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Paolo Pelosi

Publications and source records attributed to Paolo Pelosi.

At least 19 recordsLinked to original sources
PubMed2006

Secretory proteins as potential semiochemical carriers in the horse.

Two soluble proteins were isolated as major secretory products of horse sweat and of the parotid gland and characterized for structural and functional properties. The first protein, lipocalin allergen EquC1, was characterized for its glycosylation sites and bound glycosidic moieties. Only one (Asn53) of the two putative glycosylation sites within the sequence was post-translationally modified; a different glycosylation pattern was determined with respect to data previously reported. When purified from horse sweat, this protein contained oleamide and other organic molecules as natural ligands. Ligand binding experiments indicated good protein selectivity toward volatile compounds having a straight chain structure of 9-11 carbon atoms, suggesting a role of this lipocalin in chemical communication. The second protein, here reported for the first time in the horse, belongs to the group of parotid secretory proteins, part of a large superfamily of binding proteins whose function in most cases is still unclear. This protein was sequenced and characterized for its post-translational modifications. Of the three cysteine residues present, two were involved in a disulfide bridge (Cys155-Cys198). A model, built up on the basis of similar proteins, indicated a general fold characterized by the presence of a long hydrophobic barrel. Binding experiments performed with a number of different organic compounds failed to identify ligands for this protein with a well-defined physiological role.

Amino Acid Sequence↗
PubMed2006

Solution structure of a chemosensory protein from the desert locust Schistocerca gregaria.

Chemical stimuli, generally constituted by small volatile organic molecules, are extremely important for the survival of different insect species. In the course of evolution, insects have developed very sophisticated biochemical systems for the binding and the delivery of specific semiochemicals to their cognate membrane-bound receptors. Chemosensory proteins (CSPs) are a class of small soluble proteins present at high concentration in insect chemosensory organs; they are supposed to be involved in carrying the chemical messages from the environment to the chemosensory receptors. In this paper, we report on the solution structure of CSPsg4, a chemosensory protein from the desert locust Schistocerca gregaria, which is expressed in the antennae and other chemosensory organs. The 3D NMR structure revealed an overall fold consisting of six alpha-helices, spanning residues 13-18, 20-31, 40-54, 62-78, 80-90, and 97-103, connected by loops which in some cases show dihedral angles typical of beta-turns. As in the only other chemosensory protein whose structure has been solved so far, namely, CSP from the moth Mamestra brassicae, four helices are arranged to form a V-shaped motif; another helix runs across the two V's, and the last one is packed against the external face. Analysis of the tertiary structure evidenced multiple hydrophobic cavities which could be involved in ligand binding. In fact, incubation of the protein with a natural ligand, namely, oleamide, produced substantial changes to the NMR spectra, suggesting extensive conformational transitions upon ligand binding.

Amino Acid Sequence↗
PubMed2006

Effects of partial ventilatory support modalities on respiratory function in severe hypoxemic lung injury.

OBJECTIVE: The early phase of acute respiratory distress syndrome (ARDS) is characterized by impaired respiratory mechanics, ventilation-perfusion mismatch, and severe hypoxemia. Partial ventilatory support can effectively unload the respiratory workload and improve pulmonary gas exchange with less hemodynamic compromise. The partial ventilatory support mode most indicated in early phases of ARDS has not been determined. This study compares the effects of assisted ventilatory techniques on breathing pattern, gas exchange, hemodynamic function, and respiratory effort with those of controlled mechanical ventilation in similarly sedated subjects. DESIGN: Prospectively randomized crossover animal study. SETTING: Animal research laboratory. SUBJECTS: Eleven anesthetized and mechanically ventilated pigs. INTERVENTIONS: Acute lung injury was induced by lung lavage. Pressure-controlled ventilation (PCV), pressure-controlled assisted ventilation (P-ACV), bilevel positive airway pressure (BIPAP), and pressure support ventilation (PSV) with equal airway pressures and sedation were applied in random order. MEASUREMENTS AND MAIN RESULTS: Gas exchange, respiratory effort, and hemodynamic function were measured, and ventilation-perfusion distributions were calculated by multiple inert-gas-elimination techniques. The results revealed that partial ventilatory support was superior to PCV in maintaining adequate oxygenation and hemodynamic function with reduced sedation. The effects of P-ACV, BIPAP, and PSV were comparable with respect to gas exchange and hemodynamic function, except for a more pronounced reduction in shunt during BIPAP. P-ACV and PSV were superior to BIPAP to reduce respiratory drive and work of breathing. PSV affected the pattern of breathing and deadspace to a greater degree than did P-ACV. CONCLUSIONS: In acute lung injury, P-ACV preserves oxygenation and hemodynamic function with less respiratory effort compared with BIPAP and reduces the need for sedation compared with PCV.

