Psychoactive substances use and associated factors among middle and high school students in the North Center of Morocco: a cross-sectional questionnaire survey.

BACKGROUND: Data on psychoactive substance (PAS) consumption among adolescents in the North Center of Morocco are not at all available. Therefore, the current study aimed at investigating the prevalence and the determinants of psychoactive substances use among middle and high school students in this region. METHODS: A cross-sectional study was conducted from April 2012 to November 2013 in public middle and high schools in the North Central Region of Morocco. An anonymous self-administered questionnaire was used to assess psychoactive substances use among a representative sample of school students from the 7th to the 12th grade, aged 11-23 years, selected by stratified cluster random sampling. Factors associated with psychoactive substance use were identified using multivariate stepwise logistic regression analyses. RESULTS: A total of 3020 school students completed the questionnaires, 53.0 % of which were males. The overall lifetime smoking prevalence was 16.1 %. The lifetime, annual and past month rates of any psychoactive substance use among the study subjects were 9.3, 7.5, and 6.3 % respectively. Cannabis recorded the highest lifetime prevalence of 8.1 %, followed by alcohol 4.3 %, inhalants 1.7 %, psychotropic substances without medical prescription 1.0, cocaine 0.7, heroine 0.3, and amphetamine with only 0.2 %. Psychoactive substance use was associated with males more than females. The risk factors identified by multivariate stepwise logistic regression analyses were being male, studying in secondary school level, smoking tobacco, living with a family member who uses tobacco, and feeling insecure within the family. CONCLUSIONS: The prevalence among all school students reported by the current study was comparable to the national prevalence. Efforts to initiate psychoactive substance prevention programs among school students should be made by designing such programs based on the significant factors associated with psychoactive substance use identified in this study.

Suicidal behaviors among Moroccan school students: prevalence and association with socio-demographic characteristics and psychoactive substances use: a cross-sectional study.

BACKGROUND: Suicidal behavior is a major cause of injury and death worldwide, especially among adolescents and young adults. Few studies have tackled this issue in the Arab world. The present study investigated the prevalence and the risk factors of suicidal behaviors among Moroccan school students. METHODS: From April 2012 to November 2013, a cross-sectional study was conducted in the North-Centre region of Morocco among students in public secondary schools selected using stratified cluster random sampling. The data were collected via anonymous self-administered questionnaires. The Mini International Neuropsychiatric Interview was used in its Moroccan Colloquial Arabic version to assess suicidality according to the DSM-IV criteria. RESULTS: A total of 3020 students (53 % boys) aged 11-23 years (average age = 16 ± 2.1 years) were included in the study. The prevalence of suicide ideation, suicide planning and suicide attempts during the last month were 15.7, 6.3, and 6.5 % respectively. Univariate analyses demonstrated that suicidal behaviors followed different epidemiological patterns. According to the multivariate analyses, the risk factors for all suicidal behaviors among Moroccan school students were the female gender, middle school level, urban locations, low family income, parents' divorce, tobacco consumption and psychoactive substances (alcohol and cannabis) use. CONCLUSIONS: The intervention of preventive programs has become an emergency to overcome the issue of suicidality in Morocco. Further researches on adolescents' suicidal behaviors are suggested to update temporal data and assess the effectiveness of potential interventions.

Frequency, types and determinants of degenerative complications of type 2 diabetes in Morocco: "EpiDiaM" cohort inclusion data.

Degenerative complications as a result of diabetes impose a heavy disease burden and increase mortality. This study presents epidemiological and clinical profiles of diabetic patients in the EpiDiaM cohort study, which include 1196 diabetic cases recruited from the basic health care network in the city of Fez. The mean age of the participants was 57.5 (SD 10.4) years with 47.1% aged between 50 and 60 years. The majority (77.7%) were women. The mean duration of diabetes was 8 (SD 6.6) years. Hypertension was found in 49.3% of the cohort, 77.9% were overweight or obese and 63.8% had one or more complications. Among those with complications, retinopathy was the most common (69.4%), followed by heart conditions (50.8%), neuropathy (45.6%) and renal disease (4.8 %). The high prevalence of complications emphasizes the need to address the avoidable risk factors and prevent complications.

