The role of plasma membrane STIM1 and Ca(2+)entry in platelet aggregation. STIM1 binds to novel proteins in human platelets.

Ca(2+) elevation is essential to platelet activation. STIM1 senses Ca(2+) in the endoplasmic reticulum and activates Orai channels allowing store-operated Ca(2+) entry (SOCE). STIM1 has also been reported to be present in the plasma membrane (PM) with its N-terminal region exposed to the outside medium but its role is not fully understood. We have examined the effects of the antibody GOK/STIM1, which recognises the N-terminal region of STIM1, on SOCE, agonist-stimulated Ca(2+) entry, surface exposure, in vitro thrombus formation and aggregation in human platelets. We also determined novel binding partners of STIM1 using proteomics. The dialysed GOK/STIM1 antibody failed to reduced thapsigargin- and agonist-mediated Ca(2+) entry in Fura2-labelled cells. Using flow cytometry we detect a portion of STIM1 to be surface-exposed. The dialysed GOK/STIM1 antibody reduced thrombus formation by whole blood on collagen-coated capillaries under flow and platelet aggregation induced by collagen. In immunoprecipitation experiments followed by proteomic analysis, STIM1 was found to extract a number of proteins including myosin, DOCK10, thrombospondin-1 and actin. These studies suggest that PM STIM1 may facilitate platelet activation by collagen through novel interactions at the plasma membrane while the essential Ca(2+)-sensing role of STIM1 is served by the protein in the ER.

The effect of self-sampled HPV testing on participation to cervical cancer screening in Italy: a randomised controlled trial (ISRCTN96071600).

BACKGROUND: In Italy, cervical cancer screening programmes actively invite women aged 25-64 years. Programmes are hindered by low participation. METHODS: A sample of non-responder women aged 35-64 years, belonging to three different programmes (in Rome, Florence and Teramo), was randomly split into four arms: two control groups received standard recall letters to perform either Pap-test (first group) or human papillomavirus (HPV) test (second group) at the clinic. A third arm was sent letters offering a self-sampler for HPV testing, to be requested by phone, whereas a fourth group was directly sent the self-samplers home. RESULTS: Compliance with standard recall was 13.9% (N619). Offering HPV test at the clinic had a nonsignificant effect on compliance (N616, relative risk (RR)=1.08; 95% CI=0.82-1.41). Self-sampler at request had the poorest performance, 8.7% (N622, RR=0.62; 95% CI=0.45-0.86), whereas direct mailing of the self-sampler registered the highest compliance: 19.6% (N616, RR=1.41; 95% CI=1.10-1.82). This effect on compliance was observed only in urban areas, Florence and Rome (N438, RR=1.69; 95% CI=1.24-2.30), but not in Abruzzo (N178, RR=0.95; 95% CI=0.61-1.50), a prevalently rural area. CONCLUSIONS: Mailing self-samplers to non-responders may increase compliance as compared with delivering standard recall letters. Nevertheless, effectiveness is context specific and the strategy costs should be carefully considered.

SVCT1 and SVCT2: key proteins for vitamin C uptake.

Vitamin C is accumulated in mammalian cells by two types of proteins: sodium-ascorbate co-transporters (SVCTs) and hexose transporters (GLUTs); in particular, SVCTs actively import ascorbate, the reduced form of this vitamin. SVCTs are surface glycoproteins encoded by two different genes, very similar in structure. They show distinct tissue distribution and functional characteristics, which indicate different physiological roles. SVCT1 is involved in whole-body homeostasis of vitamin C, while SVCT2 protects metabolically active cells against oxidative stress. Regulation at mRNA or protein level may serve for preferential accumulation of ascorbic acid at sites where it is needed. This review will summarize the present knowledge on structure, function and regulation of the SVCT transporters. Understanding the physiological role of SVCT1 and SVCT2 may lead to develop new therapeutic strategies to control intracellular vitamin C content or to promote tissue-specific delivery of vitamin C-drug conjugates.

