Anti-inflammatory Steroid Therapy Research Articles

A Rare Case of Plasma Cell Granuloma

Plasma cell granulomas (PCGs) or inflammatory pseudotumors are nonneoplastic lesions that consist of predominantly antibody-secreting plasma cells and innate immune cells such as neutrophils, macrophages, and eosinophils. Unlike in multiple myeloma, the plasma cells are polyclonal and present in a spindly fibroblast-rich stromal background. These lesions mainly occur in the lungs; however, they can arise in other organs. PCGs from the gingiva are extremely rare, and a proper diagnosis is crucial to treat these patients further. These tumors have an increased number of plasma cells that are immunoreactive with CD138 and are polyclonal for kappa and lambda light chains, confirming these proliferations' nonneoplastic nature. Surgical resection with clear margins, when possible, is the primary choice of treatment. Radiation and anti-inflammatory steroid therapy are other therapeutic approaches. Critical and careful examination by a pathologist is necessary to rule out plasma cell neoplasms. Here, we report a rare occurrence of gingival PCG in an elderly male.

Involvement of adipose tissue inflammation and dysfunction in virus-induced type 1 diabetes.

The etiopathogenesis of type 1 diabetes (T1D) remains poorly understood. We used the LEW1.WR1 rat model of Kilham rat virus (KRV)-induced T1D to better understand the role of the innate immune system in the mechanism of virus-induced disease. We observed that infection with KRV results in cell influx into visceral adipose tissue soon following infection prior to insulitis and hyperglycemia. In sharp contrast, subcutaneous adipose tissue is free of cellular infiltration, whereas β cell inflammation and diabetes are observed beginning on day 14 post infection. Immunofluorescence studies further demonstrate that KRV triggers CD68+ macrophage recruitment and the expression of KRV transcripts and proinflammatory cytokines and chemokines in visceral adipose tissue. Adipocytes from naive rats cultured in the presence of KRV express virus transcripts and upregulate cytokine and chemokine gene expression. KRV induces apoptosis in visceral adipose tissue in vivo, which is reflected by positive TUNEL staining and the expression of cleaved caspase-3. Moreover, KRV leads to an oxidative stress response and downregulates the expression of adipokines and genes associated with mediating insulin signaling. Activation of innate immunity with Poly I:C in the absence of KRV leads to CD68+ macrophage recruitment to visceral adipose tissue and a decrease in adipokine expression detected 5 days following Poly (I:C) treatment. Finally, proof-of-principle studies show that brief anti-inflammatory steroid therapy suppresses visceral adipose tissue inflammation and protects from virus-induced disease. Our studies provide evidence raising the hypothesis that visceral adipose tissue inflammation and dysfunction may be involved in early mechanisms triggering β cell autoimmunity.

Effects of dexamethasone on the Li-pilocarpine model of epilepsy: protection against hippocampal inflammation and astrogliosis

BackgroundTemporal lobe epilepsy (TLE) is the most common form of partial epilepsy and is accompanied, in one third of cases, by resistance to antiepileptic drugs (AED). Most AED target neuronal activity modulated by ionic channels, and the steroid sensitivity of these channels has supported the use of corticosteroids as adjunctives to AED. Assuming the importance of astrocytes in neuronal activity, we investigated inflammatory and astroglial markers in the hippocampus, a key structure affected in TLE and in the Li-pilocarpine model of epilepsy.MethodsInitially, hippocampal slices were obtained from sham rats and rats subjected to the Li-pilocarpine model of epilepsy, at 1, 14, and 56 days after status epilepticus (SE), which correspond to the acute, silent, and chronic phases. Dexamethasone was added to the incubation medium to evaluate the secretion of S100B, an astrocyte-derived protein widely used as a marker of brain injury. In the second set of experiments, we evaluated the in vivo effect of dexamethasone, administrated at 2 days after SE, on hippocampal inflammatory (COX-1/2, PGE2, and cytokines) and astroglial parameters: GFAP, S100B, glutamine synthetase (GS) and water (AQP-4), and K+ (Kir 4.1) channels.ResultsBasal S100B secretion and S100B secretion in high-K+ medium did not differ at 1, 14, and 56 days for the hippocampal slices from epileptic rats, in contrast to sham animal slices, where high-K+ medium decreased S100B secretion. Dexamethasone addition to the incubation medium per se induced a decrease in S100B secretion in sham and epileptic rats (1 and 56 days after SE induction). Following in vivo dexamethasone administration, inflammatory improvements were observed, astrogliosis was prevented (based on GFAP and S100B content), and astroglial dysfunction was partially abrogated (based on Kir 4.1 protein and GSH content). The GS decrease was not prevented by dexamethasone, and AQP-4 was not altered in this epileptic model.ConclusionsChanges in astroglial parameters emphasize the importance of these cells for understanding alterations and mechanisms of epileptic disorders in this model. In vivo dexamethasone administration prevented most of the parameters analyzed, reinforcing the importance of anti-inflammatory steroid therapy in the Li-pilocarpine model and possibly in other epileptic conditions in which neuroinflammation is present.

Steroid therapy and conduction disturbances after transcatheter aortic valve implantation.

Direct mechanical compression of the frame struts on the adjacent bundle branch with local inflammatory reaction might cause conduction system disturbances and need for pacemaker implantation following transcatheter aortic valve implantation (TAVI). We assessed the impact of preprocedural anti-inflammatory steroid therapy on the occurrence of conduction disturbances following TAVI. From a cohort of 324 patients who underwent transfemoral TAVI, 39 (12%) were pretreated with steroids because of iodine allergy (n=29) or active obstructive pulmonary disease (n=10). We compared the rate of occurrence of new conduction disturbances and pacemaker implantation between TAVI patients with (n=39) and without (n=285) steroid treatment, using Cox logistic regression estimates and proportional hazards models. The overall occurrence of new conduction defects and the need for new pacemaker implantation were similar among steroid and non-steroid-treated patients (38.4% vs 37.5% and 25.6% vs 25.3%, respectively). New conduction disturbances were more prevalent in patients treated with CoreValve prosthesis, low implantation, and smaller aortic annulus diameter (P<.001, P<.001, and P=.006, respectively). Thirty-day mortality and complication rates were similar between the groups. Although safe, steroid treatment prior to TAVI failed to reduce the incidence of new conduction defects and the need for pacemaker implantation.