Association of the ENPP1 K121Q polymorphism with type 2 diabetes and obesity in the Moroccan population.

AIM: The ectonucleotide pyrophosphatase/phosphodiesterase 1 enzyme (ENPP1), which downregulates insulin signaling by inhibiting insulin-receptor tyrosine kinase activity, is encoded by the ENPP1 gene. A common functional ENPP1 K121Q polymorphism has been suggested to contribute to insulin resistance, obesity and type 2 diabetes (T2D) in various ethnic groups. For this reason, we assessed the association between the ENPP1 K121Q polymorphism in T2D and obesity phenotypes in the Moroccan population. METHODS: Using LightCycler((R)) technology, we genotyped the ENPP1 K121Q polymorphism in 503 subjects with T2D and 412 normoglycaemic individuals. RESULTS: There was no evidence of an association between ENPP1 K121Q and T2D in either an additive (P=0.99) or recessive mode of inheritance (P=0.47). However, the Q121 variant was significantly more frequent in obese than in non-obese subjects after adjusting for age, gender and T2D status. We observed genetic heterogeneity between obese and non-obese T2D patients (P=0.02). The K121Q polymorphism was associated with T2D in the presence of obesity in both additive (1.55 [95% CI 1.16-2.07]; P=0.003) and recessive (2.31 [95% CI 1.34-3.97]; P=0.002) modes of inheritance. CONCLUSION: Although there was no evidence of an association between the ENPP1 K121Q variant and the general phenotype of T2D, we did find an association with adult obesity and T2D. The Q121 allele frequency in Morocco is 37.3%, placing it between European Caucasians (15%) and Black Africans (79%). This study is the first to report an association between K121Q and metabolic diseases in the Moroccan population.

Is Ramadan fasting safe in type 2 diabetic patients in view of the lack of significant effect of fasting on clinical and biochemical parameters, blood pressure, and glycemic control?

The study objective was to determine if Ramadan fasting was safe in patients with type 2 diabetes mellitus (T2D), based upon a determination of the effect of fasting on a broad range of physiological and clinical parameters, including markers of glycemic control and blood pressure. The study was carried out in Ramadan 1422 (December 2001-January 2002) at the Diabetology Services, Hopital Ibn Sina, Rabat, Morocco. One hundred and twenty T2D Moroccan patients (62 women, 58 men), aged 48-60 yrs with well-controlled diabetes through diet and/or oral hypoglycemic drugs (OHD), received dietary instructions and readjustment of the timing of the dose of OHD (gliclazide modified release) according to the fasting/eating periods. Anthropometric indices and physiological parameters (blood pressure, lipid, hematological, and serum electrolyte profiles, as well as markers of glycemic control, nutrition, renal and hepatic function) were measured on the day before Ramadan and then on the 15(th) and 29(th) day of fasting and thereafter 15 days later. Statistical analysis was done by standard methods. Ramadan fasting had no major effect on energy intake, body weight, body mass index, blood pressure, and liver enzymes. Fasting and post-prandial glucose levels decreased, while insulin levels increased. Diabetes was well controlled, as indicated by HbA1c, fructosamine, C-peptide, HOMA-IR, and IGF-1 values. There were fluctuations in some lipid and hematological parameters, creatinine, urea, uric acid, total protein, bilirubin, and electrolytes; however, all values stayed within the proper physiological range. In conclusion, diabetes was well-controlled in patients with dietary/medical management, without serious complications. With a regimen adjustment of OHD, diet control, and physical activity, most patients with T2D whose diabetes was well-controlled before Ramadan can safely observe Ramadan fasting.

