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Fibroepithelial polyps of the urethra (FEPU) are rare entity in infancy. They are congenital benign tumors. Most patients present with acute retention, hematuria or intermittent bladder outlet obstruction. The treatment of choice is transurethral endoscopic resection. Histological study confirms the diagnosis and the prognosis is excellent. We retrospectively reviewed the medical records of three male patients with fibroepithelial polyps of the urethra that were diagnosed and treated in the department of pediatric surgery of Monastir. The diagnosis was based on voiding cystourethrogram and cystourethroscopy. The treatment was endoscopic resection and histology confirmed the diagnosis in all cases.

Hydatid cysts are endemic in certain regions of the world. It can affect any organ. However, the primary site to the spermatic cord is an unusual location. Hydatid disease has been reported 5 times in the spermatic cord. The purpose of this study was to report a new case of a child with hydatid disease in the spermatic cord. This cyst is the first case treated successfully by Albendazole without surgery.

Heritage elements, from historic buildings to stone sculptures and panels, stand as key elements in the history of humanity. Unfortunately, the deterioration of both the surface and the interior of these elements is inevitable, endangering the quality and existence of these structures of high historical value in the event of a delay in the implementation of the required maintenance tasks. InfraRed Thermography, IRT, appears as one of the most recent techniques to detect and characterize possible pathologies in structures in their early stages, being very useful for a preventive analysis in heritage elements. This paper presents a methodology for the automatic detection and characterization of one of the most severe and frequent pathologies in heritage structures, moisture, from thermal images. The proposal stands as a demonstration of the potential of the IRT technique for heritage conservation applications, and as a new step towards the automation of the inspection process and optimization of the decision-taking in conservation actions within cultural heritage. For that, two thermal criteria and a semi-automatic image rectification process are implemented as main phases of the methodology, obtaining good results for the detection of moisture zones and accurate area values with regard to the real dimensions of each moisture zone. Specifically, an F-score average of 78 % ± 19 % regarding detection performance and a percentage relative error of minimum 4 %, and maximum of 12 %, referred to the area computation in unit metrics are obtained.

Up to now, infrared thermographic approaches have been considered either passive or active. In the latter case, the heat flux is historically attributed to a non-natural heat source. The use of the sun has recently been incorporated into the active approach thanks to multi-temporal inspections. In this paper, an innovative hybrid thermographic (HIRT) approach is illustrated. It combines both the time component and the solar source to obtain quantitative information such as the defect depth. Thermograms were obtained by inspecting the facade of the Santa Maria Collemaggio church (L’Aquila, Italy), whereas quantitative results related to the sub-superficial discontinuities were obtained thanks to the use of advanced techniques. Experimental results linked to passive approach (i.e., the mosaicking procedure of the thermograms) performed by selecting a set of historic churches are also included in order to explain, when and where, the hybrid procedure should be used.

Background: Disorders of Sexual Development can cause significant psychological distress for parents, particularly in traditional societies where such conditions are stigmatized., Aim: This study aims to investigate the psychoaffective impact of sexual development disorders caused by congenital adrenal hyperplasia in children with 46, XX karyotype, in order to determine the predictive factors for the onset of anxiety and depression among parents and the coping strategies employed by parents to adapt to their child's condition., Materials and Methods: This is a retrospective, cross-sectional, descriptive, and analytical study involving parents of children treated for sexual development disorders related to congenital adrenal hyperplasia, with a 46, XX karyotype, who underwent feminizing genitoplasty during the period from January 1, 2005 and December 31, 2021. The Beck Depression Inventory, the Hamilton Anxiety Scale, and the Brief COPE, in their Arabic versions, were used to assess depression, anxiety and coping respectively., Results: This study included 54 parents. Among them 57,4 % exhibited depressive symptomatology, while 37 % reported anxiety symptoms. The most frequently adopted coping strategies among parents were acceptance (88,9 %), reliance on religion (66,7 %), planning (63 %), and active coping (63 %). Predictive factors of depression included the child's current age (OR = 1280), the age of the child at the time of feminizing genitoplasty (OR = 1273), and the non-disclosure of the genitoplasty to the child (OR = 331,522). Predictive factors of anxiety included the parent's female gender (OR = 7756), the child's current age (OR = 1499), the age of the child at the time of feminizing genitoplasty (OR = 1150), and the nondisclosure of the genitoplasty to the child (OR = 115,278)., Conclusion: Despite the various coping strategies adopted by parents of children with disorder of sexual development related to congenital adrenal hyperplasia, the occurrence of anxiety and depression remains inevitable for many of these parents, depending on several well-defined predictive factors. It is therefore imperative to implement appropriate psychological support to help these parents effectively adapt to this complex situation., Type of Study: Case-Control Study., Level of Evidence: III., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Phosphodiesterase-4 is an enzyme that regulates immune responses and contributes to the development of psoriasis. Dipyridamole and roflumilast function as phosphodiesterase-4 inhibitors, reducing pro-inflammatory cytokine expression. The aim was to evaluate the anti-psoriatic effect of the topical administration of dipyridamole and roflumilast nanoemulgel combination on imiquimod-induced psoriasiform skin inflammation in rats., Methods: Dipyridamole and roflumilast were formulated into nanoemulgel to enhance skin penetration and retention. The production of nanoemulgels involves a two-part process. A nanoemulsion is created (the aqueous phase titration method was employed to create nanoemulsions‎), which is then incorporated into the gelling agent during the second phase. The new formula was then tested in rats. The rats were divided into seven groups; all animals were treated for 16 days. Induction was achieved by 120 mg of 5% imiquimod cream, which was applied daily for 8 days. After induction, groups received one of the following: 0.05% clobetasol ointment, 1% dipyridamole nanoemulgel (D-NEG), 0.3% roflumilast nanoemulgel (R-NEG), 1% dipyridamole and 0.3% roflumilast gel combination (DR-gel), and 1% dipyridamole and 0.3% roflumilast nanoemulgel combination (DR-NEG). At the end of the experiment, all animals were euthanized, and their blood and skin tissue samples were obtained. Inflammatory markers, immunohistochemistry, and histopathology were measured., Results: The DR-NEG group showed significantly lower levels of IL17, IL23, and TNF-α, while TGF-β showed higher levels than the clobetasol group. The expression of CK16 was significantly lower compared to the clobetasol group. DR-NEG showed a significantly lower PASI and Baker score than the clobetasol group., Conclusion: The new DR-NEG's topical combination administration showed better anti-inflammatory, tissue healing, and anti-psoriatic activity than each drug alone or topical clobetasol administration; this could be attributed to the possible synergic effects of both drugs and the enhanced skin penetration offered by the nanoemulgel formulation., Competing Interests: The authors declare that no funds, grants, or other support were received during the preparation of this paper., (© 2024 Maded et al.)

