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Biomedical subjects

M Antonelli

Publications and source records attributed to M Antonelli.

At least 19 recordsLinked to original sources
PubMed1998

Glial cell line-derived neurotrophic growth factor inhibits apoptotic death of postnatal substantia nigra dopamine neurons in primary culture.

Glial cell line-derived neurotrophic factor (GDNF) was identified on the basis of its ability to enhance the development of embryonic mesencephalic dopamine neurons. It remains unknown whether GDNF is a physiologically relevant trophic factor for these neurons. We have shown that natural cell death among dopamine neurons of the substantia nigra occurs largely postnatally. To investigate whether GDNF may have the ability to support these neurons during their period of natural cell death, we have used a postnatal primary culture model. We find that GDNF is able to support the viability of postnatal nigral dopamine neurons by inhibiting apoptotic death. This ability of GDNF shows both regional specificity for the nigra and cellular specificity for the dopamine phenotype. Among eight other neurotrophic factors previously reported to support embryonic dopamine neurons, GDNF was unique in this ability. Thus, GDNF meets this criterion for a physiologically relevant trophic factor for dopamine neurons of the substantia nigra.

Animals↗
PubMed1997

An inactive mutant of the alpha subunit of protein kinase CK2 that traps the regulatory CK2beta subunit.

Protein kinase CK2 (casein kinase 2) is a ubiquitous Ser/Thr protein kinase involved in cell proliferation. Mutation of the alpha subunit of the Xenopus laevis CK2 to change aspartic acid 156 to alanine (CK2alphaA156) resulted in an inactive enzyme. The CK2alphaA156 mutant, however, binds the regulatory subunit as measured by retention of beta on a nickel chelating column mediated by (His)6-tagged CK2alphaA156. Addition of CK2alphaA156 also caused beta to shift sedimentation in a sucrose gradient from a beta2 dimer (52 kDa) to an alpha2beta2 tetramer (130,000 kDa). CK2alphaA156 can trap the beta subunit in an inactive complex reducing the stimulation of casein phosphorylation caused by addition of beta to wild-type alpha. This competitive effect depends on the ratio of alpha/alphaA156 and on the amount of beta available. Since beta inhibits the phosphorylation of calmodulin by CK2alpha, the addition of CK2alphaA156, in this case, increases calmodulin phosphorylation by the alpha and beta combination. These results suggest that CK2alphaA156 may be a useful dominant-negative mutant that can serve to explore the multiple functions of CK2beta.

Alanine↗
PubMed1997

Sonographic survey of the upper abdomen in 10 families of patients with immotile cilia syndrome.

Ten patients affected by the immotile cilia syndrome (ICS) and their families received an ultrasound examination of the upper abdomen to observe the possible familial occurrence of biliary, pancreatic, and splenic alterations. In 9 patients the liver was localized in the left hypochondrium, and in 1 patient there was an accessory spleen. In all the examined kin, the subdiaphragmatic organs were normally positioned. Two parents had an accessory spleen. We conclude that the supposed increased frequency of polysplenia, asplenia, and biliary atresia among ICS subjects and their kin is overestimated and based only upon anecdotal reports.

Abdomen↗
PubMed1997

Respiratory system mechanics in the early phase of acute respiratory failure due to severe kyphoscoliosis.

OBJECTIVE: To evaluate respiratory mechanics in the early phase of decompensation in a group of seven patients with severe kyphoscoliosis (KS) (Cobb angle > 90 degrees) requiring mechanical ventilatory support. DESIGN: Prospective clinical study with a control group. SETTING: General intensive care unit at University of Rome "La Sapienza". PATIENTS: Seven consecutive patients affected by severe KS in the early phase of acute decompensation and a control group of six ASA (American Society of Anesthesiology) 1 subjects who were mechanically ventilated during minor surgery. MEASUREMENTS AND RESULTS: Respiratory mechanics were evaluated during constant flow-controlled mechanical ventilation at zero end-expiratory pressure with the end-inspiratory and end-expiratory occlusion technique. In five patients who showed increased ohmic resistance (RRSmin), we evaluated the possibility of reversing this increase with a charge dose of 6 mg/kg doxophylline i.v. In four KS patients, in whom a reliable esophageal pressure was confirmed by a positive occlusion test, we separated respiratory system data into lung and chest wall component. All KS patients showed reduced values of respiratory compliance (CRS) and increased respiratory resistance (RRS). The average basal values of CRS were 36 +/- 10 vs 58 +/- 8.5 cmH2O in control patients; RRSmax was 20 +/- 3.1 vs. 4.5 +/- 1.2 cmH2O/1 per s; RRSmin 6.2 +/- 1.2 vs. 2 +/- 0.5 cmH2O/1 per s: delta RRS 14 +/- 2.6 cmH2O vs 2.4 +/- 0.7 cmH2O/1 per s. All KS patients showed low values of intrinsic positive end-expiratory pressure (PEEPi) (1.8 +/- 1.5 cmH2O). Separation of lung and chest-wall mechanics, performed only in four patients, showed a reduction in both lung (66.7 +/- 7.2 ml/cmH2O) and chest wall values (84 +/- 8.2 ml/cmH2O), while both RmaxL and RmaxCW were increased (16.6 +/- 2 and 2.8 +/- 0.4 cmH2O/1 per s, respectively). Infusion of doxophylline did not significantly change respiratory mechanics when evaluated 15, 30, and 45 min after the infusion. CONCLUSIONS: During acute decompensation, both lung and chest-wall compliance are severely reduced in KS patients: conversely, and, contrary to that in patients with chronic obstructive pulmonary disease, increases in airway resistance and PEEPi seem to play only a secondary role.

