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Biomedical subjects

L Betti

Publications and source records attributed to L Betti.

At least 19 recordsLinked to original sources
PubMed2006

Peripheral benzodiazepine receptors on platelets of fibromyalgic patients.

OBJECTIVE: The aim of the present study was to analyze if alterations of peripheral-type benzodiazepine receptor (PBR) characteristics occurred in platelet membranes of patients affected by primary fibromyalgia (FM). DESIGN AND METHODS: Platelets were obtained from 30 patients with FM. Evaluation of kinetic parameters of PBR was performed using [(3)H] PK11195 as specific radioligand compared with 16 healthy volunteers. RESULTS: The results showed a significant increase of PBR binding sites value in platelet membranes from FM patients (B(max) was 5366+/-188 fmol/mg vs. controls, 4193+/-341 fmol/mg, mean+/-SEM) (**p<0.01) but not for affinity value (K(d) was 4.90+/-0.39 nM vs. controls, 4.74+/-0.39 nM, mean+/-SEM) (p>0.05). Symptom severity scores (pain and tiredness) were positively correlated with B(max). CONCLUSIONS: Our results showed an up-regulation of PBR in platelets of FM patients, and this seems to be related to the severity of fibromyalgic symptoms.

Blood Platelets↗
PubMed2006

Common alterations in the serotonin transporter in platelets and lymphocytes of psychotic patients.

INTRODUCTION: Given the controversial data concerning the role of the serotonin (5-HT) transporter in psychosis, our study was aimed to investigate this structure by means of the measurements of the re-uptake kinetics and of the protein density, in both platelets and lymphocytes of 25 out- and inpatients with different psychotic disorders. METHODS: Diagnoses, according to DSM-IV criteria, were bipolar 1 disorders with mood incongruent psychotic features (14), mixed states (7) and schizophrenia (4). Twenty-five matched healthy subjects were also selected as the control group. Platelet and lymphocyte membranes were prepared according to standardized protocols, as were the [3H]5HT re-uptake and [3H]paroxetine ([3H]Par) binding. RESULTS: The results of this study showed a decreased density of the [3H]Par binding sites coupled with a reduced velocity of [3H]5-HT re-uptake in both platelets and lymphocytes of psychotic patients, as compared with healthy control subjects. CONCLUSION: These findings would suggest a general abnormality of the 5-HT system in psychotic patients, probably not confined only to the brain.

Adult↗
PubMed2004

In vitro effects of lead ions on peripheral benzodiazepine receptors and adenylyl cyclase activity in the mantle of Mytilus galloprovincialis.

As an extension of our previous work, where the density of peripheral benzodiazepine receptors (PBR) increased in mantle mitochondria of the marine mollusk Mytilus galloprovincialis Lmk. under chronic exposure to lead, the present study investigates the in vitro effects of an exogenous source of lead ions on PBR and on adenylyl cyclase (AC) complex in mantle membranes of mussels collected from a non-polluted coastal area. PBR binding experiments used the specific isoquinoline carboxamide derivative [3H]PK 11195, and AC activity was measured using a modified procedure adapted to M. galloprovincialis. Lead ions (Pb2+) dose-dependently decreased either the [3H]PK 11195 specific binding in mitochondria or basal AC velocity in plasma membranes of mussel mantle. The IC50 values for lead ions were 10 microM with [3H]PK 11195 binding and 25 microM with AC activity, with maximal inhibition values of 60% and 70%, respectively. Moreover, lead behaved as a non-competitive inhibitor on [3H]PK 11195 binding and as a 'mixed' inhibitor on AC activity. The present results suggest that some of the early effects induced by lead in mussel cell metabolism consist in significant changes of the PBR density and cyclic AMP production in the mantle of M. galloprovincialis.

Adenylyl Cyclases↗
PubMed2003

Effects of homeopathic arsenic on tobacco plant resistance to tobacco mosaic virus. Theoretical suggestions about system variability, based on a large experimental data set.

