scholarly journals Intra-Articular Slow-Release Triamcinolone Acetonide from Polyesteramide Microspheres as a Treatment for Osteoarthritis

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 372
Author(s):  
Anna Tellegen ◽  
Martijn Beukers ◽  
Imke Rudnik-Jansen ◽  
Nicolien van Klaveren ◽  
Kan Loi How ◽  
...  

Osteoarthritis (OA) is a common cause of pain and disability. Local corticosteroid injections are effective in treating OA pain and inflammation but are short-acting. Prolonged intra-articular (IA) corticosteroid exposure may even lead to cartilage deterioration. The aim of this prospective study was to assess safety and provide proof-of-concept of IA-applied biodegradable polyesteramide-based microspheres (PEAMs) gradually releasing triamcinolone acetonide (TA). Mimicking continuous exposure associated with local drug delivery in canine articular chondrocytes cultured in the continuous presence of TA tissue regeneration was not affected, whereas intermittent exposure reduced proteoglycan production. In this respect, TA-PEAMs administered IA in a proof-of-concept study in 12 client-owned dogs with established OA also showed safety by radiographic examination, without changes in OA severity and in glycosaminoglycan synovial fluid levels. Treatment also resulted in clinical improvement in 10 out of 11 dogs during the two-month follow-up period, which persisted in 6 out of 10 dogs after 6 months, based on objective gait analysis and owner questionnaires. Synovial prostaglandin E2, a pro-inflammatory marker, was decreased two months after treatment. This study showed safety and proof-of-concept of IA-administered TA-PEAMs in dogs with OA, as a first step towards translation into the veterinary and human clinic.

1983 ◽  
Vol 92 (6) ◽  
pp. 623-628 ◽  
Author(s):  
Joseph Sataloff ◽  
Robert T. Sataloff ◽  
Raymond A. Yerg ◽  
Hyman Menduke ◽  
Robert P. Gore

Most studies of the effects of noise upon hearing have dealt with continuous noise exposure. Previous reports on intermittent exposure to noise concluded that it causes less damage to hearing than does continuous exposure to noise of the same intensity. In this investigation, 12,000 workers were screened to find 295 subjects who met the strict criteria of the study. Most of the subjects were exposed to jackhammer noise at peak levels of 118 dBA. Intermittent exposure to intense noise results in very severe loss in high frequencies but relatively little or no hearing loss in the lower frequencies even after many years of exposure. This differs substantially from the effects of continuous exposure to noise of the same intensity. It remains to be determined whether this pattern of hearing results from intermittent exposure to all sorts of noise or only from the kinds of sources investigated in this study.


2009 ◽  
Vol 70 (12) ◽  
pp. 1494-1501 ◽  
Author(s):  
Elysia C. Schaefer ◽  
Allison A. Stewart ◽  
Sushmitha S. Durgam ◽  
Christopher R. Byron ◽  
Matthew C. Stewart

2006 ◽  
Vol 100 (3) ◽  
pp. 869-879 ◽  
Author(s):  
J. M. Clark ◽  
C. J. Lambertsen ◽  
R. Gelfand ◽  
A. B. Troxel

Optimization of oxygen tolerance extension by intermittent exposure was studied in groups of 20 rats exposed to systematically varied patterns of alternating oxygen and normoxic breathing periods at 4.0, 2.0, and 1.5 ATA. Oxygen periods of 20, 60, and 120 min were alternated with normoxic intervals that provided oxygen-to-normoxia ratios of 4:1, 2:1, 1:1, and 1:3. In general, median survival times had nearly linear relationships to increasing normoxic intervals with oxygen period held constant. Exceptions occurred at 4.0 and 2.0 ATA where a 5-min normoxic interval was too short for adequate recovery even with a 20-min oxygen period, and an oxygen period of 120 min was too long even with a normoxic interval of 30 min. These exceptions did not occur at 1.5 ATA. Survival time for many intermittent exposure patterns was equivalent to that for continuous exposure to an oxygen pressure definable as a time-weighted average of the alternating oxygen and normoxia periods. However, this predictive method underestimated the degree of protection achieved by several of the intermittent exposure patterns, especially those performed at 4.0 ATA. Results provided guidance for selection of intermittent exposure patterns for direct evaluation in humans breathing oxygen at 2.0 ATA. Definition of intermittent exposure patterns and conditions that produced prominent gains in oxygen tolerance can also facilitate the performance of future experiments designed to study potential mechanisms for oxygen tolerance extension by intermittent exposure. Heat shock and oxidation-specific stress proteins that are induced by exposure to oxidant injury are suggested for emphasis in such investigations.