Airway Resistance↗
PubMed1997

Exogenous reactive oxygen species deplete the isolated rat heart of antioxidants.

The effects of reactive oxygen species (ROS) on myocardial antioxidants and on the activity of oxidative mitochondrial enzymes were investigated in the following groups of isolated, perfused rat hearts. I: After stabilization the hearts freeze clamped in liquid nitrogen (n = 7). II: Hearts frozen after stabilization and perfusion for 10 min with xanthine oxidase (XO) (25 U/l) and hypoxanthine (HX) (1 mM) as a ROS-producing system (n = 7). III: Like group II, but recovered for 30 min after perfusion with XO + HX (n = 9). IV: The hearts were perfused and freeze-clamped as in group III, but without XO + HX (n = 7). XO + HX reduced left ventricular developed pressure and coronary flow to approximately 50% of the baseline value. Myocardial content of hydrogen peroxide (H2O2) and malondialdehyde (MDA) increased at the end of XO + HX perfusion, indicating that generation of ROS and lipid peroxidation occurred. Levels of H2O2 and MDA normalized during recovery. Superoxide dismutase, reduced glutathione and alpha-tocopherol were all reduced after ROS-induced injury. ROS did not significantly influence the tissue content of coenzyme Q10 (neither total, oxidized, nor reduced), cytochrome c oxidase, and succinate cytochrome c reductase. The present findings indicate that the reduced contractile function was not correlated to reduced activity of the mitochondrial electron transport chain. ROS depleted the myocardium of antioxidants, leaving the heart more sensitive to the action of oxidative injury.

Animals↗
PubMed1997

Different serological examinations in cystic fibrosis patients: response to Pseudomonas aeruginosa St-Ag.

Crossed immunoelectrophoresis (CIE), enzyme linked immunosorbent assay (ELISA) and immunoblotting (IMB) were used to look for the presence of anti-bodies to Pseudomonas aeruginosa standard antigen in the sera of cystic fibrosis patients with intermittent (CF +/- P) and chronic (CF + P) colonization. Our results show that CIE is too complex a method to use when monitoring the infection over time, that with ELISA a correlation with the patient's clinical status may be made and that IMB can evidence an early, albeit low, reaction in the CF +/- P patient.

Adult↗
PubMed1997

Comparative evaluation of the cardiorespiratory effects of assist control ventilation vs pressure support ventilation in patients following orthotopic liver transplantation.

OBJECTIVE: 1) To compare the haemodynamic tolerance of ACV and PSV in patients mechanically ventilated after orthotopic liver transplantation; 2) to compare patients comfort during ACV and PSV. DESIGN: Prospective randomized cross-over study. SETTING: General ICU of the University of Rome "La Sapienza". PATIENTS: Eighteen patients admitted in ICU after orthotopic liver transplantation. MEASUREMENT AND RESULTS: Haemodynamic, oxygen transport and blood gas data were compared during an ACV and PSV trial (30'). A statistically significant decrease of mean pulmonary and systemic arterial pressure, PCOP, LVSWI, occurred during the PSV trial. PaO2 and DO2I decreased during PSV, but were still in supranormal range; 16 out of 18 patients described PSV as more comfortable. CONCLUSIONS: ACV and PSV provided a comparable haemodynamic tolerance in our patients, although during PSV the PaO2 was slightly decreased, probably due to decreased mean airway pressure (from 9.3 +/- 1.2 cmH2O during ACV to 6.6 +/- 1 cmH2O during PSV). PSV can be considered as a good alternative to the standard weaning techniques following orthotopic liver transplantation.

