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Critical Care (London, England) Jul 2019
Topics: Algorithms; Disease Management; Humans; Intracranial Hypertension; Mannitol; Saline Solution, Hypertonic
PubMed: 31272474
DOI: 10.1186/s13054-019-2529-z -
Respiratory Medicine 2019Citric acid has been used as a cough provocation test for decades. However, the methods of administration have not been standardized. Inhaled mannitol is a novel cough...
RATIONALE
Citric acid has been used as a cough provocation test for decades. However, the methods of administration have not been standardized. Inhaled mannitol is a novel cough provocation test, which has regulatory approval and can be performed utilizing a simple disposable inhaler in a standardized manner.
OBJECTIVE
To compare the mannitol and citric acid cough provocation tests with respect to their ability to identify subjects with chronic cough and their tolerability.
METHODS
Subjects with chronic cough (n = 36) and controls (n = 25) performed provocation tests with mannitol and citric acid. Both tests were video recorded. Cough sensitivity was expressed as coughs-to-dose ratios (CDR) and the cumulative doses to mannitol or concentration to citric acid evoking 5 coughs (C5). Forced expiratory volume in 1 s (FEV), visual analogue scales (VAS), test completion rates and the total cough frequencies were analysed.
RESULTS
Mannitol and citric acid CDR both effectively separated those with cough and the control subjects (AUC 0.847 and 0.803, respectively) as did C5 (AUC 0.823 and 0.763, respectively). There was a good correlation between the cough sensitivity provoked by the two stimuli, either expressed as CDR (r = 0.65, p < 0.001) or C5 (r = 0.53, p = 0.001). Both tests were similarly tolerated in terms of VAS, although more patients discontinued the mannitol test early, primarily due to cough.
CONCLUSIONS
Mannitol and citric acid tests correlated well, equally identified subjects with chronic cough and their tolerability was similar. The feasibility issues, strict standardisation and regulatory approval may favour mannitol to be used in clinical cough research.
Topics: Adult; Aged; Aged, 80 and over; Bronchial Provocation Tests; Citric Acid; Cough; Female; Humans; Male; Mannitol; Middle Aged; Young Adult
PubMed: 31542680
DOI: 10.1016/j.rmed.2019.09.011 -
The Cochrane Database of Systematic... May 2014Mucus retention in the lungs is a prominent feature of bronchiectasis. The stagnant mucus becomes chronically colonised with bacteria, which elicit a host neutrophilic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mucus retention in the lungs is a prominent feature of bronchiectasis. The stagnant mucus becomes chronically colonised with bacteria, which elicit a host neutrophilic response. This fails to eliminate the bacteria, and the large concentration of host-derived protease may contribute to the airway damage. The sensation of retained mucus is itself a cause of suffering, and the failure to maintain airway sterility probably contributes to the frequent respiratory infections experienced by many patients.Hypertonic saline inhalation is known to accelerate tracheobronchial clearance in many conditions, probably by inducing a liquid flux into the airway surface, which alters mucus rheology in a way favourable to mucociliary clearance. Inhaled dry powder mannitol has a similar effect. Such agents are an attractive approach to the problem of mucostasis, and deserve further clinical evaluation.
OBJECTIVES
To determine whether inhaled hyperosmolar substances are effective in the treatment of bronchiectasis.
SEARCH METHODS
We searched the Cochrane Airways Group Specialised Register, trials registries, and the reference lists of included studies and review articles. Searches are current up to April 2014.
SELECTION CRITERIA
Any randomised controlled trial (RCT) using hyperosmolar inhalation in patients with bronchiectasis not caused by cystic fibrosis.
DATA COLLECTION AND ANALYSIS
Two review authors assessed studies for suitability. We used standard methods recommended by The Cochrane Collaboration.
