Erythrocyte's aging in microgravity highlights how environmental stimuli shape metabolism and morphology.

The determination of the function of cells in zero-gravity conditions is a subject of interest in many different research fields. Due to their metabolic unicity, the characterization of the behaviour of erythrocytes maintained in prolonged microgravity conditions is of particular importance. Here, we used a 3D-clinostat to assess the microgravity-induced modifications of the structure and function of these cells, by investigating how they translate these peculiar mechanical stimuli into modifications, with potential clinical interest, of the biochemical pathways and the aging processes. We compared the erythrocyte's structural parameters and selected metabolic indicators that are characteristic of the aging in microgravity and standard static incubation conditions. The results suggest that, at first, human erythrocytes react to external stimuli by adapting their metabolic patterns and the rate of consumption of the cell resources. On longer timeframes, the cells translate even small differences in the environment mechanical solicitations into structural and morphologic features, leading to distinctive morphological patterns of aging.

ATP release during cell swelling activates a Ca2+-dependent Cl- current by autocrine mechanism in mouse hippocampal microglia.

Microglia cells, resident immune cells of the brain, survey brain parenchyma by dynamically extending and retracting their processes. Cl- channels, activated in the cellular response to stretch/swelling, take part in several functions deeply connected with microglia physiology, including cell shape changes, proliferation, differentiation and migration. However, the molecular identity and functional properties of these Cl- channels are largely unknown. We investigated the properties of swelling-activated currents in microglial from acute hippocampal slices of Cx3cr1 +/GFP mice by whole-cell patch-clamp and imaging techniques. The exposure of cells to a mild hypotonic medium, caused an outward rectifying current, developing in 5-10 minutes and reverting upon stimulus washout. This current, required for microglia ability to extend processes towards a damage signal, was carried mainly by Cl- ions and dependent on intracellular Ca2+. Moreover, it involved swelling-induced ATP release. We identified a purine-dependent mechanism, likely constituting an amplification pathway of current activation: under hypotonic conditions, ATP release triggered the Ca2+-dependent activation of anionic channels by autocrine purine receptors stimulation. Our study on native microglia describes for the first time the functional properties of stretch/swelling-activated currents, representing a key element in microglia ability to monitor the brain parenchyma.

Role of fetal MRI in the diagnosis of cerebral ventriculomegaly assessed by ultrasonography.

PURPOSE: To evaluate the additional diagnostic value of fetal MRI to evaluate cerebral ventriculomegaly assessed by ultrasonography (US) for the possibility to change the diagnosis, the counseling and the management of pregnancy. MATERIALS AND METHODS: From february 2006 to october 2008, we studied 55 pregnant women by fetal MRI (mean age 28 years), 4 with twin pregnancy, for a total of 59 fetuses with mean gestational age of 27 weeks. The number of fetuses affected by ventriculomegaly assessed by US was 55. All fetuses had a US diagnosis of ventriculomegaly: 29 fetuses with isolated ventriculomegaly and 26 fetuses with ventriculomegaly associated with CNS (central nervous system) abnormalities (18) and with no CNS abnormalities (8). RESULTS: The findings showed that the two techniques are substantially in agreement in defining the degree of VM, with the exception of some cases in which the disagreement could be attributed to the possible progression of the dilatation between the US and MRI examinations, which sway between two days and two weeks. We proved a low correlation between US and MRI in the evaluation of ventriculomegaly associated either with CNS or non-CNS anomalies: in fact while fetal MRI detected 26/55 (47,3%) VM associated with CNS anomalies, US demonstrated only 18/55(32,7%). Referring to VM associated with non-CNS anomalies, MRI diagnosed 10/55 cases (18,2%) compared to 8/55 fetuses (14,5%) showed by US. CONCLUSIONS: Our experience demonstrated that fetal MRI has an important role as adjunctive tool to sonography in the evaluation of cerebral ventriculomegaly for the additional informations given to parents and for the possibility to change the diagnosis, the counseling and the management of pregnancy.

Fetal MRI of the cardiovascular system: role of steady-state free precession sequences for the evaluation of normal and pathological appearances.

