Beneficial effects of lactitol on the composition of gut microbiota in constipated patients.

OBJECTIVE: To explore the changes in microbial composition and the corresponding impact after lactitol treatment in constipated patients. METHODS: Altogether 29 consecutive outpatients diagnosed with chronic constipation from three centers were recruited and stratified based on their history of diabetes mellitus. All patients were administered with oral lactitol for 2 weeks, and a symptoms diary of constipation was recorded. Fecal samples were collected before and after lactitol treatment, and were analyzed by 16S rRNA sequencing and real-time polymerase chain reaction (PCR) to detect gut microbiota. RESULTS: Twenty patients with diabetes mellitus and nine without, all with chronic constipation, were enrolled in this study. After 2-week administration of lactitol, their subscale scores and constipation symptoms significantly decreased (P < 0.05). An analysis of fecal flora using 16S rRNA sequencing found an increasing trend of abundance of Bifidobacterium in the post-lactitol group (P = 0.08). Actinobacteria, Actinobacteria, Bifidobacteriales, Bifidobacteriaceae and Bifidobacterium were significantly more abundant after lactitol administration. Real-time PCR showed significantly high DNA copy numbers of Bifidobacterium after lactitol treatment (1.39 × 1010 vs 2.74 × 109 copies/µL, P = 0.01). The results of 16S rRNA sequencing and real-time PCR illustrated an increasing trend of Bifidobacterium in both patients with and without diabetes. In addition, Bifidobacterium was negatively correlated with constipation subscale scores. CONCLUSIONS: Alterations in fecal flora composition after lactitol supplementation, especially in terms of an increasing trend of Bifidobacterium, alleviated constipation symptoms. Lactitol may be a promising prebiotic candidate for patients with constipation, regardless of diabetes mellitus.

Prebiotic UG1601 mitigates constipation-related events in association with gut microbiota: A randomized placebo-controlled intervention study.

BACKGROUND: Constipation is a common functional gastrointestinal disorder and its etiology is multifactorial. Growing evidence suggests that intestinal dysbiosis is associated with the development of constipation. Prebiotics are subjected to bacterial fermentation in the gut to produce short-chain fatty acids (SCFAs), which can help relieve constipation symptoms. The prebiotic UG1601 consists of inulin, lactitol, and aloe vera gel, which are known laxatives, but randomized, controlled clinical trials that examine the effects of this supplement on gut microbiota composition are lacking. AIM: To assess the efficacy of the prebiotic UG1601 in suppressing constipation-related adverse events in subjects with mild constipation. METHODS: Adults with a stool frequency of less than thrice a week were randomized to receive either prebiotics or a placebo supplement for 4 wk. All participants provided their fecal and blood samples at baseline and at the end of intervention. Gastrointestinal symptoms and stool frequency were evaluated. The concentrations of serum endotoxemia markers and fecal SCFAs were determined. The relative abundance of SCFA-producing bacteria and the gut microbial community in the responders and non-responders in the prebiotics supplementation group were evaluated. RESULTS: There were no significant differences in gastrointestinal symptoms between groups, although the prebiotic group showed greater symptom improvement. However, after prebiotic usage, serum cluster of differentiation (CD) 14 and lipopolysaccharide (LPS) concentrations were significantly decreased (CD14, P = 0.012; LPS, P < 0.001). The change in LPS concentration was significantly larger in the prebiotic group than in the placebo group (P < 0.001). Fecal SCFAs concentrations did not differ between groups, while the relative abundance of Roseburia hominis, a major butyrate producer, was significantly increased in the prebiotic group (P = 0.045). The abundances of the phylum Firmicutes and the family Lachnospiraceae (phylum Firmicutes, class Clostridia) (P = 0.009) were decreased in the responders within the prebiotic group. In addition, the proportions of the phylum Firmicutes, the class Clostridia, and the order Clostridiales were inversely correlated with several fecal SCFAs (P < 0.05). CONCLUSION: Alterations in gut microbiota composition, including a decrease in the phylum Firmicutes and an increase in butyrate-producing bacteria, following prebiotic UG1601 supplementation might help alleviate symptom scores and endotoxemia.

Confirmation of a Rare Genetic Leukoencephalopathy due to a Novel Bi-allelic Variant in RPIA.

