Changes in plasma 5-HT levels and equine leukocyte SERT expression in response to treadmill exercise

Serotonin (5-HT) is a neurohormone transported from plasma into platelets and leukocytes by a specific transporter (SERT). While it is known that the brain 5-HT system is modulated by physical exercise, the peripheral serotoninergic response to exercise is not yet fully elucidated. In particular, this study aimed to evaluate changes in plasma 5-HT levels and equine leukocyte SERT expression in response to treadmill exercise in untrained horses. Analyses were carried out pre- and post-treadmill exercise. 5-HT plasma levels were analysed by HPLC. Leukocytes and platelets were isolated to perform Real Time PCR for the evaluation of SERT mRNA levels. Western blot was conducted for the detection of SERT protein levels. The presence of SERT in leukocytes was analysed by flow cytometry. The functionality of SERT on leukocytes was investigated by using paroxetine as inhibitor of 5-HT reuptake. Results showed a significant decrease in SERT levels after exercise in both leukocytes and platelets and a significant increase in plasma 5-HT levels. Flow cytometry revealed that SERT is functional in one specific horse leukocyte subpopulation, still not identified, and paroxetine was able to block 5-HT reuptake into leukocytes. The exercise may have induced an increased mobilization of free-tryptophan and a release of 5-HT from the stores in the blood. High concentrations of plasma 5-HT could have caused a reduction in SERT expression affecting cellular 5-HT storage/uptake. The increase of cortisol levels after treadmill exercise was not significant. Exercise modulates the peripheral serotonin metabolism. More research is needed to assess its physiological implications

Lymphocytes from patients with early stage of B-cell chronic lymphocytic leukaemia and long survival synthesize decorin

mRNA/cDNA gene expression of both small leucine-rich proteoglycans decorin and biglycan was evaluated by PCR real time in lymphocytes collected from patients with chronic lymphocytic leukaemia (CLL) at different stages of disease and from healthy controls. Lymphocytes obtained from healthy controls showed no or very low levels of mRNA expression of both decorin and biglycan. Biglycan expression was very low in CLL patients, values being close to those of controls. On the contrary, decorin mRNA was clearly expressed in patients with early B-cell CLL, while a low expression was found in advanced clinical stages. Furthermore, a significant higher decorin expression was found in patients with non-progressive CLL type in comparison with patients with aggressive type of the disease. Decorin expression resulted especially high in the low-progressive low-risk patients. The synthesis of decorin was also assessed by Western blot analysis. The peculiar occurrence of decorin in the non-aggressive type of CLL is consistent with its suggested anti-oncogenic role. Intracellular Bcl-2 level does not correlate with decorin mRNA transcription, suggesting that a Bcl-2 independent anti-cancer mechanism may occur. The measurement of galactosamine-containing proteoglycans concentration in plasma confirmed decorin expression results, with significant differences between CLL patients and controls. Significant changes were also seen between groups of patients of Rai stage 0 with recent diagnosis (less than 5 years, from analysis), (low amount of decorin) and less recent diagnosis (more than 5 years), (high amount of decorin)

A T2* MRI PROSPECTIVE SURVEY ON HEART AND LIVER IRON IN THALASSEMIA MAJOR PATIENTS TREATED WITH SEQUENTIAL DEFERIPRON-DESFERRIOXAMINE VERSUS DEFERASIROX

Most deaths in thalassemia major (TM) result from cardiac complications due to iron overload. No data are available in literature about possible different changes in cardiac and liver iron in TM patients treated with sequential deferipron-deferoxamine (DFP-DFO) vs. deferasirox (DFX). Magnetic Resonance (MR) is the unique non invasive suitable technique to evaluated quantitatively this issue. Aims. The aim of this multi-centre study was to assess prospectively in the clinical practice the efficacy of the DFP-DFOvs. DFX in a cohort of TM patients by quantitative MR. Methods. Among the first 739 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, 253 patients performed a MR follow up study at 18±3 months according to the protocol. We evaluated prospectively the 25 patients treated with DFP-DFOvs. the 44 patients treated with DFX between the 2 MR scans. Myocardial and liver iron concentrations were measured by T2* multislice multiecho technique. Results. The doses of the sequential treatment were DFP 70±14 mg/kg/d for 4 d/w and DFO 42±8 mg/kg/d for 3 d/w, the dose of DFX was 26±6 mg/kg/d. Excellent/good levels of compliance were similar in the 2 groups (DFP-DFO 96%vs. DFX 100%; P=0.36). At baseline the 2 groups were homogeneous for cardiac and liver iron. Among the patients with no significant myocardial iron overload at baseline (global heart T2* ≥ 20 ms), there were no significant differences between groups to maintain the patients without myocardial iron overload (DFP-DFO 95%vs. DFX 96%; P=1.0). Among the patients with myocardial iron overload at baseline (global heart T2* <20 ms), only in the DFX group there was a significant improvement in the global heart T2* value (11±5 ms at baseline vs. 16±8 at 18±3 months, P=0.0001) and in the number of segment with a normal T2* value (P=0.003). The improvement in the global heart T2* was not significantly difference in the DFP-DFO vs. the DFX group (mean difference global heart T2* 2.2±4.1 ms vs. 4.6±4.8 P=0.2). The changes in the mean serum ferritin level were not significantly different between groups. In patients with liver iron overload at baseline (liver T2* <5.1 ms), the change in the liver T2* was not significant between groups (mean difference liver T2* 0.9±2.1 ms vs. 2.4±5.2; P=0.3)

Improvement of heart iron with preserved patterns of iron store by CMR-guided chelation therapy

Aims T∗ 2 multislice multiecho cardiac magnetic resonance (CMR) allows quantification of the segmental distribution of myocardial iron overload (MIO). We evaluated whether a preferential pattern MIO was preserved between two CMR scans in regularly chelated thalassaemia major (TM) patients. Methods and results We evaluated prospectively 259TMpatients enrolled in theMIOin Thalassaemia (MIOT) network with aCMRfollow-up (FU) study at 18+3 months and significant MIO at baseline. The T∗ 2 in the 16 segments and the global value were calculated. Four main circumferential regions (anterior, septal, inferior and lateral) were defined.We identified two groups: severe (n ¼ 80, global T∗ 2 ,10 ms) and mild–moderate MIO (n ¼ 179, global T∗ 2 ¼ 10–26 ms). Based on the CMR reports, 56.4% of patients changed the chelation regimen. For each group, there was a significant improvement in the global heart as well as in regional T∗ 2 values (P , 0.0001). At the baseline, the mean T∗ 2 value over the anterior region was significantly lower than the values over the other regions, and the mean T∗ 2 over the inferior region was significantly lower than the values over the septal and the lateral regions. The same pattern was present at the FU, with a little difference for patients with mild–moderate MIO. Conclusion A preferential pattern of iron store in anterior and inferior regions was present at both CMRs, with an increment of T∗ 2 values at FU due to a baseline CMR-guided chelation therapy. The anterior region seems the region in which the iron accumulates first and is removed later

Heart T2* for Prediction of Cardiac Complications in well-treated TM patients

none15nonePepe A; Meloni A; Rossi G; Cianciulli P; Spasiano A; D’Ascola D G; Maggio A; Maddaloni D; Carollo A; Rizzo M; Quota A; Secchi G; Lai M E; Positano V; Lombardi MPepe, A; Meloni, A; Rossi, G; Cianciulli, P; Spasiano, A; D’Ascola, D G; Maggio, A; Maddaloni, D; Carollo, A; Rizzo, M; Quota, A; Secchi, G; Lai, M E; Positano, V; Lombardi,