MAIN RESULTS
Eleven studies met the inclusion criteria of the review (1021 participants).Five studies on 833 participants compared inhaled mannitol with placebo but poor outcome reporting meant we could pool very little data and most outcomes were reported by only one study. One 12-month trial on 461 participants provided results for exacerbations and demonstrated an advantage for mannitol in terms of time to first exacerbation (median time to exacerbation 165 versus 124 days for mannitol and placebo respectively (hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.63 to 0.96, P = 0.022) and number of days on antibiotics for bronchiectasis exacerbations was significantly better with mannitol (risk ratio (RR) 0.76, 95%CI 0.58 to 1.00, P = 0.0496). However, exacerbation rate per year was not significantly different between mannitol and placebo (RR 0.92 95% CI 0.78 to 1.08). The quality of this evidence was rated as moderate. There was also an indication, from only three trials, again based on moderate quality evidence, that mannitol improves health-related quality of life (mean difference (MD) -2.05; 95% CI -3.69 to -0.40). An analysis of adverse events data, also based on moderate quality evidence, revealed no difference between mannitol and placebo (OR 0.96; 95% CI 0.61 to 1.51). Two additional small trials on 25 participants compared mannitol versus no treatment and the data from these studies were inconclusive.Four studies (combined N = 113) compared hypertonic saline versus isotonic saline. On most outcomes there were conflicting results and the opportunities for the statistical aggregation of data from studies was very limited. It is not possible to draw robust conclusions for this comparison and judgments should be reserved until further data are available.
AUTHORS' CONCLUSIONS
There is an indication from a single, large, unpublished study that inhaled mannitol increases time to first exacerbation in patients with bronchiectasis. In patients with near normal lung function, spirometry does not change dramatically with mannitol and adverse events are not more frequent than placebo. Further investigation is required in a patient population with impaired lung function.It is not possible to draw firm conclusions regarding the effect of nebulised hypertonic saline due to significant differences in the methodology, patient groups, and findings amongst the limited data available. The data suggest that it is unlikely to have benefit over isotonic saline in patients with milder disease, and hence future studies should test its use in those with more severe disease.
Topics: Anti-Bacterial Agents; Bronchiectasis; Cross-Over Studies; Health Status; Humans; Hypertonic Solutions; Mannitol; Mucociliary Clearance; Osmolar Concentration; Powders; Randomized Controlled Trials as Topic
PubMed: 24817558
DOI: 10.1002/14651858.CD002996.pub3 -
Frontiers in Immunology 2022Serum resistance is recognized as one of the most important pathogenic traits of bacterial pathogens, and no control measure is available. Based on our previous...
Serum resistance is recognized as one of the most important pathogenic traits of bacterial pathogens, and no control measure is available. Based on our previous discovery that pathogenic represses glycine, serine, and threonine metabolism to confer serum resistance and that the reactivation of this pathway by exogenous glycine could restore serum sensitivity, we further investigate the mechanism underlying the action of glycine in . Thus, is treated with glycine, and the proteomic change is profiled with tandem mass tag-based quantitative proteomics. Compared to the control group, glycine treatment influences the expression of a total of 291 proteins. Among them, a trap-type mannitol/chloroaromatic compound transport system with periplasmic component, encoded by N646_0992, is the most significantly increased protein. In combination with the pathway enrichment analysis showing the altered fructose and mannitol metabolism, mannitol has emerged as a possible metabolite in enhancing the serum killing activity. To demonstrate this, exogenous mannitol reduces bacterial viability. This synergistic effect is further confirmed in a - infection model. Furthermore, the mechanism underlying mannitol-enabled serum killing is dependent on glycolysis and the pyruvate cycle that increases the deposition of complement components C3b and C5b-9 on the bacterial surface, whereas inhibiting glycolysis or the pyruvate cycle significantly weakened the synergistic effects and complement deposition. These data together suggest that mannitol is a potent metabolite in reversing the serum resistance of and has promising use in aquaculture.
Topics: Vibrio alginolyticus; Proteomics; Escherichia coli; Complement System Proteins; Glycine; Mannitol; Pyruvates
PubMed: 36389821
DOI: 10.3389/fimmu.2022.1010526 -
The Journal of Physiology Jul 19781. Free water clearances were measured during infusion of hypotonic saline, glucose, urea, and mannitol in Brattleboro rats. For each solute the free water clearances...
1. Free water clearances were measured during infusion of hypotonic saline, glucose, urea, and mannitol in Brattleboro rats. For each solute the free water clearances were plotted using either V or (C(H2O) + C(Na)) as the distal tubular delivery term.2. In all cases the use of (C(H2O) + C(Na)) as distal delivery term yielded a steeper relationship than when V was used. There were no significant differences in the C(H2O) to V relationship when saline, glucose and mannitol was the solute infused. Urea, however, resulted in a curve with a slope significantly less than that for the other solutes.3. When C(H2O) was plotted against (C(H2O) + C(Na)) there was still no significant difference between the slopes of the curves during saline or mannitol infusion. Use of this delivery term, however, resulted in a slope during glucose infusion which was significantly greater than that during saline or mannitol infusion. The slope for urea infusion remained lower than that for any other solute.4. Regardless of the delivery term used, there was no significant difference in the slopes of the curves for awake Wistar and awake Brattleboro rats during mannitol infusion. This indicates that the awake rat is a suitable model for free water clearance studies.5. The results indicate that NaCl and mannitol are both adequate for free water clearance and that (C(H2O) + C(Na)) is a better index of distal delivery than V.
