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Biomedical subjects

R Longo

Publications and source records attributed to R Longo.

At least 55 records · Page 3Linked to original sources

Opposite modulation of 4-aminopyridine and hypoxic hyperexcitability by A1 and A2 adenosine receptor ligands in rat hippocampal slices.

The effects of the adenosine receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), and of the adenosine agonists N6-cyclopentyladenosine (CPA), N6-(2-phenylisopropyl)adenosine (R-PIA), and 2-[p-(carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadenosin e (CGS 21680) were investigated on the hyperexcitability induced in the CA1 area of rat hippocampal slices by hypoxia or the epileptogenic agent 4-aminopiridine. Slice perfusion with the mixed adenosine receptor agonist R-PIA (0.2 microM) significantly (P < 0.05) decreased: (i) the number of slices showing a transient CA1 epileptiform bursting during the hypoxic period; (ii) the duration of the hypoxia-induced epileptiform bursting. Conversely, slice perfusion with the selective A1 adenosine receptor antagonists DPCPX (0.2 microM) or with the selective A2 adenosine receptor agonist CGS 21680 significantly (P < 0.05) increased the number of slices showing a transient CA1 epileptiform bursting during the hypoxic period but did not affect the duration of the hypoxia-induced epileptiform bursting. Neither drug significantly affected the number of slices showing functional recovery after hypoxia. Slice perfusion with DPCPX (0.2 microM) also significantly increased (P < 0.05) the number of slices showing a persistent CA1 epileptiform bursting during the reoxygenation period, while the other drugs failed to affect it. Slice perfusion with the selective A1 adenosine receptor agonist CPA (2 microM) or R-PIA (5 microM) significantly (P < 0.05) decreased the duration of the CA1 epileptiform bursting induced by 100 microM 4-aminopyridine. CGS 21680 (5 microM) perfused together with CPA (2 microM) significantly (P < 0.05) counteracted the inhibitory effects of the A1 adenosine receptor agonist on 4-aminopyridine epileptiform bursting, while it failed by itself to directly affect the 4-aminopyridine epileptiform bursting duration. The results produce evidence for a selective opposite modulation by A1 and A2 adenosine agonists in the control of hippocampal hyperexcitability induced by hypoxia or 4-aminopyridine but not in the post-hypoxic functional recovery.

4-Aminopyridine↗

Felbamate selectively blocks in vitro hippocampal kainate-induced irreversible electrical changes.

The influence of the anticonvulsant felbamate has been tested on in vitro excitotoxicity induced by treatment of hippocampal slices with elevated concentrations of NMDA, AMPA and kainic acid. For comparison, the effects of the glutamate antagonist 7-chlorokynurenic acid and of the anticonvulsants pentobarbitone and lamotrigine, were also studied. Slice perfusion with 50 microM NMDA or 25 microM AMPA or 12 microM kainic acid produced within 30 min a disappearance or a pronounced irreversible amplitude reduction of the CA1 electrical synaptic responses. Slice perfusion with 1.2-1.6 mM felbamate or 100 microM lamotrigine significantly decreased the incidence of the irreversible disappearance of the CA1 electrical response induced by kainic acid. On the contrary, slice perfusion with the same concentrations of the drugs did not affect the irreversible disappearance of the CA1 electrical response induced by NMDA or AMPA. By contrast, slice perfusion with 100 microM of 7-chlorokynurenic acid significantly prevented the neurotoxic effects induced by both NMDA and kainic acid, while 100 microM of pentobarbitone failed to affect kainic acid-induced neurotoxicity. The different profile of neuroprotection elicited by felbamate with respect to reference drugs indicates that a different mechanism of action than antagonism of NMDA response or potentiation of GABA response underlies the neuroprotectant effects of felbamate.

Animals↗

Quality assessment in in vivo NMR spectroscopy: IV. A multicentre trial of test objects and protocols for performance assessment in clinical NMR spectroscopy.

A multicentre trial of test objects and protocols for performance assessment in single volume and slice selective magnetic resonance spectroscopy (MRS) was conducted by the European Community Concerted Action on MRI and MRS. The trial assessed phosphorus and proton localisation techniques implemented on commercially available MR systems at ten sites in Europe. At each site, a number of parameters devised by the Concerted Action were measured using prototype test objects. Some of these parameters related to the quality of localisation and others to the overall performance of the spectrometer. Results were obtained for the ISIS, DRESS, STEAM, and PRESS sequences with a range of acquisition parameters, allowing evaluation of the assessment methodology and comparison of the efficacy of various implementations of these localisation techniques. The results of this trial have been important in the development of the Concerted Action's final recommendations for MRS performance assessment, and demonstrate that such assessment provides valuable information in the comparison of spectroscopy data from different sites and in the development of new localisation sequences, and provides a means of quality assurance in MRS.