Pharmacological studies on hypotensive, diuretic and vasodilator activities of chrysin glucoside from Calycotome villosa in rats.

The present study was undertaken in normotensive anaesthetized male rats that received a continuous perfusion of a chrysin glucoside isolated from the flowers and leaves of Calycotome villosa subsp intermedia at a dose of 2.5 mg/kg, or furosemide (control diuretic) at a dose of 0.5 mg/kg. Compared with the control rats receiving NaCl (0.9%), the urine flow, glomerular filtration and electrolyte excretion (Na+, K+) increased significantly in rats treated with chrysin glucoside (p < 0.001). A similar effect was observed in the rats perfused with furosemide. Intravenous injections of bolus doses (1-3 mg/kg) of the chrysin glucoside to anaesthetized rats elicited an immediate and dose-dependent decrease in mean arterial blood pressure (MABP). Pretreatment of the rats with the nitric oxide synthase inhibitor, l-NOArg (10 mg/kg), reduced partially, but significantly (p < 0.01), the maximal decrease in MABP elicited by chrysin glucoside. In the rat isolated aorta preparation, chrysin glucoside (10-100 microm) inhibited in a concentration-dependent manner the noradrenaline (1 microm) induced contractions (IC(50) = 52 microm). This relaxant activity of chrysin glucoside was significantly reduced by incubation of the endothelium-intact rings with l-NOArg (100 microm), (80 +/- 4.7% vs 48 +/- 5.06% in the absence of L-NOArg). In conclusion, these results demonstrate a diuretic and hypotensive action of a chrysin glucoside from Calycotome villosa in anaesthetized rats and indicating an action on renal function, and an active vascular relaxation mediated partially through nitric oxide release.

[Diabetes and erectile dysfunction in Morocco: epidemiological study among outpatients]. / Diabète et dysfonction erectile au Maroc : etude epidémiologique auprès d'une population de consultants.

We studied the relationship between erectile dysfunction (ED) and diabetes among 189 men (> 40 years) attending primary health care centres in Morocco. Of the 89 diabetic men, 82% had ED while only 17% of the 100 non-diabetic men had ED. The frequency of ED among diabetic men increased with age, from 60% in those aged 40-49 years to 94.95% in those aged > or = 60 years (from 6.3% to 35.4% in men without diabetes for similar ages). ED was reported by 93.3% of diabetic men who had had diabetes for > 15 years. The frequency of ED did not differ with type of diabetes but it was significantly commoner in diabetic men with a low level of education and with hypertension.

Ethnopharmacological survey of plants used in the traditional treatment of hypertension and diabetes in south-eastern Morocco (Errachidia province).

This survey was undertaken in the Errachidia province in south-eastern Morocco in order to inventory the main medicinal plants used in folk medicine to treat arterial hypertension and diabetes mellitus. Four hundred individuals who knew about and/or had used the medicinal plants for the indicated diseases, including some herbal healers, were interviewed throughout different regions of the province. The inventory of medicinal plants is summarized in a synoptic table, which contains the scientific, vernacular and common name of the plant, its ecological distribution, the part of the plant and the preparation used and the therapeutic indication. Extensive investigations have brought to light 64 medicinal plants belonging to 33 families; of these, 45 are used for diabetes, 36 for hypertension, and 18 for both diseases. Of these plants, 34% grow in the wild, 44% are cultivated, and 22% are not indigenous to the area and are brought from other parts of Morocco or from outside the country. The survey shows that 78% of the patients regularly use these medicinal plants. In this region, the most frequently used plants to treat diabetes include Ajuga iva, Allium cepa, Artemisia herba-alba, Carum carvi, Lepidium sativum, Nigella sativa, Olea europaea, Peganum harmala, Phoenix dactylifera, Rosmarinus officinalis, and Zygophyllum gaetulum, and those to treat hypertension include Ajuga iva, Allium cepa, Allium sativum, Artemisia herba-alba Asso, Carum carvi, Nigella sativa, Olea europea, Rosmarinus officinalis, Origanum majorana, Peganum harmala, and Phoenix dactylifera. The local people recognize the toxic plants and are very careful in using such plants, which are Citrullus colocynthis, Datura stramonium, Nerium oleander, Nigella sativa, Peganum harmala and Zygophyllum gaetulum. Our survey shows that traditional medicine in the south-eastern Moroccan population has not only survived but has thrived in the transcultural environment and intermixture of many ethnic traditions and beliefs.

