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1.
Clin Res Cardiol ; 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31401672

RESUMO

AIMS: In the placebo-controlled, double-blind BOne marrOw transfer to enhance ST-elevation infarct regeneration (BOOST) 2 trial, intracoronary autologous bone marrow cell (BMC) transfer did not improve recovery of left ventricular ejection fraction (LVEF) at 6 months in patients with ST-elevation myocardial infarction (STEMI) and moderately reduced LVEF. Regional myocardial perfusion as determined by adenosine stress perfusion cardiac magnetic resonance imaging (S-CMR) may be more sensitive than global LVEF in detecting BMC treatment effects. Here, we sought to evaluate (i) the changes of myocardial perfusion in the infarct area over time (ii) the effects of BMC therapy on infarct perfusion, and (iii) the relation of infarct perfusion to LVEF recovery at 6 months. METHODS AND RESULTS: In 51 patients from BOOST-2 (placebo, n = 10; BMC, n = 41), S-CMR was performed 5.1 ± 2.9 days after PCI (before placebo/BMC treatment) and after 6 months. Infarct perfusion improved from baseline to 6 months in the overall patient cohort as reflected by the semi-quantitative parameters, perfusion defect-infarct size ratio (change from 0.54 ± 0.20 to 0.43 ± 0.22; P = 0.006) and perfusion defect-upslope ratio (0.54 ± 0.23 to 0.68 ± 0.22; P < 0.001), irrespective of randomised treatment. Perfusion defect-upslope ratio at baseline correlated with LVEF recovery (r = 0.62; P < 0.001) after 6 months, with a threshold of 0.54 providing the best sensitivity (79%) and specificity (74%) (area under the curve, 0.79; 95% confidence interval, 0.67-0.92). CONCLUSION: Infarct perfusion improves from baseline to 6 months and predicts LVEF recovery in STEMI patients undergoing early PCI. Intracoronary BMC therapy did not enhance infarct perfusion in the BOOST-2 trial.

2.
J Am Heart Assoc ; 8(12): e012429, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31181983

RESUMO

Background Acute complete occlusion of a coronary artery results in progressive ischemia, moving from the endocardium to the epicardium (ie, wavefront). Dependent on time to reperfusion and collateral flow, myocardial infarction ( MI ) will manifest, with transmural MI portending poor prognosis. Late gadolinium enhancement cardiac magnetic resonance imaging can detect MI with  high diagnostic accuracy. Primary percutaneous coronary intervention is the preferred reperfusion strategy in patients with ST -segment-elevation MI with <12 hours of symptom onset. We sought to visualize time-dependent necrosis in a population with ST -segment-elevation MI by using late gadolinium enhancement cardiac magnetic resonance imaging (STEMI-SCAR project). Methods and Results ST -segment-elevation MI patients with single-vessel disease, complete occlusion with TIMI (Thrombolysis in Myocardial Infarction) score 0, absence of collateral flow (Rentrop score 0), and symptom onset <12 hours were consecutively enrolled. Using late gadolinium enhancement cardiac magnetic resonance imaging, the area at risk and infarct size, myocardial salvage index, transmurality index, and transmurality grade (0-50%, 51-75%, 76-100%) were determined. In total, 164 patients (aged 54±11 years, 80% male) were included. A receiver operating characteristic curve (area under the curve: 0.81) indicating transmural necrosis revealed the best diagnostic cutoff for a symptom-to-balloon time of 121 minutes: patients with >121 minutes demonstrated increased infarct size, transmurality index, and transmurality grade (all P<0.01) and decreased myocardial salvage index ( P<0.001) versus patients with symptom-to-balloon times ≤121 minutes. Conclusions In MI with no residual antegrade and no collateral flow, immediate reperfusion is vital. A symptom-to-balloon time of >121 minutes causes a high grade of transmural necrosis. In this pure ST -segment-elevation MI population, time to reperfusion to salvage myocardium was less than suggested by current guidelines.

