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Frontiers in Bioengineering and... 2023The aim of this study was to investigate the influence of excipients on retaining the particle size of methotrexate (MTX) loaded chitosan nanocarriers (CsNP) during...
The aim of this study was to investigate the influence of excipients on retaining the particle size of methotrexate (MTX) loaded chitosan nanocarriers (CsNP) during lyophilization, which relates to the ability to enlarge the particle size and target specific areas. The nanocarriers were prepared using the ionic gelation technique with tripolyphosphate as a crosslinker. Three lyophilized formulations were used: nanosuspension without Lyoprotectant (NF), with mannitol (NFM), and with sucrose (NFS). The lyophilized powder intended for injection (PI) was examined to assess changes in particle size, product integrity, and comparative biodistribution studies to evaluate targeting ability. After lyophilization, NFS was excluded from studies due to the product melt-back phenomenon. The particle size of the NF lyophile significantly increased from 176 nm to 261 nm. In contrast, NFM restricted the nanocarrier size to 194 nm and exhibited excellent cake properties. FTIR, XRD, and SEM analysis revealed the transformation of mannitol into a stable β, δ polymorphic form. Biodistribution studies showed that the nanocarriers significantly increased MTX accumulation in tumor tissue (NF = 2.04 ± 0.27; NFM = 2.73 ± 0.19) compared to the marketed PI (1.45 ± 0.25 μg), but this effect was highly dependent on the particle size. Incorporating mannitol yielded positive results in restricting particle size and favoring successful tumor targeting. This study demonstrates the potential of chitosan nanocarriers as promising candidates for targeted tumor drug delivery and cancer treatment.
PubMed: 37545888
DOI: 10.3389/fbioe.2023.1222693 -
European Journal of Emergency Medicine... Aug 2024Occurrence of mydriasis during the prehospital management of traumatic brain injury (TBI) may suggest severe intracranial hypertension (ICH) subsequent to brain... (Observational Study)
Observational Study Comparative Study
BACKGROUND AND IMPORTANCE
Occurrence of mydriasis during the prehospital management of traumatic brain injury (TBI) may suggest severe intracranial hypertension (ICH) subsequent to brain herniation. The initiation of hyperosmolar therapy to reduce ICH and brain herniation is recommended. Whether mannitol or hypertonic saline solution (HSS) should be preferred is unknown.
OBJECTIVES
The objective of this study is to assess whether HSS, compared with mannitol, is associated with improved survival in adult trauma patients with TBI and mydriasis.
DESIGN/SETTING AND PARTICIPANTS
A retrospective observational cohort study using the French Traumabase national registry to compare the ICU mortality of patients receiving either HSS or mannitol. Patients aged 16 years or older with moderate to severe TBI who presented with mydriasis during prehospital management were included.
OUTCOME MEASURES AND ANALYSIS
We performed propensity score matching on a priori selected variables [i.e. age, sex and initial Coma Glasgow Scale (GCS)] with a ratio of 1 : 3 to ensure comparability between the two groups. The primary outcome was ICU mortality. The secondary outcomes were regression of pupillary abnormality during prehospital management, pulsatility index and diastolic velocity on transcranial Doppler within 24 h after TBI, early ICU mortality (within 48 h), ICU and hospital length of stay.
RESULTS
Of 31 579 patients recorded in the registry between 2011 and 2021, 1417 presented with prehospital mydriasis and were included: 1172 (82.7%) received mannitol and 245 (17.3%) received HSS. After propensity score matching, 720 in the mannitol group matched 240 patients in the HSS group. Median age was 41 years [interquartile ranges (IQR) 26-60], 1058 were men (73%) and median GCS was 4 (IQR 3-6). No significant difference was observed in terms of characteristics and prehospital management between the two groups. ICU mortality was lower in the HSS group (45%) than in the mannitol group (54%) after matching [odds ratio (OR) 0.68 (0.5-0.9), P = 0.014]. No differences were identified between the groups in terms of secondary outcomes.
