Validation of the

The cluster structure of the neutron-rich isotope ^{10}Be has been probed via the (p,pα) reaction at 150 MeV/nucleon in inverse kinematics and in quasifree conditions. The populated states of ^{6}He residues were investigated through missing mass spectroscopy. The triple differential cross section for the ground-state transition was extracted for quasifree angle pairs (θ_{p},θ_{α}) and compared to distorted-wave impulse approximation reaction calculations performed in a microscopic framework using successively the Tohsaki-Horiuchi-Schuck-Röpke product wave function and the wave function deduced from antisymmetrized molecular dynamics calculations. The remarkable agreement between calculated and measured cross sections in both shape and magnitude validates the molecular structure description of the ^{10}Be ground-state, configured as an α-α core with two valence neutrons occupying π-type molecular orbitals.

Prevention of arterial hypotension after spinal anaesthesia using vena cava ultrasound to guide fluid management.

BACKGROUND: Significant hypotension is frequent after spinal anaesthesia and fluid administration as therapy is usually empirical. Inferior vena cava (IVC) ultrasound (US) is effective to assess fluid responsiveness in critical care patients. The aim of this study was to evaluate the IVCUS-guided volume optimization to prevent post-spinal hypotension. METHODS: In this prospective, randomized, cohort study, 160 patients scheduled for surgery under spinal anaesthesia were randomized into a study group (IVCUS-group), consisting of an IVCUS analysis before spinal anaesthesia with IVCUS-guided volume management and a control group (group C) with no IVCUS assessment. The primary outcome was a relative risk reduction in the incidence of hypotension between the groups; secondary outcomes were the need for vasoactive drugs and the amounts of fluids required after spinal anaesthesia. We also tested the hypothesis of a correlation between IVC collapsibility index and hypotension after spinal anaesthesia. RESULTS: The relative risk reduction of hypotension between the groups was 35% (IVCUS-group 27.5%, Group C 42.5%, P=0.044, CI=95%). The need for vasoactive drugs in the IVCUS-group was significantly lower compared to the C-group (P=0.015), while the total amount of fluids was significantly superior higher in the IVCUS group (P<0.0001) compared to Group C. IVC collapsibility index was correlated with the amount of fluid administered (r2=0.32), but could not be used to predict postspinal anaesthesia hypotension. CONCLUSIONS: IVCUS is an effective method to prevent postspinal anaesthesia hypotension by IVCUS-guided fluid administration before spinal anaesthesia. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov - NCT02271477.

The diagnosis and clinical management of the neuropsychiatric manifestations of lupus.

Neuropsychiatric (NP) involvement in Systemic Lupus Erythematosus (SLE), can be a severe and troubling manifestation of the disease that heavily impacts patient's health, quality of life and disease outcome. It is one of the most complex expressions of SLE which can affect central, peripheral and autonomous nervous system. Complex interrelated pathogenetic mechanisms, including genetic factors, vasculopathy, vascular occlusion, neuroendocrine-immune imbalance, tissue and neuronal damage mediated by autoantibodies, inflammatory mediators, blood brain barrier dysfunction and direct neuronal cell death can be all involved. About NPSLE a number of issues are still matter of debate: from classification and burden of NPSLE to attribution and diagnosis. The role of neuroimaging and new methods of investigation still remain pivotal and rapidly evolving as well as is the increasing knowledge in the pathogenesis. Overall, two main pathogenetic pathways have been recognized yielding different clinical phenotypes: a predominant ischemic-vascular one involving large and small blood vessels, mediated by aPL, immune complexes and leuko-agglutination which it is manifested with more frequent focal NP clinical pictures and a predominantly inflammatory-neurotoxic one mediated by complement activation, increased permeability of the BBB, intrathecal migration of autoantibodies, local production of immune complexes and pro-inflammatory cytokines and other inflammatory mediators usually appearing as diffuse NP manifestations. In the attempt to depict a journey throughout NPSLE from diagnosis to a reasoned therapeutic approach, classification, epidemiology, attribution, risk factors, diagnostic challenges, neuroimaging techniques and pathogenesis will be considered in this narrative review based on the most relevant and recent published data.