Development ◽  
1980 ◽  
Vol 60 (1) ◽  
pp. 71-82
Author(s):  
G. Siracusa ◽  
D. G. Whittingham ◽  
M. De Felici

The sensitivity of early preimplantation mouse embryos to drugs which disrupt microfilament function (cytochalasin B-CB and cytochalasin D-CD) and microtubule assembly (colchicine, colcemid, vinblastine and griseofulvin) was examined. CD inhibited cleavage at a concentration 35-fold lower than CB (3 × 10−7 M ν. 1 × 10−5 M). Treatment of 2-cell embryos for 6 h with 1 × 10−5 M CB or 1 × 10−6 M CD or continuous exposure to lower concentrations of CB or CD did not affect development to the blastocyst stage in vitro. Vinblastine inhibited cleavage at a concentration tenfold lower than colcemid or colchicine (1 × 10−8 M ν. 1 × 10−7 M). The continuous presence of colcemid at 10−8 M did not affect the development of 2-cell embryos to the blastocyst stage, but development was reduced with vinblastine at 1 × 10−8 M and completely inhibited with colchicine at 1 × 10−8 M. The drugs produced similar responses when 2-cell embryos were treated for 6 h with concentrations that inhibited cleavage. Complete inhibition of cleavage was obtained after only a 2 h exposure to 2 × 10−7 M colchicine. A similar concentration of lumicolchicine did not affect cleavage or blastocyst formation. Embryos were less sensitive to griseofulvin; the first cleavage division was unaffected by concentrations as high as 3 × 10−4 M and only 50% of 2-cell embryos failed to cleave in 1 × 10 1 and 3 × 10−4 M griseofulvin. At these concentrations a small proportion of 1-cell embryos and the majority of the 2-cell embryos showed unequal cytoplasmic division probably caused by the formation of multipolar spindles. The continuous exposure of 2-cell embryos to 3 × 10−5 M griseofulvin did not affect blastocyst formation.


2018 ◽  
Vol 59 (2) ◽  
pp. 179-188 ◽  
Author(s):  
Naofumi Kameyama ◽  
Shotaro Chubachi ◽  
Ahmed E. Hegab ◽  
Hiroyuki Yasuda ◽  
Shizuko Kagawa ◽  
...  

1988 ◽  
Vol 254 (6) ◽  
pp. H1194-H1199
Author(s):  
T. H. Adair ◽  
J. P. Montani ◽  
A. C. Guyton

We explored whether the blood vascular system of the chick embryo adapts its structure to meet the maximum or average oxygen needs of the tissue cells. Chick embryos were grown in continuous 12% oxygen, continuous 16% oxygen, and intermittent 12% oxygen in which the embryos were exposed to 12% oxygen for 4 h each day. Control groups were grown in room air. Measurements of structural vascular resistance (SVR), i.e., the resistance of the maximally dilated vasculature, were used to estimate the whole body vascularity of the 14- or 15-day-old embryos. Continuous exposure to 12% oxygen decreased SVR by 63.1 +/- 1.2 (SE) %, and intermittent exposure to 12% oxygen decreased SVR by 55.6 +/- 0.5% when compared with a 15-day-old normoxic control group. Based on studies with continuous exposure to different levels of low oxygen, it was predicted that exposure to 19.5% oxygen, the average concentration for the intermittent hypoxia group, would decrease SVR by 15.0 +/- 0.3%. These results indicate that intermittent hypoxia at 12% oxygen was approximately 90% as effective as continuous hypoxia at the same level in decreasing SVR and about four times more effective than 19.5% continuous oxygen. Therefore, the results support the hypothesis that the blood vascular system adapts its structure to meet almost entirely the maximum oxygen needs of the tissue cells.


