Diltiazem reverses tissue Doppler velocity abnormalities in pre-clinical hypertrophic cardiomyopathy

BACKGROUND: Abnormalities in systolic and diastolic function shown by tissue Doppler imaging have been shown to be present in patients with hypertrophic cardiomyopathy who do not yet show clinical or echocardiographic evidence of the disease. These become more marked as left ventricular hypertrophy develops. We attempted to show that these abnormalities could be reversed by treatment with diltiazem. METHODS AND RESULTS: Six adults, who were carriers of a mutation involving the cardiac myosin binding, protein-C gene and who did not show clinical electrocardiographic or echocardiographic evidence of the disease were given a dose of 240mg of diltiazem daily. Tissue Doppler peak systolic and early diastolic velocities at the lateral mitral annulus were examined before treatment and at a mean of 8 weeks after starting treatment. Improvement in both parameters occurred with early diastolic velocities returning to normal and most systolic velocities also becoming normal. CONCLUSION: Diltiazem may have a role in helping to prevent abnormalities of function and perhaps the development of left ventricular hypertrophy in patients with pre-clinical hypertrophic cardiomyopathy.     

Celecoxib inhibits production of MMP and NO via down-regulation of NF-κB and JNK in a PGE2 independent manner in human articular chondrocytes

The purpose of this study was to examine the effects of celecoxib on matrix metalloproteinases (MMP-1 and MMP-3), nitric oxide (NO), and the phosphorylation of nuclear factor-κB (NF-κB) and three mitogen-activated protein kinases (MAPKs), (p38, JNK and ERK) in human articular chondrocytes from normal, osteoarthritis, and rheumatoid arthritis cartilages. Celecoxib at 100 nM reduced the IL-1β-induced productions of MMP-1, MMP-3, iNOS, and NO, whereas indomethacin at 100 nM showed no effect. The additional stimulation of prostaglandin E2 (PGE2) failed to restore those productions, while the production of PGE2 were reduced by 1 and 10 μM but not 100 nM of celecoxib. The inhibitors of NF-κB, JNK and p38, but not ERK, decreased IL-1β-enhanced MMP-1, MMP-3 and NO production, respectively, and 100 nM celecoxib down-regulated the phosphorylation of NF-κB and JNK but has no effect on either p38 or ERK. Celecoxib has inhibitory effects on MMP-1, MMP-3 and NO productions, suggesting the protective roles directly on articular chondrocytes. Despite the COX-2 selectivity, celecoxib affects those productions via not PGE2 but NF-κB and JNK MAPK.     

Relationship between measures of left ventricular systolic and diastolic dysfunction and clinical and biomarker status in patients with hypertrophic cardiomyopathy

The evaluation of left ventricular (dys)function is at the core of clinical cardiology practice in patients with hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy proceeds along paradigms that are profoundly different and follows disease-specific patterns of progression towards heart failure. By automatically applying a standard approach, much information is lost or misplaced, and severe degrees of dysfunction may be erroneously interpreted as mild by such an assumption. This is mostly evident during the assessment of systolic function, in which a superficial evaluation of standard variables, often relatively preserved (even in advanced stages), may lead to underestimation of clinical severity, with potential consequences, such as late referral for transplantation. Currently, specific biomarkers–particularly N-terminal prohormone of B-type natriuretic peptide and high-sensitivity cardiac troponin I–play a key role in the diagnosis, treatment and risk stratification of hypertrophic cardiomyopathy. Elevated biomarkers seem to depict patients with more severe disease, adding diagnostic and prognostic information to conventional assessments, such as left ventricular ejection fraction, New York Heart Association class and left ventricular outflow tract obstruction. For all these reasons, we provide a review of current knowledge on systo-diastolic function in patients with hypertrophic cardiomyopathy, in an attempt to define clinically significant degrees of dysfunction, biomarker status and specific “red alert” thresholds in clinical practice.     

血管紧张素原基因多态性与肥厚型心肌病的相关性分析

目的 探讨血管紧张素原(AGT)基因的单核苷酸多态性(SNP)位点A943580G与肥厚型心肌病(HCM)的相关性.方法 用PCR-RFLP方法对225个HCM病人和243个正常人的AGT的SNP位点A943580G进行基因分型(此位点与黑色人种中的高血压病人的最大早期充盈速度有关).结果 携带AA和AG基因型的HCM病人的左心室流出道梗阻率明显高于GG基因型的梗阻率(30.1%比17.0%,P＜0.05).通过对发病年龄,性别,室间隔厚度,HCM家族史以及家族猝死史进行调整后,携带A等位基因(AA AG)的HCM病人左心室流出道梗阻率要高于GG基因型病人(OR=2.4,95%CI 1.2 to 4.8).结论 AGT的A等位基因可能是HCM病人发生左心室流出道梗阻的危险因子.     

