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Biomedical subjects

F Conti

Publications and source records attributed to F Conti.

At least 127 records · Page 7Linked to original sources
PubMed1995

Alterations in energy metabolism of hypertrophied rat cardiomyocytes: influence of propionyl-L-carnitine.

Alterations in energy metabolism, reduced fatty acid oxidation, and cardiac carnitine content have been implicated in the evolution from compensated to decompensated cardiac hypertrophy. We determined high-energy nucleotide levels in hypertrophied quiescent cardiomyocytes isolated from rat hearts 4 weeks after banding of abdominal aorta. In hypertrophied quiescent cardiomyocytes, a decrease in ATP content (p = 0.03), and ratios of ATP/total adenine nucleotides and of ATP/ADP were observed, together with an increase in ADP. In addition, palmitate, but not glucose oxidation, was markedly reduced in hypertrophied myocytes. In the presence of 25 microM propionyl-L-carnitine (PLC) or L-carnitine (LC), palmitate oxidation was significantly stimulated in hypertrophied myocytes. The ATP/ADP ratio was significantly increased only with PLC. This effect was not due to an enhanced PLC uptake, since total PLC uptake was 50% lower than that of LC. Changes in the energy generating system of quiescent myocytes occur early in pressure overload hypertrophy, and these alterations can be attenuated by PLC.

Adenosine Diphosphate↗
PubMed1995

GAT-1, a high-affinity GABA plasma membrane transporter, is localized to neurons and astroglia in the cerebral cortex.

High affinity, GABA plasma membrane transporters influence the action of GABA, the main inhibitory neurotransmitter. The cellular expression of GAT-1, a prominent GABA transporter, has been investigated in the cerebral cortex of adult rats using in situ hybridization with 35S-labeled RNA probes and immunocytochemistry with affinity purified polyclonal antibodies directed to the C-terminus of rat GAT-1. GAT-1 mRNA was observed in numerous neurons and in some glial cells. Double-labeling experiments were performed to compare the pattern of GAT-1 mRNA containing and GAD67 immunoreactive cells. The majority of neurons expressing GAT-1 mRNA also contained GAD67 immunoreactivity (ir), but GAT-1 mRNA was also observed in a few pyramidal neurons. GAT-1-ir was localized to numerous puncta and fibers and to astrocytic processes, was not observed in sections incubated in GAT-1 antibodies preadsorbed with rat GAT-1 C-terminal peptide, and was observed in sections incubated in GAT-1 antibodies preadsorbed with the C-terminal portion of the related peptides rat GAT-3(607-627) or rat glycine transporter-1(625-633). The highest number of GAT-1-ir puncta was in layer IV, followed by layers II-III. GAT-1 positive puncta appeared to have a preferential relationship to the soma and proximal dendrites of unlabeled pyramidal cells. All GAT-1 positive axon terminals formed symmetric synapses. This study demonstrates that (1) GAT-1 is expressed by both neurons and astrocytes, (2) the majority of GAT-1 expressing neurons contain GAD67, and (3) GAT-1 uptake system is more extensive than the GABA synthetizing system. These observations support the hypothesis that, in addition to its role in terminating GABA action by uptake into GABAergic axon terminals, GAT-1 influences both excitatory and inhibitory transmission by modulating the "paracrine" spread of GABA (Isaacson et al., 1993), and suggest that astrocytes may play an important role in this process.

Animals↗
PubMed1994

Cellular localization and laminar distribution of AMPA glutamate receptor subunits mRNAs and proteins in the rat cerebral cortex.

The cellular and laminar distributions of the alpha-amino-3-hydroxy-5- methyl-4-isoxazole propionate (AMPA) receptor subunits GluR1-4 have been investigated in the cerebral cortex of adult rats by in situ hybridization with 35S-labeled cRNA probes and by immunocytochemistry with subunit-specific antibodies. In sections incubated with the GluR1-4 antisense probes, specific hybridization signal was observed in many but not all cortical cells. Experiments with in situ hybridization and antibodies to glial fibrillary acidic protein (GFAP) showed that percentages of GFAP-immunoreactive cells labeled by the GluR1-4 probes were 20%, 9.4%, 8.2%, and 57.3%, respectively. A semiquantitative evaluation revealed that about 56% of cortical neurons contained the GluR1 subunit, 80% the GluR2, 63% the GluR3, and 44% the GluR4. The number of grains associated with every neuron was determined from sections exposed for 15 days, the background level was subtracted, and labeled neurons were divided into four groups: A (< or = 10 grains), B (11-20 grains), C (21-30 grains), and D (> 30 grains). The number of neurons belonging to each of these groups was then evaluated for their occurrence in each cortical layer. Immunocytochemistry with subunit-specific antibodies showed that 1) GluR1-immunoreactive neurons were mostly layers V and VI nonpyramidal neurons; 2) GluR2/3-immunoreactive neurons were more numerous in layers II-III and V-VI, and most of them were pyramidal; and 3) GluR4-positive cells were the least numerous, and they were either neurons (pyramidal and nonpyramidal) or astrocytes. These observations indicate that cortical neurons exhibit a remarkable degree of heterogeneity with regard to both the composition and the number of AMPA receptors and suggest that this diversity might be correlated with the functional attributes of neurons receiving glutamatergic afferents and with the physiological features of corticifugal neurons.