Topics: Animals; Diuresis; Female; Glucose; Inappropriate ADH Syndrome; Male; Mannitol; Rats; Sodium Chloride; Urea; Water
PubMed: 690907
DOI: 10.1113/jphysiol.1978.sp012396 -
Molecules (Basel, Switzerland) Apr 2022Heterogeneous laborious analytical methodologies for the determination of urinary lactulose and mannitol limit their utility in intestinal permeability testing.
BACKGROUND
Heterogeneous laborious analytical methodologies for the determination of urinary lactulose and mannitol limit their utility in intestinal permeability testing.
METHODS
We developed an assay using a Shimadzu HPLC system, an Aminex HPX87C column, and refractive index detection. The test was calibrated using a series of dilutions from standard stock solutions of lactulose and mannitol 'spiked' into urine samples. The utility to quantify urinary excretion during the dual sugar absorption test over 6 h was also determined.
RESULTS
Lactulose and mannitol were eluted isocratically at 5.7 and 10.1 min, respectively, with water as a mobile phase at a flow rate of 0.3 mL min, 858 psi, 60 °C. The calibration curves for both sugars were linear up to 500 µg mL with a limit of detection in standard solutions at 4 µg mL and in 'spiked' urine samples at 15 µg mL. The intra-assay and inter-assay CVs were between 2.0-5.1% and 2.0-5.1% for lactulose and 2.5-4.4% and 2.8-3.9% for mannitol. The urinary profiles of the 6 h absorption of lactulose and mannitol showed similar peak-retention times to standard solutions and were well-resolved at 5.9 and 10.4 min, respectively.
CONCLUSIONS
The assay was easy to automate, using commonly available equipment and convenient requiring no prior laborious sample derivatization. The simplicity, reproducibility, and robustness of this assay facilitates its use in routine clinical settings for the quantification of intestinal permeability.
Topics: Chromatography, High Pressure Liquid; Intestinal Absorption; Lactulose; Mannitol; Permeability; Reproducibility of Results
PubMed: 35566024
DOI: 10.3390/molecules27092677 -
Cell Transplantation 2014Ischemic brain injury in adults and neonates is a significant clinical problem with limited therapeutic interventions. Currently, clinicians have only tPA available for... (Review)
Review
Ischemic brain injury in adults and neonates is a significant clinical problem with limited therapeutic interventions. Currently, clinicians have only tPA available for stroke treatment and hypothermia for cerebral palsy. Owing to the lack of treatment options, there is a need for novel treatments such as stem cell therapy. Various stem cells including cells from embryo, fetus, perinatal, and adult tissues have proved effective in preclinical and small clinical trials. However, a limiting factor in the success of these treatments is the delivery of the cells and their by-products (neurotrophic factors) into the injured brain. We have demonstrated that mannitol, a drug with the potential to transiently open the blood-brain barrier and facilitate the entry of stem cells and trophic factors, as a solution to the delivery problem. The combination of stem cell therapy and mannitol may improve therapeutic outcomes in adult stroke and neonatal cerebral palsy.
Topics: Animals; Blood-Brain Barrier; Cord Blood Stem Cell Transplantation; Humans; Ischemia; Mannitol; Nerve Growth Factors; Stem Cell Transplantation; Stem Cells; Stroke
PubMed: 24480552
DOI: 10.3727/096368914X678337 -
European Journal of Clinical... Dec 2022Successful bowel preparation (BP) for colonoscopy depends on the instructions, diet, the laxative product, and patient adherence, which all affect colonoscopy quality....
BACKGROUND
Successful bowel preparation (BP) for colonoscopy depends on the instructions, diet, the laxative product, and patient adherence, which all affect colonoscopy quality. Nevertheless, there are no laxatives which combine effectiveness, safety, easy self-administration, good patient acceptance, and low cost. However, mannitol, a sugar alcohol, could be an attractive candidate for use in clinical practice if it is shown to demonstrate adequate efficacy and safety.
