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Biomedical subjects

A Siniscalchi

Publications and source records attributed to A Siniscalchi.

At least 37 records · Page 2Linked to original sources
PubMed2004

Modifications of plasma concentrations of hormonal and tissue factors during mechanical ventilation with positive end-expiratory pressure.

AIM: The aim of this study is to analyse if the decrease of cardiac performance due to positive end-expiratory pressure (PEEP) application, within low values applied in clinical practice (5 cm H(2)O) is able to trigger a response of the main endogenous factors which control and maintain the mean arterial pressure (MAP). METHODS: This study was applied to 18 patients, admitted to the Intensive Care Unit (ICU) of the University Hospital of Modena, who underwent oro-tracheal intubation and mechanical ventilation. On admission, patients did not suffer from cardiac or lung disease. This study analyses plasma concentrations of epinephrine, norepinephrine, ET-1, NO metabolites, renin, aldosterone at 4 different times: before PEEP application, 60 minutes after the beginning of mechanical ventilation with PEEP, and respectively 30 and 60 minutes after withdrawal of PEEP. At the same time, MAP values and heart rate (HR) have been observed. RESULTS: Results show an increase of epinephrine and norepinephrine after PEEP application and a decrease to basal values at PEEP withdrawal. All variations are statistically significant. After PEEP introduction, ET-1 showed an increased concentration, although it was not statistically significant, while a significant decreasing trend was observed after PEEP withdrawal. A significant increase of NO metabolite values has been observed together with the increase of ET-1, followed by a decrease to basal values after the withdrawal of PEEP. Concentrations of renin increased when PEEP was applied even though they were not significant and decreased significantly when PEEP was withdrawn. A similar trend was revealed by aldosterone even though it underwent constant significant variations. CONCLUSION: The administration of PEEP produces an effective response of endogenous substances whose function is to maintain a proper tissue perfusion.

Adult↗
PubMed2003

Effects of cholecystokinin tetrapeptide (CCK(4)) and of anxiolytic drugs on GABA outflow from the cerebral cortex of freely moving rats.

The effect of cholecystokinin tetrapeptide (CCK(4)) and of different anxiolytic drugs on GABA outflow from the cerebral cortex was investigated in freely moving rats, by using the epidural cup technique. CCK(4) (3-30 microg/kg, i.p.) increased GABA outflow and induced objective signs of anxiety. These neurochemical and behavioral responses were prevented by the CCK(B) antagonist GV150013 at 0.1 microg/kg (i.p.). At higher doses (up to 30 microg/kg) this compound per se reduced GABA release and caused sedation, suggesting the presence of a CCKergic positive tonic modulation on GABA interneurons. Similarly the GABA(A) receptors modulator, diazepam (2mg/kg, i.p.) and the 5-HT(1A) agonist buspirone (3mg/kg, i.p.) reduced GABA outflow and caused the expected behavioral effects (reduced muscle tone, mild 5-HT syndrome) which were prevented by the respective, selective antagonists, flumazenil (1mg/kg, i.p.) and NAN-190 (3mg/kg, i.p.). These findings support the idea that GV150013, diazepam and buspirone inhibit GABAergic cortical activity, through the respective receptors. This neurochemical effect may represent the end-effect of various anxiolytic compounds affecting the cortical circuitry.

Adamantane↗
PubMed2003

[Living donor liver transplantation, adult to adult].

