Effect Of Triamcinolone Acetonide Research Articles

Treatment With Triamcinolone Acetonide Prevents Decreased Retinal Levels of Decorin in a Rat Model of Oxygen-Induced Retinopathy

Purpose: To investigate the effect of triamcinolone acetonide (TA) on retinal expression of decorin in a rat model of oxygen-induced retinopathy (OIR).Materials and Methods: OIR was stimulated by exposing Sprague-Dawley (SD) rats to hyperoxia (80 ± 1.3% O2) from postnatal day (P) 2 to P14 and then returning them to normoxia (room air, 21 ± 1.5% O2). Control rats were maintained in normoxia. At P15, TA (40 mg/ml) was injected into the right vitreous of OIR rats and saline into the left vitreous of control rats. All rats were sacrificed at P18. RT-PCR, western blot and immunohistochemistry, TUNEL assay were performed to detect the effects of TA on molecular and morphological changes in retinal decorin levels in P18 OIR rats.Results: In P18 OIR rats, mRNA and protein of retinal levels and immunoreactivity of retinal decorin were significantly less (p-value = 0.0000000012, 0.0007, 0.000003; n = 5; respectively) than in control rats. In addition, neuronal cell death was increased in P18 OIR rats (p-value = 0.0028; n = 5) relative to controls. However, treatment with TA prevented the decrease of mRNA, protein levels, and immunoreactivity in retinal decorin in P18 OIR rats (p-value = 0.00023, 0.003, 0.000079; n = 5, respectively), and restored neuronal cell death in P18 OIR rats (p-value = 0.0022, n = 5).Conclusion: Our results suggest that decorin is involved in hypoxic retinal damage and that TA protects retinal neurons damaged by relative hypoxia from decreased decorin levels.

Effect of Triamcinolone Acetonide on Vascular Endothelial Growth Factor and Occludin Levels in Branch Retinal Vein Occlusion

To investigate the molecular mechanism by which triamcinolone acetonide (TA) may reduce edema in a porcine model of branch retinal vein occlusion (BRVO). Animal study. After baseline ophthalmoscopic examination and fundus photography, a BRVO was created photothrombotically in each eye of 6 pigs, using argon green photocoagulation and intravenous Rose Bengal. Following this, the left eye was injected intravitreally with 4 mg/0.1 ml TA. After 11 weeks, the eyes were re-examined. Fluorescein angiography, in addition to ophthalmoscopy and fundus photography, was performed. Following sacrifice of the animals, the eyes were enucleated and processed. The distribution of vascular endothelial growth factor (VEGF), occludin, and glial fibrillary acidic protein (GFAP) were localized by immunofluorescence cytochemistry on 10 microm frozen retinal sections of TA-treated and untreated eyes. Retinal VEGF levels were significantly lower in the TA-treated eyes as compared with the untreated eye (P = .002). Conversely occludin levels were significantly higher in the treated eye (P = .026). There was also a significant reduction in GFAP immunoreactivity in the Muller cells of the treated eyes (P = .015) with no statistical significance in the astrocytes (P = .065). Intravitreal TA down regulates VEGF, which may prevent a decrease in occludin and also inhibits an increase in GFAP expression in Muller cells. These events may contribute to a reduction in the blood retinal barrier breakdown that occurs in BRVO and promote resolution of the associated retinal edema.

Triamcinolone acetonide prevents oxidative stress-induced tight junction disruption of retinal pigment epithelial cells