CONTEXT: This research aimed at verifying the efficacy of homeopathic treatments by plant-based bioassays, which may be suitable for basic research, because they lack placebo effects and provide large datasets for statistical analyses. OBJECTIVE: To evaluate the effects of homeopathic treatments of arsenic trioxide (As2O3) on tobacco plants subjected to tobacco mosaic virus (TMV) inoculation as biotic stress. DESIGN: Blind, randomized experiment using tobacco leaf disks. MATERIALS AND METHODS: Tobacco plants (Nicotiana tabacum L. cultivar Samsun) carrying the TMV resistance gene N. TMV inoculated leaf disks were floated for 3 days in the following: Distilled water (control). H2O 5 and 45 decimal and centesimal potencies. As2O3 5 and 45 decimal and centesimal potencies. The main outcome measures is the number of hypersensitive lesions observed in a leaf disk. RESULTS: Homeopathic treatments of arsenic induce two effects on the plant: (i) increased resistance to TMV; (ii) decrease variability between experiments (system variability). CONCLUSIONS: In this experimental model two actions of homeopathic treatment were detected: decrease in system variability and enhancement of the natural tendency of the system towards an 'equilibrium point'.

Antiviral Agents↗
PubMed2002

Regional brain injury epidemiology as the basis for planning brain injury treatment. The Romagna (Italy) experience.

AIM: Neurosurgical services for traumatic brain injury (TBI) should be based upon the understanding of the epidemiology of TBI in the region as well as the clinical parameters. Our objective was to measure incidence and epidemiologic factors associated with TBI in the Romagna region of Northeastern Italy and correlate those parameters with neurosurgical imaging and related clinical features. METHODS: Guidelines for brain injury management in our region were derived following meetings of all physicians involved in the treatment of brain injury. An epidemiologic study was undertaken in 1998. The study population was all patients admitted for hospital care in the Region following a TBI with a discharge diagnosis of pertinent International Classification Disease, 9(th) revision, codes. Data on the extent, diagnoses, severity, external causes and hospital course were abstracted from the hospital record and computer entered for analyses. RESULTS: Using data for the population of Romagna of about 1000000 persons we identified, in the full year 1998, 2430 TBI patients or an incidence rate of 250 per 100000 resident population. There were, in addition, 460 nonresident patients who were admitted in the region. External causes of injury were generally similar to reports from other places in Western Europe, with the exception of a very low frequency of cases stemming from violence. Age specific incidence rates were highest among young children, persons aged 15-24, and those aged 65 and older. Computerized tomography scans were given to 1732 patients and intracranial traumatic lesions were identified in 497 (28.6%) patients or a rate of 38 /100000. We performed 128 craniotomies, an incidence rate of 11/100000. The case fatality rate (CFR) was 2.8% among admitted patients with the highest rate among those aged 75 or older. CONCLUSION: Incidence of TBI in Italy is similar to other published European series. The number of minor brain injuries admitted for hospital care remains high and can be significantly reduced with better use of CT scans in adults whenever possible. The workload for a neurosurgical unit servicing a population of 1 million is limited and does not justify the opening of new units for trauma care or the use of craniotomies outside the Neurosurgical Unit.

Adolescent↗
PubMed2001

Synthesis, biological evaluation, and pharmacophore generation of new pyridazinone derivatives with affinity toward alpha(1)- and alpha(2)-adrenoceptors.

A series of new pyridazin-3(2H)-one derivatives (3 and 4) were evaluated for their in vitro affinity toward both alpha(1)- and alpha(2)-adrenoceptors by radioligand receptor binding assays. All target compounds showed good affinities for the alpha(1)-adrenoceptor, with K(i) values in the low nanomolar range. The polymethylene chain constituting the spacer between the furoylpiperazinyl pyridazinone and the arylpiperazine moiety was shown to influence the affinity and selectivity of these compounds. Particularly, a gradual increase in affinity was observed by lengthening the polymethylene chain up to a maximum of seven carbon atoms. In addition, compound 3k, characterized by a very interesting alpha(1)-AR affinity (1.9 nM), was also shown to be a highly selective alpha(1)-AR antagonist, the affinity ratio for alpha(2)- and alpha(1)-adrenoceptors being 274. To gain insight into the structural features required for alpha(1) antagonist activity, the pyridazinone derivatives were submitted to a pharmacophore generation procedure using the program Catalyst. The resulting pharmacophore model showed high correlation and predictive power. It also rationalized the relationships between structural properties and biological data of, and external to, the pyridazinone class.

Adrenergic alpha-Antagonists↗
PubMed2001

Structure-activity relationships in a series of 8-substituted xanthines as A1-adenosine receptor antagonists.

