Xylitol fermentation characteristics with a newly isolated yeast Wickerhamomyces anomalus WA.

Xylitol is an increasingly popular functional food additive, and the newly isolated yeast Wickerhamomyces anomalus WA has shown extensive substrate utilization capability, with the ability to grow on hexose (d-galactose, d-glucose, d-mannose, l-fructose, and d-sorbose) and pentose (d-xylose and l-arabinose) substrates, as well as high tolerance to xylose at concentrations of up to 300 g/L. Optimal xylitol fermentation conditions were achieved at 32 °C, 140 rpm, pH 5.0, and initial cell concentration OD600 of 2.0, with YP (yeast extract 10 g/L, peptone 20 g/L) as the optimal nitrogen source. Xylitol yield increased from 0.61 g/g to 0.91 g/g with an increase in initial substrate concentration from 20 g/L to 180 g/L. Additionally, 20 g/L glycerol was found to be the optimal co-substrate for xylitol fermentation, resulting in an increase in xylitol yield from 0.82 g/g to 0.94 g/g at 140 rpm, enabling complete conversion of xylose to xylitol.

Comparative Conformational Analysis of Acyclic Sugar Alcohols Ribitol, Xylitol and d-Arabitol by Solution NMR and Molecular Dynamics Simulations.

Ribitol (C5H12O5) is an acyclic sugar alcohol that was recently identified in O-mannose glycan on mammalian α-dystroglycan. The conformation and dynamics of acyclic sugar alcohols such as ribitol are dependent on the stereochemistry of the hydroxyl groups; however, the dynamics are not fully understood. To gain insights into the conformation and dynamics of sugar alcohols, we carried out comparative analyses of ribitol, d-arabitol and xylitol by a crystal structure database search, solution NMR analysis and molecular dynamics (MD) simulations. The crystal structures of the sugar alcohols showed a limited number of conformations, suggesting that only certain stable conformations are prevalent among all possible conformations. The three-bond scholar coupling constants and exchange rates of hydroxyl protons were measured to obtain information on the backbone torsion angle and possible hydrogen bonding of each hydroxyl group. The 100 ns MD simulations indicate that the ribitol backbone has frequent conformational transitions with torsion angles between 180∘ and ±60∘, while d-arabitol and xylitol showed fewer conformational transitions. Taking our experimental and computational data together, it can be concluded that ribitol is more flexible than d-arabitol or xylitol, and the flexibility is at least in part defined by the configuration of the OH groups, which may form intramolecular hydrogen bonds.

Metabolic Effects of Selected Conventional and Alternative Sweeteners: A Narrative Review.

Sugar consumption is known to be associated with a whole range of adverse health effects, including overweight status and type II diabetes mellitus. In 2015, the World Health Organization issued a guideline recommending the reduction of sugar intake. In this context, alternative sweeteners have gained interest as sugar substitutes to achieve this goal without loss of the sweet taste. This review aims to provide an overview of the scientific literature and establish a reference tool for selected conventional sweeteners (sucrose, glucose, and fructose) and alternative sweeteners (sucralose, xylitol, erythritol, and D-allulose), specifically focusing on their important metabolic effects. The results show that alternative sweeteners constitute a diverse group, and each substance exhibits one or more metabolic effects. Therefore, no sweetener can be considered to be inert. Additionally, xylitol, erythritol, and D-allulose seem promising as alternative sweeteners due to favorable metabolic outcomes. These alternative sweeteners replicate the benefits of sugars (e.g., sweetness and gastrointestinal hormone release) while circumventing the detrimental effects of these substances on human health.

Natural intestinal metabolite xylitol reduces BRD4 levels to mitigate renal fibrosis.

