[Early hypertrophic scar after surgery on the nasal region: value of long-acting corticosteroid injections]. / Hypertrophie cicatricielle précoce post-chirurgicale de la région nasale : intérêt des injections de corticoïde retard.

BACKGROUND: "Pincushioning" is a complication of post-surgical scarring following use of transposition flaps particularly when surgery is performed on the nasal region. The transposition flap technique is very useful for the repair of certain defects of the tip of the nose, the medial canthus or of the ala nasi. The aim of this study is to define the clinical characteristics of this scarring dystrophy, which we propose to call "early hypertrophy scarring", to clarify the nature thereof and to assess the efficacy of intralesional injection of corticosteroids at the first signs of hypertrophy. PATIENTS AND METHOD: A prospective, open, non-comparative, single-centre study examined the clinical and histological characteristics of early hypertrophy scarring and the effectiveness of therapy with one or two injections of corticosteroids performed on the 15th day post-operatively and optionally repeated at D45 depending on the outcome. From January 2011 to January 2013, 12 consecutive patients with early hypertrophy scarring were included (ten men and two women - mean age: 64 years). All had undergone surgery for basal cell carcinoma under local anaesthesia with one-stage repair by means of a rhombic flap or a bilobed flap located in the nasal area. Scars were injected strictly intra-lesionally with triamcinolone acetate (40 mg/1 mL) until whitening occurred. A single injection was performed in three cases of rhombic flap while a second injection was given at D45 in the remaining nine cases. RESULTS: Complete regression of the early hypertrophy scarring was obtained in ten of the 12 patients by D90. Incomplete regression was observed but with a marked improvement in the other two patients. DISCUSSION: Early hypertrophy scarring is distinguished by its clinical characteristics of hypertrophic or keloid scars. Biopsy performed in two cases showed the fibrous but non-fatty nature of early hypertrophy scarring. Biomechanical factors particular to the nasal region and the transposition flap technique could account for the early and excessive collagen production causing early hypertrophy scarring. Early injection of corticosteroids, which was consistently effective in our study, could represent a simple treatment for early hypertrophy scarring, thus avoiding surgical correction. These preliminary results in a small number of patients require confirmation by a comparative, multicentre, prospective controlled study.

Identification and characterization of triamcinolone acetonide, a microglial-activation inhibitor.

Recent studies show that necrotic neuronal cells (NNC) activate microglia, thereby leading to neuronal cell death. This suggests that chemicals that inhibit microglia activation may be used as neuroprotective drugs. In this context, we screened a chemical library for inhibitors of microglia activation. Using a screening system based on a nitrite assay, we isolated two chemicals that inhibit nitric oxide (NO) release from activated microglia: triamcinolone acetonide (TA) and amcinonide. The half-maximal inhibitory concentrations (IC50) of TA and amcinonide for NO release inhibition were 1.78 nM and 3.38 nM, respectively. These chemicals also inhibited NNC-induced expression of the proinflammatory genes iNOS, TNF-α, and IL-1ß in glial cells. A study based on a luciferase assay revealed that TA attenuated NNC-induced microglia activation by blocking the NF-κB signaling pathway. In addition, TA protected cortical neurons in coculture with microglia from LPS/IFN-γ-induced neuronal cell death. In conclusion, TA may inhibit microglia activation and may protect neuronal cells from death induced by microglial activation.

Repeat percutaneous epicardial mapping and ablation of ventricular tachycardia: safety and outcome.