Rapamycin attenuates articular cartilage degeneration by inhibiting β-catenin in a murine model of osteoarthritis

Purpose: To investigate whether systemic injection of rapamycin attenuates articular cartilage degeneration by inhibiting β-catenin in a murine model of osteoarthritis (OA).

Materials and methods: Ten-week-old male C57BL/6j wild-type (WT) mice and SOST-knockout (SOST^?/?) mice were randomized to a sham group, a vehicle-treated group, and a rapamycin-treated group. Mice in the vehicle-treated group underwent destabilizing of the medial meniscus (DMM) in the right knee, and were then treated with vehicle. Mice in the rapamycin treatment group underwent DMM and were treated with rapamycin. Safranin O-Fast green staining and Osteoarthritis Research Society International (OARSI) modified Mankin score were used to evaluate the histopathological features of the articular cartilage in the knee. The expression of light chain 3 (LC3) was evaluated by immunofluorescence, whereas the expression of ATG5, matrix metallopeptidase 13 (MMP-13), vascular endothelial growth factor (VEGF), sclerostin, and β-catenin were evaluated by immunohistochemistry. TUNEL staining was used to determine apoptosis of chondrocytes.

Results: In vehicle-treated mice when compared with mice in the sham group, the OARSI scores, expression of MMP-13, VEGF, sclerostin, β-catenin, and chondrocyte apoptosis were significantly increased, whereas the expression of LC3 and ATG5 were significantly decreased. A systemic injection of rapamycin activated chondrocyte autophagy, which increased the expression of LC3 and ATG-5, and reduced OARSI scores, the expression of β-catenin, MMP-13, and VEGF, and chondrocyte apoptosis in rapamycin treated mice when compared with vehicle-treated mice.

Conclusions: Systemic injection of rapamycin attenuated articular cartilage degeneration by inhibiting β-catenin in a murine model of OA.     

Effects of Pulsed Electromagnetic Fields on Human Articular Chondrocyte Proliferation

Low-energy, low-frequency pulsed electromagnetic fields (PEMFs) can induce cell proliferation in several cell culture models. In this work we analysed the proliferative response of human articular chondrocytes, cultured in medium containing 10% FBS, following prolonged exposure to PEMFs (75 Hz, 2.3 mT), currently used in the treatment of some orthopaedic pathologies. In particular, we investigated the dependence of the proliferative effects on the cell density, the availability of growth factors and the exposure lengths. We observed that PEMFs can induce cell proliferation of low density chondrocyte cultures for a long time (6 days), when fresh serum is added again in the culture medium. In the same conditions, in high density cultures, the PEMF-induced increase in cell proliferation was observed only in the first three days of exposure. The data presented in this study show that the availability of growth factors and the environmental constrictions strongly condition the cellular proliferative response to PEMFs.     

Free-Breathing Motion-Corrected Single-Shot Phase-Sensitive Inversion Recovery Late-Gadolinium-Enhancement Imaging: A Prospective Study of Image Quality in Patients with Hypertrophic Cardiomyopathy