A series of 8-substituted xanthines were synthesized and their affinity in vitro towards A1, A2A-adenosine receptors was evaluated by radioligand receptor binding assays. All compounds showed a greater affinity and selectivity towards the A1-adenosine receptor than theophylline. The compounds in which the n-proyl group is in 1-position of the xanthine nucleus and the pyridazinone system in 8-position is linked through a chain of two or four carbon atoms, showed the highest affinity and selectivity.

Animals↗
PubMed2001

[3H]Ro 15-1788 binding sites to brain membrane of the saltwater Mugil cephalus.

The equilibrium binding parameters of the benzodiazepine antagonist [3H]Ro 15-1788 (8-fluoro-3-carboethoxy-5,6-dihydro-5-methyl-6-oxo-4H-imidazol-[1,5-a]-1,4 benzodiazepine) were evaluated in brain membranes of the saltwater teleost fish, Mugil cephalus. To test receptor subtype specificity, displacement studies were carried out by competitive binding of [3H]Ro 15-1788 against six benzodiazepine receptor ligands, flunitrazepam [5-(2-fluoro-phenyl)-1,3-dihydro-1-methyl-7-nitro-2H-1,4-benzodiazepin-2-one], alpidem [N,N-dipropyl-6-chloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridine-3-acetamide], zolpidem [N,N-6 trimethyl-2-(4-methyl-phenyl)imidazo[1,2-a]pyridine-3-acetamide hemitartrate], and beta-CCM (methyl beta-carboline-3-carboxylate). Saturation studies showed that [3H]Ro 15-1788 bound saturatably, reversibly and with a high affinity to a single class of binding sites (Kd value of 1.18-1.5 nM and Bmax values of 124-1671 fmol/mg of protein, depending on brain regions). The highest concentration of benzodiazepine recognition sites labeled with [3H]Ro 15-1788 was present in the optic lobe and the olfactory bulb and the lowest concentration was found in the medulla oblongata, cerebellum and spinal cord. The rank order of displacement efficacy of unlabelled ligands observed suggested that central-type benzodiazepine receptors are present in one class of binding sites (Type I-like) in brain membranes of Mugil cephalus. Moreover, the uptake of 36Cl- into M. cephalus brain membrane vesicles was only marginally stimulated by concentrations of GABA that significantly enhanced the 36Cl- uptake into mammalian brain membrane vesicles. The results may indicate a different functional activity of the GABA-coupled chloride ionophore in the fish brain as compared with the mammalian brain.

Animals↗
PubMed2001

Distribution of [3H]GR65630 binding in human brain postmortem.

We investigated the distribution of serotonin (5-HT) receptors of type 3 (5-HT3) in human brain areas, by means of the the specific binding of [3H]GR65630. The brains were obtained during autoptic sessions from 6 subjects. Human brain membranes and the binding of [3H]GR65630 were carried out according to standardized methods. The highest density (Bmax +/- SD, fmol/mg protein) of [3H]GR65630 binding sites was found in area postrema (13.1+/-9.7), followed at a statistically lower level, by nucleus tractus solitarius (6.7+/-3.4), nervus vagus (5.5+/-2.1), striatum (4.8+/-2.4) with a progressive decrease in amygdala, olivar nuclei, hippocampus, olfactory bulbus and prefrontal cortex, and then by the other cortical areas and the cerebellum, where no binding was detected. These observations extend previous findings on the distribution of 5-HT3 receptors and confirm interspecies variations that might explain the heterogeneous properties of 5-HT3 receptors in different animals.

Aged↗
PubMed2001

Correlation between platelet alpha(2)-adrenoreceptors and symptom severity in major depression.

BACKGROUND: Abnormalities in different parameters of the norepinephrine system have been widely described in major depression. The presence of alpha(2)-adrenoreceptors in blood platelets, similar to those in the brain, prompted us to evaluate them in depressed patients, as compared with healthy controls. METHODS: Fifteen outpatients affected by major depression, according to DSM IV criteria, and 15 comparable healthy control subjects, were included in the study. The alpha(2)-adrenoreceptors were measured by means of the specific binding of [(3)H]rauwolscine, a highly selective antagonist for this receptor subtype. The severity of depression was assessed by means of the Hamilton Rating Scale for Depression (HRSD). RESULTS: The results did not show any difference in [(3)H]rauwolscine binding parameters (B(max) and K(d)) between patients and controls. However, in the patients, a significant and positive correlation between B(max), which measures the density of the receptors, and HRSD total score was detected. CONCLUSIONS: Therefore, although no change in alpha(2)-adrenoreceptors seems to occur in major depression, the density of these receptors would seem to be related to the severity of depressive symptoms.

