scholarly journals The Anti-Arthritic Efficacy of Khellin Loaded in Ascorbyl Decanoate Nanovesicles after an Intra-Articular Administration

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1275
Author(s):  
Giulia Vanti ◽  
Lorenzo Di Cesare Mannelli ◽  
Laura Micheli ◽  
Lorenzo Cinci ◽  
Lucia Grifoni ◽  
...  

Osteoarthritis is the most widespread joint-affecting disease. The management of persistent pain remains inadequate and demands new therapeutic strategies. In this study, we explored the pain relieving and protective properties of a single intra-articular (i.a.) injection of khellin loaded in nanovesicles (K-Ves) based on ascorbyl decanoate plus phosphatidylcholine in a rat model of osteoarthritis (OA) induced by monosodium iodoacetate (MIA) treatment. The developed nanovesicles (approximately 136 nm) had a narrow size distribution (PdI 0.26), a good recovery (about 80%) and a worthy encapsulation efficiency (about 70%) with a ζ-potential of about −40 mV. The stability of K-Ves was assessed in simulated synovial fluid. Seven days after the articular damage with MIA, both K-Ves and a suspension of khellin (K, 50 μL) were i.a. injected. K-Ves significantly counteracted MIA-induced hypersensitivity to mechanical noxious (paw pressure test) and non-noxious stimuli (von Frey test) and significantly reduced the postural unbalance related to spontaneous pain (incapacitance test) and the motor alterations (beam balance test) 7 and 14 days after the i.a. injection. K was partially active only on day 7 after the treatment. The histology emphasized the improvement of several morphological factors in MIA plus K-Ves-treated animals. In conclusion, K-Ves could be successfully used for the local treatment of osteoarthritis.

2016 ◽  
Vol 29 (4) ◽  
pp. 1006-1014
Author(s):  
MARIA TERESA DE ALVARENGA FREIRE ◽  
RODRIGO RODRIGUES PETRUS ◽  
JOZETI APARECIDA BARBUTTI GATTI ◽  
MARIA FERNANDA BARBOSA LEITE ◽  
MARIANA TOMIE KUNITAKE ◽  
...  

ABSTRACT Cupuaçu (Theobroma grandiflorum Schum.) is an exotic fruit with a promising economic potential, particularly due to its strong aroma and creamy texture. This study aimed to produce sweetened cupuaçu puree and evaluate the effects of packaging corrosion on its sensory properties and shelf-life in tinplated cans. After 240 days of storage, the commercially sterile product had average sensory analysis scores of 5.89 ± 0.21, 5.39 ± 0.30, 5.45 ± 0.21 and 5.49 ± 0.25, for appearance, aroma, flavor and overall appreciation, respectively. Sensory acceptance scores did not change during storage (p>0.05). Corrosion potential and low tin and iron levels in the product, which are parameters used to evaluate food-packaging interaction, demonstrated the product remained food-safe throughout its shelf-life. Tinplate is a promising packaging material for sweetened cupuaçu puree due to its mechanical and protective properties. Furthermore, tin plating is an economically viable food technology to extend the shelf-life of cupuaçu products and expand its domestic and international markets.


2018 ◽  
Author(s):  
Robert L. Anderson ◽  
Darshan V. Trivedi ◽  
Saswata S. Sarkar ◽  
Marcus Henze ◽  
Weikang Ma ◽  
...  

Summary:Mutations in β-cardiac myosin, the predominant motor protein for human heart contraction, can alter power output and cause cardiomyopathy. However, measurements of the intrinsic force, velocity and ATPase activityof myosin have not provided a consistent mechanism to link mutations to muscle pathology. An alternative modelpositsthat mutations in myosin affect the stability ofa sequestered, super-relaxed state (SRX) of the proteinwith very slow ATP hydrolysis and thereby change the number of myosin heads accessible to actin. Here, using a combination of biochemical and structural approaches, we show that purified myosin enters aSRX thatcorresponds to a folded-back conformation, which in muscle fibersresults insequestration of heads around the thick filament backbone. Mutations that cause HCM destabilize this state, while the small molecule mavacamtenpromotes it. These findings provide a biochemical and structural link between the genetics and physiology ofcardiomyopathywith implications for therapeutic strategies.


