In cattle fattening, the illicit use of growth promoters (GPs) represents a major problem. The synthetic corticosteroid dexamethasone (DEX) is the GP mostly used, alone or in combination with other steroids or beta-agonists. Recently, GPs were shown to disrupt some cattle cytochromes P450 (CYPs) at the post-transcriptional level; therefore, the effects of two illicit protocols containing DEX (alone or together with 17beta-estradiol, 17betaE) upon main cattle liver drug metabolizing enzymes (DMEs) mRNAs and related transcription factors were investigated by quantitative real time RT-PCR. Eleven genes, out of the 18 considered, were significantly modulated by GPs. Corticosteroid-responsive genes did not respond univocally, whereas retinoic X receptor alpha (RXRalpha) and estrogen receptor alpha (ERalpha) were upregulated depending on the illicit protocol used. Nowadays, an increasing interest has been noticed toward the detection of biomarkers of response (BMRs) to be used in the screening of GPs misuse in cattle farming. In the present study, CYP2B6-like, CYP2E1, glutathione S-transferase A1- and sulfotransferase A1-like (GSTA1- and SULT1A1-like) mRNAs were significantly modulated regardless of the GP, the illicit protocol, and the animal breed, representing promising BMRs. The usefulness of these BMRs needs to be characterized more in depth. less...

Transplant vasculopathy has not been systematically investigated in composite tissue allotransplantation (CTA). The impact of multiple acute rejections (ARs) on long-term graft outcomes in reconstructive transplantation remains unknown. This study in a rat hind-limb allotransplantation model systematically analyzes vasculopathy and tissue-specific pathological changes secondary to multiple AR episodes. LEW rats were transplanted with BN rat hind limbs and treated as follows: Group 1 (Iso): isografts. Group 2 (CsA): Cyclosporine (CsA) qd; Group 3 (mult AR): CsA and dexamethasone only when AR was observed. No AR was observed in Groups 1 and 2. Multiple AR were observed in Group 3, and each episode was completely reversed (clinically) with pulsed CsA + dexamethasone treatment. Group 3 animals demonstrated significant vascular lesions along with skin and muscle atrophy, upregulation of profibrotic gene expression and fibrosis when compared to Groups 1 and 2. In addition, allograft bone was sclerotic, weak and prone to malunion and nonunion. Interestingly, vasculopathy was a late finding, whereas muscle atrophy with macrophage infiltration was seen early, after only a few AR episodes. Taken together, multiple AR episodes lead to vasculopathy and tissue-specific pathology in CTA. This is the first evidence of 'composite tissue vasculopathy and degeneration (CTVD)' in CTA. less...

Functionalization of a porous orthopedic implant with dexamethasone, a widely used anti-inflammatory drug, encapsulated within a biodegradable polymer for controlled release could help reduce or eliminate the inflammation response by the local tissue. In this research, we investigated the possibility of using supercritical carbon dioxide (CO2) for attaching dexamethasone-loaded PLGA (polylactic-co-glycolic acid) microspheres to porous CoCrMo alloy for continuous delivery of dexamethasone. Supercritical CO2 has been shown to be effective for attachment of PLGA microspheres to glass plates and porous CoCrMo alloy. Attached microspheres showed similar dexamethasone release profiles but different magnitude of burst release. Microspheres attached to the porous alloy samples using supercritical CO2 at 10 bar and 40 degrees C for 30 min showed a release profile similar to that of the nonattached microspheres. The microsphere morphology and the release profiles of microspheres attached to the glass plates and to the porous alloy samples suggest that dexamethasone burst release is enhanced by PLGA swelling at higher CO2 pressures and better dispersion of microspheres. This study shows that microspheres can be incorporated into porous solids using supercritical CO2, allowing for a wide variety of drug-biodegradable polymer formulations prepared using the proven emulsion/solvent evaporation method to be tested. less...

