Antihypertensive activity of a vegetable fibre preparation: a preliminary, double-blind, placebo-controlled study.
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Adult↗
Biomedical subjects
V Gallo
Publications and source records attributed to V Gallo.
Glutamate regulates intracellular calcium and gene expression in oligodendrocyte progenitors through the activation of DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors.
Oligodendrocytes and their progenitors (O-2A) express functional kainate- and DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-preferring glutamate receptors. The physiological consequences of activation of these receptors were studied in purified rat cortical O-2A progenitors and in the primary oligodendrocyte cell line CG-4. Changes in the mRNA levels of a set of immediate early genes were studied and were correlated to intracellular Ca2+ concentration, as measured by fura-2 Ca2+ imaging. Both in CG-4 and in cortical O-2A progenitors, basal mRNA levels of NGFI-A were much higher than c-fos, c-jun, or jun-b. Glutamate, kainate, and AMPA greatly increased NGFI-A mRNA and protein by activation of membrane receptors in a Ca(2+)-dependent fashion. Agonists at non-N-methyl-D-aspartate receptors promoted transmembrane Ca2+ influx through voltage-dependent channels as well as kainate and/or AMPA channels. The influx of Ca2+ ions occurring through glutamate-gated channels was sufficient by itself to increase the expression of NGFI-A mRNA. AMPA receptors were found to be directly involved in intracellular Ca2+ and NGFI-A mRNA regulation, because the effects of kainate were greatly enhanced by cyclothiazide, an allosteric modulator that selectively suppresses desensitization of AMPA but not kainate receptors. Our results indicate that glutamate acting at AMPA receptors regulates immediate early gene expression in cells of the oligodendrocyte lineage by increasing intracellular calcium. Consequently, modulation of these receptor channels may have immediate effects at the genomic level and regulate oligodendrocyte development at critical stages.
Animals↗
Expression and regulation of a glutamate receptor subunit by bFGF in oligodendrocyte progenitors.
Oligodendrocyte progenitor cells (O-2A) express both kainate-preferring and AMPA-preferring glutamate receptors (Gallo et al., Soc. Neurosci. Abstr., 18:653, 1992b; Gallo et al., 1994). The expression and regulation of the GluR-4c, AMPA-preferring subunit by growth factors was studied by Northern blot analysis of total RNA from purified rat cortical O-2A progenitors. Differently from cortical neurons, O-2A progenitors only expressed two high molecular weight GluR-4c transcripts (6.2 and 4.2 kb), as observed also in cultured astrocytes. Basic fibroblast growth factor (bFGF) increased GluR-4c transcript levels in O-2A progenitors and its effects were not mimicked by platelet derived growth factor (PDGF) or fetal calf serum. Therefore, bFGF may regulate O-2A progenitor responsiveness to glutamate during development through the expression of glutamate receptor subunits.
Animals↗
Excitatory amino acid receptors in glial progenitor cells: molecular and functional properties.
We have analyzed the molecular and biophysical properties of glutamate-gated channels in cells of the oligodendrocyte lineage, using both the CG-4 primary cell line (Louis et al: J. Neurosci. Res. 31:193-204, 1992a) and oligodendrocyte progenitors purified from the rat cerebral cortex. CG-4 progenitor cells, as well as primary progenitors, were stained with a specific anti-GABA antibody. In whole-cell patch-clamp recordings, rapid perfusion of the agonists L-glutamate, kainate, and AMPA produced rapidly desensitizing currents in CG-4 cells. NMDA was ineffective. Both rapidly desensitizing and steady-state components of responses to kainate were inhibited by the kainate/AMPA receptor antagonist CNQX. Northern blot analysis of total mRNA isolated from CG-4 cells revealed co-expression of both AMPA- and kainate-preferring glutamate receptor subunits. The activation of glutamate receptors in CG-4 cells caused a rapid and transient elevation of mRNAs for the immediate early gene NGFI-A.
6-Cyano-7-nitroquinoxaline-2,3-dione↗
Glial cells of the oligodendrocyte lineage express both kainate- and AMPA-preferring subtypes of glutamate receptor.
mRNAs for AMPA- and kainate-preferring glutamate receptor subunits are expressed abundantly in the CNS, yet functional studies of neurons and glia from brain suggest selective expression of AMPA receptors. We now show that glial cells of the O-2A lineage express rapidly desensitizing responses to kainate, mRNAs for GluR6, GluR7, KA-1, and KA-2, rapidly desensitizing responses to AMPA, and mRNAs for GluR-B, -C, and -D. Analysis of glutamate receptor currents in single cells reveals two receptor populations with high and low affinity for kainate and different sensitivity for potentiation by concanavalin A and for block of desensitization by cyclothiazide. Our experiments describe the characterization of native kainate-preferring receptors in glia and reveal coexpression in single cells of functional AMPA- and kainate-preferring receptors.
