Increase in the hypotensive effect of bromocriptine induced by spinal transection in rats: contribution of spinal dopamine receptors.

Intravenous (i.v.) administration of bromocriptine (150 micrograms/kg) in conscious normotensive rats with chronic spinal cord transection (at T5-T7), pretreated or not with i.v. propranolol (0.5 mg/kg), induced significant decreases in mean arterial blood pressure (MAP) which were greater and longer lasting than those in intact rats (-15 to -20 as compared with -10 mm Hg) for 8 days after transection. To assess the spinal and/or peripheral origin of this phenomenon, rats were also pretreated with either i.v. (0.3 mg/kg) or intrathecal (i.t.; 93 nmol/rat; at T9-T10) administration of domperidone, a selective dopamine (DA)2 receptor antagonist incapable of crossing the blood-brain barrier (BBB) freely. The increase in hypotension induced by spinal section was suppressed by i.t. but not by i.v. domperidone. In intact rats, bromocriptine elicited an increase in heart rate (HR; approximately 50 beats/min more), which was prevented by i.v. propranolol treatment. In spinal cord-transected rats, however, it had a significant bradycardic effect (approximately 50 beats/min less), which was antagonized by i.t.-administered domperidone. These results suggest that enhancement of the hypotensive effects induced by systemic administration of bromocriptine after a complete thoracic spinal transection is fully mediated by spinal DA2 receptors. This finding may help explain the increased orthostatic hypotension induced by DA receptor agonists in Parkinsonian patients with spinal lesions.     

Rostrocaudal localization of cardiovascular responses induced by intrathecal administration of apomorphine in conscious, freely moving rats.

In conscious freely moving rats, administration of apomorphine (179 nmol), a dopamine receptor agonist, into the intrathecal (i.t.) space decreased mean aortic blood pressure (MBP) and heart rate (HR). Both the magnitude and the time of appearance of the response varied according to the spinal level of administration. The largest and immediately appearing effect was observed after the injection at the upper thoracic site, whereas the magnitude of the responses was smaller with an immediate or slightly delayed (0.5-1.5 min) onset at lower thoracic and midcervical levels. More caudal responses appeared to be due to spreading of the drug along the spinal axis (onset in 1-2 min after administration). Behavioral responses (stereotyped movements) were observed within 2-3 min after administration and were nearly the same whatever the site of administration. These results corroborate, as do those provided by i.t. injections of tritiated apomorphine, the spinal origin of cardiovascular effects of i.t. apomorphine. Furthermore, spinal transection at the T5-T7 level did not change the magnitude and duration of decreases in MBP and HR elicited by i.t. apomorphine injected at the T2-T4 level. Moreover, this procedure enhanced responses to i.t. administration at the T9-T10 level. In conclusion, these results favor the existence of a spinal site of action for the cardiovascular effects of apomorphine. Furthermore, they indicate that spinal transection is accompanied by development of a hypersensitive phenomenon (of a mechanism to be determined).     

Hypersensitivity of the corticotropic axis to the serotoninergic agent clomipramine in obese women

Serotoninergic control of food intake has been shown to be abnormal in obese persons with a decrease in serotoninergic tone. The neuroendocrine effects of intravenous I.V. administration of clomipramine (CMI), a serotonin uptake inhibitor, were studied in normal-weight (n=7) and obese subjects before (n=12) and after (n=6) dietary restriction. Under double-blind, placebo-controlled conditions, a single 12.5 mg dose of CMI was administered. There was no difference in baseline values of prolactin (PRL), corticotropin (ACTH) and cortisol in non-obese controls, obese before and obese after weight loss. CMI led to significant increases of PRL, ACTH, and cortisol concentrations in the controls as well as the obese group. The ACTH and cortisol responses to CMI in obese subjects were somewhat greater than the responses in normal-weight subjects. The area under the curve AUC for ACTH after clomipramine was 6202 +/- 976 pg/ml x 150 minutes for tile obese before weight loss and 3274 +/- 512 pg/ml x 150 minutes for the controls and the difference was significant at the level of p=0.052. The cortisol peak value after clomipramine was 163.71 +/- 14.31 ng/ml in the non-obese and 214.66 +/- 12.59 ng/ml in the obese (p=0.025). However, there was no difference in the obese subjects before and after weight loss. These data support the assumption that obese women have an abnormal sensitivity to the serotoninergic control of the hypothalamic pituitary adrenal axis (HPA), and that a mild weight loss does not significantly modify their serotoninergic tone.     

Propolis attenuates cobalt induced-nephrotoxicity in adult rats and their progeny

The aim of this study was to evaluate the biochemical changes in cobalt-exposed rats and to investigate the potential role of Tunisian propolis against the cobalt-induced renal damages. Twenty-four pregnant Wistar rats were divided into four groups and were treated as follows: group 1 (control) received distilled water; group 2 received 350 ppm of CoCl₂ in drinking water; group 3 received 350 ppm CoCl₂ in drinking water and a propolis-supplemented diet (1 g/100 g of diet); group 4 received a propolis-supplemented diet (1 g/100 g of diet) without cobalt. In the cobalt group, a significant decrease in body, absolute and relative weights was noted when compared to controls. The administration of cobalt to pregnant rats from the 14th day of pregnancy until day 14 after delivery resulted in an increased level of renal malondialdehyde, a decreased renal content of glutathione and antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase in lactating rats and their pups. A statistically significant increase in plasma urea and creatinine serum levels was seen in treated female rats and their pups. Histopathologically, the cobalt-administration induced degenerative changes in the kidney of lactating rats and their pups. When compared with cobalt-treated rats, those receiving the propolis supplementation (along with cobalt-treatment) had lower malondialdehyde levels, higher antioxidant activities and the cobalt-related histopathological changes in the kidneys were at lower severity.Our results suggested that the propolis might be a potential candidate agent against cobalt-induced nephrotoxicity in adult and juvenile rats when administered to female rats during the late pregnancy and the early postnatal period.     

L’infarctus du myocarde au Maroc : les données du registre FES-AMI

Background

Acute myocardial infarction is the most dangerous complication of coronary atherothrombosis. There are several disparities in regard to its management around the world. The aim of this study is to analyze the specificities of management of acute myocardial infarction in Morocco.

Methods

FES-AMI (Fès Acute Myocardial Infarction) is a prospective monocentric registry conducted in cardiology department of Hassan II university hospital in Fès. In this registry, we enrolled patients with acute myocardial infarction who presented within 5 days after symptom onset.

Results

From January 2005 to August 2015, we enrolled 1835 patients. Seventy-five percent of patients were males and mean age was 60 years old. Fifty-one percent of patients were smokers, 27% were hypertensives and 14% were diabetics. Sixty-six percent of patients had more than 2 risk factors. Time from symptom onset to hospital admission was less than six hours for 40% of the patients. Thirty-six percent of patients were admitted more than twelve hours after the onset of chest pain. Only 37% of patients received reperfusion therapy, 31% with in-hospital thrombolysis and 6% with primary angioplasty. In-hospital mortality was 7.6%.

Conclusion

The patients enrolled in our registry have late presentation of acute myocardial infarction and less rate of reperfusion therapy. Furthermore, the majority of our patients have multiple risk factors and this result underlines the failure of preventive interventions.