Our objective was to optimize a medium for preadipocyte differentiation into adipocytes. METHODS: The differentiation medium contains fixed components as well as 7 variable ones. To perform this study, different experiments were designed and the study was carried out in 4 stages. The first two stages tested the influence of serum, dexamethasone, hydrocortisone and an cAMP activator. In the third stage, two new variables were added: rosiglitazone and insulin. In the final stage, the medium selected in stage 3 was validated. The differentiation selection criteria consisted of the number of mature adipocytes and adiponectin secretion Results: We have shown that each variable was indispensable and that positive interactions occurred between some variables. No negative interactions were found and it was possible to optimize the concentration of each variable. CONCLUSIONS: We selected the following medium, which provides optimal adipocyte size and adiponectin secretion: DMEM/HAMF12+10% Foetal Clone Serum (FCS)+2 nM triiodothyronine+10 nM hydrocortisone +0.5 mM IsoButyl Methyl Xanthine (IBMX)+500 nM dexamethasone+1 microM rosiglitazone+0.15 UI/ml insulin+antibiotics. less...

The rare occurrence of T-cell lymphoblastic lymphoma as a primary tumor in the cavernous sinus is described. The patient, a 17-year-old girl, presented with right-sided ophthalmic and maxillary neuropathy and diplopia due to neuropathies of cranial nerves III and VI. An enhancing mass in the cavernous sinus was identified on MR imaging. Dexamethasone was prescribed but did not provide symptomatic relief. Rapid progression of symptoms led to open biopsy, and a diagnosis of T-cell lymphoblastic lymphoma was made. The patient promptly underwent aggressive chemotherapy in which a modified hyper-cyclophosphamide, vincristine, and dexamethasone without doxorubicin regimen with concurrent radiotherapy was used. The patient achieved complete remission and is currently completing the 2-year maintenance phase of chemotherapy. less...

Objective-To investigate the effects of dexamethasone or levothyroxine sodium on endotoxin-induced alterations in glucose and insulin dynamics. Animals-24 horses. Procedures-Horses were randomly allocated to 3 treatment groups and received 48 mg of levothyroxine mixed with 200 g of oats, 20 mg of dexamethasone plus oats, or oats alone (control) for 15 days, followed by IV infusion of lipopolysaccharide (20 ng/kg) while individually housed in stalls. Frequently sampled IV glucose tolerance tests were performed prior to pretreatment, after pretreatment, and 20 hours after lipopolysaccharide administration. Area under the curve for plasma glucose and serum insulin concentrations was calculated, and minimal model analyses were performed. Results-Significant treatment-by-time effects were detected for insulin sensitivity (SI) and area under the curve for glucose and insulin in the 15-day pretreatment period. Insulin sensitivity significantly decreased over time in all treatment groups, with the largest decrease detected in the dexamethasone group. Administration of lipopolysaccharide further decreased mean SI by 71% and 63% in the dexamethasone and control groups, respectively, but did not affect horses in the levothyroxine group. Mean SI was the lowest in the dexamethasone group, but percentage reduction was the same for dexamethasone and control groups. Conclusions and Clinical Relevance-Insulin sensitivity decreased during the pretreatment period in all 3 groups, indicating that hospitalization affected glucose and insulin dynamics. Dexamethasone significantly lowered SI, and endotoxemia further exacerbated insulin resistance In contrast, there was no additional effect of endotoxemia on SI in horses pretreated with levothyroxine, suggesting that this treatment prevented endotoxemia-induced insulin resistance less...

Histone H3 methylation at lysine 4 (K4) is associated with euchromatic regions and is thought to be important for the transcriptional activation of genes during differentiation. In this study, we found that di- and tri-methylation of histone H3 at K4 and acetylation of histones H3 and H4 from the promoter/enhancer to the transcribed region close to the transcription initiation site of the solute carrier family 2, member 5 (SLC2A5) gene, and its expression, were induced by differentiation of intestine-like Caco-2 cells. These effects were accompanied by contact inhibition of cell growth of these cells. Furthermore, these modifications were induced by co-treatment with a synthetic glucocorticoid hormone dexamethasone and a p44/42 mitogen-activated protein kinase inhibitor PD89059. Our results suggest that methylation of histone H3 at K4 and acetylation of histones H3 and H4 are involved in SLC2A5 gene induction associated with intestinal differentiation of Caco-2 cells. less...