Animals↗
PubMed2006

AIDS vaccination studies with an ex vivo feline immunodeficiency virus model: analysis of the accessory ORF-A protein and DNA as protective immunogens.

Determining which antigen must be included in AIDS vaccines to confer maximum protection is of utmost importance. In primate models, vaccines consisting of or including accessory viral proteins have yielded conflicting results. We investigated the protective potential of the accessory protein ORF-A of feline immunodeficiency virus (FIV) in cats. All three immunization strategies used (protein alone in alum adjuvant, DNA alone, or DNA prime-protein boost) clearly generated detectable immune responses. Upon challenge with ex vivo homologous FIV, ORF-A-immunized cats showed distinct enhancement of acute-phase infection relative to mock-immunized animals given alum or empty vector DNA. This effect was tentatively attributed to increased expression of the FIV receptor CD134 that was observed in the immunized cats. However, at subsequent sampling points that were continued for up to 10 months postchallenge, the average plasma viral loads of the ORF-A-immunized animals were slightly but consistently reduced relative to those of the control animals. In addition, CD4(+) T lymphocytes in the circulation system declined more slowly in immunized animals than in control animals. These findings support the contention that immunization with lentiviral accessory proteins can improve the host's ability to control virus replication and slow down disease progression but also draw attention to the fact that even simple immunogens that eventually contribute to protective activity can transiently exacerbate subsequent lentiviral infections.

AIDS Vaccines↗
PubMed2006

Chest wall mechanics during pressure support ventilation.

INTRODUCTION: During pressure support ventilation (PSV) a part of the breathing pattern is controlled by the patient, and synchronization of respiratory muscle action and the resulting chest wall kinematics is a valid indicator of the patient's adaptation to the ventilator. The aim of the present study was to analyze the effects of different PSV settings on ventilatory pattern, total and compartmental chest wall kinematics and dynamics, muscle pressures and work of breathing in patients with acute lung injury. METHOD: In nine patients four different levels of PSV (5, 10, 15 and 25 cmH2O) were randomly applied with the same level of positive end-expiratory pressure (10 cmH2O). Flow, airway opening, and oesophageal and gastric pressures were measured, and volume variations for the entire chest wall, the ribcage and abdominal compartments were recorded by opto-electronic plethysmography. The pressure and the work generated by the diaphragm, rib cage and abdominal muscles were determined using dynamic pressure-volume loops in the various phases of each respiratory cycle: pre-triggering, post-triggering with the patient's effort combining with the action of the ventilator, pressurization and expiration. The complete breathing pattern was measured and correlated with chest wall kinematics and dynamics. RESULTS: At the various levels of pressure support applied, minute ventilation was constant, with large variations in breathing frequency/ tidal volume ratio. At pressure support levels below 15 cmH2O the following increased: the pressure developed by the inspiratory muscles, the contribution of the rib cage compartment to the total tidal volume, the phase shift between rib cage and abdominal compartments, the post-inspiratory action of the inspiratory rib cage muscles, and the expiratory muscle activity. CONCLUSION: During PSV, the ventilatory pattern is very different at different levels of pressure support; in patients with acute lung injury pressure support greater than 10 cmH2O permits homogeneous recruitment of respiratory muscles, with resulting synchronous thoraco-abdominal expansion.

