Detection of occult Scedosporium species in respiratory tract specimens from patients with cystic fibrosis by use of selective media.

Respiratory samples from cystic fibrosis outpatients were cultured on Sabouraud's dextrose agar (SABD) containing antibiotics, Mycosel, and Scedosporium-selective medium (SceSel+). Thirty-two (14.7%) of 218 specimens from 11/69 (15.9%) patients yielded a Scedosporium sp., most frequently Scedosporium aurantiacum (17/218). Scedosporium was recovered on SceSel+, Mycosel, and SABD from 90.6%, 50.0%, and 46.9% of the specimens tested, respectively.

Sinonasal and sino-orbital aspergillosis in 23 cats: aetiology, clinicopathological features and treatment outcomes.

Aetiology, clinicopathological findings and treatment outcomes were documented in 23 cats (1.5-13 years of age) with sinonasal (SNA, n=6) or sino-orbital (SOA, n=17) aspergillosis. Cases recruited retrospectively and prospectively were included if fungal hyphae were identified on cytological or histological examination and the fungal pathogen was identified by PCR and DNA sequencing (ITS1 or ITS1-5.8S-ITS2 regions, rDNA gene cluster). Fungal culture was positive in 22/23 cases. In cases of SNA, the fungal pathogen was Aspergillus fumigatus (n=4), Neosartorya fischeri or A. lentulus (n=1) or a non-speciated Neosartorya spp. (n=1). In all cases of SOA (n=17), the fungal pathogen was identified as Neosartorya spp. Nine cats had brachycephalic conformation. Cats with SNA were more likely to be infected with A. fumigatus and had a better prognosis than cats with SOA.

Conversion to sirolimus allows preservation of renal function in kidney and kidney-pancreas allograft recipients.

The major causes of graft failure are chronic allograft nephropathy (CAN) and patient mortality. Sirolimus (SRL) is a powerful immunosuppressant with a less nephrotoxic profile as well as a lower incidence of cancer. The aim of this study was to evaluate the impact of conversion to SRL from calcineurin inhibitor (CNI)-based therapy in kidney (KT) and kidney-pancreas (SPK) allograft recipients. We analyzed renal function, allograft and patient survival, and SRL-associated adverse effects in 93 adult patients (86 KT and 7 SPK), who were converted to SRL between January 2001 and November 2008. The main reason for conversion was CAN (76; 9%) and 52 (7%) were receiving tacrolimus. Conversion occurred at a median 26.2 months. There was a significant improvement in creatinine clearance (CCr) at 6 months after conversion (CCr(baseline) 51.4 vs CCr(6m) 60.4 mL/min; P < .0001), without changes at 12 and 24 months. However, proteinuria increased significantly at 6 months compared with the baseline: 150 mg/24 hours (0-453) versus 0 mg/24 hours (range, 0-309), respectively (P < .0001), but did not progress at 12 or 24 months. At the same time we observed more extensive use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers: 60/5%; 65/3% and 70/2% at 6, 12, and 24 months. There were no changes in blood pressure control. Cholesterol significantly increased at 6 months (218.2 +/- 37 vs. 186.6 +/- 44 mg/dL; P < .0001). Graft and patient survivals at 4 years were 88% and 95%, respectively. Our experience suggested that conversion to SRL constituted a safe alternative with excellent results in patient and graft survival.

Angiotensin II AT1 receptor internalization, translocation and de novo synthesis modulate cytosolic and nuclear calcium in human vascular smooth muscle cells.

The present study was designed to verify if human (h) Angiotensin II (Ang II) type-1 receptor (hAT1R) undergoes internalization, nuclear translocation, and de novo synthesis in primary culture of human aortic vascular smooth muscle cells (hVSMCs) and if overexpression of this receptor modulates sustained free cytosolic ([Ca]c) and nuclear ([Ca]n) calcium. 3-dimensional (3-D) confocal microscopy was used to monitor free intracellular Ca2+ and hAT1R-green fluorescence protein (GFP) fusion protein in cultured hVSMCs. Immunofluorescence studies showed the presence of hAT1R and the absence of hAT2R in normal hVSMCs. Using 3-D imaging technique, hAT1 receptors were localized at the sarcolemma and in the cytosolic and nuclear compartments. In native as well as in normal hAT1R or hAT1R-GFP overexpressing hVSMCs, Ang II (10(-9) and 10(-4) M) induced internalization and nuclear translocation of this type of receptor. The internalization of hAT1Rs is mediated via clathrin-coated pits and vesicles pathway. This phenomenon of trancellular trafficking of receptors was associated with an increase of hAT1R. The Ang II induced increase of hAT1R density was prevented by the protein synthesis inhibitor cycloheximide. Overexpression of hAT1R and hAT1R-GFP decreased both basal cytosolic and nuclear Ca2+. In normal hVSMCs and low hAT1R-GFP overexpressing hVSMCs, Ang II (10(-15) to 10(-4) M) induced a dose-dependent sustained increase of [Ca]c and [Ca]n with an EC50 near 5 x 10(-11) and 5 x 10(-9) M, respectively. Our results suggest that hAT1Rs are the predominant type of Ang II receptors in aortic hVSMCs and are present in the sarcolemma, the cytosolic and the nuclear compartments. Ang II rapidly induces hAT1R internalization, nuclear translocation, as well as nuclear de novo synthesis of this receptor. The hAT1R overexpression in hVSMCs modulates sustained [Ca]c and [Ca]n.