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Biomedical subjects

G Colombo

Publications and source records attributed to G Colombo.

At least 109 records · Page 6Linked to original sources
PubMed1995

Symmetrical generalization between the discriminative stimulus effects of gamma-hydroxybutyric acid and ethanol: occurrence within narrow dose ranges.

Gamma-hydroxybutyric acid (GHB) has been shown to reduce ethanol consumption and suppress ethanol withdrawal syndrome both in laboratory animals and humans. The present study was designed to assess the similarity between the discriminative stimulus effects, or subjective feelings, of GHB and ethanol using a T-maze, food-reinforced drug discrimination procedure. Three groups of rats were trained to discriminate ethanol (1.0 or 2.0 g/kg; p.o.) or GHB (300 mg/kg; p.o.) from water. In the 1.0 g/kg ethanol-trained rats, substitution for ethanol was an inverted U-shape function of GHB dose, with only 300 mg/kg GHB resulting in complete substitution for ethanol. No dose of GHB elicited selection of ethanol-appropriate arm higher than 10% in the 2.0 g/kg ethanol-trained group. In the 300 mg/kg GHB-trained rats, complete substitution for GHB occurred only at the dose of 1.0 g/kg ethanol. Doses of ethanol lower or higher than 1.0 g/kg did not substitute for GHB. The results of the present study indicate that symmetrical generalization between ethanol and GHB occurred within narrow dose ranges. They are discussed in terms of common neurotransmitter systems involved in the mediation of GHB and ethanol effects.

Alcohol Drinking↗
PubMed1995

Sardinian alcohol-preferring rats: a genetic animal model of anxiety.

The present study was designed to assess the anxiety profile of the selectively bred alcohol-preferring sP and alcohol-nonpreferring sNP rats. Rats were offered either water (ethanol-naive rats) or a free choice of 10% (v/v) ethanol and water (ethanol-experienced rats) for 14 consecutive days prior to the test. Spontaneous exploration of an elevated plus maze was used as a behavioral measure of anxiety. Ethanol-naive sP rats spent less time in and made fewer entries into the open arms of the maze than ethanol-naive sNP rats. These results suggest a higher innate degree of anxiety in sP than in sNP rats. Moreover, time spent in and number of entries into the open arms of the maze were higher in ethanol-experienced than in ethanol-naive sP rats. This finding suggests that ethanol consumed voluntarily produces anxiolytic effects in sP rats. The results of the present study are discussed in terms of (a) anxiety as a genetic trait related to ethanol-preference in sP rats and (b) self-medication of anxiety as a possible factor promoting voluntary ethanol consumption in sP rats.

Alcohol Drinking↗
PubMed1995

Blockade of the discriminative stimulus effects of gamma-hydroxybutyric acid (GHB) by the GHB receptor antagonist NCS-382.

The present study was designed to assess the ability of the newly synthetized, selective gamma-hydroxybutyric acid (GHB) receptor antagonist, NCS-382, in blocking the discriminative stimulus effects of GHB in a T-maze, food-reinforced drug discrimination procedure. Two groups of rats were trained to run the left arm of the maze 30 min after the i.g. administration of either 300 or 700 mg/kg GHB and the right arm after water. Once discrimination was acquired, combination of different doses of NCS-382 (0, 12.5, 25.0 and 50.0 mg/kg, IP) and GHB training doses were tested for blockade of GHB discrimination. NCS-382 dose-dependently blocked GHB-appropriate responding in both the 300 and 700 mg/kg GHB rat groups. The results of the present study indicate that the discriminative stimulus properties of GHB are mediated via stimulation of GHB receptors.

Animals↗
PubMed1995

Effects of the calcium channel antagonist darodipine on ethanol withdrawal in rats.

The effect of the dihydropyridine calcium channel antagonist, darodipine, on ethanol withdrawal syndrome was examined in rats made dependent on ethanol by repeated ethanol administration for six consecutive days. Chronic co-administration of darodipine prevented the severity of ethanol withdrawal signs in a dose-dependent fashion. By contrast, acute administration of darodipine during the ethanol withdrawal phase was ineffective in reversing the withdrawal symptoms. The results suggest that the presence of darodipine in the central nervous system during the adaptative responses to ethanol is necessary to reduce the severity of the withdrawal syndrome. They also provide further evidence for a potential clinical usefulness of dihydropyridine calcium channel blockers in treatment of ethanol withdrawal.

