Trends in antihypertensives use among Moroccan patients.

PURPOSE: In this study, we analyzed the consumption trends of antihypertensives in Morocco during the 1991-2010 period and the impacts after the institution of Mandatory Health Insurance and the marketing of generic drugs. METHODS: We used sales data from the Moroccan subsidiary of IMS Health "Intercontinental Marketing Service". The consumption volumes were converted into defined daily doses (DDDs). RESULTS: Between 1991 and 2010, outpatient consumption of antihypertensives went from 4.37 to 23.14 DDD/1000 inhabitants/day, a 5.30-fold increase. In 2010, calcium channel blockers (CCBs) and angiotensin converting enzyme inhibitors (ACEI) were the most consumed (4.97 DDD/1000 inhabitants/day) for each one, followed by diuretics (4.20 DDD/1000 inhabitants/day). The most consumed products were amlodipine (4.27 DDD/1000 inhabitants/day) followed by ramipril (3.18 DDD/1000 inhabitants /day) and indapamide (1.72 DDD/1000inhabitants/day). Between 1991 and 2010, the consumption of generic antihypertensives went from 2% to 46%. CONCLUSION: Antihypertensive consumption increased between 1991 and 2010. However, despite the increase of generic drugs consumption, the levels of antihypertensive consumption remain lower than the needs of hypertensive patients.

Detection and molecular identification of human adenoviruses and enteroviruses in wastewater from Morocco.

AIMS: Reclaimed wastewater is a considerable water resource in Morocco. Its agricultural reuse requires an assessment of viral contamination. The aim of this study was to detect both infectious and noninfectious human adenoviruses (HAdV) and enteroviruses (EV) in raw wastewater and treat effluent from wastewater treatment plants (WWTPs) and domestic sewage in Morocco. METHODS AND RESULTS: A total of 22 samples were analysed. A polyethylene glycol (PEG) precipitation method was used, followed by integrated cell culture-PCR (ICC-PCR) using two cell lines: human rhabdomyosarcoma tumour tissue and laryngeal carcinoma cells (RD and Hep2 cells). Furthermore, viral genome amplification was confirmed by sequencing. HAdV were detected in 10 (45·5%) of the 22 samples involving two species: HAdV-B and HAdV-D. EV was detected in 5 (23%) samples belonging to Coxsackievirus B5 and poliovirus vaccine strain (Sabin 2). CONCLUSIONS: Human adenoviruses and EV were detected in the analysed samples from two WWTPs and HAdV in domestic sewage. SIGNIFICANCE AND IMPACT OF THE STUDY: This work is the first study in Morocco using cell culture, PCR and sequencing of enteric viruses from wastewater. The presence of infectious HAdV and EV in treated effluent emphasizes the need of wastewater treatment surveillance.

[Hepatitis B prevalence and risk factors in Morocco]. / Prévalence de l'infection par le virus de l'hépatite B et l'évaluation des facteurs de risque au Maroc.

AIM: The aim of this study was to determine the prevalence of hepatitis B and the risk factors in Morocco. STUDY DESIGN: A total number of 16,634 individuals were screened for HBsAg using the Murex HBsAg Version 3 assay and were interviewed using a structured standard questionnaire to collect information about risk factor. RESULTS: Two hundred seventy-six subjects were positive for HBsAg, the prevalence of HBV infection was 1.66%. Using a structured standard questionnaire we reported that sexual behaviours (43.84%) are among the main risk factors for HBV transmission. CONCLUSION: This study indicates that the prevalence of HBsAg in Morocco is currently estimated at 1.66% in the active population. The risk factors for HBV infection identified here indicate that prevention is the most cost-effective method for successfully controlling HBV infection, so vaccination remains the best way to control this infection and its related complications.

Detection of Shiga toxin-producing Escherichia coli in meat marketed in Casablanca (Morocco).