Animals↗
Oral lichen planus and hepatitis C virus (HCV) infection: is there a relationship? A report of 10 cases.
Ten patients are reported suffering from oral lichen planus (OLP) associated with chronic liver diseases linked to HCV. All patients were affected by varieties of erosive oral lichen planus. In six of these 10 patients the diagnosis of HCV was made as a result of the OLP diagnosis and four of them had unknown, but severe, chronic liver disease. These preliminary data support the possible existence of a relationship between oral erosive lichen planus and HCV infection.
Aged↗
[Wilson's disease: physiopathology, therapeutic approach and case report].
Wilson's disease is an hereditary recessive autosomal disorder which affects around five people per million inhabitants. The primary defect is localized in the liver and the disease is manifested by the accumulation of copper in tissues. The diminution of ceruloplasmin, which until a few years ago was mistakenly thought to be the pathogenetic cause of Wilson's disease, is an epiphenomenon of the underlying metabolic defect characterized by defective copper biliary excretion. There are four stages in the natural history of the disease: 1) an asymptomatic stage of hepatic copper accumulation; 2) dismission and redistribution of copper leading to hepatocellular necrosis and hemolysis; 3) extrahepatic accumulation of copper leading to the onset of cirrhosis and neurological damage; 4) stage of homeostasis following treatment but with possible irreversible neurological damage. Treatment of Wilson's disease takes the form of pharmacological, dietary and surgical therapy. Through the formation of copper and protein metal complexes D-penicillamine impoverishes copper deposits causing the reduction or disappearance of hepatic and neurological symptoms; a small percentage of patients treated develops a nephrotic syndrome requiring the compulsory suspension of the drug. In this case a valid alternative is triethylenetetramine dichlorohydrate (TETA) which provokes increased blood copper during copper diuresis. The response to pharmacological treatment is better the earlier treatment is started and the more regular its administration. Dietary intake of copper must be reduced in parallel avoiding foods with a high copper content. Liver transplant obviously leads to the "resolution" of the underlying metabolic problem in patients who develop fulminating hepatitis with hypercupremia and hemolysis and, of course, in cases of uncompensated cirrhosis which do not respond to chelating therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Long-term follow-up of patients with chronic hepatitis C treated with different doses of interferon-alpha 2b.
Eighty patients with chronic hepatitis C who completed a previously reported randomized controlled trial on the efficacy of interferon-alpha 2b were followed up for at least 36 mo after therapy discontinuation. Seventeen patients (21.2%) maintained normal ALT values throughout the follow-up; 63 (78.8%) either did not normalize the levels of ALT or relapsed during the follow-up. A significantly greater proportion of patients treated with 3 million units of interferon three times a week subcutaneously for 48 wk were long-term responders compared with patients treated for 24 wk. Sex, age, hepatitis C virus antibody status, source of infection and pretreatment levels of ALT were not predictive of long-term response. Cirrhosis was found to be an unfavorable predictive factor. After 3 yr of follow-up, clearance of viremia was observed in 58.9% of the 17 long-term responders but in none of the non-responders (p = 0.002). E2-NS1 antibody tested negative in 88.2% of long-term responders and in 14.3% of nonresponders (p = 0.001). Fifty-nine percent of long-term responders tested negative for C100-NS4 antibody compared with 14.3% of nonresponders (p = 0.031). No significant change was observed in other antibodies. Four long-term responders underwent liver biopsy 2 yr after discontinuation of therapy. All four patients had normal liver histology compared with baseline assessment of chronic active hepatitis in three and chronic persistent hepatitis in the other. Three of the four were negative for serum hepatitis C virus RNA.
Adult↗
[Tauro-ursodeoxycholic acid vs. ursodeoxycholic acid in the dissolution of biliary calculi. Results of a single blind study].