Using surveillance data to understand cancer trends: an overview in Morocco.

BACKGROUND: The aim was to use the existing surveillance data sources of cancer in Morocco that could be used to better describe cancer mortality and incidence trends in Morocco. METHODS: National incidence data were derived from population-based cancer registries. Mortality data were collected from the international GLOBOCAN database. RESULTS: An overview of the main results was presented. In general, the most commonly diagnosed cancers in men are lung and prostates whereas in women, breast and cervical cancers are the pre-dominant cancers. Fifty nine percent and of breast and 65.7 % of cervical cancers in women are diagnosed at stages II and III. Cancer remains the second highest cause of mortality in Morocco. CONCLUSION: The data provides a description of the cancer incidence and trends in the Moroccan population. The Moroccan national cancer program should aim for more coherent, consistent and comparable incidence data between different cancer registries in the country, and develop uniform datasets with respect to quality.

INTRODUCTION: L'objectif était d'utiliser les sources de données existantes de surveillance du cancer qui pourraient être utiles pour décrire les tendances d'incidence et de mortalité du cancer au Maroc. MÉTHODES: Les données de morbidité et mortalité nationales et internationales disponibles ont été explorées. Les registres populationnels de cancer couvrent les données d'incidence régionale. Les données de mortalité sont disponibles par les données internationales de Globocan. RÉSULTATS: Un aperçu des principaux résultats a été présenté. Globalement, les cancers les plus fréquents sont le poumon et la prostate chez les hommes; le sein et le col utérin chez les femmes; ces deux cancers représentant 56,3 % de cancers féminins. Les cancers de sein et du col sont diagnostiqués dans 59 % et 65,7 % aux stades II et III. Le cancer est la deuxième cause de mortalité au Maroc. CONCLUSION: Les données fournissent une description de l'incidence des cancers et leurs tendances dans la population marocaine. Le programme national du cancer marocaine devrait viser pour les données d'incidence cohérents et comparables entre les différents registres du cancer dans le pays, et de développer des ensembles de données uniformes par rapport à la qualité.

Effects of corticosteroids on parameters related to Na+ transport by amphibian renal distal cells (A6) in culture.

The present study addresses the effects of the hormones aldosterone and corticosterone, as well as those of dexamethasone, on cultured renal amphibian cells, focusing on parameters thought relevant for the further understanding of the regulation by these steroids of Na+ reabsorption along the renal tubule. Exposure to these steroids of A6 cell monolayers grown on a permeable support produced a motor, dose-dependent, increase in Na+ transport, reflected by the short-circuit current, Isc. (Na+ + K+)-ATPase activity and ouabain binding, both of which are linearly correlated with Isc in control tissue, also increased significantly after steroid treatment. Dexamethasone was consistently more active than corticosterone and aldosterone on the parameters studied. The increase in Isc and (Na+ + K+)-ATPase activity elicited by dexamethasone could be blocked by the glucocorticoid antagonist RU 486, whereas it was only slightly reduced by the mineralocorticoid antagonist, spironolactone. In contrast, the latter strikingly reduced the effects of aldosterone on these parameters, unlike RU 486. Furthermore, the effects of large doses of dexamethasone and aldosterone combined were not additive. Taken together, the data presented appear compatible with the view that the effects of aldosterone on Na+ transport by A6 cells are mediated by a fraction of the receptors involved in the response to dexamethasone; they furthermore raise the question of whether, in lower vertebrates, it is relevant to make a distinction between "gluco" and "mineralo"corticoids.

