Blood pressure effects of intravenous apomorphine in conscious deoxycorticosterone-acetate salt-hypertensive rats

SUMMARY: The present study reports the effects of apomorphine (APO) on blood pressure and the principal site of action of this agonist in 4-week deoxycorticosterone-acetate (DOCA)-hypertensive conscious rats. In these preprations, intravenous (i.v.) administration of APO (0.50-1 mg/kg) induced short-lasting and dose-dependent decreases in mean arterial pressure. The hypotensive response to APO (0.3 mg/kg) was reversed into a significant pressor effect by i.v. hexamethonium (30 mg/kg), whereas it was enhanced by i.v. pretreatment with the vasopressor antagonist of arginine vasopressin (AVP) d(CH2)5Tyr(Me)AVP (10 microg/kg) and/or prazosin (1 mg/kg). This depressor effect was suppressed by the central and peripheral dopamine D2 receptor antagonist metoclopramide (5 mg/kg i.v.), unaffected by the selective dopamine D1 receptor antagonist SCH 23390 (0.2 mg/kg i.v.), partly reduced by intrathecal domperidone (40 microg per rat at T9-T10 level), a dopamine D2 receptor antagonist which does not cross the blood-brain barrier, and reversed into a significant pressor effect by i.v. domperidone (0.5 mg/kg). The latter pressor effect was fully abolished by combined i.v. pretreatment with the vasopressor antagonist of AVP and prazosin. These results show that, in conscious DOCA salt-hypertensive rats, APO induced a brief, initial depressor effect, which is opposed to a central pressor component. The depressor component is related to an inhibition of norepinephrine transmission through activation of dopamine D2 receptors, some of which are located in the spinal cord and some of which are located in the peripheral circulation. The central pressor component, which became manifest after peripheral dopamine D2 receptor blockade, appears to be related to an increase in vasopressin release and sympathetic tone through activation of brain dopamine D2 receptors.     

Central bromocriptine-induced tachycardia is reversed to bradycardia in conscious, deoxycorticosterone acetate-salt hypertensive rats

A central dopaminergic origin has been demonstrated for the bromocriptine-induced tachycardia in conscious, normotensive rats. The present study investigated the effect of bromocriptine on heart rate and the principal site of action of this agonist in conscious, deoxycorticosterone acetate-salt hypertensive rats, in which altered central dopaminergic activity has been previously reported. Intravenous administration of bromocriptine (150 microg/kg) increased heart rate (49+/-5 beats/min.) in uninephrectomized control rats, while it induced a significant bradycardia (50+/-6 beats/min.) in deoxycorticosterone acetate-salt hypertensive rats. In the latter animals, intravenous (500 microg/kg) or intrathecal (40 microg/rat at T9-T10) pretreatment with domperidone, a selective dopamine D2 receptor antagonist that does not cross the blood-brain barrier, reduced partially, but significantly, the bradycardiac responses to bromocriptine (reduction of about 44% and 48% of the maximal effect, respectively). In contrast, the bromocriptine-induced bradycardia was fully abolished by intravenous pretreatment with metoclopramide (300 microg/kg), a dopamine D2 receptor antagonist that crosses the blood-brain barrier, or by combined pretreatment with intravenous and intrathecal domperidone. These results indicate that, in deoxycorticosterone acetate-salt hypertensive rats, bromocriptine decreases rather than increases heart rate, an effect that is mediated partly through a peripheral D2 dopaminergic mechanism and partly through stimulation of spinal dopamine D2 receptors. They further support the concept that, in normotensive, conscious rats, the central tachycardia of bromocriptine appears to predominate and to mask the bradycardia of this agonist at both peripheral and spinal dopamine D2 receptors.     