Purpose: The concept of interposing double dorsal preputial flaps to cover the urethroplasty was introduced in 2005 to reduce the risk of urethrocutaneous fistula (UCF). Our study aims to compare the postoperative outcomes of urethroplasty for distal hypospadias between two groups: one receiving single preputial flap coverage and another receiving double flap coverage., Materials and Methods: We conducted a retrospective analysis study of boys with primary distal hypospadias who underwent surgery by the same experienced surgeon, at our department between 2010 and 2021. The study population was divided into two groups: Group A, which underwent urethroplasty coverage with single dorsal preputial flap, and Group B, which underwent coverage with double flap. Postoperative complications were compared between the two groups., Results: We collected 105 cases, comprising 51 in Group A and 54 cases in Group B. The mean age at surgery was 29 months in Group A and 24 months in Group B. Post-operative follow-up period ranged from 6 months to 8 years. Functional and cosmetic outcomes were judged excellent in 88.7%. Only 10 boys experienced complications requiring reoperation. UCF occurred in 5 patients from Group A, while no cases were reported in Group B (p = 0.024). Meatal stenosis was identified in three patients in Group A and in two patients in Group B (p = 1). No other complications, such as glans dehiscence or penile torsion, were noted., Conclusion: Double dorsal dartos flap is an effective method for covering the new urethra and can be recommended in the treatment of patients with virgin distal hypospadias., (© 2024 The Author(s). International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Urological Association.)

This study explores developing and optimizing a nanoemulsion (NE) system loaded with dipyridamole and roflumilast, aiming to improve skin penetration and retention. The NE formulation was further transformed into a nanoemulgel to enhance its application as a topical treatment for psoriasis. Solubility studies were conducted to select the oil, surfactant, and co-surfactant. Phase diagrams were constructed using the aqueous phase titration method. All the formulations were in nanoscale, and Formula (F2) (which contains oleic acid oil as the oil phase, a mixture of Surfactant Tween 80 and co-surfactant (ethanol) at a ratio of 1:2 in addition to distilled water as an aqueous phase in a ratio of 1:5:4, respectively) was the selected formula depending on the particle size, PDI, and zeta potential. Formula (F2) has the best ratio because it gives the smallest nanoemulsion globule size (particle size average of 167.1 nm), the best homogenicity (lowest PDI of 0.195), and the highest stability (higher zeta potential of -32.22). The selected formula was converted into a nanoemulgel by the addition of 0.5% ( w / w ) xanthan gum (average particle size of 172.7 nm) and the best homogenicity (lowest PDI of 0.121%) and highest stability (higher zeta potential of -28.31). In conclusion, the selected formula has accepted physical and chemical properties, which enhanced skin penetration.

Introduction: Rifaximin is an intestinal antiseptic which has five (pseudo) polymorphs α, β, γ, δ and ε . These last (pseudo)polymorphs have different physicochemical properties. The objective of the study is to assess the impact of rifaximin polymorphism on its dissolution rate which could affect its bioavailability., Material and Methods: The analytical validation of dissolution assay method by UV-Visible spectrophotometry was carried out according to ICH Q2. The physicochemical characterization (solubility test, FTIR, DSC, XRD) was carried out on four active pharmaceutical ingredient (MP1, MP2, MP3, MP4). MP1 and MP2 were used by the manufacturer of generic brand 1 (G1) and MP3 and MP4 were used by the manufacturer of generic brand 2 (G2). The comparative in-vitro dissolution study was carried out on the leader brand (P), G1 and G2., Results: The four MPs were analyzed by XRD. The results of analysis showed that MP1 and MP4 were a mixture of α form and amorphous form. MP2 had an amorphous form and MP3 had a crystalline form β. The spectra of FTIR showed that the four MP had characteristics bands of rifaximin in the domain 4000-400 cm -1 . The differences between the spectra of the four MPs were observed among the amorphous form (MP2), around the region 1800 to 1820 cm -1 which is attributed to the vibration of the CO group. An additional difference observed among the amorphous form (MP2) is around the region 1400 cm -1 which is attributed to the banding OH. The thermograms of MP1, MP2 and MP4 showed endothermic peaks which are probably attributed to the departure of water which indicate that MP1, MP2 and MP4 are pseudopolymoph (hydrate). For the four MPs, probably the melting points are interrupted by the phenomenon of phase transformations (Crystallization) which are reflected by exothermic peaks around 200°C-250 °C.Our results showed that the crystalline polymorphism of rifaximin influences its solubility. According to the results of the solubility test, the β crystal form of rifaximin (MP3) had the lowest solubility (3.47 μg/ml). MP2 had the highest solubility (8.35 μg/ml) and MP1 and MP4 had intermediate solubilities (5.47 μg/ml and 6.74 μg/ml). Comparative in vitro dissolution results showed that the dissolution profile of P was not similar to that of G1 and G2 (% dissolution (P) 30min  = 60%; % dissolution (G1) 30 min  = 100% and % dissolution (G2) 30 min  = 115%; f1(P versus G1) = 44; f1(P versus G2) = 61) in M1, while G1 and G2 had comparatively similar dissolution profiles (% dissolution (G1) 30 min  = 100%; % dissolution (G1) 30 min  = 110%; f1 (G1 versus G2) = 14) in M1., Conclusion: This study highlighted the impact of rifaximin polymorphism on its physico-chemical properties (crystal structure, thermal behavior, solubility) and on its dissolution behavior which could affect the rifaximin bioavailability., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

In the present study, a self-nano-emulsifying drug delivery system (SNEDDS) was developed to evaluate the efficiency of thymoquinone (TQ) in hepatic ischemia/reperfusion. SNEDDS was pharmaceutically characterized to evaluate droplet size, morphology, zeta potential, thermodynamic stability, and dissolution/diffusion capacity. Animals were orally pre-treated during 10 days with TQ-loaded SNEDDS. Biochemical analyses, hematoxylin-eosin staining, indirect immunofluorescence, and reverse transcription polymerase chain reaction (RT-PCR) were carried out to assess cell injury, oxidative stress, inflammation, and apoptosis. The TQ formulation showed good in vitro characteristics, including stable nanoparticle structure and size with high drug release rate. In vivo determinations revealed that TQ-loaded SNEDDS pre-treatment of rats maintained cellular integrity by decreasing transaminase (ALT and AST) release and preserving the histological characteristics of their liver. The antioxidant ability of the formulation was proven by increased SOD activity, reduced MDA concentration, and iNOS protein expression. In addition, this formulation exerted an anti-inflammatory effect evidenced by reduced plasma CRP concentration, MPO activity, and gene expressions of TLR-4, TNF-α, NF-κB, and IL-6. Finally, the TQ-loaded SNEDDS formulation promoted cell survival by enhancing the Bcl-2/Bax ratio. In conclusion, our results indicate that TQ encapsulated in SNEDDS significantly protects rat liver from I/R injury., (© 2023. Controlled Release Society.)

