Interleukin-23 serum levels in patients affected by peripheral arterial disease.

OBJECTIVES: To clarify whether interleukin (IL)-23 is involved in peripheral arterial disease (PAD). DESIGN AND METHODS: We evaluated IL-23 serum levels, in 29 patients suffering from lower extremity PAD and in 30 healthy subjects. RESULTS: IL-23 serum levels were higher during the three times (T0, T1 and T2) compared to the control group, although only statistically significant for T0 and T2: T0 (15.83 ± 22.08 vs. 8.08 ± 8.62 pg ml, p=0.026), T1 (16.10 ± 23.71 vs. 8.08 ± 8.62 pg/ml, p=0.101), T2 (15.06 ± 16.72 vs. 8.08 ± 8.62 pg/ml, p=0.005). CONCLUSION: For the first time, our data gives us reason to believe there is an involvement of IL-23 in PAD.

High mobility group box-1 expression correlates with poor outcome in lung injury patients.

Chest trauma is frequently followed by pulmonary contusion and sepsis. High mobility group box-1 (HMGB-1) is a late mediator of severe sepsis that has been associated with mortality under experimental conditions. We studied HMGB-1 mRNA expression in patients with lung injury and its relationship with the severity of trauma and survival. A total of 24 consecutive patients with chest trauma referring to the Intensive Care Unit of Messina University Hospital, were enrolled. Lung trauma was established on the basis of chest X-ray and computed tomography. Injury Severity Score (ISS), Revised Trauma Score (RTS) and Glasgow Coma Scale (GCS) were also assessed. Accordingly to these results 6 patients were considered as controls because of no penetrating trauma and low ISS. Blood and broncho-alveolar lavage fluid (BALF) from chest trauma patients were withdrawn at admission and 24h after the beginning of the standard therapeutic protocol. HMGB-1 mRNA increased significantly in blood (r=0.84) and BALF (r=0.87) from patients with trauma and pulmonary contusion and positively correlated with the severity of trauma (based on ISS and RTS) and the final outcome. HMGB-1 protein levels were also elevated in BALF macrophages from severe trauma patients compared to control subjects, furthermore TNF-alpha and its receptor TNFR-1 mRNA levels were also markedly increased in patients with a poor outcome respect to other subjects. Our study suggests that HMGB-1 may be an early indicator of poor clinical outcome in patients with chest trauma.

Trehalose: a biophysics approach to modulate the inflammatory response during endotoxic shock.

We evaluated the effects of trehalose against endotoxic shock, a condition in which the loss of bio-membrane integrity plays a pivotal role. In addition we performed a biophysics experiment by quasi elastic neutron scattering (QENS) study, to investigate whether the membrane stability effect of trehalose might be correlated with its high capability to switch-off the water diffusive dynamics and, hence, the kinetic mechanisms of interaction. Endotoxic shock was induced in male rats by a single injection of Salmonella enteritidis lipopolysaccharide (LPS; 20 mg/kg/i.p.). Thirty minutes before and 2 h after LPS injection, the animals were randomized to receive vehicle (1 ml/kg/i.p. 0.9%NaCl), sucrose (1 g/kg/i.p.) or trehalose (1 g/kg/i.p.). Mean arterial blood pressure, nuclear factor-kappaB (NF-kappaB) binding activity, Ikappa-Balpha and toll-like receptor-4 (TLR-4) activation were evaluated in both liver and lung. Plasmatic tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6) and malondialdehyde (MDA) were also investigated. We studied liver injury by means of blood alanine aminotransferase activity (ALT); inducible nitric oxide synthase (iNOS) expression, myeloperoxidase (MPO) activity and tissue edema evaluation. Lung injury was investigated by means of tissue monocyte chemoattractant protein-1 (MCP-1) levels, MPO activity, iNOS expression and edema formation. Trehalose reduced hypotension, NF-kappaB binding activity, IkappaBalpha protein loss and TLR-4 activation. In addition trehalose reduced TNF-alpha, IL-1, IL-6 and MDA levels. Trehalose also blunted liver and lung injury. QENS measurements showed also that trehalose possesses a high "switching off" capability. Sucrose did not modify endotoxic shock-induced sequelae. Trehalose blocked the inflammatory cascade triggered by endotoxin shock, stabilizing the bio-membranes and switching off the water diffusive dynamics.

