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Journal of Bacteriology Mar 1969Pathways of mannitol biosynthesis and utilization in Aspergillus candidus NRRL 305 were studied in cell-free extracts of washed mycelia prepared by sonic and French...
Pathways of mannitol biosynthesis and utilization in Aspergillus candidus NRRL 305 were studied in cell-free extracts of washed mycelia prepared by sonic and French pressure cell treatments. A nicotinamide adenine dinucleotide-linked mannitol-1-phosphate (M1P) dehydrogenase was found in French pressure cell extracts of d-glucose-grown cells, whereas a specific mannitol-1-phosphatase was present in extracts prepared by both methods. The existence of these two enzymes indicated that mannitol may be synthesized in this organism by the reduction of fructose-6-phosphate. A specific nicotinamide adenine dinucleotide phosphate-linked mannitol dehydrogenase was also identified in both extracts. This enzyme may have been involved in mannitol utilization. However, the level of the mannitol dehydrogenase appeared to be substantially reduced in extracts from mannitol-grown cells, whereas the level of M1P dehydrogenase was increased. A hexokinase has been identified in this organism. Fructose-6-phosphatase, glucose isomerase, and mannitol kinase could not be demonstrated.
Topics: Alcohol Oxidoreductases; Aspergillus; Cell-Free System; Hexokinase; Mannitol; Mannitol Dehydrogenases; NAD; Phosphoric Monoester Hydrolases
PubMed: 4304850
DOI: 10.1128/jb.97.3.1305-1309.1969 -
Biology Open Jan 2020The ability of polyols to disrupt holometabolous insect development has not been studied and identifying compounds in food that affect insect development can further our...
The ability of polyols to disrupt holometabolous insect development has not been studied and identifying compounds in food that affect insect development can further our understanding of the pathways that connect growth rate, developmental timing and body size in insects. High-sugar diets prolong development and generate smaller adult body sizes in We tested for concentration-dependent effects on development when larvae are fed mannitol, a polyalcohol sweetener. We also tested for amelioration of developmental effects if introduction to mannitol media is delayed past the third instar, as expected if there is a developmental sensitive-period for mannitol effects. Both male and female larvae had prolonged development and smaller adult body sizes when fed increasing concentrations of mannitol. Mannitol-induced increases in mortality were concentration dependent in 0 M to 0.8 M treatments with mortality effects beginning as early as 48 h post-hatching. Larval survival, pupariation and eclosion times were unaffected in 0.4 M mannitol treatments when larvae were first introduced to mannitol 72 h post-hatching (the beginning of the third instar); 72 h delay of 0.8 M mannitol introduction reduced the adverse mannitol effects. The developmental effects of a larval mannitol diet closely resemble those of high-sugar larval diets.This article has an associated First Person interview with the first author of the paper.
Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Body Size; Disease Susceptibility; Drosophila melanogaster; Female; Larva; Longevity; Male; Mannitol
PubMed: 31822472
DOI: 10.1242/bio.047084 -
JCO Global Oncology Mar 2022Nephrotoxicity is a major dose-limiting toxicity among patients with cancer who were treated with cisplatin. Although no standard approach is available to prevent... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Nephrotoxicity is a major dose-limiting toxicity among patients with cancer who were treated with cisplatin. Although no standard approach is available to prevent cisplatin-induced nephrotoxicity, administering intravenous isotonic saline is recommended. Additionally, mannitol combined with hydration has been evaluated, but none of them have been established. Our study aimed to determine the efficacy of mannitol combined hydration to prevent cisplatin-induced nephrotoxicity.
PATIENTS AND METHODS
This study was a phase II, randomized, placebo-controlled design. All patients with solid cancers who were treated with cisplatin (n = 48) were randomly assigned to receive either placebo (n = 25) or 20 g of mannitol (n = 23) after completing 2 L of prehydration and receiving cisplatin. Serum creatinine, blood urea nitrogen, electrolyte, and glomerular filtration rate (GFR) were measured at baseline and days 2 and 7. Moreover, GFR was calculated based on the 24-hour urine creatinine clearance rate to assess renal function at baseline and 48 hours after receiving cisplatin. Severity of nausea and vomiting was evaluated using Common Terminology Criteria for Adverse Events.
