Spontaneous coronary artery dissection in a patient with hereditary polycystic kidney disease and a recent liver transplant : a case report

Background Spontaneous coronary artery dissection (SCAD) is an underestimated cause of acute coronary syndromes. A predisposing arteriopathy is often present and a stressor can sometimes be identified. Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder; its associated arteriopathy has been described as a predisposing condition for SCAD. Case summary A 44-year-old woman with ADPKD presented in the emergency room with recent onset thoracic pain radiating to the left arm at rest. She had undergone a recent liver transplant, for which she had received high-dose corticosteroids during 1 month. She was still taking tacrolimus and mycophenolate mofetil. She had no traditional risk factors but had experienced stress post-operatively. She was known with moderate chronic kidney disease. The initial electrocardiogram (ECG) was normal but high-sensitive troponin T was significantly elevated. Coronary angiography demonstrated diffuse narrowing of the distal left anterior descending artery with preserved flow, compatible with a SCAD Type 2 that was treated conservatively. However, under dual antiplatelet therapy (DAPT) with clopidogrel, the coronary dissection was progressive with new ischaemic ECG changes, further rise of troponins and development of apicoseptal hypokinesia. Because of the small vessel diameter and the preserved distal flow, conservative treatment was maintained. Clopidogrel was interrupted and the patient remained stable. Discussion As SCAD remains an underestimated cause of myocardial infarction, clinicians should be aware of the possibility of SCAD in ADPKD patients with chest pain. This case report illustrates that the decision DAPT vs. aspirin should be individualized in these patients

Editorial: Management of right ventricular failure: pathophysiology, medical treatment and use of ventricular assist devices

Left ventricular assist device; Advanced heart failure; Right ventricular failureDispositiu d'assistència ventricular esquerre; Insuficiència cardíaca avançada; Insuficiència del ventricle dretDispositivo de asistencia ventricular izquierda; Insuficiencia cardíaca avanzada; Insuficiencia del ventrículo derech

Prevalence, associated factors and management implications of left ventricular outflow tract obstruction in Takotsubo cardiomyopathy: a two-year, two-center experience

Background: Some patients with Takotsubo cardiomyopathy (TTC) develop cardiogenic shock due to left ventricular outflow tract (LVOT) obstruction -there is, however, a paucity of data regarding this condition. Methods: Prevalence, associated factors and management implications of LVOT obstruction in TTC was explored, based on two-year data from two Belgian heart centres. Results: A total of 32 patients with TTC were identified out of 3,272 patients presenting with troponin-positive acute coronary syndrome. In six patients diagnosed with TTC (19%), a significant LVOT obstruction was detected by transthoracic echocardiography. Patients with LVOT obstruction were older and had more often septal bulging, and presented more frequently in cardiogenic shock as compared to those without LVOT obstruction (P < 0.05). Moreover, all patients with LVOT obstruction showed systolic anterior motion (SAM) of the anterior mitral valve leaflet, which was associated with a higher grade of mitral regurgitation (2.2 +/- 0.7 vs. 1.0 +/- 0.6, P< 0.001). Adequate therapeutic management including fluid resuscitation, cessation of inotropic therapy, intravenous beta-blocker, and the use of intra-aortic balloon pump resulted in non-inferior survival in TTC patients with LVOT obstruction as compared to those without LVOT obstruction. Conclusions: TTC is complicated by LVOT obstruction in approximately 20% of cases. Older age, septal bulging, SAM-induced mitral regurgitation and hemodynamic instability are associated with this condition. Timely and accurate diagnosis of LVOT obstruction by echocardiography is key to successful management of these TTC patients with LVOT obstruction and results in a non-inferior outcome as compared to those patients without LVOT obstruction

Quantitative tandem affinity purification, an effective tool to investigate protein complex composition in plant hormone signaling : strigolactones in the spotlight

Phytohormones tightly regulate plant growth by integrating changing environmental and developmental cues. Although the key players have been identified in many plant hormonal pathways, the molecular mechanisms and mode of action of perception and signaling remain incompletely resolved. Characterization of protein partners of known signaling components provides insight into the formed protein complexes, but, unless quantification is involved, does not deliver much, if any, information about the dynamics of the induced or disrupted protein complexes. Therefore, in proteomics research, the discovery of what actually triggers, regulates or interrupts the composition of protein complexes is gaining importance. Here, tandem affinity purification coupled to mass spectrometry (TAP-MS) is combined with label-free quantification (LFQ) to a highly valuable tool to detect physiologically relevant, dynamic protein-protein interactions in Arabidopsis thaliana cell cultures. To demonstrate its potential, we focus on the signaling pathway of one of the most recently discovered phytohormones, strigolactones

Recessive osteogenesis imperfecta caused by LEPRE1 mutations: clinical documentation and identification of the splice form responsible for prolyl 3-hydroxylation

