Conservative three-quarter versus subtotal seven-eighths parathyroidectomy in secondary hyperparathyroidism.

OBJECTIVE: There is at present no consensus concerning surgical techniques for secondary hyperparathyroidism (SHPT) in end-stage renal disease (ESRD). Although both subtotal and total parathyroidectomy provide low rates of recurrence, they may induce hypoparathyroidism, damaging the bone and cardiovascular systems. The aim of our study was to compare 3/4 and 7/8 parathyroidectomy in this population and to discuss the potential benefit of more conservative treatment. STUDY DESIGN: Prospective observational study in a university teaching hospital between 2010 and 2014. METHODS: The study included 34 consecutive ESRD patients with SHPT: 19 underwent 3/4 parathyroidectomy (group A*3/4) and 15 underwent 7/8 parathyroidectomy (group B*7/8). Serum intact 1-84 PTH levels (before and 6 months after surgery) and hospital stay were compared between the two groups. RESULTS: Before surgery, PTH levels were similar between the two groups. At month 6 following surgery, median PTH levels were significantly higher in group A*3/4 than in group B*7/8 (109 versus 24pg/mL, respectively; P<0.0006). Hospital stay was shorter in group A*3/4 (4.79 versus 6.80 days, respectively; P=0.008). Postoperative hypoparathyroidism requiring long-term calcium and 1alpha(OH) D3 treatment was reported in 5% of patients in group A*3/4 and 26% of patients in group B*7/8 (P=0.04). CONCLUSIONS: In this preliminary study, 3/4 conservative parathyroidectomy seemed effective and safe, with less reported morbidity than 7/8 parathyroidectomy, as assessed by lower rates of irreversible hypoparathyroidism and shorter hospital stay. LEVEL OF EVIDENCE: 3b, individual case-control study.

Fecal microbiota transplantation to eradicate vancomycin-resistant enterococci colonization in case of an outbreak.

OBJECTIVE: A rapid and worrying emergence of vancomycin-resistant enterococci (VRE) gut colonization is occurring worldwide and may be responsible for outbreaks, especially in healthcare facilities. While no efficient decolonization strategies are recommended, we assessed fecal microbiota transplantation (FMT) to eradicate VRE colonization. PATIENTS AND METHOD: Our main objective was to measure the impact of FMT on decolonization of VRE carriers, confirmed by at least two consecutive negative rectal swabs at one-week interval during a 3-month follow-up period. Patients received no antibiotic prior to the FMT. RESULTS: After a month only three patients remained colonized with VRE. Decolonization was associated with 87.5% (n=7) of success after three months as only one patient remained colonized. CONCLUSION: Our first results confirm that the FMT seems to be safe, with an impact on VRE colonization over time that may help control outbreaks.

Clearance of carbapenem-resistant Enterobacteriaceae vs vancomycin-resistant enterococci carriage after faecal microbiota transplant: a prospective comparative study.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) and vancomycin-resistant enterococci (VRE) carriage are increasing worldwide. Faecal microbiota transplantation (FMT) appears to be an attractive option for decolonization. This study aimed to evaluate CRE vs VRE clearance by FMT among carriers. METHODS: A multi-centre trial was undertaken on patients with CRE or VRE digestive tract colonization who received FMT between January 2015 and April 2017. Adult patients with CRE or VRE colonization, confirmed by three consecutive rectal swabs at weekly intervals, including one in the week prior to FMT, were included in the study. Patients with immunosuppression or concomitant antibiotic prescription at the time of FMT were excluded. Successful decolonization was determined by at least two consecutive negative rectal swabs [polymerase chain reaction (PCR) and culture] on Days 7, 14, 21 and 28, and monthly for three months following FMT. RESULTS: Seventeen patients were included, with a median age of 73 years [interquartile range (IQR) 64.3-79.0]. Median duration of carriage of CRE or VRE before FMT was 62.5 days (IQR 57.0-77.5). One week after FMT, three of eight patients were free of CRE colonization and three of nine patients were free of VRE colonization. After three months, four of eight patients were free of CRE colonization and seven of eight patients were free of VRE colonization. Qualitative PCR results were concordant with culture. Six patients received antibiotics during follow-up, three in each group. No adverse events were reported. CONCLUSION: CRE and VRE clearance rates were not significantly different in this study, possibly due to the small sample size, but a trend was observed. These data should be confirmed by larger cohorts and randomized trials.