Out of 34 patients enrolled and randomized, 31 completed the 6 months study period. Fifteen were treated with TUDCA, and 16 with UDCA. Dosage for both drugs was 10 mg/kg body weight daily. Superiprisingly, TUDCA was not found to be more active than UDCA in dissolving, totally or partially, the gallbladder stones; indeed, total dissolution was more frequent in the UDCA group. Since the two groups were similar as to number and size of the stones, the better results with UDCA cannot be attributed to the characteristics of the calculosis but must be ascribed to the molecule used. Both drugs induced an improvement in dyspeptic symptoms, but from this point of view, too, UCDA was more effective than TUDCA (p < 0.01). Finally, tolerability was also significantly better for UDCA, although TUDCA was altogether acceptable.
Adolescent↗
Release of exogenous and endogenous neurotransmitter amino acids from cultured astrocytes.
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Amino Acids↗
Depression by sodium ions of calcium uptake mediated by non-N-methyl-D-aspartate receptors in cultured cerebellar neurons and correlation with evoked D-[3H]aspartate release.
In a previous study we noted that the release of D-[3H]aspartate evoked by non-N-methyl-D-aspartate (non-NMDA) receptor agonists in cultured rat cerebellar granule cells was enhanced in the absence of extracellular Na+. To explain this apparent paradox, we tried in the present investigation to correlate the effect of Na+ removal on the kainate (KA)- and quisqualate (QA)-induced D-[3H]aspartate release with that on KA- and QA-induced 45Ca2+ accumulation. The releasing activity of KA, which was only partially Ca2+ dependent in the presence of Na+, became totally Ca2+ dependent in its absence. Moreover, the releasing activity of QA, which was Ca2+ independent in the presence of Na+, became 50% Ca2+ dependent in the absence of the monovalent cation. The releasing action of both agonists was in all cases antagonized by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and that induced by KA was also sensitive to kynurenic acid. When glutamate was tested as an agonist in the presence of Na+, it was found that its D-[3H]aspartate releasing action was Ca2+ independent and was largely due to heteroexchange. The evoked release was Ca2+ independent, scarcely sensitive to CNQX, and insensitive to NMDA antagonists. In Na(+)-free medium, the glutamate-evoked D-[3H]aspartate release was lower (due to the abolishment of heteroexchange), but was totally Ca2+ dependent and antagonized by CNQX and kynurenate. KA (30 microM-1 mM) stimulated the accumulation of 45Ca2+ in a dose-dependent and CNQX-sensitive way, the effect being progressively higher as the Na+ concentration in the medium was decreased. Li+ affected KA-induced 45Ca2+ accumulation in a way similar to Na+, although 45Ca2+ uptake was somewhat lower in Li(+)-containing medium. The voltage-activated calcium channel antagonists La3+ and (-)-202-791 caused only a limited inhibition of the KA-induced 45Ca2+ influx both in the presence and in the absence of Na+. Under all the conditions tested [presence and absence of Na+ and of (-)-202-791], the kainate-induced 45Ca2+ uptake was scarcely sensitive to the NMDA antagonist 2-amino-5-phosphonovalerate. QA and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid also stimulated 45Ca2+ influx in a CNQX-sensitive way, the effect being enhanced in Na(+)-free media. These agonists were, however, less effective than KA.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Molecular cloning and development analysis of a new glutamate receptor subunit isoform in cerebellum.
The glutamate receptor gene GluR-4 is proposed to generate two spliced isoforms (Sommer et al., 1990). Screening a rat cerebellar cDNA library, we have now identified a third type of transcript derived from GluR-4 gene by differential RNA processing. This transcript encodes a protein with a "flop" module between transmembrane regions 3 and 4, but with a C-terminus segment of 36 amino acids different from the previously described GluR-4 flip/flop cDNAs. This subunit was therefore designated as GluR-4c flop. Transcripts synthesized in vitro from GluR-4c cDNA form kainate/AMPA-activated channels when expressed in Xenopus oocytes. The current-voltage relationship for kainate-evoked responses in oocytes injected with GluR-4c showed strong inward rectification. The different transcripts derived from the GluR-4 gene were studied on Northern blots hybridized with either a cDNA probe or oligonucleotides specific for the GluR-4 flip/flop and C-terminal domains. Three transcripts of 6.2, 4.2, and 3.0 kilobases (kb) derived from the GluR-4 gene were identified on Northern blots containing total RNA prepared from different brain regions, using a cDNA probe or an oligonucleotide corresponding to the N-terminal region common to all transcripts. These transcripts were much more abundant in the cerebellum than in other brain areas, and their levels increased during cerebellar development. The maximal increase was observed between postnatal days 1 and 20, an age corresponding to the division and maturation of granule neurons. The flip/flop and the C-terminal oligonucleotides hybridized to the two higher molecular weight transcripts but did not hybridize to the small RNA. Interestingly, using cerebellar cells that were cultured for up to 12 d, we observed that the three transcripts are present in granule neurons, but that astrocytes only express the 6.2 and the 4.2 kb transcripts. The 3.0 kb transcript accumulates in cerebellar granule cells during development in vitro. Furthermore, in situ hybridization histochemistry revealed that the GluR-4c transcripts are preferentially expressed in cerebellar granule cells and Bergmann glial cells, whereas the expression of GluR-4 flip mRNAs is restricted to Bergmann glial cells. Interestingly, we also show that granule cells already express GluR-4c in the premigratory zone of the external granular layer, indicating that intrinsic or highly localized cues induce GluR-4c expression before these cells reach their final position.