Renal fibrosis is a typical pathological change from chronic kidney disease (CKD) to end-stage renal failure, which presents significant challenges in prevention and treatment. The progression of renal fibrosis is closely associated with the "gut-kidney axis," therefore, although clinical intervention to modulate the "gut-kidney axis" imbalance associated with renal fibrosis brings hope for its treatment. In this study, we first identified the close relationship between renal fibrosis development and the intestinal microenvironment through fecal microtransplantation and non-absorbable antibiotics experiments. Then, we analyzed the specific connection between the intestinal microenvironment and renal fibrosis using microbiomics and metabolomics, screening for the differential intestinal metabolite. Potential metabolite action targets were initially identified through network simulation of molecular docking and further verified by molecular biology experiment. We used flow cytometry, TUNEL apoptosis staining, immunohistochemistry, and Western blotting to assess renal injury and fibrosis extent, exploring the potential role of gut microbial metabolite in renal fibrosis development. We discovered that CKD-triggered alterations in the intestinal microenvironment exacerbate renal injury and fibrosis. When metabolomic analysis was combined with experiments in vivo, we found that the differential metabolite xylitol delays renal injury and fibrosis development. We further validated this hypothesis at the cellular level. Mechanically, bromodomain-containing protein 4 (BRD4) protein exhibits strong binding with xylitol, and xylitol alleviates renal fibrosis by inhibiting BRD4 and its downstream transforming growth factor-ß (TGF-ß) pathway. In summary, our findings suggest that the natural intestinal metabolite xylitol mitigates renal fibrosis by inhibiting the BRD4-regulated TGF-ß pathway.

Evaluation of in vitro corrosion behavior and biocompatibility of poly[xylitol-(1,12-dodecanedioate)](PXDD)-HA coated porous iron for bone scaffolds applications.

The present study evaluates the corrosion behavior of poly[xylitol-(1,12-dodecanedioate)](PXDD)-HA coated porous iron (PXDD140/HA-Fe) and its cell-material interaction aimed for temporary bone scaffold applications. The physicochemical analyses show that the addition of 20 wt.% HA into the PXDD polymers leads to a higher crystallinity and lower surface roughness. The corrosion assessments of the PXDD140/HA-Fe evaluated by electrochemical methods and surface chemistry analysis indicate that HA decelerates Fe corrosion due to a lower hydrolysis rate following lower PXDD content and being more crystalline. The cell viability and cell death mode evaluations of the PXDD140/HA-Fe exhibit favorable biocompatibility as compared to bare Fe and PXDD-Fe scaffolds owing to HA's bioactive properties. Thus, the PXDD140/HA-Fe scaffolds possess the potential to be used as a biodegradable bone implant.

The food additive xylitol enhances the butyrate formation by the child gut microbiota developed in a dynamic colonic simulator.

The gut microbiota should be included in the scientific processes of risk assessment of food additives. Xylitol is a sweetener that shows low digestibility and intestinal absorption, implying that a high proportion of consumed xylitol could reach the colonic microbiota. The present study has evaluated the dose-dependent effects of xylitol intake on the composition and the metabolic activity of the child gut-microbiota. The study was conducted in a dynamic simulator of the colonic microbiota (BFBL Gut Simulator) inoculated with a child pooled faecal sample and supplemented three times per day, for 7 days, with increasing xylitol concentrations (1 g/L, 3 g/L and 5 g/L). Sequencing of 16S rRNA gene amplicons and group-specific quantitative PCR indicated a xylitol dose-response effect on the abundance of Lachnospiraceae, particularly the genera Blautia, Anaerostipes and Roseburia. The microbial changes observed with xylitol corresponded with a dose-dependant effect on the butyrate concentration that, in parallel, favoured an increase in epithelial integrity of Caco-2 cells. The study represents a detailed observation of the bacterial taxa that are the main contributors to the metabolism of xylitol by the child gut microbiota and the results could be relevant in the risk assessment re-evaluation of xylitol as a sweetener.

Organic tracers in fine and coarse aerosols at an urban Mediterranean site: contribution of biomass burning and biogenic emissions.

The concentrations of anhydrosugars (levoglucosan, mannosan, and galactosan), polyols (inositol, xylitol, sorbitol, and mannitol), and glucose were measured in PM1 and PM10 samples collected during 1 year at a traffic site in the city of Elche (southeastern Spain). Levoglucosan, mannosan, and galactosan were mainly found in the PM1 fraction since they are mainly emitted from biomass burning (BB). Likewise, inositol, xylitol, and sorbitol were primarily distributed in the fine mode, suggesting a non-negligible contribution from anthropogenic sources (specifically BB) to the levels of these compounds. This was supported by their seasonal variations, with higher concentrations during winter, and their correlations with levoglucosan concentrations. The average contributions of biomass burning and biogenic sources to OC and PM levels were calculated using levoglucosan and mannitol, respectively, as tracers. On average, BB accounted for 12% and 16% of the OC in PM1 and PM10, while the estimated contribution of fungal spores to OC and PM10 levels was 1.2 and 0.8%, respectively. The results of the present study suggest that, at least in the study area, most sugar alcohols are not appropriate tracers of biogenic emissions.