Polydeoxyribonucleotide improves angiogenesis and wound healing in experimental thermal injury.

OBJECTIVE: Polydeoxyribonucleotide contains a mixture of nucleotides and interacts with adenosine receptors, stimulating vascular endothelial growth factor expression and wound healing. The purpose of this study was to investigate the effect of polydeoxyribonucleotide on experimental burn wounds. DESIGN: Randomized experiment. SETTING: Research laboratory at a university hospital. SUBJECTS: Thermal injury in mice. INTERVENTIONS: Mice were immersed in 80 degrees C water for 10 secs to achieve a deep-dermal second-degree burn. Animals were randomized to receive either polydeoxyribonucleotide (8 mg/kg/day intraperitoneally for 14 days) or its vehicle alone (0.9% NaCl solution at 100 microL/day intraperitoneally). On days 7 and 14 the animals were killed. Blood was collected for tumor necrosis factor-alpha measurement; burn areas were used for histologic and immunohistochemical examination, for the evaluation of vascular endothelial growth factor and nitric oxide synthases by Western blot, and for the determination of wound nitric oxide products. MEASUREMENTS AND MAIN RESULTS: Polydeoxyribonucleotide increased burn wound re-epithelialization and reduced the time to final wound closure. Polydeoxyribonucleotide improved healing of burn wound through increased epithelial proliferation and maturation of the extracellular matrix as confirmed by fibronectin and laminin immunostaining. Polydeoxyribonucleotide also improved neoangiogenesis as suggested by the marked increase in microvessel density and by the robust expression of platelet-endothelial cell adhesion molecule-1. Furthermore, polydeoxyribonucleotide blunted serum tumor necrosis factor-alpha and enhanced inducible nitric oxide synthase and vascular endothelial growth factor expression and the wound content of nitric oxide products. CONCLUSIONS: Our study suggests that polydeoxyribonucleotide may be an effective therapeutic approach to improve clinical outcomes after thermal injury.

Bispectral Index in ICU: correlation with Ramsay Score on assessment of sedation level.

OBJECTIVE: The assessment of sedation level in critically ill patient remains a challenge for the intensivists in order to avoid over- or under-sedation phenomena. Scoring systems commonly used still show some limitation; the introduction of Bispectral Index (an EEG parameter) could bring potential advantages in monitoring sedation. According to the reports, Bispectral Index correlates with levels of sedation on the Ramsay Scale. We report our personal experience in this topic. METHODS: Twenty patients, diagnosed with chronic obstructive pulmonary disease (COPD), were involved in the study. For an optimal adaptation to respiratory prothesis, they were sedated (with Propofol by continuous infusion at an initial dose of 2 mg/kg/h, which could be modulated with steps of 0.5 mg/kg/h), in order to maintain a Ramsay score of 4-5. BIS value was continuously recorded, and manually calculated on a mean average of a minute during the measuring of Ramsay score (T0) and every 30' for 24 hours on par with Ramsay score. EEG, SpO2, non invasive arterial pressure, ventilatory module, ETCO2, FIO2 were also recorded. For the statistic analysis, Friedman test and Spearman coefficient were utilized. Values of p < 0.05 were considered significant. RESULTS: 980 observations were carried out. The variation range of Ramsay Score was between 2 and 6. BIS range varied from 34 to 98. Statistic analysis of the data obtained pointed out some significative correlations, particularly between Ramsay Score and BIS (p < 0.01), and between BIS and dosage of Propofol (p < 0.01). CONCLUSIONS: The results of the study are consistent with those found in the literature on this topic of study. In fact, this study demonstrates the utility of BIS to track levels of consciousness in ICU patients while still maintaining the use of the score systems to care for ICU patients.