AIM: Since living donor liver transplantation (LDLT) can offer a viable response to the lack of transplantable cadaveric organs, our center instituted an LDLT program in 2001. METHODS: The authors report their experience with the first 35 LDLT procedures successfully completed at the Liver and Multiorgan Transplant Center of the University of Modena between 9 May 2001 and 21 May 2003. The case series comprised 35 patients, 7 of which received a left-half liver and 1 a left lobe. RESULTS: The global survival rate was 77.2% (27 out of 35 patients), with a mean follow-up period of 295 days; the survival rate at 1 year was 81%. In 4 cases (11%) retransplantation was performed. The donor demographics are described; all donors returned to their normal activities before transplantation, after a mean follow-up period of 373 days. No intraoperative complications were experienced by the donors, whereas during the postoperative period, 2 donors (5.7%) developed major complications (1 biliary fistula on the cut surface, 1 stenosis of the main bile duct). CONCLUSION: Our study shows that LDLT can be safely completed in the donor, with good results achieved in the recipient as well. Underlying these results is the accurate pretransplant assessment that continued into the operation itself. Even more important was the demonstrated ability and experience of the surgical team to attain results in the donor which we believe are necessary for carrying forth a LDLT program.

Adolescent↗
PubMed2003

Intraoperative effects of combined versus general anesthesia during major liver surgery.

AIM: The study compares the intraoperative effects of combined versus general anesthesia during major liver surgery. METHODS: In this prospective randomized study, 70 patients were divided into 2 group of 35 subjects. Group A received general anesthesia (thiopentone, fentanyl, vecuronium, sevoflurane in a closed circuit) 15 minutes after placement of an epidural catheter (D9-D10) and induction of epidural anesthesia (6 ml 2% naropine). Continuous epidural infusion was initiated before surgical incision and continued with 0.2% naropine (7 ml/h) until the end of the operation. Group B received combined intraoperative anesthesia wit fentanyl doses according to hemodynamic parameters and 0.1 mg/kg morphine 30-4 minutes before cutaneous suture. Hemodynamic values were measured at base line (T0), and then at 15, 30, 60, 120 and 180 minutes after induction of general anesthesia (T1, T2, T3, T4 and T5, respectively). On recovery, patients were assessed for pain at rest and on movement reported on a visual analog scale; degree of motor blockade according to the Bromage scale; appearance of side effects; use af analgesic. RESULTS: A statistically significant decrease in the mean arterial blood pressure (ABP) and heart rate (HR) was noted within each group at 15 minutes after induction of general anesthesia. Significant differences in ABP were found between the 2 groups at T1 to T5, whereas HR values were substantially similar. The mean intraoperative use of fentanyl was significantly higher in Group B than in Group A, as was that of vecuronium. Pain intensity on recovery in patients who received epidural anesthesia was lower both at rest and on movement; only the patients in Group B required additional analgesics. No motor blockade was observed in either group. Nausea and vomiting were more frequent in Group B; hypotension was more frequent in Group A. CONCLUSION: The study confirms the safety of locoregional anesthesia in liver surgery, with good hemodynamic stability and absence of major side effects. The lower intraoperative use of opioids and muscle relaxants in patients who received epidural anesthesia confirms the neurovegetative protection this method provides. The data support the hypothesis that greater intraoperative use of opioids may be responsible for the higher incidence of side effects. Therefore, the intraoperative use of combined low-concentration anesthetic agents alone appears to offer a reasonable treatment option that provides adequate pain control at recovery from general anesthesia, with only minor side effects typically associated with analgesic (motor blockade) and opioids (nausea and vomiting). Given the complications associated with the technique, it should be performed by an expert anesthetist.

Adolescent↗
PubMed2003

Hepatic resections for hepatocellular carcinoma (HCC): short and long-term results on 106 cirrhotic patients.