Lipid nanocarriers as skin drug delivery systems: Properties, mechanisms of skin interactions and medical applications.

During the past decades, lipid nanocarriers are gaining momentum with their multiple advantages for the management of skin diseases. Lipid nanocarriers enable to target the therapeutic payload to deep skin layers or even to reach the blood circulation making them a promising cutting-edge technology. Lipid nanocarriers refer to a large panel of drug delivery systems. Lipid vesicles are the most conventional, known to be able to carry lipophilic and hydrophilic active agents. A variety of lipid vesicles with high flexibility and deformability could be obtained by adjusting their composition; namely ethosomes, transfersomes and penetration enhancer lipid vesicles which achieve the best results in term of skin permeation. Others are designed with the objective to perform higher encapsulation rate and higher stability, such as solid lipid nanoparticles and nanostructured lipid nanocarriers. In this review, we attempted to give an overview of lipid based nanocarriers developed with the aim to enhance dermal and transdermal drug delivery. A special focus is put on the nanocarrier composition, behavior and interaction mechanisms with the skin. Recent applications of lipid-based nanocarriers for the management of skin diseases and other illnesses are highlighted as well.

Diclofenac Loaded Lipid Nanovesicles Prepared by Double Solvent Displacement for Skin Drug Delivery.

PURPOSE: Herein, we detail a promising strategy of nanovesicle preparation based on control of phospholipid self-assembly: the Double Solvent Displacement. A systematic study was conducted and diclofenac as drug model encapsulated. In vitro skin studies were carried out to identify better formulation for dermal/transdermal delivery. METHODS: This method consists in two solvent displacements. The first one, made in a free water environment, has allowed triggering a phospholipid pre-organization. The second one, based on the diffusion into an aqueous phase has led to liposome formation. RESULTS: Homogeneous liposomes were obtained with a size close to 100 nm and a negative zeta potential around -40 mV. After incorporation of acid diclofenac, we obtained nanoliposomes with a size between 101 ± 45 and 133 ± 66 nm, a zeta potential between 34 ± 2 and 49 ± 3 mV, and the encapsulation efficiency (EE%) was between 58 ± 3 and 87 ± 5%. In vitro permeation studies showed that formulation with higher EE% dispayed the higher transdermal passage (18,4% of the applied dose) especially targeting dermis and beyond. CONCLUSIONS: Our results suggest that our diclofenac loaded lipid vesicles have significant potential as transdermal skin drug delivery system. Here, we produced cost effective lipid nanovesicles in a merely manner according to a process easily transposable to industrial scale. Graphical Abstract ᅟ.

Degradation of paraoxon (VX chemical agent simulant) and bacteria by magnesium oxide depends on the crystalline structure of magnesium oxide.

In this work, our goal was to study the capability of a single metallic oxide to neutralize a chemical agent and to exhibit an antibacterial effect. We tested two types of magnesium oxides, MgO. The first MgO sample tested, which commercial data size characteristic was -325 mesh (MgO-1) destroyed in 3 h, 89.7% of paraoxon and 93.2% of 4-nitrophenol, the first degradation product. The second MgO sample, which commercial data size was <50 nm (MgO-2) neutralized in the same time, 19.5% of paraoxon and 10.9% of 4-nitrophenol. For MgO-1 no degradation products could be detected by GC-MS. MgO-1 had a bactericidal activity on Escherichia coli (6 log in 1 h), and showed a decrease of almost 3 log on a Staphylococcus aureus population in 3 h. MgO-2 caused a decrease of 2 log of a E.coli culture but had no activity against S. aureus. Neither of these two products had an activity on Bacillus subtilis spores. Analytical investigations showed that the real sizes of MgO nanoparticles were 11 nm for MgO-1 and 25 nm for MgO-2. Moreover, their crystalline structures were different. These results highlighted the importance of the size of the nanoparticles and their microscopic arrangements to detoxify chemical products and to inhibit or kill microbial strains.