Oxidative stress is known to disrupt the integrity of retinal pigment epithelium (RPE) tight junctions. The goal of this study is to evaluate the effect of triamcinolone acetonide (TA) on the junctional integrity of RPE under oxidative stress and to identify the underlying mechanisms. Second passage porcine RPE cells were cultured on 6-well membrane inserts until 4 weeks after reaching confluence. Cells were incubated with TA (10(-5) M) for 30 min. FITC-containing medium was added to the upper chamber (cell's apical side). The cells were then challenged with 1 mM Hydrogen Peroxide (H(2)O(2)). After 5 h, the fluorescence intensity of the medium from lower chamber (cell's basolateral side) was measured using a fluorescence spectrofluorophotometer. This transepithelial flux of FITC-dextran was measured until the 21st day. The immunolocalization of occludin and F-actin was examined with fluorescence microscope. Reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio was determined by a colorimetric assay kit. Non-lethal oxidative stress by H(2)O(2) increased transepithelial flux of FITC-dextran significantly. TA inhibited this increase and preserved the lower flux through the whole experimental period. This permeability change by H(2)O(2) was reversible and recovered to the normal level within 3 weeks. In immunohistological study, H(2)O(2) reduced linear occludin staining at the cell border and increased actin stress fibers. TA prevented H(2)O(2)-induced disruption of junctional assembly of occludin and F-actin. Glutathione assay demonstrated that intracellular GSH/GSSG ratio decreased significantly with H(2)O(2), while TA preserved this ratio by up-regulating GSH synthesis. TA has a protective effect against oxidative stress-induced disruption of RPE tight junction by preserving cellular redox state.

Effect of triamcinolone acetonide on expression of survivin gene in cultured human retinal pigment epithelial cells

目的 观察曲安奈德(TA)对体外培养的人视网膜色素上皮(RPE)细胞表达survivin基因的影响,探讨TA治疗增生性玻璃体视网膜病变(PVR)的机制.方法 四甲基偶氮唑盐比色(MTT)法和流式细胞术检测不同质量浓度(0.01、0.1、1.0 g/L)TA对人RPE细胞增生及凋亡的作用,免疫组织化学法、RT-PCR检测药物在蛋白和基因水平对survivin表达的影响. 结果 在不同质量浓度的TA作用下,人RPE细胞的增生受到抑制,凋亡率增加,在蛋白水平和基因水平,药物均对RPE细胞survivin的表达有明显的抑制作用,且均与药物的作用时间和剂量呈正相关.各组与对照组比较差异均有统计学意义(P＜0.05).结论 TA能抑制人RPE细胞的增生及survivin蛋白和mRNA在人RPE细胞的表达,诱导RPE细胞的凋亡。

Positive Feedback Regulation between MMP-9 and VEGF in Human RPE Cells

The proteolytic activity of matrix metalloproteinases (MMPs) is involved in pathologic angiogenesis in the eye. However, it is unknown whether MMPs may stimulate the production of the major angiogenic factor, vascular endothelial growth factor (VEGF). The authors investigated whether MMP-2 and MMP-9 alter the expression of VEGF by retinal pigment epithelial (RPE) cells. They also sought to determine the effects of MMPs on cellular proliferation and migration and the effect of triamcinolone acetonide on MMP-9-evoked cellular responses. Human RPE cell cultures were stimulated with MMP-2 or MMP-9. The gene expression and secretion of MMP-9 and VEGF were determined by real-time RT-PCR and ELISA, respectively. Cellular proliferation was investigated with a bromodeoxyuridine immunoassay, and chemotaxis was examined with a Boyden chamber assay. Under control conditions, RPE cells in vitro expressed a significantly higher amount of mRNA for MMP-2 than for MMP-9. Chemical hypoxia caused upregulation of the gene expression of both MMPs, whereas VEGF increased the gene expression and secretion of MMP-9. The hypoxic expression of MMP-9 was mediated by autocrine VEGF signaling. Exogenous MMP-9 increased the gene expression and secretion of VEGF, whereas MMP-2 reduced the secretion of VEGF. MMP-2 and MMP-9 did not alter the proliferation but stimulated the migration of RPE cells. Triamcinolone fully inhibited the stimulatory effect of MMP-9 on the expression of VEGF and the VEGF-evoked increase in the expression of MMP-9. However, triamcinolone had no effect on the motogenic effect of MMP-9. There is a positive feedback regulation between MMP-9 and VEGF in RPE cells. The hypoxic expression of MMP-9 may stimulate the production and secretion of VEGF under pathologic conditions. Triamcinolone inhibits the positive feedback regulation between MMP-9 and VEGF under hypoxic conditions through inhibition of the gene expression of MMP-9 and the secretion of VEGF.