Background: Human papillomavirus is the major cause of cervical cancer, but only few cases develop into cancer. Nevertheless, HuR (ELAVL1) gene has been implicated in the oncogenesis of certain cancers. The correlation between ELAVL1 gene and the risk of cervical cancer remains unclear. Therefore, this study investigated the effect of ELAVL1 gene polymorphisms (SNPs) in cervical cancer development in Tunisian women., Method: ELAVL1 gene SNPs: ELAVL1 rs12983784 T > C, ELAVL1 rs14394 T > C, ELAVL1 rs74369359 G > T, ELAVL1 rs35986520 G > A, ELAVL1 rs10402477 C > T, ELAVL1 rs12985234 A > G and ELAVL1 rs2042920 T > G, were genotyped by High resolution melting (HRM). SNPStats software was used to perform linkage disequilibrium (LD) and haplotype analysis., Results: Comparing the cervical cancer patients with healthy control participants, the SNPs rs12983784 (P = 0.032), rs74369359 (p = < 10 - 3 ) and rs10402477 (P = 0.001) were associated with an increased cervical cancer risk. Contrary to the SNPs rs14394, rs7469359, rs35986520, rs12985234 and rs2042920 (p˃0.05). The haplotype analysis of the seven SNPs of ELAVL1 gene showed that there is no association between the different haplotypes and a possible risk of cervical cancer disease. Moreover, there was a significant Linkage disequilibrium between rs35986520 and rs2042920 (D'=0.9972) and between rs2042920 and rs10402477 (D'=0.9977)., Conclusion: Our results indicated that genetic variants in the ELAVL1 gene might be associated with susceptibility to cervical cancer in the Tunisian population., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Host genetic characteristics and environmental factors interactions may play a crucial role in cervical carcinogenesis. We investigated the impact of functional genetic variants of four xenobiotic-metabolizing genes (AhR, CYP1A1, GSTM1, and GSTT1) on cervical cancer development in Tunisian women., Methods: The AhR gene polymorphism was analyzed using the tetra-primer ARMS-PCR, whereas the CYP1A1 polymorphism genotypes were identified by PCR-RFLP. A multiplex ligation-dependent polymerase chain reaction approach was applied for the analysis of GSTM1 and GSTT1 polymorphisms., Results: The homozygous A/A genotype of the AhR gene (rs2066853) and the heterozygous T/C genotype of the CYP1A1 SNP (CYP1A1-MspI) appeared to be associated with an increased risk of cervical tumorigenesis (OR a = 2.81; OR a = 5.52, respectively). Furthermore, a significantly increased risk of cervical cancer was associated with the GSTT1 null genotype (OR a = 2.65). However, the null GSTM1 genotype showed any significant association with the risk of cervical cancer compared to the wild genotype (OR a = 1.18; p = 0.784). Considering the combined effect, we noted a significantly higher association with cancer risk for individuals with at least two high-risk genotypes of CYP1A1/GSTT1 (OR a = 4.2), individuals with at least two high-risk genotypes of CYP1A1/GSTT1/AhR (OR a = 11.3) and individuals with at least two high-risk genotypes of CYP1A1/GSTM1/GSTT1/AhR exploitation low-risk genotype as a reference., Conclusion: This study indicated that the single-gene contribution and the combined effect of xenobiotic-metabolizing gene polymorphisms (AhR, CYP1A1-MspI, GSTM1, and GSTT1) may have a considerable association with increased cervical cancer risk., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Since ancient times the oil from date palm pits (Phoenix dactylifera L.) has been used to heal wounds. In order to prove this traditional usage of the pits, this oil was extracted from the pits of the Tunisian cultivar 'Alig' and its physico-chemical properties and the chemical composition were evaluated. The fatty acid profile, evidenced by GC, allowed to classify this oil as an oleic-myristic acid oil with a clear abundance of oleic acid (53.66 %). 1 H and 13 C-NMR as well as FT-IR analyses confirmed the presence of fatty acids in triglyceride forms. Furthermore, in vivo wound healing activity of a cream formulated from the extracted oil was performed, for the first time, using a rat model and was compared to placebo cream and a commercial formulation, MEBO®. This study showed that the test cream promoted the healing of pressure ulcers better than the placebo cream and the MEBO® ointment. The results showed that this vegetable oil is able to improve the healing of infected wounds in rats, thus supporting its traditional use. The contribution of the main oleic, linoleic and myristic acids that can be derived from enzymatic hydrolysis to the healing activity of the whole pits oil was predicted by in silico study and the calculated pharmacokinetics parameters., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

According to the Center for Disease Control and Prevention (CDC), the coronavirus disease 2019, a respiratory viral illness linked to significant morbidity, mortality, production loss, and severe economic depression, was the third-largest cause of death in 2020. Respiratory viruses such as influenza, respiratory syncytial virus, SARS-CoV-2, and adenovirus, are among the most common causes of respiratory illness in humans, spreading as pandemics or epidemics throughout all continents. Nanotechnologies are particles in the nanometer range made from various compositions. They can be lipid-based, polymer-based, protein-based, or inorganic in nature, but they are all bioinspired and virus-like. In this review, we aimed to present a short review of the different nanoparticles currently studied, in particular those which led to publications in the field of respiratory viruses. We evaluated those which could be beneficial for respiratory disease-based viruses; those which already have contributed, such as lipid nanoparticles in the context of COVID-19; and those which will contribute in the future either as vaccines or antiviral drug delivery systems. We present a short assessment based on a critical selection of evidence indicating nanotechnology's promise in the prevention and treatment of respiratory infections., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2021 Mahdi Ftouh et al.)