Combined eutexia and amorphization for simultaneous enhancement of dissolution rate of triamterene and hydrochlorothiazide: preparation of orodispersible tablets.

BACKGROUND: Triamterene is an oral antihypertensive drug with dissolution-limited poor bioavailability. It can be used as monotherapy or in fixed dose combination with hydrochlorothiazide which also suffers from poor dissolution. Moreover, co-processing of drugs in fixed dose combination can alter their properties. Accordingly, pre-formulation studies should investigate the effect of co-processing and optimize the dissolution of drugs before and after fixed dose combination. This is expected to avoid deleterious interaction (if any) and to hasten the biopharmaceutical properties. OBJECTIVE: Accordingly, the aim of this work was to optimize the dissolution rate of triamterene alone and after fixed dose combination with hydrochlorothiazide. METHODOLOGY: Triamterene was subjected to dry co-grinding with xylitol, HPMC-E5 or their combination. The effect of co-grinding with hydrochlorothiazide was also tested in absence and presence of xylitol and HPMC-E5. The products were assessed using Fourier-transform infrared (FTIR), differential scanning calorimetry, X-ray powder diffraction (XRPD), in addition to dissolution studies. Optimum formulations were fabricated as oral disintegrating tablets (ODT).Results: Co-processing of triamterene with xylitol formed eutectic system which hastened dissolution rate. HPMC-E5 resulted in partial amorphization and improved triamterene dissolution. Co-grinding with both materials combined their effects. Co-processing of triamterene with hydrochlorothiazide resulted in eutexia but the product was slowly dissolving due to aggregation. This problem was vanished in presence of HPMC-E5 and xylitol. Compression of the optimum formulation into ODT underwent fast disintegration and liberated acceptable amounts of both drugs. CONCLUSION: The study introduced simple co-processing with traditional excipients for development of ODT of triamterene and hydrochlorothiazide.

Xylitol in toothpaste: is it effective in reducing the levels of Streptococcus mutans in high caries risk young children?

DESIGN: This study is an observational prospective longitudinal cohort study, following 102 children aged 1 to 12 months over a period of 24 months. At baseline, a dental examination was carried out to assess the number of carious lesions present using the ICDAS system, and a saliva sample was taken to assess the levels of Streptococcus mutans (SM) in saliva using the Dentocult SM saliva strip. Cohort caregivers received toothbrushing instruction and a 25% xylitol toothpaste tube for which they were instructed to use twice a day over a 3-month period, after which they returned to clinic at Pristina University to receive another tube. This process continued throughout the entire 24-month study period. At the end of the study, SM prevalence was recorded again. COHORT SELECTION: 102 children and their mothers were included in this study: 43 girls and 59 boys. At the beginning of the study, the child's mean age was 6.7 months, and at the end, 30.8 months. A random sample of 60 mothers was selected to analyse SM levels. DATA ANALYSIS: The data set was summarised descriptively using summary statistics, percentages and statistical tests. Values were expressed as a mean and standard deviation. SM prevalence comparison between baseline and endpoint was tested using chi-square statistics. RESULTS: At the baseline dental examination, the child's mean age was 6.7 (±3.7 months). At this point 59% of the 102 infants were edentulous. Caries was reported to be present in 12.4% of children. The mean ICDAS score was calculated as 0.70 (2.42 SD). When caries was present (87.6% of the 102 children included in the study), the majority of the caries experience (74.2%) was determined as at an early stage (ICAS score 1 or 2). 72.6% (n = 74/102) of children were infected with SM at baseline. 28 children had Level 1 (0) SM. 57 children had Level 2 and 3 (102-4) SM. 17 children had Level 4 SM (≥105) SM. The SM categorical distribution was statistically significant (p = 0.02). At endpoint, 53.5% (57/102) of children were SM infected. Parallel comparison of pre- and post-data sets show that there was a 19.1% reduction in SM levels overall following the introduction of the xylitol toothpaste. (p = 0.002). In the participant group with the highest SM level (Level 4), a net 12.2% reduction in SM prevalence occurred. The change in SM infection was deemed statistically significant. CONCLUSIONS: Brushing twice a day with toothpaste containing 25% xylitol shows a statistically significant decrease in SM levels. This shows a promising anticariogenic effect. Late SM colonisation is protective for future carious lesions. Xylitol can help prevent early childhood caries and early SM contamination.

