Block Copolymer Micelles with an Intermediate Star‐/Flower‐Like Structure Studied by 1H NMR Relaxometry

¹H NMR relaxation is used to study the self‐assembly of a double thermoresponsive diblock copolymer in dilute aqueous solution. Above the first transition temperature, at which aggregation into micellar structures is observed, the trimethylsilyl (TMS)‐labeled end group attached to the shell‐forming block shows a biphasic T₂ relaxation. The slow contribution reflects the TMS groups located at the periphery of the hydrophilic shell, in agreement with a star‐like micelle. The fast T₂ contribution corresponds to the TMS groups, which fold back toward the hydrophobic core, reflecting a flower‐like micelle. These results confirm the formation of block copolymer micelles of an intermediate nature (i.e., of partial flower‐like and star‐like character), in which a part of the TMS end groups folds back to the core due to hydrophobic interactions.

     

Effects of a personalized nine weeks intermittent exercise working program on left ventricle filling function in middle-aged women with mild diastolic dysfunction

BackgroundBeneficial effects of physical training in aged women with diastolic dysfunction (DD) remain controversial.ObjectiveTo investigate the effects of a short-term intermittent work exercise program (IWEP) among older women with and without grade I DD.Study designLongitudinal prospective study.Study participantsEighty community-dwelling women ranged in age from 52 to 78 (mean age: 65.5 ± 6.0 years), identified as being free of any cardiopulmonary disease, assigned to two groups according to their baseline mitral E-A ratio (> 0.8 vs. grade I DD).MeasurementsBefore and after the IWEP, an incremental cycle exercise test to obtain first ventilatory threshold (VT₁), maximal tolerated power (MTP) and peak oxygen uptake (VO_2peak) and a 6-minute walk test (6MWT) and a Doppler echocardiographic examination were performed. Effects of the IWEP were computed trough intra- and inter-group comparisons.ResultsBy chance 40 women were assigned to each group. The IWEP resulted in a significant increase of MTP, VO_2peak, and VT₁, with respectively, +17.4, +19.1 and +22.2% in group 1 and, +19.3, +8.2% and +27.8% in DD group. The distance walked at the 6MWT was improved in both groups. Endurance and maximal cardiorespiratory parameters were similar in both groups before and after the IWEP. For women with an E-A ratio ≤ 0.8, IWEP was associated with a slight but significant increase of mitral E wave, mitral E-A ratio and mitral E-Ea ratio.ConclusionThe IWEP enhanced endurance and maximal cardiorespiratory capacities in both groups and slightly but significantly improved the transmitral inflow.     

Functional mechanism of tracheal relaxation,antiasthmatic, and toxicological studies of 6-hydroxyflavone

Previously, we described tracheal rat rings relaxation by several flavonoids, being 6-hydroxyflavone (6-HOF) the most active derivative of the series. Thus, its mechanism of action was determined in an ex vivo tracheal rat ring bioassay. The anti-asthmatic effect was assayed in in vivo OVAlbumin (OVA)-sensitized guinea pigs. Finally, the toxicological profile of 6-HOF was studied based on Organization of Economic Cooperation and Development guidelines with modifications. 6-HOF–induced relaxation appears to be related with receptor-operated calcium channel and voltage-operated calcium channel blockade as the main mechanism of action, and also through the production of relaxant second messengers NO and cGMP. Molecular docking supports that 6-HOF acts as calcium channel blocker and by activation of nitric oxide synthase. In addition, the in vivo anti-asthmatic experiments demonstrate the dose-dependent significant anti-allergic effect of 6-HOF induced by OVA, with best activity at 50 /kg. Finally, toxicological studies determined a LD50 > 2,000 mg/kg and, after 28 day of treatment with 6-HOF (50 mg/kg) by intragastric route, mice did not exhibit evidence of any significant toxicity. In conclusion, experiments showed that 6-HOF exerts significant relaxant activity through calcium channel blockade, and possibly, by NO/cGMP-system stimulation on rat trachea, which interferes with the contraction mechanism of smooth muscle cells in the airways. In addition, the flavonoid shows potential anti-asthmatic properties in an anti-allergic pathway. Furthermore, because the pharmacological and safety evidence, we propose this flavonoid as lead for the development of a novel therapeutic agent for the treatment of asthma and related respiratory diseases.     

Structure and backbone dynamics of a microcrystalline metalloprotein by solid-state NMR

We introduce a new approach to improve structural and dynamical determination of large metalloproteins using solid-state nuclear magnetic resonance (NMR) with (1)H detection under ultrafast magic angle spinning (MAS). The approach is based on the rapid and sensitive acquisition of an extensive set of (15)N and (13)C nuclear relaxation rates. The system on which we demonstrate these methods is the enzyme Cu, Zn superoxide dismutase (SOD), which coordinates a Cu ion available either in Cu(+) (diamagnetic) or Cu(2+) (paramagnetic) form. Paramagnetic relaxation enhancements are obtained from the difference in rates measured in the two forms and are employed as structural constraints for the determination of the protein structure. When added to (1)H-(1)H distance restraints, they are shown to yield a twofold improvement of the precision of the structure. Site-specific order parameters and timescales of motion are obtained by a gaussian axial fluctuation (GAF) analysis of the relaxation rates of the diamagnetic molecule, and interpreted in relation to backbone structure and metal binding. Timescales for motion are found to be in the range of the overall correlation time in solution, where internal motions characterized here would not be observable.     

A comparative investigation of flexion relaxation phenomenon in healthy and chronic neck pain subjects

Purpose

The cervical flexion relaxation phenomenon (FRP) is a neck extensor myoelectric “silence” that occurs during complete cervical and lumbar flexion. In contrast to low back pain, the changes that occur during FRP in chronic neck pain (CNP) patients are still not clear. The aim of this study was to assess the characteristics of this phenomenon in the cervical region in CNP patients and controls.

Methods

Twenty-two women (23 ± 2.62 years) with chronic non-specific neck pain and 21 healthy women (23.4 ± 1.68 years) participated in this study. They accomplished a cervical flexion and extension from neutral position. Neck angle and surface electromyographic activity of cervical erector spinae (CES) and upper trapezius muscles were recorded. Appearance, onset and offset angle of the FRP were analysed and compared between the two groups.

Results

There were significant differences in the appearance of FRP between the two groups (P ≤ 0.001). The FRP in the CES muscles was observed in 85.7 % of healthy subjects and in 36.3 % of CNP patients, and no FRP was observed in the upper trapezius. Results of this study show that the onset and offset of FRP parameters were significantly different between the two groups (P ≤ 0.001).

Conclusions

The results of the present study indicate that FRP in CNP patients was seen less than the healthy subjects, and moreover the FRP period was reduced in CNP patients. Our results also suggest that the changes in FRP of CNP patients may be due to the increased CES activity in these patients.     

耳部瘢痕疙瘩切除后减张及抗瘢痕治疗防止复发的疗效分析

目的：探讨耳部瘢痕疙瘩的治疗方法;方法：手术切除耳部瘢痕疙瘩后减张缝合＋伤口胶固定十硅酮凝胶,部分病例配合注射曲安奈德。结果：共治疗38例,失访6例,32例随访12个月,其中治愈27例（84．3％）,未界定3例（9．3％）,复发2例占随访病例6．2％。结论：耳部瘢痕疙瘩切除术后减张缝合＋伤口胶固定＋硅酮凝胶保水是综合治疗耳部瘢痕疙瘩防止复发的有效方法。