To evaluate the short and long term outcome of liver resections for hepatocellular carcinoma in cirrhotic patients. A retrospective analysis was performed on 106 consecutive cirrhotic patients with hepatocellular carcinoma resected between June 1974 and September 2002 at the Department of Surgery "Pietro Valdoni" - University of Rome "La Sapienza" and at the Liver and Multivisceral Transplant Unit of the University of Modena. Univariate and multivariate analyses were performed on several clinicopathological variables to analyze factors affecting the long-term outcome and intrahepatic recurrence. Overall mortality and morbidity were 10.7% and 26% respectively. These rates significantly decreased in the last years: from 1997 to 2002 no hospital mortality has been recorded. After a median follow-up of 19 months (interquartile range: 10-36), tumour recurrence appeared in 25 patients (23,5%). The 1-, 3-, and 5-year overall survival rates were 86,6%, 70,3%, and 60,6%, respectively. The 1-, 3-, and 5-year disease-free survival rates were 86,3%, 58,1%, and 40,7%. On univariate analysis, viral ethiology of cirrhosis (p=0.03), presence of multiple nodules (p=0.02) and vascular invasion (p=0.05) were found to be related to a worse long-term survival. At the multivariate analysis only the viral ethiology of cirrhosis and the presence of multiple nodules were confirmed as indipendent prognostic factors. Early results after hepatic resection for HCC can be improved by using a limited surgical approach. The viral ethiology of cirrhosis, the presence of multiple nodules and vascular invasion negatively affected recurrence rate and long-term survival.

Aged↗
PubMed2001

Effects of cholecystokinin tetrapeptide (CCK(4)) and anxiolytic drugs on the electrically evoked [(3)H]5-hydroxytryptamine outflow from rat cortical slices.

The outflow of [(3)H]5-hydroxytryptamine ([(3)H]5-HT) from electrically stimulated rat cortical slices was measured to ascertain the modulatory role of endogenous cholecystokinin (CCK) on the amine outflow and to test the hypothesis that different anxiolytic compounds inhibit 5-HT secretion. The [(3)H]5-HT outflow evoked at 10 Hz was increased up to +30% by CCK(4) 300-1000 nM, the effect being prevented by the CCK(B) receptor antagonist GV 150013, 3 nM. The limited sensitivity to CCK(4) seemed to depend on 5-HT auto-receptor feedback because pre-treatment with 100 nM methiothepin enhanced the [(3)H]5-HT outflow and lowered the CCK(4) threshold concentration from 300 to 30 nM. In addition, pre-treatment with 1 microM bacitracin to inhibit CCK metabolism increased [(3)H]5-HT efflux. This effect was concentration-dependently counteracted by GV150013 suggesting the presence of an endogenous CCK positive modulation. GV150013 30 nM, the 5-HT(1A) partial agonist buspirone 300 nM and the GABA(A) receptor modulator diazepam 10 nM, known to have anxiolytic properties, all significantly reduced the [(3)H] amine outflow from cortical slices by about 20%. This inhibition depended on their interaction with their respective receptors, which seemed to restrain the activity of functionally interconnected glutamatergic interneurones. In fact, APV (50 microM) and NBQX (10 microM) prevented the effect of the anxiolytic compounds. Thus, anxiolytic drugs with different receptor targets can reduce 5-HT outflow by dampening the glutamatergic signal, and in turn, the secretory process of the serotonergic nerve ending.

Adamantane↗
PubMed2001

Cannabinoid receptor agonist WIN 55,212-2 inhibits rat cortical dialysate gamma-aminobutyric acid levels.

The effects of the cannabinoid receptor agonist WIN 55,212-2 (0.1-5 mg/kg i.p.) on endogenous extracellular gamma-aminobutyric acid (GABA) levels in the cerebral cortex of the awake rat was investigated by using microdialysis. WIN 55,212-2 (1 and 5 mg/kg i.p.) was associated with a concentration-dependent decrease in dialysate GABA levels (-16% +/- 4% and -26% +/- 4% of basal values, respectively). The WIN 55,212-2 (5 mg/kg i.p.) induced-inhibition was counteracted by a dose (0.1 mg/kg i.p.) of the CB(1) receptor antagonist SR141716A, which by itself was without effect on cortical GABA levels. These findings suggest that cannabinoids decrease cortical GABA levels in vivo, an action that might underlie some of the cognitive and behavioral effects of acute exposure to marijuana.