Advances in psoriasis physiopathology and treatments: Up to date of mechanistic insights and perspectives of novel therapies based on innovative skin drug delivery systems (ISDDS).

Psoriasis is a chronic inflammatory disease affecting mainly the skin but which can be complicated by psoriatic arthritis (PsA).This autoimmune skin disorder concerns 2-5% of the world population. To date, the physiopathology of psoriasis is not still completely elucidated but many researches are ongoing which have led for example to the discovery of the Th17/Th22 pathway. The conventional therapeutic approaches (local or systemic route) appeal to various classes of drugs with complex mechanisms of action and non-negligible side effects. Although there is no therapy capable to cure psoriasis, the current goal is to relieve symptoms as longer as possible with a good benefit/risk ratio. That is one of the principal limits of conventional antipsoriatic drugs. New formulations based on nanoencapsulation are a promising opportunity to answer to this limit by offering an optimization of the conventional antipsoriatic drug use (higher activity, lower side effects and frequency of application, etc.). Herein, we tried to put in perspective the mechanistic insights (histological and immunological views) proposed into scientific literature these last years in order to have a better comprehension of psoriasis physiopathology resulting in skin lesions and PsA. The therapeutic armamentarium and the different strategies in the management of psoriasis are discussed in greater details. To finish, the field of encapsulation in nanoparticles is broached in order to put forward recent advances in innovative skin drug delivery systems (ISDDSs) of antipsoriatic active agents for a better efficacy, safety and compliance.

Carbon nanotubes from synthesis to in vivo biomedical applications.

Owing to their unique and interesting properties, extensive research round the globe has been carried out on carbon nanotubes and carbon nanotubes based systems to investigate their practical usefulness in biomedical applications. The results from these studies demonstrate a great promise in their use in targeted drug delivery systems, diagnostic techniques and in bio-analytical applications. Although, carbon nanotubes possess quite interesting properties, which make them potential candidates in the biomedical science, but they also have some inherent properties which arise great concern regarding their biosafety. In this comprehensive review, we have discussed different aspects of carbon nanotubes and carbon nanotube based systems related to biomedical applications. In the beginning, a short historical account of these tiny yet powerful particles is given followed by discussion regarding their types, properties, methods of synthesis, large scale production method, purification techniques and characterization aspects of carbon nanotubes. In the second part of the review, the functionalization of carbon nanotubes is reviewed in detail, which is not only important to make them biocompatible and stable in biological systems but also render them a great property of loading various biomolecules, diagnostic and therapeutic moieties resulting in diversified applications. In the final part of the review, emphasis is given on the pharmacokinetic aspects of carbon nanotubes including administration routes, absorption mechanisms, distribution and elimination of carbon nanotubes based systems. Lastly, a comprehensive account about the potential biomedical applications has been given followed by insights into the future.

Administration strategies for proteins and peptides.

Proteins are a vital constituent of the body as they perform many of its major physiological and biological processes. Recently, proteins and peptides have attracted much attention as potential treatments for various dangerous and traditionally incurable diseases such as cancer, AIDS, dwarfism and autoimmune disorders. Furthermore, proteins could be used for diagnostics. At present, most therapeutic proteins are administered via parenteral routes that have many drawbacks, for example, they are painful, expensive and may cause toxicity. Finding more effective, easier and safer alternative routes for administering proteins and peptides is the key to therapeutic and commercial success. In this context, much research has been focused on non-invasive routes such as nasal, pulmonary, oral, ocular, and rectal for administering proteins and peptides. Unfortunately, the widespread use of proteins and peptides as drugs is still faced by many obstacles such as low bioavailability, short half-life in the blood stream, in vivo instability and numerous other problems. In order to overcome these hurdled and improve protein/peptide drug efficacy, various strategies have been developed such as permeability enhancement, enzyme inhibition, protein structure modification and protection by encapsulation. This review provides a detailed description of all the previous points in order to highlight the importance and potential of proteins and peptides as drugs.

