Spontaneous fluctuations in Heart Period (HP) and Mean Arterial Pressure (MAP) make it possible to evaluate baroreceptor-heart rate reflex sensitivity (BRS). 30-s sequences of HP and MAP beat-to-beat ...values were considered in the different wake-sleep states (Wake, W; Quiet Sleep, QS; Active Sleep, AS) in rats to assess whether 1) BRS changes between states and 2) the different indexes supply consistent BRS measures. BRS indexes were calculated according to validated literature procedures as regression coefficients of HP vs. MAP 1) within all ramps of increasing or decreasing MAP of four beats or more, with HP and MAP changing in the same direction (baroreflex-mediated fluctuations, BRSp), 2) within all such ramps irrespective of the relative direction of HP and MAP changes (baroreflex + non-baroreflex, i.e. non-homeostatic centrally driven, fluctuations, BRSA). HP vs. MAP regression coefficient along the entire 30-s sequence (bHPMAP) was also calculated.
BRSp did not change among states, BRSA decreased from QS to W to AS, bHPMAP decreased from QS to W and became negative in AS.
1) as indicated by BRSp, baroreflex sensitivity is state independent, 2) BRSp to BRS(A) to bHPMAP are increasingly affected by non-baroreflex fluctuations, BRSp being most apt to measure BRS, 3) non-homeostatic MAP and HP fluctuations increase from QS to W and prevail in AS. These potentially harmful fluctuations are normally buffered by baroreflexes: in the case of baroreflex impairment, circulatory risk may arise in conditions like AS, when they prevail.
Objective: It is known that the placenta acts as an immunological barrier between the mother and fetal “graft” allowing two antigenically different organisms to tolerate one another. Preeclampsia may ...be considered as a fetal rejection consequent to severe damage at placental endothelial and syncytiotrophoblast level. In order to verify this placental barrier damage we undertook the present study by electron microscopy.
Study design: 14 placentae from preeclaptic women, and the same number of placentae from healthy controls were examined.
Results: The results showed that endothelial cells from preeclamptic placentae express various and severe alterations, consisting of swollen and bulbous cytoplasm, degenerated inter-endothelial junctions with consequent crossing of fetal blood cells outside the vessels.
Conclusions: These lesions could be the ultrastructural evidence of the placental barrier breakage leading to rejective reaction we presumed to be basis of preeclampsia.
The direct observation of high-energy cosmic rays, up to the PeV region, will increasingly rely on highly performing calorimeters, and the physics performance will be primarily determined by their ...geometrical acceptance and energy resolution. Thus, it is extremely important to optimize their geometrical design, granularity, and absorption depth, with respect to the total mass of the apparatus, which is among the most important constraints for a space mission. Calocube is a homogeneous calorimeter whose basic geometry is cubic and isotropic, so as to detect particles arriving from every direction in space, thus maximizing the acceptance; granularity is obtained by filling the cubic volume with small cubic scintillating crystals. This design forms the basis of a three-year R &D activity which has been approved and financed by INFN. A comparative study of different scintillating materials has been performed. Optimal values for the size of the crystals and spacing among them have been studied. Different geometries, besides the cubic one, and the possibility to implement dual-readout techniques have been investigated. A prototype, instrumented with CsI(Tl) cubic crystals, has been constructed and tested with particle beams. An overview of the obtained results will be presented and the perspectives for future space experiments will be discussed.
Mutation of genes encoding for various components of a metabolic pathway named the ubiquitin-proteasome system (UP) leads to inherited forms of Parkinson's disease (PD), whereas various components of ...the UP are constantly present within neuronal inclusions, Lewy bodies, that characterize most genetic and sporadic forms of PD. It has been hypothesized that impairment of this metabolic pathway might be a common mechanism for the onset of PD, and a recent study demonstrated a dysfunction of the UP system within the substantia nigra of patients affected by sporadic PD. In search for the mechanisms underlying the selective toxicity for nigral neurons after inhibition of the UP system, we explored the selective effects after striatal microinfusions of lactacystin or epoxomycin and potential retrograde changes within the ipsilateral substantia nigra. We found that neurotoxicity was selective for striatal dopamine (DA) components and led to retrograde apoptosis within nigral DA cells, which developed neuronal inclusions staining for antigens of the UP system. We found the same ultrastructural features characterizing inclusions obtained in vivo and in vitro after UP inhibition. In vivo, lactacystin-epoxomycin-induced toxicity was suppressed by inhibiting DA synthesis. Similarly, in vitro inclusions and apoptosis were prevented by reducing endogenous DA. On the other hand, toxicity of proteasome inhibition was enhanced by drugs augmenting DA availability: l-3,4-dihydroxyphenylalanine, monoamine oxidase blockers, and DA beta-hydroxylase blockers. These findings demonstrate that impairment of the UP system produces cell death and neuronal inclusions selectively for DA-containing neurons that depend on the occurrence of endogenous DA.