AIMS
The present phase II dose-finding study compared three doses of mannitol (50, 100, and 150 g) to identify the best dose to be used in a subsequent phase III study.
METHODS
The Boston Bowel Preparation Scale, caecal intubation rate, adherence, acceptability, and safety profile, including measurement of potentially dangerous colonic gas concentrations (CH, H, O), were considered in all patients. A weighted algorithm was used to identify the best mannitol dose for use in the subsequent study.
RESULTS
The per-protocol population included 60 patients in the 50 g group, 54 in the 100 g group, and 49 in the 150 g group. The 100 g dose was the best as it afforded optimal colon cleansing efficacy (94.4% of patients had adequate BP), adherence, acceptability, and safety, including negligible gas concentrations.
CONCLUSIONS
The present study demonstrated that the colon cleansing efficacy and safety of mannitol were dose dependent. Conversely, gas concentrations were not dose dependent and negligible in all patients. Combined evaluation of efficacy, tolerability, and safety, using a weighted algorithm, determined that mannitol 100 g was the best dose for the phase III study.
Topics: Humans; Cathartics; Colonoscopy; Laxatives; Mannitol; Administration, Oral
PubMed: 36287232
DOI: 10.1007/s00228-022-03405-z -
The Cochrane Database of Systematic... May 2020Several agents are used to clear secretions from the airways of people with cystic fibrosis. Mannitol increases mucociliary clearance, but its exact mechanism of action... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several agents are used to clear secretions from the airways of people with cystic fibrosis. Mannitol increases mucociliary clearance, but its exact mechanism of action is unknown. The dry powder formulation of mannitol may be more convenient and easier to use compared with established agents which require delivery via a nebuliser. Phase III trials of inhaled dry powder mannitol for the treatment of cystic fibrosis have been completed and it is now available in Australia and some countries in Europe. This is an update of a previous review.
OBJECTIVES
To assess whether inhaled dry powder mannitol is well tolerated, whether it improves the quality of life and respiratory function in people with cystic fibrosis and which adverse events are associated with the treatment.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic databases, handsearching relevant journals and abstracts from conferences. Date of last search: 12 December 2019.
SELECTION CRITERIA
All randomised controlled studies comparing mannitol with placebo, active inhaled comparators (for example, hypertonic saline or dornase alfa) or with no treatment.
DATA COLLECTION AND ANALYSIS
Authors independently assessed studies for inclusion, carried out data extraction and assessed the risk of bias in included studies. The quality of the evidence was assessed using GRADE.
MAIN RESULTS
Six studies (reported in 36 unique publications) were included with a total of 784 participants. Duration of treatment in the included studies ranged from 12 days to six months, with open-label treatment for an additional six months in two of the studies. Five studies compared mannitol with control (a very low dose of mannitol or non-respirable mannitol) and the final study compared mannitol to dornase alfa alone and to mannitol plus dornase alfa. Two large studies had a similar parallel design and provided data for 600 participants, which could be pooled where data for a particular outcome and time point were available. The remaining studies had much smaller sample sizes (ranging from 22 to 95) and data could not be pooled due to differences in design, interventions and population. Pooled evidence from the two large parallel studies was judged to be of low to moderate quality and from the smaller studies was judged to be of low to very low quality. In all studies, there was an initial test to see if participants tolerated mannitol, with only those who could tolerate the drug being randomised; therefore, the study results are not applicable to the cystic fibrosis population as a whole. While the published papers did not provide all the data required for our analysis, additional unpublished data were provided by the drug's manufacturer and the author of one of the studies. Pooling the large parallel studies comparing mannitol to control, up to and including six months, lung function (forced expiratory volume at one second) measured in both mL and % predicted was significantly improved in the mannitol group compared to the control group (moderate-quality evidence). Beneficial results were observed in these studies in adults and in both concomitant dornase alfa users and non-users in these studies. In the smaller studies, statistically significant improvements in lung function were also observed in the mannitol groups compared to the non-respirable mannitol groups; however, we judged this evidence to be of low to very low quality. For the comparisons of mannitol and control, we found no consistent differences in health-related quality of life in any of the domains except for burden of treatment, which was less for mannitol up to four months in the two pooled studies of a similar design; this difference was not maintained at six months. It should be noted that the tool used to measure health-related quality of life was not designed to assess mucolytics and pooling of the age-appropriate tools (as done in some of the included studies) may not be valid so results were judged to be low to very low quality and should be interpreted with caution. Cough, haemoptysis, bronchospasm, pharyngolaryngeal pain and post-tussive vomiting were the most commonly reported side effects in both treatment groups. Where rates of adverse events could be compared, statistically no significant differences were found between mannitol and control groups; although some of these events may have clinical relevance for people with CF. For the comparisons of mannitol to dornase alfa alone and to mannitol plus dornase alfa, very low-quality evidence from a 12-week cross-over study of 28 participants showed no statistically significant differences in the recorded domains of health-related quality of life or measures of lung function. Cough was the most common side effect in the mannitol alone arm but there was no occurrence of cough in the dornase alfa alone arm and the most commonly reported reason of withdrawal from the mannitol plus dornase alfa arm was pulmonary exacerbations. In terms of secondary outcomes of the review (pulmonary exacerbations, hospitalisations, symptoms, sputum microbiology), evidence provided by the included studies was more limited. For all comparisons, no consistent statistically significant and clinically meaningful differences were observed between mannitol and control treatments (including dornase alfa).
