Gabriele E. M. Biella - Profile on Academia.edu (original) (raw)

Papers by Gabriele E. M. Biella

The descending inhibitory pathways. Their role in analgesia, after consideration of specific spinal adrenergic involvement

PubMed, 1989

The four main descending pathways - from the cortex, the diencephalon, the mesencephalon and the ... more The four main descending pathways - from the cortex, the diencephalon, the mesencephalon and the pontobulbar structures - are briefly examined with regard to their role as regulatory systems with an overall inhibitory action processing the afferents to the spinal cord. Sketches are given of the possible analgesic properties in the selective gating of C and Ad nociceptive afferences. The involvement of neuronal subpopulations in the spinal cord presenting alpha-2 and alpha-1 receptors, their hypothetic role in certain reactive analgesic processes, and their coactivation are mentioned briefly.

Effects of tenoxicam on nociceptive thalamic neuronal firing in arthritic rats

PubMed, 1987

The antinociceptive action of tenoxicam, a new non-steroidal anti-inflammatory drug, has been inv... more The antinociceptive action of tenoxicam, a new non-steroidal anti-inflammatory drug, has been investigated by exploring the spontaneous and evoked electrophysiological patterns of firing of thalamic neurons in arthritic rats. A marked decrease in the firing activity evoked by ankle mobilization has been found to be present at doses of tenoxicam of 0.6 mg/kg i.v. A similar effect is obtainable with aspirin (as reference drug) but with doses of 54 mg/kg i.v. On studying the effects of increasing doses of tenoxicam a progressively longer time-course inhibition has been found and the analysis confirmed a linear correlation. Findings are discussed postulating that the final antinociceptive effect of tenoxicam can be correlated with its anti-inflammatory activity.

Frontiers in Human Neuroscience, 2012

We analyzed rest tremor, one of the etiologically most elusive hallmarks of Parkinson disease (PD... more We analyzed rest tremor, one of the etiologically most elusive hallmarks of Parkinson disease (PD), in 12 consecutive PD patients during a specific task activating the locus coeruleus (LC) to investigate a putative role of noradrenaline (NA) in tremor generation and suppression. Clinical diagnosis was confirmed in all subjects by reduced dopamine reuptake transporter (DAT) binding values investigated by single photon computed tomography imaging (SPECT) with [ 123 I] N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) tropane (FP-CIT). The intensity of tremor (i.e., the power of Electromyography [EMG] signals), but not its frequency, significantly increased during the task. In six subjects, tremor appeared selectively during the task. In a second part of the study, we retrospectively reviewed SPECT with FP-CIT data and confirmed the lack of correlation between dopaminergic loss and tremor by comparing DAT binding values of 82 PD subjects with bilateral tremor (n = 27), unilateral tremor (n = 22), and no tremor (n = 33). This study suggests a role of the LC in Parkinson tremor.

Evaluation of three quinoline-carboxamide derivatives as potential radioligands for the in vivo pet imaging of neurodegeneration

Neurochemistry International, May 1, 2004

The peripheral-type benzodiazepine receptors (PBRs) are only minimally expressed in normal brain ... more The peripheral-type benzodiazepine receptors (PBRs) are only minimally expressed in normal brain parenchyma, where they are primarily localized in glial cells. Their basal expression rises in different neurodegenerative disorders, due to the presence of infiltrating inflammatory cells and activated microglia. [11C]PK11195, a selective PBR antagonist, has been used for the in vivo PET monitoring of neurodegeneration in clinical observations. We recently developed and labeled with carbon-11 three new carboxamide derivatives: [11C]VC193M, [11C]VC195 and [11C]VC198M. Aim of this study was to evaluate these ligands for the in vivo measuring of PBRs expression in neurodegenerations and compare their kinetic behavior with that of the reference tracer [11C]PK11195. Radioligands were evaluated in a preclinical model of Huntington's disease consisting in the monolateral striatal injection of quinolinic acid (QA). Activated microglia and astrocytic gliosis was present only within the affected striatum. A concomitant increase in radioactivity accumulation was observed for all the tracers examined (P<0.01). Among the new compounds, [11C]VC195 showed higher levels of lesioned/unlesioned striatum ratios (3.28+/-0.44), in comparison with [11C]VC193M and [11C]VC198M (2.69+/-0.53 and 1.52+/-0.36, respectively), but slightly inferior to that observed for [11C]PK11195 (3.76+/-1.41).In conclusion, the results of the study indicate that [11C]VC195 is a promising candidate for in vivo PET monitoring of neurodegenerative processes but its in vivo behavior overlap that of [11C]PK11195.