INTRODUCTION: Epicardial mapping and ablation of ventricular tachycardia (VT) has been increasingly performed. Occasionally additional ablation is necessary, requiring repeat percutaneous access to the pericardial space. METHODS AND RESULTS: We studied 30 consecutive patients who required a repeat epicardial procedure. We specifically examined the success and safety of repeat percutaneous pericardial access as well as the ability to map and ablate epicardial VT targets. Percutaneous pericardial access at a median of 110 days after the last procedure was successful in all 30 patients. Significant adhesions interfering with catheter mapping were encountered in 7 patients (23%); 6 had received intrapericardial triamcinolone acetate (IPTA) with prior procedures. Using blunt dissection with a deflected ablation catheter and a steerable sheath, adhesions were divided allowing for complete catheter mapping in 5 patients with areas of dense adherence compartmentalizing the pericardium in 1 patient and precluding ablation over previously targeted ablation site in the second. Targeted VT noninducibility was achieved in 27 (90%) patients including 7 patients with adhesions. No direct complications related to pericardial access or adhesions disruption occurred. One periprocedural death occurred from refractory cardiogenic shock in patient with LV ejection fraction of 10%. Another patient developed asymptomatic positive Haemophilus influenzae pericardial fluid cultures identified at second procedure, which was successfully treated. CONCLUSIONS: Repeat access can be obtained after prior epicardial ablation. Adhesions from prior procedures may limit mapping, but can usually be disrupted mechanically and allow for ablation of recurrent VT. IPTA may not completely prevent adhesions.

MMP-mediated collagen breakdown induced by activated protein C in equine cartilage is reduced by corticosteroids.

The plasma serine protease activated protein C (APC) is synthesized by human chondrocytes at sites of pathological cartilage fibrillation. APC levels are increased in osteoarthritis (OA) synovial fluid, and in vitro APC has been shown to synergize with interleukin-1beta (IL-1) to promote degradation from ovine cartilage. A model of equine cartilage degradation was established and used to explore corticosteroid activities. Intraarticular corticosteroids are a commonly prescribed treatment for joint disease, however their role in disease modification remains unclear. APC synergized with IL-1 or tumor necrosis factor-alpha (TNFalpha), promoting significant collagen degradation from equine cartilage explants within 4 days, but did not augment glycoaminoglycan (GAG) release. APC activated pro-matrix metalloproteinases (MMP)-2 but not pro-MMP-9, as assessed by gelatin zymography. APC did not directly activate pro-MMP-13. Dexamethasone, triamcinolone, and methylprednisolone acetate (MPA) were evaluated at concentrations between 10(- 5)M and 10(-10)M. High concentrations significantly increased GAG release from IL-1+APC-treated explants. With the exception of MPA at 10(-10)M, all concentrations of corticosteroids caused significant decreases in IL-1+APC-driven hydroxyproline loss. Treatment with corticosteroids suppressed expression of MMP-1, -3, and -13 mRNA. The collagenolysis associated with IL-1+APC synergy, and the inhibition of this effect by corticosteroids may involve gelatinase activation and downregulation of MMP expression, respectively.

[Intralesional corticosteroid therapy in infantile hemangiomas]. / Miejscowa sterydoterapia w naczyniakach krwionosnych u dzieci.

INTRODUCTION: This study was undertaken to evaluate the effectiveness of intralesional corticosteroid therapy in infantile hemangiomas. MATERIAL AND METHODS: The study was done in 38 patients aged 1 month to 14 years with infants accounting for 84% of all patients. Physical investigation was carried out before and after treatment. Localization, size of tumor, pressure, and surface features were recorded. Doppler ultrasound was performed concomitantly and served to measure tumor size and blood flow in tumor vasculature. Midazolanium 1-2 mg/kg was administered intravenously without general anesthesia. Treatment consisted of 3-5 doses of Polcortolon with intervals of 5-6 weeks between doses. The corticosteroid dose was individualized and depended on tumor size and age of patient. The results were analyzed with the modified Sloan's scale. RESULTS: Hemangioma was disclosed immediately after birth in 30 patients (78%). The tumor had an intense cherry color and demonstrated increased pressure and fast enlargement during the first weeks of life. In the remaining eight patients (22%), the tumor appeared after the second month of life and failed to show features of fast growth during the first year of life. The location of hemangioma was on the head and neck in 22 children (58%) and on the chest, extremities, abdomen, or lower back (lumbar region) in the remaining children. Doppler ultrasound revealed increased vascular flow in the tumor of all patients. Intralesional corticosteroid therapy resulted in reduction of tumor volume of more than 50% in 18 (47%), less than 50% in 12 (32%), and little or no change in eight (21%) cases. A very good result in one patient was achieved with two weeks of supplemental oral Prednisolon therapy. Total or partial excision of the tumor for aesthetic reasons was done in eight patients in whom intralesional corticosteroid therapy produced substantial reduction in tumor size. CONCLUSIONS: Intralesional corticosteroid therapy is an effective and safe modality particularly suitable for the management of extensive hemangiomas of the head and neck when surgical options are limited.

