scholarly journals Canine Mesenchymal Cell Lyosecretome Production and Safety Evaluation after Allogenic Intraarticular Injection in Osteoarthritic Dogs

Animals ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3271
Author(s):  
Michela Mocchi ◽  
Elia Bari ◽  
Silvia Dotti ◽  
Riccardo Villa ◽  
Priscilla Berni ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Functional Disability ◽  
Musculoskeletal Diseases ◽  
Safety Evaluation ◽  
Mesenchymal Cell ◽  
Intraarticular Injection ◽  
Dependent Manner ◽  
Current Standard ◽  
Disability Score ◽  
Freeze Dried

In recent years, mesenchymal stromal cells (MSCs) have shown promise as a therapy in treating musculoskeletal diseases, and it is currently believed that their therapeutic effect is mainly related to the release of proteins and extracellular vesicles (EVs), known as secretome. In this work, three batches of canine MSC-secretome were prepared by standardized processes according to the current standard ISO9001 and formulated as a freeze-dried powder named Lyosecretome. The final products were characterized in protein and lipid content, EV size distribution and tested to ensure the microbiological safety required for intraarticular injection. Lyosecretome induced the proliferation of adipose tissue-derived canine MSCs, tenocytes, and chondrocytes in a dose-dependent manner and showed anti-elastase activity, reaching 85% of inhibitory activity at a 20 mg/mL concentration. Finally, to evaluate the safety of the preparation, three patients affected by bilateral knee or elbow osteoarthritis were treated with two intra-articular injections (t = 0 and t = 40 days) of the allogeneic Lyosecretome (20 mg corresponding 2 × 106 cell equivalents) resuspended in hyaluronic acid in one joint and placebo (mannitol resuspended in hyaluronic acid) in the other joint. To establish the safety of the treatment, the follow-up included a questionnaire addressed to the owner and orthopaedic examinations to assess lameness grade, pain score, functional disability score and range of motion up to day 80 post-treatment. Overall, the collected data suggest that intra-articular injection of allogeneic Lyosecretome is safe and does not induce a clinically significant local or systemic adverse response.

scholarly journals Secreted KIAA1199 promotes the progression of rheumatoid arthritis by mediating hyaluronic acid degradation in an ANXA1-dependent manner

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wei Zhang ◽  
Guoyu Yin ◽  
Heping Zhao ◽  
Hanzhi Ling ◽  
Zhen Xie ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Hyaluronic Acid ◽  
Dependent Manner ◽  
Collagen Induced Arthritis ◽  
Intracellular Degradation ◽  
Main Pathway ◽  
First Time

AbstractIn inflamed joints, enhanced hyaluronic acid (HA) degradation is closely related to the pathogenesis of rheumatoid arthritis (RA). KIAA1199 has been identified as a hyaladherin that mediates the intracellular degradation of HA, but its extracellular function remains unclear. In this study, we found that the serum and synovial levels of secreted KIAA1199 (sKIAA1199) and low-molecular-weight HA (LMW-HA, MW < 100 kDa) in RA patients were significantly increased, and the positive correlation between them was shown for the first time. Of note, treatment with anti-KIAA1199 mAb effectively alleviated the severity of arthritis and reduced serum LMW-HA levels and cytokine secretion in collagen-induced arthritis (CIA) mice. In vitro, sKIAA1199 was shown to mediate exogenous HA degradation by attaching to the cell membrane of RA fibroblast-like synoviosytes (RA FLS). Furthermore, the HA-degrading activity of sKIAA1199 depended largely on its adhesion to the membrane, which was achieved by its G8 domain binding to ANXA1. In vivo, kiaa1199-KO mice exhibited greater resistance to collagen-induced arthritis. Interestingly, this resistance could be partially reversed by intra-articular injection of vectors encoding full-length KIAA1199 instead of G8-deleted KIAA119 mutant, which further confirmed the indispensable role of G8 domain in KIAA1199 involvement in RA pathological processes. Mechanically, the activation of NF-κB by interleukin-6 (IL-6) through PI3K/Akt signaling is suggested to be the main pathway to induce KIAA1199 expression in RA FLS. In conclusion, our study supported the contribution of sKIAA1199 to RA pathogenesis, providing a new therapeutic target for RA by blocking sKIAA1199-mediated HA degradation.