Ribose 5-phosphate isomerase deficiency is a rare genetic leukoencephalopathy caused by pathogenic sequence variants in RPIA, that encodes ribose 5-phosphate isomerase, an enzyme in the pentose phosphate pathway. Till date, only three individuals with ribose 5-phosphate isomerase deficiency have been described in literature. We report on a subject with RPIA associated progressive leukoencephalopathy with elevated urine arabitol and ribitol levels and a novel missense variant c.770T > C p.(Ile257Thr) in exon 8 of RPIA. We also compare the phenotypes of all the four subjects. Our report confirms the phenotype and the genetic cause of this condition.

Influence of Lactitol and Psyllium on Bowel Function in Constipated Indian Volunteers: A Randomized, Controlled Trial.

Psyllium and lactitol have been reported to increase fecal volume, moisture content and bowel movement frequency (BMF). However, the benefits of their combined use on constipation has not been examined. The aim of this study was to evaluate the effects of a 4-week intervention with lactitol and/or psyllium on bowel function in constipated volunteers. Adults (N = 172) who were diagnosed with functional constipation per Rome III criteria were randomized to four treatment groups: 10 g lactitol, 3.5 g psyllium, a combination of 10 g lactitol and 3.5 g psyllium, or placebo. The primary endpoint was change in BMF from Day 0 to 28 as compared to placebo. Secondary endpoints were assessed by inventories, including stool consistency, patient assessment of constipation symptoms and quality of life, relief of constipation, 24-h food recall, physical activity, product satisfaction and adverse events (AE). BMF increased by 3.0 BMs with lactitol, by 2.9 with psyllium, and by 3.1 with the combination, but was not different from placebo (3.7 BMs). Other clinical endpoints were similar between treatments. No serious AEs were reported. In conclusion, this study showed a similar effect on relief of constipation in all treatment groups. The treatments that were administered to the volunteers were well tolerated.

The effect of a new mixture of sugar and sugar-alcohols compared to sucrose and glucose on blood glucose increase and the possible adverse reactions: A phase I double-blind, three-way randomized cross-over clinical trial.

INTRODUCTION: Several sweeteners are introduced to replace sucrose in the human diet. However, they had their own limitations and concerns, particularly in terms of their taste and their long-term health consequences. This study examined the effect of a new mixture of sugars and sugar alcohol on the postprandial blood glucose levels and its possible gastrointestinal (GI) adverse reactions in human adults. METHODS: In this double-blind three-way randomized clinical trial, adults (21 with type 2 diabetes and 20 healthy) received 300ml of three beverages containing 50g glucose, sucrose, and lacritose (a mixture of lactose, fructose, sucrose, and erythritol) when they were in the fasted state in a random order. Postprandial serum glucose was checked every 30min up to 2h and the gastrointestinal reactions were collected. RESULTS: The mean serum glucose was significantly lower in all time points after ingestion of the lacritose for participants with type 2 diabetes compared to glucose and sucrose (P<0.05). The blood glucose levels were significantly lower in the 30th and 60th min for healthy subjects (P<0.05). Adverse GI reactions were not significant between the test beverages. CONCLUSIONS: The ingestion of a 50g dose of lacritose containing lactose, fructose, sucrose, and erythritol, led to an improved blood glucose levels without any significant adverse effect compared to the same amount of glucose and sucrose. Studying the long-term effects of lacritose on appetite, metabolic markers and adverse reactions is recommended. The trial was registered in Iranian registry of clinical trials: IRCT2015050912571N2.

Comparison of three oral contrast preparations for magnetic resonance enterography in pediatric patients with known or suspected Crohn disease: a prospective randomized trial.

