The effect of liver transplantation on circulating levels of estradiol and progesterone in male patients: parallelism with hepatopulmonary syndrome and systemic hyperdynamic circulation improvement

The correction of hepatopulmonary syndrome (HPS) after liver transplantation (LT) remains controversial. The aims of our study were to: 1) analyze whether LT reverses HPS; 2) note any relationship between HPS and the systemic hemodynamic disturbance; and 3) note changes in circulating sex hormones and the possible association with pulmonary and systemic hemodynamic changes. Systemic hemodynamic parameters, cardiac output and systemic vascular resistance (SVR), sex hormones, and intrapulmonary vasodilatation assessed by contrast transesophageal echocardiography, and gas exchange abnormalities were investigated in 19 patients with advanced cirrhosis prior to and 6 months (176.8+/-30 days) after LT. LT was followed by a marked reduction in cardiac output (6.6+/-1.7 vs 3.5+/-0.5 l/min; p<0.001) and SVR (1039+/-460 vs 1978+/-294 dyn x sec x cm(-5); p<0.005). Before LT, circulating estradiol and progesterone levels were invariably elevated (66+/-22 pg/ml and 1.8+/-1.1 ng/ml, respectively, normal values <31 pg/ml and 0.35 ng/ml, respectively), and dropped after LT (28+/-12 pg/ml p<0.001 and 0.38+/-0.2 ng/ml; p<0.001, respectively). Seventeen of 19 patients had intrapulmonary vasodilatation and increased alveolar-arterial oxygen difference, thereby fulfilling diagnostic criteria for HPS. Patients with HPS presented higher cardiac output (p<0.05), lower SVR (p<0.01), and higher progesterone and estradiol levels than patients without HPS (p<0.05). LT produced normalization of intrapulmonary vasodilatation in all patients. LT normalized hyperdynamic circulation and is a useful therapeutic option in patients with HPS. Normalization of sex hormone levels after LT suggests that they could play a pathogenic role in the development of HPS.     

Rescue percutaneous coronary intervention for failed thrombolysis in a patient with anomalous coronary arteries

Coronary artery anomalies (CAA) often render technically difficult the completion of coronary angiography and intervention. Their presence in patients undergoing emergency angiography for acute myocardial infarction (AMI) is particularly challenging for interventional cardiologists. In this article, we report, for the first time in the literature, a case of rescue percutaneous coronary intervention for failed thrombolysis in a patient with AMI due to occlusion of a left circumflex coronary artery with anomalous origin from right sinus of Valsalva (in an anomalous left coronary system also including an anomalous origin of the left anterior descending artery from the right sinus). In particular, the present clinical vignette emphasizes the importance of a thorough search for the culprit vessel during cardiac catheterization. Especially in the emergency setting, non-invasive methods of ischemia localization, such as ST-segment elevation at the ECG and wall motion abnormalities at echocardiography, are of pivotal usefulness to guide the interventional cardiologist in identifying and treating the diseased coronary vessel in a timely and effective fashion.     

Differential recognition of a tyrosine-dependent signal in the basolateral and endocytic pathways of thyroid epithelial cells

Trafficking of receptors is of crucial importance for the physiology of most exocrine and endocrine organs. It is not known yet if the same mechanisms are used for sorting in the exocytic and endocytic pathways in the different epithelial tissues. In this work, we have used a deletion mutant of the human neurotrophin receptor p75(hNTR) that is normally localized on the apical membrane when expressed in Madin-Darby canine kidney cells. This internal 57-amino acid deletion of the cytoplasmic tail leads to a relocation of the protein from the apical to the basolateral membrane and to rapid and efficient endocytosis. These events are mediated by a signal localized within 9 amino acids of the mutated cytoplasmic tail that is strictly dependent on a tyrosine residue (Tyr-308). We have analyzed the basolateral sorting efficiency and endocytic capacity of this signal in Fischer rat thyroid (FRT) cells, in which basolateral and endocytic determinants have not yet been identified. We found that this targeting signal can mediate efficient transport to the basolateral membrane also in FRT cells with similar tyrosine dependence as in MDCK cells. In contrast to MDCK cells, this Tyr-based signal was not able to mediate coated pits localization and endocytosis in FRT cells. These data represent the first characterization of basolateral/endocytic signals in thyroid epithelial cells. Furthermore, our results indicate that requirements for tyrosine-dependent basolateral sorting signals are conserved among cell lines from different tissues but that the recognition of the colinear endocytic signal is tissue specific.     

