HIV-Associated Cryptococcal Meningitis Patients Treated with Amphotericin B Deoxycholate Plus Flucytosine under Routine Care Conditions in a Referral Center in São Paulo,Brazil

Mycopathologia - Cryptococcal meningitis remains a common cause of mortality in low- and middle-income countries, where amphotericin B deoxycholate (amphotericin) plus fluconazole is the most...     

Induction of heme oxygenase-1 can halt and even reverse renal tubule-interstitial fibrosis

Background

The tubule-interstitial fibrosis is the hallmark of progressive renal disease and is strongly associated with inflammation of this compartment. Heme-oxygenase-1 (HO-1) is a cytoprotective molecule that has been shown to be beneficial in various models of renal injury. However, the role of HO-1 in reversing an established renal scar has not yet been addressed.

Aim

We explored the ability of HO-1 to halt and reverse the establishment of fibrosis in an experimental model of chronic renal disease.

Methods

Sprague-Dawley male rats were subjected to unilateral ureteral obstruction (UUO) and divided into two groups: non-treated and Hemin-treated. To study the prevention of fibrosis, animals were pre-treated with Hemin at days -2 and -1 prior to UUO. To investigate whether HO-1 could reverse established fibrosis, Hemin therapy was given at days 6 and 7 post-surgery. After 7 and/or 14 days, animals were sacrificed and blood, urine and kidney tissue samples were collected for analyses. Renal function was determined by assessing the serum creatinine, inulin clearance, proteinuria/creatininuria ratio and extent of albuminuria. Arterial blood pressure was measured and fibrosis was quantified by Picrosirius staining. Gene and protein expression of pro-inflammatory and pro-fibrotic molecules, as well as HO-1 were performed.

Results

Pre-treatment with Hemin upregulated HO-1 expression and significantly reduced proteinuria, albuminuria, inflammation and pro-fibrotic protein and gene expressions in animals subjected to UUO. Interestingly, the delayed treatment with Hemin was also able to reduce renal dysfunction and to decrease the expression of pro-inflammatory molecules, all in association with significantly reduced levels of fibrosis-related molecules and collagen deposition. Finally, TGF-β protein production was significantly lower in Hemin-treated animals.

Conclusion

Treatment with Hemin was able both to prevent the progression of fibrosis and to reverse an established renal scar. Modulation of inflammation appears to be the major mechanism behind HO-1 cytoprotection.     

Usefulness of Yeast Cell Counting and Lack of Clinical Correlation of the Antifungal Susceptibility Testing Results in Management of Aids-associated Cryptococcal Meningitis

Cryptococcal meningitis is one of the most seriously opportunistic infections in people living with HIV. We evaluated clinical and laboratorial features (minimum inhibitory concentrations for fluconazole, initial fungal burden in cerebrospinal fluid) and risk factors associated with in-hospital mortality. There is no good evidence for the use of minimum inhibitory concentrations for fluconazole in routine practice for the management of cryptococcosis patients. Counting yeast cells at cerebrospinal fluid can predict positive culture by not death. Data from 46 cryptococcal meningitis patients were reviewed, retrospectively. Patients who presented yeast cell count greater than 400 yeast cells/μ in their initial cerebrospinal fluid sample were associated with higher mortality (p = 0.014); moreover, the yeast cell count is an easy and cheap assay, with high values possibly associated to poor prognosis. Additionally, we verified no significant differences between fluconazole susceptibility profile, molecular type, clinical presentation, cytological analyses, time to sterilize the cerebrospinal fluid, agent recovering out of central nervous system, previous diagnosis of cryptococcal meningitis or usage of fluconazole, and overall mortality.     

Acute aerocystitis in Piaractus mesopotamicus: Participation of eicosanoids and pro-inflammatory cytokines

A total of 360 pacus (Piaractus mesopotamicus) were used to study vascular permeability (VP) and inflammatory cell component (CC) in induced aerocystitis in P. mesopotamicus through inoculation of inactivated Aeromonas hydrophila, and the effect of steroidal and nonsteroidal anti-inflammatory drugs. It was observed that after inoculation of A. hydrophila, the maximum VP occurred 180 min post-stimulus (MPS). Pretreatment with anti-inflammatory drugs inhibited VP, and the inhibitory effect of dexamethasone was seen earlier than the effects caused by meloxicam and indomethacin. Inoculation of the bacterium caused a gradual increase in the accumulation of cells, which reached a maximum 24 h post-stimulus (HPS). Pretreatment with dexamethasone, indomethacin and meloxicam reduced the accumulation of lymphocytes, thrombocytes, granulocytes and macrophages. There was no significant difference between the different doses of the drugs tested. The results suggest that eicosanoids and pro-inflammatory cytokines participate in chemical mediation in acute inflammation in pacus.