Isospin Mixing in

The isospin mixing was deduced in the compound nucleus ^{80}Zr at an excitation energy of E^{*}=54 MeV from the γ decay of the giant dipole resonance. The reaction ^{40}Ca+^{40}Ca at E_{beam}=136 MeV was used to form the compound nucleus in the isospin I=0 channel, while the reaction ^{37}Cl+^{44}Ca at E_{beam}=95 MeV was used as the reference reaction. The γ rays were detected with the AGATA demonstrator array coupled with LaBr_{3}:Ce detectors. The temperature dependence of the isospin mixing was obtained and the zero-temperature value deduced. The isospin-symmetry-breaking correction δ_{C} used for the Fermi superallowed transitions was extracted and found to be consistent with ß-decay data.

Isospin character of low-lying pygmy dipole states in 208Pb via inelastic scattering of 17O ions.

The properties of pygmy dipole states in 208Pb were investigated using the 208Pb(17O, 17O'γ) reaction at 340 MeV and measuring the γ decay with high resolution with the AGATA demonstrator array. Cross sections and angular distributions of the emitted γ rays and of the scattered particles were measured. The results are compared with (γ, γ') and (p, p') data. The data analysis with the distorted wave Born approximation approach gives a good description of the elastic scattering and of the inelastic excitation of the 2+ and 3- states. For the dipole transitions a form factor obtained by folding a microscopically calculated transition density was used for the first time. This has allowed us to extract the isoscalar component of the 1- excited states from 4 to 8 MeV.

Giant cell granuloma of the temporal bone: a case report.

PROBLEM: Giant cell granuloma (GCG) is a rare nonneoplastic bone lesion that occurs mostly in the jawbones; few cases arise in the remainder of the skull, including the temporal bone. Previously, giant cell lesions of the temporal bone were regarded as giant cell tumours (GCT). The importance of distinguishing GCG from GCT lies in the presumed difference in prognosis; GCTs have higher rates of recurrence, metastasis, and malignant transformation. METHODOLOGY: We describe the case of a 12-year-old child with temporal bone GCG extending to the middle cranial fossa. The patient underwent a subtotal petrosectomy via retroauricular approach, associated with resection of the zygomatic process. RESULTS: No evidence of recurrence was found 36 months later. CONCLUSION: The diagnosis of GCG was based on clinical history, histology, imaging, and response to treatment. The patient was treated with the standard surgical approach, and has a good outcome at three years follow-up.

Lateral sinus thrombosis as a complication of acute mastoiditis.

Lateral sinus thrombosis is a rare complication of middle ear diseases: in children, it is usually related to acute otitis media, but it is also found in adults with chronic otitis. It was more frequent in the pre-antibiotic era and mortality was high. The Authors present a paediatric case of lateral sinus thrombosis in which they describe the clinical approach and related literature.

Enlarged vestibular aqueduct: Audiological and genetical features in children and adolescents.

BACKGROUND: Enlarged Vestibular Aqueduct (EVA) is one of the most common congenital malformations associated with sensorineural or mixed hearing loss. The association between hearing loss and EVA is described in syndromic (i.e. Pendred Syndrome, BOR, Waardenburg) and non-syndromic disorders, as isolate or familiar mutations of the SLC26A4 gene. The audiological phenotype of the EVA syndrome is heterogeneous, the type and entity of hearing loss may vary and vertigo episodes might also be present. OBJECTIVE: The aim of this retrospective study was to describe the clinical and genetic features of a group of adolescent subjects presenting an EVA clinical profile, considering the presence of SLC26A4 gene mutations. METHODS: 14 Caucasian patients were assessed (24 ears in total; 4 patients presented a monolateral EVA), 10 females and 4 males. Their age at the time of diagnosis was between 1 and 6 years (mean age 2.5 years). Subjects were assessed by an ENT microscopy evaluation with a complete audiometric assessment, CT & MRI scans and genetic tests for the evaluation of the pendrin gene mutations (SLC26A4). RESULTS: Considering the presence of SLC26A4 mutations and thyroid function, we could identify three sub-groups of patients: group 1, non syndromic EVA (ns EVA, no SLC26A4 mutation and no thyroid dysfunction); group 2, EVA with DFNB4 (single SLC26A4 gene mutation and no thyroid dysfunction); group 3, EVA with Pendred Syndrome (two pathological mutation of SLC26A4 and thyromegaly with thyroid dysfunction). Patients of group 1 (ns-EVA) showed various degrees of hearing loss from mild (55%) to severe-profound (45%). In groups 2 (DFNB4) and 3 (PDS), the degree of hearing loss is severe to profound in 70-75% of the cases; middle and high frequencies are mainly involved. CONCLUSIONS: The phenotypic expressions associated with the EVA clinical profile are heterogeneous. From the available data, it was not possible to identify a representative audiological profile, in any of the three sub-groups. The data suggest that: (i) a later onset of hearing loss is usually related to EVA, in absence of SLC26A4 gene mutations; and (ii) hearing loss is more severe in patients with SLC26A4 gene mutations (groups 2 and 3 of this study).