Modeling the cost-effectiveness of a new treatment for MS (natalizumab) compared with current standard practice in Sweden

2008 ◽  
Vol 14 (5) ◽  
pp. 679-690 ◽  
Author(s):  
G Kobelt ◽  
J Berg ◽  
P Lindgren ◽  
B Jonsson ◽  
L Stawiarz ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cost Effectiveness ◽  
Societal Perspective ◽  
Functional Disability ◽  
Health Benefit ◽  
Base Case ◽  
Current Standard ◽  
Disease Modifying Drugs ◽  
New Treatment ◽  
The Cost

Objective To estimate the cost-effectiveness of a new treatment (natalizumab) for multiple sclerosis (MS) compared with current standard therapy with disease-modifying drugs (DMDs) in Sweden. Methods A Markov model was constructed to illustrate disease progression based on functional disability (the Expanded Disability Status Scale (EDSS)). The effectiveness of natalizumab was based on a 2-year clinical trial in 942 patients (AFFIRM). The effectiveness of current DMDs was estimated from a matched sample of 512 patients in the Stockholm MS registry. Patients withdrawing from treatment were assumed to follow the disease course of 824 patients with relapsing–remitting disease at onset in the Ontario natural history cohort. Costs and utilities are based on a recent observational study in 1339 patients. All data sets were available at the patient level. Main results are presented from the societal perspective, over a 20-year time frame, in 2005 Euros (€1 = 9.25 SEK). Results In the base case, treatment with natalizumab was less expensive and more effective than treatment with current DMDs. When only healthcare costs were considered, the cost per quality-adjusted life year gained with natalizumab was €38 145. Results are sensitive only to the time horizon of the analysis and assumptions about effectiveness of natalizumab beyond the trial. Conclusions This cost-effectiveness analysis used registry data, cohort and observational studies to extrapolate the efficacy findings of natalizumab from the AFFIRM clinical trial to measure effectiveness in clinical practice. The analysis results suggest that for the population considered, natalizumab provides an additional health benefit at a similar cost to current DMDs from a societal perspective.

scholarly journals A Preliminary Preparation of Endophytic Bacteria CE3 Wettable Powder for Biological Control of Postharvest Diseases

2015 ◽  
Vol 43 (1) ◽  
pp. 159-164 ◽  
Author(s):  
Hua CHENG ◽  
Linling LI ◽  
Juan HUA ◽  
Honghui YUAN ◽  
Shuiyuan CHENG
Keyword(s):  
Biological Control ◽  
Synergistic Effects ◽  
Lethal Dose ◽  
Safety Evaluation ◽  
Field Application ◽  
Fruit Rot ◽  
Postharvest Diseases ◽  
Freeze Dried ◽  
Wettable Powder ◽  
Endothia Parasitica

Recently, there has been an increasing interest among researchers in using combinations of biological control agents to exploit potential synergistic effects among them. In the present study, there were investigated commercially acceptable formulations of Bacillus cereus CE3 wetting powder with long storage life and retained efficacy to control chestnut and other fruit rot caused by Endothia parasitica (Murr) and Fusarium solani. The study sought to develop a new B. cereus formulation that would be more effective and better suited to the conditions of field application. By a series of experiments, the formulation was confirmed as follows: 60% B. cereus freeze-dried powder, 28.9% diatomite as carrier, 4% sodium lignin sulfonate as disperser, 6% alkyl naphthalene sulfonate as wetting agent, 1% K2HPO4 as stabilizer, 0.1% β-cyclodextrin as ultraviolet protectant. The controlling experiments showed that the diluted 100 times of 60% B. cereus wetting powder had 79.47% corrosion rate to chestnut pathogens; and this result is comparable to the diluted 1,000 times of 70% thiophanate-methyl. Safety evaluation results showed that rats acute oral lethal dose 50% was 5,000.35, therefore application of B. cereus wettable powder could not cause a person or animal poisoning. This work illustrated that 60% B. cereus wetting powder had commercial potential; however, to apply this formulation as a biological pesticide in the field, masses production processes need to be further studied.