The contamination of meat and meat products with Shiga toxin-producing O157:H7 and non-O157 Escherichia coli (STEC), obtained from markets in Casablanca, Morocco, was investigated. A total of 460 meat and meat products were sampled between March 2004 and July 2006 analysed and 176 strains of E. coli were isolated from these samples. The presence of the stx1, stx2, eae and ehxA genes, recognized as major virulence factors of STEC, was tested in E. coli isolates by polymerase chain reaction (PCR). STEC was detected in 4 (0.9%) samples. The result of serotyping by molecular method showed that two of these STEC isolates corresponded to the serotype O157:H7. The others Shiga toxin-producing E. coli non-O157 corresponded to O6:H21 and O76:H19. The presence of O157:H7 and non-O157 STEC in meat and meat products marketed in Casablanca, Morocco, emphasizes the importance of implementing the Hazard Analysis and Critical Control Point (HACCP) system, as well as the need for implementing, evaluating, and validating antimicrobial interventions to reduce the presence of potential pathogenic microorganisms.

Microbiological impact of treatment lagoons on the economics of water for reuse in agriculture a case study in Morocco (Settat and Soualem regions).

This study was undertaken to enumerate pathogens: fecal coliforms, Escherichia coli, fecal enterococci and Salmonella in the areas irrigated with treated wastewater. The samples were isolated from Settat (33°00'N, 7°37'W) and Soualem regions (34°26'N, 5°53'W). A total of (n= 48) raw water, (n=48) treated water, (n=71) of vegetables samples irrigated by treated water taken from Waste Water Treatment Plant Settat; A total of (n=24) raw water, (n=24) treated water, (n=97) of vegetables samples irrigated by treated water taken from Waste Water Treatment Plant Soualem. The results show the total average in the two stations of raw water 7.9, 6.1 log MPN 100 ml⁻¹ for respectively fecal coliforms and E. coli, 5.4 log CFU 100 ml⁻¹ for fecal enterococci and 5.2 log MPN L⁻¹ for Salmonella; for treated water 4.6, 3.1 log MPN 100 ml⁻¹ for respectively fecal coliforms and E.coli and 3.5 log CFU 100 ml⁻¹ for fecal enterococci. Regarding plants, four types of crops were harvested and analyzed (forage, herbs, cereals and vegetables), the germs charges were found with fecal coliforms, E.coli and fecal enterococci respectively 3.2, 2.8 and 4.1 log CFUg⁻¹. Salmonella was never detected in both treated water and crops samples.

Bartonella clarridgeiae, B. henselae and Rickettsia felis in fleas from Morocco.

A total of 554 fleas were collected in the Moroccan Casablanca and Tiznit regions from domesticated animals and ruminants between August 2007 and October 2008 and were tested for the presence of Rickettsia spp. and Bartonella spp. using molecular methods. For the first time in Morocco, we found Rickettsia felis, the agent of flea-borne spotted fever in Ctenocephalides felis; B. henselae, an agent of cat scratch disease; and Bartonella clarridgeiae, a cat pathogen and potentially a human pathogen.

Molecular typing of Escherichia coli strains isolated from food in Casablanca (Morocco).

Serotyping of O- and H- antigens is regarded as the gold standard in classification of E. coli for taxonomic and epidemiological purposes similar to the Kaufmann-White scheme for Salmonella enterica. Molecular methods to replace or to support the serotyping were recently applied. Using the molecular polymorphism of the somatic (O- antigen) gene rfb cluster and flagella (H- antigen) gene fliC, 74 E. coli strains carrying the virulent genes isolated from food were characterised by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results showed that 49 (66%) of the isolates revealed a reproducible and clear cut classification, with a very good correlation to the collection of reference strains, were found.

Rapid detection of Listeria monocytogenes in food by polymerase chain reaction.