Adult↗
PubMed1996

Cloning, expression and properties of the alpha' subunit of casein kinase 2 from zebrafish (Danio rerio).

The protein kinase casein kinase 2 (CK2) is ubiquitous in eukaryotic cells and is apparently involved in the control of cell division. The holoenzyme is a tetramer composed of two catalytic subunits (alpha and/or alpha') and regulatory subunits (beta 2). The alpha and alpha' subunits are encoded by different genes but are very similar in amino acid sequence, except that alpha' is normally considerably shorter. There have been extensive biochemical studies with recombinant alpha and beta subunits of many species, but only one previous description of the activity of an isolated recombinant alpha' subunit from human CK2 (Bodenbach, L., Fauss, J., Robitzki, A., Krehan, A., Lorenz, P., Lozeman, F. J. & Pyerin, W. (1994) Recombinant human casein kinase II. A study with the complete set of subunits (alpha, alpha', and beta), site-directed autophosphorylation mutants and a bicistronically expressed holoenzyme, Eur. J. Biochem. 220, 263-273). In the present work, the isolation and bacterial expression of a cDNA coding for the alpha' subunit of zebrafish (Danio rerio) is reported. The clone covers the complete coding region that generates a protein of 348 amino acids that is 86% identical to the alpha' subunits of human and chicken, and 82% identical to the sequenced portion of the CK2 alpha subunit of zebrafish. The recombinant alpha' subunit has apparent K(m) values for ATP (6 microM), GTP (20 microM), casein (2.0 mg/ml) and the model peptide RRRDDDSEDD (0.3 mM) which are very similar to those of the recombinant alpha subunit of Xenopus laevis. The alpha' subunit kcat was 7.2 min-1 which is again similar to that of Xenopus laevis alpha subunit (7.5 min-1). The alpha' subunit also behaved similarly to CK2 alpha with regard to optimal concentrations for Mg+2 or Mn+2 and to the inhibition by heparin and the poly(Glu80Tyr20) peptide. However alpha' kinase activity was less sensitive to poly(U) inhibition than alpha, it was more heat stable than alpha, and alpha' was slightly more sensitive to KCl inhibition than alpha. The difference in salt sensitivity, however, was enhanced by the presence of the regulatory beta subunit which shifted the optimal salt concentration of the phosphorylating activity. The alpha' 2 beta 2 holoenzyme was inhibited by KCl concentrations above 100 mM, while the alpha 2 beta 2 enzyme was stimulated by KCl concentrations up to 150 mM and required 180 mM for inhibition. Another important difference between alpha and alpha' is seen in the degree of the stimulation of casein phosphorylation activity in the presence of the regulatory beta subunit. When assayed at 100 mM KCl stoichiometric amounts of CK2 beta produced maximal stimulation of both alpha' (D. rerio) and alpha (X. laevis), however the activity levels with alpha' were stimulated 20-fold by beta while the addition of beta stimulated alpha (X. laevis) only 7-8-fold.

Amino Acid Sequence↗
PubMed1996

Precipitating Pseudomonas aeruginosa antibodies and antimicrobial therapy in cystic fibrosis patients.

Forty patients with cystic fibrosis were studied bacteriologically and serologically. Precipitating Pseudomonas aeruginosa antibodies were monitored by crossed-immunoelectrophoresis (CIE) in order to evaluate the possibility of preventing chronic colonization by Pseudomonas aeruginosa by cycles of antimicrobial therapy. Sputum or pharyngeal aspirate and serum samples from all patients were analyzed by means of spread on selective media and CIE, respectively. Significant differences in the number of precipitins were obtained: noncolonized and intermittently colonized patients had no precipitins, whereas the number of precipitins in the chronically colonized patients varied from 11 to 44. An increase in the number of precipitins could be a good marker for initiation of therapy with antimicrobial agents that are either active against Pseudomonas aeruginosa or able to inhibit the release of virulence factors.

Adolescent↗
PubMed1996

Early and late onset bacteremia have different risk factors in trauma patients.