A Longitudinal Analysis of Functional Disability, Recovery, and Nursing Home Utilization After Hospitalization for Ambulatory Care Sensitive Conditions Among Community-Living Older Persons

2021 ◽  
Vol 16 (8) ◽  
Author(s):  
Cameron J Gettel ◽  
Arjun K Venkatesh ◽  
Linda S Leo-Summers ◽  
Terrence E Murphy ◽  
Evelyne A Gahbauer ◽  
...  
Keyword(s):  
Nursing Home ◽  
Ambulatory Care ◽  
Functional Recovery ◽  
Older Persons ◽  
Functional Disability ◽  
Ambulatory Care Sensitive Conditions ◽  
Disability Score ◽  
Patient Reported ◽  
The Mean ◽  
Monthly Probability

BACKGROUND/OBJECTIVE: Hospitalizations for ambulatory care sensitive conditions (ACSCs) are considered potentially preventable. With little known about the functional outcomes of older persons after ACSC-related hospitalizations, our objectives were to describe: (1) the 6-month course of postdischarge functional disability, (2) the cumulative monthly probability of functional recovery, and (3) the cumulative monthly probability of incident nursing home (NH) admission. METHODS: The analytic sample included 251 ACSC-related hospitalizations from a cohort of 754 nondisabled, community-living persons aged 70 years and older who were interviewed monthly for up to 19 years. Patient-reported disability scores in basic, instrumental, and mobility activities ranged from 0 to 13. Functional recovery was defined as returning within 6 months of discharge to a total disability score less than or equal to that immediately preceding hospitalization. RESULTS: The mean age was 85.1 years, and the mean disability score was 5.4 in the month prior to the ACSC-related hospitalization. After the ACSC-related hospitalization, total disability scores peaked at month 1 and improved modestly over the next 5 months, but remained greater than the pre-hospitalization score. Functional recovery was achieved by 70% of patients, and incident NH admission was experienced by 50% within 6 months after the 251 ACSC-related hospitalizations. CONCLUSIONS: During the 6 months after an ACSC-related hospitalization, older persons exhibited total disability scores that were higher than those immediately preceding hospitalization, with 3 of 10 not achieving functional recovery and half experiencing incident NH admission. These findings provide evidence that older persons experience clinically meaningful adverse patient-reported outcomes after ACSC-related hospitalizations.

scholarly journals Evaluation of allogeneic freeze-dried platelet lysate in cartilage exposed to interleukin 1-β in vitro

2019 ◽  
Vol 15 (1) ◽  
Author(s):  
Livia Camargo Garbin ◽  
C. Wayne McIlwraith ◽  
David D. Frisbie
Keyword(s):  
Musculoskeletal Diseases ◽  
Platelet Rich Plasma ◽  
Autologous Blood ◽  
Interleukin 1 ◽  
Platelet Lysate ◽  
Freeze Dried ◽  
Platelet Concentration ◽  
High Concentrations ◽  
Disease Modifying Treatment