3.
J Cardiovasc Magn Reson ; 21(1): 33, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31230593

RESUMO

BACKGROUND: Adenosine is used in stress perfusion cardiac imaging to reveal myocardial ischemia by its vasodilator effects. Caffeine is a competitive antagonist of adenosine. However, previous studies reported inconsistent results about the influence of caffeine on adenosine's vasodilator effect. This study assessed the impact of caffeine on the myocardial perfusion reserve index (MPRI) using adenosine stress cardiovascular magnetic resonance imaging (CMR). Moreover, we sought to evaluate if the splenic switch-off sign might be indicative of prior caffeine consumption. METHODS: Semiquantitative perfusion analysis was performed in 25 patients who underwent: 1) caffeine-naïve adenosine stress CMR demonstrating myocardial ischemia and, 2) repeat adenosine stress CMR after intake of caffeine. MPRI (global; remote and ischemic segments), and splenic perfusion ratio (SPR) were assessed and compared between both exams. RESULTS: Global MPRI after caffeine was lower vs. caffeine-naïve conditions (1.09 ± 0.19 vs. 1.24 ± 0.19; p <  0.01). MPRI in remote myocardium decreased by caffeine (1.24 ± 0.19 vs. 1.49 ± 0.19; p <  0.001) whereas MPRI in ischemic segments (0.89 ± 0.18 vs. 0.95 ± 0.23; p = 0.23) was similar, resulting in a lower MPRI ratio (=remote/ischemic segments) after caffeine consumption vs. caffeine-naïve conditions (1.41 ± 0.19 vs. 1.64 ± 0.35, p = 0.01). The SPR was unaffected by caffeine (SPR 0.38 ± 0.19 vs. 0.38 ± 0.18; p = 0.92). CONCLUSION: Caffeine consumption prior to adenosine stress CMR results in a lower global MPRI, which is driven by the decreased MPRI in remote myocardium and underlines the need of abstinence from caffeine. The splenic switch-off sign is not affected by prior caffeine intake.

4.
Clin Res Cardiol ; 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31236694

RESUMO

BACKGROUND: Up to 30% of patients with acute coronary syndrome have no culprit lesion. Coronary microvascular spasm is an alternative cause for such a clinical presentation. However, this has rarely been investigated systematically. The aim of our study was to assess the frequency of coronary microvascular spasm in patients with NSTEMI without culprit lesion (MINOCA) by intracoronary acetylcholine testing (ACH-test). METHODS: Between 2014 and 2017, 940 patients with NSTEMI underwent coronary angiography and 125 (13%) had no culprit lesion (< 50% stenosis on visual assessment). Of the latter, 29 patients had other causes for the clinical presentation (e.g. tako-tsubo-syndrome or myocarditis). The remaining 96 patients were recruited for the study and underwent ACH-testing according to a standardized protocol. RESULTS: The ACH-test was normal in 40 (42%) and abnormal in the remaining 56 (58%) patients. Of the latter, 26 patients (46%) had epicardial spasm (epicardial narrowing ≥ 90%, reproduction of symptoms and ischemic ST-segment changes) and 30 (54%) microvascular spasm (ischemic ST-shifts and angina without epicardial vasoconstriction ≥ 90%). The peak high-sensitive troponin-T concentration was 113 (42-255) pg/ml. Patients with coronary spasm had more often a positive family history compared to those without and patients with epicardial compared to microvascular spasm were more often smokers. CONCLUSION: Coronary microvascular spasm is frequently found in patients with NSTEMI without culprit lesion and represents a likely cause of myocardial injury. ACH-testing is useful for detection of vasomotor disorders allowing tailored treatment with calcium antagonists and/or nitrates in addition to secondary prevention to improve symptoms and prognosis. Microvascular spasm in non-ST-segment elevation myocardial infarction without culprit lesion (MINOCA) .

5.
Heart ; 105(16): 1219-1220, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31113809
6.
Stem Cells ; 37(8): 1057-1074, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31002437

RESUMO

In this study, we report the beneficial effects of a newly identified dermal cell subpopulation expressing the ATP-binding cassette subfamily B member 5 (ABCB5) for the therapy of nonhealing wounds. Local administration of dermal ABCB5+ -derived mesenchymal stem cells (MSCs) attenuated macrophage-dominated inflammation and thereby accelerated healing of full-thickness excisional wounds in the iron-overload mouse model mimicking the nonhealing state of human venous leg ulcers. The observed beneficial effects were due to interleukin-1 receptor antagonist (IL-1RA) secreted by ABCB5+ -derived MSCs, which dampened inflammation and shifted the prevalence of unrestrained proinflammatory M1 macrophages toward repair promoting anti-inflammatory M2 macrophages at the wound site. The beneficial anti-inflammatory effect of IL-1RA released from ABCB5+ -derived MSCs on human wound macrophages was conserved in humanized NOD-scid IL2rγ null mice. In conclusion, human dermal ABCB5+ cells represent a novel, easily accessible, and marker-enriched source of MSCs, which holds substantial promise to successfully treat chronic nonhealing wounds in humans. Stem Cells 2019;37:1057-1074.