Adult↗
PubMed2006

Bench-to-bedside review: the role of glycosaminoglycans in respiratory disease.

The extracellular matrix (ECM) plays a significant role in the mechanical behaviour of the lung parenchyma. The ECM is composed of a three-dimensional fibre mesh that is filled with various macromolecules, among which are the glycosaminoglycans (GAGs). GAGs are long, linear and highly charged heterogeneous polysaccharides that are composed of a variable number of repeating disaccharide units. There are two main types of GAGs: nonsulphated GAG (hyaluronic acid) and sulphated GAGs (heparan sulphate and heparin, chondroitin sulphate, dermatan sulphate, and keratan sulphate). With the exception of hyaluronic acid, GAGs are usually covalently attached to a protein core, forming an overall structure that is referred to as proteoglycan. In the lungs, GAGs are distributed in the interstitium, in the sub-epithelial tissue and bronchial walls, and in airway secretions. GAGs have important functions in lung ECM: they regulate hydration and water homeostasis; they maintain structure and function; they modulate the inflammatory response; and they influence tissue repair and remodelling. Given the great diversity of GAG structures and the evidence that GAGs may have a protective effect against injury in various respiratory diseases, an understanding of changes in GAG expression that occur in disease may lead to opportunities to develop innovative and selective therapies in the future.

Biomechanical Phenomena↗
PubMed2006

Oleic acid vs saline solution lung lavage-induced acute lung injury: effects on lung morphology, pressure-volume relationships, and response to positive end-expiratory pressure.

OBJECTIVE: To compare two lung injury models (oleic acid [OA] and saline solution washout [SW]) regarding lung morphology, regional inflation, and recruitment during static pressure-volume (PV) curves, and the effects of positive end-expiratory pressure (PEEP) below and above the lower inflection point (Pflex). METHODS: Fourteen adult pigs underwent OA or SW lung injury. Lung volumes were measured using CT. PV curves were obtained with simultaneous CT scanning at lung apex and base. Fractional inflation and recruitment were compared to data on PEEP above and below Pflex. RESULTS: Severity of lung injury was comparable. At zero PEEP, SW showed an increased amount of edema and poorly aerated lung volume, recruitment during inspiration, and a better oxygenation response with PEEP. Whole-lung PV curves were similar in both models, reflecting changes in alveolar inflation or deflation. On the inspiratory PV limb, recruitment and inflation were on the same line, while there was a substantial difference between deflation and derecruitment on the expiratory limb. PEEP-induced recruitment at lung apex and base was at or above the derecruitment line on the expiratory limb and showed no relationship to the whole-lung expiratory PV curve. CONCLUSIONS: The following conclusions were made: (1) OA and SW models are comparable in mechanics but not in lung injury characteristics; (2) neither inspiratory nor expiratory whole-lung PV curves are useful to select PEEP in order to optimize recruitment; and (3) after recruitment, there is no difference in derecruitment between the models at high PEEP, while more collapse occurs at lower PEEP in the basal sections of SW lungs.

Animals↗
PubMed2005

Clinical review: Positive end-expiratory pressure and cardiac output.

In patients with acute lung injury, high levels of positive end-expiratory pressure (PEEP) may be necessary to maintain or restore oxygenation, despite the fact that 'aggressive' mechanical ventilation can markedly affect cardiac function in a complex and often unpredictable fashion. As heart rate usually does not change with PEEP, the entire fall in cardiac output is a consequence of a reduction in left ventricular stroke volume (SV). PEEP-induced changes in cardiac output are analyzed, therefore, in terms of changes in SV and its determinants (preload, afterload, contractility and ventricular compliance). Mechanical ventilation with PEEP, like any other active or passive ventilatory maneuver, primarily affects cardiac function by changing lung volume and intrathoracic pressure. In order to describe the direct cardiocirculatory consequences of respiratory failure necessitating mechanical ventilation and PEEP, this review will focus on the effects of changes in lung volume, factors controlling venous return, the diastolic interactions between the ventricles and the effects of intrathoracic pressure on cardiac function, specifically left ventricular function. Finally, the hemodynamic consequences of PEEP in patients with heart failure, chronic obstructive pulmonary disease and acute respiratory distress syndrome are discussed.