[A comparative clinical study of the treatment of hypertrophic scars with either intralaesional steroid or silicone gel sheeting]. / A hypertrophiás hegek intralaesionalis szteroid és polisziloxán-tapaszos kezelésének összehasonlító klinikai vizsgálata.

The linear (or "surgical") hypertrophic scar is the most common type of pathologic scarring. There has been a steady increase in the number of patients with hypertrophic scars over the years due to the rising number of operative interventions altogether. However, the therapeutic protocols are not homogeneous and they show significant variations. 200 cases with hypertrophic scars were treated by the authors from April 2001 to March 2004. 24 patients were selected in the study from these cases; and two randomized groups were formed. Each group included 12-12 patients, who were treated with either intralaesional steroid or silicone gel sheeting. The therapeutic protocols were defined by the authors. The aim of this study was to compare and determine the roles of these two commonly used treatment options of hypertrophic scars. The authors present patient demographics; and analyze the results and outcome of the study. Both methods were efficient significantly, however intralaesional steroid therapy had a more rapid effect and it lasted longer than silicone gel sheeting. These results confirmed the role of these two treatment modalities in the protocols. The authors concluded that silicone gel sheeting is the first line, while intralaesional steroid is the second line treatment for primary linear hypertrophic scars. Based on the authors' experience, in recurrent linear hypertrophic scars, intralaesional steroid therapy is recommended in first line, because silicone gel sheeting was largely ineffective. Prospective randomized clinical trials should be needed to further clarify their role in the treatment protocols.

Treatment of oral submucous fibrosis by collagenase: effects on oral opening and eating function.

OBJECTIVE: Patients with oral submucous fibrosis (OSF) suffer from the limitation of the oral opening. The aim of this study was to develop a simple and rapid method to improve the opening of the oral cavity and determine its effect on the incidence of developing oral carcinoma. METHODS: We first induced an OSF-like lesion in rabbits which histopathologically resembles OSF in betel nut chewers and evaluated the effects of exogenous collagenase on these lesions. We then applied the collagenase treatment regimen to patients with OSF. RESULTS: Endogenous collagenase activities in normal oral mucosa of patients exhibited 3- to 5-fold higher levels than that of OSF tissues. The collagenase treatment not only resulted in a significant improvement of oral opening, but patients also experienced a striking reduction in hypersensitivity to spices, sour, cold, and heat which helped restore eating function. Sub-mucosal fibrous proliferation, persistently good vascularization, and a mild increase in thickness of the sub-mucosal fibrous tissues were noticed 10 months after collagenase treatment. Within the 2-year follow-up period none of the treated patients developed an oral squamous cell carcinoma. CONCLUSION: A reduced content of functional collagenase observed in OSF mucosa of patients might be one mechanism responsible for collagen accumulation. Intervention of OSF by collagenase treatment at the early stage may reduce the incidence of developing oral carcinoma.

Vitrectomy and internal limiting membrane peeling for myopic foveoschisis.

