Sanjad-Sakati syndrome in a Tunisian child.

Sanjad-Sakati syndrome (SSS) (OMIM 241410) is a rare autosomal recessive disorder characterized by congenital hypoparathyroidism with growth and mental retardation associated with seizures and a characteristic physiognomy. SSS molecular pathology has been shown to be due to mutations in the TBCE gene on chromosome 1q42-q43. All affected patients of Arab origin are homozygous for a 12-bp (155-166del) deletion in exon 3 of this gene. We report on a Tunisian child with SSS who was homozygous for the 155-166del mutation. Our findings provide additional support of the common (155-166del) deletion founder effect in exon 3 of the TBCE gene in Arab patients. It is very likely that this mutation originated in the Middle East and was introduced in Tunisia by the Banu Hilal invaders.

Molecular characterization of piebaldism in a Tunisian family.

OBJECTIVE: The present study is aimed at performing the molecular characterization of a Tunisian family with piebaldism. METHODS: As the proband and her mother showed a severe phenotype, we first chose to screen exons 10, 11, 12, 13, 16, 17 and 18 of the KIT proto-oncogene by direct sequencing. RESULTS: Direct sequencing analysis showed a C to T substitution at 1939 in exon 13 (c.1939C>T) in heterozygous state in the patient and her mother. The mutation was not found in their unaffected family members or normal controls. CONCLUSION: Our results provide additional support that mutations in the tyrosine kinase domain of the KIT gene are responsible for the severe form of piebaldism.

[Preparation of citrulline microspheres by spray drying technique for colonic targeting]. / Préparation des microsphères de citrulline à ciblage colique par la technique de spray drying.

INTRODUCTION: Citrulline is an amino acid that becomes essential in situations of intestinal insufficiency such as short bowel syndrome. It is therefore interesting to provide the patients with dosage forms for routing citrulline to the colon. The aim of this work is to formulate microspheres of citrulline for colonic targeting by the technique of spray drying. MATERIAL AND METHODS: Eudragit(®) FS 30D was selected as polymer to encapsulate citrulline using the spray drying technique. Citrulline and Eudragit(®) FS 30D were dissolved in water and ethanol, respectively. The aqueous and the ethanolic solutions were then mixed in 1:2 (v/v) ratio. Microspheres were obtained by nebulizing the citrulline-Eudragit(®) FS 30D solution using a Mini spray dryer equipped with a 0.7mm nozzle. The microspheres have been formulated using citrulline and Eudragit(®) FS 30D. The size distribution of microspheres was determined by light diffraction. The morphology of the microspheres was studied by electron microscopy. Manufacturing yields, encapsulation rate and dissolution profiles were also studied. RESULTS AND DISCUSSION: The microspheres obtained had a spherical shape with a smooth surface and a homogeneous size except for the microspheres containing the highest concentration of polymer (90 %). The formulation showed that the size and morphology of the microspheres are influenced by the polymer concentration. Manufacturing yields were about 51 % but encapsulation rate were always very high (above 90 %). The in vitro dissolution study showed that the use of the Eudragit(®) FS 30D under these conditions is not appropriate to change the dissolution profile of the citrulline. CONCLUSION: This technique has led to the formulation of microspheres with good physical properties in terms of morphology and size. The compression of the microspheres should help to control citrulline release for colonic targeting.

Particles from preformed polymers as carriers for drug delivery.

Biodegradable and biocompatible polymers are widely used for the encapsulation of drug molecules. Various particulate carriers with different sizes and characteristics have been prepared by miscellaneous techniques. In this review, we reported the commonly used preformed polymer based techniques for the preparation of micro and nano-structured materials intended for drug encapsulation. A description of polymer-solvent interaction was provided. The most widely used polymers were reported and described and their related research studies were mentioned. Moreover, principles of each technique and its crucial operating conditions were described and discussed. Recent applications of all the reported techniques in drug delivery were also reviewed.

Drug carriers in osteoporosis: preparation, drug encapsulation and applications.

Carriers are largely used to enhance therapy efficiency via the encapsulation of active molecules. The encapsulation enhances the stability of drug molecules, improves the targeting properties and prolongs pharmacological activity via continuous local release of active molecules. The aim of this review is to report the carrier systems used in osteoporosis therapy. This state of the art research has mainly focused on describing all types of carriers used in this area, their elaboration and properties, the drug characteristics used in such specific application, and drug release and efficiency. In this field, various processes have been used in order to obtain well-defined capsules, spheres and more complex carriers. In this exhaustive review, each process is described, illustrated and discussed.

[Drug's administration via feeding tubes: evaluation of practices in an intensive care unit of a Tunisian hospital]. / Administration des médicaments par sonde de nutrition entérale : évaluation des pratiques dans un service de réanimation médicale d'un hôpital tunisien.