Animals↗
PubMed1995

Different affinity of cortical GHB binding sites in sardinian alcohol-preferring (sP) and -non preferring (sNP) rats.

Specific gamma-hydroxybutyric acid (GHB) binding sites in cortical membranes of selectively bred alcohol-preferring sP and alcohol-non preferring sNP rats were compared using [2,3(-3)H]GHB ligand. The sP rat line showed an increased affinity (approximately 40% lower Kd) of both the high- and low-affinity sites in comparison with the sNP line. No significant difference in GHB receptor density (Bmax) was detected between the two rat lines. The results raise the possibility that differences in GHB binding sites may play a role in the genetic predisposition to ethanol preference in our rat line.

Alcohol Drinking↗
PubMed1995

NonHodgkin's lymphoma of the male urethra.

Ten cases of malignant lymphoma of the female urethra have been reported. To our knowledge we report the first such case in a man who presented in acute urinary retention with a mass protruding from the urethral meatus. Multiple subcutaneous nodules developed over the anterior abdominal wall and a 3 x 3 cm. mass developed above the umbilicus. Wedge resection of this mass was consistent with large cell lymphoma. Treatment consisted of 2 courses of arabinoside C, doxorubicin and prednisone. Followup 6 months later showed no urethral or other recurrence. Local excision, radical excision, radiotherapy (external beam and intracavitary) and chemotherapy have been used with success in other cases.

Humans↗
PubMed1995

Multicentre evaluation of Capture Assay Radim Liquid Allergen for measurement of specific IgE antibodies.

A multicentre trial of Capture Assay Radim Liquid Allergen was performed to define the sensitivity, specificity and clinical reliability of the system in diagnostic allergology. The results of the evaluation were compared with clinical data and in vivo testing. Good agreement was obtained for Dermatophagoides pteronyssinus (D1), Cat's epithelium (E1), Betula verrucosa (T3) and Olea europea (T9), Artemisia vulgaris (W6) and Parietaria officinalis (W19). Some spreading of data was observed for Artemisia absinthium (W5), Cynodon dactylon (G2), and Lolium perenne (G5). We found a high number of negative cases for Alternaria alternata (M6). The advantages offered by the system are the automation, the small quantity of serum requested, the supply of quantitative results in international units of specific IgE, the user-friendly software. The data are sufficiently reliable for the diagnostic system to be introduced into the clinical laboratory allergological routine.

Adolescent↗
PubMed1994

Blockade of ethanol discrimination by isradipine.

The effect of the dihydropyridine Ca2+ channel antagonist, isradipine, on ethanol discrimination was assessed in rats trained to discriminate 1.5 g/kg ethanol from water in a T-maze, food-reinforced drug discrimination procedure. Pretreatment with isradipine (0, 1.0, 3.0 and 5.0 mg/kg i.p.) resulted in a dose-dependent blockade of ethanol discrimination. The results of the present study suggest that L-type Ca2+ channels are involved in the mediation of ethanol discriminative stimulus effects.

Animals↗
PubMed1994

Locomotor activity in spinal man.

We studied whether spinal locomotor centres of patients with paraplegia can be activated by external stimuli. In patients with complete paraplegia, coordinated stepping movements were induced by weight support and standing on a moving treadmill. The pattern of leg muscle electromyographic (EMG) activity was similar to that seen in healthy subjects although EMG amplitude was smaller. With daily training the amplitude of gastrocnemius EMG activity increased during weight-bearing phase of stepping and the degree of inappropriate tibialis anterior activity decreased. Patients with incomplete paraplegia profited from the training programme in that their walking on a stationary surface improved even when unsupported. Our results may suggest new ways to improve mobility of patients with paraplegia.

Adult↗
PubMed1994

Naloxone antagonizes ethanol- but not gamma-hydroxybutyrate-induced sleep in mice.

The present study examined the effect of naloxone on ethanol- and gamma-hydroxybutyric acid-induced narcosis in mice and the changes induced by these drugs on striatal dopamine metabolism. The results show that naloxone (1-10 mg/kg s.c.) markedly reduced ethanol-induced narcosis but failed to modify the duration of sleep induced by gamma-hydroxybutyrate. Naloxone (10 mg/kg) modified neither ethanol- nor gamma-hydroxybutyrate-induced changes in striatal dopamine and dihydroxyphenylacetic acid (DOPAC) content. The results suggest that gamma-hydroxybutyrate- and ethanol-induced narcosis are mediated by different mechanisms and that opioid receptors are not involved in the changes in dopamine metabolism induced by these compounds.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Dietary nucleotides: effects on the gastrointestinal system in swine.