Evaluation of acute perihematomal regional apparent diffusion coefficient abnormalities by diffusion-weighted imaging.

In this study, we investigated 40 patients (18 male, 22 female; mean age = 64.5 +/- 11.0; GCS = 9 to 14) with acute supratentorial spontaneous intracerebral hemorrhage (SICH) at admission by using a 1-tesla magnetic resonance imaging (MRI) unit equipped for single-shot echo-planar spin-echo isotropic diffusion-weighted imaging (DWI) sequences. All DWI studies were obtained within 48 hours after symptom onset. Regional apparent diffusion coefficient (rADC) values were measured in 3 different regions of interest (ROIs) drawn freehand on the T2-weighted images at b 0 s/mm2 on every section in which hematoma was visible: 1) the perihematomal hyperintense area; 2) 1 cm of normal appearing brain tissue surrounding the perilesional hyperintense rim; 3) an area mirroring the region including the clot and perihematomal hyperintense area placed in the contralateral hemisphere. rADC mean values were higher in perihematomal hyperintense and in contralateral than in normal appearing areas (p < 0.001), with increased rADC mean levels in all regions examined. Our findings show that rADC values indicative of vasogenic edema were present in the perihematomal area and in normal appearing brain tissue located both ipsilateral and contralateral to the hematoma, with lower levels in non-injured areas located in the T2 hyperintense rim around the clot.

PROtocolized care to reduce HYpotension after spinal anaesthesia (ProCRHYSA randomized trial): Study protocol for a randomized controlled trial.

BACKGROUND: The PROtocolized Care to Reduce HYpotension after Spinal Anaesthesia (ProCRHYSA trial) is an unblinded, randomized, monocentric, prospective, three-arm, parallel-group trial aimed at assessing the role of a controlled volemic repletion in reducing both clinically significant hypotension rate and total amount of fluid administered in patients undergoing spinal anaesthesia. METHODS/DESIGN: Aim of the study is assessing the effectiveness of a non-invasive tests to guide a titrated volemic repletion before spinal anesthesia in order to reduce post-spinal hypotension rate. After local ethical committee approval of the study (Comitato Etico Cantonale Ref. N. CE2796), we will randomize patients undergoing elective surgery under spinal anesthesia into two parallel groups: in the first vena cava ultrasound will be used in order to assess adequacy of patients' volemic status and consequently guide the administration of crystalloids boluses; in the second passive legs raising test will be used instead of ultrasound for the same purpose. DISCUSSION: The hypothesis we want to test is that the using of these two experimental methods before spinal anaesthesia, compared to the standard method (empirical fluid administration) can reduce the impact of systemic hypotension through an adequate titrated volemic repletion, avoiding both hypotension and fluid overload. The final purpose is to ensure that spinal anaesthesia is performed in the safest way possible. CONCLUSIONS: The study will offer a new insight on the possible role of vena cava ultrasound and passive legs raising test as screening tools to prevent hypotension after spinal anesthesia. These tests were already validated in a critical environment, but to the best of our knowledge this is the first time they are applied to an elective surgical population. TRIAL REGISTRATION: The trial was registered on May 2014 on www.clinicalstrial.gov with the number NCT02070276.

Assessment of acute spontaneous intracerebral hematoma by CT perfusion imaging.