Where thought lives: place or palace?

Springer eBooks, 2002

... Author Index Acernese F 165 Apolloni B 301 Aversano G 178 Barone F 165 BastiG 313 Bertoni A 8... more ... Author Index Acernese F 165 Apolloni B 301 Aversano G 178 Barone F 165 BastiG 313 Bertoni A 87 Bianchini M 96 Biella GEM 328 Bisio GM ... 187 Ferrari-Trecate G 114 Fiori S 63 Frattale Mascioli FM 23 Fruhwirth M 228 Funaro M 187 GaitoS 301 Gers FA 193 Giordano F 201 ...

PLOS ONE, Jan 28, 2009

This research focuses on the extraction yield and composition of essential oil obtained from Kore... more This research focuses on the extraction yield and composition of essential oil obtained from Korean orange peel waste by using supercritical CO 2 extraction method. Various parameters were observed, such as temperature, pressure, particle size, and co-solvent participation. The result showed that the extraction yield increased at high pressure, low temperature, and small particle size. The high pressure increased CO 2 density which leads to high solvating power while low temperature increased the solubility of terpenes and small particle size enables the CO 2 molecules to spread widely and penetrate deeply on the orange peel, reducing its mass transfer resistance. Gas chromatography (GC) was conducted to observe the compounds inside the essential oil and the result showed that terpenes (monoterpenes and sesquiterpenes) and other compounds (alcohol, esters, ketones) were present. Limonene, as the main compound in the essential oil, was mostly extracted at 40 o C and 100-200 bar, with the yield ranges from 0.7-1.0% (w/w). Ethanol was used as co-solvent and proven to increase the yield of essential oil by 1.4 times.

Paclitaxel alters angiogenesis in the peripheral and central nervous system of neuropathic rats

74 Congresso della Società Italiana di Anatomia ed Istologia, 2021

Monte Carlo simulation of near-infrared light propagation in a realistic, three-dimensional human head and brain model

Cefoperazone pharmacokinetics and sputum levels after single/multiple i.m. injections in bronchopneumopathic patients and bone, pulmonary and prostatic tissue penetration

PubMed, 1983

Cefoperazone is a third-generation semisynthetic injectable cephalosporin. It has been reported t... more Cefoperazone is a third-generation semisynthetic injectable cephalosporin. It has been reported that cefoperazone has beta-lactamase resistance and quite a broad antimicrobial spectrum against many Gram-positive and Gram-negative microorganisms and most anaerobes. In this study, the pharmacokinetics of cefoperazone were examined in a group of 10 patients suffering from acute exacerbations of chronic bronchitis, with purulent or mucopurulent expectorations. Cefoperazone was administered at the dose of 1 g i.m. every 12 hours. Serum and urinary parameters and the profile of bronchial mucus diffusion were assessed after the first administration and during the whole period of treatment which lasted for 7 days. In a second, third, and fourth group of volunteer patients who had to undergo surgical operations, bone, lung and prostatic penetration of cefoperazone was determined in correlation with serum levels.

Evaluation of domifen bromide in the treatment of acute infectious oral diseases

PubMed, 1983

By means of a double blind, placebo controlled trial, we have studied 29 patients (14 M and 15 F)... more By means of a double blind, placebo controlled trial, we have studied 29 patients (14 M and 15 F) affected by different acute infectious oral diseases. Our results suggest that domifen bromide may be useful in treating infectious oral diseases in combination with antibiotics, and in relieving pain and inflammation.

Comparative study on the electrophysiological responses at thalamic level to different analgesic peptides

PubMed, 1985

Using electrophysiological methods to detect the extracellular activity of single neurons in the ... more Using electrophysiological methods to detect the extracellular activity of single neurons in the thalamus of anaesthetized rats, their response to mechanical and thermal noxious stimuli were assessed before and after administration of 4 analgesic peptides of various types. Dermophin, a peptide extracted from frog's skin, was found to have an opioid-like antinociceptive activity antagonized by naloxone. Caerulein, which has a similar origin, failed to suppress the nociceptive responses of thalamic neurons evoked by peripheral stimuli. Calcitonin, a peptide found at brain level, induced an alteration of the increased firing characteristic of noxious stimuli, and its action was not reversed by naloxone. FK 33-824, a synthetic peptide, induced a morphine-like action when injected i.c.v. at a dosage 1000 times lower than that of morphine on a molar basis. It is concluded that electrophysiological investigations on peptides endowed with analgesic activity contribute greatly to a more precise profile of the peptides as candidate drugs in pain control.