Effects of dexamethasone on (Na+ + K+)-ATPase and other parameters related to transepithelial Na+ transport by amphibian renal distal cells (A6) in culture.

In the present report, the effects exerted by dexamethasone on transepithelial, electrogenic Na+ transport across A6 cell monolayers grown on permeable support were further characterized in terms of time course and relationship to the rate of Na+ transport; furthermore this agonist was compared to vasopressin and insulin. (Na+ + K+)-ATPase activity and density of ouabain binding sites were measured in cell homogenates and on dispersed cells, respectively, after documenting transepithelial electrical parameters of the preparations. Na+ transport, measured by short-circuit current (Isc), was increased almost five-fold (control: 6.7 +/- 0.1 microA/cm2) after incubation with 10(-7) M dexamethasone for 24 h. Stimulation of Na+ transport rate was associated with a 2.3-fold increase in (Na+ + K+)-ATPase activity (control: 5.5 +/- 0.3 micromol Pi/mg prot.h), and ouabain binding site density almost doubled (control: 236 +/- 10 fmol/10(6) cells). The steroid acted on the Na+ pump of A6 cells in the absence of transepithelial Na+ transport, with intracellular Na+ ion activity playing an additional role in terms of cell Na+ pump numbers. In the case of insulin and vasopressin, in contrast, there was no effect on Na+ pump activity in the absence of Na+ transport by A6 cell monolayers. The increase in (Na+ + K+)-ATPase activity observed in A6 cell monolayers treated with dexamethasone is therefore a result of the direct induction of Na+ pump biosynthesis, with an almost proportional insertion of operational Na+ pumps into the basolateral membrane. In contrast, increased Na+ entry at the apical cell pole appears to be essential for insulin and vasopressin action on A6 cell Na+ pump.

Hypoglycemic effect of Suaeda fruticosa in streptozotocin-induced diabetic rats.

The purpose of this study was to examine the hypoglycemic activity of the aqueous extract of the aerial part of Suaeda fruticosa (SF) in normal and streptozotocin-induced diabetic rats. The aqueous extract was administered intravenously (i.v.) and the blood glucose changes were determined within 4 h after starting the treatment. Plasma insulin, cholesterol and triglycerides levels were also determined. The aqueous extract at a dose of 192 mg/kg produced a significant decrease in blood glucose levels in normal rats (P < 0.05), and even more in diabetic rats (P < 0.001). This hypoglycemic effect might be due to an extra-pancreatic action of the aqueous extract of SF, since that the levels of plasma insulin were unchanged between the values before and after treatment. In the other hand, the effect of the aqueous extract on the plasma cholesterol were also significant in both normal and diabetic rats (P < 0.05). But, there is no significant effect of SF on plasma triglycerides in both groups. In order to characterize the active principle(s), which could be responsible for the therapeutic effect, preliminary phytochemical analysis of the aqueous extract of the plant has been investigated.

Effects of the flavonoids extracted from Spergularia purpurea Pers. on arterial blood pressure and renal function in normal and hypertensive rats.

The antihypertensive and diuretic effects of the flavonoids extracted from Spergularia purpurea Pers. (SP) were studied both in normotensive (NTR) and spontaneously hypertensive conscious rats (SHR). Daily oral administration of the flavonoid mixture (5 mg/kg for 1 week) exhibited a significant decrease in blood pressure with variation coefficient (Delta) of 20 in SHR rats and 11 in NTR rats. The systolic and diastolic blood pressure decreased significantly and respectively with 17 and 24% in SHR, and with 11 and 16% in NTR. The flavonoid mixture enhanced significantly the water excretion in hypertensive (P<0.001) and normal rats (P<0.001). Furthermore, oral administration of flavonoids mixture at a dose of 5 mg/kg produced a significant increase of urinary excretion of sodium (P<0.01), potassium (P<0.05) and chlorides (P<0.05) in SHR. Similarly, the flavonoid administration induced a significant increase of urinary electrolytes elimination in NTR (P<0.01 versus controls). No significant changes were noted on heart rate after flavonoids treatment in SHR as well as in NTR. While, glomerular filtration rate showed a significant increase after administration of flavonoids in all groups (P<0.05). These results suggest that oral administration of flavonoids obtained from Spergularia purpurea exhibited antihypertensive and diuretic actions.