The fabrication of flame-retardant viscose fabrics with phytic acid-based flame retardants: Balancing efficient flame retardancy and tensile strength.

Viscose fabrics have been widely used in various applications, but their potential fire hazard has been a concern. To address this issue, improving the flame retardancy of viscose fabrics has become a significant priority. Phytic acid (PA) and xylitol were used to create a novel flame retardant, PAXY. PAXY was finished on viscose fabrics by pad-dry-curing process, and the performance of coated viscose fabrics was investigated. The results showed that the limiting oxygen index value of PAXY13-100 (fabrics finished with a 100 g/L flame-retardant solution and the flame retardant synthesized by a 1: 3 M ratio of PA to xylitol) reached 32.8 % and the heat release rate value was decreased by 77 %. Based on the findings from the analysis of both the gas phase and condensed phase products, PAXY promoted the dehydration of viscose fabrics to produce a denser char layer, which inhibited the production of flammable gases. Surprisingly, the breaking force retention of PAXY13-100 reached 90 % in warp and 114 % in weft. Compared with that of 100 g/L PA-treated fabrics, the breaking force of PAXY13-100 increased by nearly 400 %. This work provides a new strategy for PA-based flame-retardant finishing with the synergy of flame retardancy and breaking force retention.

Xylitol associated or not with fluoride: Is the action the same on de- and remineralization?

OBJECTIVES: This study evaluated the effect of xylitol combined or not with fluoride (F) on reduction of demineralization and increase of remineralization of shallow and deep artificial enamel lesions. METHODS: Bovine enamel samples were allocated to the following solutions groups: no xylitol (negative control), 5% xylitol, 10% xylitol, 20% xylitol, 500 ppm F (as NaF), 5% xylitol+F, 10% xylitol+F or 20% xylitol+F (n = 12-15). For the demin study, a pH-cycling model (demineralization-6 h, pH 4.7/remineralization 18 h, pH 7.0) was employed for 7 days. Treatments were applied 2 × 1 min. In the remin study, specimens were pre-demineralized for 2, 5 or 10 days. Afterwards, a pH-cycling protocol was conducted (2 h demineralizing and 22 h remineralizing solution/day for 8 days) and the same treatments were done. The response variables were percentage surface hardness loss (%SHL) and transverse microradiography. Data were analyzed by RM ANOVA/Tukey or Kruskal-Wallis/Dunn (p < 0.05) RESULTS: F and Xylitol combined with F reduced the %SHL (23-30%) compared to the negative control (61.5%). The integrated mineral loss and the lesion depth were not reduced by any treatment. Surface hardness recovery was seen only for shallow lesions in case of 20% xylitol+F compared to negative control. No lesion depth recovery, but significant mineral recovery was seen for F (2-days and 10-days lesion). CONCLUSIONS: All concentrations of xylitol+F reduced enamel surface demineralization, while only 20% xylitol+F improved surface remineralization of shallow lesions in vitro. CLINICAL SIGNIFICANCE: Our results suggest that while F or any concentration of xylitol + F reduces surface demineralization, only 20% xylitol+F improves surface remineralization of shallow lesions in vitro. Therefore, xylitol may be added into oral products, combined to F, to control dental caries.

Detoxification of areca nut acid hydrolysate and production of xylitol by Candida tropicalis (MTCC 6192).

Areca nut husk is the most promising alternative source of low-cost raw materials because it contains a considerable amount of five-carbon monosaccharide sugar in the form of xylose. This polymeric sugar can be isolated and transformed into a value-added chemical using fermentation. To extract sugars from areca nut husk fibers, preliminary pretreatment, such as dilute acid hydrolysis (H2SO4), was performed. The hemicellulosic hydrolysate of areca nut husk can produce xylitol through fermentation, but toxic components inhibit the growth of microorganisms. To overcome this, a series of detoxification treatments, including pH adjustment, activated charcoal, and ion exchange resin, were carried out to reduce the concentration of inhibitors in the hydrolysate. This study reports a remarkable 99% removal of inhibitors in the hemicellulosic hydrolysate. Subsequently, a fermentation process using Candida tropicalis (MTCC6192) was executed with the detoxified hemicellulosic hydrolysate of areca nut husk, yielding an optimum xylitol yield of 0.66 g/g. This study concludes that detoxification techniques like pH adjustment, activated charcoal, and ion exchange resins are the most economical and effective methods for eliminating toxic compounds in hemicellulosic hydrolysates. Therefore, the medium derived after detoxification from areca nut hydrolysate may be considered to have significant potential for xylitol production.

