Information concerning the mechanisms underlying oxidative stress and low-grade inflammation in young healthy women predisposing eventually to future diseases is scarce. We investigated the relationship of oxidative stress and high-sensitivity C-reactive protein (hsCRP) in fertile-age women by oral combined contraceptive (OC) use. Caucasian Italian healthy non-obese women (n = 290; 100 OC-users; 190 non-OC-users; mean age 23.2 ± 4.7 years) were analyzed. Blood hydroperoxides, as oxidative stress biomarkers, were assessed by Free Oxygen Radical Test (FORT). Serum hsCRP was determined by an ultra-sensitive method (hsCRP). Markedly elevated oxidative stress (≥400 FORT Units) was found in 77.0% of OC-users and 1.6% of non-OC-users, odds ratio (OR) = 209, 95% CI = 60.9–715.4, p < 0.001. Elevated hsCRP levels ≥ 2.0 mg/L, considered risky for cardiovascular diseases (CVDs), were found in 41.0% of OC-users and 9.5% of non-OC-users, OR = 6.6, 95%CI 3.5–12.4, p < 0.001. Hydroperoxides were strongly positively correlated to hsCRP in all women (rs = 0.622, p < 0.001), in OC-users (rs = 0.442, p < 0.001), and in non-OC-users (rs = 0.426, p < 0.001). Women with hydroperoxides ≥ 400 FORT Units were eight times as likely to have hsCRP ≥ 2 mg/L. In non-OC-users only, hydroperoxides values were positively correlated with weight and body mass index, but negatively correlated with red meat, fish and chocolate consumption. Our research is the first finding a strong positive correlation of serum hydroperoxides with hsCRP, a marker of low-grade chronic inflammation, in young healthy women. Further research is needed to elucidate the potential role of these two biomarkers in OC-use associated side-effects, like thromboembolism and other CVDs.

The clinical significance of neuroendocrine differentiation in patients who have undergone surgery for localized prostate cancer is still unclear. The aims of this study were to assess the relationship between serum neuroendocrine markers and well-known prognostic factors in prostate cancer (pathological staging, definitive Gleason score and serum PSA) and to search for correlations between serum chromogranin A (CgA) levels and pathological findings. Forty-one consecutive patients who had undergone radical retropubic prostatectomy for clinically localized prostate cancer were evaluated. Serum PSA, CgA and neuron-specific enolase were measured immediately before surgery. Twenty-six surgical specimens were phenotypically and immunohistochemically evaluated using an antibody against CgA. Significant correlations were found between serum CgA, pathological staging and Gleason score (p=0.049 and p=0.038, respectively). Serum CgA did not correlate with PSA, patient age, or immunohistochemical findings. There was a significant correlation between positive immunohistochemical CgA staining and Gleason score (p=0.014). An increase in serum CgA levels, independent of PSA values, might be the expression of pathologically more advanced tumor stage and higher Gleason score; this could help to identify a high-risk patient group eligible for adjuvant therapy.