7.
Coron Artery Dis ; 30(3): 222-231, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30633029

RESUMO

BACKGROUND: The diagnostic performance of adenosine stress cardiovascular magnetic resonance (CMR) for the detection of significant stenosis in infarct-related arteries is widely unknown. Two different types of perfusion defects can be observed: (a) larger than or (b) equal size as scar.We hypothesized that: (a) defect>scar predicts significant coronary stenosis, and (b) defect=scar predicts an unobstructed infarct-related artery, and (c) angina symptoms might be of additional value in stratification. PATIENTS AND METHODS: Patients with previous myocardial infarction referred for work-up of myocardial ischemia undergoing adenosine stress CMR were included if they had coronary angiography within 4 weeks of CMR. RESULTS: Two hundred patients with a mean age of 66±11 years, ischemic scars (subendocardial/transmural), and a mean left ventricular ejection fraction of 53% were included. In patients with defect>scar, the positive predictive value was excellent (88%) and typical angina was reported only in the stenosis group (P=0.002). However, patients with defect=scar (with 50% showing subendocardial scar) had a prevalence of 37% for stenosis, yielding a low negative predictive value of 63%. In this group, symptoms of typical angina were independent of stenosis (P=1.0). CONCLUSION: A perfusion defect larger than scar is highly predictive for significant stenosis in infarct-related arteries. However, more than a third of the patients with perfusion defect of equal size as scar also showed significant coronary stenosis. As half of these patients showed still viable (subendocardial) scars, there is a high-risk of reinfarction. The addition of angina symptoms seems to increase diagnostic accuracy only in patients with perfusion defects larger than scar.

9.
Artigo em Inglês | MEDLINE | ID: mdl-30291394

RESUMO

PURPOSE: This systematic review intends to give an overview of the current knowledge on how allografts used for the reconstruction of cruciate ligaments and menisci are integrated and specifically perform regarding their biomechanical function. METHODS: Two reviewers reviewed the PubMed and Central Cochrane library with focus on the biomechanical integration of tendon ligament and meniscus allografts. The literature search was conducted in accordance with the PRISMA statement for reporting systematic reviews and meta-analyses. RESULTS: The analysed literature on tendon allografts shows that they are more vulnerable to overstretching in the phase of degradation compared to autografts as the revascularization process starts later and takes longer. Therefore, to avoid excessive graft loads, allografts for cruciate ligament replacement should be selected that exhibit much higher failure loads than the native ligaments to counteract the detrimental effect of degradation. Further, placement techniques should be considered that result in a minimum of strain differences during knee joint motion, which is best achieved by near-isometric placement. The most important biomechanical parameters for meniscus allograft transplantation are secure fixation and proper graft sizing. Allograft attachment by bone plugs or by a bone block is superior to circumferential suturing and enables the allograft to restore the chondroprotective biomechanical function. Graft sizing is also of major relevance, because too small grafts are not able to compensate the knee joint incongruity and too large grafts may fail due to extrusion. Only adequate sizing and fixation together can lead to a biomechanically functioning allograft. The objective assessment of the biomechanical quality of allografts in a clinical setting is challenging, but would be highly desirable for monitoring the remodelling and incorporation process. CONCLUSIONS: Currently, indicators like ap-stability after ACL reconstruction or meniscal extrusion represent only indirect measures for biomechanical graft integration. These parameters are at best clinical indicators of allograft function, but the overall integration properties comprising e.g. fixation and graft stiffness remain unknown. Therefore, future research should e.g. focus on advanced imaging techniques or other non-invasive methods allowing for in vivo assessment of biomechanical allograft properties.