Animals↗
[Oral lichen planus and liver pathology. I. The prevalence of liver damage in a case load of 96 patients with oral lichen planus].
In order to evaluate if oral lichen planus (OLP) may be regarded as a marker of even unknown liver disease, 96 incident OLP cases were screened through anamnestic, laboratory, instrumental investigations and gastroenterology consultation. The frequency of hepatopathies was 23/96 (24%): 7 had cirrhosis, 3 had chronic active hepatitis, 2 had chronic persistent hepatitis, 10 steatosis and 1 had undetermined liver disease. Eleven of these 23 patients (48%) had unknown hepatopathies, although five of them had severe liver disorders (cirrhosis, chronic hepatitis). Forty-four of 73 patients without definite liver disorders (60%) had at least one abnormal liver parameter. This results confirm frequent association of OLP with hepatic damage and moreover it shown that OLP may be an important clinical sign of symptomless hepatopathies.
Adult↗
[Paget's disease: the prospects with ipriflavone].
Paget's disease is a bone disorder characterized by high rates of bone remodelling. We have evaluated the efficacy of the new drug, ipriflavone, which has a double effect on the inhibition of bone reabsorption and on the activation of bone neodeposition. We studied 20 patients with active Paget's disease: 10 have been treated with 600 mg/die and 10 with 1200 mg/die of ipriflavone, for six months. In pharmacological wash-out, we have measured alkaline phosphatase, plasmatic BGP, the urinary hydroxyproline/creatinine ratio and the urinary calcium (Nordin Test). These valuations have been repeated after three and six months from the beginning of the administration of the drug. We have verified a propitious and speedy effect on pain, independent of dosage, and efficacy of treatment in function of bone turn-over parameter changes, by using no parametric statistical tests. In all subjects favourable effects have been found after three months treatment with 1200 mg/die. These have shown a greater efficacy than the lower dosage. After six months treatment we have not found significant differences as regards the efficacy of both dosages. These results may suggest to start therapy with higher initial doses and to carry-on with lower supporting doses. It's necessary to investigate further confirmation regarding the consolidation and perseverance of obtained favourable results, even after interruption of the treatment.
Aged↗
Distant metastases in differentiated thyroid cancer: long-term results of radioiodine treatment and statistical analysis of prognostic factors in 214 patients.
Long-term results and statistical analysis of prognostic factors in a series of 214 patients with distant metastases from differentiated thyroid cancer (DTC) are reported here. These 214 were part of a total series of 1457 patients with DTC referred to our center from 1967 to 1987. All patients underwent surgery and 131-I therapy and were treated with TSH suppressive doses of thyroid hormones. After a mean follow-up of 7.3 years including clinical, scintigraphic, radiological and laboratory investigations, 24.4% of patients were alive without disease, 36.5% alive with disease, 1.8% dead without disease and 37.3% dead with disease. One of the main factors influencing the survival in our series was 131-I uptake (RIU) by metastatic tissue. No case of complete remission of disease was observed among patients with nonfunctioning metastases. Another important factor was the site of metastases, patients with bone metastases having the worst prognosis. The patient's age at diagnosis represented another important factor for survival; patients over 40 years, particularly those over 60 years had a bad prognosis. A clear interrelation was found among the factors advanced age, nonfunctioning metastases and bone metastases. Patients with these last clinical features were considered to be at high risk and generally had a fatal outcome. Another significant prognostic factor revealed by univariate analysis was the histologic type. Patients with follicular tumor showed a poorer prognosis in comparison to papillary tumor. When multivariate analysis was applied, the factors age at diagnosis, site of metastases and RIU proved to have a significant influence on survival, but not the histologic type. Lastly, the relative rate of males was higher in the group of patients with metastases in comparison to the whole series of DTC patients. Despite this, the factor sex did not influence survival.