Brain natriuretic peptide level as marker of cardiac function in imatinib-treated chronic myeloid leukemia patients: no evidence of cardiotoxicity of imatinib therapy To the Editor: In the last year, the issue of cardiotoxicity of imatinib mesylate (IM) was on focus. After the original work from Kerkelä et al. [1], various papers reported a low incidence of severe cardiac adverse events in large groups of patients treated with imatinib for chronic myeloid leukemia (CML) [2][3][4][5] and gastrointestinal stromal tumor (GIST) [6]. Safety issues are particularly important, as imatinib is the frontline treatment of CML [7], and patients are expected to receive treatment for indefinite time.B-type natriuretic peptide (BNP) is released by the heart in response to myocardial tension [8] and is considered an accurate test for the diagnosis of heart failure. The measurement of BNP in the serum is a rapid and easy tool for evaluation of left ventricular ejective function (LFEV), also in asymptomatic patients [9].We have measured BNP level in 49 consecutive patients with chronic phase CML during imatinib therapy and in five newly diagnosed CML patients that were tested before IM start and after 1, 2, and 3 months of therapy. BNP level was measured using a direct chemiluminescent sandwich immunoassay: the analytical range extends from 0 to 5,000 pg/ml, with a sensitivity <2 pg/ml. Normal range is as follows: <100 pg/dl.Characteristics of the 49 patients studied while in treatment with IM are provided in Table I. All patients were asymptomatic and without signs of cardiac impairment at time of BNP evaluation. The mean level of BNP was 22.4 pg/ml (SD ± 26.6); only two patients had values >100 pg/ml. As expected [10], there was a linear correlation between age and BNP levels (t-value ¼ 3.850). Fifteen out of 24 (62.5%) patients aged !60 had BNP >22 pg/ml (mean 37.2 ± 31.4), compared to only 1/25 (4%) in the cohort <60-years-old (mean 8.2 ± 5.7) (P < 0.0001). BNP level was not affected by IM daily dose or by therapy duration. Patients with hypertension had higher levels of BNP (33.4 ± 35.6 vs 16.5 ± 18.3, P ¼ 0.03), despite an equivalent IM dose and treatment duration. This data could be explained by a higher incidence of hypertension in the older patients. No patient experienced major cardiac adverse event during IM therapy. An echocardiogram was performed in the two patients with higher BNP values: both of them were older than 60 and suffered from hypertension, but echocardiogram revealed a normal cardiac function (LVEF >65%). In the five consecutive patients (Table II) tested for BNP before start of IM and monthly during treatment there was no significant change in BNP levels during imatinib therapy (Fig. 1). Mean BNP value before start of IM was 20.9 ± 10.6, after three months of therapy was 14.8 ± 13.8.With the limits of a relatively small study population, our data indicates that imatinib therapy does not cause an increase in BNP, a rapid and reliable marker for the assessment of ventricular function. The role of BNP in ...

Summary Vitamin D receptor (VDR) polymorphisms may confer susceptibility to immunologically mediated liver diseases. We aimed to verify whether recipient VDR polymorphisms might affect the incidence of acute cellular rejection (ACR) of the graft after liver transplantation (LT). Two hundred and fifty‐one liver‐transplanted patients surviving at least 1 month were studied. ACR in the first post‐LT year was graded according to the Banff score. Recipients genotyping for VDR polymorphic sites (FokI C>T, BsmI G>A, ApaI T>G, TaqI T>C) was performed. A significant difference was found between patients with and without ACR episodes in allele frequencies of BsmI (G: 0.660 vs. 0.545, P = 0.017) and TaqI (T: 0.667 vs. 0.543, P = 0.010). Patients carrying the G‐*‐T/G‐*‐T diplotypes of the BsmI G>A, ApaI T>G and TaqI T>C experienced more frequently ACR: 33/79 Vs 42/172, P = 0.005. Carriage of G‐*‐T/G‐*‐T diplotypes was an independent predictor of ACR (OR 2.41, P = 0.006), with CMV reactivation (OR 2.34, P = 0.033) and HCV aetiology (OR 1.86, P = 0.036). In conclusion, recipient VDR polymorphic loci are strongly associated with ACR occurrence during the first year after LT. The knowledge of VDR genetic polymorphisms may be helpful in identifying recipients at higher risk of ACR and in selecting them for a more aggressive immunosuppressive therapy.

ABSTRACT:The clinical significance of neuroendocrine differentiation in patients who have undergone surgery for localized prostate cancer is still unclear. The aims of this study were to assess the relationship between serum neuroendocrine markers and well-known prognostic factors in prostate cancer (pathological staging, definitive Gleason score and serum PSA) and to search for correlations between serum chromogranin A (CgA) levels and pathological findings. Forty-one consecutive patients who had undergone radical retropubic prostatectomy for clinically localized prostate cancer were evaluated. Serum PSA, CgA and neuron-specific enolase were measured immediately before surgery. Twenty-six surgical specimens were phenotypically and immunohistochemically evaluated using an antibody against CgA.