Calocube—A highly segmented calorimeter for a space based experiment D׳Alessandro, R.; Adriani, O.; Agnesi, A. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
07/2016, Letnik:
824
Journal Article
Recenzirano
Odprti dostop
Future research in High Energy Cosmic Ray Physics concerns fundamental questions on their origin, acceleration mechanism, and composition. Unambiguous measurements of the energy spectra and of the ...composition of cosmic rays at the “knee” region could provide some of the answers to the above questions. Only ground based observations, which rely on sophisticated models describing high energy interactions in the earth׳s atmosphere, have been possible so far due to the extremely low particle rates at these energies.
A calorimeter based space experiment can provide not only flux measurements but also energy spectra and particle identification, especially when coupled to a dE/dx measuring detector, and thus overcome some of the limitations plaguing ground based experiments. For this to be possible very large acceptances are needed if enough statistic is to be collected in a reasonable time. This contrasts with the lightness and compactness requirements for space based experiments. A novel idea in calorimetry is discussed here which addresses these issues while limiting the mass and volume of the detector. In fact a small prototype is currently being built and tested with ions. In this paper the results obtained will be presented in light of the simulations performed.
Recently, we described the occurrence of a dehydroascorbate reductase within the rat CNS. This enzyme regenerates ascorbate after it is oxidized during normal aerobic metabolism. In this work, we ...describe the neuronal compartmentalization of the enzyme, using transmission electron microscopy of those brain areas in which the enzyme was most densely present when observed under light microscopy. In parallel biochemical studies, we performed immunoblotting and measured the enzyme activity of the cytoplasm and different nuclear fractions. Given the abundance of ascorbate in the caudate–putamen, we focused mostly on the occurrence of dehydroascorbate reductase at the striatal subcellular level. We also studied cerebellar Purkinje cells, hippocampal CA3 pyramidal cells and giant neurons in the magnocellular part of the red nucleus. In addition to neurons, immunolabeling was found in striatal endothelial cells, in the basal membrane of blood vessels and in perivascular astrocytes. In neuronal cytosol, the enzyme was observed in a peri-nuclear position and on the nuclear membrane. In addition, in both the striatum and the cerebellum, we found the enzyme within myelin sheets. Dehydroascorbate reductase was also present in the nucleus of neurons, as further indicated by measuring enzyme activity and by immunoblotting selected nuclear fractions. Immunocytochemical labeling confirmed that the protein was present in isolated pure nuclear fractions.
Given the great amount of free radicals which are constantly generated in the CNS, the discovery of a new enzyme with antioxidant properties which translocates into neuronal nuclei appears to be a potential starting point to develop alternative strategies in neuroprotection.
: Amphetamine derivatives, such as methamphetamine (METH) and 3,4‐methylenedioxymethamphetamine (MDMA), act as monoaminergic neurotoxins in the central nervous system. Although there are slight ...differences in their mechanism of action, these compounds share a final common pathway, which involves dopamine release and oxidative stress. Apart from striatal toxicity involving monoamine axons, no previous report evidenced any alteration at the striatal level concerning postsynaptic sites. Given the potential toxicity for extracellular dopamine at the striatal level, and the hypothesis for neurotoxic effects of dopamine on striatal medium‐sized neurons in Huntington's disease, we evaluated at an ultrastructural level the effects of MDMA on intrinsic striatal neurons of the mouse. In this study, administering MDMA, we noted ultrastructural alterations of striatal postsynaptic GABAergic cells consisting of neuronal inclusions shaped as whorls of concentric membranes. These whorls stained for ubiquitin but not for synuclein and represent the first morphologic correlate of striatal postsynaptic effects induced by MDMA.