The effect of intravitreal triamcinolone on intraocular pressure

ABSTRACTObjective: To evaluate the effect of triamcinolone acetonide (ITA) on intraocular pressure (IOP) following intravitreal injection, and, in those patients who experience post-injection elevation of IOP, to determine the time course, effect of multiple injections, and risk factors for the pressure rise.Methods: A retrospective chart review of 85 consecutive patients who received ITA (0.1 mL of 40 mg/mL solution) at the University of Texas South­western Medical Center between January 2002 and April 2004 was performed. Patient age, history of open-angle glaucoma (OAG), previous intraocular surgery, prior steroid exposure, type of retinal pathology treated, pre- and post-injection IOP, and post-injection glaucoma medications were tabulated. Patients with previous exposure to topical, intraocular or systemic steroids, and those without at least 16 weeks of follow-up were excluded. A student's paired t‑test was used for statistical analysis.Results: Seventy-seven eyes of 70 patients were included. Forty-eight eyes (62.3%) experienced an increase in IOP of at least 5 mmHg. Twenty-five eyes (32.5%) experienced elevation in IOP of 5–9 mmHg, and 23 eyes (29.9%) experienced an increase in IOP of ≥ 10 mmHg during the review period. The mean time for elevations of 5–9 mmHg and ≥ 10 mmHg to occur following injection were 6.9 weeks and 8.8 weeks, respectively. Fifty percent of eyes (3/6) in patients with OAG experienced a maximum IOP level of > 30 mmHg. Of all eyes with IOP elevation following injection, 32.5% required topical glaucoma therapy. Thirteen eyes received a second ITA injection. All eight eyes with IOP elevation after the first injection experienced another rise in IOP after the second. Of the five eyes which had no rise in IOP after the first injection, four had no rise after the second. At the final visit, 50% of eyes (3/6) with OAG required additional glaucoma medication compared to baseline. No patients required surgery for IOP control during the period under review.Conclusions: ITA is frequently associated with a signif­icant elevation in IOP, typically within the first 2‑months after injection. Most patients who do not have an elevated IOP after an initial injection will not experience a pressure rise after an additional one. About one-third will require topical glaucoma therapy for IOP control. Patients with OAG may be more difficult to control and require a longer duration of therapy. The inconsistent post-injection follow-up visit intervals among patients in this retrospective review may have affected our results, as some patients with maximum IOP changes may have been missed between office visits. In addition, practice patterns among treating physicians typically differ as to thresholds for the treatment of elevated IOP. A randomized, prospective, controlled trial could better address these issues.

Focus on triamcinolone acetonide as an adjunct to glaucoma filtration surgery

Glaucoma is one of the most common causes of irreversible blindness worldwide. Despite continued advances in medical and laser therapy, incisional surgery still appears to be an important and for many cases the only option by which intraocular pressure is controlled. Unlike many other types of surgery in which complete healing of tissue would be a desirable outcome, glaucoma surgery seeks to achieve incomplete healing to allow aqueous humor to escape the eye. Pharmacologic modulation of wound healing is a hot topic in glaucoma filtration surgery. Although routine antifibrotic medications are associated with good results in modulating wound healing in glaucoma surgery, they carry with them the possibility for significant morbidity due to the adverse effects of treatment. Challenge continues to be to find a safe and effective agent for this purpose. Because of beneficial effects of triamcinolone acetonide in some conditions which are associated with secondary glaucoma and also potential effects of this agent in modulating wound healing process, we propose it as a useful adjunct to glaucoma filtration surgery. This approach may allow modulation of wound healing with less of the toxicity associated with commonly used antifibrotics (5-FU and mitomycin C).