PURPOSE: Myopic foveoschisis is common in high myopia. We report results of a pilot study of vitrectomy for patients with myopic foveoschisis. DESIGN: Interventional case series. METHODS: In an institutional setting five patients with high myopia (six eyes), and who had progressive visual impairment presumably due to myopic foveoschisis were studied. No eyes had a macular hole preoperatively based on optical coherence tomography (OCT). We performed vitrectomy including vitreous cortex removal, internal limiting membrane (ILM) peeling, and gas tamponade. Patients were followed for at least 6 months. Best-corrected visual acuity (BCVA), OCT. Scanning laser ophthalmoscope (SLO) microperimetry was examined in three eyes. RESULTS: The foveal detachment resolved completely in five eyes and partially in one eye. No serious complications developed including macular hole formation or retinal detachment; BCVA improved more than two lines in all eyes (100%) 6 months postoperatively (P <.01); SLO microperimetry showed smaller scotoma compared with preoperatively and stabilized fixation. CONCLUSIONS: Vitrectomy with vitreous cortex removal, ILM peeling, and gas tamponade could be useful to treat myopic foveoschisis in highly myopic eyes. Because the natural course of the disease is not well-understood, further study should establish indications for this surgery.

High injection pressure during intralesional injection of corticosteroids into capillary hemangiomas.

BACKGROUND: Intralesional injection of corticosteroids is an effective treatment for tumors of the head and neck. Complications are rare but include permanent loss of vision. We designed a study to investigate the mechanism for this complication. METHODS: Three fellowship-trained pediatric ophthalmologists participated in the study in a nonmasked fashion. Four patients received 5 separate treatment sessions of an intralesional injection of a 50-50 mixture of triamcinolone diacetate (40 mg/mL) and betamethasone sodium phosphate and betamethasone acetate (6 mg/mL) into capillary hemangiomas. Injection pressure was obtained in real time using a cannula designed for this purpose. Maximum pressure, mean pressure, and volume of corticosteroid were measured from each injection. RESULTS: A total of 71 injections (range, 8-33 injections per patient) was performed. The total volume of corticosteroid ranged from 0.9 to 2.1 mL. In 63 of 71 injections, the maximum pressure exceeded 100 mm Hg (range, 18.65-842.18 mm Hg). Each surgeon produced injection pressures greater than the systemic arterial pressures of each patient. CONCLUSIONS: Injection pressures exceeding the systemic arterial pressures routinely occur during intralesional injections of corticosteroids into capillary hemangiomas. Experienced surgeons participating in a nonmasked protocol were unable to prevent high injection pressures of corticosteroid. A sufficient volume of corticosteroid injected at high injection pressure would account for the embolization of corticosteroid particles into the ocular circulation from retrograde arterial flow. We recommend limiting the volume of corticosteroid and performing indirect ophthalmoscopy on all patients receiving injections of long-acting corticosteroids into the orbit and periorbital soft tissue.

Multifocal eosinophilic granuloma of the jaw: long-term follow-up of a novel intraosseous corticoid treatment for recalcitrant lesions.

Eosinophilic granuloma of the jaws is a rather benign and localized form of Langerhans' cell histiocytosis. Treatment is usually required in larger lesions that cause local pain and swelling and pose the risk of spontaneous fractures. There are several accepted forms of treatment, which include surgery, radiation therapy, systemic and local therapy with corticoids, and systemic chemotherapy. No studies exist that compare the effectiveness of these treatment modalities. We report a novel therapeutic regimen that uses repeated intraosseous injections of triamcinolone-1 16 alpha 21-diacetat, a synthetic corticoid, which led to a rapid, complete, and durable treatment. The patient had a multilocal eosinophilic granuloma of the mandible in which radiation therapy, systemic corticoid therapy, and systemic chemotherapy had failed.

Comparison of intramuscular triamcinolone and oral prednisone in the outpatient treatment of acute asthma: a randomized controlled trial.