A single-section deconvolution-derived computerized tomographic perfusion imaging was performed in 45 patients (22 male and 23 female; mean age=69.89+/-10.07 years) with acute supratentorial spontaneous intracerebral hemorrhage. Mean rCBF and rCBV were lower in the hemorrhagic core than in the perihematomal low density area (p<0.001), and in the perihematomal low density area than in normal appearing brain parenchyma (p<0.001). Mean rMTT values were higher in perihematomal low density area than in normal appearing area (p<0.01) and in both hemorrhagic and perihematomal area than in controlateral ROI (p<0.001). There were no differences in rMTT mean values between hemorrhagic core and perihematomal area, as well as between normal appearing and controlateral areas. We found a concentric distribution of all CT perfusion parameters characterized by an improvement from the core to the periphery, with low perihematomal rCBF and rCBV values suggesting edema formation.

Adenosine- and 2-chloro-adenosine-induced cytopathic effects on myoblastic cells and myotubes: involvement of different intracellular mechanisms.

We recently suggested that, in muscular dystrophies, the excessive accumulation of adenosine as a result of an altered purine metabolism may contribute to progressive functional deterioration and muscle cell death. To verify this hypothesis, we have taken advantage of C2C12 myoblastic cells, which can be differentiated in vitro into multinucleated cells (myotubes). Exposure of both proliferating myoblasts and differentiated myotubes to adenosine or its metabolically-stable analog, 2-chloro-adenosine, resulted in apoptotic cell death and myotube disruption. Cytotoxicity by either nucleoside did not depend upon extracellular adenosine receptors, but, at least in part, by entry into cells via the membrane nitro-benzyl-thio-inosine-sensitive transporter. The adenosine kinase inhibitor, 5-iodotubercidin, prevented 2-chloro-adenosine-induced (but not adenosine-induced) effects, suggesting that an intracellular phosphorylation/activation reaction plays a key role in 2-chloro-adenosine-mediated cytotoxicity. Conversely, adenosine cytotoxicity was aggravated by the addition of homocysteine, suggesting that adenosine effects may be due to the accumulation of S-adenosyl-homocysteine, which blocks intracellular methylation-dependent reactions. Both nucleosides markedly disrupted the myotube structure via an effect on the actin cytoskeleton; however, also for myotubes, there were marked differences in the morphological alterations induced by these two nucleosides. These results show that adenosine and 2-chloro-adenosine induce apoptosis of myogenic cells via completely different metabolic pathways, and are consistent with the hypothesis that adenosine accumulation in dystrophic muscles may represent a novel pathogenetic pathway in muscle diseases.

Characterization of the signalling pathways involved in ATP and basic fibroblast growth factor-induced astrogliosis.

1. A brief challenge of rat astrocytes with either alpha, beta-methyleneATP (alpha, beta-meATP) or basic fibroblast growth factor (bFGF) resulted, three days later, in morphological differentiation of cells, as shown by marked elongation of astrocytic processes. The P2 receptor antagonist suramin prevented alpha, beta-meATP- but not bFGF-induced astrocytic elongation. Similar effects on astrocytic elongation were also observed with ATP and other P2 receptor agonists (beta, gamma meATP, ADP beta S, 2meSATP and, to a lesser extent, UTP). 2. Pertussis toxin completely abolished alpha, beta-meATP- but not bFGF-induced effects. No effects were exerted by alpha, beta-meATP on cyclic AMP production; similarly, neomycin had no effects on elogation of processes induced by the purine analogue, suggesting that adenylyl cyclase and phospholipase C are probably not involved in alpha, beta-meATP-induced effects (see also the accompanying paper by Centemeri et al., 1997). The tyrosine-kinase inhibitor genistein greatly reduced bFGF- but not alpha, beta-meATP-induced astrocytic elongation. 3. Challenge of cultures with alpha, beta-meATP rapidly and concentration-dependently increased [3H]-arachidonic acid (AA) release from cells, suggesting that activation of phospholipase A2 (PLA2) may be involved in the long-term functional effects evoked by purine analogues. Consistently, exogenously added AA markedly elongated astrocytic processes. Moreover, various PLA2 inhibitors (e.g. mepacrine and dexamethasone) prevented both the early alpha, beta-meATP-induced [3H]-AA release and/or the associated long-term morphological changes, without affecting the astrocytic elongation induced by bFGF. Finally, the protein kinase C (PKC) inhibitor H7 fully abolished alpha, beta-meATP- but not bFGF-induced effects. 4. Both alpha, beta-meATP and bFGF rapidly and transiently induced the nuclear accumulation of Fos and Jun. Both c-fos and c-jun induction by the purine analogue could be fully prevented by pretreatment with suramin. In contrast, the effects of bFGF were unaffected by this P2 receptor antagonist. 5. It was concluded that alpha, beta-meATP- and bFGF-morphological differentiation of astrocytes occurs via independent transductional pathways. For the purine analogue, signalling involves a Gi/G(o) protein-coupled P2Y-receptor which may be linked to activation of PLA2 (involvement of an arachidonate-sensitive PKC is speculated); for bFGF, a tyrosine kinase receptor is involved. Both pathways merge on some common intracellular target, as suggested by induction of primary response genes, which in turn may regulate late response genes mediating long-term phenotypic changes of astroglial cells. 6. These findings implicate P2 receptors as novel targets for the pharmacological regulation of reactive astrogliosis, which has intriguing implications in nervous system diseases characterized by degenerative events.