Ascorbic acid concentration in rabbit vitreous measured by microdialysis with HPLC-electrochemical detection before and after vitreous surgery

Microdialysis with high performance liquid chromatography and electrochemical detection (HPLC–ECD) was used to measure ascorbic acid (AA) concentrations in rabbit vitreous before and after vitrectomy. A cellulose microdialysis probe was implanted in the vitreous humor, and after stabilization, AA measurements were made daily over a 10 day period. The effect of removing two-thirds of the vitreous by vitrectomy was examined. The effect of triamcinolone acetonide (TA) was evaluated in four groups of rabbits: Group 1, sub-tenon TA (20 mg) alone; Group 2, intravitreous TA (4 mg) alone; Group 3, sub-tenon TA (20 mg) after vitrectomy, and Group 4, intravitreous TA (4 mg) after vitrectomy. The results showed that the AA concentration after vitrectomy was significantly lower from days 2 to10 with a maximum reduction of 49.5% ( P<0.005) on day 7. No significant changes in the AA level was observed in Groups 1 and 2, a mild recovery of AA concentration reduction after vitrectomy was detected in Group 3. The highest recovery of the AA concentration reduction was observed in Group 4. The attenuating effect of TA treatment on the reduction of AA in the vitreous after vitrectomy was significant. This attenuating effect of the TA may be due to prevention of the disruption of the blood-aqueous barrier by its anti-inflammatory action.

Therapeutic effect of triamcinolone acetonide on blood-retinal barrier breakdown in diabetic rat

目的 探讨曲安奈德(TA)玻璃体注射在糖尿病Wistar鼠血-视网膜屏障(BRB)破坏方面的保护作用.方法选择健康成年Wistar鼠,链脲佐菌素(STZ)诱导大鼠糖尿病.分为正常对照组,糖尿病4个月(DM4)组和6个月(DM6)组,每组各分为形态学观察组和BRB测定组,BRB测定组再分为未行TA治疗(NT)组、TA治疗1周组和2周组.行消化铺片HE染色观察视网膜血管形态,利用视网膜标准化Evans blue(EB)含量测定大鼠BRB的变化.结果正常对照组各组间EB含量差异无统计学意义(P>0.05).同正常对照组相比,DM4组大鼠出现毛细血管管径粗细不一,血管闭锁,内皮细胞增生,周细胞丢失等形态学改变;DM6组上述病变进一步加重,出现无细胞性毛细血管,糖尿病NT组EB含量明显升高(P>0.01),且6个月组高于4个月组,差异有统计学意义(P>0.01).同糖尿病NT组相比,各糖尿病治疗组EB含量均显著降低(P>0.01),但除4个月治疗2周组EB含量基本恢复正常(P>0.05)外,余治疗组均仍高于正常对照组(P 0.05).结论糖尿病大鼠视网膜的形态学变化与BRB的破坏有关,TA对糖尿病大鼠BRB的破坏具有保护作用。

Ischemia-Reperfusion Causes Exudative Detachment of the Rabbit Retina

To characterize the activation of macroglial (Müller) and microglial cells, as well as neuronal cell degeneration, during ischemia-reperfusion in rabbit retina and to test the possible effect of triamcinolone acetonide on gliosis. Transient retinal ischemia was produced by increasing intraocular pressure for 60 minutes. Triamcinolone (8 mg) was intravitreally applied immediately after the cessation of ischemia. At 3 and 8 days after reperfusion, the K+ currents of acutely isolated Müller cells were recorded, and the Ca2+ responses of Müller cells on stimulation of P2Y receptors were recorded fluorometrically in retinal wholemounts. Microglial/immune cells in the nerve fiber layer of retinal wholemounts were labeled with isolectin. To evaluate neuronal and Müller cell loss, the numbers of cells were counted in retinal slices. Transient ischemia caused exudative detachment of the central retina that was characterized by disruption of the pigment epithelial monolayer, the presence of scattered pigment epithelial and immune cells in the expanded subretinal space, and retinal folds. A significant loss of photoreceptor cells was observed at 8 days after reperfusion. At 3 and 8 days after reperfusion, Müller cell gliosis was apparent, as indicated by cellular hypertrophy, downregulation of K+ channel expression, and an increased number of cells that displayed P2Y receptor-mediated Ca2+ responses. The number of microglial/immune cells increased strongly after reperfusion. Intravitreal triamcinolone did not affect the parameters of Müller cell gliosis but decreased the number of microglial/immune cells. Ischemia-reperfusion of the rabbit retina causes exudative retinal detachment that is characterized by a loss of photoreceptor cells, whereas the inner retina remains largely preserved. Micro- and macroglial cells are activated early during reperfusion, even before dropout of the photoreceptor cells. Intravitreal triamcinolone may decrease the degree of microglial/immune cell activation.

