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Biomedical subjects

A Maggi

Publications and source records attributed to A Maggi.

At least 109 records · Page 6Linked to original sources

Impairment of primary haemostasis by low molecular weight heparins in rats.

Different low molecular weight (LMW) heparins were tested on primary haemostasis in rats. Four preparations were studied; one was devoid of any effect on the bleeding time, while the other three prolonged the bleeding time to varying extents. As a consequence we studied the effect of these heparins on platelet aggregation. The fractions which prolonged the bleeding time, also inhibited the ex vivo and in vitro platelet aggregation, whereas the one devoid of any effect on the bleeding time did not affect platelet aggregation. Similar results were obtained using both platelet-rich plasma (PRP) and gel-filtered platelets. The in vitro response of platelets to aggregating agents may offer a parameter to detect the presence of 'bleeding factor(s)' in some LMW heparin preparations.

Adenosine Diphosphate↗

Estrogen modulation of the gamma-aminobutyric acid receptor complex in the central nervous system of rat.

Administration of estradiol benzoate to ovariectomized rats results in an increased binding of [3H]muscimol, [3H]diazepam and 35S-t-butylbicyclophosphorothionate in various areas of the central nervous system of rats. The effect is dose-dependent and its onset can be observed as early as 12 hr after s.c. administration of the hormone. The various binding activities are differentially affected by the hormonal treatment: the maximal effect observed for [3H]diazepam binding is in the cerebellum (+42%), for [3H]muscimol binding in the frontal cortex (+84%) and for 35S-t-butylbicyclophosphorothionate binding in the striatum (+46%) indicating that the activities of the sites are not under the same cellular regulatory control. The estrogen-induced increase in [3H]diazepam binding sites does not result in an increased protection against chemoconvulsants such as pentylenetetrazole.

Animals↗

Sexual differentiation of mammalian frontal cortex.

The pattern of distribution of the progesterone binding sites was examined in selected nuclei of the brain of male and female rat. In female rats the frontal cortex resulted to be the region with the highest concentration of 3H R5020 binding sites. However, in male rats the same region showed very little progestin binding activity. When female rats were androgenized via neonatal exposure to testosterone, the progestin binding activity of the frontal cortex became similar to that we observed in male rats. The present investigation indicates that sexual differentiation of the rat brain may include also brain regions not clearly involved in sex related functions like the frontal cortex.

Animals↗

Antithrombotic properties of dermatan sulphate in a rat venous thrombosis model.

It has been suggested that glycosaminoglycans (GAG) such as heparan sulphate (HS), dermatan sulphate (DS), chondroitin-4-sulphate and chondroitin-6-sulphate contribute to the nonthrombogenic properties of the vascular wall. We have investigated the potential role of DS and HS as antithrombotic agents in an experimental model of stasis-induced venous thrombosis in rats. We utilized a range of doses of both DS and HS (0.25-4 mg/kg BW) to test both their antithrombotic activity and potential bleeding effects. The results were evaluated with reference to an unfractionated heparin (0.5-2 mg/kg BW). We report that the antithrombotic activity of DS is not related to its anticoagulant activity as measured by the activated partial thromboplastin time (APTT), thrombin time (TT) and anti-Xa tests. The dose of DS which was able to inhibit thrombus formation by 70% did not prolong the bleeding time measured using two techniques (template and tail transection); in contrast, with HS a prolongation of both times could clearly be seen. On the other hand, standard unfractionated heparin, at a dose which is equipotent to that of DS in preventing thrombus formation, significantly prolonged the bleeding time. These results suggest that DS may be a useful antithrombotic agent with a lower haemorrhagic effect than heparin, unlike HS which expresses a haemorrhagic risk similar to heparin.

Animals↗

Dermatan sulphate induces plasminogen activator release in the perfused rat hindquarters.

Heparin or heparin-like substances have been described to induce the release of plasminogen activator (PA) activity in different animal perfusion models. In this paper we report that Dermatan Sulphate (DS) is able to induce PA activity release in the perfused rat hindquarters. Perfusion of different doses of DS (0.1 to 0.8 mg/mL) stimulates a release of PA activity that is maximum after the initial two minutes of perfusion. The amount of PA activity released rises progressively within a certain concentration range of DS (0.1 to 0.4 mg/mL) and declines thereafter (0.6 to 0.8 mg/mL). The type of PA activity increased during DS perfusion was characterized by SDS-PAGE and fibrin autography as tissue-type PA (t-PA) on the basis of its mol wt (67,000 d) and inhibition by a specific anti t-PA antiserum. This effect might be considered as potentially contributing to the antithrombotic activity of DS, at least at the local level.

Animals↗

Estrogen-induced up-regulation of gamma-aminobutyric acid receptors in the CNS of rodents.