Objective: To determine which patients should benefit from the interposition of a well-vascularized flap between the neourethra and the penile skin and if it should be performed even in mild hypospadias., Patients and Methods: A retrospective study on patients with a primary hypospadias repair was performed (2003-2017). Only patients undergoing urethroplasty based on the principle of a tubularization were selected to ensure comparable groups. Patients were assigned in two groups according to the use or not of a cover flap. Univariate analysis and adjusted logistic regression were used to evaluate the relation between postoperative complications, the severity of hypospadias, the use of flap and patients' characteristics., Results: Three-hundred and seventy-six patients were included with anterior (59.3%), midshaft (27.4%) and posterior hypospadias (13.3%). The median follow-up was 54 months (24 months-17 years). The overall rate of fistula was 11.7% (n = 44). Comparing the outcome in children with flap (n = 217) to controls (n = 159) showed that the use of a flap reduces the rate of fistula (6.5 vs 18.9%, p < 0.001). Stratification of the study according to the phenotype reveals that the more severe the hypospadias, the more protective was the flap (OR = 2.6 for anterior, 5.5 for midpenile, 7.1 for posterior hypospadias). The flap remains nevertheless significantly effective whatever the phenotype (p < 0.05 for anterior, p = 0.01 for midpenile, p = 0.02 for posterior hypospadias)., Conclusions: The more severe the hypospadias, the more effective is the cover flap to avoid fistula. It remains nevertheless suitable even in anterior hypospadias and the use of a cover flap should not be limited to the surgery of severe phenotypes., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

In this study, we focused on quetiapine fumarate (QTF), a class II BCS drug. QTF is an atypical antipsychotic used in the treatment of schizophrenia and bipolar disorders. Our objective was to develop a new QTF-loaded self-emulsifying drug delivery system (SEDDS) to improve the dissolution and absorption of the drug. An experimental design approach was used to develop and optimize QTF-loaded SEDDS. The optimized formulation was characterized for droplets size, zeta potential, PDI, and stability. It was then evaluated using an in-vitro combined test for dissolution and Everted gut sac technique. Mathematical modeling and Transmission electron microscopy (TEM) were used to elucidate the mechanism of release. The optimal formulation was type IIIB SEDDS, constituted of 9.1% of oleic acid, 51.6% of Tween ® 20, and 39.3% of Transcutol ® P. It showed a droplets size of 144.8 ± 4.9nm with an acceptable PDI and zeta potential. For in-vitro evaluation tests, we noticed an enhancement of the dissolution rate of the optimal QTF-loaded SEDDS compared to the free drug (98.82 ± 1.24% for SEDDS after 30 min compared to 85.65 ± 2.5% for the pure drug). The release of QTF fitted with the Hopfenberg model indicating the drug was released by water diffusion and erosion mechanism. This result was confirmed by TEM images which showed a smaller droplet size after release. We also found an amelioration of the permeability of QTF of 1.69-fold from SEDDS compared to the free drug. Hence, the SEDDS formulation represented a new way to improve the dissolution and absorption of QTF.

Objective: This study investigates the effectiveness of self-nanoemulsifying drug delivery system (SNEDDS) in improving voriconazole transcorneal permeability., Methods: Voriconazole-SNEDDS was prepared with isopropyl myristate, PEG 400, Tween 80 ® and Span 80 ® and was subjected for physicochemical characterization after reconstitution with NaCl 0.9% (1/9; v/v). In-vitro antifungal activity was assessed and compared with the marketed formulation. In-vivo studies, namely ocular irritation test via modified Draize test and pharmacokinetic study, were investigated using rabbit as animal model., Key Findings: Voriconazole-SNEDDS presented a droplet size of 21.353 ± 0.065 nm, a polydispersity index of 0.123 ± 0.003, a pH of 7.205 ± 0.006 and an osmolarity of 342.667 ± 2.517 mOsmol/l after reconstitution with NaCl 0.9%. Voriconazole-SNEDDS minimum inhibitory concentration (MIC 90 ) was similar to the one of marketed formulation for Candida species while it was significantly lower (P < 0.001) for Aspergillus fumigatus. Draize test revealed that Voriconazole-SNEDDS was safe for ocular administration. Voriconazole maximum concentration (5.577 ± 0.852 µg/ml) from SNEDDS was higher than marketed formulation (C max  = 4.307 ± 0.623 µg/ml), and the T max was delayed to 2 h. The area under the concentration-time curve value of Voriconazole-SNEDDS was improved by 2.419-fold., Conclusion: Our results suggest that SNEDDS is a promising carrier for voriconazole ocular delivery and this encourages further clinical studies., (© 2020 Royal Pharmaceutical Society.)

The aim of this study was to develop self- nanoemulsifying drug delivery system (SNEDDS) to improve the transcorneal permeability of voriconazole. A 'mixture design around a reference mixture' approach was applied. This latter included four components, namely, isopropyl myristate, PEG 400, Tween ® 80 and Span ® 80 as oil, co-solvent, surfactant and co-surfactant, respectively. Droplet size was selected as response. The effect of mixture components on droplet size was analyzed by means of response trace method. Optimal formulation was subjected to stability studies and characterized for droplet size, polydispersity index (PDI), pH, osmolarity, viscosity and percentage of transmittance. Ex-vivo transcorneal permeation of the optimal and the marketed formulations was carried out on excised bovine cornea using Franz cell diffusion apparatus. Optimal voriconazole loaded-SNEDDS showed moderate emulsification efficiency and was characterized by a droplet size of 21.447 ± 0.081 nm, a PDI of 0.156 ± 0.004, a pH of 7.205 ± 0.006, an osmolarity of 310 mosmol/Kg and a viscosity of 8.818 ± 0.076 cP. Moreover, it presented an excellent stability and exhibited a significant improvement ( p  < 0.05) in apparent permeability coefficient (1.982 ± 0.187 × 10 -6  cm/s) when compared to commercialized formulation (1.165 ± 0.106 × 10 -6  cm/s). These results suggest that SNEDDS is a promising carrier for voriconazole ocular delivery.