Effect of triamcinolone acetonide on the regrowth of nasal polyps after surgical treatment

Objectives: Nasal corticosteroids are widely used in the treatment the polypoid patients and to prevent the recurrence of polyps. The aim of this research was to study the effect of nasal steroid triamcinolone acetonide on the prevention of the regrowth of nasal polyps after surgical polypectomy. The study design was randomized, double-blind, placebo-controlled, and prospective. Methods: There were 60 patients, 23 women and 37 men. The polypectomy was either uni- or bilateral (re-) polypectomy. The patients were followed-up 2 weeks, and 3, 6, 9, and 12 months postoperatively. Results: During the follow-up period the polyps grew significantly slower in the treatment group than in the placebo group. In acoustic rhinometry, the difference between treatment groups was in favor of the active treatment. However, in rhinomanometry no statistically significant differences between the 2 groups were seen. Mean monthly rescue medication consumption was significantly lower in the treatment group than in the placebo group. In the treatment group the smell test results improved significantly. Conclusion: After surgical polypectomy regrowth of the polyps was slower in the treatment group as compared to the placebo group, but the treatment did not completely prevent the regrowth. In the active treatment group the smaller amount of rescue medication used, and the significantly better results in acoustic rhinometry and olfactometry showed that nasal triamcinolone acetonide spray can slow down the regrowth and reduce the symptoms caused by nasal polyps.

Effect of triamcinolone acetonide on the development of the pulmonary airways in the fetal rat.

Triamcinolone acetonide (TAC) has a potent teratogenic effect on various mammalian fetal tissues as well as a steroid effect on the lung. Less well documented is the fact that it produces profound oligohydramnios. We wished to determine what effect TAC would have on branching morphogenesis and other aspects of lung development, using an in vivo model described previously. Thirty rats were randomized to receive 0.6 mg/kg of TAC or saline on days 12, 13, and 14 of gestation. At gestational days 15, 17, 18, and 21, the left lungs of 365 fetuses were studied by dissecting microscopy, histology, and morphometry. TAC produced profound pulmonary hypoplasia (dry Jung weight/body weight 0.025, compared with 0.06 in controls) on day 21. TAC decreased maternal weight gain, fetal weight, placental weight, aminiotic fluid, and pole to pole length (PTP), while it increased the peripheral airway count (PAC). The number of central and intermediate airway branches was reduced, and they were dilated. Growth of peripheral airways was enhanced. In treated fetuses epithelial cells lining these airspaces were histologically more mature and the mesenchyme thinner than in controls. These findings were confirmed by the morphometric measurements. We conclude that when TAC is administered in the early phase of fetal rat lung development, the lungs become hypoplastic, with hypoplasia of the intermediate airways, an increase in the number of peripheral airways, and increased differentiation. We speculate that these effects are primarily due to the steroid action of TAC and that the mechanisms of monopodial branching are different from those of dichotomous branching.

Effect of triamcinolone acetonide on the development of the pulmonary airways in the fetal rat

Effect of triamcinolone acetonide on the development of the pulmonary airways in the fetal rat

Growth inhibition of the androgen responsive DDT1MF-2 cell line by glucocorticoids: the role of ornithine decarboxylase

While testosterone (T) stimulates the growth of DDT(1)MF-2 cells, glucocorticoids arrest the growth of these cells in the G(0)/G(1) stage of the cycle. Ornithine decarboxylase (ODC), the first and rate-limiting enzyme in the polyamine biosynthetic pathway, is highly sensitive both to growth and inhibitory stimuli. To assess the mechanism of glucocorticoid inhibition of cell growth, the effect of triamcinolone acetonide (TA) on growth and ODC was studied. DDT(1)-MF-2 cell growth was inhibited by TA and difluoromethyl ornithine (DFMO), an irreversible inhibitor of ODC. TA (10NM: ) inhibited the ODC activity to 10% of the control levels by 12 h and inhibition was maintained at all later intervals studied. Ten μM: DFMO inhibited ODC activity to a maximum of 50% of control. The concentration of ODC mRNA was maximally decreased at 15 h after TA administration.Though TA and DFMO inhibited cell growth and ODC activity in DDT(1)-MF2 cells, growth inhibition by DFMO, but not by TA, was overcome by the addition of putrescine, the product of ODC reaction. Thus, inhibition of ODC is one pathway through which glucocorticoids inhibit DDT(1)MF-2 cell growth. ODC inhibition, however, is not the only pathway through which glucocorticoids act.