Adult↗
PubMed2000

A novel class of highly potent and selective A1 adenosine antagonists: structure-affinity profile of a series of 1,8-naphthyridine derivatives.

A series of 1,8-naphthyridine derivatives (12-36), bearing a phenyl group in position 2 and various substituents in positions 4 and 7, were synthesized in an attempt to obtain potent, selective antagonists for the A1 adenosine receptor subtype. The compounds were tested to evaluate their affinity for A1 compared with A2A and A3 adenosine receptor subtypes. In binding studies in bovine brain cortical membranes, most of the compounds showed an affinity for A1 receptors in the low nanomolar range and two in the subnanomolar range with an interesting degree of A1 versus A2A and A3 selectivity. Comparison of the 4-substituted derivatives indicated that 4-OH substitution, with a 4-quinoid structure, causes an increase in the A1 and A2A affinity and generally also in A1 selectivity. The kind of substitution in position 7 can greatly modulate the affinity: the most interesting substituents in this position seemed to be electron-withdrawing groups; in particular the 7-chloronaphthyridine 25d showed a remarkable selectivity (A2A/A1 ratio of 670, A3/A1 ratio of 14,000) associated with a higher A1 affinity (Ki = 0.15 nM). NMR studies on these compounds 12-36 indicated that the 4-OH-substituted ones prefer the tautomer in which the oxygen in position 4 is in the quinoid form and the nitrogen in position 1 is protonated. Theoretical calculations are in agreement with the NMR data.

Adenylyl Cyclases↗
PubMed2000

Autoradiographic distribution of peripheral benzodiazepine receptors in the retina of the albino rabbit, Lepus cunicula.

The distribution of peripheral benzodiazepine receptors (PBRs) in the retina of the albino rabbit, Lepus cunicula, was studied by autoradiography using [3H]-PK11195, a isoquinoline carboxamide, as a tracer. Autoradiograms obtained by directly placing the slides containing the retina sections on tritium-sensitive film provide evidence for the presence of PBRs in rabbit retina. Furthermore, the dark field examination of photomicrographs taken from autoradiograms showed two dense horizontal bands corresponding to the outer and inner photoreceptor segments, and to the inner plexiform layer. The retinal regions where [3H]-PK11195 binding was more dense are rich in mitochondria, suggesting that as in other neuronal tissues, retinal PBRs are involved in the mitochondrial activity.

Animals↗
PubMed2000

Peripheral-type benzodiazepine receptors in human blood cells of patients affected by migraine without aura.

The kinetic parameters at equilibrium of peripheral benzodiazepine receptors in platelets, lymphocytes and granulocytes of 15 patients affected by migraine without aura were tested using [3H]PK 11195, a specific radioligand for this receptor and compared with the same number of healthy controls: a statistically significant increase (platelets 212%, lymphocytes 203%, granulocytes 171%, as absolute percentage) in the maximal number of binding sites (B(max)) in all three patient samples, compared with healthy controls was detected; on the contrary, the values of the dissociation constant (K(d)) at equilibrium do not show any statistically significant variations between the two groups. These data further confirm the presence of peripheral biochemical alterations in migraine without aura. As peripheral benzodiazepine receptors appear to be involved in the regulation of the mitochondrial respiratory chain, the observed increase in B(max) might be related to the mitochondrial anomalies found in migraine disorders.

Adult↗
PubMed2000

Statistical analysis of the effect of high dilutions of arsenic in a large dataset from a wheat germination model.

This paper describes the statistical analysis of a series of experiments using a simple biological model (wheat germination in vitro), where a large number of wheat seeds were treated with homeopathic potencies of Arsenic trioxide. Some potencies, such as As2O3 40x, 42x and 45x, have repeatedly shown a significant stimulating effect on germination compared to controls, whereas As2O3 35x has a significant inhibiting effect. In some experiments the seeds were stressed before the experiment with a sublethal dose of the same substance. We performed a statistical analysis, both for stressed and non-stressed seed groups, using Poisson distribution as a suitable model for representing the number of non-germinated seeds in a standard experiment with 33 seeds in the same Petri dish. Finally, we have considered the most repeated potencies (30x and 45x), computing the sample odds ratio (OR) and a 95% confidence interval (CI) for the population OR. Our results show significant reproducible effects of some As2O3 decimal potencies, particularly As2O3 45x. In stressed seeds, even decimal potencies of water seem to give significant results compared to control, whereas high dilutions of As2O3 without potentization never show significant effects.

