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Biomedical subjects

G Colombo

Publications and source records attributed to G Colombo.

At least 199 records · Page 11Linked to original sources

Studies on the luteolytic activity of MDL-646, a new gastroprotective PGE1 analogue, in the hamster.

MDL-646, 11,15-dihydroxy-16-methyl-16-methoxy-9-oxo- prost -13-en-1-oic acid methyl ester, is one of the most active members of a new class of PGE1 analogues with potent gastric cytoprotective and antisecretory activity. The potential luteolytic activities of MDL-646 and its corresponding PGE2 derivative, L 14224 were assessed from their ability to terminate pregnancy and to reduce plasma progesterone levels in the hamster. PGE1 and PGE2 were used as reference compounds. The biological and biochemical data clearly demonstrate that these 16-methyl-16-methoxy PGE derivatives, given s.c. or p.o. either once or for 3 days, have no luteolytic effects up to a daily dose of 2-2.5 mg/kg, and are therefore at most 1/2 to 1/4 as luteolytic as the parent natural PGEs. The dissociation between gastroprotective and luteolytic activity was interpreted to indicate that these new PGE derivatives have a specific action.

Abortion, Spontaneous↗

Inhibition of PG production by MDL 035, a new non-steroidal non-acidic anti-inflammatory compound, in rat gastric mucosa and inflammatory exudate.

The effects of 3-(1-methylethyl)-2-(4-methoxyphenyl)-3H-naphth [1,2-d]imidazole, MDL 035, a new non-steroidal non-acidic anti-inflammatory compound, on the production of prostaglandin (PG) in rat gastric mucosa in vivo and in vitro and in inflammatory exudate in vivo were studied. MDL 035 reduced PGE2 and 6-keto-PGF1 alpha levels more effectively in inflamed tissue than in gastric mucosa when assayed in in vivo experiments, whereas indomethacin and other non-steroidal anti-inflammatory drugs (NSAIDS) are equally effective in both systems. MDL 035 is almost as active as indomethacin when incubated with gastric tissue in vitro. The better gastric tolerance of MDL 035 than of other NSAIDS is discussed in relation to these differences in in vivo and in vitro effects.

6-Ketoprostaglandin F1 alpha↗

Contragestational effects of DL-alpha-difluoro-methylornithine, an irreversible inhibitor of ornithine decarboxylase, in the hamster.

In the hamster, there are remarkable changes in ODC activity in various uterine reproductive tissues during gestation. When DL-alpha-difluoromethylornithine (DFMO), a highly selective irreversible inhibitor of ODC, is given during the early post-implantation period, when ODC activity in the conceptus is rapidly rising and reaches its highest values, it causes pregnancy arrest. Low doses of DFMO are contragestational only during a short period of gestation (day 7 and 8), with primary action on the embryo. Higher doses given soon after implantation (day 5) induce early pregnancy termination by a primary effect on decidual tissue. Biochemical investigations in animals treated on day 5 or day 7 showed that DFMO induces a rapid and dramatic fall in ODC activity in the products of conception. These findings strengthen and extend previous evidence that ODC and polyamines play an essential role in the maintenance of early pregnancy in rodents.

Animals↗

Evidence for a role of progesterone in the control of uterine ornithine decarboxylase in the pregnant hamster.

Changes in uterine ornithine decarboxylase (ODC) activity throughout pregnancy and the importance of progesterone in the regulation of this enzyme during the early post-implantation period have been studied in the hamster. Soon after implantation, from day 5 to day 6 of pregnancy, ODC activity rapidly increased. It reached a plateau on day 7, then abruptly fell on day 8 and remained low until the end of pregnancy. DL-alpha-difluoromethyl-ornithine (DFMO), an irreversible inhibitor of ODC, induced pregnancy termination as a consequence of the reduction of uterine ODC activity. When pregnancy arrest was induced by removing endogenous progesterone by administration of prostaglandin F2 alpha (PGF2 alpha) or by ovariectomy, the ODC rise was completely abolished, and exogenous progesterone was able to entirely counteract this effect on the enzyme activity and the termination of pregnancy. These results suggest that progesterone play a significant role in the rise of uterine ODC activity, which appears to be essential for the early post-implantation events needed for pregnancy maintenance.

Animals↗

Lymphocyte subpopulations and surface membrane immunoglobulins in myasthenia gravis.

Lymphocyte subpopulations were studied in 16 myasthenic patients by means of E and EA7s rosettes and surface membrane immunofluorescence. Myasthenic patients showed an increase in lymphocytes with surface IgM an IgD when compared to a control group. In female patients this increase was highly significant, and lymphocytes bearing membrane IgG and IgA were also augmented. No difference was found in male patients when compared with sex-matched controls. These results suggest an activation of the B cell compartment restricted to female patients, and support the hypothesis of different immunopathogenetic mechanisms in this disease.

Adult↗

Phosphoenolpyruvate carboxykinase (guanosine 5'-triphosphate) from rat liver cytosol. Divalent cation involvement in the decarboxylation reactions.