Airway Resistance↗
PubMed2005

Respiratory compliance but not gas exchange correlates with changes in lung aeration after a recruitment maneuver: an experimental study in pigs with saline lavage lung injury.

INTRODUCTION: Atelectasis is a common finding in acute lung injury, leading to increased shunt and hypoxemia. Current treatment strategies aim to recruit alveoli for gas exchange. Improvement in oxygenation is commonly used to detect recruitment, although the assumption that gas exchange parameters adequately represent the mechanical process of alveolar opening has not been proven so far. The aim of this study was to investigate whether commonly used measures of lung mechanics better detect lung tissue collapse and changes in lung aeration after a recruitment maneuver as compared to measures of gas exchange METHODS: In eight anesthetized and mechanically ventilated pigs, acute lung injury was induced by saline lavage and a recruitment maneuver was performed by inflating the lungs three times with a pressure of 45 cmH2O for 40 s with a constant positive end-expiratory pressure of 10 cmH2O. The association of gas exchange and lung mechanics parameters with the amount and the changes in aerated and nonaerated lung volumes induced by this specific recruitment maneuver was investigated by multi slice CT scan analysis of the whole lung. RESULTS: Nonaerated lung correlated with shunt fraction (r = 0.68) and respiratory system compliance (r = 0.59). The arterial partial oxygen pressure (PaO2) and the respiratory system compliance correlated with poorly aerated lung volume (r = 0.57 and 0.72, respectively). The recruitment maneuver caused a decrease in nonaerated lung volume, an increase in normally and poorly aerated lung, but no change in the distribution of a tidal breath to differently aerated lung volumes. The fractional changes in PaO2, arterial partial carbon dioxide pressure (PaCO2) and venous admixture after the recruitment maneuver did not correlate with the changes in lung volumes. Alveolar recruitment correlated only with changes in the plateau pressure (r = 0.89), respiratory system compliance (r = 0.82) and parameters obtained from the pressure-volume curve. CONCLUSION: A recruitment maneuver by repeatedly hyperinflating the lungs led to an increase of poorly aerated and a decrease of nonaerated lung mainly. Changes in aerated and nonaerated lung volumes were adequately represented by respiratory compliance but not by changes in oxygenation or shunt.

Animals↗
PubMed2005

An integrated approach to prevent and treat respiratory failure in brain-injured patients.

PURPOSE OF REVIEW: Brain-injured patients are at increased risk of extracerebral organ dysfunction, in particular ventilator-associated pneumonia. The purpose of this review is to discuss functional abnormalities, clinical treatment, and possible prevention of respiratory function abnormalities in brain-injured patients. RECENT FINDINGS: Ventilator-associated pneumonia worsens the neurologic outcome and increases the intensive care unit and hospital stay, costs, and risk of death. The respiratory dysfunction can be due to several causes, but atelectasis and/or consolidation of the lower lobes predominates in the most severe cases. Strategies should be implemented to prevent lung infections and accelerate weaning from mechanical ventilation to reduce the incidence of respiratory dysfunction and ventilator-associated pneumonia. SUMMARY: An integrated approach including appropriate ventilatory, antibiotic, and fluid management could be extremely useful, not only to prevent and more rapidly treat respiratory failure but also to improve neurologic outcome and reduce hospital stay. Further studies are warranted to better elucidate the pathophysiology and clinical treatment of respiratory dysfunction in brain-injured patients.

Brain Injuries↗
PubMed2005

Incidence and prognosis of intraabdominal hypertension in a mixed population of critically ill patients: a multiple-center epidemiological study.