Author(s):  
Cloé L. Esposito ◽  
Plamen Kirilov

With the increase in occupation-specific risks of lip cancer associated with solar radiation, there is a need for developing photoprotective lipsticks to protect skin against harmful effects of UV radiation. Considering the unique chemical and physical properties of low-molecular-weight organogelators (LMOGs), the present study intended to assess the UV protective properties of LMOGs-based lipstick formulations. In this study, dibenzylidene-D-sorbitol (DBS) and 12-hydroxystearic acid (12-HSA) were used to formulate lipsticks : L1 (1% DBS), L2 (10% 12-HSA), L3 (1.5% DBS) and L4 (control, no LMOGs). The lipstick formulations were tested for in vitro sun protection factors (SPF), UVA protection factor (UVA-PF), thermal, mechanical and texture analyses. Lipsticks with LMOGs exhibited higher UVA-PF and SPF, and more particularly 12-HSA-based lipstick. Results showed also the viscoelastic and heat-resistant properties of LMOGs and their effect of increasing pay-off values. In general, texture analysis indicating that 12-HSA-based lipstick was significantly harder to bend compared to control, while other formulations became softer and easier to bend throughout the stability study. Finally, sensorial and instrumental analyses permitted to classify lipsticks into two groups. This work suggests the potential use of LMOGs as a structuring agent for lipsticks paving the way towards more photoprotective and sustainable-derived alternatives.


2021 ◽  
Vol 937 (4) ◽  
pp. 042052
Author(s):  
Galina Ambrosova ◽  
Anastasiia Kruglikova

Abstract This scientific work is devoted to the results of the local treatment facilities’ work for food enterprises sewerage. The complex under consideration is intended for the anaerobic processing of whey, formed during fermented milk production. Whey is one of the specific organic substances, which main component is lactose (sucrose). It is converted under anaerobic conditions into lactic acid, which is a metabolic dead end. The capacity can be used as a homogenizing tank, obtained in this way. In the future, it is proposed to increase the homogenizer volume to 100 m3. It is recommended to use ammonium hydroxide or sulfate to ensure the required ratio between COD and biogenic element (nitrogen) in the loaded whey. Possible biogenic additives can be sewage sludge or slurry. The experience of adjustment was shown that slurry from cattle farms was quite simple, inexpensive and quite effective. Slurry can be injected in 3-4 m3 every 2-3 days. The stability of pH values in the bioreactor can be ensured by the correct placement of sensors for monitoring this indicator and by changing the method of alkali introduction. It is recommended to install pH control sensors at the bottom of the bioreactor, instead of whey loading pipeline. In order to provide for fractional injection of alkali, we should introduce part of the alkali at the homogenization stage, and part directly into the bioreactor. For an unimpeded build-up of anaerobic biomass, it is recommended to replace the centrifuge thickener operating with flocculant with the classic version of thickening in a compactor without flocculant adding.


2020 ◽  
Vol 133 (2) ◽  
pp. 408-425 ◽  
Author(s):  
Guoliang Yu ◽  
Ian Segel ◽  
Zhiyong Zhang ◽  
Quinn H. Hogan ◽  
Bin Pan

