Defining Endocytic Pathways of Fucoidan-Coated PIBCA Nanoparticles from the Design of their Surface Architecture.

PURPOSE: This work investigated the endocytic pathways taken by poly(isobutylcyanoacrylate) (PIBCA) nanoparticles differing in their surface composition and architecture, assuming that this might determine their efficiency of intracellular drug delivery. METHODS: Nanoparticles (A0, A25, A100, R0, R25 ) were prepared by anionic or redox radical emulsion polymerization using mixtures of dextran and fucoidan (0, 25, 100 % in fucoidan). Cell uptake was evaluated by incubating J774A.1 macrophages with nanoparticles. Endocytic pathways were studied by incubating cells with endocytic pathway inhibitors (chlorpromazine, genistein, cytochalasin D, methyl-ß-cyclodextrin and nocodazole) and nanoparticle uptake was evaluated by flow cytometry and confocal microscopy. RESULTS: The fucoidan-coated PIBCA nanoparticles A25 were internalized 3-fold more efficiently than R25 due to the different architecture of the fucoidan chains presented on the surface. Different fucoidan density and architecture led to different internalization pathway preferred by the cells. Large A100 nanoparticles with surface was covered with fucoidan chains in a loop and train configuration were internalized the most efficiently, 47-fold compared with A0, and 3-fold compared with R0 and R25 through non-endocytic energy-independent pathways and reached the cell cytoplasm. CONCLUSION: Internalization pathways of PIBCA nanoparticles by J774A.1 macrophages could be determined by nanoparticle fucoidan surface composition and architecture. In turn, this influenced the extent of internalization and localization of accumulated nanoparticles within cells. The results are of interest for rationalizing the design of nanoparticles for potential cytoplamic drug delivery by controlling the nature of the nanoparticle surface.

Intermittent catheterization: Clinical practice guidelines from Association Française d'Urologie (AFU), Groupe de Neuro-urologie de Langue Française (GENULF), Société Française de Médecine Physique et de Réadaptation (SOFMER) and Société Interdisciplinaire Francophone d'UroDynamique et de Pelvi-Périnéologie (SIFUD-PP).

INTRODUCTION: Our objective was to provide guidelines covering all aspects of intermittent catheterisation (intermittent self-catheterisation and third-party intermittent catheterisation). MATERIALS AND METHODS: A systematic review of the literature based on Pubmed, Embase, Google scholar was initiated in December 2014 and updated in April 2019. Given the lack of robust data and the numerous unresolved controversial issues, guidelines were established based on the formal consensus of experts from steering, scoring and review panels. RESULTS: This allowed the formulation of 78 guidelines, extending from guidelines on indications for intermittent catheterisation, modalities for training and implementation, choice of equipment, management of bacteriuria and urinary tract infections, to the implementation of intermittent catheterisation in paediatric, geriatric populations, benign prostatic hyperplasia patients and continent urinary diversion patients with a cutaneous reservoir as well as other complications. These guidelines are pertinent to both intermittent self-catheterisation and third-party intermittent catheterisation. CONCLUSION: These are the first comprehensive guidelines specifically aimed at intermittent catheterisation and extend to all aspects of intermittent catheterisation. They assist in the clinical decision-making process, specifically in relation to indications and modalities of intermittent catheterisation options. These guidelines are intended for urologists, gynaecologists, geriatricians, paediatricians, neurologists, physical and rehabilitation physicians, general practitioners and other health professionals including nurses, carers….

[Long-term outcomes of intradetrusor botulinum toxin A in multiple sclerosis patients]. / Efficacité au long terme de la toxine botulique dans l'hyperactivité de vessie chez les patients atteints de sclérose en plaques.

