Unbalanced oxidative status in idiopathic sudden sensorineural hearing loss.

An impaired cochlear perfusion seems to be an important etiopathogenetic event in idiopathic sudden sensorineural hearing loss (ISSNHL). Recently, oxidative stress has been proposed as risk factors of microvascular damage. This observational study aimed to evaluate the possible role of oxidative stress in ISSNHL. In thirty-nine ISSNHL patients and seventy healthy subjects serum reactive oxygen species concentrations (ROS) and total antioxidant capacity (TAC) were measured by spectrophotometric methods on F.R.E.E. analyzer (Diacron International, Italy). Moreover, a global oxidative stress index (Oxidative-INDEX), reflecting both oxidative and antioxidant counterparts, was also calculated. 25/39 patients showed oxidative stress due to ROS levels significantly higher than controls (348.2 ± 84.8 vs. 306.75 ± 46.7 UCarr; p = 0.001). The Oxidative-INDEX was significantly higher in patients than in controls (0.75 ± 2.4 vs. -0.0007 ± 1.28 AU, p = 0.03). As oxidative stress is a key determinant in endothelial dysfunction, our findings could suggest vascular impairment involvement in ISSNHL etiopathogenesis.

TLR9 agonists oppositely modulate DNA repair genes in tumor versus immune cells and enhance chemotherapy effects.

Synthetic oligodeoxynucleotides expressing CpG motifs (CpG-ODN) are a Toll-like receptor 9 (TLR9) agonist that can enhance the antitumor activity of DNA-damaging chemotherapy and radiation therapy in preclinical mouse models. We hypothesized that the success of these combinations is related to the ability of CpG-ODN to modulate genes involved in DNA repair. We conducted an in silico analysis of genes implicated in DNA repair in data sets obtained from murine colon carcinoma cells in mice injected intratumorally with CpG-ODN and from splenocytes in mice treated intraperitoneally with CpG-ODN. CpG-ODN treatment caused downregulation of DNA repair genes in tumors. Microarray analyses of human IGROV-1 ovarian carcinoma xenografts in mice treated intraperitoneally with CpG-ODN confirmed in silico findings. When combined with the DNA-damaging drug cisplatin, CpG-ODN significantly increased the life span of mice compared with individual treatments. In contrast, CpG-ODN led to an upregulation of genes involved in DNA repair in immune cells. Cisplatin-treated patients with ovarian carcinoma as well as anthracycline-treated patients with breast cancer who are classified as "CpG-like" for the level of expression of CpG-ODN modulated DNA repair genes have a better outcome than patients classified as "CpG-untreated-like," indicating the relevance of these genes in the tumor cell response to DNA-damaging drugs. Taken together, the findings provide evidence that the tumor microenvironment can sensitize cancer cells to DNA-damaging chemotherapy, thereby expanding the benefits of CpG-ODN therapy beyond induction of a strong immune response.

Determination of serum holotranscobalamin concentrations with the AxSYM active B(12) assay: cut-off point evaluation in the clinical laboratory.

BACKGROUND: A reliable early marker is required for diagnosis of cobalamin deficiency. We calculated an appropriate holotranscobalamin (HoloTC) cut-off point for identifying cobalamin deficiency using an immunoenzymatic assay. METHODS: Determination of the cut-off threshold and correlation between HoloTC and the other diagnostic parameters routinely used for vitamin B(12) deficiency [total vitamin B(12) (tB(12)), folate, homocysteine] were measured in 250 routine blood specimens from 107 men (mean age 59.0+/-18.8 years) and 143 women (mean age 54.2+/-23.1 years). The inclusion criterion was serum tB(12) concentration