3D printed mold-based capsaicin candy for the treatment of oral ulcer.

Oral ulcer is one common mucosal disease with high prevalence. Here, capsaicin candies were prepared based on the stereolithographically (SLA) 3D printed molds. The molds can be freely designed depending on the needs of patients, involving symmetric shapes (e.g., round, four-lead clover and cube), asymmetric shapes (e.g., car) and various color (e.g., blue, red and yellow). A two-part-combined mold was filled with the xylitol-based material and separated to obtain hard candies. Capsaicin was amorphous in the candies according to the differential scanning calorimetry and X-ray diffraction. Poloxamer 188 improved the release of capsaicin from the candies. Rat oral ulcer models were established on the tongue with phenol liquids. The blank candy, 0.05% capsaicin candy and dexamethasone were respectively administered on the ulcer once daily. On Day 7, a healing rate of 97.8% was achieved by the capsaicin candy, much higher than those in the other groups. Moreover, the blank candy also showed the remarkable ulcer healing effect due to the presence of xylitol and poloxamer. Capsaicin remarkably enhanced the reepithelialization of ulcer tissues and showed strong anti-inflammatory effect by reducing the expressions of THF-α and IL-6. 3D printing-based capsaicin candies provide an interesting therapeutic choice for the people with oral ulcer.

Enhancing Fluoride: Clinical Human Studies of Alternatives or Boosters for Caries Management.

Dental caries remains a major public health problem, especially for certain high-risk population groups. The goal of this study was to assess the evidence regarding strategies meant to be used as alternatives or booster/supplements to fluoride for caries prevention and management. Articles were selected for inclusion if they had a prospective longitudinal design, with a fluoride control arm, and were conducted in human subjects. Of the included studies, 7/18 studies on calcium-based strategies favored the test product (the majority of studies included exposure of fluoride in all groups). All the arginine studies (8/8) included a combination of arginine and a calcium base, and concluded that this has the potential to significantly boost the performance of fluoride. The remaining included studies focused on the addition of microbial-related strategies to a fluoride-containing vehicle (2 xylitol studies and 1 study using a probiotic milk), and all favored the combination as a booster to fluoride. Thus, the current study did not identify evidence for any strategy to effectively be used as a substitute or alternative to fluoride, but identified some consistent evidence derived from the use of prebiotic strategies (primarily from use of arginine combined with calcium) to support their potential use to boost the mechanism of action of fluoride. Thus, fluoride-based strategies remain the standard for caries prevention and management, with some evidence that boosting the effects of fluoride by the use of prebiotic strategies is a promising possibility.

Pharmacokinetics and Plasma Cellular Antioxidative Effects of Flavanols After Oral Intake of Green Tea Formulated with Vitamin C and Xylitol in Healthy Subjects.

This study aimed to test whether green tea formulated with vitamin C and xylitol (GTVX) could improve absorption of flavanols and total antioxidant activity (TAC) of plasma compared with green tea only (GT) in healthy subjects. The total radical-trapping antioxidant parameter method was used to measure the TAC of plasma. Cmax, Tmax, and area under the curve (AUC) of flavanols in plasma after consumption of GTVX were 5980.58 µg/mL, 2.14 h, and 18,915.56 h·µg/mL, respectively, indicating that GTVX showed significantly higher AUC than GT (13,855.43 µg/mL). The peak TACs occurred at 3 and 0.5 h after intake of GT and GTVX, respectively. The TAC of plasma was found to be significantly higher in GTVX than in GT at each time point. This study suggests that formulating green tea with vitamin C and xylitol could increase the absorption of flavanols in green tea, enhancing cellular antioxidative effects.

Medical prevention of recurrent acute otitis media: an updated overview.

Acute otitis media (AOM) is one of the most common pediatric diseases; almost all children experience at least one episode, and a third have two or more episodes in the first three years of life. The disease burden of AOM has important medical, social and economic effects. AOM requires considerable financial assistance due to needing at least one doctor visit and a prescription for antipyretics and/or antibiotics. AOM is also associated with high indirect costs, which are mostly related to lost days of work for one parent. Moreover, due to its acute symptoms and frequent recurrences, AOM considerably impacts both the child and family's quality of life. AOM prevention, particularly recurrent AOM (rAOM), is a primary goal of pediatric practice. In this paper, we review current evidence regarding the efficacy of medical treatments and vaccines for preventing rAOM and suggest the best approaches for AOM-prone children.