Detoxification Approaches of Bagasse Pith Hydrolysate Affecting Xylitol Production by Rhodotorula mucilaginosa.

In this study, the potential of bagasse pith (the waste of sugar and paper industry) was investigated for bio-xylitol production for the first time. Xylose-rich hydrolysate was prepared using 8% dilute sulfuric acid, at 120 °C for 90 min. Then, the acid-hydrolyzed solution was detoxified by individual overliming (OL), active carbon (AC), and their combination (OL+AC). The amounts of reducing sugars and inhibitors (furfural and hydroxyl methyl furfural) were measured after acid pre-treatment and detoxification process. Thereafter, xylitol was produced from detoxified hydrolysate by Rhodotorula mucilaginosa yeast. Results showed that after acid hydrolysis, the sugar yield was 20%. Detoxification by overliming and active carbon methods increased the reducing sugar content up to 65% and 36% and decreased the concentration of inhibitors to >90% and 16%, respectively. Also, combined detoxification caused an increase in the reducing sugar content (>73%) and a complete removal of inhibitors. The highest productivity of xylitol (0.366 g/g) by yeast was attained after the addition of 100 g/l non-detoxified xylose-rich hydrolysate into fermentation broth after 96 h, while the xylitol productivity enhanced to 0.496 g/g after adding the similar amount of xylose-rich hydrolysate detoxified by combined method (OL+AC2.5%).

Xylitol biosynthesis enhancement by Candida tropicalis via medium, process parameter optimization, and co-substrate supplementation.

The present study examines the impact of nitrogen sources (yeast extract, ammonium sulfate peptone, ammonium nitrate, urea, and sodium nitrate), salt solution (0.5 g/L MgSO4, 0.5 g/L KH2PO4, 0.3 g/L CaCl2), trace elements solution (0.1 g/L CuSO4, 0.1 g/L FeSO4, 0.02 g/L MnCl2, 0.02 g/L ZnSO4), operational parameters (temperature, aeration, agitation, initial pH and xylose concentration) and co- substrate supplementation (glucose, fructose, maltose, sucrose, and glycerol) on xylitol biosynthesis by Candida tropicalis ATCC 13803 using synthetic xylose. The significant medium components were identified using the Plackett Burman design followed by central composite designs to obtain the optimal concentration for the critical medium components in shaker flasks. Subsequently, the effect of operational parameters was examined using the One Factor At a Time method, followed by the impact of five co-substrates on xylitol biosynthesis in a 1 L bioreactor. The optimal media components and process parameters are as follows: peptone: 12.68 g/L, yeast extract: 6.62 g/L, salt solution (0.5 g/L MgSO4, 0.5 g/L KH2PO4, and 0.3 g/L CaCl2): 1.23 X (0.62 g/L, 0.62 g/L, and 0.37 g/L respectively), temperature: 30 °C, pH: 6, agitation: 400 rpm, aeration: 1 vvm, and xylose: 50 g/L. Optimization studies resulted in xylitol yield and productivity of 0.71 ± 0.004 g/g and 1.48 ± 0.018 g/L/h, respectively. Glycerol supplementation (2 g/L) further improved xylitol yield (0.83 ± 0.009 g/g) and productivity (1.87 ± 0.020 g/L/h) by 1.66 and 3.12 folds, respectively, higher than the unoptimized conditions thus exhibiting the potential of C. tropicalis ATCC 13803 being used for commercial xylitol production.

Tracking transformation behavior of soluble to insoluble components in liquid egg yolk under heat treatment and the intervention effect of xylitol.

The heat sensitivity of egg yolk limits its application, and xylitol can improve its thermal stability. The soluble and insoluble components of egg yolk and egg yolk containing xylitol treated at different temperatures were explored from the aspects of thermal instability behavior characterization and structure property. Magnetic resonance imaging and low field nuclear magnetic resonance showed that increased temperature induced liberation and transfer of hydrogen protons. Meanwhile, the apparent viscosity of soluble components increased, while that of insoluble components decreased. Microstructure showed that heat treatment induced aggregation and lipid transfer. SDS-PAGE showed that heat treatment induced aggregation and transformation of γ-livetin and apo-LDL. The change in crystal structure, Raman spectroscopy, and 3D fluorescence spectra showed that heat treatment resulted in the unfolding of yolk proteins, especially plasma proteins. Xylitol could alleviate transformation of components by stabilizing protein structure, alleviating the damage in protein integrity and elevation in aggregation size.