Animals↗
PubMed2001

Effects of two-carbon bridge region methoxylation of benztropine: discovery of novel chiral ligands for the dopamine transporter.

6-Methoxylated and 8-oxygenated benztropines were prepared and evaluated for their DAT and SERT activity (binding and uptake inhibition). Methoxylation at the two-carbon bridge of benztropine produced a novel class of potent and selective DAT ligands. An interesting enantioselectivity was also observed for this new class of chiral benztropines. The inactivity of the 8-oxygenated analogues seems to point out that, unlike cocaine and its analogues, interactions of benztropine ligands with DAT may be strongly governed by the nitrogen atom.

Benztropine↗
PubMed2001

GABA-mediated synchronization in the human neocortex: elevations in extracellular potassium and presynaptic mechanisms.

Field potential and extracellular [K(+)] ([K(+)](o)) recordings were made in the human neocortex in an in vitro slice preparation to study the synchronous activity that occurs in the presence of 4-aminopyridine (50 microM) and ionotropic excitatory amino acid receptor antagonists. Under these experimental conditions, negative or negative-positive field potentials accompanied by rises in [K(+)](o) (up to 4.1 mM from a baseline of 3.25 mM) occurred spontaneously at intervals of 3-27 s. Both field potentials and [K(+)](o) elevations were largest at approximately 1000 microm from the pia. Similar events were induced by neocortical electrical stimuli. Application of medium containing low [Ca(2+)]/high [Mg(2+)] (n=3 slices), antagonism of the GABA(A) receptor (n=7) or mu-opioid receptor activation (n=4) abolished these events. Hence, they represented network, GABA-mediated potentials mainly reflecting the activation of type A receptors following GABA release from interneurons. The GABA(B) receptor agonist baclofen (10-100 microM, n=11) reduced and abolished the GABA-mediated potentials (ID(50)=18 microM). Baclofen effects were antagonized by the GABA(B) receptor antagonist CGP 35348 (0.1-1 mM, n=6; ID(50)=0.19 mM). CGP 38345 application to control medium increased the amplitude of the GABA-mediated potentials and the concomitant [K(+)](o) rises without modifying their rate of occurrence. The GABA-mediated potentials were not influenced by the broad-spectrum metabotropic glutamate agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (100 microM, n=10), but decreased in rate with the group I receptor agonist (S)-3,5-dihydroxyphenylglycine (10-100 microM, n=9). Our data indicate that human neocortical networks challenged with 4-aminopyridine generate glutamatergic-independent, GABA-mediated potentials that are modulated by mu-opioid and GABA(B) receptors presumably located on interneuron terminals. These events are associated with [K(+)](o) elevations that may contribute to interneuron synchronization in the absence of ionotropic excitatory synaptic transmission.

4-Aminopyridine↗
PubMed2000

NMDA and AMPA/kainate receptors are involved in the anticonvulsant activity of riluzole in DBA/2 mice.

The anticonvulsant activity of riluzole against sound-induced seizures was studied in the DBA/2 mouse model. Riluzole (0.1-4 mg kg(-1), intraperitoneal (i.p.)) produced dose-dependent effects with ED(50) values for the suppression of tonic, clonic and wild running phases of 0.72, 1.38 and 2.71 mg kg(-1), respectively. Riluzole also protected DBA/2 mice from seizures induced by an intracerebroventricular (i.c.v.) injection of N-methyl-D-aspartate (NMDA) with ED(50) values of 3.03 and 5.0 mg kg(-1) for tonus and clonus, respectively. Pretreatment with glycine, an agonist to the glycine/NMDA receptors, shifted the dose-response effect of riluzole to the right (ED(50)=6.53 against tonus and 9.34 mg kg(-1) vs. clonus). Similarly, D-serine, an agonist at the glycine site, shifted the ED(50) of riluzole against the tonic component of audiogenic seizures from 0.72 to 1.97, and that against clonus from 1.38 to 2.77 mg kg(-1). Riluzole was also potent to prevent seizures induced by administration of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), an AMPA/kainate receptor agonist (ED(50)=1.80 and 3.35 mg kg(-1), against tonus and clonus, respectively). Pretreatment with aniracetam, a positive allosteric modulator of AMPA/kainate receptors, shifted the dose-response curve of riluzole to the right (ED(50)=1.78 against tonus and 2.58 mg kg(-1) vs. clonus). The data indicate that riluzole is an effective anticonvulsant drug in the genetic model of seizure-prone DBA/2 mice. Our findings suggest that the anticonvulsant properties of riluzole depend upon its interaction with neurotransmission mediated by both the glycine/NMDA and the AMPA/kainate receptor complex.