CONCLUSION
In this propensity-matched observational study, the prehospital osmotherapy with HSS in TBI patients with prehospital mydriasis was associated with a lower ICU mortality compared to osmotherapy with mannitol.
Topics: Humans; Mannitol; Saline Solution, Hypertonic; Brain Injuries, Traumatic; Female; Male; Retrospective Studies; Middle Aged; Adult; Emergency Medical Services; France; Glasgow Coma Scale; Registries; Propensity Score; Cohort Studies; Intracranial Hypertension; Aged; Diuretics, Osmotic
PubMed: 38691014
DOI: 10.1097/MEJ.0000000000001138 -
Fungal Biology and Biotechnology Nov 2023Asexually developed fungal spores (conidia) are key for the massive proliferation and dispersal of filamentous fungi. Germination of conidia and subsequent formation of...
BACKGROUND
Asexually developed fungal spores (conidia) are key for the massive proliferation and dispersal of filamentous fungi. Germination of conidia and subsequent formation of a mycelium network give rise to many societal problems related to human and animal fungal diseases, post-harvest food spoilage, loss of harvest caused by plant-pathogenic fungi and moulding of buildings. Conidia are highly stress resistant compared to the vegetative mycelium and therefore even more difficult to tackle.
RESULTS
In this study, complementary approaches are used to show that accumulation of mannitol and trehalose as the main compatible solutes during spore maturation is a key factor for heat resistance of conidia. Compatible solute concentrations increase during conidia maturation, correlating with increased heat resistance of mature conidia. This maturation only occurs when conidia are attached to the conidiophore. Moreover, conidia of a mutant Aspergillus niger strain, constructed by deleting genes involved in mannitol and trehalose synthesis and consequently containing low concentrations of these compatible solutes, exhibit a sixteen orders of magnitude more sensitive heat shock phenotype compared to wild-type conidia. Cultivation at elevated temperature results in adaptation of conidia with increased heat resistance. Transcriptomic and proteomic analyses revealed two putative heat shock proteins to be upregulated under these conditions. However, conidia of knock-out strains lacking these putative heat shock proteins did not show a reduced heat resistance.
CONCLUSIONS
Heat stress resistance of fungal conidia is mainly determined by the compatible solute composition established during conidia maturation. To prevent heat resistant fungal spore contaminants, food processing protocols should consider environmental conditions stimulating compatible solute accumulation and potentially use compatible solute biosynthesis as a novel food preservation target.
PubMed: 37957766
DOI: 10.1186/s40694-023-00168-9 -
Infectious Diseases (London, England) Jun 2024This study details the accumulated experience of more than 31 years using a low-dose systematic dexamethasone protocol with mannitol and antiseizure prophylaxis for...
OBJECTIVES
This study details the accumulated experience of more than 31 years using a low-dose systematic dexamethasone protocol with mannitol and antiseizure prophylaxis for the treatment of suspected pneumococcal meningitis.
METHODS
Data have been prospectively collected for the period1977-2018. From 1987, patients with suspected pneumococcal meningitis received 12 mg dexamethasone followed by 4 mg/6 h for 48 h, started before or with the first antibiotic dose. They also received (1) a single intravenous dose of 0.5-1 g/Kg mannitol, and (2) antiseizure prophylaxis with phenytoin.
RESULTS
In total, 363 episodes of pneumococcal meningitis were recorded. Of these, 242 were treated with the dexamethasone protocol after 1987 and 121 were treated without the protocol. Overall mortality was 11.6% (28/242) among patients treated with dexamethasone and 35% (43/121) among those treated without dexamethasone ( = 0.000). Early mortality was significantly lower at 5.8% (14/242) with dexamethasone and 24% (29/121) without dexamethasone ( = 0.000). Finally, neurological mortality was significantly lower at 7.4% (18/242) with dexamethasone and 23% (28/121) without dexamethasone ( = 0.000).
