Background: Mannitol has been used in the past for the prevention of cisplatin-induced nephrotoxicity. Studies on its efficacy have conflicting results. An educational newsletter was designed for local oncologists on the conflicting data of mannitol use in preventing cisplatin-induced nephrotoxicity. Purpose: The purpose of this study was to determine whether a pharmacist-created newsletter intervention led to changes in the mannitol prescribing practices of local oncologists. Methods: A newsletter describing the paucity of evidence to support mannitol use to prevent cisplatin-induced nephrotoxicity was distributed via e-mail to local oncologists in October 2010. Mannitol prescribing rates were retrospectively evaluated before and after newsletter distribution. The Mann-Whitney U test was used to compare nonparametric continuous data. The chi-square test was used for nominal data. Descriptive statistics were performed for baseline demographics, and odds ratios were calculated for possible risk factors for acute kidney injury (AKI). The primary endpoint was a change in mean mannitol dose before and after the newsletter intervention. The secondary endpoint was the difference in the rate of AKI before and after the intervention. Data were collected for 67 patients with various malignancies. Results: There was a difference in the average mannitol dose before and after newsletter intervention (P = .02). The rates of AKI before and after newsletter were similar. Conclusion: A pharmacist-led newsletter intervention was associated with significantly decreased rates of mannitol usage after intervention.

No / Mannitol is a polymorphic pharmaceutical excipient, which commonly exists in three forms: alpha, beta and delta. Each polymorph has a needle-like morphology, which can give preferred orientation effects when analysed by X-ray powder diffractometry (XRPD) thus providing difficulties for quantitative XRPD assessments. The occurrence of preferred orientation may be demonstrated by sample rotation and the consequent effects on X-ray data can be minimised by reducing the particle size. Using two particle size ranges (<125 and 125¿500 ¿m), binary mixtures of beta and delta mannitol were prepared and the delta component was quantified. Samples were assayed in either a static or rotating sampling accessory. Rotation and reducing the particle size range to <125 ¿m halved the limits of detection and quantitation to 1 and 3.6%, respectively. Numerous potential sources of assay errors were investigated; sample packing and mixing errors contributed the greatest source of variation. However, the rotation of samples for both particle size ranges reduced the majority of assay errors examined. This study shows that coupling sample rotation with a particle size reduction minimises preferred orientation effects on assay accuracy, allowing discrimination of two very similar polymorphs at around the 1% level.

No / In this paper, molecular modelling was used to investigate the nature of probe/surface interactions during the analysis of Dß-mannitol using inverse gas chromatography (IGC). IGC was used to experimentally measure the dispersive components of surface free energy () and the specific components of free energy of adsorption () of Dß-mannitol by calculating the retention time of non-polar (n-alkanes) and polar (tetrahydrofuran and chloroform) probes, respectively. The results showed that Dß-mannitol surface is acidic in nature because the basic probe had more interaction with the surface as compared to acidic probe. Cerius2 software package was used to model the two morphologically important surfaces, which showed the presence of surface hydroxyl groups. Molecular dynamics simulations were performed in Cerius2 to model the adsorption of the same probes (n-alkanes, tetrahydrofuran and chloroform) on the Dß-mannitol surfaces. The adsorption energies calculated from the simulation showed a close match to those determined experimentally. The calculated values are slightly higher for all probes except chloroform, but as a single perfect crystal was modelled without considering the effect of impurities, solvent and other physical factors this is not unexpected.