INTRODUCTION: Drugs' administration via feeding tubes is a potential source of iatrogenic events for the intensive care patients because of the problem of not adapted galenic forms. OBJECTIVES: We analyzed the prescriptions of patients with enteral feedings to determine if the galenic forms were compatible with administration via feeding tubes. We also observed and analyzed the methods of drugs passage by nurses. PATIENTS AND METHODS: We analyzed 30 prescriptions of patients with enteral feedings in the intensive care unit of Habib Bourguiba Sfax hospital, by a prospective and exhaustive way. We also, observed and evaluated the practices of preparation and administration of drugs to these patients via feeding tube by nurses. RESULTS: Only 12% of drugs were liquids. Eighty-eight percent of the drugs were pulverised and capsule open before administration. The galenic form was not in conformity for 20% of drugs because of the prohibition to crushing tablet or opening capsule (gastroresistant form was dissolved), or because of the administration of a parenteral form (risk of irritation). Among 78 drugs administered by 10 different nurses, the time between passage of the drug and enteral nutrition were not respected for 59% of the observations. The drugs were managed in mixture for 90% of the observations. The gloves were not worn in 80% of observations. No rinsing is made between consecutive administrations and before administration. CONCLUSION: This study shows that it is possible to reduce risk of administration errors in the intensive care unit and to facilitate the administration of drug via feeding tube by prescribing liquid oral form or soluble solid oral form. It also shows the need for cooperation with the pharmacist in order to adapt the galenic forms and to redact protocol of administration.

Administration of resveratrol: What formulation solutions to bioavailability limitations?

Resveratrol (3,5,4'-trihydroxystilbene), a naturally occurring polyphenol, has attracted considerable interest for its beneficial potentials for human health, which include anti-oxidant, anti-inflammatory, cardioprotective and anti-tumor activities. However, the in vivo biological effects of resveratrol appear strongly limited by its low bioavailability, which is a barrier to the development of therapeutic applications. In this context, an increasing number of recent studies have aimed at designing novel resveratrol formulations to overcome its poor solubility, limited stability, high metabolization and weak bioavailability. This review outlines physicochemical and pharmacokinetic limitations to resveratrol bioavailability, describes formulations tested for resveratrol administration, controlled release and targeting, and identifies future opportunities for resveratrol delivery.

Liposome preparation using a hollow fiber membrane contactor--application to spironolactone encapsulation.

In this study, we present a novel liposome preparation technique suitable for the entrapment of pharmaceutical and cosmetic agents. This new method uses a membrane contactor in a hollow fiber configuration. In order to investigate the process, key parameters influence on the liposome characteristics was studied. It has been established that the vesicle size distribution decreased with the organic phase pressure decrease, the phospholipid concentration decreases and the aqueous to organic phase volume ratio increases. Liposomes were filled with a hydrophobic drug model, spironolactone that could be used for a paediatric medication. The mean size of drug-free and drug-loaded liposomes was, respectively, 113 ± 4 nm and 123 ± 3 nm. The zeta potential of drug-free and drug-loaded liposomes was, respectively, -43 ± 0.7 mV and -23 ± 0.6 mV. High entrapment efficiency values were successfully achieved (93 ± 1.12%). Transmission electron microscopy images revealed nanometric sized and spherical shaped oligo-lamellar vesicles. The release profile showed a rapid and complete release within about 5h. Additionally, special attention was paid on process reproducibility and long term lipid vesicles stability. Results confirmed the robustness of the hollow fiber module based technique. Moreover, the technique is simple, fast and has a potential for continuous production of nanosized liposome suspensions at large scale.

Establishment of reference serum insulin-like growth factor-I and insulin-like growth factor binding protein-3 levels of Tunisian children during childhood and adolescence.

BACKGROUND: The aim of the present study is to establish age- and sex-related reference ranges of serum IGF-I and IGF binding protein-3 (IGFBP-3) levels in a pattern of Tunisian children. SUBJECTS AND METHODS: Two hundred healthy Tunisian children (103 boys and 97 girls), aged between 6 and 16 yr, were considered in the study. RESULTS: Mean serum levels of IGF-I and IGFBP-3 are observed to be higher in girls compared to boys of the same age interval. However, these differences were statistically significant only in pubertal ages (11-14 yr) for IGF-I and in pre-pubertal ages (6-10 yr) for IGFBP- 3 (p<0.05). Steeper variations in IGF-I concentrations were obtained earlier in girls than in boys (11-12 vs 12-13 yr, Tanner stage 3-4). Peak of IGF-I levels are observed at almost the same age interval (12-14 yr). IGFBP-3 levels significantly increased at steeper variations of IGF-I for both sexes followed by steady values. CONCLUSIONS: Variations of IGF-I and IGFBP- 3 with the considered parameters (sex, age, and puberty stage), which concord with previous studies on various populations, emphasize the importance of locally established reference levels to construct a SD score prediction model. Establishment of reference serum IGF-I and IGFBP-3 ranges during childhood and adolescence in Tunisian subjects can help to enhance the diagnostic efficiency of IGF-I and IGFBP-3 in evaluating growth disorders in our population.