Pharmacokinetics and sputum levels of josamycin after single and multiple administrations in bronchopneumopathic patients

PubMed, 1983

Josamycin is a new macrolide antibiotic with low toxicity and effective therapeutic activity in m... more Josamycin is a new macrolide antibiotic with low toxicity and effective therapeutic activity in many bacterial diseases, particularly bronchopulmonary infections. In the present study the pharmacokinetics of josamycin were investigated in a group of 10 patients suffering from acute exacerbation of chronic bronchitis, with purulent or mucopurulent expectoration. Patients were given one oral administration of 1 g of josamycin every 12 hours for seven days. Serum, urinary parameters and the profile of bronchial mucus diffusion were assessed after the first and the last administration.

Eseroline depresses the responses of dorsal horn neurons to C-fiber afferents in the spinal rat

Neuroscience Letters, Oct 1, 1986

Eseroline not only has some structural features in common with morphine but also has a specific a... more Eseroline not only has some structural features in common with morphine but also has a specific antinociceptive action like opioid drugs. The effects of eseroline on the responses of rat dorsal horn lamina V neurons to C-fiber-related noxious stimuli were investigated. The data obtained showed that 15 min after eseroline administration, the neuronal responses to C-fiber-related afferents were almost totally suppressed. Morphine was used as reference drug. The postulated action of eseroline on opioid receptors was confirmed by reversal of eseroline-driven cell activity after naloxone injection.

Effect of Melatonin on Sleep Microstructure: Preliminary Results in Healthy Subjects

Sleep, Dec 1, 1993

The ability of melatonin (MLT) to potentiate the effects of gamma-aminobutyric acid and the benzo... more The ability of melatonin (MLT) to potentiate the effects of gamma-aminobutyric acid and the benzodiazepines has been demonstrated repeatedly in animal models, and recent experimental data favored the hypothesis that MLT, given together with threshold doses of benzodiazepines, could significantly improve the quality of sleep. This preliminary study was designed to compare the effects of MLT (100 mg) with those of a benzodiazepine hypnotic [triazolam (TRI) 0.125 mg] and to explore the effects of a combination of MLT and TRI at a low dose in healthy volunteers. No significant changes in the classical polysomnographic variables were observed following MLT, TRI and MLT + TRI, whereas MLT and especially MLT + TRI resulted in significant modulation of some microstructural parameters. These changes were paralleled by ameliorated subjective sleep quality. A combination of MLT and low benzodiazepine doses could avoid the residual, dose-related benzodiazepine effects.

Regulatory Peptides, Aug 1, 1987

The effects of synthetic human calcitonin gene-related peptide (CGRP) on nociceptive response wer... more The effects of synthetic human calcitonin gene-related peptide (CGRP) on nociceptive response were evaluated in rats by two behavioral tests (tail-flick and hotplate) and by electrophysiological recording of the firing of thalamic neurons evoked by peripheral noxious mechanical stimuli. CGRP was administered intracerebroventricularly (i.c.v.) and its effects were compared with that of salmon calcitonin (sCT). In the tail-flick test, CGRP (0.25, 2.5 and 5/~g/rat) dose-dependently increased response latencies, whereas sCT (0.125, 2.5, 5 and 10/~g/rat) did not. Conversely, in the hot-plate test CGRP was effective in enhancing response latencies only at the highest dose of 10/~g/rat, while sCT (0.125, 0.25 and 2.5 pg/rat) inhibited the hotplate response dose-dependently. In electrophysiological studies, CGRP (2.5/~g/rat, i.c.v.) completely inhibited the evoked neuronal thalamic firing and the same dose of sCT induced only a partial reduction. Furthermore, the antinociceptive effects of CGRP in the tail-flick test and in the electrophysiological studies were not prevented by naloxone. These results demonstrate that central administration of CGRP is effective in inhibiting nociceptive responses and its action like that of sCT does not involve an opioid mechanism. The differences in the antinociceptive profiles of CGRP and sCT suggest that the inhibitory effects of these peptides may involve different neuronal pathways.