BACKGROUND: We explored the addition of rituximab to high-dose cytarabine (ara-C), oxaliplatin (L-OHP), and dexamethasone [R-DHAOx], in resistant and relapsed patients with CD20-positive follicular non-Hodgkin's lymphoma. METHODS: Twenty-two patients were included; they were treated previously with one to five chemotherapy regimens, including 13 patients who had also received rituximab. R-DHAOx consisted of rituximab, 375mg/m(2), day 1; dexamethasone, 40mg/d, days one to four; L-OHP, 130mg/m(2), day 1; and ara-C, 2000mg/m(2) every 12 h, day 2. Courses were repeated every 21 days for eight courses. RESULTS: Twenty-one patients (95%) achieved a complete response and one had a partial response. Responses were obtained in patients with and without resistance to prior treatment, either alone or combined with rituximab. The median follow-up time was 58.3 months (range, 8.7-92.6 months). Progression-free survival reached a plateau at 84% at 38.2 months. Only two of the 21 complete responders have relapsed. Tumor molecular markers disappeared in all 10 complete responders whose markers were found before treatment. Peripheral neuropathy related to the cumulative dose of L-OHP, and myelosuppression were the most prominent toxic effects. CONCLUSIONS: R-DHAOx is highly active for salvage treatment of patients with follicular non-Hodgkin's lymphoma, and it produces long-term antitumor efficacy. less...

Th2 cytokine interleukin (IL)-13 plays a central role in the pathogenesis of allergic asthma. IL-13 exhibits a direct effect on airway smooth muscle cells (ASMCs) to cause airway hyperresponsiveness. IL-13 has been demonstrated to regulate Ca(2+) signaling in ASMCs, but the underlying mechanisms are not fully understood. Store-operated Ca(2+) entrySOCEplays an important role in regulating Ca(2+) signaling and cellular responses of ASMCs, whether IL-13 affects SOCE in ASMCs has not been reported. In this study, by using confocal Ca(2+) fluorescence imaging, we found that IL-13 (10 ng/ml) treatment increased basal intracellular Ca(2+) ([Ca(2+)](i)) level, Ca(2+) release and SOCE induced by SERCA inhibitor thapsigargin in rat bronchial smooth muscle cells. The glucocorticoid dexamethasone and the short-acting beta2 adrenergic agonist (beta2 agonist) salbutamol suppressed IL-13-augumented basal [Ca(2+)](i), Ca(2+) release and SOCE, whereas the long-acting beta2 agonist salmeterol had no effect on altered Ca(2+) signaling in IL-13-treated ASMCs. Membrane-permeable cAMP analog dibutyryl-cAMP (db-cAMP) similarly decreased Ca(2+) release and SOCE induced by thapsigargin in IL-13-treated ASMCs, confirmed a role of cAMP/PKA signaling pathway in the regulation of SOCE. IL-13 promoted the proliferation of ASMCs stimulated by serum; this effect was inhibited by nonspecific Ca(2+) channel blockers SKF-96365 and NiCl(2), by salmeterolbut not by salbutamol and dexamethasone. IL-13 treatment did not change the expression of SOC channel-associated molecules STIM1, Orai1 and TRPC1 at mRNA level. Our findings identified a promoting effect of IL-13 on Ca(2+) release and SOCE in ASMCs, which partially contributes to its effect on the proliferation of ASMCs; the differences of glucocorticoids and beta2 agonists in inhibiting Ca(2+) signal and proliferation potentiated by IL-13 suggest that these therapies of asthma may have distinct effect on the relief of airway contraction and remodeling in bronchial asthma. less...

A 7-year-old, neutered male cat was presented with a 6-month history of progressive polyuria, polydipsia, polyphagia, aggression, and weight gain. Previous blood work, urinalysis, and radiographs did not delineate a cause for the clinical signs. An ultrasound revealed bilateral adrenal gland enlargement. A low-dose dexamethasone suppression test was consistent with hyperadrenocorticism. Based on these findings, bilateral adrenalectomy was attempted and successfully performed. Histopathology was consistent with a cortical adenoma in the right adrenal gland and a pheochromocytoma in the left adrenal gland. This association has never been reported in the cat. less...