Therapeutic Potential of Resveratrol in Type I Gaucher Disease

Resveratrol is a natural polyphenol that possesses various beneficial properties, such as anti‐inflammatory, anti‐oxidant, and neuroprotective effects. This study evaluated the potential therapeutic effects of resveratrol on primary fibroblasts derived from a patient with Gaucher disease. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assays were carried out to determine whether resveratrol affects cell survival. Changes in the expression levels of apoptosis‐inducing factor (AIF), Bax, cleaved caspase‐3, acetyl‐coenzyme A acetyltransferase 1 (ACAT1), E3‐binding protein (E3BP), and citrate synthase (CS) were determined by western immunoblot to characterize the effect of resveratrol treatment on Gaucher disease cells. Intracellular glucosylceramide levels in resveratrol‐treated patient cells were determined by thin‐layer chromatography (TLC). Resveratrol significantly increased the viability of patient cells in comparison with that of control cells. After exposure to resveratrol, expression levels of the apoptotic factors AIF, Bax, and cleaved caspase‐3 dose‐dependently decreased, while those of ACAT1, E3BP, and CS dose‐dependently increased. TLC showed a significant decrease in glucosylceramide levels in patient cells treated with resveratrol. These findings demonstrate that resveratrol can reduce apoptotic events and glucosylceramide levels in Gaucher disease cells, and that it merits further research as a possible therapeutic compound. Copyright © 2015 John Wiley & Sons, Ltd.     

Ancistrobreveines A–D and related dehydrogenated naphthylisoquinoline alkaloids with antiproliferative activities against leukemia cells,from the West African liana Ancistrocladus abbreviatus

A unique series of six biaryl natural products displaying four different coupling types (5,1′, 7,1′, 7,8′, and 5,8′) were isolated from the roots of the West African liana Ancistrocladus abbreviatus (Ancistrocladaceae). Although at first sight structurally diverse, these secondary metabolites all have in common that they belong to the rare group of naphthylisoquinoline alkaloids with a fully dehydrogenated isoquinoline portion. Among the African Ancistrocladus species, A. abbreviatus is so far only the second one that was found to produce compounds with such a molecular entity. Here, we report on four new representatives, named ancistrobreveines A–D (12–14, and 6). They were identified along with the two known alkaloids 6-O-methylhamateine (4) and ent-dioncophylleine A (10). The two latter naphthylisoquinolines had so far only been detected in Ancistrocladus species from Southeast Asia. All of these fully dehydrogenated alkaloids have in common being optically active despite the absence of stereogenic centers, due to the presence of the rotationally hindered biaryl axis as the only element of chirality. Except for ent-dioncophylleine A (10), which lacks an oxygen function at C-6, the ancistrobreveines A–D (12–14, and 6) and 6-O-methylhamateine (4) are 6-oxygenated alkaloids, and are, thus, typical ‘Ancistrocladaceae-type’ compounds. Ancistrobreveine C (14), is the first – and so far only – example of a 7,8′-linked fully dehydrogenated naphthylisoquinoline discovered in nature that is configurationally stable at the biaryl axis. The stereostructures of the new alkaloids were established by spectroscopic (in particular HRESIMS, 1D and 2D NMR) and chiroptical (electronic circular dichroism) methods. Ancistrobreveine C (14) and 6-O-methylhamateine (4) exhibited strong antiproliferative activities against drug-sensitive acute lymphoblastic CCRF-CEM leukemia cells and their multidrug-resistant subline, CEM/ADR5000.

Ancistrobreveines A–D belong to the rare group of naphthylisoquinoline alkaloids with a non-hydrogenated isoquinoline portion, some of them, like ancistrobreveine C, occurring in the plants only in a scalemic, yet nearly enantiopure form.     