Brain Research, Mar 1, 1984

Eseroline is a new agent, derived from physostigmine but lacking in pseudocholinesterase activity... more Eseroline is a new agent, derived from physostigmine but lacking in pseudocholinesterase activity, that possesses opioid properties in vivo and in vitro in cats and rodents. The electrophysiological effect of this drug has been investigated. Our findings show that Eseroline (5 mg/kg i.p.), suppresses the nociceptive responses evoked by noxious (mechanical and thermal) stimuli, without affecting the spontaneous firing of neurons in the thalamus of anesthetized rat. This effect starts about 5 rain after the administration and lasts on average for about 60 min. Naloxone (1 mg/kg i.p.), injected 10 min before Eseroline, antagonized the antinociceptive action of this drug.

Dermorphin, a new peptide from amphibian skin, inhibits the nociceptive thalamic neurons firing rate evoked by noxious stimuli

Neuroscience Letters, Nov 1, 1984

Depressant effects of suprofen, a new non-steroidal anti-inflammatory drug on thalamic evoked neuronal firing in arthritic rats

Neuropharmacology, Sep 1, 1986

The effects of suprofen, a new non-steroidal anti-inflammatory drug, (NSAID), the activity of whi... more The effects of suprofen, a new non-steroidal anti-inflammatory drug, (NSAID), the activity of which is mainly antinociceptive, were compared with those of aspirin (as a reference drug) in a study of spontaneous and evoked firing of thalamic neurons (nucleus lateralis and ventrobasalis) in rats rendered arthritic by injection of Freund's adjuvant into the paw. Suprofen (3.7 mg/kg, i.v.) induced a marked decrease in the firing evoked in arthritic rats by ankle mobilization. This effect, after a rapid onset, lasted on the average for 60 min. A similar effect was obtained with aspirin, but with 54 mg/kg (i.v.) (14 times more than suprofen). With increasing doses of suprofen, it was possible to obtain an increased long-lasting inhibition of the evoked activity, with a significant dose-effect linear regression. The possibility that there are both CNS and peripheral effects of suprofen is discussed in relation to the possible role of aspirin (the reference standard for NSAIDs) in enhancing presynaptic inhibition, thus reducing the effectiveness of incoming sensory stimuli.

Melatonin signal transduction and mechanism of action in the central nervous system: using the rabbit cortex as a model

Endocrinology, 1992

The cortex of the rabbit (Oryctolagus cuniculus) is rich in melatonin binding sites, and particul... more The cortex of the rabbit (Oryctolagus cuniculus) is rich in melatonin binding sites, and particularly abundant is the parietal cortex. Consequently, we characterized the putative melatonin receptor in the parietal cortex by a series of in vitro ligand-receptor binding experiments and biochemical and electrophysiological studies. The in vitro saturation and competition experiments demonstrated that the binding in the crude cortical membrane preparations was of high affinity and specificity. Guanine nucleotides (GDP, GTP, and GTP gamma S) inhibited the specific 2-[125I]iodomelatonin binding in a dose-dependent manner. Coincubation with a nonhydrolyzable GTP analog provoked a shift in the binding affinity; the numerical values of the Kd increased from 20-30 to 200-600 pM. Melatonin, in nanomolar concentrations, was able to inhibit the forskolin-stimulated accumulation of cAMP in parietal cortex explants, and preincubation with pertussis toxin counteracted this effect of melatonin. Apparently, the melatonin binding site in the rabbit parietal cortex is linked to its second messenger via a pertussis toxin-sensitive G-protein, probably of the inhibitory Gi class, similar to what has been described for different parts of the brain of other vertebrates. The experiments on the spontaneous firing activity of single neurons in the third to fourth layer of the parietal cortex in anesthetized animals showed that melatonin and its potent agonist 2-iodomelatonin exhibited gamma-aminobutyric acid (GABA)-like effects and were able alone, in nanomolar concentrations, to significantly slow the neuronal firing activity. Moreover, both melatonin and 2-iodomelatonin potentiated the effect of GABA on the neuronal activity, leading to powerful inhibition of the tested neurons. Undoubtedly, the binding site in the rabbit parietal cortex possesses all of the characteristics of a functional receptor. We suggest that melatonin is involved in the control of fundamental cortical functions and that it acts in concert with GABA, one of the two major inhibitory neurotransmitters in the central nervous system.