STUDY OBJECTIVE: To determine whether a one-time dose of triamcinolone diacetate, 40 mg intramuscular (i.m.), given to adult patients treated in the emergency department for mild to moderate exacerbation of asthma would decrease the rate of relapse during the following week, compared with a nontapering course of oral prednisone, 40 mg/day over 5 days. METHODS: A randomized, double-blind, controlled clinical trial was conducted at two university-affiliated community teaching hospitals with a combined annual census of 97,000. Patients were eligible if they were between the ages of 18 and 50 years, had an initial peak expiratory flow rate of less than 350 L/minute, and were to be discharged from the ED taking steroids. Patients were randomly assigned to receive either triamcinolone (40 mg i.m.) and placebo tablets or a placebo injection and prednisone (40 mg/day orally for 5 days). Patients were instructed to use a beta-agonist metered-dose inhaler, to continue other routine medications, to complete symptom diary cards, and to return in 7 to 10 days for follow-up. The main outcome measure was relapse, which was defined as an unscheduled visit to a physician's office or ED for worsening or persistent symptoms within 7 days of the initial ED visit. RESULTS: A total of 168 patients were initially enrolled; 6 patients were withdrawn for protocol violations and 8 because they could not be contacted for follow-up. A total of 154 patients were available for outcome analysis, 78 in the triamcinolone group and 76 in the prednisone group. There were no differences between the two patient groups with regard to demographics, smoking history, weight, or symptom severity. Mean initial peak flows were 244+/-64 L/minute for the triamcinolone group and 245+/-83 L/minute for the prednisone group. Fifty percent of the study patients were current smokers. The relapse rates were 9.0% (7/78) in the triamcinolone group and 14.5% (11/76) in the prednisone group (P=.29). The absolute difference in relapse rates was 5.5% (95% confidence interval [CI], 4.6% to 15.6%). There was no difference in symptom frequency or severity between the two groups during the first 5 days of outpatient treatment. Analysis between the groups stratified for smoking showed no difference in relapse rate between smokers and nonsmokers. CONCLUSION: A single dose of triamcinolone diacetate, 40 mg i.m., produced a relapse rate similar to that of prednisone, 40 mg/day orally for 5 days, after ED treatment of mild to moderate exacerbations of asthma. Intramuscular triamcinolone would appear to be an attractive alternative when compliance with a daily oral regimen is of concern.

Increased plasma interleukin-6 in cutaneous plasmacytoma: the effect of intralesional steroid therapy.

Cutaneous plasmacytosis is a rare disorder without systemic plasma cell proliferation in organs other than the skin, with a possible malignant transformation. However, there are few effective therapies available. It has been reported that interleukin-6 (IL-6), which is a cytokine inducing B-cell differentiation to immunoglobulin-producing cells, plays a part in systemic plasmacytosis. In this study, we performed intralesional steroid therapy in the lesions of cutaneous plasmacytosis in three patients, which resulted in sufficient clinical effects. We demonstrated that before treatment, plasma IL-6 levels were significantly elevated in all the patients, and that levels were reduced in parallel with the clinical improvement after therapy. Immunohistochemistry revealed IL-6 protein expression on tumour cells in the lesional skin. Reverse transcription-polymerase chain reaction (RT-PCR) detected IL-6 mRNA in the lesional skin in all cases, levels of which were decreased after the effective intralesional steroid therapy, but which were unchanged after ineffective topical photochemotherapy (PUVA). Peripheral blood mononuclear cells from the patients produced significantly large quantities of IL-6 which were reduced by addition of steroid in vitro. These results suggest that the generation of IL-6 plays the key role in cutaneous plasmacytosis and that intralesional steroid therapy is effective in reducing the production of IL-6 in this disorder.

Annexin 1 regulation in human epidermal cells.

Annexin 1 (named p35, lipocortin I or calpactin II), initially described as a glucocorticoid induced protein, belongs to a new characterized family of intracellular proteins. In the skin, the role of annexins has still not been elucidated. In a previous study, we reported the localization of annexin 1 in both freshly isolated human epidermal cells and in cultured keratinocytes using immunofluorescence, FACS analysis and immunoblotting techniques. The protein was characterized by Western blot and immunoprecipitation as a 35 kDa protein. Results from in vivo studies confirmed the presence of annexin 1 in basal and suprabasal layers of normal human skin with modified reactivity patterns in hyperproliferative lesions. In the present study, the role of glucocorticoids in annexin 1 regulation was investigated in epidermal cells by Western blot and immunoprecipation assays. In contrast to other studies, we found that glucocorticoid treatment of epidermal cells led to a decrease in annexin 1 content in the cytoplasm and the membranes of cells. As annexin 1 was not detected in the nucleus of cells, we conclude that there was a down regulation of annexin 1 after glucocorticoid treatments rather than a translocation of the protein to the nucleus. Despite the absence of the signal peptide sequence necessary for protein secretion, annexin 1 was released in the keratinocyte culture medium. We found that the protein was secreted only in low Ca2+ medium (0.15 mM), this process required an active metabolism.

