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Biomedical subjects

M Colombo

Publications and source records attributed to M Colombo.

At least 235 records · Page 13Linked to original sources
PubMed1988

Antagonism by N-methyl levallorphan-methane sulphonate (SR 58002 C) of morphine-elicited acute and chronic central and peripheral effects.

The peripheral activity of the quaternary narcotic antagonist N-methyl levallorphan-methane sulphonate (SR 58002 C) at opioid sites located in the periphery and in the central nervous system (CNS), was studied by different approaches in rats after subcutaneous injection (s.c.). Pretreatment with SR 58002 C 2,8 or 32 mg/kg s.c. 10, 50 or 110 min before buprenorphine consistently reduced buprenorphine in vivo binding only in the small intestinal longitudinal muscle with attached myenteric plexus (MP), whereas naloxone (1 mg/kg s.c.) 10 min before buprenorphine lowered buprenorphine binding in MP and brain (without cerebellum). Plasma levels were not altered by SR 58002 C or naloxone. The same doses of SR 58002 C injected 10, 50 or 110 min before morphine selectively antagonized the inhibition of transit of a charcoal meal along the small intestine (mainly a peripheral effect) induced by the agonist, but did not antagonize morphine-elicited analgesia in the hot-plate test (central effect). Naloxone (1 mg/kg s.c.) injected 10 min before morphine antagonized both agonist effects simultaneously. In morphine-dependent rats SR 58002 C (0.25, 1, 4 and 32 mg/kg s.c.) induced diarrhea, dose-dependently, in most animals within the first 30 min, while jumping, measured in the same rats, occurred in some animals, not dose-dependently, from 60 min on. Naloxone (1 mg/kg s.c.) induced both effects in most rats. These findings suggest that, although SR 58002 C probably penetrates the blood-brain barrier in some morphine-dependent rats, it discriminates peripheral and CNS opioid effects.

Animals↗
PubMed1988

Prospective study of hepatitis after factor VIII concentrate exposed to hot vapour.

A factor VIII concentrate prepared from large plasma pools and then exposed to hot vapour to inactivate blood-borne viruses was evaluated in 28 factor-VIII deficient patients (14 vaccinated against the hepatitis B virus, HBV) who had not been treated with any blood product and hence were highly susceptible to the development of post-transfusion hepatitis. Tests for aminotransferases and HBV markers were made every 2 weeks in the first 4 months and at 5, 6 and 12 months. Twenty-four patients were considered not to have developed hepatitis, either because they had no elevations of aminotransferases or did not become seropositive for HBV markers. The four remaining unvaccinated patients (three treated with the same batch and the fourth with a different one) developed HBV infection 8-24 weeks after the first concentrate infusion. Hence, this method of viral inactivation did not afford complete protection from hepatitis B.

Adolescent↗
PubMed1988

Representation of serial order in monkeys (Cebus apella).

Cebus monkeys were trained on a five-item serial learning task, symbolized as ABCDE; the initial stages of training were on the shorter subseries AB, ABC, and ABCD. To assess the monkeys' knowledge of the sequential position of each item, pair-wise tests were given to 2 subjects after acquisition of the ABCD series and to 4 subjects after reaching criterion on the ABCDE series. In both tests, the monkeys performed at high levels on the interior pairs, which were BC for the ABCD series, and BC, BD, and CD for the ABCDE series. These results, as well as the orderly relations observed in the pair-wise tests between first-item response latency and first-item position and between second-item response latency and number of missing items, indicated that the monkeys had developed a well-organized internal representation of the four- and five-item series. Although pigeons are also capable of learning four-item and five-item series, they apparently do not develop a comparable representational structure. The disparity between the monkeys' and pigeons' representational competence for serial order is predictable from the difference in their capacities for associative transitivity.

Animals↗
PubMed1987

Clinical studies with treated clotting factor concentrates.

We carried out safety studies in 45 previously untreated patients with congenital coagulatory defects, who needed to be treated with clotting factor concentrates. Non-A, non-B hepatitis developed in patients who received dry heated F VIII preparations with or without chloroform, but not in those who were infused with hot-steam treated F VIII or chromatography treated F IX. Hepatitis B developed in 3 unvaccinated patients who received the same lot of hot steam treated F VIII. None of the 45 patients we have investigated developed HTLV-III/LAV antibody. Thus, dry heating of concentrates does not prevent hepatitis transmission. Hot-steam and hydrophobic interaction chromatography seem to be more effective in preventing hepatitis transmission, but not completely safe. All the above procedures except hot steam seem to protect from hepatitis B. They all seem to prevent HTLV-III/LAV transmission.

Antibodies, Viral↗
PubMed1987

Pharmacological properties of besulpamide, a new diuretic, in rats and dogs.

Besulpamide, a newly synthesized compound, has demonstrated significant diuretic activity in rats and dogs, similar to that of chlorthalidone, clopamide and xipamide. Antihypertensive activity of besulpamide is similar to that of hydrochlorothiazide and was demonstrated in rat one-kidney desoxycorticosterone acetate (DOCA)-salt hypertension. In addition, besulpamide, like hydrochlorothiazide, potentiated the antihypertensive activity of captopril in spontaneously hypertensive rats (SHR). Doses of besulpamide exceeding those normally required for pharmacological activity did not evoke adverse reactions in rats and mice.