The descending inhibitory pathways. Their role in analgesia, after consideration of specific spinal adrenergic involvement

PubMed, 1989

The four main descending pathways - from the cortex, the diencephalon, the mesencephalon and the ... more The four main descending pathways - from the cortex, the diencephalon, the mesencephalon and the pontobulbar structures - are briefly examined with regard to their role as regulatory systems with an overall inhibitory action processing the afferents to the spinal cord. Sketches are given of the possible analgesic properties in the selective gating of C and Ad nociceptive afferences. The involvement of neuronal subpopulations in the spinal cord presenting alpha-2 and alpha-1 receptors, their hypothetic role in certain reactive analgesic processes, and their coactivation are mentioned briefly.

Effects of tenoxicam on nociceptive thalamic neuronal firing in arthritic rats

PubMed, 1987

The antinociceptive action of tenoxicam, a new non-steroidal anti-inflammatory drug, has been inv... more The antinociceptive action of tenoxicam, a new non-steroidal anti-inflammatory drug, has been investigated by exploring the spontaneous and evoked electrophysiological patterns of firing of thalamic neurons in arthritic rats. A marked decrease in the firing activity evoked by ankle mobilization has been found to be present at doses of tenoxicam of 0.6 mg/kg i.v. A similar effect is obtainable with aspirin (as reference drug) but with doses of 54 mg/kg i.v. On studying the effects of increasing doses of tenoxicam a progressively longer time-course inhibition has been found and the analysis confirmed a linear correlation. Findings are discussed postulating that the final antinociceptive effect of tenoxicam can be correlated with its anti-inflammatory activity.

Frontiers in Human Neuroscience, 2012

We analyzed rest tremor, one of the etiologically most elusive hallmarks of Parkinson disease (PD... more We analyzed rest tremor, one of the etiologically most elusive hallmarks of Parkinson disease (PD), in 12 consecutive PD patients during a specific task activating the locus coeruleus (LC) to investigate a putative role of noradrenaline (NA) in tremor generation and suppression. Clinical diagnosis was confirmed in all subjects by reduced dopamine reuptake transporter (DAT) binding values investigated by single photon computed tomography imaging (SPECT) with [ 123 I] N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) tropane (FP-CIT). The intensity of tremor (i.e., the power of Electromyography [EMG] signals), but not its frequency, significantly increased during the task. In six subjects, tremor appeared selectively during the task. In a second part of the study, we retrospectively reviewed SPECT with FP-CIT data and confirmed the lack of correlation between dopaminergic loss and tremor by comparing DAT binding values of 82 PD subjects with bilateral tremor (n = 27), unilateral tremor (n = 22), and no tremor (n = 33). This study suggests a role of the LC in Parkinson tremor.

Evaluation of three quinoline-carboxamide derivatives as potential radioligands for the in vivo pet imaging of neurodegeneration

Neurochemistry International, May 1, 2004

The peripheral-type benzodiazepine receptors (PBRs) are only minimally expressed in normal brain ... more The peripheral-type benzodiazepine receptors (PBRs) are only minimally expressed in normal brain parenchyma, where they are primarily localized in glial cells. Their basal expression rises in different neurodegenerative disorders, due to the presence of infiltrating inflammatory cells and activated microglia. [11C]PK11195, a selective PBR antagonist, has been used for the in vivo PET monitoring of neurodegeneration in clinical observations. We recently developed and labeled with carbon-11 three new carboxamide derivatives: [11C]VC193M, [11C]VC195 and [11C]VC198M. Aim of this study was to evaluate these ligands for the in vivo measuring of PBRs expression in neurodegenerations and compare their kinetic behavior with that of the reference tracer [11C]PK11195. Radioligands were evaluated in a preclinical model of Huntington's disease consisting in the monolateral striatal injection of quinolinic acid (QA). Activated microglia and astrocytic gliosis was present only within the affected striatum. A concomitant increase in radioactivity accumulation was observed for all the tracers examined (P<0.01). Among the new compounds, [11C]VC195 showed higher levels of lesioned/unlesioned striatum ratios (3.28+/-0.44), in comparison with [11C]VC193M and [11C]VC198M (2.69+/-0.53 and 1.52+/-0.36, respectively), but slightly inferior to that observed for [11C]PK11195 (3.76+/-1.41).In conclusion, the results of the study indicate that [11C]VC195 is a promising candidate for in vivo PET monitoring of neurodegenerative processes but its in vivo behavior overlap that of [11C]PK11195.