AUTHORS' CONCLUSIONS
There is moderate-quality evidence to show that treatment with mannitol over a six-month period is associated with an improvement in some measures of lung function in people with cystic fibrosis compared to control. There is low to very low-quality evidence suggesting no difference in quality of life for participants taking mannitol compared to control. This review provides very low-quality evidence suggesting no difference in lung function or quality of life comparing mannitol to dornase alfa alone and to mannitol plus dornase alfa. The clinical implications from this review suggest that mannitol could be considered as a treatment in cystic fibrosis; but further research is required in order to establish who may benefit most and whether this benefit is sustained in the longer term. Furthermore, studies comparing its efficacy against other (established) mucolytic therapies need to be undertaken before it can be considered for mainstream practice.
Topics: Administration, Inhalation; Adult; Child; Cystic Fibrosis; Deoxyribonuclease I; Forced Expiratory Volume; Humans; Mannitol; Mucociliary Clearance; Powders; Randomized Controlled Trials as Topic; Recombinant Proteins; Respiratory Function Tests; Vital Capacity
PubMed: 32358807
DOI: 10.1002/14651858.CD008649.pub4 -
Molecules (Basel, Switzerland) Apr 2022Media supplementation with exogenous chemicals is known to stimulate the accumulation of important lipids produced by microalgae and thraustochytrids. However, the roles...
Media supplementation with exogenous chemicals is known to stimulate the accumulation of important lipids produced by microalgae and thraustochytrids. However, the roles of exogenous chemicals in promoting and preserving the terpenoids pool of thraustochytrids have been rarely investigated. Here, we realized the effects of two media supplements-mannitol and biotin-on the biomass and squalene production by a thraustochytrid strain ( sp. ATCC 26185) and elucidated their mechanism of action. A significant change in the biomass was not evident with the exogenous addition of these supplements. However, with mannitol (1 g/L) supplementation, the ATCC 26185 culture achieved the best concentration (642 ± 13.6 mg/L) and yield (72.9 ± 9.6 mg/g) of squalene, which were 1.5-fold that of the control culture (non-supplemented). Similarly, with biotin supplementation (0.15 mg/L), the culture showed 459 ± 2.9 g/L and 55.7 ± 3.2 mg/g of squalene concentration and yield, respectively. The glucose uptake rate at 24 h of fermentation increased markedly with mannitol (0.31 g/Lh) or biotin (0.26 g/Lh) supplemented culture compared with non-supplemented culture (0.09 g/Lh). In addition, the reactive oxygen species (ROS) level of culture supplemented with mannitol remained alleviated during the entire period of fermentation while it alleviated after 24 h with biotin supplementation. The ∆ROS with mannitol was better compared with biotin supplementation. The total antioxidant capacity (T-AOC) of the supplemented culture was more than 50% during the late stage (72-96 h) of fermentation. Our study provides the potential of mannitol and biotin to enhance squalene yield and the first lines of experimental evidence for their protective role against oxidative stress during the culture of thraustochytrids.
Topics: Antioxidants; Biotin; Culture Media; Dietary Supplements; Fermentation; Glucose; Mannitol; Squalene; Stramenopiles
PubMed: 35458647
DOI: 10.3390/molecules27082449