Protective effect of dietary xylitol on influenza A virus infection.

Xylitol has been used as a substitute for sugar to prevent cavity-causing bacteria, and most studies have focused on its benefits in dental care. Meanwhile, the constituents of red ginseng (RG) are known to be effective in ameliorating the symptoms of influenza virus infection when they are administered orally for 14 days. In this study, we investigated the effect of dietary xylitol on influenza A virus infection (H1N1). We designed regimens containing various fractions of RG (RGs: whole extract, water soluble fraction, saponin and polysaccharide) and xylitol, and combination of xylitol with the RG fractions. Mice received the various combinations orally for 5 days prior to lethal influenza A virus infection. Almost all the mice died post challenge when xylitol or RGs were administered separately. Survival was markedly enhanced when xylitol was administered along with RGs, pointing to a synergistic effect. The effect of xylitol plus RG fractions increased with increasing dose of xylitol. Moreover, dietary xylitol along with the RG water soluble fraction significantly reduced lung virus titers after infection. Therefore, we suggest that dietary xylitol is effective in ameliorating influenza-induced symptoms when it is administered with RG fractions, and this protective effect of xylitol should be considered in relation to other diseases.

Effects of xylitol as a sugar substitute on diabetes-related parameters in nondiabetic rats.

Abstract The present study was examined the effects of xylitol feeding on diabetes-associated parameters in nondiabetic rats. Seven-week-old male Sprague-Dawley rats were randomly divided into three groups: control (five rats), sucrose (six rats), and xylitol (six rats). Animal had free access to a commercial rat pellet diet, and ad libitum water, 10% sucrose solution, and 10% xylitol solution were supplied to the control, sucrose, and xylitol groups, respectively. After 3 weeks of feeding of experimental diets, food intakes were significantly (P<.05) lower in the sucrose and xylitol groups compared with the control group. Drink intake was significantly higher in the sucrose group but significantly lower in the xylitol group compared with the control group. Body weight gain was significantly lower in the xylitol group compared with the sucrose group. Weekly nonfasting blood glucose was significantly increased, but fasting blood glucose was significantly decreased, in the sucrose group compared with the control and xylitol groups. Significantly better glucose tolerance was observed in the xylitol group compared with the control and sucrose groups. Serum insulin and fructosamine concentrations were not significantly influenced by the feeding of xylitol or sucrose. Relative liver weight and liver glycogen were significantly increased in the xylitol group compared with the sucrose group, whereas no difference was observed between the xylitol and control groups. Serum total cholesterol and low-density lipoprotein-cholesterol were significantly decreased in the sucrose and xylitol groups, and serum triglyceride of the xylitol group, but not the sucrose group, was significantly increased compared with the control group. Data of this study suggest that xylitol can be a better sweetener than sucrose to maintain diabetes-related parameters at a physiologically safer and stable condition.

The effects of oral xylitol administration on bone density in rat femur.

To examine the effects of oral xylitol administration on rat femur bone density, 36 four-week-old male Wistar rats divided into three groups were fed CE-2 diet (control, n = 12) alone or supplemented with 10% (n = 12) or 20% (n = 12) dietary xylitol for 40 days. Biochemical, morphological, and histological analyses were performed. The 10% and 20% xylitol groups showed higher levels of both serum Ca and alkaline phosphatase activity and lower levels of serum tartrate-resistant acid phosphatase than the control group. Although no significant differences in the three-dimensional bone structure or trabecular bone structure of the femur were observed, both xylitol groups showed significantly higher bone density than the control group. Compared to the control group, the 10% and 20% xylitol groups showed an increase in trabeculae. Thus, oral administration of xylitol appears to affect bone metabolism, leading to increased bone density in rat femur.

Too much of too little: xylitol, an unusual trigger of a chronic metabolic hyperchloremic acidosis.