The standard conventional methods for the detection of Listeria monocytogenes in foods require high time 7 to 10 days to give ready results. To dissolve this problem we have evaluate a short method using Polymerase Chain Reaction (PCR) to analyze food samples. In parallel with this study, a comparison was made between PCR amplification from templates directly prepared from food and the official standard ISO procedure 11290-1. In this study we have used a Half Frazer broth as an enrichment medium; there were positive results of PCR detection of L. monocytogenes in different food sample analyzed (milk, cheese and meat) with approximately 1.5 10(1) Colony Forming Units /25 g in less than 36 h. This PCR procedure has proved to be rapid and sensitive method suitable for the routine analysis; firstly, because this assay required just a short pre-enrichment step before PCR. Secondly, this procedure is very simple and time-saving; it could take less than one working day to obtain results if initial microbiological load was very important.

Analysis of the drug formulary and the purchasing process at a Moroccan university medical center.

AIM: To give an overview of the pharmaceutical policy in the largest medical center in Morocco, a developing country in socio-economic transition. METHODS: This is an analytical descriptive study of the drug formulary and the purchasing process carried out at the Ibn Sina University Medical Center. RESULTS: Our formulary included 830 drugs belonging to 14 classes according to the Anatomical, Therapeutic and Chemical (ATC) Classification System. There was a respective predominance of class N (21.8%), class B (13.5%), and class J (12.6%). Injectable route was dominant (46%). Drugs had a significant actual benefit in 70% (according to the French Data), reimbursable in 42.8%, essential in 29.2% according to World Health Organization (WHO) list, and in 36.9% according to the Moroccan list. The calls for tenders included 542 drugs representing 65% of the formulary, and the attribution rate was 71%. The main reason for non-attribution was the lack of offers. Generics accounted for 45% by volume and 26.5% by value. CONCLUSION: With this first study, we were able to identify key indicators on drugs used in the largest medical center in Morocco. The current challenge is to introduce pharmacoeconomics in decision making concerning the updates of the drug formulary.

[Cardiovascular risk factors in Algeria. Analysis of the subgroup from the "Africa/Middle East Cardiovascular Epidemiological" Study]. / Facteurs de risque cardio-vasculaires en Algérie. Une analyse du sous-groupe de l'étude « Africa/Middle East Cardiovascular Epidemiological ¼.

OBJECTIVES: This cross-sectional epidemiological study aimed at determining the prevalence of cardiovascular risk factors (CVRF; including obesity, dyslipidaemia, hypertension, diabetes and smoking), among patients from the Algerian sub-population of the "Africa/Middle East Cardiovascular Epidemiological" study attending general practitioners at primary healthcare facilities, and stratified according to their environment (rural/urban), sex and age. PATIENTS AND METHODS: The study sites, located in 10 wilayas (administrative regions), were situated in urban and rural areas (rural populations defined as living at least 50km away from urban centres, or lacking access to suburban transport). RESULTS: Four hundred and ten subjects (262 female, 148 male) were enrolled; 287 subjects were from an urban environment and 123 from a rural environment. Mean age was 50.4 years. Ninety one point eight percent of patients had ≥1 CVRF; 48.2% had ≥3 CVRF. Prevalence for the different CVRF was: 61.7% for dyslipidaemia; 39.5% for hypertension; 25.0% for diabetes; 10.0% for smoking, 70.0% for abdominal obesity and 32.0% for a body mass index ≥30kg/m2. CONCLUSION: The high prevalence of all CVRF observed in the Algeria sub-group, especially among the rural population, should encourage us to develop a carefully planned strategy for primary prevention, opportunistic screening and early management, in both urban and rural settings, and with particular attention to young adults. These actions should involve all state bodies and those active in civil society, in order to guarantee full achievement of set goals. The ACE trial is registered under NCT01243138.

"Uniformed" consent and the wealthy volunteer: an analysis of patient volunteers in a clinical trial of a new anti-inflammatory drug.