Magnetic Resonance Spectroscopy↗

Absolute quantitation of brain 1H nuclear magnetic resonance spectra. Comparison of different approaches.

RATIONALE AND OBJECTIVES: Three different calibration techniques of 1H localized nuclear magnetic resonance (NMR) spectra were applied to a group of healthy volunteers. Absolute concentrations of the metabolites and their standard deviations were compared, and the clinical feasibility of these calibration technique is discussed. METHODS: Eighteen healthy volunteers were included in the study. Both water and creatine were used as internal standard, and a pertinent solution of metabolites was used as an external standard. The T2 relaxation times of the brain metabolites were evaluated in each examination. RESULTS AND CONCLUSIONS: The concentrations obtained using water as an internal standard and using an external standard are very similar, and the first of these methods show smaller standard deviations. The authors' results show that the use of creatine as an internal standard may induce systematic errors in absolute calibration because of the uncertainty on the true creatine concentration.

Adult↗

P-glycoprotein expression in acute myeloblastic leukemia analyzed by immunocytochemistry and flow cytometry.

Using the APAAP technique, we assessed the reactivity of five monoclonal antibodies, JSB1, C219, Mab 57, 2F8 and MRK16, to gp 170 in 60 cases of de novo acute myeloid leukemia (AML) and 13 relapses. Reactivity, varied between the five antibodies, and positivity was obtained with 2F8 > JSB1 > MRK16 > Mab57 > C219. Sixteen of the 60 cases were also studied by flow cytometry. In 10 cases, the results with the two techniques corresponded, in the other 6 cases, flow cytometry proved more sensitive than APAAP in detecting small amounts of gp170. In the flow cytometry analysis, the cells fixed in methanol and paraformaldehyde were more fluorescent than unfixed samples or those fixed in paraformaldehyde or methanol alone. Our results thus reveal that positivity for gp 170 depends on various factors, including the specificity of the monoclonal antibodies, the techniques used and the preservation of the samples. This suggests the need for a clear standardization of the methods to detect gp170.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Felbamate displays in vitro antiepileptic effects as a broad spectrum excitatory amino acid receptor antagonist.

The in vitro antiepileptic activity of the novel anticonvulsant drug felbamate was tested in rat hippocampal slices on the CA1 epileptiform bursting induced by different chemical epileptogenic agents. The effects of felbamate were compared with those of the anticonvulsant drugs diphenylhydantoin and pentobarbitone and with the effects of excitatory amino acid antagonists acting at both N-methyl-D-aspartate (NMDA) and non-NMDA receptors. Like the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), felbamate at a minimum effective concentration of 1 mM induced a significant (P < 0.01) reduction of the duration of the CA1 epileptiform bursting due to the K+ channel blocker, 4-aminopyridine, and the excitatory amino acids, kainate and quisqualate. Like the NMDA receptor antagonist ketamine, felbamate (1.6 mM) significantly (P < 0.01) decreased the duration of the CA1 epileptiform bursting caused by 'Mg(2+)-free' solutions. Conversely, felbamate (1.6 mM), CNQX (100 microM) and ketamine (100 microM) failed to affect the epileptiform bursting induced by the GABA antagonist penicillin. Pentobarbitone (100 microM) significantly (P < 0.01) decreased the duration of the CA1 epileptiform bursting caused by 'Mg(2+)-free' solutions, 4-aminopyridine or penicillin, while diphenylhydantoin (up to concentrations of 100 microM) failed to have an effect. The results indicate that felbamate displays a unique profile of in vitro antiepileptic effects as a broad spectrum antagonist of excitatory amino acid transmission.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Effects of calcium antagonists on hypoxic and NMDA injury in rat hippocampal slices.

The effects of various calcium antagonists, acting at the different neuronal calcium channels, were studied towards two models of in vitro neuronal injury in rat hippocampal slices. In particular, the influence of the drugs were tested on the electrical failure induced by treatment of hippocampal slices with hypoxia or high concentrations of the excitatory amino acid N-methyl-D-aspartate (NMDA). The L-type calcium antagonists, nifedipine (100 microM) and diltiazem (100 microM) or the T-type calcium antagonist amiloride (100 microM) failed to significantly affect the recovery from the CA1 electrical failure induced by both hypoxia or NMDA (50 microM). The N-type calcium antagonists, omega-conotoxin GVIA (0.5 microM) and neomycin (300 microM) significantly (P < 0.01) increased the probability of the recovery of the CA1 population spike after hypoxia but not after NMDA (50 microM). The glutamate antagonist dizocilipine (50 microM), tested for comparison, significantly (P < 0.01) increased the probability of the recovery of the CA1 population spike after hypoxia and NMDA (50 microM). The results suggest an involvement of calcium channels especially of N-type in the genesis of hypoxic but not NMDA neuronal injury.