ObjectiveMotion-corrected averaging with a single-shot technique was introduced for faster acquisition of late-gadolinium-enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging while free-breathing. We aimed to evaluate the image quality (IQ) of free-breathing motion-corrected single-shot LGE (moco-ss-LGE) in patients with hypertrophic cardiomyopathy (HCM).Materials and MethodsBetween April and December 2019, 30 patients (23 men; median age, 48.5; interquartile range [IQR], 36.5–61.3) with HCM were prospectively enrolled. Breath-held single-shot LGE (bh-ss-LGE) and free-breathing moco-ss-LGE images were acquired in random order on a 3T MR system. Semi-quantitative IQ scores, contrast-to-noise ratios (CNRs), and quantitative size of myocardial scar were assessed on pairs of bh-ss-LGE and moco-ss-LGE. The mean ± standard deviation of the parameters was obtained. The results were compared using the Wilcoxon signed-rank test.ResultsThe moco-ss-LGE images had better IQ scores than the bh-ss-LGE images (4.55 ± 0.55 vs. 3.68 ± 0.45, p < 0.001). The CNR of the scar to the remote myocardium (34.46 ± 11.85 vs. 26.13 ± 10.04, p < 0.001), scar to left ventricle (LV) cavity (13.09 ± 7.95 vs. 9.84 ± 6.65, p = 0.030), and LV cavity to remote myocardium (33.12 ± 15.53 vs. 22.69 ± 11.27, p < 0.001) were consistently greater for moco-ss-LGE images than for bh-ss-LGE images. Measurements of scar size did not differ significantly between LGE pairs using the following three different quantification methods: 1) full width at half-maximum method; 23.84 ± 12.88% vs. 24.05 ± 12.81% (p = 0.820), 2) 6-standard deviation method, 15.14 ± 10.78% vs. 15.99 ± 10.99% (p = 0.186), and 3) 3-standard deviation method; 36.51 ± 17.60% vs. 37.50 ± 17.90% (p = 0.785).ConclusionMotion-corrected averaging may allow for superior IQ and CNRs with free-breathing in single-shot LGE imaging, with a herald of free-breathing moco-ss-LGE as the scar imaging technique of choice for clinical practice.     

强脉冲光在烧伤后增生性瘢痕中的应用效果分析

【摘要】 目的 探讨强脉冲光在烧伤后增生性瘢痕中的应用效果。方法 选取2019 年3 月至2020 年4 月中国人民解放军联勤保障部队第九八八医院收治的66 例烧伤后增生性瘢痕患者作为研究对象,并按照随机数表法将其随机分为观察组与对照组,每组33 例。对照组患者采用压力疗法联合硅酮凝胶治疗,观察组患者在对照组治疗的基础上联合应用强脉冲光治疗,对比两组患者瘢痕评分、疼痛程度、临床疗效以及不良反应发生情况。结果 治疗后,观察组患者温哥华瘢痕量表(VSS) 评分、视觉模拟评分法(VAS) 评分均明显低于对照组(t =3.051、3.028,P =0.003、0.004),临床疗效明显优于对照组(Z = - 2.117,P = 0.034); 治疗过程中,观察组患者不良反应发生情况与对照组无明显差异(χ2 =0.569,P =0.451)。结论 在压力疗法与硅酮凝胶治疗的基础上,给予烧伤后增生性瘢痕患者强脉冲光治疗,可有效提高瘢痕改善效果,减轻患者疼痛等临床症状,且不会增加不良反应发生率。     

Comparative study of the use of poly(glycolic acid), calcium alginate and pluronics in the engineering of autologous porcine cartilage

New cartilage formation has been successfully achieved by a technology referred to as tissue engineering. Polymers and hydrogels such as poly(glycolic acid), calcium alginate, and poly(ethylene) and poly(propylene) hydrogels have been used as cell carriers to regenerate cartilage in the nude mouse model. The next step toward human applications of engineered cartilage is to demonstrate their potential in immunocompetent animal models. This study compared the suitability of three polymers for generating tissue engineered elastic cartilage using autologous cells in an immuno-competent porcine animal model. Auricular cartilage was obtained from pigs. Chondrocytes were isolated and seeded onto fiber based poly(glycolic acid) (PGA) scaffolds or suspended in calcium alginate or pluronic F127 gel at constant concentrations. Chondrocyte-polymer constructs were either implanted (PGA) or injected (calcium alginate and pluronic) as autologous implants subcutaneously into the pigs from which the cells had been isolated. Specimens were harvested and analyzed grossly and histologically after 6 weeks in vivo. All explants demonstrated cartilage formation to a variable degree. When using PGA or calcium alginate, the overall histological appearance of the tissue formed is that of fibrocartilage with thick bundles of collagen dispersed in the tissue. When using pluronics as scaffold, histologic features resemble those of native elastic cartilage, showing a more organized arrangement of the cells, which seems to correlate to functional properties as elastin presence in the tissue engineered cartilage. Elastic cartilage engineered in an immunocompetent animal model varies with the type of polymer used. The behavior of the cell-polymer constructs is not fully understood and outcome seems to be related to several factors, including inflammatory reaction. Further studies with similar models are needed to determine the feasibility of engineering tissue generated from different cell-polymer constructs prior to human application.