INTRODUCTION: The objective of this study was to analyze the long-term efficiency and tolerance of TB in the management of anticholinergic refractory hyperactive bladder in patients with MS. MATERIAL AND METHOD: Retrospective mono-centric cohort study of all patients with MS who had a TB injection for anticholinergic refractory hyperactivity from 2005 to 2015. The primary endpoint was clinical efficiency based on the frequency of urinary leakage and symptomatic urinary tract infections. RESULTS: One hundred and nineteen patients received the first injection. Median follow-up was 26.5 months. After an injection, there was a significant decrease in the number of leaks, with 69.7% of patients without leaks and 93.3% of patients without urinary tract infections. After 7 injections 44% of the patients were still dry and 62.07% had no symptomatic urinary tract infections. The failure rate was 24.37%, the average duration before discharge was 34.7 months. 19 (66%) patients stop treatment for loss of efficacy, 9 (31%) for disease progression and 1 (3%) for cessation of treatment without cause. Of the 774 injections performed, there were complications for 26 of them (3.35%). CONCLUSION: Botulinum toxin remains the second-line reference treatment for detrusor overactivity of neurological origin. There is, at least in the short term, a good answer in a large number of cases. This response can be maintained for many years, especially if patients use intermittent catheterization, with excellent tolerance. LEVEL OF EVIDENCE: 4.

[The impact of mellitus diabetes on the lower urinary tract: A review of Neuro-urology Committee of the French Association of Urology]. / Le retentissement du diabète sur le bas appareil urinaire : une revue du comité de neuro-urologie de l'Association française d'urologie.

OBJECTIVES: Specify urinary functional impairment associated with diabetic pathology. Propose guidance for screening, monitoring of clinical signs of lower urinary tract (LUTS) and describe the specifics of the urological treatment of patients. METHODS: A review of literature using PubMed library was performed using the following keywords alone or in combination: "diabetes mellitus", "diabetic cystopathy", "overactive bladder", "bladder dysfunction", "urodynamics", "nocturia". RESULTS: LUTS are more common in the diabetic population with an estimated prevalence between 37 and 70 %, and are probably underevaluated in routine practice. They are heterogeneous and are frequently associated with other diabetic complications. Both storage and voiding symptoms can coexist. Despite a major evaluation in the literature, no recommendation supervises the assessment and management of LUTS in this specific population. An annual screening including medical history, bladder and kidney ultrasound and post-void residual measurement is required in the follow-up of diabetic patients. Specific urologial referral and urodynamic investigations will be performed according to the findings of first-line investigations. The type of bladder dysfunction, the risk of urinary tract infections and dysautonomia should be considered in the specific urological management of these patients. CONCLUSION: Diabetes mellitus significantly impacts on the lower urinary tract function. A screening of LUTS is required as well as other complications of diabetes. The management of LUTS must take into consideration the specific risks of the diabetic patient regarding the loss of bladder contractility, the possibility of dysautonomia and infectious complications.

Antimicrobial activity of ß-lapachone encapsulated into liposomes against meticillin-resistant Staphylococcus aureus and Cryptococcus neoformans clinical strains.

The aim of this study was to determine whether encapsulation of ß-lapachone (ß-lap) into liposomes interferes with its in vitro antimicrobial activity against meticillin-resistant Staphylococcus aureus (MRSA) and Cryptococcus neoformans clinical strains. Liposomes (ß-lap:lipo or ß-lap:HPß-CD-lipo) were prepared using the hydration of thin lipid film method followed by sonication. The in vitro antimicrobial activities of ß-lap-loaded liposomes against MRSA and C. neoformans were evaluated using the microdilution method according to the Clinical and Laboratory Standards Institute (CLSI). The liposomes presented a mean particle size ranging from 88.7±1.5nm to 112.4±1.9nm with a polydispersity index ranging from 0.255 to 0.340, zeta potential from -0.26±0.01mV to +0.25±0.05mV and drug encapsulation efficiency from 97.4±0.3% to 98.9±0.4%. ß-Lap and ß-lap:HPß-CD had minimum inhibitory concentrations (MICs) ranging from 2mg/L to 4mg/L, whereas the MICs of ß-lap-lipo or ß-lap:HPß-CD-lipo ranged from 4mg/L to 16mg/L for the MRSA strains tested. ß-Lap and ß-lap:HPß-CD were able to inhibit fungal growth [MIC=2-8mg/L and minimum fungicidal concentration (MFC)=4-8mg/L]. However, ß-lap-lipo and ß-lap:HPß-CD-lipo were more efficient, with MICs and MFCs of <4mg/L. These findings suggest that the liposomal formulations tested do not interfere significantly with ß-lap antibacterial activity against MRSA and improve its antifungal properties against C. neoformans.