PURPOSE: This study aimed to evaluate the feasibility of fetal magnetic resonance imaging (MRI) with steady-state free precession (SSFP) sequences to visualise the normal and pathological appearances of the cardiovascular system. MATERIALS AND METHODS: This is a prospective observational study of 83 pregnant women who underwent fetal cardiac MRI: 43 patients (cases) had echocardiographic suspicion of congenital heart disease; 40 patients (controls) did not. Fetal cardiac MRI consisted of a static phase with multiplanar SSFP sequences and a dynamic phase with real-time SSFP sequences. Two radiologists evaluated the diagnostic quality of the SSFP images in both the controls and cases, the MRI morphological and functional features in the controls and the MRI signs of congenital heart disease in the cases. RESULTS: In both groups, SSFP sequences produced goodquality MR images and good visualisation of morphological features. Functional data appeared to be unavailable due to the current small temporal resolution and the technical impossibility of fetal cardiac triggering. MRI detected direct signs of congenital heart disease in 21 fetuses, indirect signs in six and both signs in 15. CONCLUSIONS: SSFP sequences are effective in demonstrating the morphological features of the cardiovascular system, whereas dynamic SSFP cine-MRI sequences may provide adjunctive albeit suboptimal functional information.

Fetal MRI with diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) assessment in the evaluation of renal development: preliminary experience in normal kidneys.

PURPOSE: The study aimed to investigate the correlation between apparent diffusion coefficient (ADC) and gestational age by applying diffusion-weighted imaging (DWI) in the study of normal fetal kidneys. MATERIALS AND METHODS: We performed magnetic resonance (MR) imaging on 88 fetuses (gestational age range 17-40 weeks) after ultrasound had ruled out urinary system malformations. A multiplanar study of the urinary system was obtained by using conventional T2-weighted sequences and echoplanar imaging (EPI). DW sequences with ADC maps were subsequently acquired, and kidney ADC values were correlated with gestational age by diving the fetuses into six groups according to age. RESULTS: We found a correlation between ADC values and gestational age. The ADC values, ranging from 0.99 to 1.62x10(-3) mm(2)/s [mean 1.22; 95% confidence interval (CI) 1.19-1.25, standard deviation (SD) 0.147], showed a tendency to decrease with increasing gestational age. The relationship between ADC values and gestational age was expressed by a linear regression equation: ADC (mm(2)/s)=1.69-0.0169 (GA) (R(2)=37.7%, R(2) ADJ=37.0%, p<0.005, Pearson correlation=-0.614). CONCLUSIONS: DWI with ADC mapping provides functional information on fetal renal parenchyma development and may thus become a useful tool in the management of pregnancy and treatment of the newborn child.

Assessment of congenital heart disease (CHD): is there a role for fetal magnetic resonance imaging (MRI)?

PURPOSE: To review our experience with fetal magnetic resonance imaging (MRI) to evaluate congenital heart disease (CHD). METHODS: We performed fetal MRI in 32 fetuses with an echocardiographically assessed CHD. Both direct and indirect signs of CHD were investigated. Direct signs considered were: morpho-volumetric abnormalities of the heart; malrotations; ventricular and atrial septal defects; anomalies of the origin, size and course of the great arteries. Indirect signs considered were: difficulty to recognize a "normal" anatomical structures in the reference projections; increase of the vascular size before a stenosis; hypertrophy of the papillary muscles; cardiomegaly and pericardial effusion. All MRI findings were compared with postnatal or autoptic findings. RESULTS: MRI allowed the CHD to be visualised by direct signs in 17 fetuses, indirect signs in 5 and both direct and indirect signs in 9 fetuses, excluding the prenatal echocardiographic suspect of hypoplastic left heart syndrome in 1 fetus. Postnatal echocardiograms or autoptic findings confirmed a normal heart in 1 fetus and CHD in 31 fetuses including a single cardiac anomaly or syndrome in 19 fetuses, 2 associated cardiac abnormalities in 11 and 3 cardiac anomalies in 1 fetus. However, in 2 fetuses MRI detected a ventricular septal defect successively disclosed by gold standard. CONCLUSIONS: MRI is a promising method for further assessment of the cardiovascular pathologies diagnosed by echocardiography, and may be a valuable tool in assessing associated extracardiac anomalies.