Background: Pulmonary hydatid disease remains an important healthcare problem. Conservative operative interventions including cystotomy or cystotomy with capitonnage are the two commonly used techniques. However, there is no scientific consensus over selection of these operative interventions., Aim: The aim of this study is to compare these two methods: capitonnage and uncapitonnage in the surgery of childhood pulmonary hydatid cyst in regard to the postoperative period., Methods: This is a retrospective analysis of 136 patients operated for pulmonary hydatid disease between January 2010 and July 2017 according to two techniques. Group A was cystotomy with capitonnage (n = 76), and group B was cystotomy alone (n = 60). We compared the postoperative outcomes., Results: Our data showed pneumothorax(PNO) and emphysema were seen in 30% of Group B and only in 13.2% in Group A, and the persistence of residual cavity in 23.3% in Group B and 7.9% in Group A (p = 0.014). We have not seen any case of recurrence with capitonnage., Conclusion: We conclude that capitonnage appears to prevent PNO and emphysema formation and a remaining residual cavity in the long term with a significant difference. And it prevents prolonged postoperative air leak and hospitalization with a slightly nonsignificant difference. It is difficult to say with absolute certainty that the noncapitonnage group is inferior to the capitonnage group, since several factors can influence the evolution., Type of Study: Clinical research article Level of evidence III., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The present work attempts to develop and optimize the formula of a lipidic nanoemulsion (NE) containing sodium hyaluronate (HNa) and indomethacin (Ind) as HNa-Ind for enhanced transdermal antiarthritic activity. NEs were prepared by the spontaneous emulsification method and characterized by Fourier-transform infrared (FTIR) spectroscopy. The composition of the optimal formulation was statistically optimized using Box-Behnken experimental design method with three independent factors and was characterized for particle size, polydispersity index, and percent transmittance. The selected formula was tested for its in vitro antioxidant activity and in vivo anti-inflammatory activity. The optimized HNa-Ind NE formula was characterized and displayed a particle size of 12.87 ± 0.032 nm, polydispersity index of 0.606 ± 0.082, and 99.4 ± 0.1 percentage of transmittance. FTIR showed no interaction between HNa and Ind as a physical mixture. In addition, the optimized HNa-Ind NE was able to preserve the antioxidant ability of the two drugs, as evidenced through a 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition assay used to assess free radical scavenging ability. The cell viability was increased while the free radical scavenging activity was decreased (94.28% inhibition at higher concentrations compared with vitamin C as a reference with an inhibition of 100%). Moreover, the pharmacological anti-inflammatory potential of the optimized HNa-Ind NE formulation was assessed using an in vivo model. Compared with reference drugs (ibuprofen gel 5%), the remarkable activity of the optimized formulation was established using xylene-induced ear edema in mice model, in which the inflamed region reduced by 92.5% upon treatment. The optimized HNa-Ind NE formulation showed considerably higher skin permeation and drug deposition capability compared with the HNa-Ind solution. HNa-Ind NE was demonstrated to be a successful carrier with enhanced antioxidant and anti-inflammatory potential while showing better skin penetration, thus being a promising vehicle for transdermal drug delivery.

Introduction: To evaluate if torsion of an otherwise healthy ovary (THO) has a different prognosis than torsion with an underlying ovarian mass (TUOM) in children., Material and Methods: Children with an ovarian torsion who were treated in our department from 1997 to 2016 were studied retrospectively. Patients with prenatal ovarian torsion and isolated oviduct torsion were excluded. Trophicity of the ovary was assessed by ultrasonography at the end of follow-up., Results: Fifty-four girls were included. Twenty-seven presented a TUOM; the others had a THO. Beside the deleterious effect of late surgical management, another prognostic factor was identified. THO was more prone to an ovarian hypotrophy or atrophy than TUOM (n = 20 vs n = 5, p < 0.01). This was confirmed by logistic regression analysis (OR = 5.08, p = 0.01). To explain this finding, we further compared TUOM and THO. The diagnosis of TUOM was more frequently suspected on US at the first visit (p = 0.005). TUOM also occurred more often after puberty (>12 years, 52.9% vs 11.1%, p < 0.001) than THO., Conclusion: THO is more frequently associated with an ovarian atrophy or hypotrophy than TUOM. A less obvious diagnosis at US and the early occurrence of THO before puberty with a less favorable hormonal climate may explain this finding., Level of Evidence: III., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to document clinical features of inguinal hernia (IH) in the pediatric population. It provides data to evaluate associated risk factors of incarcerated hernia, its recurrence as well as the occurrence of contralateral metachronous hernia., Materials and Methods: We report a retrospective analytic study including 922 children presenting with IH and operated from 2010 to 2013 in our pediatric surgery department., Results: We managed 143 girls (16%) and 779 boys (84%). The mean age was 2 years; the right side was predominantly affected (66.8%, n = 616). Incarcerated hernia was documented in 16% of cases with an incidence of 33% in neonates. The incarceration occurrence was 15.5% in males versus 2.09% in females. The surgical repair was done according to Forgue technique. Postoperatively, four cases of hernia recurrence were documented, and contralateral metachronous hernia was reported in 33 children with 7.7% females versus 2.8% males. Forty-five percent of them were infants. The mean follow-up period was 4 years. We think that incarceration can be related to several risk factors such as feminine gender, prematurity, and the initial left side surgical repair of the hernia., Conclusion: IH occurs mainly in male infants. Prematurity and male gender were identified as risk factors of incarceration. Contralateral metachronous hernia was reported, especially in female infants and after a left side surgical repair of the hernia., Competing Interests: There are no conflicts of interest.

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., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Recently, we developed a new approach to rationalize an optimized design for self-emulsifying drug delivery system (SEDDS) by introducing the HLB and the response surface as determinant factors in SEDDS development. The aim of this current paper is to assess the suitability of this HLB-RSM approach to enhance the oral bioavailability of BCS class II compounds using fenofibrate as drug model. Eight SEDDS formulations (I→VIII) were pre-selected regarding their self-emulsification capacity and their effect on increasing in vitro drug release. They were firstly evaluated for their thermodynamic stability and zeta potential. Unstable SEDDS were discarded meanwhile the structural morphology of the stable ones (I, VI and VIII) was characterized using transmission electron microscopy (TEM). A pharmacokinetic study was then undertaken on male BALB/cJRj mices. The in vivo results showed a significant increase of fenofibrate absorption for all the three stable SEDDS formulations compared to the commercialized form, (LIPANTHYL micronized(®) (p<0.05)). The highest enhancement was recorded for SEDDS I, where AUC and Cmax values respectively increased by 2 and 4.4 folds. This justifies the fact that HLB-RSM approach could be considered as a promising method for the development of efficient and highly stable SEDDS aiming to increase the poor bioavailability of BCS class II molecules., (Copyright © 2015. Published by Elsevier B.V.)

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., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

The incidence of ventilator-associated pneumonia (VAP) is particularly high in patients with trauma. The efficacy and safety of selective digestive decontamination (SDD) was not studied extensively. We aimed in our randomized double-blind, placebo-controlled study to evaluate whether SDD prevents VAP onset in multiple trauma patients. All adult patients admitted in our intensive care unit for multiple trauma with a predicted duration of mechanical ventilation (MV) over 48 hours were included. We included 44 patients who were divided into 4 groups: group A receiving subglottic and gastric treatment suspension (polymyxin E 100 mg, vancomycin 1 g, and amphotericin B 500 mg), group B receiving placebo, group C receiving subglottic placebo and gastric treatment suspension, and group D receiving subglottic treatment suspension and gastric placebo. The suspension was given 4 times a day during 7 consecutive days. To this topical treatment, we associated an intravenous administration of cefotaxime (1 g 3 times a day during 4 consecutive days). The incidence of VAP in the 4 groups was, respectively, 45.5%, 46.2%, 22.2%, and 27.3% (P=0.236). In multivariate analysis, none of the 3 tested regimens was identified as a protective factor against VAP. However, prolonged duration of MV was the only independent factor predicting VAP onset (odds ratio=1.1; 95% confidence interval [1.1-1.4]; P=0.049).