Effects of triamcinolone acetonide on pulmonary function and bronchoalveolar lavage cytologic features in horses with chronic obstructive pulmonary disease

Summary Effects of triamcinolone acetonide (ta) on pulmonary function, bronchoalveolar lavage cytologic features and serum cortisol concentration, were studied in 5 control horses and 5 horses with chronic obstructive pulmonary disease (copd). In experiment 1, horses were brought in from pasture 3 weeks before administration of 1 injection of ta (0.09 mg/kg of body weight, im), and were stabled in dusty conditions throughout the experimental period. Measurements of respiratory rate (f), tidal volume, minute ventilation, expiratory-to-inspiratory time ratio, maximal change in transpulmonary pressure (ΔPL), pulmonary resistance (RL), and dynamic compliance (Cdyn) were obtained during quiet breathing, immediately before (baseline) and 1, 2, 3, 5, and 9 weeks after administration of ta. Pulmonary airway cells were collected by bronchoalveolar lavage while horses were at pasture, at baseline, and 2, 5, and 9 weeks after ta administration. Serum cortisol concentration was measured before and after adrenocortical stimulation with 100 IU of adrenocorticotropic hormone, 1 week prior to ta administration, and 4 and 8 weeks thereafter. In experiment 2, 4 months after ta injection, pulmonary function measurements were repeated in all horses immediately before and 30 minutes after administration of atropine (0.015 mg/kg, iv), to evaluate the reversibility of airway obstruction. In experiment 1 at baseline, COPD-affected horses had significantly (P &lt; 0.05) higher values than did controls for f, ΔPL, RL, and percentage of neutrophils, and had lower values for Cdyn and percentage of lymphocytes and macrophages. There were significant reductions in ΔPL and RL, and increase in macrophage percentage after ta administration in copd-affected horses only. The degree and duration of these changes varied among individual copd-affected horses, but ΔPL, and RL, values had returned to or were above baseline in all horses 5 weeks after treatment. Baseline cortisol concentration was decreased 4 weeks after ta administration, but the mean increase in cortisol values after adrenocorticotropic hormone stimulation was similar to that observed prior to treatment. In experiment 2, values of ΔPL, RL, and Cdyn, after atropine administration were similar to those of controls in the 2 copd-affected horses that had improved most after ta, but were only partially improved in the 3 other horses, indicating possible irreversible lesions in the latter.

Effects of triamcinolone acetonide on plasma amino acids and urinary urea output in rabbits

1. 1. The effect of administering triamcinolone acetonide (10 mg/kg/day), 6 consecutive s.c. injections given daily, on plasma free amino acids and urinary urea output was studied in rabbits. 2. 2. The total free amino acids in plasma decreased significantly from day 2 while ammonia increased significantly only on day 2, glutamine, lysine and branched amino acids increased significantly from day 3 or 5. 3. 3. The output of urinary urea increased significantly from day 3. 4. 4. These findings suggest the inhibition of protein synthesis observed in steroid myopathy may result from a decrease in the amino acid pool in skeletal muscle.

Corticosteroid Regulation of Gonadotropin Secretion and Induction of Ovulation in the Rat