Cyclo-oxygenase-2 mediates P2Y receptor-induced reactive astrogliosis.

Excessive cyclo-oxygenase-2 (COX-2) induction may play a role in chronic neurological diseases characterized by inflammation and astrogliosis. We have previously identified an astroglial receptor for extracellular nucleotides, a P2Y receptor, whose stimulation leads to arachidonic acid (AA) release, followed, 3 days later, by morphological changes resembling reactive astrogliosis. Since COX-2 may be upregulated by AA metabolites, we assessed a possible role for COX-2 in P2Y receptor-mediated astrogliosis. A brief challenge of rat astrocytes with the ATP analogue alpha,beta-methylene ATP (alpha,beta(me)ATP) resulted, 24 h later, in significantly increased COX-2 expression. The selective COX-2 inhibitor NS-398 completely abolished alpha,beta(me)ATP-induced astrocytic activation. Constitutive astroglial COX-1 or COX-2 did not play any role in purine-induced reactive astrogliosis. PGE2, a main metabolite of COX-2, also induced astrocytic activation. These data suggest that a P2Y receptor mediates reactive astrogliosis via induction of COX-2. Antagonists selective for this receptor may counteract excessive COX-2 activation in both acute and chronic neurological diseases.

Apoptosis by 2-chloro-2'-deoxy-adenosine and 2-chloro-adenosine in human peripheral blood mononuclear cells.

Adenosine has profound effects on immune cells and has been implicated in the intrathymic apoptotic deletion of T-cells during development. In order to characterize adenosine effects on quiescent peripheral blood mononuclear cells (PBMC), we have evaluated the ability of the previously characterized adenosine receptor agonist 2-chloro-adenosine (2CA; Ceruti, Barbieri et al., 1997) and of the antineoplastic drug 2-chloro-2'-deoxy-adenosine (2CdA, cladribine) to trigger apoptosis of PBMC. Apoptosis was assessed by morphological changes, DNA fragmentation by agarose gel electrophoresis and appearance of hypodiploid DNA peak by flow cytometry. 2CA (10 microM) and 2CdA (1 microM) induced apoptosis in human PBMC, which are relatively insensitive to apoptosis. For both agents, the effect was concentration- and time-dependent, although 2CdA induced apoptosis more potently than 2CA. Evaluation of mitochondrial function in parallel samples using the mitochondrial membrane-potential-specific dye JC-1 showed that mitochondrial damage followed the same kinetics as apoptosis, hence an early damage of mitochondria is likely not responsible for adenosine-induced death of PBMC. The effect of 2CA was partially prevented by addition of dipyridamole (DP), a nucleoside transport inhibitor, hence some of the apoptotic effect of this nucleoside is, at least in part, due to intracellular action. Alternatively, DP did not affect 2CdA-induced apoptosis, suggesting that 2CdA may enter cells via a DP-insensitive transporter. 5-Iodotubercidin (5-Itu), a nucleoside kinase inhibitor, was also able to partially prevent the action of 2CA and was not able to affect 2CdA-induced apoptosis, suggesting a different role for phosphorylation in 2CA- vs 2CdA-induced apoptosis. To test the role of P1 receptors, agonists and antagonists selective at various P1 receptor subtypes were used. Data suggest that, for 2CA, apoptosis is partially sustained by activation of the A2A receptor subtype, whereas no role is exerted by P1 receptors in 2CdA-dependent apoptosis. Moreover, in these cells, apoptosis could also be triggered through intense activation of the A3 receptor via selective agonists such as 2-chloro-N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide (Cl-IB-MECA), but this mechanism plays no role in either 2CA- or 2CdA-induced apoptosis. On the whole, our results suggest that 2CA and 2CdA follow different pathways in inducing apoptosis of immune cells. Moreover, our data also suggest that there are at least three different ways by which adenosine derivatives may induce apoptosis of human PBMC: (i) through an A2A-like extracellular membrane receptor; (ii) through entry of nucleosides into cells and direct activation of intracellular events involved in the apoptotic process; or (iii) through activation of the A3 receptor.