: The psychostimulant 3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) is an amphetamine derivative that is widely abused. In previous studies, depending on the animal species, neurotoxicity has ...been demonstrated for either serotonin (5‐HT) or/and dopamine (DA) nerve endings. These studies focused on the basal ganglia circuitry; however, in humans chronic abuse of MDMA often results in neurological symptoms that last after MDMA withdrawal and are not related to the extrapyramidal system such as electroencephalographic (EEG) abnormalities and cognitive impairment. These alterations might be due to the concomitant intake of other illicit compounds, the consequence of MDMA‐induced hyperthermia, or to a primary neurotoxicity directed to extrastriatal regions. These observations call for a more in‐depth analysis on the potential involvement of brain areas outside the basal ganglia in the toxic effects induced primarily by MDMA. In the present study, we treated C57Black mice chronically (25 days) with daily injections of MDMA (2.5 mg/kg). During treatments, mice were monitored in order to detect behavioral modifications, and epidural electrodes were installed to perform EEG recording. Behavioral data showed a sensitization as measured by locomotor activity, which related to progressive and long‐lasting EEG changes and neuronal degeneration within the hippocampus.
Lewy bodies (LB) were first described by Lewy in 1912 1 as neuronal pale eosinophilic inclusions which became a pathological hallmark of Parkinson s disease (PD). In his original study, Lewy defined ...these inclusions as pale eosinophilic cytoplasmic structures, and studies since then have revealed LB to be ubiquitin-, alpha-synuclein-, and parkin-containing inclusions. This suggests that knowledge of the biochemical steps involved in the genesis of LB might disclose a final common pathway which might be responsible for different types of inherited and sporadic parkinsonism. This would lead to the identification of new therapeutic targets for interfering with disease progression. Although LB were originally described solely in PD, in the last decade these inclusions were described in a spectrum of degenerative disorders ranging from pure movement disorders to dementia. This suggests that common biochemical alterations leading to the formation of intracellular inclusions might underlie various pathological conditions. Consequently, the knowledge of the biochemical steps involved in the formation of neuronal inclusions could represent a key to develop new therapeutic strategies. In recent years it has been possible to develop both in vitro and in vivo neuronal inclusions resembling Lewy bodies. These experimental approaches have ranged from the use of alpha-synuclein transgenic mice to the continuous exposure to a mitochondrial complex I inhibitor. The aim of the present paper is to review briefly, recent advances on Lewy body research to achieve new insight into the etiology of PD and the molecular events leading to neurodegeneration.
: Apomorphine, given by a single injection, repeated injections, or by continuous infusion, was tested for neuroprotective effects in mice administered methamphetamine or ...N‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) in order to induce striatal dopamine (DA) depletion. In the first part of the study, the DA agonist (R)‐apomorphine was administered at various doses (1, 5, and 10 mg/kg), 15 min before methamphetamine (5 mg/kg × 3, 2 h apart). Mice were sacrificed 5 days later. In the second part, apomorphine was administered either continuously by subcutaneous minipump (cumulative daily dose of 0.5, 1, and 3.15 mg/kg), or as single, repeated daily injections (up to 5 mg/kg) starting 40 h after an acute administration of MPTP (30 mg/kg). Mice were sacrificed at different time intervals (up to 1 month) following MPTP injection. In all the animals, the integrity of striatal DA terminals was evaluated by measuring striatal DA levels and TH immunohistochemistry. Apomorphine dose‐dependently prevented methamphetamine toxicity. These effects were neither due to a decrease in the amount of striatal methamphetamine nor to the hypothermia, and they were not reversed by the DA antagonist haloperidol. Moreover, chronic, continuous (but not pulsatile) administration of apomorphine rescued damaged striatal dopaminergic terminals. These findings confirm a protective effect of apomorphine that also consists of a neurorescue of damaged striatal DA terminals. This suggests a new hypothesis about the long‐term benefits observed during continuous apomorphine administration in Parkinson's disease patients.
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