BACKGROUND: Oral contrast preparation is fundamental to ensuring diagnostic examination quality for magnetic resonance enterography (MRE), yet little is known about the relative palatability and tolerability of various oral contrast agents in pediatric patients with known or suspected inflammatory bowel disease. OBJECTIVE: We prospectively compared three MRE oral preparations in pediatric patients with known or suspected Crohn disease with respect to patient-reported tolerability and radiologist-determined small-bowel distension and opacification. MATERIALS AND METHODS: Seventy-five pediatric patients (mean age 14.8 years, 55% female) with known or suspected Crohn disease referred for MRE were randomized to an oral preparation with a sugar alcohol-based flavored beverage (Breeza), polyethylene glycol preparation (MiraLAX), or low-concentration barium sulfate suspension (VoLumen). Patients were instructed to consume oral contrast agent (using a weight-based protocol) beginning 60 min prior to MRE imaging. Following MRE, patients completed a questionnaire regarding their oral preparation solution including: taste (1-5 scale), feeling of well-being (1-5 scale) and willingness to consume again (yes/no). Two radiologists reviewed all MRE exams and rated exams for global features (active disease, overall small-bowel distention [1-4 scale]) and features specific to individual small-bowel segments (extent of distention, maximal luminal diameter, opacification, and susceptibility artifact). Statistical methods included one-way analysis of variance (ANOVA) with Tukey honest difference and Fisher exact tests. RESULTS: The overall rate of completion of the entire prescribed contrast volume was 53% (40/75), with a significantly higher rate of completion for MiraLAX than for VoLumen (70% vs. 30%, P=0.007). Crossover to a different preparation occurred in nine patients (12%) and was significantly more frequent when the initial preparation was VoLumen versus MiraLAX (29% vs. 0%, P=0.005). Mean subjective taste ratings for both MiraLAX (3.4, P<0.0001) and Breeza (2.8, P=0.006) were superior to those of VoLumen (1.9), which persisted in the subset of patients with MRE evidence of active Crohn disease. Patients who consumed MiraLAX were more likely to be willing to drink it again compared to those consuming VoLumen (82% vs. 46%, P=0.009). Overall small-bowel distention and bowel-segment-specific metrics (distention, maximal diameter, opacification and susceptibility) did not significantly differ among groups. CONCLUSION: In pediatric patients with known or suspected Crohn disease, MiraLAX and Breeza were rated as more palatable than VoLumen, and all three preparations achieved a similar degree of small-bowel distension and opacification on MRE. Imaging centers performing MRE should stock multiple oral contrast preparations because a sizable proportion of children require more than one agent to ingest the requisite oral contrast volume.

The low FODMAP diet in the management of irritable bowel syndrome: an evidence-based review of FODMAP restriction, reintroduction and personalisation in clinical practice.

Dietary restriction of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) is effective in the management of functional gastrointestinal symptoms that occur in irritable bowel syndrome (IBS). Numerous reviews have been published regarding the evidence for their restriction in the low FODMAP diet; however, few reviews discuss the implementation of the low FODMAP diet in practice. The aim of this review is to provide practical guidance on patient assessment and the implementation and monitoring of the low FODMAP diet. Broadly speaking, the low FODMAP diet consists of three stages: FODMAP restriction; FODMAP reintroduction; and FODMAP personalisation. These stages can be covered in at least two dietetic appointments. The first appointment focuses on confirmation of diagnosis, comprehensive symptom and dietary assessment, detailed description of FODMAPs and their association with symptom induction, followed by counselling regarding FODMAP restriction. Dietary counselling should be tailored to individual needs and appropriate resources provided. At the second appointment, symptoms and diet are re-assessed and, if restriction has successfully reduced IBS symptoms, education is provided on FODMAP reintroduction to identify foods triggering symptoms. Following this, the patient can follow FODMAP personalisation for which a less restrictive diet is consumed that excludes their personal FODMAP triggers and enables a more diverse dietary intake. This review provides evidence and practice guidance to assist in delivering high-quality clinical service in relation to the low FODMAP diet.

Continuous combined intake of polydextrose and lactitol stimulates cecal fermentation and salivary IgA secretion in rats.

Immunoglobulin A (IgA), which plays an important role in infection defense, is upregulated in the large intestine and oral cavity through dietary fiber intake. However, the mechanism underlying salivary IgA increase through dietary fiber intake remains unknown. This study investigated time-dependent effects of non-absorbable polydextrose (PDX) and lactitol intake on salivary IgA secretion and cecal fermentation. Five-week-old rats were fed a fiber-free diet with or without 25 g/kg PDX and 25 g/kg lactitol for 1, 4, and 8 weeks. Compared to control, those who ingested PDX and lactitol had higher salivary IgA flow rates per weight of submandibular gland tissue at 4 and 8 weeks (P < 0.05), greater cecal weight and digesta at 1, 4, and 8 weeks (P < 0.05), and lower concentrations of short chain fatty acids (SCFAs) in cecal digesta (P = 0.0003). These findings suggest that the consumption of PDX and lactitol may upregulate salivary IgA secretion possibly by stimulating absorption of SCFAs produced by cecal fermentation. Thus, continuous ingestion of PDX and lactitol for up to 4 weeks could increase salivary IgA and promote immune defense against pathogen invasion through the oral route.