In the human polycystic ovarian syndrome, glucocorticoids have been demonstrated to have beneficial effects in inducing ovulation in a number of cases. These beneficial effects were assumed to be due to suppression of adrenal overproduction of androgens. However, the possibility exists that glucocorticoids may directly regulate gonadotropin secretion and thereby improve menstrual rhythm and ovulatory activity. Herein, we report that the corticoid, deoxycorticosterone, and the synthetic glucocorticoid, triamcinolone acetonide, like progesterone (P4), are able to induce luteinizing hormone and follicle-stimulating hormone surges and facilitate ovulation in the pregnant mare serum gonadotropin-primed rat. This effect is not shared by cortisol. Prolactin release was also stimulated by deoxycorticosterone, cortisol, and progesterone, but not by triamcinolone acetonide. Similar to progesterone, triamcinolone acetonide and deoxycorticosterone administration caused a loss of fluid retention in the uterus. This effect of triamcinolone acetonide and deoxycorticosterone may be related to progesterone action as opposed to anti-inflammatory action since cortisol had no effect on uterine fluid retention. These findings raise the possibility that the beneficial effects seen with glucocorticoids in inducing ovulation in polycystic ovarian syndrome may be due in part to their direct effects upon the release of gonadotropins.

Diacylglycerols Enhance the Anti‐tumor Effect of Glucocorticoid on L5178Y Lymphoblasts in vivo

1,2‐Dioleoyl‐rac‐glycerol, a potent activator of protein kinase C, was found to enhance the growth‐inhibitory effect of triamcinolone acetonide on L5178Y lymphoblasts in adrenalectomized, male DBA/2 mice. On the other hand, in mice without adrenalectomy, it markedly inhibited tumor growth without increasing the plasma level of corticosterone or adrenocorticotropic hormone or reducing the body weight. These results suggest that diacylglycerol enhances the action of endogenous glucocorticoid to a sufficient level to inhibit the growth of lymphoblasts. Of various diacylglycerols with different carbon chain lengths tested, 1,2‐dioleoyl‐rac‐glycerol was the most potent growth inhibitor and was maximally effective at a dose of above 30 μg/100 g body weight. This finding suggests that diacylglycerols may he useful for enhancing the antitumor effect of a low dose of glucocorticoid or endogenous glucocorticoid on lymphoblasts without any significant side effect.

Effect of heat treatment on the glucocorticoid-receptor complex dependence on steroid structure

The Arrhenius plot of heat inactivation of the rat liver glucocorticoid receptor protein gave a straight line with ΔH + + = 115 kJ/mol over the 0–44°C range. Molybate ions were considerably protective but did not affect the linearity or slope of the Arrhenius plot. The effect of triamcinolone acetonide on heat stability of the receptor was similar to that of molybdate. On the other hand, glucocorticoid antagonists, although bound to the receptor, did not protect it from heat inactivation. Incubation of the complex of the glucocorticoid receptor with optimal glucocorticoids under activating conditions (elevated temperature or ionic strength) resulted in a considerable decrease in the dissociation rate. However, if the complex was incubated at 25°C in the presence of molybdate, its dissociation rate did not change. Heat treatment without molybdate of complexes of gluococorticoid antagonists did not decrease the dissociation rate. These findings indicate that the decrease in dissociation rate is probably related to nucleophilic transformation. An 11β-hydroxyl group in the steroid structure seems to be an absolute requirement both for protection of the receptor against heat inactivation and for stabilization of the complex under conditions that promote neucleophilic transformation.

Triamcinolone acetonide induces transient changes in accumulation and fluxes of calcium in cultured bone cells

The effects of triamcinolone acetonide on the pattern of 45calcium efflux were investigated in cultured bone cells. Efflux was measured after equilibrating the cells with 45calcium for 24 hours and a short (3 hours) or a long (24 hours) preincubation with the hormone. The results were analyzed by fitting them to a model of three exponential terms, using a computer program based on the non-linear least square method. As reported previously the results indicated the presence of three exchangeable calcium pools which differ in their rates of calcium exchange. A short preincubation with the hormone (3 hours) caused the following changes: (1) A marked increase in the amount of exchangeable calcium in the “slow turnover” calcium pool (S 3) which is probably in the mitochondria. (2) A lesser but significant increase in the amount of calcium in the “fast turnover” calcium pool (S 2) which is probably the calcium in the cytosol. (3) An increase in the rates of calcium exchange between S 2 and the medium (ϱ 20) and between S 3 and S 2 (ϱ 32). All these changes were transient. After 24 hours of preincubation with triamcinolone acetonide the amounts of calcium in S 2 and S 3 decreased below the control levels and the fluxes were not significantly different from those of the controls.