Comparison of textilinin-1 with aprotinin as serine protease inhibitors and as antifibrinolytic agents

Textilinin-1 (Q8008) was isolated from the venom of the Pseudonaja textilis and has a 47% sequence identity to the antihaemorrhagic therapeutic agent aprotinin. When equimolar concentrations of enzyme and aprotinin were pre-incubated, plasmin was inhibited 100%, plasma kallikrein 58%, and tissue kallikrein 99%. Under the same conditions, textilinin-1 inhibited plasmin 98%, plasma kallikrein 16% and tissue kallikrein 17%. Whole blood clot lysis was inhibited strongly by both aprotinin and textilinin-1, as shown by thrombelastography. At 2 microM inhibitor lysis initiated by t-PA was greater than 99% inhibited by aprotinin (LY60 = 0.4 +/- 0.1) whereas textilinin-1, inhibited lysis by 91% (LY60 = 8.9 +/- 0.7). The same trend was found with the lysis of euglobulin fractions. From these data textilinin-1 appears to be a more specific plasmin inhibitor than aprotinin but aprotinin inhibits clot lysis to a greater extent.     

The use of PTFE graft to correct anomalous drainage of persistent left superior vena cava

A new technique to correct persistent left superior vena cava (LSVC) drainage into the left atrium is described in a 14-year-old patient with situs inversus, left atrial isomerism common atrium, and mitral valve regurgitation. During surgery, occlusion of the LSVC markedly increased the venous pressure, precluding its ligation. Because of the malposition of the heart and the unusual atrial anatomy, correction with an intra-atrial baffle was not attempted. After correcting the intra-cardiac anomaly, the LSVC was divided and anastomosed to the "right" atrial appendage using a segment of PTFE graft. The postoperative course was uneventful and an angiogram demonstrated excellent performance of the graft.     

Maldistribution of pulmonary blood flow in patients after the Fontan operation is associated with worse exercise capacity

Background

Maldistribution of pulmonary artery blood flow (MPBF) is a potential complication in patients who have undergone single ventricle palliation culminating in the Fontan procedure. Cardiovascular magnetic resonance (CMR) is the best modality that can evaluate MPBF in this population. The purpose of this study is to identify the prevalence and associations of MPBF and to determine the impact of MPBF on exercise capacity after the Fontan operation.

Methods

This retrospective single-center study included all patients after Fontan operation who had maximal cardiopulmonary exercise test (CPET) and CMR with flow measurements of the branch pulmonary arteries. MPBF was defined as >?20% difference in branch pulmonary artery flow. Exercise capacity was measured as percent of predicted oxygen consumption at peak exercise (% predicted VO₂). Linear and logistic regression models were used to determine univariate and multivariable predictors of exercise capacity and correlates of MPBF, respectively.

Results

A total of 147 patients who had CMR between 1999 and 2017 were included (median age at CMR 21.8?years [interquartile range (IQR) 16.5–30.6]) and the median time between CMR and CPET was 2.8?months [IQR 0–13.8]. Fifty-three patients (36%) had MPBF (95% CI 29–45%). The mean % predicted VO₂ was 63?±?16%. Patients with MPBF had lower mean % predicted VO₂ compared to patients without MPBF (60?±?14% versus 65?±?16%, p?=?0.04). On multivariable analysis, a lower % predicted VO₂ was independently associated with longer time since Fontan, higher ventricular mass-to-volume ratio, and MPBF. On multivariable analysis, only compression of the branch pulmonary arteries by the ascending aorta or aortic root was associated with MPBF (OR 6.5, 95% CI 5.6–7.4, p?<?0.001).

Conclusion

In patients after the Fontan operation, MPBF is common and is independently associated with lower exercise capacity. MPBF was most likely to be caused by pulmonary artery compression by the aortic root or the ascending aorta. This study identifies MPBF as an important risk factor and as a potential target for therapeutic interventions in this fragile patient population.

     

Interdigestive motility pattern in subjects with duodenogastric bile reflux

The role of antroduodenal motility in the pathogenesis of duodenogastric biliary reflux is widely accepted, but few and conflicting data are available on the possible motor abnormalities related to this phenomenon in the fed and in the fasting state. In an attempt to define the motility pattern of the antroduodenal region associated with bile reflux in the fasting state, 20 subjects with proven duodenogastric reflux and without disorders of the upper gastrointestinal tract have been studied, and the results have been compared with those observed in 6 control subjects without evidence of reflux. The interdigestive motility complex (IDMC) has been evaluated (mean duration of IDMC and frequency and site of onset of migrating motor complexes). In subjects with duodenogastric reflux a significant increase (p less than 0.01) in the mean duration of IDMCs (179 +/- 22.19 min) was observed, in comparison with controls (108.5 +/- 37 min). A considerable reduction in the frequency of migrating motor complexes (MMC) was also observed, while no differences in the site of onset and the propagation of MMCs and in the percentage of time recorded occupied by the single phases of IDMC were found. This evidence suggests a strict relationship between duodenogastric reflux and the occurrence of phase III of IDMC and supports the hypothesis that the IDMC abnormalities are the cause and not the consequence of biliary reflux. The reduced incidence of MMC may also account for the high incidence of chronic gastritis due to prolonged contact in the fasting state between the gastric mucosa and the duodenal content.     

Cloning and functional expression of venom prothrombin activator protease from Pseudonaja textilis with whole blood procoagulant activity

The snake venom group C prothrombin activators contain a number of components that enhance the rate of prothrombin activation. The cloning and expression of full-length cDNA for one of these components, an activated factor X (factor Xa)-like protease from Pseudonaja textilis as well as the generation of functional chimeric constructs with procoagulant activity were described. The complete cDNA codes for a propeptide, light chain, activation peptide (AP) and heavy chain related in sequence to mammalian factor X. Efficient expression of the protease was achieved with constructs where the AP was deleted and the cleavage sites between the heavy and light chains modified, or where the AP was replaced with a peptide involved in insulin receptor processing. In human kidney cells (H293F) transfected with these constructs, up to 80% of the pro-form was processed to heavy and light chains. Binding of the protease to barium citrate and use of specific antibodies demonstrated that gamma-carboxylation of glutamic acid residues had occurred on the light chain in both cases, as observed in human factor Xa and the native P. textilis protease. The recombinant protease caused efficient coagulation of whole citrated blood and citrated plasma that was enhanced by the presence of Ca2+. This study identified the complete cDNA sequence of a factor Xa-like protease from P. textilis and demonstrated for the first time the expression of a recombinant form of P. textilis protease capable of blood coagulation.     

Hood Colonoscopy in Trainees: A Useful Adjunct to Improve the Performance

Background

The use of a transparent hood to improve colonoscopic performance has recently been proposed.

Aims

The purpose of this study was to evaluate whether using the hood might improve the cecal intubation rate, cecal intubation time, number of attempts needed to intubate the ileo-cecal valve, and polyp detection rate in trainees.

Methods

Patients undergoing colonoscopy (n = 378) were randomized in two groups, one studied with hood colonoscopy (n = 179) and the other (n = 199) with standard examination.

Results

No differences were found between hood and standard colonoscopy with respect to cecal intubation rate (95 vs 92 %), whereas hood colonoscopy significantly shortened the cecal intubation time, the number of attempts needed to intubate the ileo-cecal valve, and the overall polyp detection rate (p < 0.01 for all these variables).

Conclusions

Hood colonoscopy might represent a useful adjunct to standard colonoscopy, especially improving the performance of endoscopic trainees.