OBJECTIVE: The aim of this study was to identify risk factors and to describe epidemiological patterns for early-(EOB) and late-onset bacteremias (LOB) after trauma. DESIGN: A prospective study conducted on 141 consecutive trauma patients. SETTING: A general intensive care unit (ICU) of a university hospital. PATIENTS: All multiple trauma patients admitted to our general intensive care unit (ICU) from December 1990 to May 1992 were prospectively enrolled in the study. The following information was collected for each patient and recorded in a computer database: demography, severity of trauma according to the Abbreviated Injury Scale (AIS), severity of coma according to the Glasgow Coma Scale (GCS), presence of pneumothorax, pulmonary contusion, rib fractures, hemothorax, and abdominal trauma, use of mechanical ventilation, and placement of central venous catheters. Bacteremias were defined as EOB when onset occurred within 96 h after trauma, and as LOB when appearing after 96 h from trauma. RESULTS: Thirty-seven patients developed bacteremia during their ICU stay (26%): 11 (29.7%) EOB and 26 (70.3%) LOB. Gram-positive cocci were isolated more frequently in EOB than in LOB (chi 2 = 4.1, P = 0.04). The risk of EOB was significantly increased by the presence of pulmonary contusion [relative risk (RR) 15.0; confidence interval (CI) 1.99-113.25], pneumonia before the onset of bacteremia (RR 3.56; CI 1.17-10.69), AIS score greater than 32 and an abdominal injury score greater than 9 (RR 3.11; CI 1.02-9.49), while intravascular catheters and mechanical ventilation did not represent risk factors for EOB. LOB had a very different pattern and their risk was significantly increased by exposure to intravascular catheters (RR 4.96; CI 1.23-19.94) and to mechanical ventilation lasting more than 7 days (RR 3.6; CI 1.6-8.1). CONCLUSIONS: Scoring with the AIS of the abdominal and thoracic trauma at admission to the ICU appears a useful tool for identifying trauma patients at increased risk of EOB. A rigorous policy of catheter placement and maintenance as a means of reducing late bacteremias in trauma patients is essential.

Abdominal Injuries↗
PubMed1996

O2 consumption-O2 delivery relationship and arteriolar resistance in the forearm of critically ill patients measured by near infrared spectroscopy.

Eight patients with severe sepsis, four with septic shock, and eight without sepsis were studied to investigate whether skeletal muscle influences the whole body O2 consumption (VO2)-O2 delivery relationship and hemodynamics. A forearm VO2-O2 delivery dependency was observed only in nonseptic patients, in whom no whole body VO2-O2 delivery dependency appeared. No forearm VO2-O2 delivery relationship was observed in septic and shock patients, in whom whole body VO2-O2 delivery dependency was found. In shock patients the lack of forearm VO2-O2 delivery dependency was associated with low forearm arteriolar resistance (FAR) even at a relatively low forearm blood flow (FBF). Neither a relationship between forearm VO2 and whole body VO2 nor between FAR and SVR was found in any groups of patients. Septic shock was associated with low FAR that was not affected by the FBF decrease, indicating that in this condition, hemodynamics could be influenced by skeletal muscle resistance.

Aged↗
PubMed1996

Noninvasive positive-pressure ventilation via face mask during bronchoscopy with BAL in high-risk hypoxemic patients.

STUDY OBJECTIVE: The aim of this study was to assess the feasibility and safety of noninvasive positive-pressure ventilation (NPPV) via a face mask to aid in performing fiberoptic bronchoscopy (FOB) with BAL in immunosuppressed patients with gas exchange abnormalities that contraindicate using conventional unassisted FOB. STUDY POPULATION: Eight consecutive immunosuppressed patients (40 +/- 14 years old) with suspected pneumonia entered the study. Entrance criteria included the following: (1) PaO2/fraction of inspired oxygen (FIo2) of 100 or less; pH of 7.35 or more; and (3) improvement in O2 saturation during NPPV before initiating FOB. INTERVENTION: Patients had routine application of topical anesthesia to the nasopharynx. A full face mask was connected to a ventilator (Servo 900C; Solna, Sweden) set to deliver continuous positive airway pressure (CPAP) of 4 cm H2O, pressure support ventilation of 17 cm H2O, and 1.0 FIo2. The mask was secured to the patient with head straps. NPPV began 10 min before starting FOB and continued for 90 min or more after the procedure was completed. The bronchoscope was passed through a T-adapter and advanced through the nose. BAL was obtained by sequential instillation and aspiration of 5 to 25 mL aliquots of sterile saline solution through a bronchoscope wedged in a radiographically involved subsegment. Oxygen saturation, heart rate, respiratory rate, and arterial blood gases were monitored during the study. RESULTS: NPPV significantly improved PaO2/FIo2 and O2 saturation. FOB with NPPV was well tolerated, and no patient required endotracheal intubation. A causative pathogen was identified by BAL in all patients. Six patients responded to treatment and survived hospital admission. Two patients died 5 to 7 days after FOB from unrelated complications of the underlying illness. CONCLUSIONS: NPPV should be considered during bronchoscopy of immunosuppressed patients with severe hypoxemia.

