeletal muscle phosphorus content.

Serum phosphorus levels (Ps), dietary intake of phosphorus, and renal phosphate handling indexes were evaluated in 158 patients with chronic obstructive pulmonary disease (COPD) of varying degrees of severity; moreover, skeletal muscle phosphorus content (Pm) was measured in muscle samples obtained by quadriceps femoris needle biopsy in 14 of the same patients. Hypophosphatemia (Ps less than or equal to 2.5 mg/dl) was found in 34 (21.5 percent) of 158 patients without differences between groups of COPD patients presenting increasing severity of respiratory illness. No relationship was found between serum levels and dietary intake of phosphorus; hypophosphatemia was associated with low renal phosphate threshold (TmPO4/GFR) values in 31 (91 percent) of 34 patients. The prevalence of hypophosphatemia was significantly higher among COPD patients taking one or more drugs commonly used in COPD and known as negatively influencing renal phosphate handling: xanthine derivatives, corticosteroids, loop diuretics, and beta 2-adrenergic bronchodilators. Short-term administration of therapeutic doses of these drugs in COPD patients previously not taking any drug reduced TmPO4/GFR values; phosphaturic effect of short-term theophylline administration on renal phosphate handling was additive to that of long-term assumption of the drug. Muscle phosphorus content was both reduced in COPD patients as compared with control subjects and significantly correlated to serum phosphorus levels and to TmPO4/GFR values. The present investigation revealed a high prevalence of hypophosphatemia among COPD patients as well as a defect in renal phosphate reabsorption secondary, at least in part, to pharmacologic therapy. Moreover, it also suggests that in COPD patients muscle phosphorus content is likely to be reduced in presence of hypophosphatemia.

Adult↗
PubMed1990

[Clinical evaluation of atracurium besylate in patients at risk: major burns].

Atracurium besylate 0.5 mg/kg-1, an intermediate-duration non-depolarizing neuromuscular relaxant, was administered slowly (over 75 sec) in anesthesia induction of 61 patients with major thermal injury undergoing surgical excision and immediate skin-grafting procedures. Patients' mean +/- SD age was 40 +/- 9, body weight 64 +/- 2, burn size ranging from 20% to 90% of body surface area (BSA), postburn day of surgery 5th and more. Induction of anesthesia was carried out with sodium thiopental 2-5 mg/kg-1 plus fentanyl 2.8 micrograms/kg-1 e.v. and after few minutes atracurium 0.5 mg/kg-1 e.v. Anesthesia was maintained with N2O/O2 (70%/30%), isoflurane and small amounts of fentanyl. The mean arterial pressure and heart rate were recorded at I, II, III, IV, V min post atracurium administration. The endotracheal intubation conditions were assessed by a "IOT score". Results are expressed as mean value +/- standard deviation. The significance of the difference in mean values was analysed by t-test. Little haemodynamic changes occurred; intubating conditions showed a relative hyposensitivity of burn patients to atracurium, more severely burned patients (greater than 50-60%) exhibiting greater resistance.

Adolescent↗
PubMed1990

A comparative clinical study on the effects of cardiopulmonary bypass with different flows and pressures on skeletal muscle cell metabolism in patients undergoing coronary bypass grafting.

This study compares the effects of cardiopulmonary bypass with different flows and pressures on intracellular energy metabolism, acid-base equilibrium, and muscle water compartments in two groups of patients undergoing coronary artery bypass grafting. Eighteen patients (16 men and two women aged 54 +/- 7 years, New York Heart Association class I-II) undergoing low flow (flow rate 1.5 L/min/m2 at 26 degrees C), low pressure (mean arterial pressure 40 to 60 mm Hg) cardiopulmonary bypass, as well as 10 age-matched and sex-matched patients undergoing normal flow (flow rate 2.2 L/min/m2 at 26 degrees C), normal pressure (mean arterial pressure 60 to 80 mm Hg) bypass were studied. Intracellular acid-base equilibrium (intracellular pH and intracellular bicarbonate), cell energetics (adenosine triphosphate, diphosphate, and monophosphate, phosphocreatine, and lactate), and muscle water compartments were evaluated in specimens of the quadriceps femoris muscle obtained by needle biopsy before and at the end of cardiopulmonary bypass. In both the low flow-low pressure and normal flow-normal pressure groups, adenosine triphosphate levels were unchanged at the end of bypass, whereas phosphocreatine concentration was decreased; muscle total water and extracellular water increased without variations of intracellular water; muscle and plasma lactate increased as intracellular bicarbonate decreased; intracellular pH values remained unchanged. The present study suggests the following: (1) Cardiopulmonary bypass is associated with the overall preservation of intracellular compartment metabolism in skeletal muscle (about 40% of body cell mass) of patients undergoing coronary bypass grafting, even though low phosphocreatine values and increased plasma and muscle lactate values found at the end of bypass could be an expression of cell functional reserve exhaustion; (2) the effects of cardiopulmonary bypass on cell metabolism are comparable, regardless of the flows and pressures used.

Blood Pressure↗
PubMed1989

Studies on the potential neurotoxic and convulsant effects of increased blood levels of quinolinic acid in rats with altered blood-brain barrier permeability.