Factors associated with failure of lumbar epidural steroids.

BACKGROUND AND OBJECTIVES: The purpose of this study was to investigate factors that may influence the outcome of epidural steroid treatment for low back pain. Although the correlation of multiple factors with treatment outcome has been demonstrated, no previous studies have assessed the magnitude of risk of treatment failure associated with these factors. METHODS: Thirty-three factors derived from patient evaluation and physical examination were selected according to previous studies, clinical importance, and ease of assessment in a typical clinic setting. Two hundred nine patients were included in the analysis. Factors were analyzed by univariate and logistic regression analyses both for independent association with treatment outcome and for magnitude of risk of failure associated with each factor after adjustment for other factors. RESULTS: An increased risk of treatment failure was associated in univariate analysis with lower levels of education, smoking, lack of employment at start of treatment, constant pain, sleep disruption, nonradicular diagnosis, prolonged duration of pain, change in recreational activities, or extreme values on psychologic scales. Alcohol use was associated with decreased risk of treatment failure. With logistic regression analysis, only prolonged duration, nonradicular diagnosis, lack of employment, and smoking were independently associated with treatment outcome. CONCLUSIONS: These results suggest that several factors should be considered in treating patients with low back pain with epidural steroids. This study supports the belief that pain is a multidimensional problem and that a variety of factors may influence treatment outcome.

Localized depigmentation after steroid injection of a ganglion cyst on the hand.

Presented is the case of a man who had localized depigmentation after local injection of triamcinolone diacetate. Search of the literature indicates that this is a rare complication of such therapy. Localized depigmentation may have important cultural implications for dark-skinned patients. There is some experimental evidence that less-potent and shorter-acting steroid preparations have a lower likelihood for depigmenting side effects, and such agents may be more appropriate when injecting subcutaneous structures to prevent this complication.

Synthesis and pharmacological evaluation of new topical anti-inflammatory steroids.

The purpose of this research was to develop new topical steroid derivatives showing reduced systemic effects. Pregna-16 alpha,17-carboxycyclic acetal derivatives have been recently synthesized by reacting triamcinolone with methyl acetylalkanoate in the presence of a catalytic amount of perchloric acid. In testing for the anti-inflammatory activity of the compounds, rat cotton-pellet granuloma inhibition bioassay and mouse croton-oil-induced ear oedema inhibition bioassay were employed. One of the synthesized compounds, (22R)-9 alpha-fluoro-11 beta,21-dihydroxy-3,20-dioxo-16 alpha, 17-(methyl, methoxycarbonylmethyl)methylenedioxy-1,4-pregnadiene (I), showed more or less the same activity as shown by prednisolone in the granuloma inhibition test. However, compound I showed higher activity in the ear oedema inhibition test when applied topically (ID50 = 0.002 mg), as compared to prednisolone (ID50 = 0.006 mg) and triamcinolone (ID50 = 0.026 mg). When compound I was applied to mice, and thymus involution was measured for judging systemic effects, it was found that compound I did not show any significant thymus involution up to 0.1 mg/mouse (systemic administration) and 0.5 mg/mouse (topical administration). Because of its significantly reduced systemic effects, this compound is a promising topical anti-inflammatory steroid.

[Osteoporosis caused by long-term steroid therapy of patients with chronic asthmatic bronchitis]. / Osteoporoza w przebiegu przewleklej sterydoterapii u chorych z przewleklym astmatycznym niezytem oskrzeli.