Hypoglycaemic effect of spergularia purpurea in normal and streptozotocin-induced diabetic rats.

Single and repeated oral administration of the water extracts of Spergularia purpurea (SP) at a dose of 10 mg/kg were tested on hypoglycaemic activity in normal and streptozotocin-induced diabetic rats. In normal rats, the water extract of SP decreased significantly the plasma glucose levels 4 h after single oral administration (P<0.01), and one week after repeated oral administration (P<0.05). A significant decrease of plasma glucose levels was observed 6 h after a single oral administration of the water extract of S. purpurea in severe hyperglycaemic rats (n=6) from 22.78+/-0.60 to 11.21+/-0.49 mmol/l (P<0.001). On other hand, water extract of S. purpurea normalised plasma glucose levels after two weeks of repeated oral administration in diabetic rats; 24.05+/-1.16 versus 7.18+/-0.51 mmol/l (P<0.001) at the start and 2 weeks after water extract administration, respectively. We conclude that the water extract of SP induces hypoglycaemic activity when administered orally in normal and STZ diabetic rats. In order to determine the active principle (s) responsible of the hypoglycaemic effect, preliminary phytochemical analysis of the water extract has been investigated.

Experimental diuretic effects of Rosmarinus officinalis and Centaurium erythraea.

Herbal remedies are widely used in Moroccan pharmacopoeia. We assessed the diuretic effect of two medicinal plants: Rosmarinus officinalis L., Labiatae, and Centaurium erythraea L., Gentianaceae, both reputed for the treatment of urinary ailments. To determine the action of these herbs on urinary volume (UV) and the excretion of sodium (U(Na)V), potassium (U(K)V), and chloride (U(Cl)V), the aqueous extracts of both plants were administered daily to Wistar rats for 1 week. The concentration of electrolytes and urea in plasma and creatinine clearance were also investigated. Daily oral administration of the aqueous extracts of R. officinalis and C. erythraea at the dose of 10 ml/kg of 8 or 16% extract in distilled water significantly enhanced diuresis in rats compared to the control group from the fifth day of treatment. For R. officinalis at the dose of 8% the peak of urinary excretion of sodium, potassium and chloride was reached after 6 days of treatment (P<0.001). The aqueous extract of of R. officinalis at the dose of 16% did not significantly affect the excretion of water and electrolytes over a similar period but slight increases in urinary excretion of sodium and chloride on the seventh day and of potassium on the sixth day (P<0.05) were observed. No increase was recorded for 24 h urinary excretion of Na+, K+ and Cl- during the first 4 days of treatment for the groups treated with C. erythraea at the doses of 8 and 16% whereas their effects on the same parameters were highly significant thereafter. No change was observed in plasma electrolytes and urea in any group, except for a decrease in sodium and chloride concentration in the group treated with 16% of R. officinalis. A decrease in creatinine clearance was demonstrated after treatment with 8% of R. officinalis and C. erythraea. Our findings demonstrate a diuretic effect of aqueous extracts of R. officinalis L. and C. erythraea L. with the most effective dose for water and electrolyte excretion being 8% for both plants.

In vitro cell-toxicity of Peganum harmala alkaloids on cancerous cell-lines.

