Outcome Analysis of Invasive Aspergillosis in Hematologic Malignancy and Hematopoietic Stem Cell Transplant Patients: The Role of Novel Antimold Azoles

Invasive aspergillosis (IA) continues to be a leading cause of morbidity and mortality in hematologic malignancy (HM) patients. In HM patients, persistent neutropenia and the need for intensive care are associated with failure to respond to antifungal therapy. Use of novel antimold azoles, either as primary or salvage therapy, improves the overall outcome and IA-attributable death of HM patients with IA

Role of Coccidioides Antigen Testing in the Cerebrospinal Fluid for the Diagnosis of Coccidioidal Meningitis

Background. Coccidioidal meningitis (CM), a common cause of chronic meningitis in endemic area, is usually diagnosed by detection of anti-Coccidioides antibodies in cerebrospinal fluid (CSF), and findings may be negative in up to one-third of cases. CSF cultures and cytology are infrequently positive. Antigen detection has been used for the diagnosis of other forms of coccidioidomycosis and meningitis caused by other mycoses. The purpose of this study was to assess the diagnostic utility of CSF Coccidioides antigen (CAg) detection for the diagnosis of CM. Methods. The medical records of patients with clinically suspected meningitis, in whom CSF was tested for Coccidioides antibodies and CAg, were retrospectively reviewed, and CSF CAg testing was prospectively conducted in patients with CM. All specimens were submitted for CAg testing. Results. Thirty-six patients with 42 episode of CM were studied. The sensitivity and specificity of CAg were 93% and 100%, respectively. Cultures of CSF were positive in 7%, antibodies were demonstrated by immunodiffusion in 67% and complement fixation in 70%, and immunoglobulin M and G antibodies were demonstrated by enzyme immunoassay in 8% and 85%, respectively. Conclusions. Testing CSF for CAg is a useful addition to diagnostic methods in suspected CM and complements testing with CSF antibodies and culture

Fatty acid transporter CD36 mediates hypothalamic effect of fatty acids on food intake in rats.

Variations in plasma fatty acid (FA) concentrations are detected by FA sensing neurons in specific brain areas such as the hypothalamus. These neurons play a physiological role in the control of food intake and the regulation of hepatic glucose production. Le Foll et al. previously showed in vitro that at least 50% of the FA sensing in ventromedial hypothalamic (VMH) neurons is attributable to the interaction of long chain FA with FA translocase/CD36 (CD36). The present work assessed whether in vivo effects of hypothalamic FA sensing might be partly mediated by CD36 or intracellular events such as acylCoA synthesis or β-oxidation. To that end, a catheter was implanted in the carotid artery toward the brain in male Wistar rats. After 1 wk recovery, animals were food-deprived for 5 h, then 10 min infusions of triglyceride emulsion, Intralipid +/- heparin (IL, IL(H), respectively) or saline/heparin (SH) were carried out and food intake was assessed over the next 5 h. Experimental groups included: 1) Rats previously injected in ventromedian nucleus (VMN) with shRNA against CD36 or scrambled RNA; 2) Etomoxir (CPT1 inhibitor) or saline co-infused with IL(H)/S(H); and 3) Triacsin C (acylCoA synthase inhibitor) or saline co-infused with IL(H)/S(H). IL(H) significantly lowered food intake during refeeding compared to S(H) (p<0.001). Five hours after refeeding, etomoxir did not affect this inhibitory effect of IL(H) on food intake while VMN CD36 depletion totally prevented it. Triacsin C also prevented IL(H) effects on food intake. In conclusion, the effect of FA to inhibit food intake is dependent on VMN CD36 and acylCoA synthesis but does not required FA oxidation

Schematic representations of proteins mediating FA effect on food intake in a fatty acid sensing cell.

<p>Schematic representations of proteins mediating FA effect on food intake in a fatty acid sensing cell.</p

Composition in FA in whole hypothalamus measured by GS-MS and expressed in percentage.

*<p>p<0.05 vs. S_H group.</p

Hypothalamic mRNA expression normalized with HKG.

<p>A: expression of different fatty acids transporters. B: photomicrograph showing the JetPEI injection site. C: expression of CD36 in shRNA and scramble rats. Values are means ±SEM; n≥5 rats/group. *p<0.05, significantly different from scramble rats.</p

Food intake measurement after 10 min infusion toward brain of S_H (open bars; control), S_H+treatment (light grey bars), IL_H (solid bars) and IL_H+treatment (dark grey bars) groups.

<p>A, B: 1 h-food intake (A) and 5 h-food intake (B) in scramble and CD36 shRNA rats infused with S_H or IL_H. C, D: 1 h-food intake (C) and 5 h-food intake (D) in S_H and IL_H groups co-infused with triacsin C (80 µM). E,F: 1 h-food intake (E) and 5 h-food intake (F) in S_H and IL_H groups co-infused with etomoxir (150 µM). Values are means ±SEM; n ≥4 rats/group. ***p<0.001, significantly different from S_H; ^§§p<0.01 significantly different from S_H+treatment. ^#p<0.05, ^##p<0.01 significantly different from IL_H.</p

Food intake measurement after 10 min infusion toward brain of saline (S; open bars; control) and Intralipid 20% at 20 µL/min (IL; solid bars) without (A, B) or with heparin (C,D) in Wistar rats.

<p>The same experiment was realized in Sprague Dawley rats (E,F). A, C, E: 1 h-food intake. B, D, F: 5 h-food intake. Values are means ±SEM; n≥6 rats/group. *p<0.05, **p<0.01, significantly different from controls.</p