CONCLUSIONS
A low dose of dexamethasone along with a single dose of mannitol and antiseizures prophylaxis might be useful for reducing both overall and early mortality in pneumococcal meningitis in adult patients.
PubMed: 38922314
DOI: 10.1080/23744235.2024.2370967 -
American Journal of Ophthalmology Case... Mar 2024This case report presents an event of retrobulbar hemorrhage (RH) occurring during the initial stage of strabismus surgery after incision of the conjunctiva and Tenon's...
PURPOSE
This case report presents an event of retrobulbar hemorrhage (RH) occurring during the initial stage of strabismus surgery after incision of the conjunctiva and Tenon's capsule.
OBSERVATION
Significant bleeding with subsequent proptosis was observed intraoperatively after the incision of conjunctiva and Tenon's capsule during routine strabismus surgery on the medial rectus muscle in a 5-year-old boy. Intravenous mannitol was administered intraoperatively and surgery was completed as planned. The RH receded within 24 hours without the necessity of orbital decompression. Tenon's capsule prolapse was noted on the first postoperative day and managed with surgical excision under shallow intravenous anesthesia. No damage to the optic nerve or ganglion cells was detected a week after and three months post-surgery.
CONCLUSIONS AND IMPORTANCE
Strabismus surgery bears a risk of RH at every stage of the operation. Careful hemostasis should be provided at each step of the procedure to decrease the risk of such an event. Patients after events of serious intraoperative bleeding should undergo careful post-operative investigation towards coagulation insufficiencies, though no such deficits were identified in the present case.
PubMed: 38292880
DOI: 10.1016/j.ajoc.2024.101991 -
Chinese Journal of Traumatology =... Jan 2024Mannitol is one of the first-line drugs for reducing cerebral edema through increasing the extracellular osmotic pressure. However, long-term administration of mannitol...
PURPOSE
Mannitol is one of the first-line drugs for reducing cerebral edema through increasing the extracellular osmotic pressure. However, long-term administration of mannitol in the treatment of cerebral edema triggers damage to neurons and astrocytes. Given that neural stem cell (NSC) is a subpopulation of main regenerative cells in the central nervous system after injury, the effect of mannitol on NSC is still elusive. The present study aims to elucidate the role of mannitol in NSC proliferation.
METHODS
C57 mice were derived from the animal house of Zunyi Medical University. A total of 15 pregnant mice were employed for the purpose of isolating NSCs in this investigation. Initially, mouse primary NSCs were isolated from the embryonic cortex of mice and subsequently identified through immunofluorescence staining. In order to investigate the impact of mannitol on NSC proliferation, both cell counting kit-8 assays and neurospheres formation assays were conducted. The in vitro effects of mannitol were examined at various doses and time points. In order to elucidate the role of Aquaporin 4 (AQP4) in the suppressive effect of mannitol on NSC proliferation, various assays including reverse transcription polymerase chain reaction, western blotting, and immunocytochemistry were conducted on control and mannitol-treated groups. Additionally, the phosphorylated p38 (p-p38) was examined to explore the potential mechanism underlying the inhibitory effect of mannitol on NSC proliferation. Finally, to further confirm the involvement of the p38 mitogen-activated protein kinase-dependent (MAPK) signaling pathway in the observed inhibition of NSC proliferation by mannitol, SB203580 was employed. All data were analyzed using SPSS 20.0 software (SPSS, Inc., Chicago, IL). The statistical analysis among multiple comparisons was performed using one-way analysis of variance (ANOVA), followed by Turkey's post hoc test in case of the data following a normal distribution using a Shapiro-Wilk normality test. Comparisons between 2 groups were determined using Student's t-test, if the data exhibited a normal distribution using a Shapiro-Wilk normality test. Meanwhile, data were shown as median and interquartile range and analyzed using the Mann-Whitney U test, if the data failed the normality test. A p < 0.05 was considered as significant difference.