[Impact on cognitive function of anticholinergic drugs used for the treatment of overactive bladder in the elderly]. / Traitement anticholinergique de l'hyperactivité vésicale de la personne âgée et ses impacts sur la cognition. Revue de la littérature.

OBJECTIVES: Describe the central nervous system (CNS) adverse effects of anticholinergic drugs used for the treatment of overactive bladder (OAB) in the elderly. PATIENTS AND METHODS: Relevant data from the literature were identified primarily through a Medline search of articles published through December 2013. The search terms included overactive bladder, central nervous system, elderly, anticholinergic, and antimuscarinic. Articles were chosen for inclusion based on their pertinence to the focus on treatment of OAB in the elderly. RESULTS: Several anticholinergic drugs are available for the treatment of OAB, including oxybutinin, tolterodine, trospium chloride, solifenacine, fesoterodine. Among the agents reviewed, penetration of the blood-brain barrier (as predicted by lipophilicity, polarity, and molecular size and structure) is highest for oxybutinin, lower for tolterodine, solifenacine, and darifenacine, and lowest for fesoterodine and trospium chloride. Unwanted CNS adverse effects depend in part on patient specific variability in pharmacokinetic parameters, blood-brain barrier permeability, degree of cholinergic neuronal degeneration, total anticholinergic drug burden and patient's baseline cognitive status. The spectrum of anticholinergic CNS adverse effects ranges from drowsiness to hallucinations, severe cognitive impairment, and coma. Among the different anticholinergic agents, oxybutinin has been associated with cognitive impairment and trospium chloride and fesoterodine have shown favorable CNS tolerability. CONCLUSIONS: Anticholinergic drugs improve significatively overactive bladder symptoms in older adults. However, potential CNS adverse effects of anticholinergic agents used in OAB must lead to a full evaluation before and during the treatment in order to evaluate benefice, risks and central side effects in this frail population.

[Lower urinary tract dysfunctions in parkinsonian syndromes: a review by the Neuro-Urology Comittee of the French Association of Urology]. / Troubles vésicosphinctériens des syndromes parkinsoniens: une revue du comité de neuro-urologie de l'Association française d'urologie.

INTRODUCTION: Lower urinary tract disorders (LUTD) are common in Parkinson's disease (PD) and other parkinsonian syndromes (PS). They are responsible for a significant morbidity and mortality and impair patients' quality of life. The therapeutic management of these LUTD requires to know how to distinguish the PD from other PS and their epidemiology and pathophysiology. OBJECTIVE: To provide a diagnostic and therapeutic management of LUTD in patients with PS. METHOD: A review of litterature using PubMed library was performed using the following keywords: Parkinson's disease, multiple system atrophy, lower urinary tract disorders, neurogenic bladder, overactive bladder, obstruction, anticholinergics, dopamine, prostate surgery. RESULTS: Sometimes revealing the neurological disease, LUTD in PS raise a diagnostic problem because they occur at an age when various urogynecological disorders can be intricated with neurogenic bladder dysfunction. The differential diagnosis between PD and multiple system atrophy is important to know by the urologist. The distinction is based on the semiological analysis, the clinical response to dopaminergic therapy and the clinical outcome but also on data from urodynamic explorations. The therapeutic management of these LUTD cannot be easy due to the difficulty of use of some pharmacological treatments and the risk of deterioration after inappropriate surgery. The different treatments include the careful use of anticholinergics, posterior tibial nerve stimulation, deep thalamic stimulation and low-dose intradetrusor injections of botulinum toxin without approval. The decision to perform prostate surgery will be taken with caution after proving the bladder obstruction. CONCLUSION: When analysing LUTD in PS, the urologist must know to question the initial diagnosis of PD. Treatments in order to reduce morbidity and mortality of these LUTD and to improve the quality of life of patients suffering from these degenerative diseases, will be proposed after multidisciplinary neuro-urologic concertation. The decision to perform prostate surgery must be taken with caution after proving sub-vesical obstruction.

[Expert opinion on surgical care pathway management of neurologic patients from Neuro-Urology Committee of the French National Association of Urology (AFU)]. / Le parcours de l'opéré en neuro-urologie: de la programmation opératoire à la convalescence. L'avis d'expert du Comité de Neuro-Urologie de l'AFU.