Characterization of different vitamin E carriers intended for pulmonary drug delivery.

The targeted release of drugs intended for pulmonary delivery is a research field which has been so far rather unexploited but is currently becoming increasingly attractive. Liquid dispersions encapsulating vitamin E (liposomes, micelles, nano-emulsion, and solid lipid particles) were prepared using various methods based on membrane contactor. The dispersions were nebulized and aerodynamic characteristics of the generated aerosols were assessed using two different methods: laser light scattering and cascade impaction. When the laser diffraction technique was used, results showed that fine particle fractions (<5 µm) were 19, 29, 38 and 71% for solid lipid particles, micelles, nano-emulsion and liposomes, respectively. When the impaction method was applied, using a next generation pharmaceutical impactor operated at 30 l/min, results showed that fine particle fractions were 39, 78, 82 and 87% for solid lipid particles, micelles, nano-emulsion and liposomes, respectively. The differences observed between the results obtained from both methods confirm that the laser diffraction method is not always suitable for aerodynamic characterization of aerosols and should be validated against an impaction method. Nebulization of the drug-carrier systems led to an increase of their size most likely due to aggregation phenomena. The size was increased by a factor of 2-26 depending on the encapsulation system. The most important aggregation was obtained with nano-emulsion; the less one with solid lipid particles. The mass median aerodynamic diameter (MMAD) of the generated aerosols ranged from 1.76 to 6.10 µm. The application of a mathematical model, the Multiple-Path Particle Dosimetry (MPPD), for the prediction of the pulmonary deposit gave encouraging results. The rate of vitamin E able to reach the lung ranged from 37.6 (for the liposomes) to 51.6% (for the micelles). The obtained results showed that the different systems developed for vitamin E encapsulation were suitable to target the lung after pulmonary administration by nebulization.

Preparation and characterization of amorphous solid dispersions of nimesulide in cyclodextrin copolymers.

A study to enhance the dissolution rate of nimesulide (NIM), a poorly water-soluble, non-steroidal anti-inflammatory drug, was carried out through developing new amorphous solid dispersions (ASD) based on soluble or insoluble water cyclodextrin copolymers (alpha-cyclodextrin, beta-cyclodextrin and y-cyclodextrin polymers) synthesized by direct melt polycondensation. Amorphous solid dispersions of NIM in cyclodextrin copolymers, obtained by solvent evaporation, were characterized by thermogravimetric analyzer (TGA), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and fourier transform-infrared spectroscopy (FT-IR). These analyses provided the existence of interactions between amorphous drug and its carrier. A burst release of more than 80% NIM within approximately 70 minutes was seen with soluble alpha-cyclodextrin polymers (poly-alpha-sol) and insoluble gamma-cyclodextrin polymers (poly-gamma-insol) where no significant differences were observed with the other copolymers. Mathematical kinetic models such as zero order, Higuchi and Korsmeyer-Peppas were used to evaluate the kinetic and mechanism of release of NIM from the different ASD compared to lactose reference matrix. The kinetic of release of NIM from different ASD followed a Higuchi model and the mechanism of release was explained by Korsmeyer-Peppas model in which a fickian diffusion for lactose and soluble beta-cyclodextrin polymers (poly-beta-sol) was observed. However, an anomalous non-Fickian transport was found for the other copolymers.

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.

Gene therapy and DNA delivery systems.