Animals↗
PubMed1987

[Use of the monoclonal antibody KI-67 in the study of the proliferative activity of urologic tumors. Preliminary data].

The authors report the preliminary data of a study on the proliferative activity in urologic cancers. They use the monoclonal antibody KI-67 which can find out a nuclear antigen present only in cells in proliferative phase. They describe the methodology and report the results concerning 12 cancers of the kidney, 17 of the bladder, 17 of the prostate and 2 of the testicle. The most interesting results were obtained in the study of bladder cancer where they could pick out, in the context of the cancers with grading G2, a sub-group with proliferative characteristics similar to those of cancers G3 and vice-versa. They also obtained important results in the study of prostate cancer in hormonal therapy, as they could demonstrate the disappearance of the proliferative activity in patients responding clinically to the treatment.

Animals↗
PubMed1987

Comparative light and electron microscopic observations of the lesive effects of two non-steroid anti-inflammatory drugs plus stress on rat gastric mucosa.

In this histological study it has been demonstrated that a single-dose administration of piroxicam, at the same dosage (4 mg/kg) as droxicam, has a greater erosive potential on the gastric mucosa of rats later exposed to cold stress. For this purpose the depth of all lesions found was evaluated by light microscopy and results showed that piroxicam produces lesions deeper and more numerous than those of droxicam. The transmission and scanning electron microscopic studies showed that the lesive mechanism was very similar for both drugs and that both local and general factors induced by these drugs and stress come into play. Absorption or penetration and uptake by the cells of the mucosa have been considered among the most important local factors in the development of erosive gastric lesions caused by non-steroid anti-inflammtaory drugs. As this absorption is in direct relation to the depth of the lesions, it can be considered from the results of this study that the lesser lesive effect of droxicam on the gastric mucosa when compared to that of piroxicam is due to the fact that, owing to its hydrolysis to piroxicam the absorption rate is slower.

Animals↗
PubMed1986

Cloning of the gene coding for human L apoferritin.

A recently reported cDNA clone coding for human promyelocytic L apoferritin, shows some differences with a liver L apoferritin cDNA. We have investigated if these differences are due to the expression of different genes or to an alternative transcription of an unique gene. In this paper we report data suggesting that a single gene is mainly expressed in several tissues examined. This gene has been cloned and characterized. Its sequence shows three introns: the exon sequence is identical to that of cDNA clone isolated from human liver. A minimum of five related pseudogenes have been also analysed. One of them is a processed pseudogene interrupted by an intron-like fragment.

Amino Acid Sequence↗
PubMed1986

Structure of gene and pseudogenes of human apoferritin H.

Ferritin is composed of two subunits, H and L. cDNA's coding for these proteins from human liver (1,2,3), lymphocytes (4) and from the monocyte-like cell line U937 (5) have been cloned and sequenced. Southern blot analysis on total human DNA reveals that there are many DNA segments hybridizing to the apoferritin H and L cDNA probes (1,2,4,6). In view of the tissue heterogeneity of ferritin molecules (7,8), it appeared possible that apoferritin molecules could be coded by a family of genes differentially expressed in various tissues (1,2). In this paper we describe the cloning and sequencing of the gene coding for human apoferritin H. This gene has three introns; the exon sequence is identical to that of cDNA's isolated from human liver, lymphocytes, HeLa cells and endothelial cells. In addition we show that at least 15 intronless pseudogenes exist, with features suggesting that they were originated by reverse transcription and insertion. On the basis of these results we conclude that only one gene is responsible for the synthesis of the majority of apoferritin H mRNA in various tissues examined, and that probably all the other DNA segments hybridizing with apoferritin cDNA are pseudogenes.

Apoferritins↗
PubMed1986

Immunohistochemical evidence for extrinsic and intrinsic opioid systems in the guinea pig superior cervical ganglion.

Immunohistochemical localization of the opioid peptides alpha-neo-endorphin (alpha-neo-END), dynorphin A (DYN) and leu-enkephalin (leu-ENK) in the guinea pig superior cervical ganglion (SCG) was studied following central denervation, peripheral axotomy, and after application of the depleting drug reserpine and of the neurotoxin 6-hydroxydopamine. The paraganglionic cells of the SCG are shown to form an intrinsic opioid--(alpha-neo-END, DYN, leu-ENK)--immunoreactive system being not visibly responsive to the experimental procedures. Leu-ENK-immunoreactive fibres ascend in the preganglionic trunk and supply fibre baskets to defined clusters of postganglionic neurones. Principal ganglion cells of the SCG containing alpha-neo-END- and DYN-immunoreactivity project to extraganglionic targets via the postganglionic nerves. These findings are indicative of a sympathetic alpha-neo-END-ergic and DYN-ergic innervation of effector organs. They also point to a modulatory function of opioids on neuronal activity in a paravertebral ganglion.