The alkaloidic fraction of the methanol extract of Peganum harmala seeds was tested in vitro on three tumoral cell-lines: UCP-Med and Med-mek carcinoma, and UCP-Med sarcoma. Proliferation was significantly reduced at all tested concentrations (20-120 micrograms/ml) during the first 24 h of contact. A cell lysis effect occurred after 24 h and increased thereafter to complete cell death within 48-72 h, depending on tested concentration.

Effects of saponins from Herniaria glabra on blood pressure and renal function in spontaneously hypertensive rats.

Experiments were performed on male and female spontaneously hypertensive rats weighing 310-340 g (10 animals per group). The oral administration of 200 mg/kg/day of saponins from Herniaria glabra for 30 days, resulted in a significant decrease in blood pressure in hypertensive rats. The systolic and diastolic blood pressure decreased significantly and respectively from 187.60 +/- 20.63/119.00 +/- 7.09 mmHg at day 0 (D0) to 141.60 +/- 7.51/90.40 +/- 7.68 mmHg at day 30 (D30), p < 0.001 (vs. 186.30 +/- 11.27/114.10 +/- 12.00 mm Hg at D0 to 154.50 +/- 6.38/132.3 +/- 7.68 mmHg at D30 in furosemide-treated group, p < 0.001). Control animals receiving placebo did not show any significant variation in the mean arterial pressure. The effect of saponins of Herniaria glabra on renal function was evaluated in spontaneously hypertensive rats using clearance techniques. Glomerular filtration rate was constant in the control rats and increased significantly in the hypertensive rats after saponins treatment (5.55 +/- 0.32 vs. 6.03 +/- 0.43 ml.min-1.kg-1 in the control (C) and saponins (S) groups, respectively, p < 0.05). Saponins administration provoked an increase in urinary flow (59.38 +/- 5.85 ml.kg-1.24 h-1 vs. 36.92 +/- 5.17 ml.kg-1.24 h-1, p < 0.001). Saponins also increased potassium excretion (6.89 +/- 0.81 mmol.kg-1.24 h-1 vs. 5.40 +/- 0.51 mmol.kg-1.24 h-1, p < 0.001) and sodium excretion (10.74 +/- 1.21 mmol.kg-1.24 h-1 vs. 7.25 +/- 0.54 mmol.kg-1.24 h-1, p < 0.001) as well as chloride excretion (13.59 +/- 1.04 mmol. kg-1.24 h-1 vs. 9.67 +/- 0.77 mmol.kg-1.24 h-1, p < 0.001). It is concluded that chronic oral administration of saponins from Herniaria glabra decreased the arterial blood pressure and affected salt and water transport in renal tubules.

Antitumour principles from Peganum harmala seeds.

From ancient times, Peganum harmala was claimed to be an important medicinal plant. Its seeds were known to possess hypothermic, and essentially hallucinogenic properties. Various authors have undertaken studies on the antibacterial, antifungal and antiviral effects of Peganum harmala seeds, but studies on the antitumour activity are not to be found in the literature. In Moroccan traditional medicine, seed powder is sometimes used on skin and subcutaneous tumours. This work was designed to investigate some aspects of the antineoplastic properties of the plant Peganum. Varying concentrations (10 to 120 micrograms/ml) of total alkaloid extracts of Peganum harmala seeds (collected in Morocco) were tested in vitro on four tumoural cell-lines: Med-mek and UCP-Med carcinoma, UCP-Med sarcoma and Sp2/O-Ag14. In vivo experiments were performed with the Sp2/O cell-line grafted subcutaneously in syngenic BALB/c mice. In vitro, proliferation of tumoural cell lines was significantly reduced by all tested concentrations of the Peganum alkaloid extracts during the first 24 h of contact. A cell lysis effect occurred after 24 h and progressed to complete cell death within 48 to 72 h depending on the alkaloid concentration. Results obtained indicate that alkaloids of Peganum have a high cell toxicity in vitro. The active principle at a dose of 50 mg/kg given orally to mice for 40 days was found to have significant antitumoural activity. Peganum harmala alkaloids thus possess significant antitumour potential, which could prove useful as a novel anticancer therapy.