The relationship between crystalline disorder and electronic structure of Pd nanoparticles and their hydrogen storage properties

We investigated the relationship between crystalline disorder and electronic structure deviations of Pd nanoparticles (NPs) and their hydrogen storage properties as a function of their particle diameter (2.0, 4.6 and 7.6 nm) using various synchrotron techniques. The lattice constant of the 2.0 nm-diameter Pd NPs was observed to be larger than that of the 4.6 or 7.6 nm-diameter Pd NPs. With increasing particle diameter the structural ordering was improved, the lattice constant and atomic displacement were reduced and the coordination numbers increased, as determined using high-energy X-ray diffraction, reverse Monte Carlo modelling and X-ray absorption fine structure spectroscopy. The structural order of the core part of the larger NPs was also better than that of the smaller NPs. In addition, the bond strength of the Pd–H formation increased with increasing particle diameter. Finally, the surface order of the Pd NPs was related to enhancement of the hydrogen storage capacity and Pd–H bond strength.

Smaller Pd nanoparticles have a high degree of disordering and a lower coordination number on the surface part, which causes a change in electronic structure to have different hydrogen storage properties.     

Detection of neck recurrence in patients with differentiated thyroid cancer: comparison of ultrasound, contrast-enhanced CT and 18F-FDG PET/CT using surgical pathology as a reference standard: (ultrasound vs. CT vs. 18F-FDG PET/CT in recurrent thyroid cancer)

Objectives

To compare the diagnostic performance of ultrasound, contrast-enhanced computed tomography (CT) and ¹⁸F-FDG positron emission tomography (PET)/CT for detecting recurrent differentiated thyroid cancer in the neck.

Methods

Twenty patients who had undergone previous surgery for differentiated thyroid cancer (19 papillary carcinomas; 1 medullary carcinoma) and presented with pathologically proven recurrence in the neck were included. All patients had undergone ultrasound, CT and PET/CT in the 2 months before further surgery. In each patient, ultrasound, CT and PET/CT images were retrospectively reviewed to determine the presence of loco-regional recurrence by level-by-level analysis. Imaging results were correlated with the histological evaluation of the neck dissection as a standard of reference.

Results

Recurrences were found at 52 out of 110 cervical nodal levels surgically explored. The sensitivity, specificity and accuracy were 69.2 %, 89.7 % and 80.0 % for ultrasound; 63.5 %, 94.8 % and 80.0 % for CT; and 53.8 %, 79.3 % and 67.3 % for PET/CT, respectively. ROC analysis revealed higher diagnostic performance with ultrasound than with PET/CT for detecting recurrent tumour.

Conclusions

Although no significant difference was found among the three techniques, the sensitivity and specificity of ultrasound and CT were higher than those of PET/CT for the evaluation of cervical recurrence in patients with differentiated thyroid cancer.

Key Points

? Ultrasound, CT and ¹⁸ F-FDG PET/CT can all detect recurrent thyroid cancer. ? Ultrasound and CT have higher sensitivity and specificity. ? Ultrasound, CT and ¹⁸ F-FDG PET/CT frequently demonstrated discordant findings     

An alternative method to create extramedullary references in total knee arthroplasty

Purpose

Historically, extramedullary techniques have focused on finding the femoral head center and referred mainly to the anterosuperior iliac spine (the FHC method) in total knee arthroplasty (TKA). The purpose of this study was to evaluate a new extramedullary alignment system that uses neutral overall limb mechanical alignment as an extramedullary reference (the MA method).

Methods

A retrospective review of 1018 TKAs (508 FHC group, 510 MA group) was performed to compare the radiographic results obtained using these two methods. There were 75 male patients and 577 female patients with varus osteoarthritis of the knee. Limb and prosthesis alignments in the coronal plane were investigated at 2?months after surgery.

Results

The accuracies of postoperative alignments of implanted prostheses were better in the MA group than in the FHC group, as assessed by (1) overall limb alignment (MA group, varus 1.4°?±?2.7°; FHC group, varus 2.2°?±?2.9°), and (2) femoral component coronal alignment (MA group, 89.4°?±?2.3°; FHC group, 88.0°?±?2.7°). Overall limb alignment was within 0°?±?5° of the mechanical axis in 96.1% of the MA group and in 86.6% of the FHC group. Mean femoral component medial angle was within 0°?±?5° in 98.4% of the MA group and in 92.5% of the FHC group.