Gene therapy is a promising new technique for treating many serious incurable diseases, such as cancer and genetic disorders. The main problem limiting the application of this strategy in vivo is the difficulty of transporting large, fragile and negatively charged molecules like DNA into the nucleus of the cell without degradation. The key to success of gene therapy is to create safe and efficient gene delivery vehicles. Ideally, the vehicle must be able to remain in the bloodstream for a long time and avoid uptake by the mononuclear phagocyte system, in order to ensure its arrival at the desired targets. Moreover, this carrier must also be able to transport the DNA efficiently into the cell cytoplasm, avoiding lysosomal degradation. Viral vehicles are the most commonly used carriers for delivering DNA and have long been used for their high efficiency. However, these vehicles can trigger dangerous immunological responses. Scientists need to find safer and cheaper alternatives. Consequently, the non-viral carriers are being prepared and developed until techniques for encapsulating DNA can be found. This review highlights gene therapy as a new promising technique used to treat many incurable diseases and the different strategies used to transfer DNA, taking into account that introducing DNA into the cell nucleus without degradation is essential for the success of this therapeutic technique.

Preparation of liposomes: a novel application of microengineered membranes--from laboratory scale to large scale.

A novel ethanol injection method using microengineered nickel membrane was employed to produce POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and Lipoid(®) E80 liposomes at different production scales. A stirred cell device was used to produce 73ml of the liposomal suspension and the product volume was then increased by a factor of 8 at the same transmembrane flux (140lm(-2)h(-1)), volume ratio of the aqueous to organic phase (4.5) and peak shear stress on the membrane surface (2.7Pa). Two different strategies for shear control on the membrane surface have been used in the scaled-up versions of the process: a cross flow recirculation of the aqueous phase across the membrane surface and low frequency oscillation of the membrane surface (∼40Hz) in a direction normal to the flow of the injected organic phase. Using the same membrane with a pore size of 5µm and pore spacing of 200µm in all devices, the size of the POPC liposomes produced in all three membrane systems was highly consistent (80-86nm) and the coefficient of variation ranged between 26 and 36%. The smallest and most uniform liposomal nanoparticles were produced in a novel oscillating membrane system. The mean vesicle size increased with increasing the pore size of the membrane and the injection time. An increase in the vesicle size over time was caused by deposition of newly formed phospholipid fragments onto the surface of the vesicles already formed in the suspension and this increase was most pronounced for the cross flow system, due to long recirculation time. The final vesicle size in all membrane systems was suitable for their use as drug carriers in pharmaceutical formulations.

Preparation of Bovine Serum Albumin (BSA) nanoparticles by desolvation using a membrane contactor: a new tool for large scale production.

Albumin nanoparticles are attractive drug delivery systems as they can be prepared under soft conditions and incorporate several kinds of molecules. The aim of this study was to upscale the desolvation process for preparing Bovine Serum Albumin (BSA) nanoparticles using a membrane contactor. At a first step, the BSA nanoparticles were prepared at small scale using a syringe pump. BSA nanoparticles of 139 nm in size, with a polydispersity index of 0.046, were obtained at the optimal conditions: pH 8.2, 100 mg mL(-1) BSA albumin solution (2 mL), and 1 mL min(-1) flow rate of ethanol addition (8 mL). The upscaling with a membrane contactor was achieved by permeating ethanol through the pores of a Shirasu Porous Glass (SPG Technology Co., Japan) membrane and circulating the aqueous phase tangentially to the membrane surface. By increasing the pressure of the ethanol from 1 to 2.7 bars, a progressive decrease in nanoparticle size was obtained with a high nanoparticles yield (around 94-96%). In addition, the flow rate of the circulating phase did not affect the BSA nanoparticle characteristics. At the optimal conditions (pH 8.2, 100 mg mL(-1) BSA albumin solution, pressure of ethanol 2.7 bars, flow rate of the circulating phase 30.7 mL s(-1)), the BSA nanoparticles showed similar characteristics to those obtained with the syringe pump. Large batches of BSA nanoparticles were prepared up to 10 g BSA. The BSA nanoparticles were stable at least during 2 months at 4 °C, and their characteristics were reproducible. It was then concluded that the membrane contactor technique could be a suitable method for the preparation of albumin nanoparticles at large scale with properties similar to that obtained at small scale.