OBJECTIVE: Intraabdominal hypertension is associated with significant morbidity and mortality in surgical and trauma patients. The aim of this study was to assess, in a mixed population of critically ill patients, whether intraabdominal pressure at admission was an independent predictor for mortality and to evaluate the effects of intraabdominal hypertension on organ functions. DESIGN: Multiple-center, prospective epidemiologic study. SETTING: Fourteen intensive care units in six countries. PATIENTS: A total of 265 consecutive patients admitted for >24 hrs during the 4-wk study period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Intraabdominal pressure was measured twice daily via the bladder. Data recorded on admission were the patient demographics with Simplified Acute Physiology Score II, Acute Physiology and Chronic Health Evaluation II score, and type of admission; during intensive care stay, Sepsis-Related Organ Failure Assessment score and intraabdominal pressure were measured daily together with fluid balance. Nonsurvivors had a significantly higher mean intraabdominal pressure on admission than survivors: 11.4 +/- 4.8 vs. 9.5 +/- 4.8 mm Hg. Independent predictors for mortality were age (odds ratio, 1.04; 95% confidence interval, 1.01-1.06; p = .003), Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.1; 95% confidence interval, 1.05-1.15; p < .0001), type of intensive care unit admission (odds ratio, 2.5 medical vs. surgical; 95% confidence interval, 1.24-5.16; p = .01), and the presence of liver dysfunction (odds ratio, 2.5; 95% confidence interval, 1.06-5.8; p = .04). The occurrence of intraabdominal hypertension during the intensive care unit stay was also an independent predictor of mortality (relative risk, 1.85; 95% confidence interval, 1.12-3.06; p = .01). Patients with intraabdominal hypertension at admission had significantly higher Sepsis-Related Organ Failure Assessment scores during the intensive care unit stay than patients without intraabdominal hypertension. CONCLUSIONS: Intraabdominal hypertension on admission was associated with severe organ dysfunction during the intensive care unit stay. The mean intraabdominal pressure on admission was not an independent risk factor for mortality; however, the occurrence of intraabdominal hypertension during the intensive care unit stay was an independent outcome predictor.

APACHE↗
PubMed2005

Computed tomography scan assessment of lung volume and recruitment during high-frequency oscillatory ventilation.

OBJECTIVE: This review describes how computed tomography has increased our understanding of the pathophysiology of acute respiratory distress syndrome. It summarizes current knowledge about lung volume changes and alveolar recruitment during high-frequency oscillatory ventilation (HFOV) assessed by computed tomography (CT), outlines potential problems when comparing HFOV with conventional ventilation (CV) as a result of the different pressure-time profiles, and describes future research directions. DATA SOURCE: CT allows accurate assessment of total lung volumes and differentiation between overinflated, normally aerated, poorly aerated, and nonaerated lung regions. It allows for classification of different patterns of consolidation and may be predictive for the potential for recruitment. DATA SUMMARY: Experimental data suggest that HFOV at mean airway pressures (mPaw) set according to a static PV curve leads to effective lung recruitment but results in overall lung volumes that are considerably higher than those predicted from the PV relationship. In saline-lavaged sheep, similar changes in total lung volumes and subvolumes were observed during HFOV and CV. One single study specifically assessed lung volume recruitment during HFOV as compared with CV in eight patients with acute respiratory distress syndrome from pneumonia or sepsis. After 48 hrs on HFOV, total ventilated lung volume was significantly increased, whereas only a minor increase in overinflated lung volume was observed. These changes correlated with a significant improvement in gas exchange. CONCLUSION: CT is a valuable tool to quantify recruitment and overinflation during HFOV. Additional studies are needed to better characterize the specific effects of HFOV on lung volume and morphology.

Animals↗
PubMed2004

Tracheostomy must be individualized!