14 patients with chronic bronchitis were observed after from 1.5 to 8 years of regular treatment with corticosteroids of sustained action given intramuscularly. The patients were analysed from the standpoint of age, sex, duration of corticosteroid treatment, type and dose of the drugs, and smoking. In 9 of them accelerated development of osteoporosis was noted its appearance depended significantly only on age and sex.

Allergic or pseudoallergic reaction following epidural steroid deposition and skin testing.

A 46-year-old female with a history of low back pain and sciatica was referred for evaluation for epidural steroid injection. Following appropriate history, physical examination and laboratory testing, an epidural injection was performed using triamcinolone diacetate (Aristocort Intralesional (R), Lederle Pharmaceuticals) and lidocaine. Despite good pain relief, the patient presented one week later to a hospital emergency room with signs and symptoms consistent with a delayed allergic or pseudoallergic reaction. Subsequent skin testing, performed one month following the epidural injection, with the same drug precipitated the onset of an accelerated but similar reaction 12 hours later. To our knowledge, this is the first known report of allergic or pseudoallergic reactions following epidural steroid deposition and subsequent skin testing in the medical literature.

Trypsin inhibitors inhibit induction by interferon-gamma of HLA-DR antigen expression on human skin cells.

Serine protease inhibitors with a specificity for trypsin inhibit interferon-gamma (INF-gamma)-induced HLA-DR expression on a hybrid human epidermal cell line (H12), dermal fibroblasts, and primary keratinocytes. Protease inhibitors with a specificity for chymotrypsin or papain fail to inhibit IFN-gamma. The inhibitory effect of the trypsin inhibitors is similar to that of glucocorticoids in that it is a transient event, fading with length of exposure to IFN-gamma, and is reversed by the addition of dibutyryl cyclic AMP (dbcAMP) and phospholipase C(PLC) from Clostridium perfringens. In H12 cells, dbcAMP and PLC enhance the IFN-gamma induction of HLA-DR, but do not induce in the absence of INF-gamma. Evidence suggests that the protease inhibitors, as well as dbcAMP and PLC, may modulate HLA-DR expression at a post-translational site as well as during IFN-gamma signal transduction. These results suggest that trypsin-like protease activity may be required for cellular HLA-DR antigen expression following exposure to IFN-gamma.

Inhibition of prostaglandin synthesis in brain of rat by dexamethasone: lack of effect of dexamethasone phosphate ester and various hormonal steroids.

The present study was designed in order to characterize the inhibitory effect of dexamethasone upon the synthesis of prostaglandins (PG) in the brain of the rat. Rats were treated with dexamethasone (20 mg/kg b.w.) and sacrificed 0-76 hr after administration of the drug. The rate of synthesis and release of PGE2 was followed by 1 hr of incubation of slices of cortex taken from these rats, in Krebs-Ringer solution. A significant inhibition occurred at 8 hr and maximal inhibition (45%) was attained at 16 hr after injection. A gradual increase in the rate of synthesis up to control values occurred between 24 and 76 hr. A dose-response study, at the range of 2-40 mg/kg, showed that a significant decrease was noted at 6 mg/kg and it was maximal (45% inhibition) at 20 and 40 mg/kg. Administration of dexamethasone-sodium-phosphate, as well as other synthetic glucocorticoids and various steroidal hormones (20 microM), failed to inhibit the biosynthesis of prostaglandins under the same experimental conditions. The effect of dexamethasone and dexamethasone phosphate on synthesis of PGE2 was also studied under in vitro conditions at 5 and 20 microM. When slices of cortex from intact rats were incubated for 1 or 2 hr in the presence of either dexamethasone or dexamethasone phosphate only dexamethasone was effective in inhibiting the synthesis of PGE2. The present results demonstrate that the inhibition of the synthesis of prostaglandins in brain by dexamethasone is both time- and dose-dependent. The lack of effect of closely related glucocorticoids demonstrate that the effect is highly specific to dexamethasone.