Where thought lives: place or palace?

Springer eBooks, 2002

... Author Index Acernese F 165 Apolloni B 301 Aversano G 178 Barone F 165 BastiG 313 Bertoni A 8... more ... Author Index Acernese F 165 Apolloni B 301 Aversano G 178 Barone F 165 BastiG 313 Bertoni A 87 Bianchini M 96 Biella GEM 328 Bisio GM ... 187 Ferrari-Trecate G 114 Fiori S 63 Frattale Mascioli FM 23 Fruhwirth M 228 Funaro M 187 GaitoS 301 Gers FA 193 Giordano F 201 ...

PLOS ONE, Jan 28, 2009

This research focuses on the extraction yield and composition of essential oil obtained from Kore... more This research focuses on the extraction yield and composition of essential oil obtained from Korean orange peel waste by using supercritical CO 2 extraction method. Various parameters were observed, such as temperature, pressure, particle size, and co-solvent participation. The result showed that the extraction yield increased at high pressure, low temperature, and small particle size. The high pressure increased CO 2 density which leads to high solvating power while low temperature increased the solubility of terpenes and small particle size enables the CO 2 molecules to spread widely and penetrate deeply on the orange peel, reducing its mass transfer resistance. Gas chromatography (GC) was conducted to observe the compounds inside the essential oil and the result showed that terpenes (monoterpenes and sesquiterpenes) and other compounds (alcohol, esters, ketones) were present. Limonene, as the main compound in the essential oil, was mostly extracted at 40 o C and 100-200 bar, with the yield ranges from 0.7-1.0% (w/w). Ethanol was used as co-solvent and proven to increase the yield of essential oil by 1.4 times.

Paclitaxel alters angiogenesis in the peripheral and central nervous system of neuropathic rats

74 Congresso della Società Italiana di Anatomia ed Istologia, 2021

Monte Carlo simulation of near-infrared light propagation in a realistic, three-dimensional human head and brain model

Cefoperazone pharmacokinetics and sputum levels after single/multiple i.m. injections in bronchopneumopathic patients and bone, pulmonary and prostatic tissue penetration

PubMed, 1983

Cefoperazone is a third-generation semisynthetic injectable cephalosporin. It has been reported t... more Cefoperazone is a third-generation semisynthetic injectable cephalosporin. It has been reported that cefoperazone has beta-lactamase resistance and quite a broad antimicrobial spectrum against many Gram-positive and Gram-negative microorganisms and most anaerobes. In this study, the pharmacokinetics of cefoperazone were examined in a group of 10 patients suffering from acute exacerbations of chronic bronchitis, with purulent or mucopurulent expectorations. Cefoperazone was administered at the dose of 1 g i.m. every 12 hours. Serum and urinary parameters and the profile of bronchial mucus diffusion were assessed after the first administration and during the whole period of treatment which lasted for 7 days. In a second, third, and fourth group of volunteer patients who had to undergo surgical operations, bone, lung and prostatic penetration of cefoperazone was determined in correlation with serum levels.

Evaluation of domifen bromide in the treatment of acute infectious oral diseases

PubMed, 1983

By means of a double blind, placebo controlled trial, we have studied 29 patients (14 M and 15 F)... more By means of a double blind, placebo controlled trial, we have studied 29 patients (14 M and 15 F) affected by different acute infectious oral diseases. Our results suggest that domifen bromide may be useful in treating infectious oral diseases in combination with antibiotics, and in relieving pain and inflammation.

Comparative study on the electrophysiological responses at thalamic level to different analgesic peptides

PubMed, 1985

Using electrophysiological methods to detect the extracellular activity of single neurons in the ... more Using electrophysiological methods to detect the extracellular activity of single neurons in the thalamus of anaesthetized rats, their response to mechanical and thermal noxious stimuli were assessed before and after administration of 4 analgesic peptides of various types. Dermophin, a peptide extracted from frog's skin, was found to have an opioid-like antinociceptive activity antagonized by naloxone. Caerulein, which has a similar origin, failed to suppress the nociceptive responses of thalamic neurons evoked by peripheral stimuli. Calcitonin, a peptide found at brain level, induced an alteration of the increased firing characteristic of noxious stimuli, and its action was not reversed by naloxone. FK 33-824, a synthetic peptide, induced a morphine-like action when injected i.c.v. at a dosage 1000 times lower than that of morphine on a molar basis. It is concluded that electrophysiological investigations on peptides endowed with analgesic activity contribute greatly to a more precise profile of the peptides as candidate drugs in pain control.