Homeopathic globules are frequently used in children as a first-line treatment. Most of these globules are coated with sugar substitutes like xylitol; these substitutes are known for their laxative effect. Our patient shows that consumption of globules coated with xylitol does not have only laxative effects. It may cause indeed considerable weight loss and life-threatening enteral bicarbonate loss by diarrhea when overdosed in an infant.

Xylitol-supplemented nutrition enhances bacterial killing and prolongs survival of rats in experimental pneumococcal sepsis.

BACKGROUND: Xylitol has antiadhesive effects on Streptococcus pneumoniae and inhibits its growth, and has also been found to be effective in preventing acute otitis media and has been used in intensive care as a valuable source of energy. RESULTS: We evaluated the oxidative burst of neutrophils in rats fed with and without xylitol. The mean increase in the percentage of activated neutrophils from the baseline was higher in the xylitol-exposed group than in the control group (58.1% vs 51.4%, P = 0.03 for the difference) and the mean induced increase in the median strength of the burst per neutrophil was similarly higher in the xylitol group (159.6 vs 140.3, P = 0.04). In two pneumococcal sepsis experiments rats were fed either a basal powder diet (control group) or the same diet supplemented with 10% or 20% xylitol and infected with an intraperitoneal inoculation of S. pneumoniae after two weeks. The mean survival time was 48 hours in the xylitol groups and 34 hours in the control groups (P < 0.001 in log rank test). CONCLUSION: Xylitol has beneficial effects on both the oxidative killing of bacteria in neutrophilic leucocytes and on the survival of rats with experimental pneumococcal sepsis.

Effects of a long-term dietary xylitol supplementation on collagen content and fluorescence of the skin in aged rats.

BACKGROUND: Dietary xylitol has been shown to increase the amounts of newly synthesized collagen, and to decrease fluorescence of the collagenase-soluble fraction in the skin of both healthy and diabetic rats. As in diabetic rats, a decreased rate of collagen synthesis and increased collagen fluorescence has also been detected in the skin of aged rats. We hypothesize that dietary xylitol supplementation may protect against these changes during aging. OBJECTIVE: The purpose of the present study was to investigate whether a long-term dietary supplementation can protect against the decrease in the amounts of newly synthesized collagen, and against the increase in fluorescence in the collagenase-soluble fraction in the skin of aged rats. METHODS: Twenty-four male Sprague-Dawley rats were used in the study. After weaning, the rats were divided into 2 groups of 12 animals. The rats in the control group were fed a basal RM1 diet, while the rats in the experimental group were fed the same diet supplemented with 10% xylitol. After 20 months, the rats were killed and pieces of skin from their dorsal areas were excised. The thickness of the samples was measured with a micrometer screw gauge. The collagen contents of rat skin were measured as hydroxyproline, and glycosylation as fluorescent intensity of collagen. Statistical significances of the differences between the groups were determined using the unpaired t test. RESULTS: No general side effects were detected in the rats during the experimental period. The skin of the xylitol-fed rats was a little thicker than that of the control rats. The hydroxyproline content of the acid-soluble fraction was significantly greater in the xylitol group as compared to the controls. However, there were no significant differences in the hydroxyproline content of the collagenase-soluble fraction between the groups. The fluorescence of the collagenase-soluble fraction was significantly smaller in the xylitol-fed aged rats than in the aged rats fed the basal diet. CONCLUSIONS: The results of this study indicate that xylitol caused an increase in the amount of newly synthesized collagen and a decrease in collagen fluorescence in the skin of aged rats.

The effect of a simultaneous dietary administration of xylitol and ethanol on bone resorption.