RESULTS
Primary NSC were isolated from the mice, and the characteristics were identified using immunostaining analysis. Thereafter, the results indicated that mannitol held the capability of inhibiting NSC proliferation in a dose-dependent and time-dependent manner using cell counting kit-8, neurospheres formation, and immunostaining of Nestin and Ki67 assays. During the process of mannitol suppressing NSC proliferation, the expression of AQP4 mRNA and protein was downregulated, while the gene expression of p-p38 was elevated by reverse transcription polymerase chain reaction, immunostaining, and western blotting assays. Subsequently, the administration of SB203580, one of the p38 MAPK signaling pathway inhibitors, partially abrogated this inhibitory effect resulting from mannitol, supporting the fact that the p38 MAPK signaling pathway participated in curbing NSC proliferation induced by mannitol.
CONCLUSIONS
Mannitol inhibits NSC proliferation through downregulating AQP4, while upregulating the expression of p-p38 MAPK.
Topics: Humans; Animals; Mannitol; Brain Edema; Neural Stem Cells; MAP Kinase Signaling System; p38 Mitogen-Activated Protein Kinases; Cell Proliferation
PubMed: 37953130
DOI: 10.1016/j.cjtee.2023.10.004 -
Scientific Reports May 2024Cisplatin (CDDP)-induced nephrotoxicity is a common dose-limiting toxicity, and diuretics are often administered to prevent nephrotoxicity. However, the efficacy and... (Observational Study)
Observational Study Comparative Study
Cisplatin (CDDP)-induced nephrotoxicity is a common dose-limiting toxicity, and diuretics are often administered to prevent nephrotoxicity. However, the efficacy and optimal administration of diuretics in preventing CDDP-induced nephrotoxicity remain to be established. This study aimed to evaluate the efficacy of combining furosemide and mannitol to prevent CDDP-induced nephrotoxicity. This was a post-hoc analysis of pooled data from a multicenter, retrospective, observational study, including 396 patients who received one or two diuretics for CDDP-based chemotherapy, compared using propensity score matching. Multivariate logistic regression analyses were used to identify risk factors for nephrotoxicity. There was no significant difference in the incidence of nephrotoxicity between the two groups (22.2% vs. 28.3%, P = 0.416). Hypertension, CDDP dose ≥ 75 mg/m, and no magnesium supplementation were identified as risk factors for nephrotoxicity, whereas the use of diuretics was not found to be a risk factor. The combination of furosemide and mannitol showed no advantage over a single diuretic in preventing CDDP-induced nephrotoxicity. The renal function of patients receiving CDDP-based chemotherapy (≥ 75 mg/m) and that of those with hypertension should be carefully monitored. Magnesium supplementation is important for these patients.
Topics: Furosemide; Cisplatin; Humans; Mannitol; Male; Female; Diuretics; Middle Aged; Retrospective Studies; Aged; Risk Factors; Kidney Diseases; Drug Therapy, Combination; Antineoplastic Agents; Adult
PubMed: 38714773
DOI: 10.1038/s41598-024-61245-6 -
Journal of Neurosciences in Rural... 2023Polyuria is urine output exceeding 3 L/d in adults, primarily due to solute and water diuresis. In a hospital setting, mannitol and diuretics commonly lead to polyuria....
Polyuria is urine output exceeding 3 L/d in adults, primarily due to solute and water diuresis. In a hospital setting, mannitol and diuretics commonly lead to polyuria. We have found an interesting association of polyuria with glycopyrrolate; to the best of our knowledge, no case is reported in the literature. Here, we are describing a case of Guillain-Barre Syndrome, which developed polyuria during the hospital stay, which was secondary to glycopyrrolate.