Background Dorsal root ganglion field stimulation is an analgesic neuromodulation approach in use clinically, but its mechanism is unknown as there is no validated animal model for this purpose. The authors hypothesized that ganglion stimulation is effective in reducing pain-like behaviors in preclinical chronic pain models. Methods The authors provided ganglion stimulation or spinal cord stimulation to rats with traumatic neuropathy (tibial nerve injury), or osteoarthritis induced by intraarticular knee monosodium iodoacetate, or without injury (naïve). Analgesia was evaluated by testing a battery of pain-related reflexive, functional, and affective behaviors. Results In rats with nerve injury, multilevel L4 and L5 ganglion stimulation decreased hypersensitivity to noxious mechanical stimulation more (area under curve, −1,447 ± 423 min × % response; n = 12) than single level ganglion stimulation at L4 ([−960 ± 251 min × % response; n = 8; P = 0.012] vs. L4 and L5), and L5 ([−676 ± 295 min × % response; n = 8; P < 0.0001] vs. L4 and L5). Spontaneous pain-like behavior, evaluated by conditioned place preference, responded to single L4 (Pretest [−93 ± 65 s] vs. Test [87 ± 82 s]; P = 0.002; n = 9), L5 (Pretest [−57 ± 36 s] vs. Test [137 ± 73 s]; P = 0.001; n = 8), and multilevel L4 and L5 (Pretest: −81 ± 68 s vs. Test: 90 ± 76 s; P = 0.003; n = 8) ganglion stimulation. In rats with osteoarthritis, multilevel L3 and L4 ganglion stimulation reduced sensitivity to knee motion more (−156 ± 28 min × points; n = 8) than L3 ([−94 ± 19 min × points in knee bend test; n = 7; P = 0.002] vs. L3 and L4) or L4 ([−71 ± 22 min × points; n = 7; P < 0.0001] vs. L3 and L4). Conditioned place preference during osteoarthritis revealed analgesic effectiveness for ganglion stimulation when delivered at L3 (Pretest [−78 ± 77 s] vs. Test [68 ± 136 s]; P = 0.048; n = 9), L4 (Pretest [−96 ± 51 s] vs. Test [73 ± 111 s]; P = 0.004; n = 9), and L3 and L4 (Pretest [−69 ± 52 s; n = 7] vs. Test [55 ± 140 s]; P = 0.022; n = 7). Conclusions Dorsal root ganglion stimulation is effective in neuropathic and osteoarthritic preclinical rat pain models with peripheral pathologic origins, demonstrating effectiveness of ganglion stimulation in a placebo-free setting and justifying this model as a suitable platform for mechanistic studies. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New


2019 ◽  
Vol 95 (7) ◽  
pp. 669-675
Author(s):  
I. V. Novikova ◽  
G. V. Agafonov ◽  
E. A. Korotkikh ◽  
Vladislav N. Kalaev ◽  
M. S. Nechaeva ◽  
...  

There were performed studies of the occurrence of cells with pathologies in the buccal epithelium of volunteers who consume drinks based on mixtures ofpowdered malt and polymalt extracts of buckwheat, peas, corn and barley. There was shown their impact on the stability of the genetic material of examined cases. There was established activation of apoptosis, which leads to the elimination of cells with cytogenetic deteriorations. Poliymalt extracts possess protective properties, contribute to the suppression ofprocesses offormation of cells with genetic disorders (micronuclei (from 4.38 ± 0.67 %%, up to 2.53 ± 0.39 %% after intake), protrusions (from 1,98 ± 0,42 %%, up 0,85 ± 0,25 %% after intake), incisures (from 3.34 ± 0.44 %%, up 2.17 ± 0.35 %% after intake), two cores (from 1.63 ± 0.26 %%, up 0.65 ± 0.21 %% after intake) and rid the body of aberrant cells, as evidenced by the increase in the number of cells with karyolysis (up to 5.98 ± 0,91 %%, up 9.55 ± 1.74 %% after intake), karyopyknosis (from 10.71 ± 0.90 %%, up to 11.97 ± 0.85 %% after intake) and perinuclear vacuoles (from 9.24 ± 1.63 %%, up to 12.94 ± 2.57 %% after intake). In women, anti-mutagenic effects ofpolymalt extracts are more pronounced than in men. Antimutagenic effects of extracts can be explained by the properties of contained in them B vitamins and sulfur-containing amino acids (cysteine and methionine).


2019 ◽  
Vol 1 (2) ◽  
Author(s):  
Matthias Illgner ◽  
Maximilian Binder ◽  
Georg Schlick ◽  
Christian Seidel ◽  
Gunther Reinhart

Laser beam melting (LBM) offers the opportunity to manufacture highly complex structures and geometries and thus provides a big potential to produce lightweight parts. In previous research projects, a software tool has been developed that achieves the placement of hexagonal honeycombs (of any size and wall thickness) on free formed surfaces in a load-oriented manner and thus offers entirely new possibilities for designing lightweight components in CAD (e.g. [1–2]). This work examines the production of metal hexagonal honeycombs from the material AlSi10Mg with the LBM-process. By adapting the exposure and process parameters, it was possible to manufacture overhanging structures with an overhang angel < 30° (relative to build platform) without support structures, while still achieving an acceptable surface roughness (in the context of this study: Ra = 45 µm). Conventional complex and time consuming post-processing steps can thus be avoided and a higher utilization of building space can be achieved. Furthermore, since the critical size for a lightweight structure is the minimum possible density, it was investigated to which minimum values the wall thicknesses of the hexagonal structures can be reduced using LBM. Apart from that, the stability of the manufactured honeycombs was analyzed in as-built condition and heat treated by pressure test and related to the honeycomb density. This has been used to compare additively manufactured honeycombs with conventionally manufactured ones.


