Effects of Gram-negative Rod Blood Stream Infection on Acute GVHD in Allogeneic Hematopoietic Stem Cell Transplantation: A Single-institute Analysis.

A bloodstream infection (BSI) is the most common serious infectious complication of hematopoietic stem cell transplantation (HSCT). BSI promotes an inflammatory state, which exacerbates acute graft-versus-host disease (GVHD). We investigated whether a Gram-negative rod bloodstream infection (GNR-BSI), which develops early after allo-HSCT, affected the onset or exacerbated acute GVHD in 465 patients who underwent allo-HSCT from 1995 through 2015 at a single institution. Eighty-eight patients (19%) developed BSI during the study period. Among the cultures, 50 (57%) were Gram-positive cocci (GPC) and 31 (35%) were GNR. Of the 465 patients, 187 (40%) developed acute GVHD of grade II or higher within the first 100 days post-allogeneic HSCT: 124 (27%) had acute GVHD grade II, 47 (10%) had grade III, and 16 (3%) had grade IV. Multivariate analysis revealed that GNR-BSI was a significant risk factor for grade II-IV acute GVHD (grade II-IV: hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.03-2.97; grade III-IV: HR 2.37, 95% CI 1.03-5.43). These results suggest that GNR-BSI may predict the onset and exacerbation of acute GVHD.

Protective effect of lactoferrin on Cisplatin-induced nephrotoxicity in rats.

Although cisplatin (cis-diamminedichloroplatinum II) is one of the most effective chemotherapeutic agents, its clinical use is limited because of its strong side effects on the kidneys. The aim of this study was to investigate the renoprotective effect of bovine lactoferrin (bLf) in cisplatin-induced renal failure in rats. To assess the renoprotective effect of bLf, oral bLf (300 mg/kg) was administered from the day before to the fifth day after cisplatin (7 mg/kg, i.p.) injection. Daily administration of bLf histologically reduced renal tubular injury induced by cisplatin and suppressed the deterioration of renal function. Accumulated platinum content in the kidney was significantly decreased by the daily administration of bLf. Moreover, the administration of intravenous bLf caused a significant increase in urine volume in a dose-dependent manner. These results suggest that pretreatment with bLf produces a protective effect against cisplatin-induced nephrotoxicity. This protective effect of bLf involves the reduction of accumulated cisplatin in the kidney.

Expressions of lipid oxidation markers, N(ε)-hexanoyl lysine and acrolein in cisplatin-induced nephrotoxicity in rats.

The purpose of this study was to evaluate whether N(ε)-hexanoyl lysine (N(ε)-HEL) and acrolein reflect the severity of cisplatin-induced nephrotoxicity. Immunoexpression of N(ε)-HEL and acrolein in kidneys and their urinary concentration were examined up to day 4 post-cisplatin injection in rats. Cisplatin-induced tubular injury was observed histopathologically on days 2-4 after injection and became more severe time-dependently. On days 2-4, N(ε)-HEL and acrolein were immunostained in the cytoplasm of damaged tubular cells. Their immunostaining intensity and urinary levels increased as tubular injury became more severe. These results suggest that expressions of N(ε)-HEL and acrolein were associated with the pathogenesis of cisplatin-induced nephrotoxicity.

Expressions of protein oxidation markers, dityrosine and advanced oxidation protein products in Cisplatin-induced nephrotoxicity in rats.

The purpose of this study was to evaluate whether dityrosine and advanced oxidation protein products (AOPP) reflect the severity of cisplatin-induced nephrotoxicity. Immunoexpression of dityrosine in kidneys and plasma AOPP concentration were examined up to day 4 post-cisplatin injection in rats. Cisplatin injection induced tubular injury on days 2-4 after injection and increased serum creatinine and BUN on days 3 and 4. On days 2-4, dityrosine was immunostained in the cytoplasm of damaged tubular cells, and their immunostaining intensity increased time-dependently. Plasma AOPP levels were significantly increased on days 3 and 4. These results suggest that expressions of dityrosine and AOPP were associated with the severity of renal injury and may be useful markers for the development of cisplatin-induced nephrotoxicity.