Multimetal organic frameworks as drug carriers: Aceclofenac as a drug candidate

Background: Multimetal organic frameworks (M-MOFs) were synthesized by including a second metal ion with the main base metal in the synthesis process to enhance their applications for drug delivery. Aceclofenac (ACF), a nonsteroidal anti-inflammatory analgesic drug of low aqueous solubility, was selected as a candidate for the drug delivery system Purpose: This study aimed to evaluate the loading capacity (LC) and entrapment efficiency (EE) percentages of multi-Material of Institute Lavoisier (MIL)-100(Fe) (M-MIL-100(Fe)) for ACF. Materials and methods: Hydrothermal synthesis procedure was used to prepare multi-MIL-100(Fe) samples (Zn I-MIL-100(Fe), Zn II-MIL-100(Fe), Ca I-MIL-100(Fe), Ca II-MIL-100-(Fe), Mg I-MIL-100(Fe), Mg II-MIL-100(Fe), Mn I-MIL-100(Fe), and Mn II-MIL-100(Fe)). The characterization of M-MIL-100(Fe) samples was evaluated by X-ray powder diffraction (XRD), Fourier transform infrared spectra, scanning electron microscope (SEM), TGA, and N2 adsorption isotherms. The LC of M-MIL-100(Fe) and EE of ACF were determined. Nuclear magnetic resonance (NMR) and zeta-potential analyses were employed to confirm qualitatively the drug loading within M-MIL-100(Fe). Results: The ACF LC of MIL-100(Fe) was 27%, whereas the LC of M-MIL-100(Fe) was significantly increased and ranged from 37% in Ca I-MIL-100(Fe) to about 57% and 59% in Mn II-MIL-100(Fe) and Zn II-MIL-100(Fe), respectively. The ACF@M-MOFs release profiles showed slow release rates in phosphate buffer solutions at pH 6.8 and 7.4 as compared to the ACF@MIL-100(Fe). Conclusion: Therefore, M-MOFs showed a significant potential as a carrier for drug delivery systems

Physiological responses to shuttle repeated-sprint running

This study investigated the influence of 180° changes of direction during a repeated-sprint running test on performance, cardiorespiratory variables, muscle deoxygenation and post-exercise blood lactate ([La]b) levels. Thirteen team-sport athletes (22±3 yr) performed 6 repeated maximal sprints with (RSS, 6×[2×12.5 m]) or without (RS, 6×25 m) changes of direction. Best and mean running time, percentage speed decrement (%Dec), pulmonary oxygen uptake (V˙ O2), vastus lateralis deoxygenation (Hbdiff) and [La]b were calculated for each condition. Best and mean times for both protocols were largely correlated (r=0.63 and r=0.78, respectively), and were ‘almost certainly’ higher for RSS compared with RS (e. g., 5.30±0.17 vs. 4.09±0.17 s for mean time, with the qualitative analysis revealing a 100% chance of RSS time being greater than RS). In contrast, %Dec was‘possibly’ lower for RSS (2.6±1.2 vs. 3.2±1.3%, with a 79% chance of a real difference). Compared with RS,V˙ O2 (40.4±4.2 vs. 38.9±3.8 mL.min−1.kg−1, with a 90% chance of a real difference) and [La]b (10.0±1.7 vs. 9.3±2.4 mmol.L−1, with a 70% chance of a real difference) were‘possibly’ higher. Conversely, there were no differences in Hbdiff (11.5±3.2 vs. 10.9±3.0 μM, with the comparison rated as‘unclear’). To conclude, the present results suggest that the ability to repeat sprints can be considered as a general quality. They also suggest that repeated shuttle sprints might be an effective training practice for eliciting a greater systemic physiological load, but perhaps not a greater loading of the vastus lateralis

Contrasts in top soil infiltration processes for degraded vs. Restored lands. a case study at the perijá range in Colombia

Governments are increasingly committing to significant ecological restoration. However, the impacts of forest restoration on local hydrological services are surprisingly poorly understood. Particularly, limited information is available about the impacts of tree planting on soil infiltration processes and runoff pathways. Thus, we investigated the saturated hydraulic conductivity (Ks ) and preferential flow pathways in three land-cover types: (i) Active Restoration, (ii) Degraded Land, and (iii) Reference Forest, with contrasting differences in soil profile and land use history in the municipality of La Jagua de Ibirico, César department, Colombia. We conducted soil sampling, using the Beerkan method to determine Ks values. We also measured vegetation attributes (i.e., canopy cover, vegetation height, diameter at breast height, and total number of trees) and carried out three dye tracer experiments for each study site. The blue dye experiments revealed that near surface matrix infiltration was dominant for Degraded Land, while at the Active Restoration and Reference Forest, this only occurred at local surface depressions. The general infiltration pattern at the three land uses is indicated as being macropore flow with mixed interaction with the matrix and highly affected by the presence of rock fragments. The deeper infiltration patterns occur by preferential flow due to the presence of roots and rock fragments. The mean Ks for the Active Restoration (240 mm h−1 ) was much higher than the Ks at Degraded Land (40 mm h−1 ) but still considerably lower than the Reference Forest (324 mm h−1 ). These results indicate that top soil infiltration capacity and soil physical parameters not only directly regulate the amount of infiltration but also infiltration patterns and runoff processes, leading to lower infiltration and increased excess overland flow for Degraded Land than for other land uses