The surgical care pathway of neurologic patients has two aims: preventing urinary morbidity and mortality and improving their quality of life. It requires taking into account the specificities of disabilities in domains of body functions: circulatory, ventilation and digestive physiology, motor functions, sensory functions, mental functions, and skin fragility which are responsible of dependencies in this heterogeneous group of patients. This management is necessarily multidisciplinary to be optimal and through specific clinical care pathway, providing guidance to the surgical procedure: preparation of the surgery, its realization, and post-operative rehabilitation. The indication for surgery must be coordinated and validated in neuro-urology multidisciplinary staff. Preoperative stay in a physical and rehabilitation medicine center may be useful to ensure a complete assessment and anticipate problems related to surgery. The patient will be hospitalized in the urology department in a single room suited to their disabilities and handicaps. The chronic treatments should be not modified if possible. The lack of sensitivity does not dispense anesthesia to prevent autonomic hyperreflexia, the most severe complication after high complete spinal cord injury. The laparoscopy and sub-peritoneal surgery, the early removal nasogastric tube and early refeeding make it possible to early resumption of intestinal transit. In many cases, the patients should be transferred to a physical and rehabilitation medicine during post-operative period where the nursing care will be most suitable. A quickly adapted rehabilitation must be able to reduce loss of function and physical dependence.

"In vitro" antifungal activity of ozonized sunflower oil on yeasts from onychomycosis

The "In vitro" antifungal activity of ozonized sunflower oil (Bioperoxoil®) was tested on 101 samples of yeasts originating from onychomycosis using the disk diffusion method. The oil was efficacious against several clinical fungal strains: Candida parapsilosis, Candida albicans, Trichosporonasahii, Candida tropicalis and Candida guilliermondii.

Bladder dysfunction in hereditary spastic paraplegia: a clinical and urodynamic evaluation.

OBJECTIVES: Hereditary spastic paraplegia (HSP) is a degenerative central nervous system disorder characterized by progressive spasticity and hyperreflexia of the lower limbs. Often, patients with HSP experience symptoms of voiding dysfunction. Urodynamic evaluations of these patients are rarely reported in the literature and the etiology of voiding dysfunction remains unclear. The present study characterizes lower urinary tract dysfunction in a large series of patients. METHODS: The medical records of 29 HSP patients who underwent urodynamic evaluation were retrospectively analyzed. The history of lower urinary tract symptoms was noted and the urodynamic findings analyzed. RESULTS: Urgency was the most dominant complaint (72.4%), followed by frequency (65.5%), urinary incontinence (55.2%) and hesitancy (51.7%). The urodynamic findings showed signs of central neurogenic bladder in 24 patients (82.7%), with detrusor overactivity (DO) in 15 patients (51.7%) and detrusor sphincter dyssynergia (DSD) in 19 (65.5%). Post-void residual (PVR) of >10% of the voided volume was found in 12 patients (41.4%). There were significant relationships between detrusor overactivity and PVR (P=0.005), frequency (P=0.046) and nocturia (P=0.045). Ultrasound examination revealed no upper urinary tract complications. CONCLUSION: Despite the presence of DO and DSD, HSP patients do not seem to have a high risk of developing ultrasonographically-assessed upper urinary tract complications after a mean follow-up of 22 years, contrary to spinal cord injury population. These results may guide practitioners in their decision-making about the appropriate evaluation and treatment of bladder disturbances that accompany hereditary spastic paraplegia.

"In vitro" antifungal activity of ozonized sunflower oil on yeasts from onychomycosis.

The "in vitro" antifungal activity of ozonized sunflower oil (Bioperoxoil®) was tested on 101 samples of yeasts originating from onychomycosis using the disk diffusion method. The oil was efficacious against several clinical fungal strains: Candida parapsilosis, Candida albicans, Trichosporon asahii, Candida tropicalis and Candida guilliermondii.

First report of Tritirachium oryzae infection of human scalp.

The natural habitat of Tritirachium oryzae is soil and decaying plant material. It is also an insect pathogen. As a human pathogen, it has been reported as a cause of corneal ulcers and otomycosis. The case of a 4-year-old infant is reported with Tritirachium oryzae infection of the scalp. Diagnosis was established by direct mycological study and culture that showed Tritirachium oryzae as the only agent in a pure culture. The topical treatment involved an antifungal medication to a complete cure. We report the first case of scalp dermatomycosis due to Tritirachium oryzae infection, illustrating a novel clinical manifestation.