Essential oil of Croton nepetaefolius decreases blood pressure through an action upon vascular smooth muscle: studies in DOCA-salt hypertensive rats

Experiments tested the hypothesis that hypotensive effects of intravenous (i.v.) treatment with the essential oil of Croton nepetaefolius (EOCN) result from its vasodilatory effects directly upon vascular smooth muscle. In both deoxycorticosterone-acetate (DOCA)-salt hypertensive and uninephrectomised control, conscious rats, i.v. bolus injections of EOCN (1 to 50 mg/kg) decreased mean aortic pressure (MAP) and heart rate (HR) in a dose-related manner. Treatment with DOCA-salt significantly enhanced EOCN-induced decreases in MAP without affecting bradycardia. Likewise, both maximal percent and absolute decreases in MAP elicited by i.v. hexamethonium (30 mg/kg), a ganglion blocker, were significantly greater in DOCA-salt hypertensive than in control rats. In DOCA-salt hypertensive rats, i.v. pretreatment with hexamethonium (30 mg/kg) reduced the bradycardia elicited by EOCN (50 mg/kg) without affecting the enhancement of EOCN-induced hypotension. In isolated thoracic aorta preparations from DOCA-salt hypertensive rats, EOCN (1-300 micrograms/ml) induced a concentration-dependent reduction of phenylephrine-induced contraction. Arteries from DOCA rats showed increased sensitivity to EOCN, as evidenced by the significant decrease in the IC50 for EOCN-induced reduction of phenylephrine-induced contraction (16.4 +/- 3.6 vs. 112.9 +/- 23.4 micrograms/ml in uninephrectomized controls). These results show that i.v. treatment with EOCN dose-dependently decreases blood pressure in conscious DOCA-salt hypertensive rats, and this action is enhanced when compared with uninephrectomized controls. This enhancement appears to be related mainly to an increase in EOCN-induced vascular smooth muscle relaxation rather than to enhanced sympathetic nervous system activity in this hypertensive model. Thus, the hypothesis that EOCN may be a direct vasorelaxant agent is supported by the results of the present study.     

Liposarcome multiple du mésentère et du mésocôlon

Liposarcoma represent the single most common type of soft tissue sarcoma. Its abdominal localization is rare, occurring in only 5% of cases. A 60-year-old male was found to have a case of primary multiple liposarcoma of the mesentery and mesocolon. Computed tomography revealed the presence of a peritoneal mass presenting a homogeneous density with an adipose component. Preoperative biopsies were falsely reassuring. A laparotomy confirmed the presence of multiple tumors in the mesentery and the mesocolon. The masses were removed and the histopathological report noted a well-differentiated liposarcoma. Chemotherapy was prescribed. The patient was well at 18 months follow-up. Surgery currently represents the best curative therapy for this type of tumor. Chemotherapy seems promising in liposarcoma. Diagnostic and therapeutic problems related to this type of neoplasm as well as a literature reviews are reported.     

Peut-on changer les comportements alimentaires ?

The naïve model of feeding behaviour determination, stating it stems from individual conscious will alone, is widespread but fallacious and roots many a failure in diets and public health campaigns.Feeding behaviour is determined at three levels: technico-economics, psychology, and sociology. Individual capacity of change, facing a whole system of affordances and habits, is limited. Changes are possible, but not when relying upon individual will alone. We list some realistic paths to foster and support change.     

Kinetic analysis of the binding of nomegestrol acetate to the progesterone receptors in rat uterus by competition studies

The characteristics of binding (Kinetic and equilibrium binding analysis) of nomegestrol acetate (NOM, 17 alpha-acetoxy-6 alpha-methyl-19-nor-pregna-4.6-diene-3.20-dione) to the progesterone receptor (PgR) in rat uterine cytosolic fraction were determined in comparison to progesterone (P), to fully appreciate the amplitude and specificity of the induced biological response. Since an appropriate radio-labelled form of this steroid molecule was not available, competition studies were performed against the synthetic progestin: [3H]-Organon 2058 [( 3H]-ORG). This allowed a direct comparison between the unlabelled forms of NOM and P, the kinetic constants of which were respectively: Inhibition constant (Ki): 22.8 and 34.3 nM; Association rate constant (k1): 0.39 X 10(3) and 0.21 X 10(3) M-1.s-1; Dissociation rate constant (k-1): 1.81 X 10(-5) and 2.16 X 10(-5) s-1. These results are much more informative than the mere determination of relative binding affinities which only reflect the specificity of the PgR. It was concluded that NOM behaves like the natural hormone in the cytosol of rat uterus.     