Pharmacokinetics and sputum levels of josamycin after single and multiple administrations in bronchopneumopathic patients

PubMed, 1983

Josamycin is a new macrolide antibiotic with low toxicity and effective therapeutic activity in m... more Josamycin is a new macrolide antibiotic with low toxicity and effective therapeutic activity in many bacterial diseases, particularly bronchopulmonary infections. In the present study the pharmacokinetics of josamycin were investigated in a group of 10 patients suffering from acute exacerbation of chronic bronchitis, with purulent or mucopurulent expectoration. Patients were given one oral administration of 1 g of josamycin every 12 hours for seven days. Serum, urinary parameters and the profile of bronchial mucus diffusion were assessed after the first and the last administration.

Eseroline depresses the responses of dorsal horn neurons to C-fiber afferents in the spinal rat

Neuroscience Letters, Oct 1, 1986

Eseroline not only has some structural features in common with morphine but also has a specific a... more Eseroline not only has some structural features in common with morphine but also has a specific antinociceptive action like opioid drugs. The effects of eseroline on the responses of rat dorsal horn lamina V neurons to C-fiber-related noxious stimuli were investigated. The data obtained showed that 15 min after eseroline administration, the neuronal responses to C-fiber-related afferents were almost totally suppressed. Morphine was used as reference drug. The postulated action of eseroline on opioid receptors was confirmed by reversal of eseroline-driven cell activity after naloxone injection.

Effect of Melatonin on Sleep Microstructure: Preliminary Results in Healthy Subjects

Sleep, Dec 1, 1993

The ability of melatonin (MLT) to potentiate the effects of gamma-aminobutyric acid and the benzo... more The ability of melatonin (MLT) to potentiate the effects of gamma-aminobutyric acid and the benzodiazepines has been demonstrated repeatedly in animal models, and recent experimental data favored the hypothesis that MLT, given together with threshold doses of benzodiazepines, could significantly improve the quality of sleep. This preliminary study was designed to compare the effects of MLT (100 mg) with those of a benzodiazepine hypnotic [triazolam (TRI) 0.125 mg] and to explore the effects of a combination of MLT and TRI at a low dose in healthy volunteers. No significant changes in the classical polysomnographic variables were observed following MLT, TRI and MLT + TRI, whereas MLT and especially MLT + TRI resulted in significant modulation of some microstructural parameters. These changes were paralleled by ameliorated subjective sleep quality. A combination of MLT and low benzodiazepine doses could avoid the residual, dose-related benzodiazepine effects.

Regulatory Peptides, Aug 1, 1987

The effects of synthetic human calcitonin gene-related peptide (CGRP) on nociceptive response wer... more The effects of synthetic human calcitonin gene-related peptide (CGRP) on nociceptive response were evaluated in rats by two behavioral tests (tail-flick and hotplate) and by electrophysiological recording of the firing of thalamic neurons evoked by peripheral noxious mechanical stimuli. CGRP was administered intracerebroventricularly (i.c.v.) and its effects were compared with that of salmon calcitonin (sCT). In the tail-flick test, CGRP (0.25, 2.5 and 5/~g/rat) dose-dependently increased response latencies, whereas sCT (0.125, 2.5, 5 and 10/~g/rat) did not. Conversely, in the hot-plate test CGRP was effective in enhancing response latencies only at the highest dose of 10/~g/rat, while sCT (0.125, 0.25 and 2.5 pg/rat) inhibited the hotplate response dose-dependently. In electrophysiological studies, CGRP (2.5/~g/rat, i.c.v.) completely inhibited the evoked neuronal thalamic firing and the same dose of sCT induced only a partial reduction. Furthermore, the antinociceptive effects of CGRP in the tail-flick test and in the electrophysiological studies were not prevented by naloxone. These results demonstrate that central administration of CGRP is effective in inhibiting nociceptive responses and its action like that of sCT does not involve an opioid mechanism. The differences in the antinociceptive profiles of CGRP and sCT suggest that the inhibitory effects of these peptides may involve different neuronal pathways.