This study provides, for the first time, an ex vivo comparative evaluation of formulations of budesonide with crystallised β-form mannitol, commercial DPI grade mannitol and lactose. The lactose-budesonide was the marketed Easyhaler® 200 g formulation. Ex vivo assessment of deposition using the Easyhaler® multi-dose high resistance inhaler with reservoir was compared with the RS01® single dose capsule low resistance inhaler at two different inhalation rates. Aerodynamic characteristics, flow and surface energies were investigated together with in vitro and ex vivo assessment of drug deposition. Dose emission was greater for all formulations with higher inhalation flow, indicating greater detachment of drug from carrier, and greater with the Easyhaler®, highlighting the importance of correct device for formulation. Emission was lowest at both inhalation rates for crystallised mannitol due to poor flowability associated with elongated particle shape which resulted in interception deposition. Surface energies were also implicated; closely matched polar surface energy of carrier and drug may be an important inhibiting factor. The promising aerodynamic characteristics of crystallised mannitol with the RS01® inhaler and lactose-budesonide from in vitro assessment were not supported by ex vivo results, highlighting the need for careful selection of device.

No description available.

Les accidents sont la cause la plus fréquente de décès chez l’enfant, la plupart du temps à cause d’un traumatisme cranio-cérébrale (TCC) sévère ou d’un choc hémorragique. Malgré cela, la prise en charge de ces patients est souvent basée sur la littérature adulte. Le mannitol et le salin hypertonique (3%) sont des traitements standards dans la gestion de l’hypertension intracrânienne, mais il existe très peu d’évidence sur leur utilité en pédiatrie. Nous avons entrepris une revue rétrospective des traumatismes crâniens sévères admis dans les sept dernières années, pour décrire l’utilisation de ces agents hyperosmolaires et leurs effets sur la pression intracrânienne. Nous avons établi que le salin hypertonique est plus fréquemment utilisé que le mannitol, qu’il ne semble pas y avoir de facteurs associés à l’utilisation de l’un ou l’autre, et que l’effet sur la pression intracrânienne est difficile à évaluer en raison de multiples co-interventions. Il faudra mettre en place un protocole de gestion du patient avec TCC sévère avant d’entreprendre des études prospectives. La transfusion sanguine est employée de façon courante dans la prise en charge du patient traumatisé. De nombreuses études soulignent les effets néfastes des transfusions sanguines suggérant des seuils transfusionnels plus restrictifs. Malgré cela, il n’y a pas de données sur les transfusions chez l’enfant atteint de traumatismes graves. Nous avons donc entrepris une analyse post-hoc d’une grosse étude prospective multicentrique sur les pratiques transfusionnelles des enfants traumatisés. Nous avons conclu que les enfants traumatisés sont transfusés de manière importante avant et après l’admission aux soins intensifs. Un jeune âge, un PELOD élevé et le recours à la ventilation mécanique sont des facteurs associés à recevoir une transfusion sanguine aux soins intensifs. Le facteur le plus prédicteur, demeure le fait de recevoir une transfusion avant l’admission aux soins, élément qui suggère probablement un saignement continu. Il demeure qu’une étude prospective spécifique des patients traumatisés doit être effectuée pour évaluer si une prise en charge basée sur un seuil transfusionnel restrictif serait sécuritaire dans cette population. / Trauma is the leading cause of death of children, with the burden of mortality related both to traumatic brain injury and hemorrhagic shock. Despite the frequency of trauma in the pediatric population, the management of these patients is often based on adult literature due the sparse amount of literature in pediatric trauma. The studies presented below were intended to establish current practice, and prepare for future prospective studies in pediatric trauma. The management of raised intracranial pressure (ICP) following traumatic brain injury (TBI) involves intracranial monitoring and the escalation of care to prevent secondary insults to the brain. Hyperosmolar therapy with mannitol (20%) and hypertonic saline (3%) are standard of care for the reduction of ICP, despite little evidence for their use. Our retrospective, single center study aimed to describe the clinical practice of hyperosmolar therapy in pediatric severe TBI, and its effect on ICP. We found that both mannitol and hypertonic saline are frequently used without a clear indication for one agent over another. There was insufficient power to confirm an effect on ICP, and multiple co-interventions given after boluses of hyperosmolar therapy may have contributed this lack of effect. In order to prospectively evaluate the effect of hyperosmolar therapy on ICP, a standardized approach to TBI care and hyperosmolar agents is necessary. Red blood cell transfusion is a key component of the management of the unstable trauma patient. Literature now suggests that transfusion is associated with increased mortality, and practices have shifted toward restrictive transfusion strategies in many clinical populations. We sought to describe the transfusion practices in pediatric trauma patients based on a secondary analysis of a large prospective study on blood loss in pediatric intensive care unit (PICU) patients. Compared to non-trauma patients, trauma patients were more likely to be transfused and transfused early in their course of stay. Younger age, higher PELOD and mechanical ventilation were associated with receiving a red blood cell transfusion in the PICU. Receiving a blood transfusion prior to PICU admission was most strongly associated with receiving a transfusion after PICU admission, suggesting ongoing bleeding in those transfused early. Future prospective studies geared specifically for trauma patients are necessary to determine whether osmotherapy for high ICP, and restrictive transfusion strategies can be applied to them, in order to improve the quality of the evidence based care provided to children.