Our previous studies have shown that dietary xylitol supplementation diminishes bone resorption in rats, as well as protects against ovariectomy-induced increase of bone resorption during experimental osteoporosis. Interestingly, ethanol, when given simultaneously with xylitol, is known to increase blood concentration of xylitol. On the other hand, ethanol, when given alone, has been shown to increase bone resorption. The aim of the present study was to evaluate the effects of a simultaneous dietary administration of 10% xylitol and 10% ethanol on bone resorption. Bone resorption was determined using measurement of urinary excretion of hydrogen 3 (3H) radioactivity in 3H-tetracycline prelabeled rats. Already 4 days after the beginning of dietary supplementations, excretion of 3H was about 15% lower in the xylitol group (diet supplemented with 10% xylitol) and about 25% lower in the xylitol-ethanol group (diet supplemented with 10% xylitol and 10% ethanol) as compared to the controls. The excretion of 3H in these groups remained smaller than that of the controls throughout the entire study period of 40 days. The excretion of 3 H in the xylitol-ethanol group remained also smaller than that of the xylitol group. Bone mineral density and bone mineral content were determined with a peripheral quantitative computed tomography (pQCT) system from the rat tibiae at the end of the experiment. Trabecular bone mineral density and trabecular bone mineral content were significantly greater in the xylitol group and in the xylitol-ethanol group compared to the controls. They were also greater in the xylitol-ethanol group as compared to the xylitol group. Cortical bone mineral density and cortical bone mineral content did not differ significantly between the groups. In conclusion, a simultaneous dietary supplementation with 10% xylitol and 10% ethanol seems to diminish bone resorption and to increase trabecular bone mineral density and trabecular bone mineral content in rats. These effects seem to be stronger than the effects induced by 10% xylitol supplementation alone.

Effects of dietary xylitol on collagen content and glycosylation in healthy and diabetic rats.

The effects of three-month dietary xylitol supplementation on the amounts and hexose contents of acid-soluble collagen as well as on the amounts and fluorescence of collagenase-soluble collagen were studied in healthy and streptozotocin-diabetic male rats. Collagen was extracted from skin samples. In the healthy rats, supplementation with xylitol (10%) increased the hydroxyproline content of the acid-soluble fraction and skin thickness. In diabetic rats receiving and not receiving xylitol, the acid-soluble collagen fraction was markedly lower than in healthy rats. However, its amount was significantly elevated when xylitol had been added to the diet. Supplementation with xylitol caused no changes in the amounts of collagenase-soluble fraction in either healthy or diabetic rats. Supplementation with xylitol (10%) significantly decreased the hexose content of acid-soluble collagen and the fluorescence of the collagenase-soluble fraction in both healthy and diabetic rats. The results indicate that dietary xylitol affects collagen synthesis and collagen glycosylation.

Efficacy of a slow-release device containing fluoride, xylitol and sorbitol in preventing infant caries.

A novel slow-release administration device, the "Fall-Asleep Pacifier" (FAP), was studied as a prophylactic measure against mutans streptococcal oral infection and dental caries in a risk group of 1-year-old children by comparing the test (T, n = 34) and control (C, n = 88) groups in a prospective cohort study. In the T group the children received their fluoride tablets (Fludent, containing NaF corresp. 0.25 mg F0- , xylitol 159 mg and sorbitol 153 mg) in the evenings in FAP. In the C group the children received the same dose of Fludent crushed in food in the evenings. The proportion of children, whose plaque samples from the upper incisors were mutans streptococcus positive at the age of 24 months, was significantly (P < 0.05) greater in group C (25%) than in group T (9%). The children in the T group developed significantly (P < 0.001) less (none) new dentinal carious lesions in their primary dentitions than the children in the C group between 2 and 3 1/2 years of age. Fifty-four percent of the children to whom the FAP was offered complied with regular use of it. The beneficial effect observed in the T group compared with the C group was apparently mostly due to the administration mode via FAP, which could prolong the intra-oral bioavailability of the prophylactic preparation.

Improved bone biomechanical properties in rats after oral xylitol administration.

The effects of 5, 10, and 20% dietary xylitol supplementations on the biomechanical properties, histological architecture, and the contents of collagen, pyridinoline, and deoxypyridinoline in long bones of rats were studied. Tibiae were used for the three-point bending test, and femurs were used for the torsion and loading test of the femoral neck. The 10 and 20% oral xylitol administrations caused a significant increase of tibial stress, femoral shear stress, and stress of the femoral neck as compared with the controls. Parallel, but not significant, effects were also seen in the 5% xylitol supplementation group. No significant differences in strain or Young's modulus of the tibiae were detected between the groups. An increased shear modulus of elasticity in femurs was detected in the 20% supplementation group as compared with the controls. The histomorphometrical data for the secondary spongiosa of the proximal tibia revealed that trabecular bone volume was significantly greater in all dietary xylitol supplementation groups as compared with the controls. The bone volume increased along with increasing xylitol content. No significant differences between the groups were detected concerning the amount of collagen per dry weight of organic matrix, the concentrations of pyridinoline or deoxypyridinoline in collagen, or the ratio of these crosslinks. This suggests no xylitol-dependent selective changes in these structures of bone collagen. In conclusion, dietary xylitol supplementation in rats improves the biomechanical properties of bone and increases the trabecular bone volume dose dependently.

