Effect of positive end-expiratory pressure on pulmonary shunt and dynamic compliance during abdominal surgery.

BACKGROUND: General anaesthesia decreases pulmonary compliance and increases pulmonary shunt due to the development of atelectasis. The presence of capnoperitoneum during laparoscopic surgery may further decrease functional residual capacity, promoting an increased amount of atelectasis compared with laparotomy. The aim of this study was to evaluate the effects of different levels of positive end-expiratory pressure (PEEP) in both types of surgery and to investigate whether higher levels of PEEP should be used during laparoscopic surgery. METHODS: This prospective observational study included 52 patients undergoing either laparotomy or laparoscopic surgery. Three levels of PEEP were applied in random order: (1) zero (ZEEP), (2) 5 cmH2O and (3) 10 cmH2O. Pulmonary shunt and ventilation/perfusion mismatch were assessed by the automatic lung parameter estimator system. RESULTS: Pulmonary shunt was similar in both groups. However, in laparotomy, a PEEP of 5 cmH2O significantly decreased shunt when compared with ZEEP (12 vs 6%; P=0.001), with additional PEEP having no further effect. In laparoscopic surgery, a significant reduction in shunt (13 vs 6%; P=0.001) was obtained only at a PEEP of 10 cmH2O. Although laparoscopic surgery was associated with a lower pulmonary compliance, increasing levels of PEEP were able to ameliorate it in both groups. CONCLUSION: Both surgeries have similar negative effects on pulmonary shunt, while the presence of capnoperitoneum reduced only the pulmonary compliance. It appears that a more aggressive PEEP level is required to reduce shunt and to maximize compliance in case of laparoscopic surgery.

SINEUPs: A new class of natural and synthetic antisense long non-coding RNAs that activate translation.

Over the past 10 years, it has emerged that pervasive transcription in mammalian genomes has a tremendous impact on several biological functions. Most of transcribed RNAs are lncRNAs and repetitive elements. In this review, we will detail the discovery of a new functional class of natural and synthetic antisense lncRNAs that stimulate translation of sense mRNAs. These molecules have been named SINEUPs since their function requires the activity of an embedded inverted SINEB2 sequence to UP-regulate translation. Natural SINEUPs suggest that embedded Transposable Elements may represent functional domains in long non-coding RNAs. Synthetic SINEUPs may be designed by targeting the antisense sequence to the mRNA of choice representing the first scalable tool to increase protein synthesis of potentially any gene of interest. We will discuss potential applications of SINEUP technology in the field of molecular biology experiments, in protein manufacturing as well as in therapy of haploinsufficiencies.

Effect of warfarin treatment on thrombin activatable fibrinolysis inhibitor (TAFI) activation and TAFI-mediated inhibition of fibrinolysis.

BACKGROUND: Severe clotting deficiencies are associated with enhanced in vitro fibrinolysis due to insufficient thrombin activatable fibrinolysis inhibitor (TAFI) activation. Because oral anticoagulant therapy (OAT) with warfarin causes a partial deficiency of vitamin K-dependent factors, its effect on clot lysability remains unclear. OBJECTIVES: To evaluate plasma and blood fibrinolytic capacity in patients under stable OAT (n = 221) as compared with controls (n = 132). METHODS: Fibrinolysis resistance of plasma (turbidimetry) and blood (thromboelastography) clots was calculated as the lysis time of tissue factor-induced clots exposed to 30 and 100 ng mL(-1) t-PA, respectively. RESULTS: Plasma PAI-1 was similar in the two groups, whereas TAFI was slightly lower in patients. OAT plasma clots lysed faster than controls (P = 0.001). The addition of the TAFIa inhibitor PTCI reduced lysis time by 14% in OAT and 34% in controls, and the difference between the groups disappeared. Similar data were obtained with blood clots. Thrombin and TAFIa generation in OAT plasma amounted to roughly 50% of controls, supporting a reduced thrombin-dependent TAFI activation. Clot resistance of OAT plasma was normalized by Ba-citrate plasma eluate or prothrombin but not by BaSO(4) serum eluate, rFVIIa or FX. Surprisingly, circulating levels of TAFIa and its inactive derivative TAFIai were higher in warfarin patients (P < 0.0001) and correlated with plasmin-antiplasmin (P = 0.0001) but not with prothrombin F(1) (+) (2) . CONCLUSIONS: OAT enhances both plasma and blood fibrinolysis by reducing thrombin-dependent TAFI activation, a phenomenon largely determined by low prothrombin levels. At variance with in vitro data, 'basal' in vivo TAFIa/ai levels seem related to plasmin rather than thrombin generation.

The role of thrombin activatable fibrinolysis inhibitor and factor XI in platelet-mediated fibrinolysis resistance: a thromboelastographic study in whole blood.

BACKGROUND: The resistance of platelet-rich thrombi to fibrinolysis is generally attributed to clot retraction and platelet PAI-1 release. The role of TAFI in platelet-mediated resistance to lysis is unclear. OBJECTIVE: We investigated the contribution of TAFI to the antifibrinolytic effect of platelets in whole blood by thromboelastography. METHODS: Platelet-poor (PP-WB, < 40 × 10(3) µL(-1) ) and platelet-rich (PR-WB, > 400 × 10(3) µL(-1) ) blood samples were obtained from normal human blood (N-WB, 150-220 × 10(3) µL(-1) ). Clot lysis time was measured by thromboelastography in recalcified blood supplemented with t-PA (100 ng mL(-1) ) and tissue factor (1:1000 Recombiplastin). RESULTS: t-PA-induced lysis time increased in parallel with platelet concentration (up to 3-fold). Neutralization of TAFI, but not of PAI-1, shortened the lysis time by ∼ 50% in PR-WB and by < 10% in PP-WB. Accordingly, prothrombin F1+2 and TAFIa accumulation was greater in PR-WB than in PP-WB. A similar TAFI-dependent inhibition of fibrinolysis was observed when clot retraction was prevented by cytochalasin D or abciximab, or when platelet membranes were tested. Moreover, in blood with an intact contact system, platelet-mediated fibrinolysis resistance was attenuated by an anti-FXI but not by an anti F-XII antibody. Finally, platelets made the clots resistant to the profibrinolytic effect of heparin concentrations displaying a strong anticoagulant activity. CONCLUSIONS: Our data indicate that TAFI activation is one major mechanism whereby platelets make clots resistant to fibrinolysis and underscore the importance of TAFI inhibitors as new antithrombotic agents.

Assessment of ground water quality in a fractured aquifer under continue wastewater injection.

Experimental studies have been carried out in a fractured coastal aquifer of the Salento Region (Nardò (Le), Italy), subject since 1991 to injection of 12,000 m3/d of treated municipal wastewater in a natural sink. The analytical parameters of ground water sampled in monitoring wells, have been compared before and after the injection started. The mound of water table (1.5 m), the reduction of seawater extent of 2 km and the spreading of pollutants injected were evaluated by means of mathematical model results. After ten years operation, the volume of the available resource for agricultural and drinking use has been increased, without notable decrease of the preexistent ground water quality. Moreover for preserving such resource from pollution, the mathematical model allowed the standards of wastewater quality for recharge to be identified. Around the sink, a restricted area was also defined with prohibition of withdrawals, to avoid infection and other risks on human health.