Steady-state visual evoked potentials and phase synchronization in migraine patients.

We investigate phase synchronization in EEG recordings from migraine patients. We use the analytic signal technique, based on the Hilbert transform, and find that migraine brains are characterized by enhanced alpha band phase synchronization in the presence of visual stimuli. Our findings show that migraine patients have an overactive regulatory mechanism that renders them more sensitive to external stimuli.

[New experimental evidence of complex dynamics of heart beat. II. Correlation dimension, Lyapunov's exponents]. / Nuove evidenze sperimentali per la dinamica complessa del battito cardiaco. II: Dimensione di correlazione, esponenti di Lyapounov.

In this paper we applied mathematical techniques of non-linear dynamics, to an ECG signal. The first step is to compute the shift-delay time, via average displacement of the digital ECG. Phase space is constructed at a prescribed shift-delay and correlation dimension and dominant Lyapounov exponent versus the embedding dimension are monitored. This technique was applied to 5 healthy volunteers and 4 patients with VVI pacemaker.

QTc and not QTc dispersion behavior affects the occurrence of ventricular extrasystole during exercise in infarcted patients.

Both a long QTc and a large QTc dispersion (QTcd) can predispose infarcted patients to ventricular arrhythmias. The former simply reflects a general prolongation of ventricular recovery time, whereas QTcd is useful for revealing regional inhomogeneities of ventricular repolarization. The aim of our study was to evaluate QTc and QTcd behavior during exercise in 50 patients (all men) with previous myocardial infarction, and its possible correlation with the occurrence of exercise-induced premature ventricular complexes (EIPVC). Our patients underwent ergometric stress test with a load increase of 25 W, every 2 min, until the maximal age-related heart rate or symptoms were obtained, followed by a 10-min recovery phase. QTc and QTcd measurement was performed at rest (BS) and during exercise at two progressively increasing heart rate steps: 100-115 beats/min (T1) and 116-130 beats/ min (T2). The patients were divided into two groups according to the absence (group A; n = 22) or presence (group B; n = 28) of EIPVC. In terms of QTcd, no significant difference was found between the two groups at BS, T1, and T2. As for the mean QTc (QTcm), it was significantly longer in group B at BS (416 +/- 22 ms versus 395 +/- 19 ms; P = 0.001) and at T1 (431 +/- 24 ms versus 410 +/- 8 ms; P = 0.0001). When group B was further differentiated into two subgroups-Bx and Bz-according to the severity of EIPVC, we noted that patients with the most severe arrhythmic response (group Bz; n = 12) showed a persisting, significantly longer QTcm than group A (BS, 426 +/- 28 ms versus 395 +/- 19 ms; P < 0.05; T1, 445 +/- 24 ms versus 410 +/- 8 ms; P < 0.05; T2, 427 +/- 17 ms versus 412 +/- 14 ms; P < 0.05), and group Bx (n = 16) (BS, 426 +/- 28 ms versus 409 +/- 15 ms; P < 0.05; T1, 445 +/- 24 ms versus 420 +/- 19 ms; P < 0.05; T2, 427 +/- 17 ms versus 410 +/- 17 ms; P < 0.05). Group Bx showed a significantly longer QTcm than group A only at BS (409 +/- 15 ms versus 395 +/- 19 ms; P < 0.05). No significant difference in QTcd was found between the three groups at BS, T1, and T2. We also noted that the relationship between QTcm and QTcd was modified by the exercise, changing from a trend of direct relation at BS, towards an inverse one during effort, which reached significance at T2 (r = -0.319; P = 0.037). Based on our data, EIPVC occurrence seems to be more affected by the total duration rather than by regional inhomogeneities of the ventricular recovery time. In those patients with the most severe arrhythmic response, the autonomic modifications generated by the exercise succeed in attenuating only the regional inhomogeneities, but do not eliminate the differences in total duration of the repolarization period.