Intravenous injection of 450 mg/kg quinolinic acid (Quin), an endogenous kynurenine metabolite with excitotoxic properties, induced only minor electroencephalographic (EEG) modifications and no neurotoxicity in rats with a mature blood-brain barrier (BBB). BBB permeability was altered in rats by focal unilateral irradiation of the cortex (7 mm in diameter and 5 mm in depth) with protons (60 Gy, 9 Gy/min). Three days after irradiation, Evans blue dye staining showed BBB breakdown in the dorsal hippocampus of the irradiated hemisphere. No neurotoxic or convulsant effects were observed as a consequence of the radiation itself. When BBB-lesioned rats were challenged with 225 mg/kg Quin iv, epileptiform activity was observed on EEG analysis. Tonic-clonic seizures were induced by 225-450 mg/kg Quin. Light microscopic analysis showed a dose-related excitotoxic type of lesion restricted to the hippocampus ipsilateral to the irradiated side. Neuro-degeneration was prevented by local injection of 120 nmol D(-)2-amino-7-phosphonoheptanoic acid, a selective N-methyl-D-aspartate receptor antagonist. No lesions or EEG or behavioral modifications occurred after 450 mg/kg nicotinic acid, an inactive analog of Quin. The potential neurotoxic and convulsant effects of increased blood levels of Quin under conditions of altered BBB permeability are discussed.

2-Amino-5-phosphonovalerate↗
PubMed1989

Cell metabolism in patients undergoing major valvular heart surgery: relationship with intra and postoperative hemodynamics, oxygen transport, and oxygen utilization patterns.

The relationships between cell metabolism and both hemodynamics and oxygen transport/utilization (VO2/DO2) pattern were evaluated intra and postoperatively in eight patients undergoing major valvular heart surgery with the aid of moderately hypothermic cardiopulmonary bypass (CPB). Quadriceps femoris specimens were obtained by the needle biopsy technique for muscle ATP, ADP, AMP, phosphocreatine (PCr), creatine and lactate determination at anesthesia induction, after CPB, as well as in the ICU 18 h after surgery. Moreover, hemodynamic variables, oxygen transport and utilization indices, and plasma lactate were measured at the same intervals and throughout the CPB period. After CPB, muscle ATP and PCr contents were reduced (p less than .05) as compared to those of both pre-CPB patients and healthy control subjects; muscle and plasma lactate levels were increased (p less than .05). Mean VO2 and DO2 values measured during CPB significantly decreased (p less than .05), but VO2 reduction was proportionally greater than that of DO2 (-62% vs. -41%). No correlation was found between VO2 and DO2 at that time, but a significant relationship (p less than .05) was found at the end of CPB. A further decrease in muscle ATP and PCr levels was measured in the ICU, as muscle and plasma lactate levels were still elevated. At that time, VO2 and DO2 were not significantly different from pre-CPB values, but were significantly (p less than .05) correlated with each other.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed1989

Kinetics of MK-801 and its effect on quinolinic acid-induced seizures and neurotoxicity in rats.

MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclo-hepten-5,10-imine maleate], a noncompetitive antagonist of the N-methyl-D-aspartate-type of excitatory aminoacid receptors, was measured in plasma and brain tissues after i.p. administration to rats by using a novel high-performance liquid chromatography assay. The drug reached maximal concentrations in plasma and brain within 10 to 30 min of injection (2 mg/kg) with an elimination half-life of 1.9 and 2.05 hr, respectively. Mean ratio of brain area concentration-time curve to plasma area concentration time curve was 12.5, referring to total plasma concentrations. MK-801 distributed almost equally between plasma and red cells (mean blood-to-plasma ratio averaged 1.2 +/- 0.2 when calculated 30 and 180 min from drug administration). Plasma and brain concentrations of MK-801 rose almost linearly from 0.5 to 4 mg/kg 30 min after injection and the brain-to-plasma ratio (12.9 +/- 2.8) was constant in the dose range studied. The distribution of the drug in various brain regions 30 and 180 min after 2 mg/kg i.p. showed no preferential concentration or retention in any of the areas studied. The anticonvulsant effect of MK-801 was evaluated against limbic seizures (measured by EEG) induced by intrahippocampal injection of 120 nmol of quinolinic acid, an agonist of the N-methyl-D-aspartate-type receptors, in freely moving rats. At 0.25 and 0.5 mg/kg, MK-801 significantly lowered by 71 to 77% the number of seizures and by 80% the total time spent in seizures (P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Stimulation of [3H]norepinephrine release from hippocampal slices by excitatory amino acids.

[3H]norepinephrine efflux from preloaded rat hippocampal slices was increased in a dose-dependent manner by excitatory amino acids (EAA) in the following potency order: N-methyl-D-aspartic acid (NMDA) greater than kainic acid greater than L-glutamic acid greater than or equal to D,L-homocysteic acid greater than L-aspartic acid greater than quinolinic acid greater than quisqualic acid. The effect of EAA was blocked by physiological concentration of Mg2+, with the exception of kainic acid. D,L-2-amino-7-phosphonoheptanoic acid (APH) dose-dependently inhibited NMDA effect (IC50 = 69 mumol/L), whereas at 1 mmol/L it was ineffective versus kainic acid. The release of [3H]norepinephrine induced by quinolinic acid was blocked by APH 0.1 mmol/L. gamma-D-glutamylglycine dose-dependently inhibited kainic acid effect with an IC50 = 1.15 mmol/L. Tetrodotoxin 2 mumol/L reduced NMDA and kainic acid effects by 40 and 20%, respectively. The data indicate a possible involvement of central noradrenergic system in the modulation of excitotoxic action of EAA and offer a reliable system for testing new compounds acting at EAA-receptors by measuring norepinephrine release in vitro.

2-Amino-5-phosphonovalerate↗