The aim of this work was to elaborate a novel approach for the development and optimization of self-emulsifying drug delivery system (SEDDS), using response surface methodology and hydrophilic lipophilic balance (HLB). Fenofibrate was selected as drug model. Rapid selection of excipients was operated with reference to their toxicity and capacity to solubilize the drug. A three level Box-Behnken design was used. The independent variables were (X1) surfactants/oil, (X2) cosurfactant/surfactant and (X3) percentage of cosolvent. The high and low levels of these factors were selected with reference to the experimental domain that covers an interval of HLB from 7.8 to 15. This interval of HLB is assumed to lead to oil in water emulsification and to contain the required HLB. The responses were (Y1) droplet size and (Y2) cumulative percentage drug released in 20 mn.Various response surface graphs were constructed to understand the effects of different factor level combinations. The optimized SEDDS with predicted drug release 83.6%, and droplet size 137 nm was prepared; the experimental values were in close agreement. The required HLB was 9.85. Optimized SEDDS showed significant increase in dissolution rate compared to conventional prepared gelatin capsules. In conclusion, this paper demonstrated the reliability, rapidity, and robustness of the approach., (Copyright © 2014. Published by Elsevier B.V.)

The aim of the present study was to develop and characterize a resveratrol self-emulsifying drug delivery system (Res-SEDDS), and to compare the uptake of resveratrol by bovine aortic endothelial cells (BAECs), and the protection of these cells against hydrogen peroxide-mediated cell death, versus a control resveratrol ethanolic solution. Three Res-SEDDSs were prepared and evaluated. The in vitro self-emulsification properties of these formulations, the droplet size and the zeta potential of the nanoemulsions formed on adding them to water under mild agitation conditions were studied, together with their toxicity on BAECs. An optimal atoxic formulation (20% Miglyol® 812, 70% Montanox® 80, 10% ethanol 96% v/v) was selected and further studied. Pre-incubation of BAECs for 180 min with 25 μM resveratrol in the nanoemulsion obtained from the selected SEDDS significantly increased the membrane and intracellular concentrations of resveratrol (for example, 0.076±0.015 vs. ethanolic solution 0.041±0.016 nmol/mg of protein after 60 min incubation, p<0.05). Resveratrol intracellular localization was confirmed by fluorescence confocal microscopy. Resveratrol nanoemulsion significantly improved the endothelial cell protection from H2O2-induced injury (750, 1000 and 1500 μM H2O2) in comparison with incubation with the control resveratrol ethanolic solution (for example, 55±6% vs. 38±5% viability after 1500 μM H2O2 challenge, p<0.05). In conclusion, formulation of resveratrol as a SEDDS significantly improved its cellular uptake and potentiated its antioxidant properties on BAECs., (Copyright © 2013 Elsevier B.V. All rights reserved.)

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., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

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.

PTEN plays a well-established role in the negative regulation of the PI3K pathway, which is frequently activated in several cancer types, including breast cancer. A nuclear function in the maintenance of chromosomal stability has been proposed for PTEN but is yet to be clearly defined. In order to improve understanding of the role of PTEN in mammary tumorigenesis in terms of a possible gene dosage effect, its PI3K pathway function and its association with p53, we undertook comprehensive analysis of PTEN status in 135 sporadic invasive ductal carcinomas. Four PTEN status groups were defined; complete loss (19/135, 14%), reduced copy number (19/135, 14%), normal (86/135, 64%) and complex (11/135, 8%). Whereas the PTEN complete loss status was significantly associated with estrogen receptor (ER) negativity (p=0.006) and in particular the basal-like phenotype (p<0.0001), a reduced PTEN copy number was not associated with hormone receptor status or a particular breast cancer subtype. Overall, PI3K pathway alteration was suggested to be involved in 59% (79/134) of tumors as assessed by human epidermal growth factor receptor 2 overexpression, PIK3CA mutation or a complete loss of PTEN. A complex PTEN status was identified in a tumor subgroup which displayed a specific, complex DNA profile at the PTEN locus with a strikingly similar highly rearranged pan-genomic profile. All of these tumors had relapsed and were associated with a poorer prognosis in the context of node negative disease (p=1.4 × 10(-13) ) thus may represent a tumor subgroup with a common molecular alteration which could be targeted to improve clinical outcome., (Copyright © 2013 UICC.)

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., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Citrulline possesses a highly specific metabolism that bypasses splanchnic extraction because it is not used by the intestine or taken up by the liver. The administration of citrulline may be used to deliver available nitrogen for protein homeostasis in peripheral tissues and as an arginine precursor synthesized de novo in the kidneys and endothelial and immune cells. Fresh research has shown that citrulline is efficiently transported across the intestinal luminal membrane by a set of transporters belonging to the B⁰,⁺, L, and b⁰,⁺ systems. Several pharmacokinetic studies have confirmed that citrulline is efficiently absorbed when administered orally. Oral citrulline could be used to deliver arginine to the systemic circulation or as a protein anabolic agent in specific clinical situations, because recent data have suggested that citrulline, although not a component of proteins, stimulates protein synthesis in skeletal muscle through the mammalian target of rapamycin signaling pathway. Hence, citrulline could play a pivotal role in maintaining protein homeostasis and is a promising pharmaconutrient in nutritional support strategies for malnourished patients, especially in aging and sarcopenia., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The oxidant stress, expected to increase in obese adults, has an important role in the pathogenesis of many diseases. It results when free radical formation is greatly increased or protective antioxidant mechanisms are compromised. The main objective of this study is to evaluate the antioxidant response to obesity-related stress in healthy children., Methods: A hundred and six healthy children (54 obese and 52 controls), aged 6-12 years old, participated in this study. The collected data included anthropometric measures, blood pressure, fasting glucose, total cholesterol, triglycerides and enzymatic antioxidants (Superoxide dismutase: SOD, Catalase: CAT and Glutathione peroxidase: GPx)., Results: The first step antioxidant response, estimated by the SOD activity, was significantly higher in obese children compared with normal-weight controls (p < 0.05). Mean activities of anti-radical GPx and CAT enzymes were not affected by the BMI increase. Although, total cholesterol levels were statistically higher in the obese group, there was no significant association with the SOD activity., Conclusions: The obesity-related increase of the oxidant stress can be observed even in the childhood period. In addition to the complications of an increased BMI, obesity itself can be considered as an independent risk factor of free radical production resulting in an increased antioxidant response.