Animals↗
PubMed1994

Proline mutations on the S4 segment of rat brain sodium channel II.

We have studied S4-proline mutants of the rat brain sodium channel II. In mutant A224P one proline was added on the S4 segment of repeat I, and in mutant P1313V a proline was removed from the segment S4 of the repeat II. In both mutants, the activation curve was shifted to more positive potentials, without changing the steepness of the voltage dependence. The time course of inactivation, consisting of two exponential components, was similar in the wild type and in mutant A224P. Differently, the decay of the current in mutant P1313V had only one component, with a time constant similar to that of the fast component of wild type channels. This change in kinetics was accompanied in mutant P1313V by a change in the voltage dependence of the apparent steady-state inactivation. We conclude that the addition or deletion of prolines in segment S4 does not affect significantly the activation of sodium channels, but alters their mode of inactivation.

Animals↗
PubMed1994

Cellular localization and laminar distribution of NMDAR1 mRNA in the rat cerebral cortex.

N-methyl-D-aspartate (NMDA) receptors, which play a critical role in many cortical functions, are composed of a heteromeric assembly of different subunits: of these, the NMDA receptor subunit 1 (NMDAR1) is a constant component of, and thus an excellent marker for, NMDA receptors. In this study, we have investigated the cellular localization and laminar distribution of NMDAR1 mRNA in the cerebral cortex of adult rats by in situ hybridization histochemistry with a 35S-labeled cRNA probe. Specificity and background levels were determined in adjacent sections incubated with a 35S-labeled sense RNA. In sections incubated with the antisense RNA probe, specific hybridization signal was observed in a large number of cells. Some cells, however, did not appear to contain NMDAR1 mRNA. The vast majority of these unlabeled cells were small, suggesting that they are astrocytes or other small nonneuronal cells. Double-labeling studies with in situ hybridization histochemistry and immunocytochemistry with antibodies to glial fibrillary acidic protein (GFAP) showed that about 95.7% of the GFAP-positive cells did not express NMDAR1 mRNA, indicating that virtually all astrocytes do not contain this transcript. A semiquantitative evaluation of cortical neurons, defined as those cells larger than the GFAP-positive astrocytes, revealed that about 80% were associated with silver grains. The number of silver grains associated with every neuron was determined from sections exposed for 15 days, the background level was subtracted, and all labeled neurons were grouped into five groups: A (< or = 10 grains), B (11-20 grains), C (21-30 grains), D (31-40 grains), and E (> 40 grains). The number of neurons belonging to each group was then evaluated according to their occurrence in each cortical layer. In layer I all labeled neurons were in group A, whereas in layers II-III and V-VI positive neurons were in group A-E. In layer IV most neurons were in groups A and B, whereas only a few were in group E. These observations indicate that 1) virtually all cortical cells containing NMDAR1 mRNA in adult rats are neurons; 2) about 80% of all cortical neurons express NMDAR1 mRNA; and 3) labeled neurons can be divided into several groups on the basis of NMDAR1 mRNA levels expressed, which presumably reflect the number of NMDA receptors. The existence of neurons with a different number of receptors may be a critical factor for determining the physiological effect of NMDA receptor activation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Effect of acetyl-L-carnitine on recovery of brain phosphorus metabolites and lactic acid level during reperfusion after cerebral ischemia in the rat--study by 13P- and 1H-NMR spectroscopy.

