Right-to-left shunt with hypoxemia in pulmonary hypertension

<p>Abstract</p> <p>Background</p> <p>Hypoxemia is common in pulmonary hypertension (PH) and may be partly related to ventilation/perfusion mismatch, low diffusion capacity, low cardiac output, and/or right-to-left (RL) shunting.</p> <p>Methods</p> <p>To determine whether true RL shunting causing hypoxemia is caused by intracardiac shunting, as classically considered, a retrospective single center study was conducted in consecutive patients with precapillary PH, with hypoxemia at rest (PaO₂< 10 kPa), shunt fraction (Qs/Qt) greater than 5%, elevated alveolar-arterial difference of PO₂(AaPO₂), and with transthoracic contrast echocardiography performed within 3 months.</p> <p>Results</p> <p>Among 263 patients with precapillary PH, 34 patients were included: pulmonary arterial hypertension, 21%; PH associated with lung disease, 47% (chronic obstructive pulmonary disease, 23%; interstitial lung disease, 9%; other, 15%); chronic thromboembolic PH, 26%; miscellaneous causes, 6%. Mean pulmonary artery pressure, cardiac index, and pulmonary vascular resistance were 45.8 ± 10.8 mmHg, 2.2 ± 0.6 L/min/m², and 469 ± 275 dyn.s.cm^-5, respectively. PaO₂in room air was 6.8 ± 1.3 kPa. Qs/Qt was 10.2 ± 4.2%. AaPO₂under 100% oxygen was 32.5 ± 12.4 kPa. Positive contrast was present at transthoracic contrast echocardiography in 6/34 (18%) of patients, including only 4/34 (12%) with intracardiac RL shunting. Qs/Qt did not correlate with hemodynamic parameters. Patients' characteristics did not differ according to the result of contrast echocardiography.</p> <p>Conclusion</p> <p>When present in patients with precapillary PH, RL shunting is usually not related to reopening of patent <it>foramen ovale</it>, whatever the etiology of PH.</p

Conditional Transgenesis Using Dimerizable Cre (DiCre)

Cre recombinase is extensively used to engineer the genome of experimental animals. However, its usefulness is still limited by the lack of an efficient temporal control over its activity. We have recently developed a conceptually new approach to regulate Cre recombinase, that we have called Dimerizable Cre or DiCre. It is based on splitting Cre into two inactive moieties and fusing them to FKBP12 (FK506-binding protein) and FRB (binding domain of the FKBP12-rapamycin associated protein), respectively. These latter can be efficiently hetero-dimerized by rapamycin, leading to the reinstatement of Cre activity. We have been able to show, using in vitro approaches, that this ligand-induced dimerization is an efficient way to regulate Cre activity, and presents a low background activity together with a high efficiency of recombination following dimerization. To test the in vivo performance of this system, we have, in the present work, knocked-in DiCre into the Rosa26 locus of mice. To evaluate the performance of the DiCre system, mice have been mated with indicator mice (Z/EG or R26R) and Cre-induced recombination was examined following activation of DiCre by rapamycin during embryonic development or after birth of progenies. No recombination could be observed in the absence of treatment of the animals, indicating a lack of background activity of DiCre in the absence of rapamycin. Postnatal rapamycin treatment (one to five daily injection, 10 mg/kg i.p) induced recombination in a number of different tissues of progenies such as liver, heart, kidney, muscle, etc. On the other hand, recombination was at a very low level following in utero treatment of DiCre×R26R mice. In conclusion, DiCre has indeed the potentiality to be used to establish conditional Cre-deleter mice. An added advantage of this system is that, contrary to other modulatable Cre systems, it offers the possibility of obtaining regulated recombination in a combinatorial manner, i.e. induce recombination at any desired time-point specifically in cells characterized by the simultaneous expression of two different promoters

Efficacy of Dabrafenib plus Trametinib plus trametinib combinationin patients with BRAF V600E-mutant NSCLC in real word setting

International audienc

Impact of Gluma Desensitizer on the tensile strength of zirconia crowns bonded to dentin: an in vitro study

This study tested the impact of Gluma Desensitizer on the tensile strength of zirconia crowns bonded to dentin. Human teeth were prepared and randomly divided into six groups (N = 144, n = 24 per group). For each tooth, a zirconia crown was manufactured. The zirconia crowns were cemented with: (1) Panavia21 (PAN), (2) Panavia21 combined with Gluma Desensitizer (PAN-G), (3) RelyX Unicem (RXU), (4) RelyX Unicem combined with Gluma Desensitizer (RXU-G), (5) G-Cem (GCM) and (6) G-Cem combined with Gluma Desensitizer (GCM-G). The initial tensile strength was measured in half (n = 12) of each group and the other half (n = 12) subjected to a chewing machine (1.2 Mio, 49 N, 5°C/50°C). The cemented crowns were pulled in a Universal Testing Machine (1 mm/min, Zwick Z010) until failure occurred and tensile strength was calculated. Data were analyzed with one-way and two-way ANOVA followed by a post hoc Scheffé test, t test and Kaplan-Meier analysis with a Breslow-Gehan analysis test (α = 0.05). After the chewing simulation, the self-adhesive resin cements combined with Gluma Desensitizer showed significantly higher tensile strength (RXU-G, 12.8 ± 4.3 MPa; GCM-G, 13.4 ± 6.2 MPa) than PAN (7.3 ± 1.7 MPa) and PAN-G (0.9 ± 0.6). Within the groups, PAN, PAN-G and RXU resulted in significantly lower values when compared to the initial tensile strength; the values of all other test groups were stable. In this study, self-adhesive resin cements combined with Gluma Desensitizer reached better long-term stability compared to PAN and PAN-G after chewing simulation