Conclusion

The accuracies of the postoperative radiographic alignments of implanted prostheses were found to be improved when the mechanical axis of the overall lower limb was used as an extramedullary reference. This new reference system would help to achieve correct limb and prostheses alignments during TKA.

Level of evidence

III.     

Analysis of perfusion defects by causes other than acute pulmonary thromboembolism on contrast-enhanced dual-energy CT in consecutive 537 patients

Objective

To assess causes, incidence and patterns of perfusion defects (PDs) on dual-energy perfusion CT angiography (DECTA) in clinically suspected acute pulmonary thromboembolisms (PTE).

Materials and methods

Consecutive 537 patients who underwent DECTA for suspicion of PTE were retrospectively reviewed. After excluding patients with possible PTE or unsatisfactory perfusion map quality, 299 patients with 1697 lobes were included. The DECTA (Somatom Definition, Siemens) was performed at 140 kV and 80 kV. Color-coded perfusion images were obtained with a lung PBV application of the workstation software (Syngo Dual Energy). The presence, incidence, three patterns of PDs (wedge-shaped, heterogeneous, and regionally homogeneous), pulmonary diseases, and the matchedness between the PD and the disease extent were studied.

Results

315 of 1697 lobes (18.6%) in 156 of 299 patients (81.3%) showed PDs. Among them, 51 (3%), 257 (15.1%), and 7 (0.4%) lobes had PDs due to vascular, nonvascular, and unidentifiable causes, respectively. Vascular causes include: pulmonary arterial (PA) hypertension (0.7%), extrinsic occlusion of PA by fibrosis (0.6%), PA hypoplasia (0.6%), vasculitis (0.5%), cancer mass compressing PA, venous occlusion, AVM, and pulmonary angiosarcoma. Most of PDs were wedge-shaped and well-matched. Nonvascular causes include: mosaic attenuation (4.1%), emphysema (3.2%), interstitial fibrosis (1.6%), bronchitis (1.4%), GGO (1.2%), cellular bronchiolitis (1%), bronchiectasis, airway obstruction, compensaroty lung hyperinflation, air trapping, cor-pulmonale, bronchopneumonia, physiologic decreased ventilation, and segmental bronchial atresia. Most of PDs showed heterogeneous pattern and were not matched.

Conclusions

Various vascular and nonvascular diseases cause PDs on DECTA. Each disease shows different pattern of PD depending on pathophysiology and physiologic compensation.     

Symptomatic residual instability with grade II acromioclavicular injury

PurposeOur objective was to evaluate the effectiveness of arthroscopic distal clavicle resection in cases presenting with pain and subtle instability after neglected grade II acromioclavicular (AC) joint dislocation.MethodsFrom February 1998 to May 2006, 17 patients with symptomatic AC instability following chronic grade II AC joint injury were studied. Sixteen patients were male and one female, with a mean age of 48 years. An all-arthroscopic procedure comprising disk removal and distal clavicle resection was performed in all cases. All patients were reviewed clinically, preoperatively and at final follow-up (mean 38 months) using the pain score on a visual analog scale and the Constant score. Strength was measured using an Isobex digital strength analyzer. Patient's personal satisfaction after the procedure was documented as excellent, good or poor. Postoperative AC joint radiographs were routinely obtained in all patients to measure the amount of clavicle resection.ResultsTwo patients underwent additional reconstructive surgery for disabling pain and dysfunction even after the arthroscopic resection procedure. The remaining 15 patients were analyzed. The pain scores improved significantly (p = 0.03). The mean pain score was 5.8 (range 5–9) before treatment and 1.6 (range 0–3) at follow-up. The Constant scores had improved significantly at the final follow-up (p = 0.001). The median Constant score increased from 46 (range 36–69) preoperatively to 71 (range 48–84) postoperatively. Strength had improved at the last follow-up. Eleven patients were satisfied and six were not satisfied with this procedure at the final follow-up.ConclusionsArthroscopic distal clavicle resection statistically improved the pain score, Constant score and strength for grade II AC injury with subtle distal clavicle instability. However, six patients (33.5 %) were not satisfied subjectively. This procedure seemed to be a reasonable initial treatment option with lower morbidity.