The effects of acetyl-L-carnitine (ALCAR) treatment on brain energy state recovery and lactic acid levels following 20 min ischemia and 2, 24 and 48 h reperfusion were investigated by 31P and 1H-NMR spectroscopy. Transient forebrain ischemia was induced by four-vessel occlusion method in fed 6-month-old Fischer rats. ALCAR or saline was administered by intraperitoneal route immediately after 20 min ischemia and again at 1, 4, 24 and 30 h during reperfusion. Twenty-min severe forebrain ischemia was associated with a marked decrease in phosphocreatine (PCr) and ATP levels and a corresponding increase in lactic acid, inorganic phosphate (Pi), AMP, creatine, glycerol 3-phosphate and alanine levels. Following reperfusion, a general tendency to restore pre-ischemic metabolite levels was observed. However, after 2 h reperfusion in saline-treated rats, lactic acid and Pi levels remained significantly higher, while ATP levels were still significantly lower than in non-ischemic controls. On the contrary, in ALCAR-treated animals a complete recovery of all metabolites including Pi and ATP was observed, while PCr levels were even more elevated compared with those in saline-treated rats. Furthermore lactic acid content was significantly lower than that in both saline-treated and non-ischemic control rats. It is concluded that a potential therapeutic role may be claimed for ALCAR in the treatment of cerebral ischemia through mechanisms that include faster recovery and improvement of brain energy production as well as a decreased lactic acid content during early post-ischemic reperfusion.

Acetylcarnitine↗
PubMed1994

Dexamethasone-dependent modulation of human lymphoblastoid B cell line through sphingosine production.

The relationship between dexamethasone-dependent changes in intracellular sphingosine levels, energy and phospholipid metabolism have been investigated by 31P-NMR spectroscopy and high-performance liquid chromatography. The cellular functions have been evaluated by cellular growth and immunoglobulin M secretion (IgM). Significant increases in intracellular phosphorylcholine (PCho), extracellular choline (Cho), and endogenous sphingosine levels were observed only at 30 min incubation with dexamethasone. These results confirmed a sphingosine-dependent hydrolysis of choline-linked phospholipids (Miccheli, A., Ricciolini, R., Piccolella, E., Delfini, M. and Conti, F. (1991) Biochim. Biophys. Acta 1093, 29-35). Furthermore, no significant variations were evidenced at hours 1, 2, 6 and 18 of incubation. Dexamethasone causes an inhibition of cellular growth and IgM secretion as well as the sphingosine treatment. The results suggest that the effect of dexamethasone may be mediated by endogenous sphingosine production in Epstein-Barr virus transformed B lymphocytes.

B-Lymphocytes↗
PubMed1994

Dexamethasone-dependent modulation of cholesterol levels in human lymphoblastoid B cell line through sphingosine production.

The effect of dexamethasone on lipid composition of Epstein-Barr virus transformed human B lymphocytes have been investigated by 31P- and 1H-NMR spectroscopy and compared to the effects due to exogenous sphingosine treatment. Furthermore, the effects of dexamethasone and sphingosine on membrane structure was evaluated by fluorimetry. No significant changes were evidenced in phospholipid composition and in the ratio of unsaturated to total fatty-acid chains. A significant increase in total cholesterol levels was evident at 30 min incubation with dexamethasone or sphingosine; a parallel increase in DPH polarization at 30 min was also demonstrated. TMA-DPH intensity measurements suggest a slowing of vesicular intracellular traffic due to the treatment. The results suggest a dexamethasone- and sphingosine-dependent inhibition of intracellular cholesterol transport.

B-Lymphocytes↗
PubMed1994

Activation and deactivation properties of rat brain K+ channels of the Shaker-related subfamily.

We studied the activation properties of members of the Shaker-related subfamily of voltage-gated K+ channels cloned from rat brain and expressed in Xenopus oocytes. We find that Kv1.1, Kv1.4, Kv1.5, and Kv1.6 have similar activation and deactivation kinetics. The k+ currents produced by step depolarisations increase with a sigmoidal time course that can be described by a delay and by the derivative of the current at the inflection point. The delay tends to zero and the logarithmic derivative seems to approach a finite value at large positive voltages, but these asymptotic values are not yet reached at +80 mV. Deactivation of the currents upon stepping to negative membrane potentials below -60 mV is fairly well described by a single exponential. The decrease of the deactivation time constant at increasingly negative voltages tends to become less steep, indicating that this parameter also has a finite limiting value, which is not yet reached, however, at -160 mV. The various clones studied have very similar voltage dependencies of activation with half-activation voltages ranging between -50 and -11 mV and maximum steepness yielding and e-fold change for voltage increments between 3.8 and 7.0 mV. The shallower activation curve of Kv1.4 is likely to be due to coupling with the fast inactivation process present in this clone.

Animals↗
PubMed1994

Chronic fatigue: a peculiar evolution of eosinophilia myalgia syndrome following treatment with L-tryptophan in four Italian adolescents.

We describe four Italian adolescents in whom a persistent, debilitating fatigue appeared after therapeutic ingestion of products containing L-tryptophan and subsequent to the development of a transient rise in eosinophil count and severe myalgia (Eosinophilia Myalgia Syndrome-EMS). Their clinical picture was indistinguishable from that of the so-called Chronic Fatigue Syndrome. A chronic fatigue may occur after diverse triggering agents and its represents the peculiar clinical evolution of these four paediatric cases of EMS.