Previous studies have identified an effect of estrogen administration on the number of central GABAergic binding sites of rat. We have further characterized this effect by performing a series of experiments in vitro where we analyzed the changes of gamma-aminobutyric acid (GABA) binding in slices of nervous tissue incubated in a physiological medium in presence of estradiol. The tissues were dissected from ovariectomized rats. In such a system, estrogen augmented the amount of [3H]muscimol binding within 3 h of incubation. The effect was dose-dependent and could be blocked by the addition of the anti-estrogen tamoxifen. The increase in [3H]muscimol binding could not be observed by addition of estradiol to broken membranes or by incubation of the slices with steroids deprived of estrogenic activity. Furthermore, the estrogen-induced increase of GABA binding sites could be prevented by addition of cycloheximide and alpha-amanitin in the incubation medium. Our data indicate that the estrogen may increase the number of GABA binding sites by direct interaction with the GABA receptor gene or genes involved in the metabolism of GABA receptor.

Animals↗

Sexual dimorphism in the response of the GABAergic system to estrogen administration.

Administration of estradiol benzoate to gonadectomized female rats results in up-regulation of CNS gamma-aminobutyric acid (GABA) receptors. The increase of [3H]muscimol binding activity is observed in six of the seven brain areas examined. The same treatment, performed in castrated male or androgenized female rats, induced an increase of [3H]muscimol binding only in the striatum. Evidence is provided suggesting that the dimorphic sensitivity of GABA receptor is not correlated with the difference in spontaneous motor activity reported between male and female rats.

Animals↗

Role of female gonadal hormones in the CNS: clinical and experimental aspects.

The large body of evidence presented indicates that in the brain the action of sex hormones cannot be thought as restricted to the regulation of endocrine functions and mating behavior. Estrogens and progesterone seem to act in numerous regions of the CNS to regulate motor as well as limbic functions. Furthermore, the data reviewed indicate that these hormones may modulate neuronal activity through a wide variety of mechanisms. More studies should focus on such mechanisms in order to better understand the role of sex hormones in the CNS and to devise ways of limiting their effects on depression, epilepsy etc. It is known that in peripheral target organs these hormones modulate cell activities by binding to specific receptors which can recognize the DNA sequence and activate the transcription of selected genes (135, 136). There is evidence supporting the hypothesis that this mechanism of action has been conserved also in the brain. First, the brain receptors for progesterone and estrogens are functionally and biochemically indistinguishable from those in the periphery (4, 5): they may be concentrated in neuronal nuclei and bind chromatin "in vitro" (7). Second, a temporal relationship has been observed between administration of steroids and the increase of polymerase II activity (137) and protein synthesis (4, 5). Third, various hormone-induced behaviors may be blocked by inhibitors of the protein synthesis (138, 139, 140, 141). However, sex hormones must be capable to regulate neuronal functions by mechanisms other then genomic. In fact, the topical application of estrogen or progesterone on nervous tissue results in a rapid change of membrane potential (60, 71). Such a rapid effect is not likely to be the consequence of nuclear action, but rather must be related to events occurring on the cell surface. It has been hypothesized that sex steroids affect the fluidity of the cell membrane, therefore modifying the ion transport or neurotransmitter receptor activity (142). If this were the case we would expect to observe a similar effect after application of any steroid. Experimental evidence demonstrates that not all the steroids affect the nervous membrane potential. Moreover, two steroids, estradiol and progesterone, have been described to modulate membrane potential in an opposite way (66, 67, 69, 75). At the moment, there is no evidence for the presence of steroid receptors on neuronal membranes which could mediate the described phenomena.(ABSTRACT TRUNCATED AT 400 WORDS)

Amygdala↗

Progesterone in rat brain: modulation of beta-adrenergic receptor activity.

Cytosolic proteins binding specifically the progesterone analogue 3H R5020 can be detected in various areas of the central nervous system (CNS) of rat. Our study demonstrates that the concentration of progesterone receptors in the brain of adult, ovariectomized, female rats is maximal in frontal cortex and midbrain and lowest in the cerebellum. Short term administration of the hormone does not alter the beta-adrenergic receptor system, while a prolonged administration of progesterone results in an up-regulation of 3H-DHA binding in the frontal cortex. Such increase in binding activity is due to an increased number of beta-adrenergic receptors. Furthermore, high doses of progesterone can also increase the number of beta-adrenergic binding sites in an "in vitro" system where brain slices are incubated for few hours in a physiological medium.

Animals↗

Progesterone-binding sites of the chick oviduct receptor. Presence of a weaker ligand site which is destroyed by phosphatase treatment.