Nucleotides in the intestinal lumen may decrease the inflammatory response to ischemia-reperfusion. In a newborn-swine model, we showed that perfusion of the intestinal lumen with nucleotides in concentrations similar to those in human milk induced hyperemia. The levels of hypoxanthine (and xanthine) were not increased in the presence of nucleotides during ischemia-reperfusion, and the number of leukocytes accumulated in the intestine was reduced in the presence of nucleotides. Furthermore, nucleotides may have decreased protein leak and the production of nitric oxide during ischemia. These effects are not changed significantly in the presence of an adenosine antagonist. We interpreted our results to indicate that the protective effects of nucleotides in the intestinal lumen are not due to adenosine alone.

Adenosine↗
PubMed1994

Radiation protection and radioactive scales in oil and gas production.

Low specific-activity scales consisting of alkaline earth metal carbonates and sulfates are often present in some gaseous and liquid hydrocarbon plants. These scales contain a certain concentration of radium, uranium, and thorium which can cause a risk of gamma irradiation and internal radiocontamination when they must be mechanically removed. The gamma dose rates and the 238U, 232Th, 226Ra concentrations were determined in sludges, scales, and waters of some gas and oil hydrocarbon plants located in Italy, Congo, and Tunisia. 238U and 232Th concentrations were were low. The isotopes 238U and 234U resulted in radioactive equilibrium, while 232Th and 228Th were not always equilibrium. A rough correlation was found between the gamma dose rate and the 226Ra concentration. Some considerations and conclusions about radiation protection problems are pointed out.

Fossil Fuels↗
PubMed1993

Metal ion binding to dog osteocalcin studied by 1H NMR spectroscopy.

One-dimensional 1H NMR was employed to study the effects of Ca2+ and Lu3+ binding on the apo and calcium-saturated forms of dog bone Gla protein (BGP, osteocalcin). Titration of apo dog BGP with Ca2+ in 20 mM NaCl showed spectral perturbations consistent with the binding of 5 mol equiv of calcium in the NMR slow-exchange limit. The first 2 Ca2+ equiv induced significant conformational changes in the apoprotein, binding cooperatively with a Kd1 approximately 5.0 x 10(-4) M and a Hill coefficient H = 2.3 in 20 mM NaCl. The last 3 equiv bound with a slightly weaker affinity and did not induce significant structural changes. Neither the affinity nor the stoichiometry of calcium binding was significantly altered at 150 mM NaCl. The addition of only 1 Lu3+ equiv to apo dog osteocalcin was sufficient to induce the same spectral perturbations as 2 Ca2+ ions. The addition of 2 Lu3+ equiv to calcium-saturated osteocalcin had little effect on its 1H NMR spectrum, and BGP aggregated at [Lu3+]o/[BGP]o ratios greater than 2 in either the presence or absence of calcium. The spectrum of calcium-saturated osteocalcin was invariant at < or = 55 degrees C (< or = 50 degrees C in 150 mM NaCl), after which the proton resonances shifted to frequencies more characteristic of apo BGP. Saturation with calcium somewhat stabilized the apo dog osteocalcin protein against conformational changes induced at pH extremes; apo BGP was stable at 6.0 < or = pH < or = 10, and calcium-saturated BGP was stable at 5.8 < or = pH < or = 10. Both our NMR and gel filtration data indicate that calcium-saturated osteocalcin exists as a dimer at both high and low protein concentrations. A conformational change in dog osteocalcin was thus induced by the cooperative association of Ca2+ to two high-affinity sites on the protein and stabilized by the association of 3 additional Ca2+ equiv. The results of our temperature and calcium binding studies were consistent with an estimated Kd1 approximately 5.0 x 10(-4) M for the two high-affinity sites. Lutetium induced the same structural changes in osteocalcin as calcium, but the two high-affinity Ca2+ binding sites did not have equal affinities for Lu3+. The BGP:Ca2+ complex was unstable at the low pH conditions induced by osteoclasts during bone resorption, yet the osteocalcin protein retained a BGP:Ca(2+)-like conformation at low pH. However, unlike the calcium-saturated form of the protein, osteocalcin was monomeric at low pH.

Amino Acid Sequence↗
PubMed1993

Isolation and complete amino acid sequence of osteocalcin from canine bone.