10.
Artigo em Inglês | MEDLINE | ID: mdl-30269168

RESUMO

PURPOSE: The purpose of this study was to quantify the effect of clinically relevant open-wedge high tibial osteotomies on medial collateral ligament (MCL) strain and the resultant tibiofemoral contact mechanics during knee extension and 30° knee flexion. METHODS: Six human cadaveric knee joints were axially loaded (1 kN) in knee extension and 30° knee flexion. Strains at the anterior and posterior regions of the MCL were determined using strain gauges. Tibiofemoral contact mechanics (contact area, mean and maximum contact pressure) were investigated using pressure-sensitive sensors. Open-wedge osteotomy was performed using biplanar cuts and osteotomy angles of 5° and 10° were maintained using an external fixator. Tests were performed first with intact and then with dissected MCL. RESULTS: Nonparametric statistical analyses indicated a significant strain increase (p < 0.01) in the anterior and posterior fibres of the MCL with increasing osteotomy angle of up to 8.3% and 6.0%, respectively. Only after releasing the MCL the desired lateralisation of the mechanical axis was achieved, indicating a significant decrease in the maximum contact pressure in knee extension of - 25% (p = 0.028) and 30° knee flexion of - 21% (p = 0.027). CONCLUSIONS: The results of the present biomechanical study suggest, that an open-wedge high tibial osteotomy is most effective in reducing the medial contact pressure when spreading the osteotomy to 10° and concomitantly releasing the MCL. To transfer the results of this biomechanical study to the clinical day-to-day practice, it is necessary to factor in the individual ligamentous laxity of each patient into the treatment options e.g. particularly for patients with distinct knee ligament laxity or medial ligamentary instability, the release of the MCL should be performed with care. LEVEL OF EVIDENCE: Controlled laboratory study.

11.
J Exp Orthop ; 5(1): 25, 2018 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-29956015

RESUMO

BACKGROUND: The medial patellofemoral ligament (MPFL) is the main stabiliser of the patella and thus mostly reconstructed in the surgical treatment of patellofemoral dislocation. The aims of this study were to gain a better understanding of the influence of altered MPFL graft-fixation locations and different graft pre-tensions on patellofemoral contact pressure. METHODS: Six human cadaveric knee joints were placed in a six-degree-of-freedom knee simulator. Mean PFCP (mPFCP) was evaluated in knee flexion of 0, 30 and 90° using a calibrated pressure-measurement system. After data assessment of the native knee joint, five MPFL reconstruction conditions were conducted: Anatomical double bundle; non-anatomical proximal patellar; non-anatomical distal patellar; non-anatomical proximal femoral; non-anatomical ventral femoral. The gracilis graft was fixed at a defined knee flexion of 30° and pre-tensioned to 2, 10 and 20 N. RESULTS: Kruskal-Wallis testing resulted in no mPFCP differences between the native and anatomical reconstruction states. Comparing the native and anatomical reconstruction states with the non-anatomical reconstruction states, no difference in the mPFCP both in knee extension (0°) (p>0.366) and in 30° knee flexion (p>0.349) was found. At 90° knee flexion, the following differences were identified: compared to the native knee state, the mPFCP increased after non-anatomical proximal femoral and non-anatomical ventral femoral reconstruction by 257% (p=0.04) and 292% (p=0.016), respectively. Compared to the anatomical reconstruction state, the mPFCP increased after non-anatomical proximal femoral reconstruction by 199% (p=0.042). DISCUSSION AND CONCLUSIONS: With respect to all study findings and to restore a physiological PFCP, we recommend using the anatomical footprints for MPFL reconstruction and a moderate graft pretensioning of 2-10 N.

12.
Nat Commun ; 9(1): 361, 2018 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-29367623

RESUMO

The storage of metastable compounds and modifications of elements are of great interest for synthesis and other, e.g., semiconductor, applications. Whereas white phosphorus is a metastable modification that can be stored under certain conditions, storage of the extremely (light- and air-)sensitive form of arsenic, yellow arsenic, is a challenge rarely tackled so far. Herein, we report on the facile storage and release of these tetrahedral E4 molecules (E = P, As) using activated carbon as a porous storage material. These loaded materials are air- and light-stable and have been comprehensively characterized by solid-state 31P{1H} MAS NMR spectroscopy, powder X-ray diffraction analysis, nitrogen adsorption measurements, and thermogravimetric analysis. Additionally, we show that these materials can be used as a suitable E4 source for releasing intact white phosphorus or yellow arsenic, enabling subsequent reactions in solution. Because the uptake and release of E4 are reversible, these materials are excellent carriers of these highly reactive modifications.