2011 ◽  
Vol 331 ◽  
pp. 257-260
Author(s):  
Sha Sha Sun ◽  
Jie Jie Wang ◽  
Ren Cheng Tang

The stability of Salvia miltiorrhiza Bge (SMB) extract and its dyeing and ultraviolet protective properties on silk were investigated. The results indicated that SMB extract was stable at acidic conditions and stable to heat and ultraviolet light. The building-up and UV-protective properties of SMB extract for silk were good and can be enhanced by mordanting with ferrous and ferric sulfate and copper sulfate. The light fastness rating was improved using ferric sulfate, while the washing and light fastness properties were worsen using ferrous sulfate.


Author(s):  
Ahsan Mian ◽  
Taslema Sultana ◽  
Golam Newaz

The stability of the laser bonded titanium coated glass/polyimide microjoints were studied in-vivo (by implanting on the rat brain surface for 10 days) and were compared with the earlier in-vitro (by soaking in artificial cerebrospinal fluid, CSF at 37°C for one week) data. In the current state, the strength of the joints were measured by a specially designed instrument called “pressure test” equipment where the samples were subjected to a variable pressure load (using high pressure nitrogen) controlled by a pressure regulator. The strength of the joints seems to degrade as a result of soaking in rat brain. The bond degradation in rat brain implants is similar compared to those soaked in CSF solution. Polyimide uptakes water through existing pores in it and also water gets in the joint region through the edges of the samples. Water might have caused oxidation of the chemical bonds which are thought to have formed by the laser fabrication process. Water availability at the joint region in implanted samples is less than that of the CSF soaked samples — which explains the better retention of the joint strength of the vivo samples. The average failure load from pressure test was found to be 1.4 N/mm, which is below the average tensile strength of the joint (7.3 N/mm) as published elsewhere by the authors. The difference between the joint strengths results from the difference in applied mechanical (joint peeling in pressure testing and joint shearing in tensile testing) loads and loading rates by the experiments.


2019 ◽  
Vol 20 (8) ◽  
pp. 1923 ◽  
Author(s):  
Micheli ◽  
Bozdag ◽  
Akgul ◽  
Carta ◽  
Guccione ◽  
...  

: To study new target-oriented molecules that are active against rheumatoid arthritis-dependent pain, new dual inhibitors incorporating both a carbonic anhydrase (CA)-binding moiety and a cyclooxygenase inhibitor (NSAID) were tested in a rat model of rheumatoid arthritis induced by CFA intra-articular (i.a.) injection. A comparison between a repeated per os treatment and a single i.a. injection was performed. CFA (50 µL) was injected in the tibiotarsal joint, and the effect of per os repeated treatment (1 mg kg−1) or single i.a injection (1 mg ml−1, 50 µL) with NSAIDs-CAIs hybrid molecules, named 4 and 5, was evaluated. The molecules 4 and 5, which were administered daily for 14 days, significantly prevented CFA-induced hypersensitivity to mechanical noxious (Paw pressure test) and non-noxious stimuli (von Frey test), the postural unbalance related to spontaneous pain (Incapacitance test) and motor alterations (Beam balance test). Moreover, to study a possible localized activity, 4 and 5 were formulated in liposomes (lipo 4 and lipo 5, both 1 mg ml-1) and directly administered by a single i.a. injection seven days after CFA injection. Lipo 5 decreased the mechanical hypersensitivity to noxious and non-noxious stimuli and improved motor coordination. Oral and i.a. treatments did not rescue the joint, as shown by the histological analysis. This new class of potent molecules, which is able to inhibit at the same time CA and cyclooxygenase, shows high activity in a preclinical condition of rheumatoid arthritis, strongly suggesting a novel attractive pharmacodynamic profile.


Sign in / Sign up

Export Citation Format

Share Document