RESULTS
No difference was found regarding baseline characteristics between the two groups. Seven of 23 patients (37.4%) in the mannitol group and 10 of 25 patients (40%) in the placebo group increased serum creatinine level ≥ 0.3 mg/dL at 48 hours after intervention ( value = .48). Patients receiving mannitol exhibited significantly lower incidence of 24-hour urine GFR below 60 mL/min/1.73 m than those in the placebo group (13.6% 48.0% in the placebo group; value = .012). Univariate analysis showed the greatest benefit for administering mannitol among patients receiving cisplatin > 80 mg/m, or patients receiving concomitant radiation.
CONCLUSION
Mannitol combined with hydration significantly prevented cisplatin-induced nephrotoxicity. Additionally, mannitol should be particularly considered among patients with cancer, treated with cisplatin > 80 mg/m, or patients receiving concomitant radiation.
Topics: Antineoplastic Agents; Cisplatin; Creatinine; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Kidney Diseases; Male; Mannitol; Neoplasms; Saline Solution
PubMed: 35436142
DOI: 10.1200/GO.21.00275 -
BMC Veterinary Research Mar 2024The aim of the present study was to examine donkey sperm quality after intratesticular injection of hypertonic mannitol (HM) and saline (HS).
OBJECTIVES
The aim of the present study was to examine donkey sperm quality after intratesticular injection of hypertonic mannitol (HM) and saline (HS).
METHODS
Randomly assigned to five treatment groups were 15 adult male donkeys: (1) Control group (no treatment), (2) Surgery group (surgical castration for testosterone control), (3) NS group (normal saline intratesticular injection), (4) HS group (hypertonic saline), and (5) HM group. We injected 20 mL per testicle. We took 5 mL blood from all donkeys before injection. Castration was performed under general anesthesia 60 days later. Samples included blood and testicular tissue. Total motility (TM), progressive motility (PM), movementy features, DNA damage, morphology, viability, and plasma membrane functionality were evaluated. Hormone analyses, histomorphometric studies and oxidative stress indices including total antioxidant capacity (TAC), glutathione peroxidase (GPx), glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and NADP+/NADPH were evaluated. Apoptosis, pyroptosis-related Bax, Caspase-1, GSDMD, and Bcl-2 expression were also assessed.
RESULTS
In HS and HM groups, testosterone, epididymal sperm count, motility, viability, and plasma membrane functionality dropped while sperm DNA damage increased. HS and HM groups had significantly lower histomorphometric parameters, TAC, GPx, SOD, GSH, and Bcl-2 gene expression. MDA, NADP/NADPH, Bax, Caspase-1, and GSDMD gene expression were substantially higher in the HS and HM groups than in the control group.
CONCLUSIONS
Toxic effects of hypertonic saline and mannitol on reproductive parameters were seen following, hence, they might be considered as a good chemical sterilizing treatment in donkeys.
Topics: Animals; Male; Antioxidants; bcl-2-Associated X Protein; Caspases; Mannitol; NADP; Oxidative Stress; Saline Solution; Semen; Spermatozoa; Superoxide Dismutase; Testis; Testosterone
PubMed: 38468237
DOI: 10.1186/s12917-024-03915-1 -
Neurocritical Care Apr 2022Performing a cerebrospinal fluid (CSF) drainage challenge can be used to measure the pressure equalization (PE) ratio, which describes the extent to which CSF drainage...
Improved Pressure Equalization Ratio Following Mannitol Administration in Patients With Severe TBI: A Preliminary Study of a Potential Bedside Marker for Response to Therapy.
BACKGROUND
Performing a cerebrospinal fluid (CSF) drainage challenge can be used to measure the pressure equalization (PE) ratio, which describes the extent to which CSF drainage can equalize pressure to the height of the external ventricular drain and may serve as a correlate of cerebral edema. We sought to assess whether treatment with mannitol improves PE ratio in patients with severe traumatic brain injury (TBI) with elevated intracranial pressure (ICP).
METHODS
We studied consecutive patients with TBI and brain edema on computed tomography scan and an external ventricular drain (EVD), admitted to the neurointensive care unit. PE ratio, defined as ICP prior to CSF drainage minus ICP after CSF drainage divided by ICP prior to CSF drainage minus EVD height, was measured as previously described. Patients were treated with mannitol for raised ICP based on clinical indication and PE ratio measured before and after mannitol administration.