Glycaemia and phosphatemia after oral glucose and maltitol ingestion in subjects from two different race groups: preliminary evidence of inter-race differences in metabolism and possible implications for urinary stone disease.

PURPOSE: Glucose (Glu) and maltitol (Mal) ingestion affect calciuria and phosphaturia. Renal phosphate leak involving hypophosphatemia is thought to be a mechanism. Inter-race differences in carbohydrate metabolism are known. We investigated the effects of Glu and Mal ingestion on glycaemia and phosphatemia in subjects from two race groups to better understand potential implications for nephrolithiasis. METHODS: Healthy black (B) (n = 8) and white (W) (n = 8) males followed a self-selected standardized diet for 7 days and a strictly controlled standardized diet on Day 8. After an overnight fast, subjects provided blood samples prior to and 30 min after ingestion of a randomly assigned solution of Glu or Mal. Blood Glu and serum phosphate were measured. Protocols were swapped after a 1-week washout period. RESULTS: Following Glu ingestion, glycaemia increased significantly in W (4.8 vs 6.2 mmol/l) but not in B (4.7 vs 5.3 mmol/l) while phosphatemia decreased significantly in B (1.16 vs 1.01 mmol/l) but not in W (1.24 vs 1.15 mmol/l). After Mal ingestion, glycaemia increased significantly in B (4.7 vs 5.2 mmol/l) but not in W (4.6 vs 5.9 mmol/l), while phosphatemia decreased significantly in W (1.24 vs 1.18 mmol/l) but not in B (1.17 vs 1.06 mmol/l). CONCLUSIONS: Our results suggest that enzymes which regulate glycolysis may be less active in B than in W, or expression of renal transcellular Glu transporters may be relatively inhibited in B. Effects on phosphatemia are carbohydrate- and race-dependent, thereby prohibiting speculation of a general algorithm linking these variables. Inter-race differences in metabolic handling of carbohydrates might impact on respective nephrolithiasis risk factors in such groups.

The caries preventive effect of 1-year use of low-dose xylitol chewing gum. A randomized placebo-controlled clinical trial in high-caries-risk adults.

OBJECTIVES: The caries preventive effect of long-term use (1 year) of low-dosage (2.5 g/die) of xylitol chewing gum in a high-caries-risk adult population was evaluated. MATERIALS AND METHODS: In this randomized clinical trial, 179 high-caries-risk adults were assigned to two experimental groups, xylitol and polyols. Caries status, salivary mutans streptococci (MS), and plaque pH were re-evaluated after 2 years from baseline in 66 xylitol and 64 polyol subjects. Outcomes (the net caries increment for initial, moderate, and extensive caries lesions and for the caries experience) were evaluated using the nonparametric Mann-Whitney U test. RESULTS: The total caries experience increment was 1.25 ± 1.26 in the xylitol group and 1.80 ± 2.33 in the polyol group (p = 0.01). Subjects treated with xylitol chewing gums had a reduction of risk rate at tooth level of 23% with respect to those treated with polyols with a number needed to treat of 55 teeth. The area under the curve at pH 5.7 was statistically significantly lower (p = 0.02) during the experimental period in the xylitol group. A decrease of the concentration of salivary MS was noted in the xylitol group (p < 0.01). CONCLUSIONS: Subjects using the low-dose xylitol chewing gum showed a significantly lower increment of initial and extensive caries lesions and overall a lower increment of caries experience. CLINICAL RELEVANCE: One-year use of chewing gums provides an effective means for the prevention of caries disease. TRIAL REGISTRATION NUMBER: NCT02310308.

Gut Function-Enhancing Properties and Metabolic Effects of Dietary Indigestible Sugars in Rodents and Rabbits.