Brain Research, Mar 1, 1984

Eseroline is a new agent, derived from physostigmine but lacking in pseudocholinesterase activity... more Eseroline is a new agent, derived from physostigmine but lacking in pseudocholinesterase activity, that possesses opioid properties in vivo and in vitro in cats and rodents. The electrophysiological effect of this drug has been investigated. Our findings show that Eseroline (5 mg/kg i.p.), suppresses the nociceptive responses evoked by noxious (mechanical and thermal) stimuli, without affecting the spontaneous firing of neurons in the thalamus of anesthetized rat. This effect starts about 5 rain after the administration and lasts on average for about 60 min. Naloxone (1 mg/kg i.p.), injected 10 min before Eseroline, antagonized the antinociceptive action of this drug.

Dermorphin, a new peptide from amphibian skin, inhibits the nociceptive thalamic neurons firing rate evoked by noxious stimuli

Neuroscience Letters, Nov 1, 1984

Depressant effects of suprofen, a new non-steroidal anti-inflammatory drug on thalamic evoked neuronal firing in arthritic rats

Neuropharmacology, Sep 1, 1986

The effects of suprofen, a new non-steroidal anti-inflammatory drug, (NSAID), the activity of whi... more The effects of suprofen, a new non-steroidal anti-inflammatory drug, (NSAID), the activity of which is mainly antinociceptive, were compared with those of aspirin (as a reference drug) in a study of spontaneous and evoked firing of thalamic neurons (nucleus lateralis and ventrobasalis) in rats rendered arthritic by injection of Freund's adjuvant into the paw. Suprofen (3.7 mg/kg, i.v.) induced a marked decrease in the firing evoked in arthritic rats by ankle mobilization. This effect, after a rapid onset, lasted on the average for 60 min. A similar effect was obtained with aspirin, but with 54 mg/kg (i.v.) (14 times more than suprofen). With increasing doses of suprofen, it was possible to obtain an increased long-lasting inhibition of the evoked activity, with a significant dose-effect linear regression. The possibility that there are both CNS and peripheral effects of suprofen is discussed in relation to the possible role of aspirin (the reference standard for NSAIDs) in enhancing presynaptic inhibition, thus reducing the effectiveness of incoming sensory stimuli.

Melatonin signal transduction and mechanism of action in the central nervous system: using the rabbit cortex as a model

Endocrinology, 1992

The cortex of the rabbit (Oryctolagus cuniculus) is rich in melatonin binding sites, and particul... more The cortex of the rabbit (Oryctolagus cuniculus) is rich in melatonin binding sites, and particularly abundant is the parietal cortex. Consequently, we characterized the putative melatonin receptor in the parietal cortex by a series of in vitro ligand-receptor binding experiments and biochemical and electrophysiological studies. The in vitro saturation and competition experiments demonstrated that the binding in the crude cortical membrane preparations was of high affinity and specificity. Guanine nucleotides (GDP, GTP, and GTP gamma S) inhibited the specific 2-[125I]iodomelatonin binding in a dose-dependent manner. Coincubation with a nonhydrolyzable GTP analog provoked a shift in the binding affinity; the numerical values of the Kd increased from 20-30 to 200-600 pM. Melatonin, in nanomolar concentrations, was able to inhibit the forskolin-stimulated accumulation of cAMP in parietal cortex explants, and preincubation with pertussis toxin counteracted this effect of melatonin. Apparently, the melatonin binding site in the rabbit parietal cortex is linked to its second messenger via a pertussis toxin-sensitive G-protein, probably of the inhibitory Gi class, similar to what has been described for different parts of the brain of other vertebrates. The experiments on the spontaneous firing activity of single neurons in the third to fourth layer of the parietal cortex in anesthetized animals showed that melatonin and its potent agonist 2-iodomelatonin exhibited gamma-aminobutyric acid (GABA)-like effects and were able alone, in nanomolar concentrations, to significantly slow the neuronal firing activity. Moreover, both melatonin and 2-iodomelatonin potentiated the effect of GABA on the neuronal activity, leading to powerful inhibition of the tested neurons. Undoubtedly, the binding site in the rabbit parietal cortex possesses all of the characteristics of a functional receptor. We suggest that melatonin is involved in the control of fundamental cortical functions and that it acts in concert with GABA, one of the two major inhibitory neurotransmitters in the central nervous system.