RESULTS
We studied 20 patients with severe TBI with raised ICP. Mean ICP prior to mannitol treatment was 29 ± 7 mm Hg. PE ratio rose substantially after mannitol treatment (0.62 ± 0.24 vs. 0.29 ± 0.20, p < 0.0001), indicating an improved ability to drain CSF and equalize ICP with the preset height of the EVD. The combination of mannitol and CSF drainage led to an improved reduction in ICP compared with that seen before mannitol therapy (11 ± 2 mm Hg vs. 6 ± 2 mm Hg, p < 0.01), and led to a decrease in ICP below the 20 mm Hg threshold in 77% of cases.
CONCLUSIONS
Treatment with mannitol leads to a substantial improvement in PE ratio that reflects the ability to achieve a greater decrease in ICP when CSF drainage is performed after mannitol administration. This preliminary study raises the possibility that PE ratio may be useful to follow response to therapy in patients with cerebral edema and raised ICP. Further studies to determine whether PE ratio may serve as an easily obtained and clinically useful surrogate marker for the extent of brain edema are warranted.
Topics: Biomarkers; Brain Edema; Brain Injuries, Traumatic; Drainage; Humans; Intracranial Hypertension; Intracranial Pressure; Mannitol
PubMed: 34498204
DOI: 10.1007/s12028-021-01332-y -
European Radiology Aug 2022To compare the distention quality and patient experience of oral mannitol and polyethylene glycol (PEG) for MRE. (Observational Study)
Observational Study
Influence of oral contrast type and volume on patient experience and quality of luminal distension at MR Enterography in Crohn's disease: an observational study of patients recruited to the METRIC trial.
OBJECTIVES
To compare the distention quality and patient experience of oral mannitol and polyethylene glycol (PEG) for MRE.
METHODS
This study is a retrospective, observational study of a subset of patients enrolled in a multicentre, prospective trial evaluating the diagnostic accuracy of MRE for small bowel Crohn's. Overall and segmental MRE small bowel distention, from 105 patients (64 F, mean age 37) was scored from 0 = poor to 4 = excellent by two experienced observers (68 [65%] mannitol and 37 [35%] PEG). Additionally, 130 patients (77 F, mean age 34) completed a questionnaire rating tolerability of various symptoms immediately and 2 days after MRE (85 [65%] receiving mannitol 45 [35%] receiving PEG). Distension was compared between agents and between those ingesting ≤ 1 L or > 1 L of mannitol using the test of proportions. Tolerability grades were collapsed into "very tolerable," "moderately tolerable," and "not tolerable."
RESULTS
Per patient distension quality was similar between agents ("excellent" or "good" in 54% [37/68] versus 46% [17/37]) with mannitol and PEG respectively. Jejunal distension was significantly better with mannitol compared to PEG (40% [27/68] versus 14% [5/37] rated as excellent or good respectively). There was no significant difference according to the volume of mannitol ingested. Symptom tolerability was comparable between agents, although fullness following MRE was graded as "very tolerable" in 27% (12/45) of patients ingesting PEG, verses 44% (37/84) ingesting mannitol, difference 17% (95% CI 0.6 to 34%).
CONCLUSION
Mannitol-based solutions and PEG generally achieve comparable distension quality and side effect profiles, although jejunal distension is better quality with mannitol. Neither distension quality nor side-effect profile is altered by ingestion of more than 1 L of mannitol.
KEY POINTS
• Mannitol-based and PEG-based oral preparation agents generally achieve comparable distension quality for MRE with the exception of the jejunum which is better distended with mannitol. • Mannitol-based and PEG-based oral preparation agents used for MRE have similar side effect profiles. • Neither distension quality nor side-effect profile is altered by ingestion of more than 1 L of mannitol.
Topics: Adult; Contrast Media; Crohn Disease; Drug-Related Side Effects and Adverse Reactions; Humans; Magnetic Resonance Imaging; Mannitol; Patient Outcome Assessment; Polyethylene Glycols; Prospective Studies; Retrospective Studies
PubMed: 35243523
DOI: 10.1007/s00330-022-08614-9 -
Anesthesiology Feb 2002Mannitol and furosemide are used to reduce increased intracranial pressure (ICP) and to reduce brain bulk during neurosurgery. One mechanism by which these changes might...
BACKGROUND
Mannitol and furosemide are used to reduce increased intracranial pressure (ICP) and to reduce brain bulk during neurosurgery. One mechanism by which these changes might occur is via a reduction in brain water content. Although mannitol and furosemide are commonly used in combination, there has been no formal evaluation of the interactive effects of these two drugs on brain water. The effect of mannitol and furosemide alone and in combination on water content of normal rat brain was examined.