Adenocarcinoma↗
GABA release triggered by the activation of neuron-like non-NMDA receptors in cultured type 2 astrocytes is carrier-mediated.
Kainate (KA), quisqualate (QA), and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) stimulated gamma-aminobutyric acid [3H]gamma-aminobutyric acid (GABA) release from cultured cerebellar type 2 astrocytes and from their bipotential precursors. The evoked release was prevented by the antagonist 6-cyano-2,3-dihydroxy-7-nitro-quinoxaline (CNQX). AMPA and QA applied together with KA at concentrations around or above their EC50S (20-50 microM) antagonized the stimulatory effect of KA on [3H]GABA release. On the other hand, the releasing action of KA was potentiated by concentrations of QA in the low micromolar range (2-5 microM), particularly when the concentration of KA was at the borderline of effectiveness (10 microM). KA and QA did not elevate intracellular cyclic GMP levels in astrocyte cultures, although guanylate cyclase was present in both type 2 and type 1 astrocytes. The inability of KA to elevate cyclic GMP levels in astrocytes was the only major difference in the behavior of this glutamate agonist between astroglial and neuronal cultures. The GABA transport inhibitor nipecotic acid or replacement of NaCl with LiCl abolished [3H]GABA uptake and also KA- and QA-induced release of preaccumulated [3H]GABA. Therefore, [3H]GABA was released from type 2 astrocytes and their progenitors through its Na(+)-dependent transport system, operating in an outward direction when the cells were depolarized by non-NMDA receptor agonists.
6-Cyano-7-nitroquinoxaline-2,3-dione↗
Neuronal fodrin proteolysis occurs independently of excitatory amino acid-induced neurotoxicity.
In cultured cerebellar granule cells, the total amount of fodrin alpha subunit increased 3-fold between 0 and 10 days in vitro and fodrin mRNA increased 5-fold. The exposure of cerebellar neurons to NMDA induced the accumulation of a 150 kd proteolytic fragment of fodrin. The NMDA-induced breakdown of fodrin was time-, concentration-, and Ca2(+)-dependent and was inhibited by APV, Mg2+, or the calpain I inhibitor N-acetyl-Leu-Leu-norleucinal. Kainate caused fodrin proteolysis through indirect activation of NMDA receptors. Quisqualate was ineffective. The NMDA-induced degradation of fodrin occurred under conditions that did not cause degeneration of cultured cerebellar neurons. These results show that Ca2+/calpain I-dependent proteolysis of fodrin is selectively associated with NMDA receptor activation; however, fodrin proteolysis per se does not play a causal role in NMDA-induced toxicity in cerebellar granule cells.
Animals↗
Release of endogenous and newly synthesized glutamate and of other amino acids induced by non-N-methyl-D-aspartate receptor activation in cerebellar granule cell cultures.
Amino acid release studies were performed by an HPLC procedure using differentiated rat cerebellar granule cell cultures. Kainic acid (KA; 50 microM) caused an increase (about threefold) in the release of endogenous glutamate and a lesser, but statistically significant, increase in the release of glutamine, glycine, threonine, taurine, and alanine. Quisqualic acid (QA) and, to a lesser degree, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) (both 50 microM) enhanced the release of the following amino acids in the order glutamate greater than aspartate greater than or equal to taurine, whereas the release of other amino acids was either unaffected or affected in a statistically nonsignificant way. The release of glutamate induced by KA was partially (43%) Ca2+ dependent. The other release-inducing effects of KA and QA were not Ca2+ dependent. In all cases, the evoked release could be prevented by the non-N-methyl-D-aspartate (non-NMDA) receptor antagonist 6-cyano-2,3-hydroxy-7-nitroquinoxaline, and thus appeared to be receptor mediated. NMDA (5 and 50 microM) had no release-inducing activity. The KA-, QA-, and AMPA-evoked release of newly synthesized [3H]glutamate and [3H]aspartate (formed in the cells exposed to [3H]glutamine) was very similar to the evoked release of endogenous glutamate and aspartate. On the other hand, the release of preloaded D-[3H]aspartate (purified by HPLC in the various fractions analyzed, before radioactivity determination) induced by 50 microM KA was twice as high as that of endogenous glutamate. In the case of high [K+] depolarization, in contrast, the release of preloaded D-[3H]aspartate was approximately 30% lower than that of endogenous glutamate.(ABSTRACT TRUNCATED AT 250 WORDS)
6-Cyano-7-nitroquinoxaline-2,3-dione↗