13.
J Cardiovasc Magn Reson ; 19(1): 103, 2017 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-29254482

RESUMO

BACKGROUND: Adenosine stress cardiovascular magnetic resonance (CMR) can detect significant coronary artery stenoses with high diagnostic accuracy. Caffeine is a nonselective competitive inhibitor of adenosine2A-receptors, which might hamper the vasodilator effect of adenosine stress, potentially yielding false-negative results. Much controversy exists about the influence of caffeine on adenosine myocardial perfusion imaging. Our study sought to investigate the effects of caffeine on ischemia detection in patients with suspected or known coronary artery disease (CAD) undergoing adenosine stress CMR. METHODS: Thirty patients with evidence of myocardial ischemia on caffeine-naïve adenosine stress CMR were prospectively enrolled and underwent repeat adenosine stress CMR after intake of 200 mg caffeine. Both CMR exams were then compared for evaluation of ischemic burden. RESULTS: Despite intake of caffeine, no conversion of a positive to a negative stress study occurred on a per patient basis. Although we found significant lower ischemic burden in CMR exams with caffeine compared to caffeine-naïve CMR exams, absolute differences varied only slightly (1 segment based on a 16-segment model, 3 segments on a 60-segment model, and 1 ml in total ischemic myocardial volume, p < 0.001 each). Moreover, no relevant ischemia (≥2 segments in a 16-segment model) was missed by prior ingestion of caffeine. CONCLUSIONS: Although differences were small and no relevant myocardial ischemia had been missed, prior consumption of caffeine led to significant reduction of ischemic burden, and might lower the high diagnostic and prognostic value of adenosine stress CMR. Therefore, we suggest that patients should still refrain from caffeine prior adenosine stress CMR tests.


Assuntos
Adenosina/farmacologia , Cafeína/farmacologia , Circulação Coronária/efeitos dos fármacos , Teste de Esforço/métodos , Imagem Cinética por Ressonância Magnética/métodos , Isquemia Miocárdica/diagnóstico , Idoso , Estimulantes do Sistema Nervoso Central/farmacologia , Circulação Coronária/fisiologia , Eletrocardiografia , Feminino , Humanos , Masculino , Isquemia Miocárdica/fisiopatologia , Valor Preditivo dos Testes , Vasodilatadores/farmacologia
14.
J Am Chem Soc ; 139(40): 13981-13984, 2017 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-28933848

RESUMO

The cothermolysis of As4 and [Cp″2Zr(CO)2] (Cp″ = η5-C5H3tBu2) results in the formation of [Cp″2Zr(η1:1-As4)] (1) in high yields and the arsenic-rich complex [(Cp″2Zr)(Cp″Zr)(µ,η2:2:1-As5)] (2) as a minor product. In contrast to yellow arsenic, 1 is a light-stable, weighable and storable arsenic source for subsequent reactions. The transfer reaction of 1 with [Cp‴Fe(µ-Br)]2 (Cp‴ = η5-C5H2tBu3) yields the unprecedented bond isomeric complexes [(Cp‴Fe)2(µ,η4:4-As4)] (3a) and [(Cp‴Fe)2(µ,η4:4-cyclo-As4)] (3b). In contrast, the analogous reaction with the CpBn derivative [CpBnFe(µ-Br)]2 (CpBn = η5-C5(CH2(C6H5)5) leads exclusively to the triple decker complex [(CpBnFe)2(µ,η4:4-As4)] (4) possessing the tetraarsabutadiene-type ligand analogous to 3a. To elucidate the stability of the bonding isomers 3a and 3b, DFT calculations were performed. The oxidation of 4 with AgBF4 affords [(CpBnFe)2(µ,η5:5-As5)][BF4] (5), which is a product expanded by one arsenic atom, instead of the expected complex [(CpBnFe)2(µ,η4:4-cyclo-As4)]+.

15.
Angew Chem Int Ed Engl ; 56(23): 6655-6659, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28471032

RESUMO

The activation of yellow arsenic is possible with the silylene [PhC(NtBu)2 SiN(SiMe3 )2 ] (1) and the disilene [(Me3 Si)2 N(η1 -Me5 C5 )Si=Si(η1 -Me5 C5 )N(SiMe3 )2 ] (3). The reaction of As4 with 1 leads to the unprecedented As10 cage compound [(LSiN(SiMe3 )2 )3 As10 ] (2; L=PhC(NtBu)2 ) with an As7 nortricyclane core stabilized by arsasilene moieties containing silicon(II)bis(trimethylsilyl)amide substituents. In contrast, the compound [Cp*{(SiMe3 )2 N}SiAs]2 (4) containing a butterfly-like diarsadisilabicyclo[1.1.0]butane unit is formed by the reaction of As4 with the disilene 3. Both compounds were characterized by single-crystal X-ray diffraction analysis, NMR spectroscopy, and mass spectrometry. The reaction outcomes demonstrate the different reaction behavior of yellow arsenic (As4 ) compared to white phosphorus (P4 ) in the reactions with the corresponding silylenes and disilenes.

