Effects of estradiol metabolites on cAMP production and degradation.

(Full text is available at http://www.manu.edu.mk/prilozi). 17beta-Estradiol is metabolized to 2-hydroxyestradiol, and 2-hydroxyestradiol is converted to 2-methoxyestradiol. These steroids reduce proliferation of, migration of and collagen production by vascular smooth muscle cells with an order of potency of 2-methoxyestradiol > 2-hydroxyestradiol > 17beta-estradiol, i.e. the converse of their estrogenic potency. Since cAMP also inhibits cell growth, it is conceivable that these steroids alter cAMP synthesis or degradation, and this hypothesis was addressed in this study. In cultured preglomerular vascular smooth muscle cells pretreated with a high concentration of a broad spectrum phosphodiesterase inhibitor (3-isobutyl-1-methylxanthine, 1 mM) to eliminate phosphodiesterase activity as a confounding variable, high (100 microM), but not low (10 microM), concentrations of 17beta-estradiol, 2-hydroxyestradiol and 2-methoxyestradiol attenuated isoproterenol-induced cAMP by 15%, 19% and 55%, respectively. 2-Hydroxyestradiol (100 microM) also attenuated forskolin-induced cAMP by 31% in cells treated with 3-isobutyl-1-methylxanthine. In cells not pretreated with 3-isobutyl-1-methylxanthine and using concentrations of steroids (10 microM) that did not interfere with adenylyl cyclase, 17beta-estradiol decreased by 34%, 2-hydroxyestradiol did not alter and 2-methoxyestradiol increased by 60% isoproterenol-induced cAMP. These results indicate that in preglomerular vascular smooth muscle cells, high concentrations of 2-hydrxoyestradiol markedly inhibit adenylyl cyclase whereas 17beta-estradiol and 2-methoxestradiol only modestly inhibit adenylyl cyclase even at high concentrations. Our results also indicate that lower concentrations of 17beta-estradiol, 2-hydroxyestradiol and 2-methoxyestradiol activate, have no effect on and inhibit, respectively, phosphordiesterase activity. The effects of these compounds on phosphodiesterase activity may account in part for the greater potency of 2-methoxyestradiol as an anti-growth compound compared with 17beta-estradiol and 2-hydroxyestradiol. Key words: Estradiol, Estradiol metabolites, 2-Methoxyestradiol, Cyclic adenosine monophosphate.

Progesterone inhibits vascular remodeling and attenuates monocrotaline-induced pulmonary hypertension in estrogen-deficient rats.

(Full text is available at http://www.manu.edu.mk/prilozi). Pulmonary arterial hypertension (PH) is predominantly a disease of young females. Yet, little is known regarding the effects of female sex hormones in PH. Female rats develop less severe PH compared to male rats, and ovariectomy (OVX) exacerbates PH. Although OVX rats treated with estradiol develop less severe disease, the role of progesterone in OVX-induced exacerbation of disease has not been examined. Progesterone was shown to dilate pulmonary vessels and to inhibit proliferation of endothelial and vascular smooth muscle cells. Therefore, we hypothesized that progesterone may confer protective effects in experimental PH. A total of 30 female rats were ovariectomized and OVX rats were randomly administered either saline (OVX-Control group, n = 7), monocrotaline (60mg/kg i.p.; OVX-MCT group; n = 12), or MCT plus progesterone (30microg/kg/h via osmotic minipumps; OVX-MCT+P group; n = 11). After 32 days animals were instrumented for in situ (open chest) measurements of right ventricle (RV) peak systolic (RVSP) and end diastolic (RVEDP) pressures, and tissue samples were obtained for morphometric and histological analysis. Administration of MCT elevated RVSP (22.2 +/- 1.1 vs. 46.7 +/- 2.4 mmHg) and RVEDP (1.51 +/- 0.86 vs. 11.9+/-2.2 mmHg), increased RV/left ventricle + septum (RV/LV+S) ratio (0.256 +/- 0.010 vs. 0.582 +/- 0.033, OVX vs. OVX-MCT), and induced media hypertrophy of small size pulmonary arteries. In ovariectomized pulmonary hypertensive rats, treatment with progesterone attenuated the severity of disease (OVX-MCT+P group: RVSP = 36.6 +/- 2.3 mmHg; RV/LV+S = 0.468 +/- 0.025; RVEDP = 7.5 +/-1.5 mmHg), attenuated vascular remodeling (media % index: 28.2 +/- 1.1 vs. 34.2 +/- 1.3), and reduced mortality (9% vs. 25%; OVX-MCT+P vs. OVX-MCT). This study provides the first evidence that in estrogen-deficient rats, progesterone has protective effects in MCT-induced PH. Further evaluation of the role of progesterone and its interaction with estrogens in pulmonary hypertension is warranted. Key words: Pulmonary Hypertension, Progesterone, Estrogens, Vascular remodeling.

[Emergency management of intracerebral hematoma of nontraumatic origin]. / Urgentno zbrinjavanje intracerebralnih hematoma netraumatskog porekla.

A series of 78 consecutive non-traumatic intracerebral hematomas operated upon between 1972 and 1981 is presented; the authors analysed the etiology, age, sex, clinical manifestation and state of consciousness as well as timing of surgery as factors potentially influencing the outcome. The mortality rate before introducing of C. T. scan (before 1978) as a main diagnostic procedure, was over 50% and decreased to 25% after its use. Patients operated on in the first 24 hours after the bleeding, have mortality of 50%, on the second day 16%, and since the third day there was no mortality. The mortality rate in patients with moderate neurological deficiencies and slight disturbances of consciousness was under 10%, reached full 91% in patients with severe neurological deficiencies and deep coma. The etiology as a possible factor determining the outcome in non-traumatic intracerebral hematomas is also analysed and discussed. In patients with AVM as a cause of compressive hematoma there was no mortality, while in hematomas due to aneurysmal rupture, mortality was over 42%. Mortality in hypertensive patients was 53% and in spontaneous hematomas it was 35%.

[Scanographic picture of development of spontaneous intracerebral hematoma (report of a case)]. / Skenografski prikaz razvoja spontanog intracerebralnog hematoma (prikaz slucaja).

The authors present a case of a 25 old male with spontaneous left temporal intracerebral haematoma. The first brain scan (In-113) performed on the 8th day after the onset of symptoms was normal. The second one, on the 12th day showed an abnormal accumulation of Tc-99m in the left temporal lobe. The clinical findings completed with such scanographic evolution suggested a preoperative diagnosis of intracerebral haematoma. The real diagnosis was confirmed during the surgery with the removal of a haematoma consisting of 100 ccm partly fluid, partly coagulated blood.

Initial state, outcome, and autopsy findings in a series of 200 consecutive traumatic comas. A computerised analysis.

Based on 200 nonselected consecutive cases of primary traumatic coma a preliminary mathematical model--computed, multiple linear regression analysis--has been developed, which seems to be suitable for calculating the prognosis from some initial anamnestic and clinical data. It is to be expected that the analysis of greater material will help to establish an even better model, e.g. by a more detailed age subdivision and choice of more or other factors. It is the aim of this report to encourage further work in this field.