Kenalog
Pulmonary targeting of liposomal triamcinolone acetonide phosphate.

Gonzalez-Rothi RJ, Suarez S, Hochhaus G, Schreier H, Lukyanov A, Derendorf H, Costa TD.

Pulmonary Division, University of Florida, Gainesville, USA.

PURPOSE: To explore the use of triamcinolone acetonide phosphate liposomes as a pulmonary targeted drug delivery system. METHODS: Triamcinolone acetonide phosphate liposomes composed of 1,2-distearoyl phosphatidylcholine and 1,2-distearoyl phosphatidyl glycerol and triamcinolone acetonide 21-phosphate dipotassium salt were prepared by dispersion and extruded through polycarbonate membranes. Encapsulation efficiency and in vitro stability at 37 degrees C were assessed after size exclusion chromatography. TAP liposomes (TAP-lip) or TAP in solution (TAP-sol) were delivered to rats either by intratracheal instillation (IT) or intravenous (IV) administration. Pulmonary targeting was assessed by simultaneous monitoring of glucocorticoid receptor occupancy over time in lung (local organ) and liver (systemic organ) using an ex vivo receptor binding assay as a pharmacodynamic measure of glucocorticoid action. RESULTS: In vitro studies in different fluids over 24 hours, showed that more than 75% of the TAP remained encapsulated in liposomes. Cumulative pulmonary effects after IT administration of TAP-lip were 1.6 times higher than liver receptor occupancy. In contrast, there was no difference in the pulmonary and hepatic receptor occupancy time profiles when TAP was administered intratracheally as a solution. No preferential lung targeting was observed when TAP-lip was administered IV. As indicated by the mean effect times, lung receptor occupancy was sustained only when TAP-lip was administered IT. CONCLUSIONS: Intratracheal administration of TAP-lip provided sustained receptor occupancy, and increased pulmonary targeting which was superior to IT administration of TAP-sol or IV administration of TAP-lip. The use of liposomes may represent a valuable approach to optimize sustained delivery of glucocorticoids to the lungs via topical administration.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8956337&dopt=Abstract triamcinolone Kenalog



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Preliminary experience with triamcinolone acetonide during pregnancy.

Dombrowski MP, Brown CL, Berry SM.

Department of Obstetrics and Gynecology, Wayne State University/Hutzel Hospital, Detroit, MI 48201, USA.

Although inhaled corticosteroids have been recommended, there are no published reports of triamcinolone acetonide therapy for asthma during pregnancy. The objective of this study was to report our experience with triamcinolone acetonide during pregnancy. This was a retrospective cohort study in a tertiary care urban hospital. We compared birth weights and the proportion of subjects hospitalized for asthma exacerbations among pregnant women receiving inhaled triamcinolone acetonide, inhaled beclomethasone dipropionate, and oral theophylline. The mean triamcinolone acetonide group (n = 15) birth weight was 502 g more than the beclomethasone group (n = 14) and 316 g more than the theophylline group (n = 25); however, these differences were not statistically significantly. Fewer patients treated with triamcinolone acetonide (n = 5, 33%) required hospital admissions for asthma exacerbations compared to those treated with beclomethasone (n = 11, 79%; P < 0.05) but not theophylline (n = 7, 28%; P = NS). Our preliminary data suggest that triamcinolone acetonide appears to be at least as efficacious for the treatment of asthma during pregnancy as is beclomethasone. These results should be confirmed by a clinical trial to further evaluate the safety and efficacy of inhaled triamcinolone acetonide during pregnancy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8972405&dopt=Abstract triamcinolone Kenalog



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Inhibition of preretinal and optic nerve head neovascularization in pigs by intravitreal triamcinolone acetonide.

Danis RP, Bingaman DP, Yang Y, Ladd B.

Department of Ophthalmology, Indiana University Medical School, Indianapolis 46202-5175, USA.

PURPOSE: The authors tested the antiangiogenic properties of intravitreally administered triamcionolone acetonide in a pig model of preretinal neovascularization to determine the effectiveness of this therapy in preventing neovascularization. METHODS: In 14 eyes of seven pigs, branch retinal vein occlusions were created in a standardized manner using photodynamic thrombosis with rose bengal dye and thermal burns from the argon green laser. Intravitreal injection of approximately 4 mg of triamcinolone acetonide was performed in one eye of each animal, and eyes were followed clinically for 12 weeks with ophthalmoscopy and fundus photography. A standardized grading system was developed to permit masked assessment of disc proliferations from fundus stereophotographs. After death, all neovascularization was confirmed histopathologically and a final grade was assigned to each eye. Statistical analysis employed use of a nonparametric test of the paired data. RESULTS: Significant inhibition of neovascularization was observed in triamcinolone-treated eyes (P = 0.0156). Although none of the steroid-injected eyes demonstrated clinically evident new vessels, histopathologic and photographic analysis results demonstrated fine new vessels on the optic disc in four eyes. In all of the untreated eyes, neovascularization of a moderate (II) to high (III to IV) grade developed. CONCLUSIONS: Intravitreal triamcinolone acetonide effectively inhibited preretinal and optic nerve head neovascularization in the pig model. The grading system used permitted masked assessment of outcome and paired analysis allowed a conclusion to be drawn from a relatively small number of eyes. The mechanisms by which triamcinolone acetonide inhibits neovascularization remain to be elucidated.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9003344&dopt=Abstract triamcinolone Kenalog



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Combination anti-inflammatory and antiviral therapy of influenza in a cotton rat model.