Hyaluronan (HA) is a substance that is commonly used in biomedical applications in the form of hydrogels. One of these biomedical applications is dermatological fillers where HA is cross-linked with 1,4-Butanediol diglycidyl ether (BDDE) to reduce its rapid turnover within tissue. The filler gives a volumetric effect that can fill out wrinkles. This literature study was conducted in collaboration with Galderma to determine if there is research that explores additives to HA hydrogels that give both volumetric and biological effects when applied as filler. Biological effects that improve the skin's appearance and complexion such as a rejuvenation of the skin was preferable. Both polynucleotides and mannitol show great potential to act as additives in injectable hyaluronan hydrogels.  The main effect of polynucleotides (PN) added in hydrogels is that it is collagen stimulating and provides a more natural tissue regeneration. Rheological properties of the filler change with the addition of PN, where elasticity, viscosity and viscoelasticity have been shown to increase. PNs show no toxicity and are considered safe to inject. The study of mannitol has shown that it does not give a volumetric effect after the injected hydrogel has been broken down. What mannitol can help with, is to prolong the life of the hydrogel and reduce the swelling that is a common side effect after an injection. In addition to this, mannitol is a safe substance to inject.

Master of Science / Food Science Institute- Animal Sciences and Industry / Kelly J. K. Getty / The Food and Drug Administration’s Bacteriological Analytical Manual recommends two enumeration methods for Bacillus spp.: 1) standard plating method using mannitol-egg yolk-polymyxin (MYP) agar and 2) most probable number (MPN) method with tryptic soy broth supplemented with 0.1% polymyxin sulfate. Preliminary research evaluated three inoculum preparation methods using EZ-Spore™ B. cereus pellets. Two methods involved EZ-Spore™ B. cereus pellets that were dissolved in deionized (DI) water, grown in brain heart infusion broth with manganese sulfate, and then heated to produce spores. The third inoculum preparation method of dissolving EZ-Spore™ pellets only in DI water was the most efficient due to 100% spores being present in the inoculum. Preliminary research also determined that MPN method recovered greater (p<0.05) B. cereus populations than MYP method in inoculated ultra-high temperature pasteurized skim and 2% milk. The objective of the main study was to compare the MYP and MPN method for detection and enumeration of B. cereus in raw and high-temperature-short-time pasteurized skim, 2%, and whole milk at 4 °C for 96 h. Milk samples were inoculated with B. cereus EZ-Spores™ dissolved in DI water and sampled at 0, 48, and 96 h after inoculation. No differences (p>0.05) were observed among sampling times so data was pooled for overall mean values for each treatment. The overall B. cereus population mean of pooled sampling times for MPN method (2.59 log CFU/mL) was greater (p<0.05) than MYP plating method (1.89 log CFU/mL). B. cereus populations ranged from 3.40 log CFU/mL to 2.40 log CFU/mL for inoculated milk treatments for MYP and MPN methods, which is well below the necessary level for toxin production. Even though MPN method enumerated more B. cereus, the MYP method should be used by industry for enumeration of B. cereus due to its ease of use and rapid turnover time (2 d compared to 5 d with MPN). However, MPN method should be used for validation research due to its greater populations recovered. EZ-Spore™ B. cereus pellets were found to be an acceptable spore inoculum for validation research because the inoculum consists of 100% spores and does not contain vegetative cells.