2011 ◽  
Vol 28 (3) ◽  
pp. 143-155 ◽  
Author(s):  
Allison J. Matthews ◽  
Zee H. Wong ◽  
Joel D. Scanlan ◽  
Ken C. Kirkby

AbstractBackground: The aim of this research was to evaluate an online exposure treatment for spider phobia (www.feardrop.com) and to investigate the effects of intermittent versus continuous exposure.Methods: Spider phobic participants (N = 23) completed two 14-minute stages of laboratory-based online exposure. In the first of these stages exposure was either continuous or intermittent (alternating fearrelevant and -irrelevant images). One week later, participants commenced a sixstage home-based graded online exposure task, which was undertaken over 30 days. Subjective Units of Distress Scale (SUDS) ratings were taken throughout all exposure stages. Spider fear was assessed prior to treatment, and at 1-week and 1-month post treatment.Results: Habituation was observed across each stage for both the laboratory and home-based tasks and generalisation of habituation was found between stages. Habituation was not impaired in the alternating fear-relevant and -irrelevant image condition, though subjects experienced less summed anxiety. Adherence rates were low in home-based online exposure. However, participants who completed 30-days post-treatment assessment (n = 14) showed a significant reduction in spider fear as measured by the Fear of Spiders Questionnaire (FSQ).Conclusions: Online exposure produces habituation and generalisation of habituation to spider images as well as longer-term reductions in spider fear. Alternating fear-relevant and -irrelevant exposure is feasible in online exposure and may lead to habituation with less summed anxiety that has implications for tolerability and acceptability. Measures to increase adherence rates and hence dosage delivered are a key consideration for further online exposure research.


Author(s):  
J.C.S. Kim ◽  
M.G. Jourden ◽  
E.S. Carlisle

Chronic exposure to nitrogen dioxide in rodents has shown that injury reaches a maximum after 24 hours, and a reparative adaptive phase follows (1). Damage occurring in the terminal bronchioles and proximal portions of the alveolar ducts in rats has been extensively studied by both light and electron microscopy (1).The present study was undertaken to compare the response of lung tissue to intermittent exposure to 10 ppm of nitrogen dioxide gas for 4 hours per week, while the hamsters were on a vitamin A deficient diet. Ultrastructural observations made from lung tissues obtained from non-gas exposed, hypovitaminosis A animals and gas exposed animals fed a regular commercially prepared diet have been compared to elucidate the specific effect of vitamin A on nitrogen dioxide gas exposure. The interaction occurring between vitamin A and nitrogen dioxide gas has not previously been investigated.


Author(s):  
D.R. Mattie ◽  
C.J. Hixson

Dimethylmethylphosphonate (DMMP) is a simple organophosphate used industrially as a flame retardant and to lower viscosity in polyester and epoxy resins. The military considered the use of DMMP as a nerve gas simulant. Since military use of DMMP involved exposure by inhalation, there was a need for a subchronic inhalation exposure to DMMP to fully investigate its toxic potential.Male Fischer-344 rats were exposed to 25 ppm or 250 ppm DMMP vapor on a continuous basis for 90 days. An equal number of control rats were sham-exposed. Following the 90-day continuous exposure period, 15 male rats were sacrificed from each group. Two rats from each group had the left kidney perfused for electron microscopic examination. The kidneys were perfused from a height of 150 cm water with 1% glutaraldehyde in Sorensen's 0.1M phosphate buffer pH 7.2. An additional kidney was taken from a rat in each group and fixed by immersion in 2.5% glutaraldehyde and 2% paraformaldehyde in 0.1M cacodylate buffer pH 7.4. A portion of the 9 kidneys collected for electron microscopy were processed into Epon 812. Thin sections, stained with uranyl acetate and lead citrate, were examined with a JEOL 100B Transmission Electron Microscope. Microvilli height was measured on photographs of the cells of proximal tubules. This data, along with morphologic features of the cells, allows the proximal convoluted tubules (PCT) to be identified as being S1, S2, or S3 segment PCT.


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