Arsenic Trioxide↗
PubMed1999

Synthesis of new pyridazinone derivatives and their affinity towards alpha1-alpha2-adrenoceptors.

A series of 3(2H)-pyridazinone derivatives was evaluated for their affinity in vitro towards alpha1-alpha2-adrenoceptors by radioligand receptor binding assays. All target compounds showed good affinities for the alpha1-adrenoceptor (with Ki values in the subnanomolar range), and a gradual increase in affinity was observed by increasing the polymethylene chain length of this series up to a maximum of six and seven carbon atoms, when the fragment 4-[2-(2-methoxyphenoxy)-ethyl]-1-piperazinyl is linked in 5 position of the 3(2H)-pyridazinone ring, while a slight decrease was found for the higher homologues. Increasing the chain length when the 4-[2-(2-methoxyphenoxy)-ethyl]-1-piperazinyl group is linked in 6 position of the 3(2H)-pyridazinone ring, had a different effect: there is the highest affinity when the polymethylene chain is of four carbon atoms. The alkylic chain, a spacer between the two major constituents of the molecule, can influence the affinity and the selectivity.

Animals↗
PubMed1998

Characterization of sulfonylurea receptors in isolated human pancreatic islets.

Current information on pancreatic islet sulfonylurea receptors has been obtained with laboratory animal pancreatic beta cells or stable beta-cell lines. In the present study, we evaluated the properties of sulfonylurea receptors of human islets of Langherans, prepared by collagenase digestion and density-gradient purification. The binding characteristics of labeled glibenclamide to pancreatic islet membrane preparations were analyzed, displacement studies with several oral hypoglycemic agents were performed, and these latter compounds were tested as for their insulinotropic action on intact human islets. [3H]glibenclamide saturable binding was shown to be linear at < or =0.25 mg/ml protein; it was both temperature and time dependent. Scatchard analysis of the equilibrium binding data at 25 degrees C indicated the presence of a single class of saturable, high-affinity binding sites with a Kd value of 1.0+/-0.07 nM and a Bmax value of 657+/-48 fmol/mg of proteins. The displacement experiments showed the following rank order of potency of the oral hypoglycemic agents we tested: glibenclamide = glimepiride > tolbutamide > chlorpropamide >> metformin. This binding potency order was parallel with the insulinotropic potency of the evaluated compounds.

ATP-Binding Cassette Transporters↗
PubMed1998

Novel 3-aralkyl-7-(amino-substituted)-1,2,3-triazolo[4,5-d]pyrimidines with high affinity toward A1 adenosine receptors.

Three series of several 1,2,3-triazolo[4,5-d]pyrimidine derivatives bearing various amino substituents at the 7 position and one of three lipophilic substituents at the 3 position (benzyl, phenethyl, or 2-chlorobenzyl) were prepared starting from the corresponding 7-chloro compounds, by nucleophilic substitution by the appropriate amine. Radioligand binding assays at bovine brain adenosine A1 and A2A receptors showed that some compounds possessed a high affinity and selectivity for the A1 receptor subtype. In particular the biological results suggested the compounds bearing cycloalkylamino (cyclopentyl- and cyclohexylamino) or aralkylamino (alpha-methylbenzyl- and 1-methyl-2-phenylethylamino or amphetamino) substituents at the 7 position were the most active derivatives. The best lipophilic substituent at the 3 position was the 2-chlorobenzyl (A1 affinity Ki < 50 nM) followed by the benzyl and then the phenethyl groups. This pattern of structure-activity relationship (SAR) was similar to that previously reported for analogous 1,2,3-triazolopyridazino derivatives (Biagi et al., 1994, 1995, 1996) except for the compounds bearing substituted aromatic amines which presented a generalized and strong decrease of the A1 receptor affinity. These facts allowed us to attribute to these molecules a binding mode within the A1 adenosine receptor analogous to that of the corresponding triazolopyridazines.

Adenosine↗