Characterization of cosmetic cream with Mesembryanthemum crystallinum plant extract: influence of formulation composition on physical stability and anti-oxidant activity.

Cosmetic or pharmaceutical composition containing superoxide dismutase (SOD) was usually used in topical administration, particularly, in fighting against skin ageing and in the protection of the skin against radiation exposure. Mesembryanthemum crystallinum is a halophyte plant widely used in the traditional medicine, characterized by the presence of anti-oxidants enzymes in responses to abiotic stresses. In the present study, we prepared a formulation with M. crystallinum extract characterized by naturally occurring SOD and catalase in association with other anti-oxidants molecules. The SOD activity was measured by 3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyl-tetrazolium bromide/riboflavin method, catalase by colorimetric method and the total anti-radical activity was measured by 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) method. Formulations contain a significant SOD activity (8.33 U mg(-1)), a catalase activity (0.5 x 10(7) UC) and an anti-radical activity (30% of DPPH inhibition). The formulation storage (15 days at 4 degrees C) showed a marked loss of total anti-oxidant capacity. The addition of the M. crystallinum extract induced also a reduction in formulation viscosity and pH.

[Human genome project: a federator program of genomic medicine]. / Le projet génome humain: programme fédérateur de la médecine génomique.

The Human Genome Project improves our understanding of the molecular genetics basis of the inherited and complex diseases such as diabetes, schizophrenia, and cancer. Information from the human genome sequence is essential for several antenatal and neonatal screening programmes. The new genomic tools emerging from this project have revolutionized biology and medicine and have transformed our understanding of health and the provision of healthcare. Its implications pervade all areas of medicine, from disease prediction and prevention to the diagnosis and treatment of all forms of disease. Increasingly, it will be possible to drive predisposition testing into clinical practice, to develop new treatments or to adapt available treatments more specifically to an individual's genetic make-up. This genomic information should transform the traditional medications that are effective for every members of the population to personalized medicine and personalized therapy. The pharmacogenomics could give rise to a new generation of highly effective drugs that treat causes, not just symptoms.

La vectorisation des antibiotiques : developpement et applications therapeutiques

La vectorisation des medicaments s'est beaucoup developee ces dernieres annees grace a l'apparition de nouvelles formes galenique issues de la nanotechnologies .Ces formes d'administrastions submicroniques permettent un ciblage des antibiotiques au niveau intracelluraire ainsi que le controle de leur distribution dans le temps et dans l'espace. Nous essayons d'exposer l'evolution dans ces vecteurs ainsi que leurs application dans le traitement de certaines maladies infectieuses

Preparation and characterization of spironolactone-loaded nanocapsules for paediatric use.

Spironolactone is a steroidal diuretic showing incomplete oral behaviour because of its low solubility and slow dissolution rate. In this study, we applied the nanoprecipitation method to prepare spironolactone-loaded nanocapsules, at laboratory-scale and pilot-scale. The effect of several formulation variables on the spironolactone-loaded nanocapsules properties (average size, drug release rate and drug entrapment) was investigated. The optimized formulations at laboratory-scale and pilot-scale lead to the preparation of spironolactone-loaded nanocapsules with a mean size of 320 and 400 nm, respectively, a high encapsulation efficiency (96.21% and 90.56% respectively), both stable for 6 months. The release of spironolactone from nanocapsules was rapid and complete in a simulated gastric fluid, therefore recourse to spironolactone nanoencapsulation should enhance its oral bioavailability and probably its efficiency. The optimized formulations lead to a high drug-concentration in the liquid preparation (1.5 mg/ml) allowing minimizing the preparation volume administered for children medication.

[Theophylline release and diffusion from a compressed ethylcellulose matrix through an artificial membrane]. / Libération et diffusion à travers une membrane artificielle de la théophylline à partir d'un système matriciel.

The aim of this work was to study theophylline dissolution and diffusion from a compressed ethylcellulose matrix through an artificial membrane. The sustained release tablets were manufactured manufactured by direct compression. Dissolution and diffusion studies were performed using an absorption simulator. In the donor compartment, different pH media were used: i) 1.2, 5, 6, ii) the same media supplemented with 10% glucose and iii) an amino acid medium. The receiver medium was held at pH 7.4. The Higuchi equation was used to elucidate the dissolution mechanism. Results showed that dissolution was mainly influenced by theophylline solubility with a mechanism based on diffusion. Diffusion rate was assessed by calculating the diffusion coefficients. Diffusion was essentially dependent on rate of theophylline release.