64-slice MDCT arthrography in shoulder instability: our experience.

PURPOSE: This study was performed to assess the diagnostic accuracy of air-contrast 64-slice multidetector computed tomography (MDCT) arthrography in the evaluation of glenohumeral joint instability by comparison with conventional arthroscopy. MATERIALS AND METHODS: Fifty patients with a history of shoulder instability underwent MDCT arthrography with thin collimation scans. The raw data were transferred to a workstation and processed using multiplanar reformation (MPR) and volume rendering (VR) algorithms. All patients subsequently underwent conventional arthroscopy. The results of the two techniques were compared and their sensitivity and specificity calculated. RESULTS: We diagnosed eight anterosuperior labrum lesions (group 1), 32 anteroinferior labrum lesions (group 2) and two posterior labrum lesions (group 3). Overall sensitivity and specificity (groups 1, 2, 3) were 88% and 100%, respectively. In group 1, sensitivity was only 66% (four false negatives), whereas in groups 2 and 3, it was 94% (two false negatives) and 100%, respectively. The labrum lesions were also found to be associated, with 100% sensitivity and specificity, with 20 lax capsules, 17 Hill-Sachs lesions, five Bankart lesions, two Perthes lesions and three complete rotator-cuff tears. CONCLUSIONS: Air-contrast MDCT arthrography is fast, reproducible, well tolerated and very accurate in the evaluation of lesions causing shoulder instability.

Online convective therapies: results from a hemofiltration trial.

With the introduction of the on-line preparation of dialysis fluids, the hemofiltration technique, which has never had a widespread diffusion in its old version with the infusion bags, has gained a new interest. We planned a prospective, randomized, 3-year-long study comparing survival and morbidity in ultrapure bicarbonate dialysis (BD) with on-line predilution hemofiltration (HF). Since comorbidity is one of the main factors limiting survival, the study was addressed to patients with a severe degree of comorbidity. The paper presents the preliminary results of the trial. Sixty-four patients were enrolled and randomized to either BD (N = 32) or HF (N = 32). Mean age and dialysis vintage were comparable. Twenty patients died during the study, 12 in BD and 8 in HF. The relative risk of death was 11% higher in patients treated with BD compared to those in the HF group (p < 0.005). The number of hospitalisation events per single patient was lower, even though not significantly, in HF compared to BD (1.94 + 1.26 in HF vs 2.48 + 1.98 in BD, p = NS). As concerns biochemistry, apart from beta-2-microglobulin, any other substantial difference was not found during the study, though the small solute concentration was generally a little more elevated in HF than in BD. Dialysis hypotension showed a trend to decrease in both the dialysis modalities up to near half of the trial, then, during the last year, it remained quite stable in HF, while, on the contrary, it increased in the BD group. By the end of the protocol, patients in HF showed a 2.5% incidence of acute dialysis hypotension, while patients in BD had 23%.

Ethylene-oxide and steam-sterilised polysulfone membrane in dialysis patients with eosinophilia.

Eosinophilia and some acute dialysis side-effects, such as itching, flushing and bronchospasm, are often associated with the presence of ethylene oxide (ETO) as dialyzer sterilizing agent. This study evaluated the effects of two different polysulfone (PS) hollow-fiber dialysers sterilized with ETO and steam in 31 chronic dialysis patients with eosinophilia. Clinical symptoms, metabolic and biochemical parameters, complement (C3a and C5a) activation and production were evaluated in each patient dialysed for two months at a time with Cuprophan dialyser, ETO-PS dialyser and steam-PS dialyser. The steam-sterilizer agent does not alter the purifying capacity of the PS membrane which maintains its superiority over Cuprophan in terms of biocompatibility. Using steam-PS, intradialytic eosinophil kinetics seems to improve. In some patients with high serum levels of ETO-specific IgE these levels tend to diminish. Generic intradialytic symptoms do not differ between the two sterilization methods, although some hypersensitivity symptoms during the first dialysis hour are considerably lower in some patients when steam-sterilized PS is used.