Acoustic Stimulation↗
PubMed2000

Neurotensin increases endogenous glutamate release in rat cortical slices.

In the present study, the effects of the tridecapeptide neurotensin [NT(1-13)] and its fragments, NT(1-7) and NT(8-13), on endogenous glutamate release from rat cortical slices, were evaluated. NT(1-13) (100-1000 nM) slightly increased spontaneous glutamate release, while it was ineffective at 1 and 10 nM concentrations. Neither the biologically active NT fragment NT(8-13) nor the inactive one NT(1-7) affected basal glutamate release. NT(1-13) (1-1000 nM) enhanced potassium (35 mM)-evoked glutamate release displaying a bell-shaped concentration response curve. In addition NT(8-13) (10 nM) increased K+-evoked-glutamate release similarly to the parent peptide (10 nM), while the biologically inactive fragment NT(1-7) (10-100 nM) was ineffective. The effects of NT(1-13) and NT(8-13) were fully counteracted by the selective neurotensin receptor antagonist SR48692 (100 nM). These findings suggest that NT plays a role in regulating cortical glutamate transmission.

Animals↗
PubMed2000

[Cardiac rupture in thoracic trauma].

Thoracic trauma frequently involve damage to the cardiac structures and in the worst cases, the progressive degeneration and necrosis of the damaged tissue lead to cardiac rupture. The high mortality resulting from cardiac tamponade requires the prompt execution of diagnostic tests to provide as much useful information as rapidly as possible in order to start immediate therapy. A case of cardiac rupture manifested by the onset of atrial fibrillation in a patient admitted to Intensive Care after a car accident is described. The scarce significance of objective examination, the aspecific nature of chest X-ray and ECG alterations prompted the execution of a more thorough diagnosis. Transthoracic and transesophageal ultrasonography are both minimally invasive and highly specific: in a short time, not only did they confirm cardiac rupture, but they also focalised the site of the lesion, thus allowing a more targeted and rapid surgical approach. The relative frequency of cardiac lesions following closed thoracic trauma, the lack of incontrovertible signs and symptoms of late cardiac rupture, and the extreme severity of its clinical consequences argue in favour of using specific and sensitive diagnostic tests that can not only exclude or ascertain the presence of these lesions, but also allow subsequent serial controls aimed at diagnosing late cardiac ruptures.

Accidents, Traffic↗
PubMed1999

Neuroprotective effects of riluzole: an electrophysiological and histological analysis in an in vitro model of ischemia.

The protective effects of riluzole against the neuronal damage caused by O2 and glucose deprivation (ischemia) was investigated in rat cortical slices by recording electrophysiologically the cortico-cortical field potential and by evaluating histologically the severity of neuronal death. Five minutes of ischemia determined an irreversible depression of the amplitude of the field potential. In addition, this insult caused a clear enhancement of the number of death cells that were specifically colored with trypan blue (a vital colorant which stains altered cells). We found that riluzole, which by itself depressed the synaptic transmission, neuroprotected when perfused 15-20 min before and during ischemia. In fact, due to the treatment with riluzole, the ischemia-induced irreversible depression of the field potential recovered and less cells were stained with trypan blue. These findings demonstrate that riluzole prevents neuronal death in an in vitro model of ischemia and suggest a therapeutic use of this drug in order to reduce the pathophysiological outcomes of stroke.