Twisted topology and Bipolar Non-Hermitian Skin Effect induced by long-range asymmetric coupling

We investigate the twisted topology of the complex eigenspectrum of a one-dimensional non-Hermitian system under the influence of long-range unidirectional coupling. Unlike the complex energy spectrum of the conventional Hatano-Nelson chain, which takes the form of a single loop with a topological winding index of a definite sign, the introduction of long-range unidirectional hopping results in the creation of multiple twisted loops. These twisted loops exhibit opposite signs of the topological winding index, which correlate to alternating clockwise and anticlockwise energy windings. The simultaneous presence of both signs of the winding index translates into a bipolar non-Hermitian skin effect (NHSE), which challenges the conventional wisdom that the NHSE localization is dependent on the direction of the dominant nearest-neighbor interactions. In this bipolar NHSE, the exponents of the complex energy eigenvectors corresponding to clockwise and anti-clockwise windings, lie inside and outside of the complex unit circle, respectively. Interestingly, at the intersections of oppositely oriented energy loops where the sign of the topological winding index flips, the energy becomes real-valued, leading to a suppression of the NHSE. This marks the emergence of Bloch-like contact points, where both the bipolar NHSE and the traditional NHSE vanish. Based on the non-Hermitian model we provide analytical insights into the effects of long-range unidirectional coupling to the winding topology of its complex energy spectra and their broader implications for the field of condensed matter physics.Comment: 11 pages, 3 figure

Sirt2 promotes white matter oligodendrogenesis during development and in models of neonatal hypoxia

Delayed oligodendrocyte (OL) maturation caused by hypoxia (Hx)-induced neonatal brain injury results in hypomyelination and leads to neurological disabilities. Previously, we characterized Sirt1 as a crucial regulator of OL progenitor cell (OPC) proliferation in response to Hx. We now identify Sirt2 as a critical promoter of OL differentiation during both normal white matter development and in a mouse model of Hx. Importantly, we find that Hx reduces Sirt2 expression in mature OLs and that Sirt2 overexpression in OPCs restores mature OL populations. Reduced numbers of Sirt2+ OLs were also observed in the white matter of preterm human infants. We show that Sirt2 interacts with p27Kip1/FoxO1, p21Cip1/Cdk4, and Cdk5 pathways, and that these interactions are altered by Hx. Furthermore, Hx induces nuclear translocation of Sirt2 in OPCs where it binds several genomic targets. Overall, these results indicate that a balance of Sirt1 and Sirt2 activity is required for developmental oligodendrogenesis, and that these proteins represent potential targets for promoting repair following white matter injury

Impedance responses and size-dependent resonances in topolectrical circuits via the method of images

Resonances in an electric circuit occur when capacitive and inductive components are present together. Such resonances appear in admittance measurements depending on the circuit's parameters and the driving AC frequency. In this study, we analyze the impedance characteristics of nontrivial topolectrical circuits such as one- and two-dimensional Su-Schrieffer-Heeger circuits and reveal that size-dependent anomalous impedance resonances inevitably arise in finite $LC$ circuits. Through the \textit{method of images}, we study how resonance modes in a multi-dimensional circuit array can be nontrivially modified by the reflection and interference of current from the structure and boundaries of the lattice. We derive analytic expressions for the impedance across two corner nodes of various lattice networks with homogeneous and heterogeneous circuit elements. We also derive the irregular dependency of the impedance resonance on the lattice size, and provide integral and dimensionally-reduced expressions for the impedance in three dimensions and above.Comment: 24 pages, 10 figure

Generating a checking sequence with a minimum number of reset transitions

Given a finite state machine M, a checking sequence is an input sequence that is guaranteed to lead to a failure if the implementation under test is faulty and has no more states than M. There has been much interest in the automated generation of a short checking sequence from a finite state machine. However, such sequences can contain reset transitions whose use can adversely affect both the cost of applying the checking sequence and the effectiveness of the checking sequence. Thus, we sometimes want a checking sequence with a minimum number of reset transitions rather than a shortest checking sequence. This paper describes a new algorithm for generating a checking sequence, based on a distinguishing sequence, that minimises the number of reset transitions used.This work was supported in part by Leverhulme Trust grant number F/00275/D, Testing State Based Systems, Natural Sciences and Engineering Research Council (NSERC) of Canada grant number RGPIN 976, and Engineering and Physical Sciences Research Council grant number GR/R43150, Formal Methods and Testing (FORTEST)

