Orbital aspergillosis: voriconazole - the new standard treatment?

BACKGROUND/AIM: To describe a case of invasive orbital aspergillosis and evaluate treatments and outcomes. METHODS: A case report and review of orbital aspergillosis treatment with voriconazole in the English language literature. CONCLUSION: Amphotericin B with debridement is the current standard of care for orbital aspergillosis; however, its prognosis is unfavorable. When compared to amphotericin B, voriconazole demonstrates a survival benefit, has less systemic toxicity, and is better tolerated by patients. While a prospective trial comparing amphotericin B to voriconazole in orbital aspergillosis is not feasible, there is evidence to support the use of voriconazole as primary therapy.

Reduction of intramyocellular lipid following short-term rosiglitazone treatment in Zucker fatty rats: an in vivo nuclear magnetic resonance study.

The aim of the study was to characterize the effects of rosiglitazone, an oral insulin sensitizer, on intramyocellular lipid (IMCL) content in tibialis anterior muscle and whole body lipid deposition in Zucker fatty rats using in vivo (1)H nuclear magnetic resonance (NMR) spectroscopy. The IMCL/EMCL (extramyocellular) ratio was significantly lower in the rosiglitazone (FRSG) group at 7, 14, 21, and 28 days of treatment at 3 mg/kg/d (0.04 +/- 0.01, 0.09 +/- 0.03, 0.11 +/- 0.02, and 0.07 +/- 0.02, respectively) versus baseline (0.43 +/- 0.12, P <.01 v all time points), whereas there was no difference in the control (FC) group at these time points (0.31 +/- 0.08, 0.36 +/- 0.08, 0.40 +/- 0.14, and 0.49 +/- 0.18, respectively) versus baseline (0.37 +/- 0.07). Absolute IMCL content was also lower at 28 days in the FRSG (0.41 +/- 0.09 micromol/g) versus FC (2.13 +/- 0.40 micromol/g, P <.005) group. To further characterize the temporal nature of this change, the IMCL/EMCL ratio was examined in the FRSG group on each of the first 4 days of treatment, and a steady decline was observed (0.38 +/- 0.12, 0.21 +/- 0.08, 0.12 +/- 0.04, 0.09 +/- 0.04, 0.05 +/- 0.03 at baseline and days 1, 2, 3, and 4 respectively, P <.05 baseline v all time points). To examine the relationship between IMCL and insulin sensitivity, a euglycemic-hyperinsulinemic clamp and IMCL measurement was performed on 7-day treated FRSG and FC groups. There was a negative correlation between absolute IMCL content and glucose infusion rate (r = -0.47, P <.04). The FRSG and the FC groups had similar whole body lipid content (expressed as a percentage of whole body water content) at baseline (48% +/- 5% and 44% +/- 2%, respectively), but the value was greater in the FRSG group following 28 days of treatment (103% +/- 4 v 84% +/- 6%, respectively, P <.02). In summary, there was a rapid (days) and pronounced reduction ( downward arrow approximately 70%) in IMCL content in tibialis anterior muscle following rosiglitazone treatment. Additionally, the increase in whole body lipid in the FRSG group suggests that there was increased adipocyte lipid storage following long-term rosiglitazone treatment. These results support the hypothesis that rosiglitazone indirectly increases peripheral insulin sensitivity by decreasing adipocyte lipolysis, thereby lowering IMCL content.

Normalization of skeletal muscle glycogen synthesis and glycolysis in rosiglitazone-treated Zucker fatty rats: an in vivo nuclear magnetic resonance study.

The aim of this study was to characterize insulin-stimulated skeletal muscle glucose metabolism in Zucker fatty rats and to provide insight into the therapeutic mechanism by which rosiglitazone increases insulin-stimulated glucose disposal in these rats. Metabolic parameters were measured using combined in vivo (13)C nuclear magnetic resonance (NMR) spectroscopy to measure skeletal muscle glucose uptake and its distributed fluxes (glycogen synthesis and glycolysis), and (31)P NMR was used to measure simultaneous changes in glucose-6-phosphate (G-6-P) during a euglycemic-hyperinsulinemic clamp in awake Zucker fatty rats. Three groups of Zucker fatty rats (fatty rosiglitazone [FRSG], fatty control [FC], lean control [LC]) were treated for 7 days before the experiment (3 mg/kg rosiglitazone or vehicle via oral gavage). Rates of glycolysis and glycogen synthesis were assessed after treatment by monitoring 1,6-(13)C(2) glucose label incorporation into 1-(13)C glycogen, 3-(13)C lactate, and 3-(13)C alanine during a euglycemic ( approximately 7-8 mmol/l)-hyperinsulinemic (10 mU. kg(-1). min(-1)) clamp. The FRSG group exhibited a significant increase in insulin sensitivity, reflected by an increased whole-body glucose disposal rate during the clamp (24.4 +/- 1.9 vs. 17.6 +/- 1.4 and 33.2 +/- 2.0 mg. kg(-1). min(-1) in FRSG vs. FC [P < 0.05] and LC [P < 0.01] groups, respectively). The increased insulin-stimulated glucose disposal in the FRSG group was associated with a normalization of the glycolytic flux (52.9 +/- 9.1) to LC (56.2 +/- 16.6) versus FC (18.8 +/- 8.6 nmol. g(-1). min(-1), P < 0.02) and glycogen synthesis flux (56.3 +/- 11.5) to LC (75.2 +/- 15.3) versus FC (16.6 +/- 12.8 nmol. g(-1). min(-1), P < 0.05). [G-6-P] increased in the FRSG and LC groups versus baseline during the clamp (13.0 +/- 11.1 and 16.9 +/- 5.8%, respectively), whereas [G-6-P] in the FC group decreased (-23.3 +/- 13.4%, P < 0.05). There were no differences between groups in intramyocellular glucose, as measured by biochemical assay. These data suggest that the increased insulin-stimulated glucose disposal in muscle after rosiglitazone treatment can be attributed to a normalization of glucose transport and metabolism.