Animals↗

Pertussis toxin prevents neomycin-induced calcium-dependent electrophysiological effects in rat hippocampal slices.

1. The influence of pertussis toxin has been studied on the effects of neomycin on CA1 field potentials in rat hippocampal slices in order to determine a role played by G protein in the modulation of synaptic transmission by the drug. 2. Neomycin (500 microM), within 30 min significantly (P < 0.01) decreased the magnitude of the somatic CA1 excitatory postsynaptic potentials (EPSP) and population spike (PS) in control hippocampal slices. 3. Neomycin (500 microM), within 30 min failed to significantly affect the magnitude of the somatic CA1 EPSP and PS in slices obtained from animals treated intracerebroventricularly (ICV) with 1-2 micrograms of pertussis toxin 3 days before. 4. The results demonstrated that pertussis toxin prevents some electrophysiological effects of neomycin, suggesting a role of G protein in the modulation of the aminoglycoside antibiotic on central synaptic transmission.

Action Potentials↗

In vivo localized 1H NMR spectroscopy: an experimental characterization of the PRESS technique.

The aim of this study was the experimental characterization of the PRESS technique for image-guided in vivo 1H NMR spectroscopy, as implemented on a commercially available 1.5 T NMR whole-body system. Three characterization parameters were defined and evaluated in test object measurements: selection efficiency, suppression efficiency and contamination. The characterization parameters were evaluated in different experimental conditions. The profile of signal intensity across the volume of interest (VOI) was investigated. Our results show that the characterization parameters are slightly affected by the echo time, while they are not affected by changes in the repetition time. When the VOI is co-extensive with the inner cube of the test object the suppression efficiency is good but the selection efficiency is not very high. Contamination is affected by the synthesizer frequency offset, while the selection efficiency is quite stable. Contamination effects become significant in case of 90 degrees pulse maladjustment.

Contrast Media↗

Cytogenetic conversion in a case of polycythaemia vera treated with interferon-alpha.

Polycythaemia vera is a clonal disorder of the haemopoietic stem cell causing a pathologic expansion of the erythroid and sometimes the megakaryocytic and myeloid elements. In order to avoid the possible mutagenic effects of radioactive phosphorus, alkylating agents and hydroxyurea, since 1988 alpha-IFN has been used for the treatment of PV and has been shown to induce and maintain haematological remission. We describe a 24-year-old PV patient with chromosomal abnormalities who achieved not only a reduction of the proliferation of erythroid elements and reticulin content in the bone marrow, but also a complete cytogenetic remission after IFN treatment.

Adult↗

Protective actions of 21-aminosteroids and MK-801 on hypoxia-induced electrophysiological changes in rat hippocampal slices.

The effects of the 21-aminosteroids, U-74500A and U-78517F (drugs endowed with lipid peroxidation inhibitor properties) were tested on hypoxia-induced functional failure in rat hippocampal slices. For comparison, the effects of the non-competitive N-methyl-D-aspartate antagonist, dizocilpine (MK-801) were studied. Perfusion of slices with 50 microM of MK-801 or with 50-100 microM of U-78517F, but not with 100-200 microM of U-74500A, significantly (P < 0.01) increased the incidence of reappearance of the CA1 population spikes after reoxygenation in rat hippocampal slices subjected to a 45-min hypoxic period followed by a 45-min reoxygenation period. Perfusion of slices with 12.5 microM of MK-801 plus 12.5 microM of U-78517F significantly (P < 0.05) increased the incidence of reappearance of the CA1 population spikes after reoxygenation with respect to perfusion of slices with 12.5 microM of U-78517F alone or with 12.5 microM of MK-801 alone. The results show that 21-aminosteroids have protective effects against hypoxia-induced functional failure in rat hippocampal slices. In addition, the data show that, under the same experimental conditions, the NMDA receptor antagonist, MK-801, was also able to improve hypoxia-induced functional failure. On the whole, the results suggest that the hypoxia-induced functional electrical failure might depend on both release of excitatory amino acids and oxygen free-radical-mediated membrane lipid peroxidation.

Animals↗

Sigmoid volvulus in west Africa: a prospective study on surgical treatments.