Background: Despite entering complete remission after primary treatment, a substantial proportion of patients with early stage breast cancer will develop metastases. Prediction of such an outcome remains challenging despite the clinical use of several prognostic parameters. Several reports indicate that genomic instability, as reflected in specific chromosomal aneuploidies and variations in DNA content, influences clinical outcome but no precise definition of this parameter has yet been clearly established., Methods: To explore the prognostic value of genomic alterations present in primary tumors, we performed a comparative genomic hybridization study on BAC arrays with a panel of breast carcinomas from 45 patients with metastatic relapse and 95 others, matched for age and axillary node involvement, without any recurrence after at least 11 years of follow-up. Array-CGH data was used to establish a two-parameter index representative of the global level of aneusomy by chromosomal arm, and of the number of breakpoints throughout the genome., Results: Application of appropriate thresholds allowed us to distinguish three classes of tumors highly associated with metastatic relapse. This index used with the same thresholds on a published set of tumors confirms its prognostic significance with a hazard ratio of 3.24 [95CI: 1.76-5.96] p = 6.7 x 10(-5) for the bad prognostic group with respect to the intermediate group. The high prognostic value of this genomic index is related to its ability to individualize a specific group of breast cancers, mainly luminal type and axillary node negative, showing very high genetic instability and poor outcome. Indirect transcriptomic validation was obtained on independent data sets., Conclusion: Accurate evaluation of genetic instability in breast cancers by a genomic instability index (G2I) helps individualizing specific tumors with previously unexpected very poor prognosis.

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., (Copyright © 2012 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.)

Objectives: Clopidogrel, a thienopyridine antiplatelet agent, is a poor aqueous soluble compound and a P-glycoprotein (P-gp) efflux pump substrate. These two factors are responsible for its incomplete intestinal absorption. In this study, we have attempted to enhance the absorption of clopidogrel by improving its solubility and by inhibiting intestinal P-gp activity., Methods:   Solubility enhancement was achieved by preparing solid dispersions. Quinidine and naringin were selected as P-gp inhibitors, whilst tartaric acid was selected as the intestinal absorption enhancer. Absorption studies were performed using the everted gut sac model prepared from rat jejunum. The determination of clopidogrel was performed by high performance liquid chromatography., Key Findings: We noticed an enhancement of clopidogrel absorption by improving its solubility or by inhibiting the P-gp activity. The greatest results were obtained for solid dispersions in the presence of P-gp inhibitors at their highest concentrations, with an absorption improvement of 3.41- and 3.91-fold for naringin (15mg/kg) and quinidine (200µm), respectively. However, no clopidogrel absorption enhancement occurred in the presence of tartaric acid., Conclusions: Naringin, a natural compound which has no undesirable side effects as compared with quinidine, could be used as a pharmaceutical excipient in the presence of clopidogrel solid dispersions to increase clopidogrel intestinal absorption and therefore its oral bioavailability., (© 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.)

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., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The calcium-sensing receptor (CASR), a plasma membrane G-protein coupled receptor, is expressed in parathyroid gland and kidney, and controls systemic calcium homeostasis. Inactivating CASR mutations have previously been identified in patients with familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT). The aim of the present study is to determine the underlying molecular defect of FHH/NSHPT disease in a consanguineous Tunisian family. Mutation screening was carried out using RFLP-PCR and direct sequencing. We found that the proband is homozygous for a novel 15 bp deletion in the exon 7 (c.1952&#95;1966del) confirming the diagnosis of NSHPT. All the FHH members were found to be heterozygous for the novel detected mutation. The mutation, p.S651&#95;L655del, leads to the deletion of 5 codons in the second trans-membrane domain of the CASR which is thought to be involved in the processes of ligand-induced signaling. This alteration was associated with the evidence of mental retardation in the FHH carriers and appears to be a novel inactivating mutation in the CASR gene. Our findings provide additional support for the implication of CASR gene in the FHH/NSHPT pathogenesis.

Micronutrients as well as essential fatty acids are indispensable for the correct functioning of the organism. The risk of disturbance in the associated nutrition and metabolism is expected to increase during ageing. In addition, it seems that trace elements are involved in the fatty acids metabolism. The aim of the present study was then to assess age-related changes in trace elements status and in plasma essential fatty acids composition with an emphasis on the desaturase activity estimation. Two hundred healthy Tunisian subjects (30-85 years old) were recruited and separated into two subgroups: elderly (65-85 years old) and middle-aged (30-60 years old). The findings revealed that plasma zinc and calcium concentrations significantly decreased according to age. The prevalence of zinc deficiency was therefore shown to increase in old age (over 60% of elderly subjects were deficient or at risk of deficiency). No age-related changes were obtained for copper or magnesium status. The Δ6 desaturase, involved in the EFAs conversion, was shown to decrease according to age and to be associated with the plasma zinc level. Since elderly subjects were at risk of nutritional imbalance, it would be interesting to set optimal dietary proportion. This will help to prevent age-associated alterations and diseases for a better and healthy ageing., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: The regularity of a compressive knit is defined as its ability to perform its function in a burnt skin. This property is essential to avoid the phenomenon of rejection of the material or toxicity problems But: Make knits biocompatible with high burnet of human skin., Methods: We fabric knits of elastic material. To ensure good adhesion to the skin, we made elastic material, typically a tight loop knitted. The Length of yarn absorbed by stitch and the raw matter are changed with each sample. The physical properties of each sample are measured and compared. Surface modifications are made to these samples by impregnation of microcapsules based on jojoba oil., Results: Knits are compressif, elastic in all directions, light, thin, comfortable, and washable for hygiene issues. In addition, the washing can find their compressive properties. The Jojoba Oil microcapsules hydrated the human burnet skin. This moisturizer is used to the firmness of the wound and it gives flexibility to the skin., Conclusion: Compressive Knits are biocompatible with burnet skin. The mixture of natural and synthetic fibers is irreplaceable in terms comfort and regularity.

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., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Purpose: Oral drug administration remains the most common and most convenient way used in clinical therapy. The availability of a simple, rapid, economic and reproducible in vitro method to assess the rate, extent and mechanism of intestinal drug absorption is a very helpful tool. The purpose of this study was to compare the performance of Sartorius SM 16750 Absorption Simulator apparatus to Everted Gut Sac (EGS) technique in terms of predicting drug permeability., Methods: Permeation studies across these two in vitro models were performed with six drugs selected across the Biopharmaceutics Classification System (BCS) categories: tramadol (class I of BCS), doxycycline (class I of BCS), diclofenac (class II of BCS), clopidogrel (class II of BCS), metformin (class III of BCS) and chlorothiazide (class IV of BCS)., Results: Apparent permeability coefficient (Papp) and diffusion profiles obtained with EGS and Sartorius SM 16750 apparatus were similar for diclofenac and metformin, whereas, we noticed significant differences (p ≤ 0.05), for tramadol, doxycycline, clopidogrel and chlorothiazide., Conclusion: Compared to Everted Gut Sac model, Sartorius SM 16750 absorption simulator apparatus seems to have limited application for the assessment of intestinal drug absorption since it does not take into consideration the involvement of others processes than the passive transcellular pathway as mechanism of drug absorption.