16.
Chemistry ; 23(43): 10319-10327, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28493497

RESUMO

A detailed method for the preparation of [Cp''2 Zr(η1:1 -P4 )] (1) is presented. The coordination behavior of 1 towards Lewis acidic transition metal complexes of tungsten, manganese, and iron, respectively, and main group compounds (AlMe3 , AlEt3 ) was investigated in detail by computational and experimental studies. In doing so, a series of unprecedented complexes with different coordination modes and multiple coordination numbers of the tetraphosphabicyclo[1.1.0]butane framework were synthesized. All products, as well as the starting materials, were comprehensively characterized by NMR spectroscopy, mass spectrometry, elemental analysis, and single crystal X-ray structural analysis.

17.
Knee Surg Sports Traumatol Arthrosc ; 25(5): 1646-1652, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27295057

RESUMO

PURPOSE: The purpose of this study was to investigate whether an anterior cruciate ligament (ACL) double-bundle reconstruction with one tibial tunnel displays the same in vitro stability as a conventional double-bundle reconstruction with two tibial tunnels when using the same tensioning protocol. METHODS: In 11 fresh-frozen cadaveric knees, ACL double-bundle reconstruction with one and two tibial tunnels was performed. The two grafts were tightened using 80 N in different flexion angles (anteromedial-bundle at 60° and posterolateral-bundle at 15°). Anterior tibial translation (134 N) and translation with combined rotatory and valgus loads (10 Nm valgus stress and 4 Nm internal tibial torque) were determined at 0°, 30°, 60° and 90° flexion. Measurements were taken in intact ACL, resected ACL, three-tunnel reconstruction and four-tunnel reconstruction. Additionally, the tension on the grafts was determined. Student's t test was performed for statistical analysis of the related samples. Significance was set at p < 0.017 according to Bonferroni correction. RESULTS: The two reconstructive techniques displayed no significant differences in comparison with the intact ACL in anterior tibial translation at 0°, 60° and 90° of flexion. The same results were obtained for the anterior tibial translation with a combined rotatory load at 60° and 90°. When directly comparing both reconstructive techniques, there were no significant differences for the anterior tibial translation and combined rotatory load at all flexion angles. The measured tension on grafts displayed similar load sharing between both bundles. Except at full extension, both grafts displayed a significantly different tension increase under anterior tibial translation for both techniques (p = 0.0086). CONCLUSIONS: Tightening both bundles in ACL double-bundle reconstruction with one or two tibial tunnels in different flexion angles achieved comparable restoration of stability, although there was different load sharing on the bundles. With regard to individualized ACL reconstruction, the double-bundle technique with one tibial tunnel offers a possibility to address small tibial insertion sites without compromising the advantages of a double-bundle procedure.


Assuntos
Reconstrução do Ligamento Cruzado Anterior/métodos , Tíbia/cirurgia , Idoso , Ligamento Cruzado Anterior/cirurgia , Fenômenos Biomecânicos , Cadáver , Humanos , Articulação do Joelho/cirurgia , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Torque
18.
J Am Chem Soc ; 138(33): 10433-6, 2016 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-27513314

RESUMO

Since the discovery of the first "inorganic benzene" (borazine, B3N3H6), the synthesis of other noncarbon derivatives is an ongoing challenge in Inorganic Chemistry. Here we report on the synthesis of the first pnictogen-silicon congeners of benzene, the triarsa- and the triphospha-trisilabenzene [(PhC(NtBu)2)3Si3E3] (E = P (1a), As (1b)) by a simple metathesis reaction. These compounds are formed by the reaction of [Cp″2Zr(η(1:1)-E4)] (E = P, As; Cp″ = C5H3tBu2) with [PhC(NtBu)2SiCl] in toluene at room temperature along with the silicon pnictogen congeners of the cyclobutadiene, [(PhC(NtBu)2)2Si2E2] (E = P (2a), As (2b)), which is unprecedented for the arsenic system 2b. All compounds were comprehensively characterized, and density functional theory calculations were performed to verify the stability and the aromatic character of the triarsa- and the triphospha-trisilabenzene.

