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Biomedical subjects

G Colombo

Publications and source records attributed to G Colombo.

At least 91 records · Page 5Linked to original sources

The determination of serum concentrations of osteocalcin in growing pigs and its relationship to end-measures of bone mineralization.

Osteocalcin, a 49-amino acid, gamma-carboxyglutamic acid-containing protein produced by the osteoblast, has been shown in laboratory animals to be a better marker of bone turnover than alkaline phosphatase. To determine serum osteocalcin levels in growing pigs, we isolated pure porcine osteocalcin and developed a double-antibody RIA. To evaluate the effects of dietary Ca and P levels on serum osteocalcin, 36 individually penned crossbred pigs (19.5 kg initial BW) were fed fortified corn-soybean meal diets (.95% lysine) containing four levels of Ca (.42, .66, .90, 1.14%) and P (.35, .55, .75, .95%) in a 30-d test. Increasing dietary Ca and P improved body weight gain quadratically (P < .02). Most bone traits improved quadratically (P < .05) with increasing Ca and P. Pigs were bled on d 0, 10, 20, and 30 to determine serum levels of alkaline phosphatase, 1,25-dihydroxyvitamin D3, and osteocalcin. Osteocalcin decreased (P < .02) linearly with increasing Ca and P on d 10, 20, and 30. However, this effect was much more pronounced on d 20 and 30. Alkaline phosphatase decreased with the first incremental increase in dietary Ca and P, but was not affected by higher levels on any day measured. Osteocalcin was inversely correlated with growth rate (r = -.54, P < .01), bone strength (r = -.57, P < .01), metacarpal ash (r = -.29, P < .10), femur ash (r = -.60, P < .01), and femur ash weight (r = -.65, P < .01). Similar results were found for 1,25-dihydroxyvitamin D3. Alkaline phosphatase was not correlated with performance or most bone traits on d 30. Based on this model, these results suggest that serum osteocalcin and 1,25-dihydroxyvitamin D3 are better predictors of bone mineralization and(or) turnover in pigs than serum alkaline phosphatase.

Alkaline Phosphatase↗

[Histopathologic features in atherectomy samples obtained from patient with unstable angina, stable angina and restenosis. Directional Atherectomy Lombardi Group].

BACKGROUND: The present study was aimed at investigating the pathologic features of directional coronary atherectomy (DCA) samples obtained from 194 patients (14 females) with stable (n = 68) and unstable (n = 95) angina, and with restenosis (n = 27). METHODS: DCA samples were obtained from culprit lesions, using the Simpson technique. Unstable angina was classified according to E. Braunwald criteria. Stable angina was grouped according to the presence or absence of a prior myocardial infarction (MI). DCA samples were fixed, processed, serially cut and stained with hematoxilin-eosin and with Movat pentachrome stain. RESULTS: The major pathologic findings were thrombosis, inflammation of the superficial plaque layers, and neointimal hyperplasia which often coexisted within a same sample. Their frequencies, in that order, were distributed in the differing groups of patients as follows: 21% (n = 9), 29.2% (n = 12) and 51% (n = 21) of the 41 cases with stable angina without prior MI. 40.7% (n = 11), 40.7% (n = 11), and 51.8% (n = 14) of the 27 cases with stable angina with prior MI. 25% (n = 4), 56.2% (n = 9) and 68.7% (n = 11), of the 16 cases with BI unstable angina. 35.3% (n = 14), 55.8% (n = 19) and 44% (n = 15), of the 34 cases with BII unstable angina. 44.4% (n = 4), 33.3% (n = 3) and 33.3% (n = 3), of the 9 cases with BIII unstable angina. 48.2% (n = 14), 48.2% (n = 14) and 51.8% (n = 15), of the 29 cases with CII unstable angina at 35.8 days after MI. 60% (n = 3), 60% (n = 3) and 40% (n = 2), of the 5 cases with CIII unstable angina at 8.3 days after MI. 26% (n = 7), 48% (n = 13) and 85.1% (n = 23), of the 27 cases with restenosis. According to above observation, the frequency of coronary thrombosis increases with the increase of the severity of myocardial ischemia. However, thrombosis is not found in most unstable angina without prior MI (63% of BI-II-III unstable angina cases do not have thrombus). In addition, thrombus is not a specific finding of unstable angina, given its occurrence, although in a much lower percentage of cases, in stable angina and in restenosis. CONCLUSIONS: Present data show that different ischemic and plaque lesions. This observation questions on the pathogenetic role of thrombus in unstable angina and calls for further investigations on inflammation and neointimal hyperplasia, as well as on the the reciprocal relation between these findings which are often combined within a same lesion.

Adult↗

Oral self-administration of gamma-hydroxybutyric acid in the rat.

The present study describes the induction of gamma-hydroxybutyric acid (GHB) preference over water in rats. GHB solution (1% w/v in water) was initially offered as the sole fluid available for 14 consecutive days. Subsequently, rats were given a free choice of GHB solution and tap water for 20 consecutive weeks. Under the free-choice regimen, all rats showed periods of preference for GHB solution over water and periods of voluntary abstinence from GHB. On GHB-preference days, GHB was ingested at pharmacologically relevant doses. GHB intake occurred in 2-3 discrete episodes during the nocturnal phase. The development of an animal model of GHB self-administration may constitute a useful tool in the investigation of the neurobiological substrates of GHB-reinforcing properties.

Administration, Oral↗

Cross-tolerance to ethanol and gamma-hydroxybutyric acid.

In the present study, the development of tolerance to the motor impairing effects of gamma-hydroxybutyric acid (GHBA) and ethanol was compared (Experiment 1). Rats were required to perform a motor coordination task daily shortly after ethanol (3.5 g/kg) and GHBA (1.0 g/kg) administration for 9 consecutive days. Tolerance to the motor impairing effects of ethanol and GHBA developed to a similar extent but with different patterns. On the tenth day, the presence of cross-tolerance to the motor impairing effects of GHBA and ethanol was assessed (Experiment 2). Administration of 1.0 g/kg GHBA produced a significantly lower impairment in ethanol-tolerant rats than in ethanol-naive rats. Similarly, administration of 3.5 g/kg ethanol induced a significantly lower impairment in GHBA-tolerant rats than in GHBA-naive rats. The presence of cross-tolerance between GHBA and ethanol is discussed in terms of common pathways of neuroadaptation to chronic GHBA and ethanol.

Animals↗

Locomotor capacity of spinal cord in paraplegic patients.

The induction of complex bilateral leg muscle activation combined with coordinated stepping movements is demonstrated in patients with complete paraplegia. This was achieved by partially unloading patients who were on a moving treadmill. In comparison to healthy subjects, the paraplegic patients displayed a less dynamic mode of muscle activation. In all other respects leg muscle electromyographic activity was modulated in a similar manner to that in healthy subjects. However, the level of electromyographic activity in the gastrocnemius (the main antigravity muscle during gait) was considerably lower in the patients. During the course of a daily locomotor training program, the amplitude of gastrocnemius electromyographic activity increased significantly during the stance phase, while inappropriate tibialis anterior activation decreased. Incompletely paraplegic patients benefited from the training with respect to performance of unsupported stepping movements on solid ground. In about half of completely paraplegic patients with low muscle tone, no beneficial effect of the training was seen. This may be due to an inhibitory effect on spinal neuronal activity by drugs patients were taking (e.g., prazosin, clonidine, cannabinoids). In this study intrathecal application of clonidine drastically reduced, while epinephrine enhanced locomotor muscle electromyographic activity. The results of this study promise to be significant in the treatment of paraplegic patients.

Adolescent↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