Strong interactions between lipids and proteins occur primarily through association of charged headgroups and amino acid side chains, rendering the protonation status of both partners important. Here ...we use native mass spectrometry to explore lipid binding as a function of charge of the outer membrane porin F (OmpF). We find that binding of anionic phosphatidylglycerol (POPG) or zwitterionic phosphatidylcholine (POPC) to OmpF is sensitive to electrospray polarity while the effects of charge are less pronounced for other proteins in outer or mitochondrial membranes: the ferripyoverdine receptor (FpvA) or the voltage-dependent anion channel (VDAC). Only marginal charge-induced differences were observed for inner membrane proteins: the ammonia channel (AmtB) or the mechanosensitive channel. To understand these different sensitivities, we performed an extensive bioinformatics analysis of membrane protein structures and found that OmpF, and to a lesser extent FpvA and VDAC, have atypically high local densities of basic and acidic residues in their lipid headgroup-binding regions. Coarse-grained molecular dynamics simulations, in mixed lipid bilayers, further implicate changes in charge by demonstrating preferential binding of anionic POPG over zwitterionic POPC to protonated OmpF, an effect not observed to the same extent for AmtB. Moreover, electrophysiology and mass-spectrometry–based ligand-binding experiments, at low pH, show that POPG can maintain OmpF channels in open conformations for extended time periods. Since the outer membrane is composed almost entirely of anionic lipopolysaccharide, with similar headgroup properties to POPG, such anionic lipid binding could prevent closure of OmpF channels, thereby increasing access of antibiotics that use porin-mediated pathways.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Intravascular Imaging for Venous Interventions Brar, Vijaywant; Dhawan, Rahul; Secemsky, Eric A. ...
Current cardiovascular imaging reports,
06/2020, Volume:
13, Issue:
6
Journal Article
Peer reviewed
Purpose of Review
This review surveys the clinical landscape of intravascular imaging for endovenous interventions.
Recent Findings
Endovascular imaging has become increasingly important for ...diagnosing venous pathology and guiding venous interventions. In particular, intravascular ultrasound (IVUS) provides 3D high-resolution cross-sectional imaging of vessel and surrounding tissues, often in anatomic locations inaccessible to surface ultrasound, namely the superior vena cava, inferior vena cava, and caval-iliac veins.
Summary
Current well-established indications for venous IVUS include diagnostic studies, venoplasty, transjugular intrahepatic portosystemic shunt (TIPS) creation, inferior vena cava filter placement, and transjugular liver biopsy. In the future, optical coherence tomography may play an increasing role in venous assessment and intervention.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Plasminogen has been implicated in extracellular matrix degradation by invading cells, but few high affinity cell surface receptors for the molecule have been identified. Previous studies have ...reported that the plasma protein, histidine-rich glycoprotein (HRG), interacts with plasminogen and cell surfaces, raising the possibility that HRG may immobilize plasminogen/plasmin to cell surfaces. Here we show, based on optical biosensor analyses, that immobilized HRG interacts with soluble plasminogen with high affinity and with an extremely slow dissociation rate. Furthermore, the HRG-plasminogen interaction is lysine-dissociable and involves predominately the amino-terminal domain of HRG, and the fifth kringle domain of plasminogen, but not the carboxyl-terminal lysine of HRG. HRG was also shown to tether plasminogen to cell surfaces, with this interaction being potentiated by elevated Zn2+ levels and low pH, conditions that prevail at sites of tissue injury, tumor growth, and angiogenesis. Based on these data we propose that HRG acts as a soluble adaptor molecule that binds to cells at sites of tissue injury, tumor growth, and angiogenesis, providing a high affinity receptor for tethering plasminogen to the cell surface and thereby enhancing the migratory potential of cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The therapeutic efficacy of anticancer drugs like doxorubicin can be significantly increased by their incorporation into liposomes, but an ability to actively target the drug-containing liposomes to ...tumors could well provide an even greater curative effect. In this work, a commercial preparation of doxorubicin-loaded liposomes (Caelyx) was modified by incorporation of the metal chelator lipid 3(nitrilotriacetic acid)-ditetradecylamine (NTA3-DTDA) to enable engraftment of histidine-tagged targeting molecules. Our results show that when engrafted with p15-RGR, a His-tagged peptide containing a sequence purported to bind platelet-derived growth factor receptor β (PDGFRβ), NTA3-DTDA-containing Caelyx (3NTA-Caelyx) can be targeted to NIH-3T3 cells in vitro, leading to increased cytotoxicity compared with non-targeted 3NTA-Caelyx. PDGFRβ is known to be expressed on pericytes in the tumor vasculature; however, when radiolabeled p15-RGR liposomes were administered to mice bearing subcutaneous B16-F1 tumors, minimal accumulation into tumors was observed. In contrast, an alternative targeting peptide, p46-RGD, was found to actively direct liposomes to tumors (4.7 %ID/g). Importantly, when injected into tumor-bearing mice, p46-RGD-engrafted 3NTA-Caelyx significantly decreased the tumor growth rate compared with controls. These results indicate that the incorporation of NTA3-DTDA into liposomal drugs could represent a simple modification to the drug to allow engraftment of targeting molecules and to increase its efficacy.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background: Traumatic brain injury (TBI) is the leading cause of mortality and invalidity worldwide.