Osteocalcin was purified in high yield and to homogeneity from the diaphysis of dog femora by the following steps: (1) acid demineralization of bone powder, (2) solid-phase extraction of acid-soluble proteins on Sep-Pak C18 cartridges, (3) gel filtration on Sephadex G-50, and (4) fast protein liquid chromatography on an Accell-QMA anion-exchange column. Starting from 30 g washed bone powder, approximately 7-10 mg pure protein was obtained in 2 days. The key step is the initial solid-phase extraction of osteocalcin from a large volume of a demineralized bone solution. The primary structure was established by automated sequence analyses of two tryptic peptides, of two endoproteinase Glu-C carboxy-terminal peptides, and of the first 30 amino acid residues of the intact protein. Dog osteocalcin contains 49 amino acids, has a molecular mass of 5654 daltons, contains no Thr, Met, Hyp, or Trp, has a disulfide bond between Cys 23 and 29, and is fully gamma-carboxylated at residues 17, 21, and 24. Dog osteocalcin does not contain a pair of basic amino acids found at positions 43-44 in most other osteocalcins from mammals and birds. A computer search for homology indicated 88, 90, 84, 88, 66, and 57% sequence identity of dog osteocalcin with human, bovine, cat, monkey, chicken, and swordfish osteocalcin, respectively, and weaker homologies with the gamma-carboxylated domains of blood-clotting proteins and the Pro-rich N-terminal extensions of myosin light-chain A1 and beta-crystalline B1. The possible relevance of these homologies to the structure and potential functions of osteocalcin is discussed.

Amino Acid Sequence↗
PubMed1993

Development and characterization of a polyclonal antiserum-based radioimmunoassay for dog osteocalcin.

Determination of the serum concentration of the protein osteocalcin (OC) is useful for the noninvasive evaluation of bone metabolism. Because the dog is an excellent experimental model for the study of bone, we produced and characterized a polyclonal antiserum specific for dog OC and used it to develop a radioimmunoassay (RIA) for the measurement of the concentration of this protein in dog serum. The antiserum expresses higher affinity for Ca(2+)-bound than for Ca(2+)-free OC (B50 at 10(-5) versus 2 x 10(-4) dilution). Also, in the presence of Ca2+ affinity is higher for the carboxylated than for the decarboxylated form of the protein, and under Ca(2+)-free conditions the affinity is equal for the two forms. The study of peptide fragments of OC demonstrates competitive binding of the peptide comprising amino acids 20-44 but not of other fragments; this suggests that the antigenic epitope of dog OC is located in the midmolecular region of the protein. The RIA displays excellent sensitivity for the measurement of OC in blood (detection limit 0.31 ng/ml), with intraassay and interassay variations of 4.6 and 6.8%, respectively. Analysis of gel chromatography fractions of normal dog serum shows that greater than 90% of the antigenic material coelutes with purified radiolabeled dog OC. Test of parallelism reveals lack of interference of serum constituents with the binding assay. The antiserum displays limited species specificity since it cross-reacts with human OC, but not with the protein from rodents.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Substitution of the 5-HT1 agonist trifluoromethylphenylpiperazine (TFMPP) for the discriminative stimulus effects of ethanol: effect of training dose.

The role of the ethanol training dose on the ability of the selective 5-HT1 agonist TFMPP (m-trifluoromethylphenylpiperazine) to produce ethanol-like discriminative stimulus effects was evaluated in three groups of rats trained to discriminate 1.0 g/kg (n = 5), 1.5 g/kg (n = 6) or 2.0 g/kg (n = 7) ethanol (IG) from water using a two-lever procedure with food reinforcement available under a fixed ratio 20 (FR 20) schedule. Ethanol generalization gradients were comparable in the three groups, indicating few potency differences in the ethanol stimulus across training dose. However, the ability of TFMPP (0.1-1.7 mg/kg; IP) to substitute for ethanol was dependent on the training dose. TFMPP resulted in partial substitution in the 1.0 g/kg group, complete substitution for 1.5 g/kg group and no substitution in the 2.0 g/kg ethanol training group. The results indicate a serotonergic component to the discriminative stimulus effects of an intermediate dose of ethanol that is not prominent as the dose of ethanol is raised. These data add further support for the hypothesis that ethanol produces a mixed discriminative cue, the components of which are not uniformly amplified when the dose of ethanol is increased.

Animals↗