Animals↗
PubMed1999

5-HT4 receptor modulation of acetylcholine outflow in guinea pig brain slices.

The effect of the 5-HT4 agonist, BIMU-8 was studied on [3H]choline outflow in guinea pig brain slices and synaptosomes. BIMU-8 did not modify [3H]choline efflux in slices kept at rest, but increased [3H]choline outflow in electrically stimulated slices of cerebral cortex (CC), hippocampus (hip) and nucleus basalis magnocellularis (nbm). This effect was prevented by the selective 5-HT4 antagonist, GR 125487. Conversely, BIMU-8 did not affect [3H]choline efflux in hippocampal synaptosomes depolarized with KCl 20 mM. These results provide evidence that BIMU-8 increases the electrically triggered [3H]choline efflux in CC, hip and nbm slices. A possible role of 5-HT4 agonists in memory and learning diseases is suggested.

Acetylcholine↗
PubMed1999

Early changes in adenosine A1 receptors in cerebral cortex slices submitted to in vitro ischemia.

The effects of brain ischemia on the maximum binding capacity (Bmax) and affinity (Kd) of A1 receptors were studied in the rat cerebral cortex, with an in vitro approach. The results were correlated with changes in 3H-adenosine release, studied under identical experimental conditions. Fifteen minutes of in vitro 'ischemia' (hypoxic, glucose-free medium) induced a significant increase in both Bmax (2398+/-132 fmol/mg protein, 151% of the control, P < 0.05) and in Kd (2.43+/-0.12 nM, 161% of the control, P < 0.01). At the same time, an increase in tritium efflux from [3H]-adenosine labeled cerebral cortex slices to 324% of the control was observed. A trend toward normalization was evident 5-15 min after 'reoxygenation' (restoring normal medium), but the binding parameters were still altered after 60 min (Bmax 2110+/-82 fmol/mg protein, Kd 2.26+/-0.14 nM, P < 0.01 vs the corresponding control) as was adenosine release (196% of the control). These findings suggest that the increased availability of adenosine and its receptors may be a defense mechanism against ischemic injury, while the reduced affinity of A1 receptors, possibly due to desensitization, may be a sign of ischemia-induced cellular damage.

Adenosine↗
PubMed1999

Inhibitory effect of nociceptin on [3H]-5-HT release from rat cerebral cortex slices.

1. The effect of nociceptin (NC) on 5-hydroxytryptamine (5-HT) release was studied in rat cerebral cortex slices preincubated with [3H]-5-HT and electrically stimulated (3 Hz, for 2 min) at the 45th (St1) and the 75th (St2) min of superfusion. 2. NC (0.1 - 3 microM), present in the medium from the 70th min onward, concentration-dependently reduced electrically evoked [3H]-5-HT efflux (pEC50=6.54, Emax -54%). The inhibition was not antagonized by naloxone (1 microM) ruling out the involvement of opioid receptors. 3. Phe1psi(CH2-NH2)Gly2]NC(1-13)NH2, which acts as an opioid-like receptor (ORL1) antagonist at the peripheral level, behaved as a partial agonist in cerebral cortex slices i.e. it inhibited [3H]-5-HT efflux when added before St2, however, when present in the medium throughout the whole experiment, [Phe1psi(CH2-NH2)Gly2]NC(1-13)NH2 prevented the action of NC added at the 70th min. 4. The non-selective ORL1 receptor antagonist, naloxone benzoylhydrazone (3 microM), in the presence of 10 microM naloxone, did not modify the St2/St1 ratio but completely abolished the NC effect. 5. These findings demonstrate that NC inhibits 5-HT release from rat cerebral cortex slices via ORL1 receptors, suggesting its involvement in central processes mediated by 5-HT.

Animals↗