After a 16-week clinical trial of a new anti-inflammatory drug, the participants were given a factual test to determine whether they had understood and remembered the information given them when consent was solicited. They filled out a questionnaire about their reasons for volunteering and their views on clinical studies and on medical practice in general. Demographic information was also obtained. Two thirds of the participants did not remember that they had been informed about potential risk (gastrointestinal ulceration). Some subjects remembered, but misunderstood, what they had been told; others developed erroneous ideas about the trial and the study drug. The volunteers agreed to participate in the study to help both their own arthritis and that of other patients. They took pride in their self-sacrifice and in being commended by their friends for their altruism. Analysis of the demographic data shows that indigent persons are not necessarily the most likely to participate in clinical trials. Two thirds of the subjects were from the middle class. The median family income was $13,000. To improve the informed consent procedure, we recommend group meetings in which the participants in a clinical trial can discuss the protocol and the risks of the study. Obtaining consent again, after initial anxiety has decreased, may improve comprehension.

The rate of development of new drugs in the United States, 1963 through 1975.

Information was obtained on 1,103 new chemical entities (NCEs) first tested in man from 1963 through mid-1975 by 36 U. S.-owned and 10 foreign-owned pharmaceutical companies operating in the U. S. Of these NCEs 1,029 reached the stage of IND filing. The portion of the U. S. industry responsible for the NCEs was relatively concentrated; 7 of the 36 companies accounted for half of the NCEs and 4 of these accounted for one-third. Although the annual worldwide rate of testing of NCEs by U. S. companies appeared to rise and then fall from 1963 through 1966, since 1966 the rate has been fairly constant. With time, however, a higher proportion of U. S.-owned NCEs is being first studied in man abroad. The annual rate of IND filings for U. S.-owned NCEs generally declined from 1965 to 1972, whereas the rate was fairly constant for foreign-owned NCEs over the entire period. The overall success rate in drug development has been low; nearly 90% of the NCEs studied in man are dropped prior to NDA submission, but about 88% of the NDAs submitted are approved for market. The 1974-1975 data indicate that the mean durations of the IND and NDA phase were then 4 and 2 years, respectively. However, there were variations in the time required for DNA approval between different pharmacologic areas. The data described in this paper represent the first baselines against which future trends in the processes of drug development and approval can be measured.

Free-living volunteer's motivations and attitudes toward pharmacologic studies in man.

Two groups of volunteers who had participated in pharmacologic studies were interviewed about their impressions of such studies. One group was from a university community, the other from the pharmaceutical industry. The differences between the two groups were correlated with their respective backgrounds. Both groups had favorable impressions about drug studies and investigators. Most were satisfied with the information given them about the nature and risks of the studies, but some believed that a written description of the study that they could consult at home would improve their understanding of the information. Financial reward was the primary reason given by both groups for volunteering, but the perceived risk of the study was the ultimate deciding factor. The volunteers disliked having their mobility restricted and for this reason might not be willing to participate in long-term studies, such as those formerly carried out in prisons. Alternative sources of volunteers for long-term studies will have to be found.

Intraspecific variability and pharmacokinetic characteristics of Androctonus mauretanicus mauretanicus scorpion venom.

We evaluated the degree of venom toxicity and protein content of several specimens of Androctonus mauretanicus mauretanicus. The quantity of protein of individual venom obtained after manual extraction from 31 different scorpions varied from a minimum of 0.15 mg to a maximum of 1.53 mg. We determined the venom toxicity, in mice, by estimating the number of LD(50)s of 20 scorpions chosen randomly among the 31 scorpions. It ranged from less than 40 LD(50)s to a maximum of 272 LD(50)s. The correlation between protein content and venom lethality is not systematic. We also determined the pharmacokinetics of the venom and its specific anti-venom in rabbits to compare their distribution and elimination properties. After a subcutaneous injection, high concentrations of venom were measured by ELISA in the vascular space rapidly after the injection (T(max) = 0.5 h). The terminal half-life was 2.8 h, close the one determined after intravenous injection (t(1/2beta) = 3.2 h). The total volume of distribution (Vd(ss) or Vd(beta)) was between 317 and 380 ml/kg. The total body clearance was 82 ml/kg/h. For scorpion anti-venom, the terminal half-life, after intravenous injection, was 20.25 h; the volume of distribution was 83 ml/kg and the total body clearance was 3 ml/kg/h. After intramuscular administration, T(max) was reached at 36 h. The results show that venom lethality varies from specimen to specimen and that pharmacokinetic parameters of venom and anti-venom are totally different. This must be taken under consideration in anti-venom production (anti-venom titre) as well as in therapeutic protocols (dose, injection route) to improve serotherapy.