The A3 adenosine receptor induces cytoskeleton rearrangement in human astrocytoma cells via a specific action on Rho proteins.

In previous studies, we have demonstrated that exposure of astroglial cells to A3 adenosine receptor agonists results in dual actions on cell survival, with "trophic" and antiapoptotic effects at nanomolar concentrations and induction of cell death at micromolar agonist concentrations. The protective actions of A3 agonists have been associated with a reinforcement of the actin cytoskeleton, which likely results in increased resistance of cells to cytotoxic stimuli. The molecular mechanisms at the basis of this effect and the signalling pathway(s) linking the A3 receptor to the actin cytoskeleton have never been elucidated. Based on previous literature data suggesting that the actin cytoskeleton is controlled by small GTP-binding proteins of the Rho family, in the study reported here we investigated the involvement of these proteins in the effects induced by A3 agonists on human astrocytoma ADF cells. The presence of the A3 adenosine receptor in these cells has been confirmed by immunoblotting analysis. As expected, exposure of human astrocytoma ADF cells to nanomolar concentrations of the selective A3 agonist 2-chloro-N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (CI-IB-MECA) resulted in formation of thick actin positive stress fibers. Preexposure of cells to the C3B toxin that inactivates Rho-proteins completely prevented the actin changes induced by CI-IB-MECA. Exposure to the A3 agonist also resulted in significant reduction of Rho-GDI, an inhibitory protein known to maintain Rho proteins in their inactive state, suggesting a potentiation of Rho-mediated effects. This effect was fully counteracted by the concomitant exposure to the selective A3 receptor antagonist MRS1191. These results suggest that the reinforcement of the actin cytoskeleton induced by A3 receptor agonists is mediated by an interference with the activation/inactivation cycle of Rho proteins, which may, therefore, represent a biological target for the identification of novel neuroprotective strategies.

Effects of ATP analogues and basic fibroblast growth factor on astroglial cell differentiation in primary cultures of rat striatum.

We have used primary cultures of rat striatum to study the effects of ATP analogues on the elongation of astrocytic processes, a parameter of astroglial cell differentiation. Parallel studies were performed with basic fibroblast growth factor, a known regulator of astroglial cell function. After three days in culture, both the growth factor and alpha beta-methylene-ATP induced dramatic increases in the mean length of astrocytic processes/cell. For both agents, effects were dose-dependent. The effect of alpha beta-methylene-ATP was antagonized by the trypanoside suramin and mimicked by 2-methyl-thio-ATP, suggesting the involvement of a suramin-sensitive P2-purinoceptor. Neither an additive nor a synergistic effect between alpha beta-methylene-ATP and basic fibroblast growth factor on the elongation of processes was detected in cultures exposed to both agents. Indeed, an inhibition with respect to the effects induced by either agent alone was recorded, suggesting that the growth factor and the purine analogue can modulate astrocytic differentiation by activation of common intracellular pathways. It is concluded that, like basic fibroblast growth factor, ATP can promote the maturation of astrocytes towards a more differentiated phenotype characterized by the presence of longer astrocytic processes. These findings might have interesting implications for astroglial cell differentiation during brain development and for ischemia- and trauma-associated hypergliosis.

Activation of the A3 adenosine receptor affects cell cycle progression and cell growth.