Tumeur stromale anorectale: à propos d’une localisation rare des GIST

Gastrointestinal stromal tumours (GIST) are uncommon, undifferentiated lesions, representing 1–3% of gastrointestinal malignancy. Localisation in the anorectal area is very rare. The chances of recurrence are substantial, so high-grade stromal tumours require aggressive surgery accompanied by neoadjuvant or adjuvant chemotherapy, so as to improve resectability and reduce the risk of relapse.We report a case of anorectal stromal tumour and discuss the diagnostic, therapeutic and prognostic features in the light of information available in the literature.     

Regulation of rat uterine steroid receptors by nomegestrol acetate, a new 19-nor-progesterone derivative

The regulatory effects of nomegestrol acetate (NOM-Ac: 17 alpha-acetoxy-6 alpha-methyl-19-nor-pregna-4,6-diene-3,20-dione), a new 19-nor-progesterone derivative, active p.o. progestin, were studied on rat uterine estrogen (ER) and progestogen receptor (PgR) levels. The actions of estradiol (E2), progesterone (P) and various progestins were investigated. The effects of E2 were reproduced with 5 micrograms/animal: a 2-fold increase in activated ER level in the nucleus at 30 min, 2-fold stimulation of cytosolic ER replenishment at 48 hr and a 4-fold induction of PgR synthesis at 48 hr. The negative regulatory effects of P were also reproduced at doses ranging from 0.25 to 2 mg/animal: inhibition of basal and E2-stimulated cytosolic ER replenishment and inhibition of E2-induced PgR synthesis. NOM-Ac reproduced these negative regulatory effects. The 50% effective doses in reducing estrogen receptor levels and the corresponding potencies relative to P showed NOM-Ac to be 2.4-fold more active than P and to present, when compared to the other progestins, the highest antiestrogenic capacity. Furthermore, in contrast with norethisterone acetate, a 19-nor-testosterone derivative, it was completely devoid of estrogenic potency.     

Structure-activity and structure-affinity relationships of 19-nor-progesterone derivatives in rat uterus

19-nor-progesterone (19NP) is a potent progestagen which possesses a high affinity for the progesterone receptor (PgR). In contrast, 17 alpha-hydroxylated-progesterone (17OHP) shows no hormonal activity and does not compete with progesterone (P) for the PgR. The aim of the present work was to analyse in parallel the structure-affinity and the structure-activity relationships for new molecules obtained by modifications of 19NP and 17OHP. The attachment of a 17 alpha-hydroxyl group on 19NP led to a dramatic decrease in both affinity and activity for the end-product, 17 alpha-hydroxylated-19-nor-progesterone (17OH-19NP). The further addition of a methyl group combined with the formation of a double-bound at C6 on 17OH-19NP results in nomegestrol (NOM), the relative affinity of which remained low. Negligible activity was also associated with this affinity in comparison to the parent 19NP. Strikingly, the protection of the free 17 alpha-hydroxyl group of NOM by an acetate led to a potent progestin with high affinity for PgR. It is concluded that the sum of the modifications brought into the 17OHP-19NP molecule reestablishes both affinity and activity of the original 19NP molecule. The same conclusion holds if P is considered as the parent compound, as already stated in the literature.     

Protective effects of selenium on methimazole-induced anemia and oxidative stress in adult rats and their offspring

The present study investigates the potential ability of selenium, considered as an antioxidant with pharmacological property to alleviate oxidative stress and hematological parameter disorders induced by methimazole, an antithyroid drug. Pregnant Wistar rats were randomly divided into four groups of six each: group I served as negative control and received a standard diet; group II received 250 mg/L of methimazole in drinking water and a standard diet; group III received both methimazole (250 mg/L, orally) and selenium (0.5 mg/kg of diet) supplemented to the standard diet; group IV served as positive control and received a supplement of selenium in the diet (0.5 mg/kg of diet) as sodium selenite (Na(2)SeO(3)). Treatment was started from the 14th day of pregnancy until day 14 after delivery. Methimazole reduced the number of red blood cells, hemoglobin concentration and hematocrit in mothers and their pups. Besides, plasma iron, vitamins B(9), B(12), C and E levels were reduced. Lipid peroxidation increased, objectified by high malondialdehyde levels and lactate dehydrogenase activity in plasma, while glutathione, glutathione peroxidase, superoxide dismutase and catalase activities showed a significant decline. Co-administration of selenium through diet improved all the parameters cited above. It can be concluded that the administration of selenium alleviates methimazole-induced toxicity, thus demonstrating its antioxidant efficacy.