Abstract Background Platelet-rich plasma (PRP) as well as other platelet-derived products have been used as a potential disease-modifying treatment for musculoskeletal diseases, such as osteoarthritis (OA). The restorative properties of such products rely mainly on the high concentrations of growth factors, demonstrating encouraging results experimentally and clinically. Yet, the autologous blood-derived nature of the PRP product lead to limitations that precludes it’s widespread use. The main limitations for PRP use are; product variability, the need for minimum laboratory settings in most cases, and the need for storage at low temperatures to preserve its properties. Based on these limitations, the objective of this study was to investigate an allogeneic off-the-shelf platelet lysate (PL) in cartilage exposed to interleukin 1β (IL-1β). For this purpose, blood and cartilage were harvested from eight skeletally mature and healthy horses. Blood was processed into PL aliquots and divided into three groups (Frozen, Freeze-dried and Filtered freeze-dried), used in autologous and allogeneic conditions and in three different concentrations (1.5, 3 and 6-fold). Different PL preparations were then applied in cartilage culture with interleukin-1 beta and cultured for 10 days. Cartilage and media samples were collected and analyzed for total GAG and 35SO4-labeled GAG content. Results No significant differences between the controls and PL groups in cartilage and media were demonstrated. The effects of PL on cartilage matrix were concentration dependent and intermediate concentrations (3-fold) in PL showed increased 35SO4-labelled GAG in cartilage. Conclusion In conclusion, the allogeneic freeze-dried PL presented equivalent effects compared to frozen autologous PL. Intermediate platelet concentration on average demonstrated improved results, demonstrating less GAG loss compared to other concentrations.

scholarly journals The Pseudomonas aeruginosa product pyochelin interferes with Trypanosoma cruzi infection and multiplication in vitro

2020 ◽  
Vol 114 (7) ◽  
pp. 492-498 ◽  
Author(s):  
Gabriele Sass ◽  
Laura C Miller Conrad ◽  
Terrence-Thang H Nguyen ◽  
David A Stevens
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Trypanosoma Cruzi ◽  
Mammalian Cells ◽  
Iron Acquisition ◽  
Vero Cells ◽  
Dependent Manner ◽  
Wild Type ◽  
Current Standard ◽  
Cruzi Infection

Abstract Background Bacteria are sources of numerous molecules used in treatment of infectious diseases. We investigated effects of molecules produced by 26 Pseudomonas aeruginosa strains against infection of mammalian cell cultures with Trypanosoma cruzi, the aetiological agent of Chagas disease. Methods Vero cells were infected with T. cruzi in the presence of wild-type P. aeruginosa supernatants or supernatants of mutants with defects in the production of various virulence, quorum sensing and iron acquisition factors. Quantification of T. cruzi infection (percentage of infected cells) and multiplication (number of amastigotes per infected cell) was performed and cell viability was determined. Results Wild-type P. aeruginosa products negatively affected T. cruzi infection and multiplication in a dose-dependent manner, without evident toxicity for mammalian cells. PvdD/pchE mutation (loss of the P. aeruginosa siderophores pyoverdine and pyochelin) had the greatest impact on anti–T. cruzi activity. Negative effects on T. cruzi infection by pure pyochelin, but not pyoverdine, or other P. aeruginosa exoproducts studied, were quantitatively similar to the effects of benznidazole, the current standard therapy against T. cruzi. Conclusions The P. aeruginosa product pyochelin showed promising activity against T. cruzi and might become a new lead molecule for therapy development.

scholarly journals Comparative effectiveness of extracorporeal shock wave therapy, local corticosteroid injection, and conventional physiotherapy in treatment of chronic lateral epicondylitis

2020 ◽  
Vol 47 (1) ◽  
Author(s):  
Mona Mohamed Mohamed Ismael ◽  
Mona Mahmoud Arafa ◽  
Abeer Ahmed Kadry El Zohiery ◽  
Soha Eldessouki Ibrahim
Keyword(s):  
Functional Disability ◽  
Corticosteroid Injection ◽  
Lateral Epicondylitis ◽  
Extracorporeal Shock Wave Therapy ◽  
Considerable Change ◽  
Disability Score ◽  
Vas Score ◽  
Extracorporeal Shock Wave ◽  
Conventional Physiotherapy