Effects of Nigella sativa fixed oil on blood homeostasis in rat.

We investigated the effects of the fixed oil of Nigella sativa seeds in rats by monitoring blood homeostasis and body weight as well as toxicity. Animals were treated daily with an oral dose of 1 ml/kg body weight of the N. sativa seed fixed oil for 12 weeks. Changes in key hepatic enzymes levels were not observed in N. sativa treated rats after 12 weeks of treatment. The serum cholesterol, triglycerides and glucose levels and the count of leukocytes and platelets decreased significantly by 15.5, 22, 16.5, 35 and 32%, compared to control values, respectively; while haematocrit and haemoglobin levels increased significantly by 6.4 and 17.4%, respectively. In parallel, significant slowdown of the body weight evolution was observed in N. sativa treated animals comparatively to the animal control group. On the other hand, no mortality was noted for ten times the therapeutic dose in mice, during 15 days period after the oil administration (10 ml/kg p.o.). These results support the traditional use of N. sativa seeds as a treatment of the dyslipidemia and the hyperglycaemia, and related abnormalities; however, indicate a relative toxicity of this plant. Acute and chronic toxicity, and the mode of the action of the N. sativa fixed oil must be studied.

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.

[Experimental evidence of an antihypertensive and hypocholesterolemic effect of oil of argan, Argania sideroxylon]. / Mise en évidence expérimentale des effets antihypertenseurs et hypocholestérolémiants de l'huile d'Argan, Argania sideroxylon.

The chronic ingestion of 5 ml/kg/d of Argan oil by spontaneously hypertensive rats restores normal blood pressure and induces hypocholesterolaemia. In order to confirm these results Meriones shawi, a rodent of the Gerbillideae family, was tested as a second animal model. Meriones submitted to a hypercaloric diet and physical inactivity became fat, and exhibited hypertension, dyslipidaemia and hyperinsulinaemia. When treated for two months with the same dosage regimen, decreases in glycaemia, total plasmatic cholesterol, LDL, insulinaemia and systolic and diastolic blood pressures of 4.4 per cent, 14.4 per cent, 32.5 per cent, 26.8 per cent, 28.8 per cent and 30.5 per cent were simultaneously observed. Increases in LDH and of TG of 27.9 per cent and 16.2 per cent respectively were also observed. No effect on body weight occurred. The action of polyunsatured fatty acids of the Argan oil is predominant, but in addition, other constituents play an active part.

[Synthesis and pharmacologic study of 1,5-dialkyl-1,5-benzodiazepine-2,4-dithiones]. / Synthèse et étude pharmacologique des 1,5-dialkyl-1,5-benzodiazépine-2,4-dithiones.

The synthesis and psychotropic activity of 1,5-diakyl-1,5-benzodiazepine-2,4-dithiones (alkyl = methyl, ethyl and benzyl radicals) were studied. Alkylation reactions were performed in catalytic conditions by phase transfer. These reactions allowed us to isolate only one kind of product N-alkyl. Acute toxicity studies were conducted according to European protocols in two species of appropriate mammals in order to discover the lethal doses. The activity of the compounds on the CNS was then studied, using a battery of compartmental tests used in psychopharmacology. No toxicity was demonstrated at therapeutic doses. Each product had a sedative effect more or less pronounced and different from the reference substance clobazam (Urbanyl). They also had myorelaxant and anxiolytic effects, even lengthening the hypnotic effect of thiopental (synergic action).

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.