Titration of chick progesterone receptor over a wide range of [3H]progesterone concentration (0.15 to 90 nM) shows two distinct types of binding sites in cytosol and in partially purified receptor samples prepared from oviducts of estrogenized chicks. The difference in affinity between the two sites (Kd = 1 nM; Kd = 25 nM) is sufficient to allow analysis by Scatchard plot methods. Ligand competition studies show that both sites have the same relative specificity for progesterone compared to other steroids. Both sites seem to be on the same receptor molecule as shown by their copurification and chromatographic properties. No cooperativity between the two sites has been detected in analysis using either rate kinetics or equilibrium methods. Thus, the function of the low affinity sites is not apparent at this time; it does not appear to function as a "helper" site which influences binding to the high affinity site previously described. The binding constant of the low affinity site is sufficiently strong to allow potential occupancy of these sites in vivo, at least at certain stages of the female reproductive cycle. The hormone-binding activity of the low affinity site can be destroyed after in vitro treatment with alkaline phosphatase, but the high affinity site remains functional under these conditions. Inhibitors of the enzyme block the inactivation. Furthermore, preliminary data in vivo suggest that estrogen administration to the animal can influence the relative titer of the low affinity sites.

Alkaline Phosphatase↗

Progesterone and estrogens in rat brain: modulation of GABA (gamma-aminobutyric acid) receptor activity.

Our data indicate that estrogens and progesterone can regulate the number of GABA receptors (as detected by [3H]muscimol binding assay) in rat brain. Both hormones act in selected areas. The extent of the effect (up to 160% increase) and the number of areas responsive suggest that sex hormones may play a very important role in the regulation of the functions of GABAergic transmission in the central nervous system.

Animals↗

[Exercise testing in patients with the sick sinus syndrome].

Heart rate response to exercise was compared in three groups of subjects; 22 patients (mean age 63.7 years) with sick sinus syndrome and no other significant heart disease (Group I); 10 subjects of the same age with stable, asymptomatic sinus bradycardia at rest (Group II); 29 age-matched controls (Group III). All subjects underwent maximal, symptom-limited exercise testing and the maximal heart rate (HR max), the ratio between HR max and the theoretical maximal heart rate (HR%), exercise capacity (EC) and the ratio between heart rate % and exercise capacity (HR%/EC) % of the three groups were compared. Maximal heart rate, heart rate % and (HR%/EC) % in Group I patients were significantly lower than in Group III subjects (119.1 +/- 24.0 vs 139.0 +/- 18.2; 76.0 +/- 13.9 vs 87.9 +/- 10.8 and 83.0 +/- 19.3 vs 97.5 +/- 15.1 respectively); (HR%/EC) % was significantly lower in Group I patients compared to Group II subjects (83.0 +/- 19.3 vs 101.5 +/- 28.6). Heart rate response was the same in Group I and Group II patients and exercise capacity did not differ in the three groups. Maximal heart rate, heart rate % and (HR%/EC) % were similar in Group II and Group III subjects. The association of (HR%/EC) % less than or equal to 85% with either HR max less than or equal to 110/min or HR% less than or equal to 70% at the end of maximal exercise testing may be suggestive of sick sinus syndrome. The reduced heart rate response during exercise may be helpful in assessing sick sinus syndrome in patients with no other signs of heart disease.

Adult↗

PHA-induced neutrophil-mediated cytotoxicity.

Neutrophils activated by phytohemagglutinin (PHA) were cytotoxic to chicken red blood cells (CRBC), as determined by the 51Cr release assay. High levels of cytotoxicity were obtained when one CRBC was available for each effector cell. Neutrophils from patients with Chronic Granulomatous Disease (CGD), incapable of generating potentially toxic oxygen radicals, had a reduced cytotoxicity activity, suggesting the requirement for an intact oxidative metabolism in the PHA-induced neutrophil-mediated cytotoxicity. However, CGD neutrophils maintained approximately 50% of this activity, compared with normal cells. These findings support the conclusion that both oxygen-dependent and oxygen-independent mechanisms are necessary to achieve an efficient cytotoxicity.

Adolescent↗

[Arteriosclerosis obliterans of the lower limbs. Epidemiological study of the risk factors].

Chronic arterial occlusive disease of lower limbs is recognized as a typical multifactorial disease, but the role of some risk factors is still debated, because contrasting results have been obtained in epidemiological studies. We investigated the prevalence of hypercolesterolemia, hypertriglyceridemia, hypertension, smoking habits and diabetes in a population of 172 patients with peripheral arterial disease admitted to the III and V Medical Division of the "Ospedale Regionale" of Parma in the period January 1979 - April 1983, and in a control group of 174 subjects comparable for age and sex, free of clinical symptoms or signs of atherosclerosis. Statistically significant (p less than 0,005) increases in the prevalence of hypercolesterolemia, hypertriglyceridemia, smoking and hypertension were found in vascular patients compared with controls, the relative risk for the various considered factors being respectively: 6.40; 4.72; 4.03; 3.16.

Adult↗