Insights into GABA receptor signalling in TM3 Leydig cells

gamma-Aminobutyric acid (GABA) is an emerging signalling molecule in endocrine organs, since it is produced by endocrine cells and acts via GABA(A) receptors in a paracrine/autocrine fashion. Testicular Leydig cells are producers and targets for GABA. These cells express GABA(A) receptor subunits and in the murine Leydig cell line TM3 pharmacological activation leads to increased proliferation. The signalling pathway of GABA in these cells is not known in this study. We therefore attempted to elucidate details of GABA(A) signalling in TM3 and adult mouse Leydig cells using several experimental approaches. TM3 cells not only express GABA(A) receptor subunits, but also bind the GABA agonist {[}H-3] muscimol with a binding affinity in the range reported for other endocrine cells (K-d = 2.740 +/- 0.721 nM). However, they exhibit a low B-max value of 28.08 fmol/mg protein. Typical GABA(A) receptor-associated events, including Cl- currents, changes in resting membrane potential, intracellular Ca2+ or cAMP, were not measurable with the methods employed in TM3 cells, or, as studied in part, in primary mouse Leydig cells. GABA or GABA(A) agonist isoguvacine treatment resulted in increased or decreased levels of several mRNAs, including transcription factors (c-fos, hsf-1, egr-1) and cell cycle-associated genes (Cdk2, cyclin D1). In an attempt to verify the cDNA array results and because egr-1 was recently implied in Leydig cell development, we further studied this factor. RT-PCR and Western blotting confirmed a time-dependent regulation of egr-1 in TM3. In the postnatal testis egr-1 was seen in cytoplasmic and nuclear locations of developing Leydig cells, which bear GABA(A) receptors and correspond well to TM3 cells. Thus, GABA acts via an untypical novel signalling pathway in TM3 cells. Further details of this pathway remain to be elucidated. Copyright (c) 2005 S. Karger AG, Base

Bioeffects of 1.5T Static Magnetic Field on the DNA Strand of Human Leukocytes in Vitroduring MRI Scan

Background: The non ionization of magnetic resonance fields effect sreported   with radical pair recombination. Which   is one of the familiar methods by which static magnetic felid interact with biological systems. Exposure to static magnetic fields can effect on the paramagnetic free radicals by increasing  the concentration, the activity and life time of paramagnetic free radicals, which might lead to genetic mutation, oxidative stress, and in some times with apoptosis. Objective: To estimate the genotoxicity on DNA molecule during expose to static magnetic field 1.5T of magnetic resonance imaging. Patients and Methods: The five blood   samples were irradiated  to 1.5T static magnetic field at different periods (10,20,30,40,and 50 minutes correspondingly). All exposures were performed at room temperature. Cellular  DNA damage had been  analyzed by the alkaline comet assay.                                                                     Results: The results approved a significant increasing  in the rate of recurrence of single-strand DNA breaks next to the  exposure of  a 1.5T of magnetic resonance imaging at 50 min. According to these  results the exposure with 3T magnetic resonance imaging encourage genotoxic effects in human lymphocytes could be suggested. Conclusion: To conclude, in the present study, employing alkaline comet assay, it has been demonstrated thatmagnetic resonance imaging- induced  DNA damages is significant in  leukocytes at 50 minute after exprosure to 1.5T magnetic resonance imaging

The effect of pramipexole extended release on the levodopa equivalent daily dose in Lebanese Parkinson diseased patients

Objective: The objective of this study is to compute the potential benefit of Pramipexole ER on total levodopa equivalent dose (LED) and Unified Parkinson Disease Rating Score (UPDRS-III) compared to mono- or combined therapy of pramipexole IR and/or carbidopa/levodopa. Methods: This is a retrospective observational study conducted in a specialized PD (Parkinson Disease) and movement disease center in Lebanon between January and December 2017. Results: A total of 176 patient’s record was reviewed. Pramipexole ER showed a significant difference on the mean changes in LED and UPDRS-III score. After 13 weeks of initiating Pramipexole ER, the mean decrease in LED was -49.42 mg for all patients (p < 0.001, CI 95% [35.28-63.55]) and the mean decrease in UPDRS-III score for all patients was -6 points (P< 0.001). According to the subgroup analysis, patients aged 65 years and below, the change in mean total LED from baseline ( 350.80 mg) was a decrease of 63.19 mg with a p<0.001, CI 95% [42.07-84.31]. In patients aged more than 65 years and shifted to mono or combined pramipexole ER therapy, the change in mean total LED from baseline (559.25 mg) was a decrease of 34.67 mg with a p<0.001 CI 95% [16.16-53.18]. In addition the results showed that in patients having an UPDRS-III score of less than or equal to 33, the change in mean total LED from baseline (436.73 mg) was a decrease of 56.76 mg (p<0.001; CI 95% [41.32-72.20]). However, in patients having an UPDRS-III score of more than 33 the change in mean total LED from baseline (545.06 mg) was a decrease of 2.96 mg with a p value < 0.844 CI 95% [27.32-33.15]. Conclusions: This study demonstrated the efficacy of Pramipexole ER on decreasing the total levodopa equivalent dose (LED).The role of health care professionals is to maintain the patient on the lowest effective levodopa equivalent daily dose and optimize the treatment therapy, thus decreasing the side effects that might arise from overdosing of antiparkinsonian drugs