To evaluate the efficacy of different types of surgery, we performed a prospective, randomized trial in 31 consecutively hospitalized patients with sigmoid volvulus. These patients represented 8 percent of 377 cases of emergency surgery. At the time of surgery, the patients were divided into two groups according to the absence (Group A) or presence (Group B) of bowel gangrene. At random, each group was assigned two surgical treatments. Seventeen patients entered Group A and underwent mesosigmoidopexy (seven patients) or resection and primary anastomosis (10 patients). Fourteen patients entered Group B and underwent Hartmann's procedure (eight patients) or resection and primary anastomosis (six patients). Overall mortality was four patients among 31 (13 percent), with a significant prevalence in the group with gangrene (21.4 percent vs. 5.8 percent). In Group A, the rate of success in patients treated with resection-anastomosis was higher than that in patients undergoing mesosigmoidopexy (90 percent vs. 71.5 percent). In Group B, a meaningful difference was observed between the rate of success of patients undergoing Hartmann's procedure and that of those undergoing resection and primary anastomosis (87.5 percent vs. 50 percent). The mortality rates were 12.5 percent and 33.3 percent, respectively. The results of our study show that the therapeutic approach to sigmoid volvulus should be diversified according to the absence or presence of gangrenous colon. The treatment of choice seems to be resection with primary anastomosis in patients with viable colon and Hartmann's procedure in patients with gangrenous colon.

Adolescent↗

Alzheimer's disease histologically proven studied by MRI and MRS: two cases.

Two patients affected by severe Alzheimer's disease (AD) were investigated by MRI and image-guided 31P MRS. In one case, 1H MRS was additionally performed. In both cases the diagnosis of AD was confirmed, post mortem, by the pathologist. The spectral parameters of the 31P MR spectra were estimated by fitting the 31P MR signals in the time domain. Our 31P MRS results suggest that it is possible to detect the membrane catabolism, as indexed with the level of PDE resonances visible in in vivo 31P MRS, at least in severe AD cases. The 1H spectrum from AD brain showed a marked decrease of NAA signal respect to choline.

Aged↗

Progression of essential thrombocythemia to blastic crisis via idiopathic myelofibrosis.

We report a 61-year-old man with essential thrombocythemia (ET) whose clinical course was followed for 12 years. The ET evolved into true idiopathic myelofibrosis (IM) 6 years after the initial diagnosis and progressed to myeloid blastic transformation 6 years later. The cytogenetic analysis showed a normal karyotype during the ET phase but subsequent analysis revealed an abnormal karyotype during the IM phase which evolved clonally at blastic crisis with constant involvement of chromosome 13q and chromosome 7. The close monitoring of essential events, using clinical, morphologic, immunologic and cytogenetic parameters, allowed us to carefully identify the transition from one chronic myeloproliferative disease (MPD) to another. This is only the second case reported showing a clinical evolution of this nature. The clinical and biological aspects of the disease are briefly discussed.

Blast Crisis↗

Fatty infiltration of the liver. Quantification by 1H localized magnetic resonance spectroscopy and comparison with computed tomography.

RATIONALE AND OBJECTIVES: The authors evaluated the degree of fatty infiltration of the liver in subjects with diffuse liver steatosis using image-guided 1H localized MR spectroscopy and correlated the magnetic resonance (MR)-determined fat fraction with the computed tomography (CT) liver/spleen density ratio and histologic evaluation. METHODS: MR measurements were performed at 1.5 T by applying a double-spin-echo localization sequence. Twenty-six patients underwent MR and CT examinations and ultrasound (US)-guided biopsy. Additionally, three healthy volunteers underwent MR examination. Steatosis severity was estimated using 1) the ratio between fat and total MR signal areas; 2) the ratio between liver and spleen CT number; and 3) histologic score. RESULTS: The linear correlation between MR fat/fat-plus-water signal ratio and CT liver/spleen density values ratio is statistically significant. Both techniques correlate well with histologic score. No significant correlation exists between water or fat T2 values and the severity of steatosis. CONCLUSIONS: 1H MR spectroscopy allows a noninvasive estimate of the hepatic fat content.

Adult↗

Magnetic resonance imaging in right ventricular dysplasia.

Fifteen patients with right ventricular dysplasia were investigated by T1-weighted spin- and gradient-echo pulse sequences, using a protocol that enabled both a subjective analysis of myocardial signal intensity and a quantitative/qualitative analysis of right and left ventricular function. In 8 patients, 3 investigators independently recognized abnormally hyperintense areas in the anatomic sites usually affected by the disease. In 7 of these patients, these areas showed an overlap with a-dyskinetic areas imaged by both magnetic resonance imaging (MRI) and echocardiography. In 1 patient who underwent a cardiac transplant, MRI of the explanted heart showed an excellent correlation between the distribution of the lesions and the in vivo/in vitro features. The data were compared with those from an equivalent sample of patients affected by dilated cardiomyopathy. In the latter patients, no focal hyperintensities were attributed to any anatomic sites in the right ventricule, and no focal a-dyskinetic foci were observed. Furthermore, the 2 groups of patients were significantly different in regard to dimensional and functional quantitative parameters. The results suggest that MRI is useful in integrating echocardiographic data and can be helpful in diagnosing this disease in late stages.

Adipose Tissue↗