The acid-labile subunit of human ternary insulin-like growth factor-binding protein complex in girls with central precocious puberty before and during gonadotropin-releasing hormone analog therapy

The aim of the study was to evaluate serum acid-labile subunit (ALS) concentrations and their relationship with other parameters of the human ternary IGF-I-binding protein (IGFBP) complex in girls with central precocious puberty (CPP) before and after pharmacological arrest of puberty. We studied serum ALS, free IGF-I, total IGF-I, IGFBP-3 levels and IGFBP-3 protease activity in 13 girls, aged 1.6-7.8 yr (mean, 5.9 +/- 2.2), diagnosed as having CPP before and after 6 and 12 months of GnRH analog (GnRHa) therapy. The ALS SD score before treatment was high (1.4 +/- 0.72) and decreased significantly after 6 and 12 months of GnRHa therapy [0.4 +/- 0.54 (P < 0.01) and -0.4 +/- 0.61 (P < 0.01), respectively]. Serum IGF-I and IGFBP-3 were also increased before treatment, but both of these factors remained elevated after 6 and 12 months of GnRH-A therapy [IGF-I SD score, 3.20 +/- 1.64, 2.92 +/- 1.82, and 3.68 +/- 1.94 (P = NS), respectively; IGFBP-3 SD score, 1.02 +/- 0.53, 0.94 +/- 0.68, and 1.22 +/- 0.87 (P = NS), respectively]. Serum free IGF-I levels and IGFBP-3 proteolytic activity did not vary significantly from their pretreatment values during GnRHa therapy. In conclusion, serum ALS levels were elevated in girls with CPP and decreased significantly during the first year of GnRHa therapy. Serum IGF-I and IGFBP-3 levels were also increased before therapy, but their levels were not influenced by treatment. The ALS decrease seems to be the sole GH-dependent factor that parallels the decreases in steroid levels and growth velocity during GnRHa therapy.     

Impact of drug-eluting balloon (pre- or post-) dilation on neointima formation in de novo lesions treated by bare-metal stent: the IN-PACT CORO trial

The efficacy of DEB in modifying the high restenosis risk associated with BMS implantation is doubtful. Optical coherence tomography (OCT) may allow precise assessment of neointimal formation after stent implantation. We performed a single-center, prospective, 1:2 randomized trial comparing BMS implantation alone (BMS group) vs. additional DEB (DEB group). DEB patients were further randomized 1:1 to DEB before stenting (pre-DEB group), or after stenting (post-DEB group). Primary endpoint was OCT-assessed neointimal hyperplasia (expressed both as mean in-stent neointimal area and as percentage obstruction of the mean stent area) at 6 months. Secondary endpoints were the percentage of uncovered and malapposed stent struts. Thirty patients were enrolled and randomized to BMS (n = 10), pre-DEB (n = 10), post-DEB (n = 10). At 6-month OCT follow-up, DEB significantly reduced neointimal area compared with BMS: mean neointimal area 2.01 ± 0.89 vs. 3.03 ± 1.07 mm² (p = 0.02), percentage area obstruction 24.56 ± 12.50 vs. 37.51 ± 12.26 % (p = 0.02). The percentage of uncovered and malapposed stent struts did not differ significantly between BMS and DEB. In the comparison between pre-DEB and post-DEB, no significant difference was observed for both primary and secondary endpoints. In de novo coronary lesions treated with BMS, DEB use could be associated with a mild reduction in neointimal hyperplasia at 6 months; this effect could be unrelated to the timing of DEB dilation (pre- or post-stenting).Clinical Trial Registration Information: http://www.clinicaltrials.gov. Identifier: NCT01057563.     

Endothelin-1 and acute myocardial infarction: a no-reflow mediator after successful percutaneous myocardial revascularization.

AIMS: No-reflow after a primary percutaneous coronary intervention (PCI) is associated with a high incidence of left ventricular (LV) failure and a poor prognosis. Endothelin-1 (ET-1) is a potent endothelium-derived vasoconstrictor peptide and an important modulator of neutrophil function. Elevated systemic ET-1 levels have recently been reported to predict a poor prognosis in patients with acute myocardial infarction (AMI) treated by primary PCI. We aimed to investigate the relationship between systemic ET-1 plasma levels and no-reflow in a group of AMI patients treated by primary PCI. METHODS AND RESULTS: A group of 51 patients (age 59+/-9.9 years, 44 males) with a first AMI, undergoing successful primary or rescue PCI, were included in the study. Angiographic no-reflow was defined as coronary TIMI flow grade < or =2 or TIMI flow 3 with a final myocardial blush grade < or =2. Blood samples were obtained from all patients on admission for ET-1 levels measurement. No reflow was observed in 31 patients (61%). Variables associated with no-reflow at univariate analysis included culprit lesion of the left anterior coronary descending artery (LAD) (67 vs. 29%, P=0.006) and ET-1 plasma levels (3.95+/-0.7 vs. 3.3+/-0.8 pg/mL, P=0.004). At multivariable logistic regression analysis, ET-1 was the only significant predictor of no-reflow (P=0.03) together with LAD as the culprit vessel (P=0.04). CONCLUSION: ET-1 plasma levels predict angiographic no-reflow after successful primary or rescue PCI. These findings suggest that ET-1 antagonists might be beneficial in the management of no-reflow.