19.
Mol Ther ; 23(8): 1320-1330, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26005840

RESUMO

Restoring expression levels of the EF-hand calcium (Ca(2+)) sensor protein S100A1 has emerged as a key factor in reconstituting normal Ca(2+) handling in failing myocardium. Improved sarcoplasmic reticulum (SR) function with enhanced Ca(2+) resequestration appears critical for S100A1's cyclic adenosine monophosphate-independent inotropic effects but raises concerns about potential diastolic SR Ca(2+) leakage that might trigger fatal arrhythmias. This study shows for the first time a diminished interaction between S100A1 and ryanodine receptors (RyR2s) in experimental HF. Restoring this link in failing cardiomyocytes, engineered heart tissue and mouse hearts, respectively, by means of adenoviral and adeno-associated viral S100A1 cDNA delivery normalizes diastolic RyR2 function and protects against Ca(2+)- and ß-adrenergic receptor-triggered proarrhythmogenic SR Ca(2+) leakage in vitro and in vivo. S100A1 inhibits diastolic SR Ca(2+) leakage despite aberrant RyR2 phosphorylation via protein kinase A and calmodulin-dependent kinase II and stoichiometry with accessory modulators such as calmodulin, FKBP12.6 or sorcin. Our findings demonstrate that S100A1 is a regulator of diastolic RyR2 activity and beneficially modulates diastolic RyR2 dysfunction. S100A1 interaction with the RyR2 is sufficient to protect against basal and catecholamine-triggered arrhythmic SR Ca(2+) leak in HF, combining antiarrhythmic potency with chronic inotropic actions.


Assuntos
Insuficiência Cardíaca/genética , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Proteínas S100/metabolismo , Animais , Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Calmodulina/metabolismo , DNA Complementar/metabolismo , Eletrocardiografia , Técnicas de Transferência de Genes , Insuficiência Cardíaca/prevenção & controle , Masculino , Camundongos , Microscopia de Fluorescência , Miocárdio/metabolismo , Miócitos Cardíacos/citologia , Fosforilação , Ligação Proteica , Ratos , Ratos Sprague-Dawley , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Retículo Sarcoplasmático/metabolismo , Proteínas de Ligação a Tacrolimo/metabolismo , Engenharia Tecidual/métodos
20.
Knee Surg Sports Traumatol Arthrosc ; 23(1): 74-82, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24671386

RESUMO

PURPOSE: Numerous studies investigated the reasons for premature osteoarthritis due to partial meniscectomy (PM). However, the influence of meniscectomy on attachment forces and superficial strain of the tibial meniscus is unclear. It is hypothesised that these parameters depend on the degree of PM. METHODS: Six porcine medial menisci were placed in a custom made apparatus, and each meniscal attachment was connected to a force sensor. After printing markers onto the tibial meniscal surfaces, the menisci were positioned on a glass plate enabling optical superficial strain measurement. Additionally, contact area and pressure were investigated. Each meniscus was axially loaded up to 650 N using its respective femoral condyle. Testing was conducted intact and after 50 and 75% PM of the posterior horn and extending 75% PM to the anterior horn. RESULTS: With increasing meniscectomy, the attachment forces decreased anteriorly by up to 17% (n.s.) and posteriorly by up to 55% (p = 0.003). The circumferential strain in the peripheral meniscal zones was not affected by the meniscectomy, while in some meniscal zones the radial strain changed from compression to tension. Contact area decreased by up to 23% (p = 0.01), resulting in an increase in 40% (p = 0.02) for the maximum contact pressure. CONCLUSION: Partial meniscectomy significantly alters the loading situation of the meniscus and its attachments. Specifically, the attachment forces decreased with increasing amount of meniscal tissue loss, which reflects the impaired ability of the meniscus to transform axial joint load into meniscal hoop stress.


Assuntos
Articulação do Joelho/fisiologia , Articulação do Joelho/cirurgia , Meniscos Tibiais/fisiologia , Meniscos Tibiais/cirurgia , Animais , Fenômenos Biomecânicos , Pressão , Estresse Mecânico , Suínos , Suporte de Carga
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