[Functional compartmentation of the endocrine action of cardiac natriuretic peptides]. / Compartimentation fonctionnelle de l'action endocrine des peptides natriurétiques cardiaques.

The endocrine function of the heart is to secrete Atrial and Brain natriuretic -peptides (ANP and BNP). These peptides are biologically active via particulate guanylate cyclases which generate cyclic GMP, the second intracellular messenger. A polysaccharide antagonist, HS-142-1 has been recently described by a Japanese Group. Cyclic GMP is partly secreted from the target cells into the extra cellular medium in which its accumulation is proportional to the concentration of the natriuretic peptide. Neutral Endopeptidase (NEP) is a zinc ectoenzyme involved in the catabolism of natriuretic peptides. NEP is absent in plasma but present on the surface of endothelial and smooth muscle cells. NEP is mainly expressed at the apical pole of the epithelial cells of the proximal tubule in the nephron. Chronic increase in volume and pressure within the cardiac cavities is associated with the oversecretion of natriuretic peptides. This chronic phenomenon involves the recruitment of all the cardiac myocytes to express natriuretic peptide genes. The clinical application of this hyperplasic phenomenon is congestive heart failure, in which the plasma levels of natriuretic peptides correlate with the level of the -hemodynamic stress. Therefore the plasma levels of natriuretic peptides are good pronostic markers in both experimental and human heart failure. The degree of congestive heart failure as well as the plasma levels of ANP and BNP are also -correlated with the plasma and urinary levels of cyclic GMP. The plasma level of -cyclic GMP is correlated with the endothelial concentration of cyclic GMP but not with the cyclic GMP concentration in smooth muscle cells. From these experimental data, we can conclude that plasma cyclic GMP originates from endothelial cells and is related to particulate guanylate cyclase activity. In contrast natriuretic peptides do not modulate vascular wall cyclic GMP content. The natriuretic action of ANP is probably due to the interaction of the filtered peptide with the particulate guanylate cyclase at the apical pole of the epithelial cells. The apparition of peptiduria associated with natriuresis during NEP inhibition provides evidence of the action of the peptide in the urinary compartment. It is also by a urinary pathway via the macula densa that ANP, and its potentiation by NEP inhibition, decreases renin secretion. The fact that plasma levels of ANP and plasma and urine levels of cyclic GMP correlate with the degree of salt retention in congestive heart failure, provides evidence for chronic desensitization of the system. An up-regulation of Na(+), K(+), 2Cl(-) expression associated with experimental congestive heart failure has recently been shown. Similarly, a modulation of the different sodium transporter systems along the nephron could be one of the counter-regulations leading to desensitization to natriuretic peptides. In conclusion, natriuretic peptides are true endocrine peptides, secreted by the heart, transported in the plasma, filtered by the glomeruli and active at the nephron level. The molecular effector of ANP and cyclic GMP in the epithelial cells is probably the G-kinase II, isoform phosphorylating the cystic fibrosis transmembrane conductance regulator (CFTR). The exact mechanism of desensitization remains to be elucidated.

[Antihypertensive effect of Herniaria glabra saponins in the spontaneously hypertensive rat]. / Effet antihypertenseur des saponines de herniaria glabra chez le rat spontanément hypertendu.

We studied the antihypertension action of Herniaria glabra saponins and compared the effect with that of furosemide. Spontaneously hypertensive rats were treated with H. glabra saponins at a dosage of 200mg/Kg of body weight. Treatment led to progressive decline in both systolic and diastolic blood pressures. After one month of therapy, pressures were: 141,60+/-7,51 / 90,40+/-5.46mmHg versus 187,60+/-5,94/119,10+/-7.79mmHg (p<0,001). We did not observe any change in heart rate. H. glabra saponins were able to lower blood pressure by a multifactorial mechanism.