Xylitol for the prevention of acute otitis media episodes in children aged 1-5 years: a randomised controlled trial.

OBJECTIVE: To investigate the regular use of xylitol, compared with sorbitol, to prevent acute otitis media (AOM), upper respiratory tract infections (URTIs) and dental caries. DESIGN: Blinded randomised controlled trial with a 6-month study period. SETTING: Enrolment took place at 11 primary care practices in Ontario, Canada. PATIENTS: Children aged 1-5 years who did not use xylitol or sorbitol at enrolment. INTERVENTIONS: Children were randomly assigned to use a placebo syrup with sorbitol or xylitol syrup two times per day for 6 months. MAIN OUTCOME MEASURES: Primary outcome was the number of clinician-diagnosed AOM episodes over 6 months. Secondary outcomes were caregiver-reported URTIs and dental caries. RESULTS: Among the 250 randomised children, the mean (SD) age was 38±14 months and there were 124 girls (50%). There were three clinician-diagnosed AOM episodes in the 125 placebo group participants and six in the 125 xylitol group participants (OR 2.04; 95% CI 0.43, 12.92; p=0.50). There was no difference in number of caregiver-reported URTI episodes (rate ratio (RR) 0.88; 95% CI 0.70, 1.11) between the placebo (4.2 per participant over 6 months; 95% CI 3.6, 5.0) and xylitol (3.7; 95% CI 3.2, 4.4) groups. Dental caries were reported for four participants in the placebo group and two in the xylitol group (OR 0.42; 95% CI 0.04, 3.05; p=0.42). In a post-hoc analysis of URTIs during the COVID-19 pandemic, the rate among the 59 participants receiving placebo was 2.3 per participant over 6 months (95% CI 1.8, 3.0) and for the 55 receiving xylitol, 1.3 over 6 months (95% CI 0.92, 1.82; RR 0.56; 95% CI 0.36, 0.87). The most common adverse event was diarrhoea (28% with placebo; 34% with xylitol). CONCLUSIONS: Regular use of xylitol did not prevent AOM, URTIs or dental caries in a trial with limited statistical power. A post-hoc analysis indicated that URTIs were less common with xylitol exposure during the COVID-19 pandemic, but this finding could be spurious. TRIAL REGISTRATION NUMBER: NCT03055091.

Xylitol nasal spray for prevention of recurrent acute otitis media in children: A prospective two-center cohort study.

OBJECTIVES: The purpose of this study was to assess the effectiveness and safety of xylitol nasal spray as a prophylactic treatment for children with recurrent acute otitis media (AOM). METHODS: This is a prospective pilot study of children aged 1-4 years, diagnosed with recurrent AOM (at least three episodes in the three months before recruitment) between December 1, 2019 and January 31, 2023. Children were treated with nasal xylitol spray 2-3 times daily for 3 months. The number of AOM episodes and treatments administered were compared within 3-month intervals: before recruitment, during xylitol use, and during the three subsequent months. RESULTS: Of 68 children enrolled, 66 (97%) completed the follow-up, until July 2023. Thirty-eight (58%) were males. Sixty-three children (95%) were 12-24-months old. The mean number of AOM episodes during xylitol use, 1.06 (95% confidence interval [CI]: 0.73-1.39), was lower than in the 3-month previous interval, 4.12 (95% CI: 3.89-4.40), p < 0.001; and similar to that in the subsequent 3-month interval, 0.79 (95% CI: 0.49-1.08), p = 0.082. A similar pattern was observed in an analysis of the number of AOM episodes per patient month. The data were similar during spring and summer months as during autumn and winter months. Across the consecutive three-month intervals, decreases were observed in the mean number of AOM episodes treated with systemic antibiotics (3.35, 0.65, and 0.41), p < 0.001; and with topical antibiotics (1.38, 0.55, and 0.32), p < 0.001. No major side effects were recorded. CONCLUSIONS: The findings support the effectiveness and safety of nasal xylitol spray, for preventing recurrent AOM in children aged 1-4 years.