Ottolini M, Blanco J, Porter D, Peterson L, Curtis S, Prince G.

Department of Pediatrics, F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799, USA. mottolini usuhs.mil

The cotton rat was evaluated as a model for anti-inflammatory and antiviral influenza therapy. Beginning 3 days after intranasal infection with 10(7) tissue culture infectious doses-50% (TCID)(50) of an H3N2 human influenza, animals were treated topically via intranasal lavage with a range of doses of triamcinolone acetonide (1, 4, or 16 mg/kg), alone or in combination with a neuraminidase inhibitor or anti-influenza convalescent serum. Pulmonary histopathologic changes were dramatically decreased in animals treated with 4 or 16 mg/kg of triamcinolone, with little additional benefit from addition of a neuraminidase inhibitor or topical serum, agents which were much less effective when used alone. A high degree of suppression of IFN-gamma levels was observed in all combinations where 4 or 16 mg/kg of triamcinolone were used. Viral replication was not prolonged by corticosteroid therapy. Tissue damage during influenza infection may be greatly reduced by combination antiviral and anti-inflammatory therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12950040&dopt=Abstract triamcinolone Kenalog



Kenalog
Glucocorticoid regulation of hepatic S-adenosylmethionine synthetase gene expression.

Gil B, Pajares MA, Mato JM, Alvarez L.

Institute of Biomedical Investigation, Consejo Superior de Investigaciones Cientificas, Madrid, Spain.

The effects of glucocorticoids on the regulation of rat liver S-adenosylmethionine synthetase were studied in vivo and in two culture systems. Livers from adrenalectomized animals were examined for enzyme activity, immunoreactive protein, and messenger RNA (mRNA) content. All three parameters showed a similar trend, i.e. they decreased 3-fold after adrenalectomy and increased over the control values upon triamcinolone replacement. These results suggested that glucocorticoid regulation of hepatic S-adenosylmethionine synthetase was mediated at the mRNA level. Triamcinolone and dexamethasone increased S-adenosylmethionine synthetase mRNA content in a time- and dose-dependent manner in both rat hepatoma H35 cells and primary cultures of adult rat hepatocytes. The kinetics of mRNA induction were identical in both culture systems, indicating that the hormone-mediated response is independent of the differentiated state of the cell. Insulin blocked the inducing effect of glucocorticoids on S-adenosylmethionine synthetase mRNA in a dose-dependent manner. On the other hand, the triamcinolone-dependent increase in mRNA levels was completely abolished by treatment with actinomycin D, whereas cycloheximide did not affect this response. The transcription rate of the gene, as measured by run-on assay, increased 3-fold after hormone addition. Transient transfections of H35 cells with 1.4 kilobases of the 5'-flanking region of the hepatic S-adenosylmethionine synthetase gene fused to a luciferase reporter gene showed that promoter activity is also increased 3-fold after triamcinolone treatment, suggesting that this promoter region contains the sequence elements necessary to confer glucocorticoid responsiveness. In addition to the transcriptional control of the hepatic S-adenosylmethionine synthetase gene, our results suggest that glucocorticoids may be acting at a posttranscriptional level.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9048633&dopt=Abstract triamcinolone Kenalog



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The efficacy of treatment with triamcinolone acetonide in calcinosis cutis following extravasation of calcium gluconate: a preliminary study.

Ahn SK, Kim KT, Lee SH, Hwang SM, Choi EH, Choi S.

Department of Dermatology, Yonsei University Wonju College of Medicine, Korea.

Neonatal hypocalcemia is not an uncommon condition, especially in the premature neonate. It is effectively treated by intravenous administration of calcium gluconate. Complications of extravasation during intravenous infusion include localized calcification and occasionally necrosis. When this occurs, however, there is no specific mode of treatment except supportive management and skin graft. This experiment was designed to evaluate the efficacy and safety of treatment with triamcinolone acetonide in calcinosis cutis following extravasation of calcium gluconate. Initially, 2 cc of 10% calcium gluconate was injected subcutaneously into two rabbits at seven sites on the shaved skin of the back. Another two rabbits were injected at the same sites with 0.5 cc of triamcinolone acetonide (10 mg/dl) after injection of 2 cc of 10% calcium gluconate. As a control, 2 cc of normal saline was injected into another rabbit in the same manner. These five rabbits were observed over the next 7 weeks and underwent pathologic examination at various intervals (on days 1, 3, 8, 15, 30, 37, 45). In the 10% calcium gluconate injected rabbits, nodules and large ulcerated lesions developed after 15 days. Multiple, linear, ulcerative and indurated masses were noted on day 37. The lesions healed progressively with a decrease in ulceration, and after 2 months, the masses disappeared gradually. Histologically, on day 15 calcium deposits were seen in the walls of the arteries, veins, dermis, and muscle fibers and epidermal necrosis was seen at the injection sites. From day 37 discharge of calcium deposits began to take place by means of transepidermal elimination. After 2 months, the calcium and mucin deposition was observed focally in the dermis. In the rabbits injected with 10% calcium gluconate and triamcinolone acetonide, mild erythema and induration were seen after day 15 at the injection sites; this gradually disappeared. After 30 days the injection sites were normal in appearance. Histologically, at day 15 calcium deposition was seen in the upper dermis, but after 1 month the injection sites were histologically normal. We suggest that intralesional injection of triamcinolone acetonide for the treatment of calcinosis cutis following extravasation of calcium gluconate is effective, probably due to its antiinflammatory effect and its role in facilitating the resorption of calcium in the tissue.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9144694&dopt=Abstract triamcinolone Kenalog