Abstract: Background: Recessive forms of osteogenesis imperfecta (OI) may be caused by mutations in LEPRE1, encoding prolyl 3-hydroxylase-1 (P3H1) or in CRTAP, encoding cartilage associated protein. These proteins constitute together with cyclophilin B (CyPB) the prolyl 3-hydroxylation complex that hydroxylates the Pro986 residue in both the type I and type II collagen alpha 1-chains. Methods: We screened LEPRE1, CRTAP and PPIB (encoding CyPB) in a European/Middle Eastern cohort of 20 lethal/severe OI patients without a type I collagen mutation. Results: Four novel homozygous and compound heterozygous mutations were identified in LEPRE1 in four probands. Two probands survived the neonatal period, including one patient who is the eldest reported patient (17(7/12) years) so far with P3H1 deficiency. At birth, clinical and radiologic features were hardly distinguishable from those in patients with autosomal dominant (AD) severe/lethal OI. Follow-up data reveal that the longer lived patients develop a severe osteochondrodysplasia that overlaps with, but has some distinctive features from, AD OI. A new splice site mutation was identified in two of the four probands, affecting only one of three LEPRE1 mRNA splice forms, detected in this study. The affected splice form encodes a 736 amino acid (AA) protein with a "KDEL'' endoplasmic reticulum retention signal. While western blotting and immunocytochemical analysis of fibroblast cultures revealed absence of this P3H1 protein, mass spectrometry and SDS-urea-PAGE data showed severe reduction of alpha 1(I) Pro986 3-hydroxylation and overmodification of type I (pro) collagen chains in skin fibroblasts of the patients. Conclusion: These findings suggest that the 3-hydroxylation function of P3H1 is restricted to the 736AA splice form

Identification of Chlamydia trachomatis CT621, a protein delivered through the type III secretion system to the host cell cytoplasm and nucleus

Chlamydiae are obligate intracellular bacteria, developing inside host cells within chlamydial inclusions. From these inclusions, the chlamydiae secrete proteins into the host cell cytoplasm. A pathway through which secreted proteins can be delivered is the type III secretion system (T3SS). The T3SS is common to several gram-negative bacteria and the secreted proteins serve a variety of functions often related to the modulation of host signalling. To identify new potentially secreted proteins, the cytoplasm was extracted from Chlamydia trachomatis L2-infected HeLa cells, and two-dimensional polyacrylamide gel electrophoresis profiles of [35S]-labelled chlamydial proteins from this extract were compared with profiles of chlamydial proteins from the lysate of infected cells. In this way, CT621 was identified. CT621 is a member of a family of proteins containing a domain of unknown function DUF582 that is only found within the genus Chlamydia. Immunofluorescence microscopy and immunoblotting demonstrated that CT621 is secreted late in the chlamydial developmental cycle and that it is the first chlamydial protein found to be localized within both the host cell cytoplasm and the nucleus. To determine whether CT621 is secreted through the T3SS, an inhibitor of this apparatus was added to the infection medium, resulting in retention of the protein inside the chlamydiae. Hence, the so far uncharacterized CT621 is a new type III secretion effector protein

The expression, processing and localization of polymorphic membrane proteins in Chlamydia pneumoniae strain CWL029

BACKGROUND: Chlamydiae are obligate intracellular bacteria, which are important human pathogens. Genome sequences of C. trachomatis and C. pneumoniae have revealed the presence of a Chlamydia specific gene family encoding polymorphic outer membrane proteins, Pmps. In C. pneumoniae the family comprises twenty-one members, which are all transcribed. In the present study, the expression, processing and localisation of the sixteen full-length Pmps in C. pneumoniae strain CWL029 have been further investigated by two-dimensional gel electrophoresis and immunofluorescence microscopy. RESULTS: Ten Pmps were identified in elementary bodies (EBs). Eight of these were investigated with respect to time dependent expression and all were found to be up-regulated between 36 and 48 hours post infection. Antibodies against Pmp6, 8, 10, 11 and 21 reacted with chlamydiae when infected cells were formalin fixed. Pmp6, Pmp20 and Pmp21 were found in cleaved forms, and the cleavage sites of Pmp6 and Pmp21 were identified. CONCLUSIONS: The Pmps are heavily up-regulated at the time of conversion of RB to EB, and at least ten Pmps are present in EBs. Due to their reaction in formalin fixation it is likely that Pmp6, 8, 10, 11 and 21 are surface exposed. The identified cleavage sites of Pmp6 and Pmp21 are in agreement with the theory that the Pmps are autotransporters

Cell-penetrating peptides selectively cross the blood-brain barrier in vivo

Cell-penetrating peptides (CPPs) are a group of peptides, which have the ability to cross cell membrane bilayers. CPPs themselves can exert biological activity and can be formed endogenously. Fragmentary studies demonstrate their ability to enhance transport of differ- ent cargoes across the blood-brain barrier (BBB). However, comparative, quantitative data on the BBB permeability of different CPPs are currently lacking. Therefore, the in vivo BBB transport characteristics of five chemically diverse CPPs, i.e. pVEC, SynB3, Tat 47–57, transportan 10 (TP10) and TP10-2, were determined. The results of the multiple time regression (MTR) analysis revealed that CPPs show divergent BBB influx properties: Tat 47–57, SynB3, and especially pVEC showed very high unidirectional influx rates of 4.73 μl/ (g × min), 5.63 μl/(g × min) and 6.02 μl/(g × min), respectively, while the transportan analogs showed a negligible to low brain influx. Using capillary depletion, it was found that 80% of the influxed peptides effectively reached the brain parenchyma. Except for pVEC, all pep- tides showed a significant efflux out of the brain. Co-injection of pVEC with radioiodinated bovine serum albumin (BSA) did not enhance the brain influx of radiodionated BSA, indicat- ing that pVEC does not itself significantly alter the BBB properties. A saturable mechanism could not be demonstrated by co-injecting an excess dose of non-radiolabeled CPP. No sig- nificant regional differences in brain influx were observed, with the exception for pVEC, for which the regional variations were only marginal. The observed BBB influx transport proper- ties cannot be correlated with their cell-penetrating ability, and therefore, good CPP proper- ties do not imply efficient brain influx