Adult↗
PubMed1995

Non-dominant dorsal-prefrontal activation during chess problem solution evidenced by single photon emission computerized tomography (SPECT).

Expert chess players can recall meaningful chess positions with extraordinary precision in comparison with inexperienced players. We hypothesized, therefore, that their mental performance during chess deliberation could be an appropriate target for single photon emission computerized tomography (SPECT) studies. We studied cerebral activation with 1110 MBq 99mTc-Bicisate SPECT in five expert male chess players during mental solution of a complex chess problem. Region of interest (ROI) analysis, in comparison with average weighted cerebellar counts, showed activation by 10% or more, of the non dominant prefrontal area (right in four dominant right handed players, left in one dominant left handed player) and by 2-6% in the non-dominant middle temporal areas. Maximum variability of ROI analysis versus cerebellar counts in test/retest evaluation is in our laboratory, as in others, 1.5%. Our results are in agreement with neuropsychological studies suggesting that the non-dominant hemisphere is specialized for chess skill, and show that non-dominant prefrontal and temporal lobe activation during chess deliberation can be detected by SPECT.

Adult↗
PubMed1995

Paralysis has no effect on chest wall and respiratory system mechanics of mechanically ventilated, sedated patients.

OBJECTIVE: To evaluate the separate effects of sedation and paralysis on chest wall and respiratory system mechanics of mechanically ventilated, critically ill patients. SETTING: ICU of the University "La Sapienza" Hospital, Rome. PATIENTS AND PARTICIPANTS: 13 critically ill patients were enrolled in this study. All were affected by disease involving both lungs and chest wall mechanics (ARDS in 4 patients, closed chest trauma without flail chest in 4 patients, cardiogenic pulmonary oedema with fluidic overload in 5 patients). MEASUREMENTS AND RESULTS: Respiratory system and chest wall mechanics were evaluated during constant flow controlled mechanical ventilation in basal conditions (i.e. with the patients under apnoic sedation) and after paralysis with pancuronium bromide. In details, we simultaneously recorded airflow, tracheal pressure, esophageal pressure and tidal volume; with the end-inspiratory and end-expiratory airway occlusion technique we could evaluate respiratory system and chest wall elastance and resistances. Lung mechanics was evaluated by subtracting chest wall from respiratory system data. All data obtained in basal conditions (with the patients sedated with thiopental or propofol) and after muscle paralysis were compared using the Student's t test for paired data. The administration of pancuronium bromide to sedated patients induced a complete muscle paralysis without producing significant modification both to the viscoelastic and to the resistive parameters of chest wall and respiratory system. CONCLUSIONS: This study demonstrates the lack of additive effects of muscle paralysis in mechanically ventilated, sedated patients. Also in view of the possible side effects of muscle paralysis, our results question the usefulness of generalized administration of neuromuscular blocking drugs in mechanically ventilated patients.

Adult↗
PubMed1995

Thrombosis of cerebral veins dural sinuses after paratyphi.

A 20 year old woman was admitted to our Department 15 days after the onset of typhoid fever treated with chloramphenicol. The patient showed intracranial hypertension with generalized seizures, slight right hemiparesis and a left VI cranial nerve deficit with diplopia. Magnetic Resonance Imaging (MRI) showed occlusion of the superior longitudinal, right transverse, right sigmoid sinus combined with a single hemorrhagic infarct in the left occipito-parietal area. Serum tests were positive for Salmonella Paratyphi A and B. The results of cerebrospinal fluid (CSF) examination were normal and blood cultures were negative. Clinical data, laboratory and MRI examinations indicate that the neurological signs are the result of aseptic cerebral sinus thrombosis; the physiopathologic mechanisms of the case are discussed.

Adult↗
PubMed1995

High IL-6 serum levels are associated with septic shock and mortality in septic patients with severe leukopenia due to hematological malignancies.

The serum levels of immunoreactive interleukin-6 (IL-6) and tumor necrosis factor (TNF) were analyzed in 14 leukopenic patients with documented sepsis, at 60 min (T0), 24 h (T1), and one week (T3) after the onset of sepsis syndrome. Sera from 10 leukopenic patients without sepsis (controls) were also tested. All septic patients had high IL-6 levels at T0. These levels persisted only in the seven patients who died of septic shock, presenting a 30-fold increase (p<0.001) as compared to the survivors and the controls. At T3, 7 survivors had recovered from sepsis and showed low IL-6 serum levels. The TNF serum concentration always <30 pg/ml in both the subjects and in the controls. The C-reactive protein (CRP) and clinical parameters appeared to be less specifically associated with shock and mortality than IL-6.

Adult↗