[Alternative treatments for interstitial cystitis]. / Les traitements de recours dans la cystite interstitielle.

Interstitial cystitis is the first cause of bladder pain. In case of failure of the usual treatments, several other modalities have been proposed. These therapeutic modalities are posterior sacral root neuromodulation, posterior tibial nerve stimulation, vanilloid agent intravesical instillation, intradetrusor botulinum toxin injections and surgery. A certain efficiency of each of these treatments in the interstitial cystitis has been reported. However, the evaluation of these treatments is limited and the level of evidence is too low to propose these treatments in routine.

Anti-tumor necrosis factor-a for the treatment of steroid-refractory acute graft-versus-host disease

Allogeneic stem cell transplantation has been increasingly performed for a variety of hematologic diseases. Clinically significant acute graft-versus-host disease (GVHD) occurs in 9 to 50 percent of patients who receive allogeneic grafts, resulting in high morbidity and mortality. There is no standard therapy for patients with acute GVHD who do not respond to steroids. Studies have shown a possible benefit of anti-TNF-a (infliximab)for the treatment of acute GVHD. We report here on the outcomes of 10 recipients of related or unrelated stem cell transplants who received 10 mg/kg infliximab, iv, once weekly for a median of 3.5 doses (range: 1-6) for the treatment of severe acute GVHD and who were not responsive to standard therapy. All patients had acute GVHD grades II to IV (II = 2, III = 3, IV = 5). Overall, 9 patients responded and 1 patient had progressive disease. Among the responders, 3 had complete responses and 6 partial responses. All patients with cutaneous or gastrointestinal involvement responded, while only 2 of 6 patients with liver disease showed any response. None of the 10 patients had any kind of immediate toxicity. Four patients died, all of them with sepsis. Six patients are still alive after a median follow-up time of 544 days (92-600) after transplantation. Considering the severity of the cases and the bad prognosis associated with advanced acute GVHD, we find our results encouraging. Anti-TNF-a seems to be a useful agent for the treatment of acute GVHD.

What is the place of electroneuromyographic studies in the diagnosis and management of pudendal neuralgia related to entrapment syndrome?

Entrapment of the pudendal nerve may be at the origin of chronic perineal pain. This syndrome must be diagnosed because this can result in the indication of surgical decompression of the entrapped nerve for pain relief. Electroneuromyographic (ENMG) investigation is often performed in this context, based on needle electromyography and the study of sacral reflex and pudendal nerve motor latencies. The limits of ENMG investigation, owing to various pathophysiological and technical considerations, should be known. The employed techniques do not assess directly the pathophysiological mechanisms of pain but rather correlate to structural alterations of the pudendal nerve (demyelination or axonal loss). In addition, only direct or reflex motor innervation is investigated, whereas sensory nerve conduction studies should be more sensitive to detect nerve compression. Finally, ENMG cannot differentiate entrapment from other causes of pudendal nerve lesion (stretch induced by surgical procedures, obstetrical damage, chronic constipation...). Thus, perineal ENMG has a limited sensitivity and specificity in the diagnosis of pudendal nerve entrapment syndrome and does not give direct information about pain mechanisms. Pudendal neuralgia related to nerve entrapment is mainly suspected on specific clinical features and perineal ENMG examination provides additional, but no definitive clues, for the diagnosis or the localization of the site of compression. In fact, the main value of ENMG is to assess objectively pudendal motor innervation when a surgical decompression is considered. Perineal ENMG might predict the outcome of surgery but is of no value for intraoperative monitoring.

Anti-tumor necrosis factor-a for the treatment of steroid-refractory acute graft-versus-host disease.