[Management of end-stage kidney failure: a challenge for the countries of sub-Saharan Africa example of mineral and bone disorders in Burkina Faso]. / Prise en charge de l'insuffisance rénale terminale : un challenge pour les pays de l'Afrique subsaharienne Exemple des désordres minéralo-osseux au Burkina Faso.

INTRODUCTION: Meeting treatment targets for dialysis is a seemingly impossible challenge for most countries of sub-Saharan Africa. To assess this problem, we conducted this study of mineral and bone disorders in subjects undergoing hemodialysis at the Ouagadougou hemodialysis unit, the only such unit in Burkina Faso. PATIENTS AND METHODS: This cross-sectional descriptive study was conducted in January 2010. We included patients on hemodialysis for at least three months who had some minimal predialysis laboratory results available. The KDIGO guidelines served as our reference. Dialysis sessions lasted 5 h and took place once every five days. The statistical analysis of the data was performed with PASW statistical software, version 18 for Windows. RESULTS: The study included 32 of the 53 patients in the unit: 19 men and 13 women with a mean age of 43.5 ± 12.7 years. Their mean serum levels were 2.2 ± 0.2 mmol/L for calcium, 1.4 ± 0.5 mmol/L for phosphorus, 934 ± 887.4 pg/mL for intact parathyroid hormone and 193.4 ± 125.7 IU/L for total alkaline phosphatases. No patient reached the target for all three of the first three indicators. Patients with parathyroid hormone ≥ 800 pg/mL (n = 14) had a serum phosphorus (1.6 ± 0.6 vs 1.2 ± 0.4; p = 0.044) and alkaline phosphatases (287.5 ± 100.5 vs 120.2 ± 90; p < 0.001), significantly higher than those whose parathyroid hormone level was < 800 pg/mL. CONCLUSIONS: The bone and mineral status of our hemodialysis patients is worrisome and is due to suboptimal treatment conditions. The risk of deaths is high. Subsidies sufficient to provide adequate care would reduce these problems, which have, we note, an ethical dimension.

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.

Individual inorganic nanoparticles: preparation, functionalization and in vitro biomedical diagnostic applications.

Inorganic nanoparticles have become the focus of modern materials science due to their potential technological importance, particularly in bionanotechnology, which stems from their unique physical properties including size-dependent optical, magnetic, electronic, and catalytic properties. The present article provides an overview on the currently used individual inorganic nanoparticles for in vitro biomedical domains. These inorganic nanoparticles include iron oxides, gold, silver, silica, quantum dots (QDs) and second harmonic generation (SHG) particles. For each of these interesting nanoparticles, the main issues starting from preparation up to bio-related applications are presented.

Stability study and lyophilization of vitamin E-loaded nanocapsules prepared by membrane contactor.

In this research, we studied the accelerated stability of vitamin E-loaded nanocapsules (NCs) prepared by the nanoprecipitation method. Vitamin E-loaded NCs were optimized firstly at the laboratory scale and then scaled up using the membrane contactor technique. The optimum conditions of the membrane contactor preparation (pilot scale) produced vitamin E-loaded NCs with an average size of 253 nm, polydispersity index 0.19 and a zeta potential -16 mV. The average size, polydispersity index and zeta potential values were 185 nm, 0.12 and -15 mV, respectively for the NCs prepared at laboratory scale. No significant changes were noticed in these values after 3 and 6 months of storage at high temperature (40±2 °C) and relative humidity (75±5%) in spite of vitamin E sensitivity to light, heat and oxygen. The entrapment efficiency of NCs prepared at pilot scale was 97% at the beginning of the stability study, and became (95%, 59%) after 3 and 6 months of storage, respectively. These values at lab-scale were (98%, 96%, and 89%) at time zero and after 3 and 6 months of storage, respectively. This confirms the ability of vitamin E encapsulation to preserve its stability, which is one major goal of our work. Lyophilization of the optimized formula at lab-scale was also performed. Four types of cryoprotectants were tested (poly(vinyl pyrrolidone), sucrose, mannitol, and glucose). Freeze-dried NCs prepared with sucrose were found acceptable. The other lyophilized NCs obtained at different conditions presented large aggregates.