Clearing of Vascular Tissue in Arabidopsis thaliana for Reporter Analysis of Gene Expression.

To study the gene regulatory mechanisms modulating development is essential to visualize gene expression patterns at cellular resolution. However, this kind of analysis has been limited as a consequence of the plant tissues' opacity. In the last years, ClearSee has been increasingly used to obtain high-quality imaging of plant tissue anatomy combined with the visualization of gene expression patterns. ClearSee is established as a major tissue clearing technique due to its simplicity and versatility.In this chapter, we outline an easy-to-follow ClearSee protocol to analyze gene expression of reporters using either ß-glucuronidase (GUS) or fluorescent protein (FP) tags, compatible with different dyes to stain cell walls. We detail materials, equipment, solutions, and procedures to easily implement ClearSee for the study of vascular development in Arabidopsis thaliana, but the protocol can be easily adapted to a variety of plant tissues in a wide range of plant species.

Development of a novel direct compressible co-processed excipient and its application for formulation of Mirtazapine orally disintegrating tablets.

INTRODUCTION: Orally disintegrating tablets (ODTs) are designed to dissolve in the oral cavity within 3 min, providing a convenient option for patients as they can be taken without water. Direct compression is the most common method used for ODTs formulations. However, the availability of single composite excipients with desirable characteristics such as good compressibility, fast disintegration, and a good mouthfeel suitable for direct compression is limited. OBJECTIVE: This research was proposed to develop a co-processed excipient composed of xylitol, mannitol, and microcrystalline cellulose for the formulation of ODTs. METHODS: A total of 11 formulations of co-processed excipients with different ratios of ingredients were prepared, which were then compressed into ODTs, and their characteristics were thoroughly examined. The primary focus was on evaluating the disintegration time and hardness of the tablets, as these factors are important in ensuring the ODTs meet the desired criteria. The model drug, Mirtazapine was then incorporated into the chosen optimized formulation. RESULTS: The results showed that the formulation comprised of 10% xylitol, 10% mannitol and 80% microcrystalline cellulose demonstrated the fastest disintegration time (1.77 ± 0.119 min) and sufficient hardness (3.521 ± 0.143 kg) compared to the other formulations. Furthermore, the drug was uniformly distributed within the tablets and fully released within 15 min. CONCLUSION: Therefore, the developed co-processed excipients show great potential in enhancing the functionalities of ODTs, offering a promising solution to improve the overall performance and usability of ODTs in various therapeutic applications.

Development of a Novel Co-processed Excipitient Comprising of Xylitol, Mannitol, Microcrystalline Cellulose, and Crospovidone for the Compounding of Memantine Hydrochloride Orally Disintegrating Tablet.

Orally disintegrating tablets, which were originally developed in the pharmaceutical field to improve the compliance of patients who had difficulty swallowing tablets, have become a preferable choice in solid dosage forms since it brings advantages to the patients and consumers in the healthcare system. Among the advantages of this novel dosage form are a faster onset of action, improved bioavailability, and the ease of administration as it can be taken without water. However, there are still some limitations of orally disintegrating tablets that need to be overcome, including a lack of mechanical strength, an unpleasant taste of the drug in the mouth, and a stability issue due to its hygroscopicity nature. This objective of this study was to identify the composition of co-processed excipients comprising of mannitol, microcrystalline cellulose, xylitol, and crospovidone or croscarmellose sodium in order to formulate orally disintegrating tablets containing memantine hydrochloride. This study was carried out in two stages. Firstly, orally disintegrating tablets containing memantine hydrochloride with 6 different formulations, which differed in the percentage of crospovidone or croscarmellose sodium, were formulated and manufactured. Secondly, the orally disintegrating tablets obtained were evaluated through pre- and post-compression tests based on the standard for orally disintegrating tablets. Formulation 3, which consisted of 10% xylitol, 10% mannitol, 72% microcrystalline cellulose, and 8% crospovidone, was chosen as the optimum formulation for the co-processed excipient since it was the fastest disintegration process among all the formulations in the study. In addition, Formulation 3 also showed the acceptable and satisfying results in other evaluation tests such as - weight variation test, hardness test, and friability test. The co-processed excipient comprising of 10% xylitol, 10% mannitol, 72% microcrystalline cellulose, and 8% crospovidone, which is characterized by improved functionalities such as a fast disintegration process, plays a crucial role in the application of orally disintegrating tablets.