Convection-enhanced delivery (CED) is a proven method for targeted drug delivery to the brain that circumvents the blood-brain barrier (BBB). Little study has been conducted in understanding CED in pathological brain states. This is of importance when dealing with chemotherapeutic agent delivery to brain tumors, where vasogenic edema (VE) exists. The current study aims to characterize a model of VE suitable for studying CED.VE was produced in the right hemisphere of the rat brain using multiple infusions of hyperosmotic mannitol (0.25mL/kg/s over 30 seconds) delivered through the right internal carotid artery. Magnetic resonance imaging (MRI) revealed consistent edema formation and high water levels in the ipsilateral gray and white matter within an hour of the first infusion. Evan's Blue (EB) staining verified that VE has formed. However, apparent diffusion coefficient (ADC) and histological examination revealed also that some possible cytotoxic edema formed.This model provides a reproducible technique for generating a large area of edema for CED study. Further studies with lower doses of mannitol, while titrating to changes in ADC and values for fractional water content, may modify this model with a greater component of VE and less cerebral toxicity.

Chez Bacillus subtilis l'expression de l'opéron mtl pour l'utilisation du mannitol est contrôlé par MtlR. MtlR est un activateur transcriptionnel qui appartient à la famille des régulateurs DeoR composé d'un domaine HTH suivi de deux PRDs, un domaine EIIBGat et un domaine EIIAMtl-like.Le mécanisme général de la régulation de l'activité de MtlR est basé sur sa phosphorylation par des composants du PTS. La phosphorylation sur la Cystéine 419 du domaine EIIBGat par P~EIIAMtl a un effet négatif majeur sur l'activité de MtlR. Par conséquent, dans un mutant mtlF où EIIAMtl est délétée MtlR est constitutivement actif.Dans cette étude nous avons mis en évidence un nouveau phénomène de régulation de MtlR impliquant la protéine du PTS, EIIBMtl.Nous avons observé que lorsque on déléte l'opéron mtl ou EIIBMtl et EIIAMtl, l'activité constitutive de MtlR dans un mutant mtlF déjà observée est abolie d'où notre hypothèse que EIIBMtl aura un effet sur l'activité de MtlR. Par des expériences de double hybride nous avons montré une interaction directe, spécifique et bidirectionnelle entre les deux protéines EIIBMtl et EIIBGatEIIAMtl-like de MtlR. D'une manière comparable à la cellule où EIIBMtl est fusionnée à la protéine EIICMtl nous avons démontré que seulement la forme EIIBMtl fusionné à la perméase EIICMtl est capable d'activer MtlR mais nous avons également démontré que ce n'est pas EIICMtl qui est essentielle à l'interaction entre EIIBMtl et MtlR mais c'est le voisinage de la membrane qui est essentielle pour l'établissement de cette interaction et l'activation de MtlRUn modèle de régulation de l'activité du régulateur MtlR est proposé. Dans ce modèle l'induction de l'opéron mtl via l'activation de MtlR requiert la phosphorylation de PRDII de MtlR par P~His-HPr, la déphosphorylation de EIIBGat de MtlR par EIIAMtl et la présence de la forme non-phosphorylée de l'EIIBMtl qui est dominante en présence du substrat inducteur, le mannitol. Ainsi, l'EIIBMtl non-phosphorylée séquestre MtlR déphosphorylé sur sa cystéine 419 à la membrane, l'active et induit l'expression de l'opéron mtl.