The fatty acids composition of circulating blood lipids is expected to be altered by many factors (ageing, dietary intake, lifestyle...). In addition to the ageing consequences on their lipid status, elderly subjects represent a population at risk of nutritional imbalance. The main objective of the present study was to investigate the associations between dietary habits and the plasma fatty acids patterns in a healthy Tunisian population with an emphasis on the gender and ageing differences for the 6-desaturase activity and the EFA proportions. Nutritional habits and plasma fatty acids compositions have been therefore evaluated in 200 healthy volunteers (104 women and 96 men) aged between 40 and 82years old. The findings revealed that the 6-desaturase activity was reduced in elderly subjects (by 24% and 10% in women and men respectively). Moreover, DHA (C22:6n-3) and AA (C20:4n-6) were found to increase respectively in high fish and meat consumers. Plasma fatty acids composition could be sensitive to dietary habits according to particular food items and should then help for the establishment of optimal nutritional proportions., (Copyright 2010 Elsevier Inc. All rights reserved.)

Prostate cancer (PCa) is a complex disorder resulting from the combined effects of multiple environmental and genetic factors. Our previous single-locus analysis showed that VEGF and HSP70-hom polymorphisms were significantly associated with PCa susceptibility and prognosis. Both genes encoding these proteins were located on chromosome 6p21, and combining the neighboring single nucleotide polymorphisms (SNPs) into haplotypes may increase the association with the disease. Three tagging polymorphisms, the HSP70-hom 2437 T/C, the VEGF-1154 G/A, and the VEGF-634 G/C SNPs were genotyped in 101 cases and 80 controls. For the combined analysis of VEGF and HSP70-hom, we found a positive gradient in the odds ratios (ORs) related to the number of high-risk genotypes with a 3.53-fold increase of prostate carcinoma risk (OR = 3.53; p = 0.015). Furthermore, the TAG and CAG haplotypes at positions HSP70-hom, VEGF -1154 and VEGF -634 exhibited a two-fold (OR = 0.46; p = 0.014) and a seven-fold (OR = 0.14; p = 0.00005) reduction in PCa risk, respectively. Regarding PCa prognosis, the TAG haplotype had a negative association with the aggressive phenotype as defined by the histopathological grade (OR = 0.28; p = 0.006). Our findings confirm the role of at-risk haplotype across the HSP70-hom/VEGF gene cluster in determining susceptibility to PCa.

Trace elements like zinc and copper play an important role in maintaining metabolic homeostasis in elderly subjects and is therefore expected to have a crucial effect on antioxidant mechanism. The objective of the present study was to investigate age-related variations of zinc, copper and antioxidant enzyme activities (superoxide dismutase: SOD, glutathione peroxidase: GPx and catalase: CAT) taking into account gender differences in a Tunisian elderly population. A group of 100 healthy elderly subjects (55-85 years old) were then separated in three sub-groups according to age intervals. A control group of 100 adults aged between 30 and 45 years was considered. The obtained results confirmed the decrease of plasma zinc level with age increase in both men and women. Moreover, prevalence of zinc deficiency increased with age: normal zinc concentration was obtained in about 60% of adults and only in 35% of the elderly subjects over 75 years old. No significant variation was obtained for copper concentration. GPx and SOD activities were lower in aged subjects in comparison to adults. Zinc and antioxidant enzyme activities were found to be negatively correlated to age. However, an investigation on a large size sample with various health and well-controlled dietary statuses should be conducted for a better understanding of the zinc or copper metabolism and their effect on oxidant stress during aging.

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.

Hereditary multiple exostoses (HME) is an autosomal dominant orthopaedic disorder most frequently caused by mutations in the EXT1 gene. The aim of the present study is to determine the underlying molecular defect of HME in two multigenerational Tunisian families with 21 affected members and to examine the degree of intrafamilial variability. Linkage analysis was performed using three microsatellite markers encompassing the EXT1 locus and mutation screening was carried out by direct sequencing. In family 1, evidence for linkage to EXT1 was obtained on the basis of a maximum LOD score of 4.26 at theta = 0.00 with D8S1694 marker. Sequencing of the EXT1 revealed a heterozygous G > T transversion (c.1019G>T) in exon 2, leading to a missense mutation at the codon 340 (p.Arg340Leu). In family 2 we identified a novel heterozygous 1 bp deletion in the exon 1 (c.529&#95;531delA) leading to a premature codon stop and truncated EXT1 protein expression (p.Lys177LysfsX15). This mutation was associated with the evidence of an intrafamilial clinical variability and considered to be a novel disease-causing mutation in the EXT1 gene. These findings provide additional support for the involvement of EXT1 gene in the HME disease.

Premature infants require protein and energy for their growth and an adequate intake of calcium and phosphorus for their bone formation. However, several factors can affect the stability of intravenous lipid emulsions intended to be administered as neonatal total parenteral nutrition. This study evaluated the effect of additives and various concentrations of both calcium gluconate and glucose-1-phosphate on two intravenous lipid emulsions (Clinoleic 20% and Ivelip 20%) when using Primene 10% as source of amino acids and simulating clinical conditions (24-h storage at 37 degrees C). Two series of experiments for each lipid emulsion were carried out. One used separate ingredients (water, glucose, or amino acids) with various calcium phosphate concentrations; and the second included total parenteral nutrition admixtures with varied amino acid (1%, 2%, or 3.5%) and glucose (8% or 14%) concentrations. Evaluation was performed by visual and microscopic examination and pH, particle size, and zeta potential measurements. Calcium concentrations were determined before and after filtration by atomic absorption spectroscopy. Samples were stored 24 h at 37 degrees C. Investigations of lipid-nutrient admixtures showed a significant decrease of the pH with Primene and a visual instability when mixing with sterile water alone, while total parenteral nutrition admixtures made of Clinoleic 20% or Ivelip 20% were stable regarding pH, particle sizing, and zeta potential after storage conditions. Samples containing only calcium have their zeta potential charge reduced compared to samples containing both calcium and phosphate. Also, the evaluation of calcium phosphate solubility showed a significant decrease of the calcium concentration after filtration of the samples. Our data indicated that total parenteral nutrition admixtures could contribute to protect the lipid emulsion from its physicochemical degradation and that using organic phosphate with calcium gluconate has a less deleterious effect than using calcium alone with total parenteral nutrition. Also, the use of inline filters remains necessary for good protection from hazards of precipitates during the administration of total parenteral nutrition regimens.