PubMed: 37692823
DOI: 10.25259/JNRP_73_2023 -
Neurotoxicology Jul 2023Current guidelines for developmental neurotoxicity (DNT) evaluation are based on animal models. These have limitations so more relevant, efficient and robust approaches...
Current guidelines for developmental neurotoxicity (DNT) evaluation are based on animal models. These have limitations so more relevant, efficient and robust approaches for DNT assessment are needed. We have used the human SH-SY5Y neuroblastoma cell model to evaluate a panel of 93 mRNA markers that are frequent in Neuronal diseases and functional annotations and also differentially expressed during retinoic acid-induced differentiation in the cell model. Rotenone, valproic acid (VPA), acrylamide (ACR) and methylmercury chloride (MeHg) were used as DNT positive compounds. Tolbutamide, D-mannitol and clofibrate were used as DNT negative compounds. To determine concentrations for exposure for gene expression analysis, we developed a pipeline for neurite outgrowth assessment by live-cell imaging. In addition, cell viability was measured by the resazurin assay. Gene expression was analyzed by RT-qPCR after 6 days of exposure during differentiation to concentrations of the DNT positive compounds that affected neurite outgrowth, but with no or minimal effect on cell viability. Methylmercury affected cell viability at lower concentrations than neurite outgrowth, hence the cells were exposed with the highest non-cytotoxic concentration. Rotenone (7.3 nM) induced 32 differentially expressed genes (DEGs), ACR (70 µM) 8 DEGs, and VPA (75 µM) 16 DEGs. No individual genes were significantly dysregulated by all 3 DNT positive compounds (p < 0.05), but 9 genes were differentially expressed by 2 of them. Methylmercury (0.8 nM) was used to validate the 9 DEGs. The expression of SEMA5A (encoding semaphorin 5A) and CHRNA7 (encoding nicotinic acetylcholine receptor subunit α7) was downregulated by all 4 DNT positive compounds. None of the DNT negative compounds dysregulated any of the 9 DEGs in common for the DNT positive compounds. We suggest that SEMA5A or CHRNA7 should be further evaluated as biomarkers for DNT studies in vitro since they also are involved in neurodevelopmental adverse outcomes in humans.
Topics: Animals; Humans; Methylmercury Compounds; Rotenone; RNA, Messenger; Neuroblastoma; Neurons; Neurotoxicity Syndromes; Cell Differentiation
PubMed: 37210002
DOI: 10.1016/j.neuro.2023.05.011 -
NPJ Science of Food Sep 2023Successful sucrose replacement in cake systems requires thorough understanding of its functionality. Time-domain H NMR showed that water in the viscous aqueous phase...
Successful sucrose replacement in cake systems requires thorough understanding of its functionality. Time-domain H NMR showed that water in the viscous aqueous phase isolated from cake batter by ultracentrifugation [i.e. the batter liquor (BL)] exhibits low mobility by its low T relaxation time (T RT). This is due to its interactions with sucrose or sucrose replacers. The T RT itself is positively related with the effective volumetric hydrogen bond density of sucrose or sucrose replacers. Sucrose additionally co-determines the quantity and viscosity of cake BL and thereby how much air the batter contains at the end of mixing. Like sucrose, maltitol and oligofructose provide adequate volumes of BL with low water mobility and thus sufficient air in the batter, while the rather insoluble mannitol and inulin do not. Differential scanning calorimetry and rapid viscosity analysis revealed, however, that, in contrast to sucrose and maltitol, oligofructose fails to provide appropriate timings of starch gelatinisation and protein denaturation, resulting in poor cake texture. The shortcomings of mannitol and oligofructose in terms of respectively ensuring appropriate gas content in batter and biopolymer transitions during baking can be overcome by using mixtures thereof. This work shows that successful sucrose substitutes or substitute mixtures must provide sufficient BL with low water mobility and ensure appropriate timings of starch and protein biopolymer transitions during baking.
PubMed: 37758781
DOI: 10.1038/s41538-023-00225-y