METHODS
The lungs of rats anesthetized with halothane were mechanically ventilated to maintain normal physiologic parameters. After baseline measurement of plasma osmolality, mannitol (1, 4, or 8 g/kg), furosemide (2, 4, or 8 mg/kg), or a combination of furosemide (8 mg/kg) and mannitol (1, 4, or 8 g/kg) was administered intravenously over approximately 15 min. One hour later, plasma osmolality was measured, the animals were killed, and brain water content was determined by wet and dry weight measurements.
RESULTS
Mannitol produced a dose-dependent increase in plasma osmolality and reduction of brain water content. There was a linear relation between plasma osmolality and brain water content. Furosemide alone did not affect plasma osmolality or brain water at any dose. The combination of furosemide with mannitol resulted in a greater increase in plasma osmolality than seen with mannitol alone and a greater decrease in brain water at 4 and 8 g/kg of mannitol.
CONCLUSIONS
The doses of mannitol and furosemide utilized were much larger than clinically applicable doses and were selected to maximize the ability to detect effect on brain water. The combination of mannitol and furosemide resulted in greater reduction of brain water content than did mannitol alone. Furosemide enhanced the effect of mannitol on plasma osmolality, resulting in a greater reduction of brain water content. Potential interaction (if any) of smaller, clinically used doses of mannitol and furosemide cannot be surmised from the current study.
Topics: Animals; Body Water; Brain Chemistry; Diuretics; Diuretics, Osmotic; Dose-Response Relationship, Drug; Drug Interactions; Furosemide; Male; Mannitol; Osmolar Concentration; Rats; Rats, Sprague-Dawley; Regression Analysis
PubMed: 11818776
DOI: 10.1097/00000542-200202000-00029 -
Critical Care Medicine Jan 2012To describe patterns of use for mannitol and hypertonic saline in children with traumatic brain injury, to evaluate any potential associations between hypertonic saline...
OBJECTIVES
To describe patterns of use for mannitol and hypertonic saline in children with traumatic brain injury, to evaluate any potential associations between hypertonic saline and mannitol use and patient demographic, injury, and treatment hospital characteristics, and to determine whether the 2003 guidelines for severe pediatric traumatic brain injury impacted clinical practice regarding osmolar therapy.
DESIGN
Retrospective cohort study.
SETTING
Pediatric Health Information System database, January, 2001 to December, 2008.
PATIENTS
Children (age <18 yrs) with traumatic brain injury and head/neck Abbreviated Injury Scale score ≥ 3 who received mechanical ventilation and intensive care.
INTERVENTIONS
: None.
MEASUREMENTS AND MAIN RESULTS
The primary outcome was hospital billing for parenteral hypertonic saline and mannitol use, by day of service. Overall, 33% (2,069 of 6,238) of the patients received hypertonic saline, and 40% (2,500 of 6,238) received mannitol. Of the 1,854 patients who received hypertonic saline or mannitol for ≥ 2 days in the first week of therapy, 29% did not have intracranial pressure monitoring. After adjustment for hospital-level variation, primary insurance payer, and overall injury severity, use of both drugs was independently associated with older patient age, intracranial hemorrhage (other than epidural), skull fracture, and higher head/neck injury severity. Hypertonic saline use increased and mannitol use decreased with publication of the 2003 guidelines, and these trends continued through 2008.
CONCLUSIONS
Hypertonic saline and mannitol are used less in infants than in older children. The patient-level and hospital-level variation in osmolar therapy use and the substantial amount of sustained osmolar therapy without intracranial pressure monitoring suggest opportunities to improve the quality of pediatric traumatic brain injury care. With limited high-quality evidence available, published expert guidelines appear to significantly impact clinical practice in this area.