Dietary xylitol protects against weakening of bone biomechanical properties in ovariectomized rats.

The effects of dietary xylitol (xyl) on bone biomechanical properties in ovariectomized rats (ovx) were studied. Forty-two 3-mo-old female Wistar rats were divided into three groups of 14. Rats in two groups were ovariectomized, while those in the control group underwent a sham operation. All rats received a basal diet, and half of the ovx were given an additional 10 g/100 g dietary xyl supplementation. Three months later the rats were killed and their tibias, femurs and humeri were prepared. The tibias were used for analyses of bone density and trabecular bone volume (BV/TV) and for the three-point bending test. The femurs were used for the torsion test and for the loading test of the femoral neck. The humeri were used for analyses of bone ash weight and bone concentrations of calcium and phosphorus. Dietary xyl gave a significant protection against ovariectomy-caused decline of tibial stress in the three-point bending test, of femoral shear stress in the torsion test, and of stress of the femoral neck, without affecting bone elasticity values. Xyl restricted the ovariectomy-caused reduction in bone density, in bone ash weight and in concentrations of bone calcium and phosphorus. Furthermore, trabecular bone loss in ovx was significantly suppressed by dietary xyl. These results indicate that a 10% dietary supplementation of xyl in ovx has a protective effect against the weakening of bone biomechanical properties. This is related to greater BV/TV and maintained bone mineral content.

Dietary xylitol supplementation prevents osteoporotic changes in streptozotocin-diabetic rats.

The effects of 10% and 20% dietary xylitol supplementation on the biomechanical properties, trabeculation, and mineral content of long bones were studied in streptozotocin-diabetic rats. Forty 3-month-old male Wistar rats were divided randomly into four groups of 10. Rats in three groups were administered a single injection of streptozotocin (50 mg/kg body weight) to induce type I diabetes, while animals in the fourth group were given a sham injection of physiological saline. The sham-injected group and one of the streptozotocin-diabetic groups were fed the basal diet, while the two diabetic groups were fed the same diet supplemented with 10% and 20% xylitol (wt/wt). After 3 months, the rats were killed and the long bones were prepared for analysis. The 10% and 20% dietary xylitol supplementation significantly prevented the type I diabetes-induced decrease in the mechanical stress resistance of the tibia in the three-point bending test, the shear stress of the femur in the torsion test, and the stress resistance of the femoral neck in the loading test. No statistically significant differences were found between any groups in the values for strain or Young's modulus in the three-point bending test, or in the values for the shear modulus of elasticity in the torsion test. These findings indicate that dietary xylitol protects against the weakening of the bone strength properties of both cortical and trabecular bone without affecting the elastic-plastic properties. Supplementation with 10% and 20% dietary xylitol significantly prevented the type I diabetes-induced decrease of humeral ash weight and tibial density. Histomorphometric data for the secondary spongiosa of the proximal tibia showed that 10% and 20% dietary xylitol supplementation also significantly prevented the type I diabetes-induced loss of trabecular bone volume. In conclusion, dietary xylitol supplementation protects against the weakening of bone biomechanical properties in streptozotocin-diabetic rats. This is related to the preserved bone mineral content and preserved trabecular bone volume.

Vitamin D3, lactose, and xylitol stimulate chromaffin cell proliferation in the rat adrenal medulla.