Animals↗
PubMed1986

Pharmacological evaluation of 5-(Z,E)-13,14-didehydro-20-methyl-carboprostacyclin (FCE 22509).

FCE 22509, 5-(Z,E)-13,14-didehydro-20-methyl-carboprostacyclin, a chemically stable prostacyclin (PGI2) derivative, was 3.5 times more potent than PGI2 in relaxing bovine coronary artery in vitro; unlike PGI2, it did not contract bovine coronary vein and it antagonized PGI2-induced contractions of the coronary vein. In vitro smooth muscle (guinea pig ileum and trachea and rat stomach strip) was contracted to a lesser extent than with PGI2. FCE 22509 was about five times less potent than PGI2 in deaggregating platelet clumps formed on rabbit Achilles tendon bathed with heparinized cat blood (ED50 = 7.6 and 1.6 mcg/kg i.v. respectively). In the conscious normotensive and spontaneously hypertensive rat FCE 22509 lowered mean systemic arterial pressure (MSAP) (ED25 = 11.5 and 4.8 mcg/kg i.v.) to a lesser extent than PGI2 (ED25 = 2.1 and 2.34 mcg/kg i.v.) and increased heart rate but not dose-dependently. Orally administered, FCE 22509 likewise reduced MSAP though at high dosages (ED30 = 1.33 and 1.02 mg/kg in normotensive and hypertensive rats). Heart rate (HR) was raised after i.v. and oral treatment but not dose-dependently. In the open-chest anaesthetized dog, FCE 22509, compared with PGI2 at the same three doses, 0.2, 0.4 and 0.8 mcg/kg i.v., lowered MSAP but its hypotensive effect was less pronounced than that of PGI2. Like PGI2, FCE 22509 did not modify HR (though PGI2 showed a tendency to a decrease and FCE 22509 seemed to increase this cardiovascular function) and mean pulmonary arterial pressure (MPAP) and likewise significantly reduced myocardial contractile force. After infusion of PGI2 and FCE 22509 0.2 mcg/kg i.v. for 15 min in the open chest anaesthetized cat, the ex-vivo ADP-induced inhibition of platelet aggregation was the same for both compounds. Unlike PGI2, which reduced MSAP and MPAP, FCE 22509 had no significant lowering effect on MSAP and MPAP.

Animals↗
PubMed1986

Dendritic development in the neocortex of adult rats following a maintained prenatal and/or early postnatal life undernutrition.

The Golgi-Cox method was used to study the maturation of the large pyramidal cells of the Vth cortical layer in three groups of adult rats: one subjected to undernutrition during the first month of life, another throughout the first 2 mth of life, and the last one during gestation and the suckling period. The main alterations consist of a decrease in the number and span of dendritic basilar processes of large pyramidal cells. In animals malnourished during prenatal life and the suckling period the reduction of the basal dendritic arborization was more apparent. It is postulated that the vulnerable period for the basal dendritic development occupies the period from the end of pregnancy until the first 3 wk of postnatal life in the rat (suckling period). Noxious influences acting during this phase induce sequelae that cannot be reversed by subsequent refeeding. A maintained nutritional insult during prenatal and early postnatal life induces the most severe changes in dendritic arborizations, compared to those resulting from a prolonged postnatal malnutrition.

Animals↗
PubMed1986

Persistent elevation of the aminoterminal peptide of procollagen type III in serum of patients with acute viral hepatitis distinguishes chronic active hepatitis from resolving or chronic persistent hepatitis.

We measured the serum concentration of the aminoterminal propeptide of collagen type III (PIIIP) in 22 patients with acute viral hepatitis (19 hepatitis B, 3 hepatitis non-A, non-B). Nine patients showed persistent biochemical remission, 13 patients developed chronic active hepatitis (CAH); 6 of those underwent therapy with methylprednisolone and azathioprine. Thirteen patients with chronic persistent viral hepatitis (CPH) and 38 healthy individuals were also investigated. In the control group, PIIIP values were 9.5 +/- 2.25 ng/ml (chi +/- SD; range 4-14 ng/ml). All patients with acute hepatitis showed elevated PIIIP values (range 20-125 ng/ml). In the 9 patients with biochemical resolution, PIIIP normalized after a maximum of 6.5 months (range 7.5-14 ng/ml). In CAH, PIIIP was persistently elevated on the day of the diagnostic biopsy (range 15.6-35.7 ng/ml). In comparison, the patients with chronic persistent hepatitis showed a range of 5.0-15.4 ng/ml. Differences between controls and CAH and CPH/CAH were statistically highly significant (P less than 0.001). Treatment of patients with CAH by immunosuppression resulted in normal PIIIP values in 3 and persistently elevated values in 3. One additional patient had normal PIIIP after treatment with an increased dose of methylprednisolone of 16 mg p.d. Serum concentrations of PIIIP offer a non-invasive index for the development of chronic active hepatitis from acute viral hepatitis. This blood test may also be useful for monitoring immunosuppressive treatment in CAH.

Acute Disease↗