Glucocorticoids

Editor: Eosinophilic peritonitis is defined as the presence of an absolute eosinophil count exceeding 30 per cubic millimeter of dialysis fluid in patients receiving mainte-nance peritoneal dialysis (PD) (1,2). In adult patients, the incidence has been reported to range from 16% – 30% in intermittent PD to as high as 60% in continuous ambulatory PD (CAPD) (1,2). It usually occurs within the first 3 months after dialysis initiation, although it has been reported to occur even later (2). A 7-year-old boy with end-stage renal disease second-ary to focal segmental glomerulosclerosis who had been on automated PD (APD) for 3 months was admitted to our hospital for evaluation of a malfunctioning PD catheter and a history of turbid peritoneal effluent. We observed no fever, rash, or abdominal pain, and no past history of atopy or allergies. Physical examination was unre-markable. Radiography of the abdomen showed upward migration of the distal part of the catheter. Intravenous first-generat...

This collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence-based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA). A panel of rheumatologists, orthopedic surgeons specializing in hip and knee arthroplasty, and methodologists was convened to construct the key clinical questions to be answered in the guideline. A multi-step systematic literature review was then conducted, from which evidence was synthesized for continuing versus withholding antirheumatic drug therapy and for optimal glucocorticoid management in the perioperative period. A Patient Panel was convened to determine patient values and preferences, and the ...

Background The enzyme 11-β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes intracellular glucocorticoid reactivation by conversion of cortisone to cortisol in different tissues and have been implicated in several metabolic disorders associated with obesity. The aim of this study was to evaluate the 11β-HSD1 expression in liver, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) in morbidly obese patients undergoing bariatric surgery and its correlations with clinical, anthropometric, and biochemical variables. Methods A prospective study was conducted over a 27-month period. Hepatic, VAT, and SAT samples were obtained at the time of surgery. 11β-HSD1 and 18S gene expression was measured using real-time quantitative reverse transcriptase-polymerase chain reaction. Results Forty nine patients met the inclusion criteria [mean age: 42.2 ± 10 years, body mass index (BMI): 42 ± 6 kg/m2, 71% women and 63% with metabolic syndrome (MS)]. 11β-HSD1 mRNA levels were higher in liver than fat tissue (p < 0.001), being higher in SAT than in VAT (p < 0.001) without gender-specific differences. Hepatic expression of 11β-HSD1 correlated positively with SAT and VAT, alanine aminotransferase (ALT), and serum glucose and was inversely associated with BMI. 11β-HSD1 mRNA in VAT correlated positively with insulinemia, ALT, and LDL cholesterol. There were no associations between 11β-HSD1 mRNA in SAT and the variables analyzed. Conclusions 11β-HSD1 expression is higher in liver in comparison to adipose tissue in obese patients. The observed correlations between hepatic and VAT 11β-HSD1 expression with dyslipidemia and insulin resistance suggest that this enzyme might have a pathogenic role in obesity and related metabolic disorders.

Cortisol inhibition of phytohemagglutinin (PHA)-induced lymphocyte activation was studied in vitro in peripheral blood mononuclear cells (PBMC) of patients with pathologies of the hypothalamic-pituitary-adrenocortical (HPA) system (n = 18) as well as in students under and out of academic stress. In patients with HPA pathologies, cortisol-induced inhibition of lymphocyte interleukin-2 (IL-2) secretion in vitro positively correlated (p &lt; .005) with IL-2 synthesis, such that lymphocytes secreting less IL-2 were less cortisol sensitive. Similarly, in stressed students there was a positive correlation (p &lt; .02) between lymphocyte DNA synthesis and cortisol inhibition in vitro. Academic stress also resulted in a decrease (p &lt; .01) of lymphocyte cortisol sensitivity. The same tendency was observed in patients with Cushing&#39;s syndrome when compared with hypocortisolemic patients. Normal controls whose lymphocytes were glucocorticoid resistant showed higher lymphocyte activation ...

We investigated the effects of corticosteroid and doxycycline on expression of matrix metalloproteinase (MMP)-9 and inflammatory cytokines and activation of mitogen-activated protein kinase (MAPK) signaling pathways, c-jun N-terminal kinases (JNK), extracellular-regulated kinases (ERK) and p38, in experimental murine dry eye. Experimental dry eye (EDE) was created in C57BL6 mice, with or without or topical treatment consisting of 1% methylprednisolone, 0.025% doxycycline or balanced salt solution four times per day. MMP-9 expression in the cornea epithelia was evaluated by laser scanning confocal microscopy. Gelatinase activity in the cornea was evaluated by in situ zymography and MMP-9 activity in tear washings was evaluated by gelatin zymography. Total and phosphorylated MAPKs (JNK1/2, ERK1/2, p38) were detected by Luminex immunobead assay. Levels of MMP-9, interleukin (IL)-1alpha, IL-1beta and tumor necrosis factor (TNF)-alpha RNA transcripts were evaluated by real-time PCR. MMP-9 immunoreactivity was localized to the apical corneal epithelial cell membranes in normal control eyes. Desiccating stress significantly increased production of MMP-9 by the corneal epithelium and increased its activity in the corneal epithelium and tear fluid. Dryness also increased expression of IL-1alpha, IL-1beta and TNF-alpha mRNA and stimulated phosphorylation of JNK1/2, ERK1/2 and p38 MAPKs in the corneal epithelium. Both methylprednisolone and doxycycline reduced expression and activity of MMP-9, decreased levels of inflammatory cytokines transcripts and reduced activation of MAPKs in the corneal epithelium in response to EDE. Desiccating stress stimulates expression of MMP-9, IL-1alpha, IL-1beta and TNF-alpha mRNA , as well as activates MAPK signaling pathways in the corneal epithelium. Both corticosteroid and doxycycline suppressed this molecular stress response.