Abstract Background Lateral epicondylitis (LE) is a popular overuse syndrome involving the forearm’s extensor tendons. Corticosteroid (CS) injection is the popular injection used for management of LE. Extracorporeal shockwave therapy (ESWT) is a noninvasive alternative inducing the neovascularization, tendon repairing, and decreasing pain. Our study aimed to compare the effectiveness of ESWT versus local CS injection versus conventional physiotherapy (PT) in management of chronic LE. Results Our results revealed that the three groups displayed a significant decrease of VAS score, decrease of PRTEE score, and increase of grip strength compared to baseline (P < 0.05) at 4 weeks and 12 weeks of follow-up. However, there was a significant decrease of VAS score in ESWT and CS groups more than PT group at 4 weeks follow-up (P < 0.05) while ESWT group displayed a considerable improvement in functional disability score (decrease in PRTEE score) more than CS and PT groups at 4 and 12 weeks of follow-up (P < 0.05), with no considerable change in HGS between the three groups. Conclusion ESWT, local CS injection, and conventional PT were efficient in management of chronic LE at 12 weeks of follow-up but ESWT had a higher effect decreasing pain and improving functional disability in daily life activity at short and long term follow-up.

scholarly journals Ionic Nanocomplexes of Hyaluronic Acid and Polyarginine to Form Solid Materials: A Green Methodology to Obtain Sponges with Biomedical Potential

Nanomaterials ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 944
Author(s):  
María Gabriela Villamizar-Sarmiento ◽  
Ignacio Moreno-Villoslada ◽  
Samuel Martínez ◽  
Annesi Giacaman ◽  
Victor Miranda ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
High Capacity ◽  
Solid Material ◽  
Fibroblast Cell ◽  
High Porosity ◽  
Design Development ◽  
Solid Materials ◽  
Transmission Electron ◽  
Freeze Dried ◽  
Scanning Transmission

We report on the design, development, characterization, and a preliminary cellular evaluation of a novel solid material. This material is composed of low-molecular-weight hyaluronic acid (LMWHA) and polyarginine (PArg), which generate aqueous ionic nanocomplexes (INC) that are then freeze-dried to create the final product. Different ratios of LMWHA/PArg were selected to elaborate INC, the size and zeta potential of which ranged from 100 to 200 nm and +25 to −43 mV, respectively. Turbidimetry and nanoparticle concentration analyses demonstrated the high capacity of the INC to interact with increasing concentrations of LMWHA, improving the yield of production of the nanostructures. Interestingly, once the selected formulations of INC were freeze-dried, only those comprising a larger excess of LMWHA could form reproducible sponge formulations, as seen with the naked eye. This optical behavior was consistent with the scanning transmission electron microscopy (STEM) images, which showed a tendency of the particles to agglomerate when an excess of LMWHA was present. Mechanical characterization evidenced low stiffness in the materials, attributed to the low density and high porosity. A preliminary cellular evaluation in a fibroblast cell line (RMF-EG) evidenced the concentration range where swollen formulations did not affect cell proliferation (93–464 µM) at 24, 48, or 72 h. Considering that the reproducible sponge formulations were elaborated following inexpensive and non-contaminant methods and comprised bioactive components, we postulate them with potential for biomedical purposes. Additionally, this systematic study provides important information to design reproducible porous solid materials using ionic nanocomplexes.

Safety Evaluation for the Highway Alignment with 3D Visual Simulation

2012 ◽  
Vol 182-183 ◽  
pp. 1131-1134
Author(s):  
Xiao Jia Chen ◽  
Yi Cheng Luo
Keyword(s):  
Safety Evaluation ◽  
Visual Simulation ◽  
Horizontal Curve ◽  
Current Standard ◽  
Highway Design ◽  
Standard Requirement ◽  
Sight Distance ◽  
Real Scene ◽  
A Minor ◽  
Highway Alignment

In the current highway design, poor coordinate of the alignment has a great effect on the sight distance which would increase the danger and difficulty of driving. For this reason, safety checking for highway alignment is required by the current standard. In this paper, 3D simulation technique was used to model the real scene of driving. Based on the concept of the preview sight distance (PVSD), two typical coordinates of alignment in practice were discussed. Although the current standard requirement is met, it is demonstrated that the alignment in the location of a minor horizontal curve and combination of a tangent with a circular curve could still provide driver confusing information. Some recommendations were suggested so as to improve the highway alignment design.

Sign in / Sign up

Export Citation Format

Share Document