Allogeneic stem cell transplantation has been increasingly performed for a variety of hematologic diseases. Clinically significant acute graft-versus-host disease (GVHD) occurs in 9 to 50% of patients who receive allogeneic grafts, resulting in high morbidity and mortality. There is no standard therapy for patients with acute GVHD who do not respond to steroids. Studies have shown a possible benefit of anti-TNF-a (infliximab)for the treatment of acute GVHD. We report here on the outcomes of 10 recipients of related or unrelated stem cell transplants who received 10 mg/kg infliximab, iv, once weekly for a median of 3.5 doses (range: 1-6) for the treatment of severe acute GVHD and who were not responsive to standard therapy. All patients had acute GVHD grades II to IV (II = 2, III = 3, IV = 5). Overall, 9 patients responded and 1 patient had progressive disease. Among the responders, 3 had complete responses and 6 partial responses. All patients with cutaneous or gastrointestinal involvement responded, while only 2 of 6 patients with liver disease showed any response. None of the 10 patients had any kind of immediate toxicity. Four patients died, all of them with sepsis. Six patients are still alive after a median follow-up time of 544 days (92-600) after transplantation. Considering the severity of the cases and the bad prognosis associated with advanced acute GVHD, we find our results encouraging. Anti-TNF-a seems to be a useful agent for the treatment of acute GVHD.

Radical vaginal trachelectomy (Dargent's operation): a critical review of the literature.

AIMS: To present a review of the most recent articles about radical vaginal trachelectomy (RVT). METHODS: Recent literature has been reviewed, concentrating on surgical, oncological and obstetrical outcome of RVT. Data for this review were identified by searches of PubMed, and references from relevant articles using the search terms "trachelectomy" and "radical vaginal trachelectomy", "cervical carcinoma", and "fertility saving". FINDINGS: Although a considerable number of women in their reproductive years have been diagnosed with cervical carcinoma, conservative management of early-stage cervical carcinoma did not come into practice until the beginning of the new millennium. To date, 7 gynecologic oncologic centers worldwide have reported oncological and pregnancy outcomes since Dargent made his first announcement of radical vaginal trachelectomy (RVT) in 1994. Recurrence and death rates (4.2% and 2.8%, respectively) of RVT seem to be comparable to classical radical abdominal hysterectomy. It appears that RVT's overall recurrence and death rates were similar to early-stage cervical cancer treated by radical hysterectomy (RH) or radiotherapy. Furthermore fertility results of RVT seem to be promising. A 70% pregnancy rate was reported in the women who wanted to conceive following RVT, though such patients should be informed about the risk of second trimester loss and preterm delivery. On the other hand, there is a lack of satisfactory information about the follow-up of post-RVT patients, both after the operation and during subsequent pregnancy. CONCLUSION: RVT looks as if it is a valid uterus-conserving surgery for women of reproductive age who have early-stage cervical carcinoma. However, in order to reach a final conclusion about the oncological and obstetrical results, further studies are needed with larger sample sizes and longer follow-up periods.

Extent of the cariostatic effect on root dentin provided by fluoride-containing restorative materials.

This study evaluated the extent of the cariostatic effect on root dentin provided by four fluoride-containing restorative systems: Ketac-Fil/ESPE [Ke], Fuji II LC Improved/GC Corp [Fj], Dyract AP/Dentsply [Dy] and SureFil/Dentsply [Su], and one without fluoride: Z250/3M [control]. Ninety-five bovine root dentin fragments (5.0 x 6.0 mm) were obtained, embedded in polyester resin and planed. Cavities (1.5 x 3.5 x 1.0 mm) were made and restored by the five restorative systems (n=19) in a randomized complete block design according to the manufacturers' instructions. After 24 hours, the dentin/restoration surface was polished. The restoration surface and an adjacent area of 3.0 x 3.0 mm were demarcated and submitted to a pH-cycling model. Dentin surface Knoop microhardness values were obtained (5.0-g, 5.0-s) for 10 distances: 50, 100, 150, 300, 600, 900, 1200, 1500, 1800 and 2100 microm from the margin of the restoration. The dentin microhardness means for each restorative material at each distance was considered by the ANOVA multi-factor split-plot method. The interaction between the restorative system and distance was statistically significant (p<0.05). The Tukey test and the regression analysis showed that the means of [Ke] and [Fj] were similar up to 300 microm, the [Ke] means being higher than the [control] at distances 50, 100, 150 and 300 microm. The [Fj] means were higher than the [control] at distances 50, 100 and 150 microm. The microhardness means of [Dy] and [Su] were not statistically different from the [control] and remained steady throughout the studied distances. This study concluded that the extent of the cariostatic effect on root dentin was 300 microm for [Ke] and 150 microm for [Fj]. [Dy] and [Su] did not show any cariostatic effect.