Chronic consumption by rats of diets rich in sugars or sugar alcohols leads to an increased incidence of pheochromocytomas. This relationship is hypothesized to be based on altered Ca2+ homeostasis due to increased intestinal Ca2+ absorption. Other agents associated with pheochromocytomas in rats in long-term toxicity studies have been shown to increase chromaffin cell proliferation, leading to the suggestion that the tumors occur secondarily to increased chromaffin cell turnover. We have demonstrated marked stimulation of chromaffin cell proliferation by vitamin D3, a potent stimulus to Ca2+ absorption not previously associated with adrenal medullary toxicity. This effect is detectable during the first week of dietary supplementation and persists throughout a 4-week time course. Lactose and xylitol, representative of sugars and sugar alcohols associated with pheochromocytomas, are also mitogenic but to a lesser extent, with their effects first detectable during Week 4 of dietary supplementation. Vitamin D3, its active metabolite calcitriol, lactose, and xylitol all fail to stimulate proliferation of rat chromaffin cells in vitro. The mitogenic effects of these agents may be mediated presynaptically in vivo. The data suggest that altered Ca2+ homeostasis may increase chromaffin cell proliferation and support the hypothesis that diets containing high concentrations of sugars and sugar alcohols cause pheochromocytomas in rats secondarily by this mechanism.

The role of ascorbic acid and xylitol in etomidate-induced adrenocortical suppression in humans.

Etomidate-induced suppression of cortisol biosynthesis is a result of a blockade of 11-beta-hydroxylation in the adrenal gland, mediated by the imidazol radical of etomidate. Since the generation of steroids requires reductive and energy rich equivalents, the present study examined whether supplementation with ascorbic acid or xylitol, a major source of NADPH, could attenuate adrenal suppression by etomidate in human subjects by promoting the turnover rate of 11-beta-hydroxylase. During continuous etomidate/alfentanil anaesthesia for pelviscopic surgery 30 female patients received either Ringer's lactate, xylitol (0.25 g kg-1 h-1) or ascorbic acid (0.5 g h-1) intravenously (i.v.). The plasma concentrations of cortisol, aldosterone and dehydroepiandrosterone (DHEA) were recorded for 5 h after end of surgery and a stimulation with synthetic ACTH was performed. The results showed no evidence of a clinically relevant attenuating effect of ascorbic acid or xylitol on etomidate-induced adrenocortical suppression. However, the observed suppression of cortisol levels was not enough to allow an attenuating affect to be measured.

Effects of xylitol and carbohydrate diets on dental caries, dentine formation and mineralization in young rats.

Female Wistar rats were weaned at the age of 3 weeks and fed for 7 weeks either a high-sucrose diet, a non-cariogenic raw potato-starch diet, a high-sucrose diet with 5% xylitol supplement, a raw potato-starch diet with 5% xylitol supplement or a non-cariogenic, commercial, powdered rat food (Ewos R3) for reference. A low xylitol concentration reduced the progression and severity of carious lesions but did not affect dentine apposition or the width of predentine in rats fed high-carbohydrate diets. Widening of the predentine zone in rats fed a high-sucrose diet might reflect disturbed mineralization, which could not be explained by serum ionized calcium or phosphate ion levels and which could not be corrected by low xylitol concentrations. It is concluded that the reduced area of dentinal carious lesions after low xylitol supplementation is not dependent on dentine formation or mineralization, but rather on direct effects in the mouth.

Diminished bone resorption in rats after oral xylitol administration: a dose-response study.

The effects of 5, 10, and 20% dietary xylitol supplementations on the resorption of bone were studied. The resorption was measured by the urinary excretion of [3H] radioactivity from [3H]tetracycline-prelabeled rats. The 10 and 20% oral xylitol administrations caused a significant decrease in the excretion of [3H] as compared with the control group with no xylitol supplementation. The effect was detected as early as 2 days after the beginning of xylitol-feeding and was maintained throughout the experimental period of 31 days. The retarding effect on bone resorption was about 25% in the 10% xylitol group, about 40% in the 20% xylitol group, and undetectable in the 5% xylitol group. The amount of preserved [3H] radioactivity in the tibiae of the 10 and 20% xylitol groups after the experiment clearly exceeded the values of the control group. The mechanism of the retarded bone resorption caused by dietary xylitol still remains obscure, but an increased absorption of calcium may be involved. In conclusion, dietary xylitol supplementation in rats seems to retard the bone resorption in a dose-dependent way. The effect is achieved rapidly and is maintained at least over a period of 1 month xylitol feeding.