Objective: To explore whether traumatic brain injury may be a risk factor for subsequent stroke ...and to evaluate the role of other risk factors correlated with TBI and stroke.
Methods: We analysed 643 patients presented in the emergency department of Trauma UHC, from 1stof June 2011 - 1st of December 2011. We evaluated the following factors: age, gender, and severity of head trauma, type of head trauma, systemic hypertension, atrial fibrillation, and diabetes mellitus.
Results: During 1-year of follow upperiod 32 (4.97%) strokes occurred in TBI patients. The evaluation was done in correlation with the other risk factors taken into account in the study.
Conclusions: The role of TBI is underestimated in the evaluation of stroke. This study demonstrated that during the first year after TBI, 13.53 % of patients experienced stroke. After careful statistical cor-relations with the selected co-morbidities, we found that the diagnosis of stroke was strongly related with TBI.
Erectile dysfunction (ED) develops owing to psychogenic, organic or/and both of these two factors. The aim of this study was to investigate the relationship between penile cavernosal arterial flow ...and peripheral atherosclerosis in men with ED. This study was conducted on 102 patients who had presented to Radiology Clinic with a prediagnosis of ED. Diabetes, hypertension (HT) and smoking were recorded. Blood were taken from all patients for analysis of fasting blood glucose, total cholesterol and high-density lipoprotein level. All the patients underwent high-resolution penile colour Doppler ultrasound (CDUS). The peak-systolic velocity and the end-diastolic velocity values in the bilateral cavernosal arteries were recorded. At the same session, all the patients underwent evaluation for bilateral common carotid artery and femoral artery intima media thickness and for the presence of atherosclerotic plaque. Patients were classified as ED of arterial origin and non-arterial origin according to penile CDUS findings. Of the total 102 patients, 43 (42.2%) had arterial ED and the remaining 59 (57.8%) were contained in non-arterial ED. There was a significant difference between groups for diabetes mellitus (DM), HT, atherosclerotic cardiovascular diseases (ACVD) and total cholesterol level (P<0.05). There was also a significant difference between groups for the presence of plaque in the carotid and the femoral artery (P<0.05). The relationship between smoking and arterial ED was not found to be statistically significant (P>0.05). Non-diagnosed or silent DM, HT and ACVD can have roles in the etiology of arterial ED. Patients who are diagnosed as having arterial ED with Doppler Ultrasound should also be evaluated with B-mode ultrasonography for other peripheral vascular atherosclerotic processes. In this way, subclinical cases can be detected and further possible complications can be avoided.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Magnesium Reabsorbable Scaffold (MRS), is the newest reabsorbable technology with low thrombogenicity, short scaffolding time and almost complete resorption at 12-months (95%). Preliminary 12-months ...data in selected patients has shown that safety and efficacy are comparable with second generation Drug Eluting Stent (DES). Magmaris Multicenter registry showed 1-and 2-years clinical outcome on the first patients suitable for MRS enrolled in 4 Italian centers.