The presence of a divalent metal ion together with a catalytic amount of inosine 5'-diphosphate (IDP) is essential for the formation of pyruvate from oxalacetate catalyzed by purified rat liver cytosol phosphoenolpyruvate carboxykinase (PEPCK). With decreasing order of effectiveness, this pyruvate-forming activity was supported by micromolar levels of Cd2+, Zn2+, Mn2+, and Co2+. At the same concentrations, Mg2+ or Ca2+ was not effective. Combinations of Cd2+ with either Zn2+, Mn2+ or Co2+ were not additive with respect to the pyruvate-forming activity of PEPCK. Kinetic determination, with Cd2+ as the supporting cation, showed a 1:1 stoichiometry of interaction between each enzyme molecule and the nonconsumable substrate IDP. With 10 muM added Cd2+, the apparent Km for oxalacetate was 41 muM, and the apparent Ka for IDP was 0.25 muM. With Zn2+ or Mn2+, the apparent Ka for IDP was 0.2 or 0.13 muM, respectively. The effect of divalent transition-metal ions on PEPCK-catalyzed formation of phosphoenolpyruvate from oxalacetate was also investigated. Under steady-state conditions, the basal activity with MgITP was effectively enhanced with micromolar levels of Mn2+, Cd2+, or Co2+ included in the assay. The Vm increased 7- and 3.6-fold, and the apparent Km for MgITP changed by about a factor of 2 with the optimal concentrations of Mn2+ and Co2+, respectively. The most striking changes were in the apparent Km values for oxalacetate, which decreased to one-third and one-tenth when either Mn2+ or Co2+ was present in the assay together with Mg2+. The possible physiological importance of this kinetic effect is discussed.

Animals↗

Thrombin inhibitors in women on oral contraceptives.

Progressive antithrombin activity and the immunological levels of antithrombin III, alpha 2-macroglobulin, and alpha 1-antitrypsin were measured in women at various intervals during treatment with oral contraceptives and in a group of untreated women. No significant changes were observed in any of the above parameters. In both control and treated women, there was a positive statistical correlation between progressive antithrombin activity and antithrombin III immunological levels, whereas no correlation was found between the former and alpha 1-antitrypsin or alpha 2-macroglobulin immunological levels. This study questions the possibility of thrombin inhibitors being selective signs of hypercoagulability during treatment with oral contraceptives.

Adolescent↗

[An approach to hypertension in a native population].

In the article the authors illustrate: a) a community detection program designed to identify subjects with high blood pressure for treatment; b) the degree of participation; c) the cost of realization; d) the prevalence of arterial hypertension. A total of 4.149 subjects, or 65% of the examined population over age 8, were screened. The opportunity to have their blood pressure checked were offered with a letter of invitation to a centralized ambulatory. The cost of realization was L. 360 for every screened subject. The prevalence of hypertension was 20.4%.

Adolescent↗

[Iatrogenic risks. Medicolegal and organizational problems concerning the performance of radiographic examinations with intravenous administration of contrast media].

The forensic medicine and organizational aspects of doing X-rays with i.v. contrast medium are discussed. Special attention is paid to the pathogenetic and clinicotherapeutic aspects of X-ray and contrast medium induced accidents together with the organizational problems posed by these problems in small hospitals without anaesthesia and resuscitation departments.

Contrast Media↗

Increase of T.G lymphocytes in human one-way mixed lymphocyte culture.

Human one-way mixed lymphocyte culture induces a significant increase of EA(7S) rosette-forming cells. Using fractionation procedures, an increased number of Fc receptor-bearing cells in the T high-enriched populations was found from alloactivated lymphocytes compared with similar fractions obtained after autologous control cultures. Additional experiments showed a parallel increase of E-rosette-forming cells in the Fc receptor-enriched alloactivated fractions. The results indicate that an increase of T.G lymphocytes occurs during in vitro alloactivation in man.

Cell Count↗

A renal abnormality as a possible cause of "essential" hypertension.

The renal abnormality which causes hypertension in the Milan hypertensive strain of rats disappears as hypertension develops. Because of the many analogies between the condition in these rats and "essential" hypertension in man, the same pattern of change may occur if a renal abnormality is the cause of essential hypertension in man. This hypothesis was tested in two groups of young normotensive subjects matched for age, sex, and body-surface area; in the first group both parents were hypertensive, and in the second group both parents were normotensive. Renal plasma-flow, glomerular filtration-rate, plasma-volume, plasma-renin activity, plasma-concentrations of Na+, K+, and catecholamines, 24 h urinary excretion of Na+, K+, and aldosterone, and the cardiac index were measured so that renal function and the role of factors affecting blood-pressure regulation could be assessed. Renal plasma-flow was significantly higher (p less than 0.01) in the first group, whereas results of tests for all the other factors were almost the same in both groups. The hypothesis that a primary kidney abnormality causes hypertension in a proportion of patients with essential hypertension is proposed.

Adult↗