Topics: Adolescent; Age Factors; Brain Injuries; Child; Child, Preschool; Female; Fluid Therapy; Humans; Infant; Infant, Newborn; Injury Severity Score; Intracranial Pressure; Male; Mannitol; Retrospective Studies; Saline Solution, Hypertonic; Treatment Outcome
PubMed: 21926592
DOI: 10.1097/CCM.0b013e31822e9d31 -
Human Vaccines & Immunotherapeutics 2016Montanide ISA™51 (ISA 51) is a vaccine adjuvant which has been tested in therapeutic and prophylactic vaccine trials. The aim of this review is to present a... (Review)
Review
Montanide ISA™51 (ISA 51) is a vaccine adjuvant which has been tested in therapeutic and prophylactic vaccine trials. The aim of this review is to present a comprehensive examination of the safety and tolerability of ISA 51 containing vaccines. A systematic literature search was conducted in PubMed, EMBASE and clinicaltrials.gov . Eligible studies were categorized into: (A) uncontrolled studies with non-healthy subjects, (B) controlled studies with non-healthy subjects, and (C) controlled studies with healthy subjects. Reported adverse events (AEs) were assessed. 91 studies were included in our review. Generally observed AEs included injection site reaction; injection site pain; myalgia; headache; gastro-intestinal disorders; fatigue and fever - regardless of the administration route and subject characteristic. Specific AEs, e.g. injection site reactions and rash, were more frequently reported from subjects receiving ISA 51-adjuvanted vaccines than from subjects receiving antigen or ISA 51 only. The reported AEs were mainly mild to moderate in intensity. Serious AEs (SAEs) were reported in 27% of the uncontrolled trials and 2 trials conducted with healthy subjects. Notably, 2 other trials conducted with healthy subjects were stopped due to unacceptable AEs. Some studies indicate that the mixing procedure of antigen and adjuvant might influence the occurrence of AEs. Reports on SAEs and premature termination of 2 trials advise caution when using ISA 51. Yet, AEs might be preventable by proper mixing of vaccine and adjuvant to a stable emulsion. Trials including an active control group are needed for a fair evaluation of adjuvant safety.
Topics: Adjuvants, Immunologic; Drug-Related Side Effects and Adverse Reactions; Fatigue; Fever; Gastrointestinal Diseases; Headache; Humans; Mannitol; Oleic Acids; Pain; Skin Diseases; Vaccines
PubMed: 26378866
DOI: 10.1080/21645515.2015.1071455 -
American Journal of Kidney Diseases :... Oct 2019Intradialytic hypotension (IDH) is a common complication at the initiation of hemodialysis (HD) therapy, is associated with greater mortality, and may be related to... (Randomized Controlled Trial)
Randomized Controlled Trial
RATIONALE & OBJECTIVE
Intradialytic hypotension (IDH) is a common complication at the initiation of hemodialysis (HD) therapy, is associated with greater mortality, and may be related to relatively rapid shifts in plasma osmolality. This study sought to evaluate the effect of an intervention to minimize intradialytic changes in plasma osmolality on the occurrence of IDH.
STUDY DESIGN
Double-blind, single-center, randomized, controlled trial.
SETTING & PARTICIPANTS
Individuals requiring initiation of HD for acute or chronic kidney disease.
INTERVENTION
Mannitol, 0.25g/kg/h, versus a similar volume of 0.9% saline solution during the first 3 HD sessions.
OUTCOMES
The primary end point was average decline in systolic blood pressure (SBP). The secondary end point was the proportion of total sessions complicated by IDH (defined as a decrease ≥ 20mm Hg from the pre-HD SBP). Exploratory end points included biomarkers of cardiac and kidney injury.
RESULTS
52 patients were randomly assigned and contributed to 156 study visits. There were no significant differences in average SBP decline between the mannitol and placebo groups (15±11 vs 19±16mm Hg; P = 0.3). The proportion of total sessions complicated by IDH was lower in the mannitol group compared to placebo (25% vs 43%), with a nominally lower risk for developing an episode of IDH (OR, 0.38; 95% CI, 0.14-1.00), though this finding was of borderline statistical significance (P = 0.05). There were no consistent differences in cardiac and kidney injury biomarker levels between treatment groups.
LIMITATIONS
Modest sample size and number of events.
CONCLUSIONS
In this pilot randomized controlled trial studying patients requiring initiation of HD, we found no difference in absolute SBP decline between those who received mannitol and those who received saline solution. However, there were fewer overall IDH events and a nominally lower risk for dialysis sessions being complicated by IDH in the mannitol group. A larger multicenter randomized controlled trial is warranted.
FUNDING
Government funding to an author (Dr Mc Causland is supported by National Institute of Diabetes and Digestive and Kidney Diseases grant K23DK102511).
TRIAL REGISTRATION
Registered at ClinicalTrials.gov with study number NCT01520207.
Topics: Adult; Aged; Diuretics, Osmotic; Double-Blind Method; Female; Humans; Hypertonic Solutions; Hypotension; Kidney Failure, Chronic; Male; Mannitol; Middle Aged; Pilot Projects; Renal Dialysis
PubMed: 31040088
DOI: 10.1053/j.ajkd.2019.03.415