We evaluated 12- and 24-months clinical results in “real world” experience with Magnesium Reabosrbable Scaffold in terms of Target Lesion Failure (TLF) and scaffold thrombosis (ST). TLF is the primary endpoint and was defined as composite of cardiac mortality, target vessel myocardial infarction (MI), and ischemia-driven target lesion revascularization (ID-TLR). 4P's strategy (Patient/lesion selection, Pre-dilatation, Proper scaffold sizing and Post-dilatation) was strongly recommended. Dual Antiplatelet Therapy (DAPT) has been recommended for 12 months.
Data from 207 patients, including initial experience, have been collected. Patients were 83% male, 20% diabetic and Acute Coronary Syndrome (ACS) in 23%. Lesion type were A-B1 in 54% and B2C in 46%. 4P's strategy was respected in 94%. Procedural success was 98% (2% peri-procedural MI). Compliance at 12-months follow up was 97.6%, TLF rate was 5.4% (including 1 case of myocardial infarction with late scaffold thrombosis (ST), all patients were successfully treated with in-scaffold segment DES implantation). At 24-months compliance was 92.8% (192 patients) and TLF was 7.4%. In the period between 13 and 24 months only 4 patients had TLF (including 1 case of myocardial infarction, all patients were successfully treated with in-scaffold segment DES implantation). None of the patients died for a cardiac reason.
Our 2-years results confirm safety and efficacy showed at 12-months, reinforcing long-term performance with only 2% rate of TLF increase and no ST after 1 year.
•Magmaris Magnesium Scaffold is almost completely reabsorbed at 12 months (95%) with scaffolding time up to 3 months.•There is limited real world data including first and learning curve subjects in literature.•In this study 4-P's rule guides scaffold implantation.•At 24 months FU this scaffold confirms safety and efficacy showed at 12 months: 7.4% TLF, 1 ST and 0 cardiac death.•During second year, 2% cumulative increase of TLF rate and no ST were registered.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We describe a directed search for continuous gravitational waves in data from the sixth initial LIGO science run. The target was the nearby globular cluster NGC 6544 at a distance of ≈2.7 kpc. The ...search covered a broad band of frequencies along with first and second frequency derivatives for a fixed sky position. The search coherently integrated data from the two LIGO interferometers over a time span of 9.2 days using the matched-filtering F-statistic. We found no gravitational-wave signals and set 95% confidence upper limits as stringent as 6.0×10−25 on intrinsic strain and 8.5×10−6 on fiducial ellipticity. These values beat the indirect limits from energy conservation for stars with characteristic spin-down ages older than 300 years and are within the range of theoretical predictions for possible neutron-star ellipticities. An important feature of this search was use of a barycentric resampling algorithm which substantially reduced computational cost; this method is used extensively in searches of Advanced LIGO and Virgo detector data.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
To compare the change in anterior chamber flare after intravitreal injection of the anti-vascular endothelial growth factor agents bevacizumab, aflibercept, and ranibizumab.
Sixty-one eyes of 53 ...patients underwent intravitreal injection with anti-vascular endothelial growth factor medications for exudative age-related macular degeneration, diabetic macular edema, or retinal vein occlusion. There were a total of 26 eyes injected with bevacizumab, 14 eyes injected with aflibercept, and 21 eyes injected with ranibizumab. Anterior segment flare was measured with a laser flare meter (Kowa) before intravitreal injection and 1 day after injection. The change in flare was analyzed.
The mean change in flare after 1 day was +2.5 photons per millisecond in patients who received bevacizumab, 0.0 photons per millisecond for aflibercept, and -0.2 photons per millisecond for ranibizumab. There was a statistically significant difference between the 3 medications (P = 0.006). Pairwise analysis of the change in flare showed a statistically significant difference between bevacizumab and ranibizumab (P = 0.002). The change in flare in patients who received aflibercept was not different from that in those who received bevacizumab (P = 0.08) or ranibizumab (P = 0.99).
There was a statistically significant increase in flare after bevacizumab injection compared with ranibizumab. This difference was small and is not believed to be clinically significant. There was no statistical difference in the change in flare between aflibercept and the other medications, although the number of eyes in the aflibercept group was small.
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