Adolescent↗
PubMed1994

Lung resections concomitant to coronary artery bypass grafting.

From 1980 through 1993 ten patients underwent concomitant coronary artery bypass grafting and lung resection via median sternotomy. In eight patients a lung malignancy was resected, of which one was a small cell lung cancer. The lung resection was carried out before cardiopulmonary bypass in eight patients and during cardiopulmonary bypass in two. Coronary artery bypass grafting was performed using saphenous vein in eight patients; internal mammary artery was used as arterial conduit in two patients. There was one postoperative death while postoperative complications during hospital stay occurred in two patients. Pulmonary bleeding did not occur in any patient in whom lung resection was performed either before or during cardiopulmonary bypass. Both the patients who had internal mammary artery grafting experienced complications related to an associated lobectomy. A staged procedure is advisable if internal mammary artery has to be used and a lobectomy is required. The long-term survival in the patients with lung cancer was less than expected but the number of patients is too small to draw definite conclusions.

Carcinoma, Small Cell↗
PubMed1994

The influence of cold ischemia time on biliary complications following liver transplantation.

Biliary complications are a continuing source of morbidity and mortality following orthotopic liver transplantation. The results of 100 whole-liver allografts performed in 92 adult patients were reviewed to determine whether cold ischemia time and preservation injury influenced both the incidence and type of biliary complications. Mean cold ischemia time was 10.2 +/- 0.5 h (range 3.6-19). Eighteen patients (19.6%) developed 25 biliary complications: there were eight anastomotic leaks, eight anastomotic strictures, six non-anastomotic strictures, two cystic duct mucoceles, and one biliary fistula following T-tube removal. Despite the high rate of reoperative surgery (68%), no death was attributable to biliary complications. Neither cold ischemia time nor early graft function influenced the rate of biliary complications or strictures of either type. Furthermore, an analysis of different factors revealed no predisposing effect of the pre-operative status of the recipient, type of biliary reconstruction, blood requirement, vascular complications, rejection or cytomegalovirus infection on the incidence of biliary complications or strictures. Only chronic rejection could be singled out as a risk factor for non-anastomotic strictures (p = 0.05). These results suggest that prolonged cold ischemia time does not seem to affect the rate or type of biliary complications following orthotopic liver transplantation. In view of these data, there is no clear reason to reconsider prolonged cold ischemia up to 15 h in University of Wisconsin solution, as it has transformed liver transplantation from an emergency operation to a semi-elective procedure and allows longer back-table preparation for graft reduction of splitting.

Adolescent↗
PubMed1994

Glutamate immunoreactivity in rat cerebral cortex is reversibly abolished by 6-diazo-5-oxo-L-norleucine (DON), an inhibitor of phosphate-activated glutaminase.

Glutamate (Glu) immunocytochemistry has been widely used to identify presumed gluergic neurons and synapses, but several problems related to the fact that Glu is both a synaptic transmitter and a compound used for metabolic purposes are still unsolved. One of these concerns the intense perikaryal staining observed in perfusion-fixed tissue. Phosphate-activated glutaminase, a key enzyme for the synthesis of releasable glutamate, is inhibited by the diazoketone 6-diazo-5-oxo-L-norleucine (DON), which greatly reduces glutamate release. In the present experiments, DON was either injected intraparenchymally or applied epipially to the sensorimotor cortex of adult Sprague-Dawley rats at concentrations of 0.25-1 mM. Both intraparenchymal and epipial applications of the chemical abolished Glu immunoreactivity in neuron perikarya. Adjacent sections processed for cytochrome oxidase histochemistry, for aspartate immunoreactivity, or stained with thionine showed no changes. The effects of DON application are reversible, as shown in a second series of experiments in which, after 30 min of DON application, animals were allowed to survive for 5-10 days. In these cases, Glu immunoreactivity in cortical neurons was identical to that observed in normal untreated animals. The results reported here suggest that Glu immunoreactivity demonstrated by the present procedure in neuron perikarya is mainly due to Glu produced via phosphate-activated glutaminase.

Animals↗
PubMed1993

[Foreign body decubitus: unusual cause of acute appendicitis].

The authors describe the origin and the physiopathological events in acute appendicitis. They show an uncommon case of acute appendicitis. The aetiology was an opaque radiation foreign body causing a subacute abdominal disease. At operation the authors discovered the above body free in the abdominal cavity; the appendix was not in ischemic phase but completely cut off bycecal plant. They suppose aetiology to be of a decubitus origin.

Acute Disease↗