Otomycosis due to Aspergillus spp. in a dog: case report and literature review

This report describes the clinical findings, clinicopathology and treatment of otomycosis caused by Aspergillus spp. in an atopic dog affected by chronic unilateral purulent otitis externa unresponsive to topical and oral antibiotics and antifungal treatments. Cytology of otic exudate revealed neutrophils and septate fungal hyphae, and otic culture grew Aspergillus spp. and no bacteria. Treatments included allergen-specific immunotherapy, topical and oral antifungal therapy and anti-inflammatory steroid therapy. Final resolution occurred after treatment of the underlying hypersensitivity disorder, administration of topical ketoconazole and debridement of infectious ear exudate. Otomycosis due to filamentous fungi may, as in humans, occur in dogs with ear canals compromised by pre-existing allergic or bacterial otitis, and possibly previous antibiotic therapy. Antifungal medications provided clinical improvement, but the key to successful treatment was the restoration of the normal physiology of the external auditory canal.

Enhanced Diabetogenic Effects of Combined Treatment with Hydrochlorothiazide and Prednisone in Adjuvant Arthritic Rats

Adjuvant arthritic rats received either hydrochlorothiazide (HCT) alone, prednisone (PR) alone, both drugs, or vehicle. HCT combined with PR enhanced the extent of hyperglycemia, hyperlipidemia, hypercholesterolemia, and elevation of serum urea concentration and glutamic pyruvic transaminase activity observed when either drug was given alone. These results suggest that administration of thiazide diuretics to treat edema encountered during anti-inflammatory steroid therapy may increase the risk of diabetes mellitus, atherosclerosis and certain thrombotic disorders. HCT did not reduce the anti-inflammatory activity of PR.

Rebound of rat carrageenin granuloma following cessation of anti-inflammatory steroid therapy

Glucocorticoid therapy induced rapid involution of chronic granulomatous inflammation in rats by subcutaneous injection of carrageenin. Hydrocortisone acetate injected into the granuloma pouch at doses higher than 3 mg/kg/day for 3 days caused maximum involution. After withdrawal of the corticoid therapy, rebound of the granulomatous inflammation took place resulting in rapid recovery of the wet weight and total content of tissue DNA and non-collagen proteins. A dose of 3 mg/kg/day was optimal for observing this rebound phenomenon. In order to investigate metabolic aspects of the rebound phenomenon minced granuloma was incubated in vitro with [ 3H] thymidine or [ 3H] proline. The rate of incorporation of the labeled precursor into non-collagen protein was elevated near to the normal level by 24 hr after the interruption of the corticoid treatment. A second step in the course of the recovery was a rapid increase in the incorporation of labeled thymidine into DNA which was attained by 48 hr after the last injection of the corticoid. The rate of recovery of the total amount of non-collagen protein, however, was rather slow compared with that of DNA which reached the control level 3 days after the withdrawal of the corticoid therapy. The total non-collagen protein of the granuloma reached almost complete recovery 1 day later. These results suggest that the synthesis of some fractions of the granuloma proteins which involve proteins essential for DNA synthesis was activated before the reactivation of the synthesis of DNA and some other proteins. Recovery of collagen synthesis was not complete until 4 days after the cessation of the corticoid treatment. Consequently, the total amount of collagen was still lower than that of the control on the last day of the experiment.

ASEPTIC BONE NECROSIS AND CORTICOSTEROID THERAPY.

Among the complications of anti-inflammatory steroid therapy is aseptic necrosis of the femoral and humeral heads, an effect not predicted from animal experiments. The pathogenesis of this steroid-related degenerative process is obscure. The first case report of aseptic necrosis of bone occurring in association with the administration of cortisone was published in 1957.¹However, a more recent report has included an instance of this phenomenon which was observed in 1952.² We have recently observed seven such cases in the 750-bed VA Hospital, Pittsburgh, and one instance in another hospital of the University of Pittsburgh Medical Center. Our cases closely resemble others which have been reported. Because of the increasing frequency with which degeneration of the femoral and humeral heads occurring in association with corticosteroid therapy is being observed, and since much of the pertinent literature is not in English-language journals, our experience is being reported together with a

Effect of rubeola, rubella, varicella, and a viral upper respiratory infection upon the severity of childhood asthma: With a note on the role of corticosteroids

From Jan. 1, 1958, to June 30, 1959, observations were made of the effects of epidemics of rubeola, rubella, varicella, and an acute undifferentiated upper respiratory infection on patients at the Jewish National Home for Asthmatic Children. These observations suggest that: 1. 1. An amelioration of asthma occurs during a number of acute febrile illnesses. 2. 2. Such improvement may be related to the degree of pyrexia and may last from one to six weeks or more. 3. 3. Children on prolonged anti-inflammatory steroid therapy show the same beneficial response to these intercurrent illnesses as do children who have not received steroids. 4. 4. Anti-inflammatory steroids do not necessarily alter the course or mask the symptoms of an acute infection. 5. 5. Prolonged anti-inflammatory steroid therapy, at least in the dosage occasionally required in the management of asthma, does not seem, in the authors' experience, to be associated with an increased incidence of complications of the childhood exanthemata.