The A3 adenosine receptor has been implicated in modulation of cell growth. As a first step to the characterization of the underlying mechanisms, we exposed Chinese hamster ovary (CHO) cells transfected with the human A3 receptor (A3R-CHO) to selective A3 receptor ligands. At micromolar concentrations, the A3 agonists N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA) and its 2-chloro derivative Cl-IB-MECA reduced cell number, with no effects on either parental CHO cells (not expressing any adenosine receptor), or CHO cells transfected with the human A1 receptor. Cl-IB-MECA also reduced cell number in the human HEK293 cell line transfected with the human A3 receptor cDNA as opposed to the respective untransfected wild-type cells. In A3R-CHO, agonist-induced effects were antagonized by nanomolar concentrations of A3 antagonists, including the triazoloquinazoline derivative MRS 1220, the dihydropyridine derivative MRS 1191, and the triazolonaphthyridine derivative L-249,313. A3 agonist-induced effects were not due to modulation of cell adhesion, nor to necrosis or apoptosis. Growth curves revealed highly impeded growth, and flow-cytometric analysis showed markedly reduced bromodeoxyuridine incorporation into nuclei. The effect on cell cycle was completely antagonized by MRS1191. Hence, activation of the human A3 receptor in A3R-CHO results in markedly impaired cell cycle progression, suggesting an important role for this adenosine receptor subtype in cell cycle regulation and cell growth.

SPET imaging of intracranial tumours with 99Tcm-sestamibi.

Single photon emission tomography (SPET) employing 99Tcm-sestamibi (MIBI) injected intravenously was performed in 27 patients for pre-surgical evaluation of intraparenchymal brain tumours. A computerized tomography (CT) scan was performed in 26 patients, magnetic resonance imaging (MRI) in 8 patients and digital subtraction angiography (DSA) in 14 patients. Visual analysis of the SPET scans was performed using a 4-point scale relating to background activity, to evaluate MIBI uptake in the tumour. The vascular supply and the cellular component were also evaluated using DSA and CT scans. In normal controls, MIBI uptake was observed in the scalp, in the choroid plexus and in the pituitary gland, but never in normal parenchyma. Among the astrocytoma group of patients, a trend between MIBI uptake and grade of tumour was noted. MIBI uptake in meningiomas depends primarily on the vascular supply. Our results support the hypothesis that vascular supply, integrity of the blood-brain barrier, the degree of malignancy of the neoplasm and the viability of the tumour cells may be related to MIBI uptake.

Temporal bone anomalies in the branchio-oto-renal syndrome: detailed computed tomographic and magnetic resonance imaging findings.

OBJECTIVE: To inventory computed tomographic and magnetic resonance imaging findings in the branchio-oto-renal (BOR) syndrome. STUDY DESIGN: A prospective computed tomographic and magnetic resonance imaging study on a family with the BOR syndrome. SETTING: Department of medical imaging and magnetic resonance imaging at St. Jan Brugge, Brugge, Belgium. PATIENTS: Eight affected members of a Belgian family. Younger affected family members were excluded because of their age. RESULTS: Computed tomography showed inner ear malformations in all eight affected patients. Magnetic resonance imaging was performed on five patients and showed inner ear malformations. To define hypoplasia or congenital enlargement of the inner ear structures, measurements obtained from a control group of normal subjects were used for comparison. Almost symmetrical cochlear abnormalities were observed on the three-dimensional Fourier transformation-constructive interference in steady state images of the five patients who underwent magnetic resonance imaging; four had dysplasia of the cochlea, and one had hypoplasia. The vestibule was slightly enlarged in one patient; computed tomography and magnetic resonance imaging showed semicircular canal malformations. Magnetic resonance imaging clearly showed bilateral enlarged endolymphatic sacs and ducts, whereas computed tomography showed only unilateral widening of the vestibular aqueduct and borderline widening of the vestibular aqueduct. Magnetic resonance imaging showed bilateral hypoplasia of the cochlear branch of the eighth nerve in one patient. CONCLUSION: Hypoplasia and dysplasia of the cochlea were consistent findings, and only magnetic resonance imaging was able to evaluate the intracochlear changes in detail and corrected computed tomography in most patients. Moreover, magnetic resonance imaging also detected bilateral hypoplasia of the cochlear branch of the eighth nerve in one patient. A widened vestibular aqueduct and a widened vestibular sac were frequent but not obligatory features of the BOR syndrome. Other malformations of the middle ear included a reduced middle ear cavity and malformations of the ossicular chain.