Tracheostomy is one of the most frequent procedures carried out in critically ill patients with major advantages compared to translaryngeal endotracheal intubation such as reduced laryngeal anatomical alterations, reduced inspiratory load, better patient's tolerance and nursing. Thus, tracheostomy can enhance patient's care in patients who need prolonged mechanical ventilation and/or control of airways. The right timing of tracheostomy remains controversial, however it appears that early tracheostomy in selected severe trauma, burn and neurological patients could be effective to reduce the duration of mechanical ventilation intensive care stay and costs. Percutaneous tracheostomy techniques are becoming the procedure of choice in the majority of the cases, since they are safe, easy and quick, and complications are minor. However, percutaneous tracheostomies should be always performed by experienced physicians to avoid unnecessary additional complications. It is not clear the superiority of one percutaneous technique compared to another, but experience of the operator and clinical individual anatomical, physiopathological characteristics of the patient should be always considered. We believe that the operator should have experience of at least one intrusive and one extrusive percutaneous technique. The general "optimal" tracheostomy technique and timing do not exist, but tracheostomy should be targeted on the patient's individual clinical characteristics.

Humans↗
PubMed2004

Plant stress proteins of the thaumatin-like family discovered in animals.

Thaumatin-like proteins (TLPs) are polypeptides of about 200 residues synthesized by plants in response to fungal infection. In addition to the exceptionally strong sweet taste exhibited by some members, they are also reported to be endowed with endo-beta-1,3-glucanase activity and alpha-amylase inhibiting properties. However, the detailed mechanism of their antifungal action is not completely understood. So far, TLPs have only been described in plants, with several members of the family expressed in the same species. Here, for the first time in animals, we report the identification of two genes encoding members of the thaumatin-like proteins family in the desert locust Schistocerca gregaria and show their expression in different parts of the body. Southern blot and Western blot experiments revealed the presence of orthologous genes and their expression products in the related species Locusta migratoria. A search through the available genomes yielded similar sequences in the nematode Caenorhabditis but not in Drosophila and other insects. A three-dimensional model of S. gregaria TLP suggests a glucanase function. As in plants, TLPs could play a defense role in insects against pathogens.

Amino Acid Sequence↗
PubMed2004

In vitro and in vivo evaluation of a new active heat moisture exchanger.

INTRODUCTION: In order to improve the efficiency of heat moisture exchangers (HMEs), new hybrid humidifiers (active HMEs) that add water and heat to HMEs have been developed. In this study we evaluated the efficiency, both in vitro and in vivo, of a new active HME (the Performer; StarMed, Mirandola, Italy) as compared with that of existing HMEs (Hygroster and Hygrobac; Mallinckrodt, Mirandola, Italy). METHODS: We tested the efficiency by measuring the temperature and absolute humidity (AH) in vitro using a test lung ventilated at three levels of minute ventilation (5, 10 and 15 l/min) and at two tidal volumes (0.5 and 1 l), and in vivo in 42 patients with acute lung injury (arterial oxygen tension/fractional inspired oxygen ratio 283 +/- 72 mmHg). We also evaluated the efficiency in vivo after 12 hours. RESULTS: In vitro, passive Performer and Hygrobac had higher airway temperature and AH (29.2 +/- 0.7 degrees C and 29.2 +/- 0.5 degrees C, [P < 0.05]; AH: 28.9 +/- 1.6 mgH2O/l and 28.1 +/- 0.8 mgH2O/l, [P < 0.05]) than did Hygroster (airway temperature: 28.1 +/- 0.3 degrees C [P < 0.05]; AH: 27 +/- 1.2 mgH2O/l [P < 0.05]). Both devices suffered a loss of efficiency at the highest minute ventilation and tidal volume, and at the lowest minute ventilation. Active Performer had higher airway temperature and AH (31.9 +/- 0.3 degrees C and 34.3 +/- 0.6 mgH2O/l; [P < 0.05]) than did Hygrobac and Hygroster, and was not influenced by minute ventilation or tidal volume. In vivo, the efficiency of passive Performer was similar to that of Hygrobac but better than Hygroster, whereas Active Performer was better than both. The active Performer exhibited good efficiency when used for up to 12 hours in vivo. CONCLUSION: This study showed that active Performer may provide adequate conditioning of inspired gases, both as a passive and as an active device.

Acute Disease↗