Indigestible sugars (iS) have received particular interest in food and nutrition research due to their prebiotic properties and other health benefits in humans and animals. The main aim of this review article is to summarize the current knowledge regarding digestive and health-enhancing properties of iS such as sugar alcohols, oligosacharides, and polysaccharides, in rodents and rabbits. Besides ameliorating gut health, iS ingestion also elicits laxative effects and stimulate intestinal permeability and fluid secretions, thereby shortening digesta transit time and increasing stool mass and quality. In rodents and rabbits, as hindgut fermenters, consumption of iS leads to an improved nutrient digestibility, too. Cecal fermentation of iS reduces luminal pH and extends wall tissue facilitating absorption of key dietary minerals across hindgut. The microbial fermentation of iS also enhances excessive blood nitrogen (N) flowing into the cecum to be used as N source for bacterial growth, enhancing N retention in cecotrophic animals. This review also highlights the impact of iS on improving lipid metabolism, mainly by lowering cholesterol and triglycerides levels in the blood. The paper serves as an index of the current knowledge of iS effects in rodents and rabbits and also identifies gaps of knowledge that need to be addressed by future research.

Maltitol Prevents the Progression of Fatty Liver Degeneration in Mice Fed High-Fat Diets.

Nonalcoholic fatty liver disease (NAFLD) progresses to nonalcoholic steatohepatitis, ultimately leading to cirrhosis and liver cancer. It is important to prevent this progression during the initial stages of hepatic fatty degeneration. Maltitol is a polyol produced by the hydrogenation of maltose. We investigated the efficacy of maltitol for treating hepatic fatty degeneration in C57BL/6 male mice using a high-fat diet model. Intake of 5.0% maltitol for 8 weeks significantly suppressed weight gain, hepatic fatty degeneration, hyperglycemia, and hypercholesterolemia. With maltitol intake, sterol regulatory element-binding protein 1c (SREBP1c) mRNA expression was significantly decreased, and farnesoid X receptor (FXR), peroxisome proliferator-activated receptor α (PPARα), and hydroxymethylglutaryl-Co reductase expressions were significantly higher in the liver. The increase in SREBP1c and suppression of FXR and PPARα expressions are correlated with NAFLD. Our results suggest that maltitol may prevent steatosis of NAFLD with a high-fat diet.

Health benefits of prebiotic fibers.

This chapter describes the various compounds that can act as prebiotic fibers: their structure, occurrence, production, and physiological effects (health effects) will be presented. The basis for the description is the latest definitions for dietary fibers and for prebiotics. Using as much as possible data from human studies, both the fiber and the prebiotic properties will be described of a variety of compounds. Based on the presented data the latest developments in the area of prebiotics, fibers and gut and immune health will be discussed in more detail as they show best what the potential impact of prebiotics on health of the human host might be.

Effects of synbiotic food consumption on glycemic status and serum hs-CRP in pregnant women: a randomized controlled clinical trial.

OBJECTIVE: The aim of this study was to determine the effects of synbiotic food consumption on glycemic status and serum high sensitivity C-reactive protein (hs-CRP) levels of Iranian pregnant women. DESIGN: This randomized placebo-controlled clinical trial was performed among 52 pregnant women, primigravida, aged 18-35 year old, in their third trimester. After a 2-wk run-in period, subjects were randomly assigned to consume either a synbiotic (n=26) or control food (n=26) for 9 weeks. The synbiotic food consisted of a probiotic Lactobacillus sporogenes (1×107 CFU), 0.04 g inulin as prebiotic with 0.38 g isomalt, 0.36 g sorbitol and 0.05 g stevia as sweetener per 1 g. Control food (the same substance without probiotic bacteria and inulin) was packed in identical 9-gram packages. Patients were asked to consume the synbiotic and control foods two times a day. Fasting blood samples were taken at baseline and after a 9-wk intervention for quantification of related factors. RESULTS: Consumption of a synbiotic food did not show any significant change regarding the impact of insulin actions in the synbiotic group; nonetheless, compared to the control food, it resulted in a significant decrease in serum insulin levels (-0.26 vs. 6.34 µIU/mL, P=0.014) and HOMA-IR (-0.13 vs. 1.13, P=0.033), a significant difference in HOMA-B (5.30 vs. 34.22, P=0.040) and a significant rise in QUICKI score (0.002 vs. -0.02, P=0.022). CONCLUSIONS: Consumption of a synbiotic food for 9 weeks by pregnant women had beneficial effects on insulin actions compared to the control food, but did not affect FPG and serum hs-CRP concentrations.

Alditols and monosaccharides from sorghum vinegar can attenuate platelet aggregation by inhibiting cyclooxygenase-1 and thromboxane-A2 synthase.

ETHNOPHARMACOLOGICAL RELEVANCE: Vinegar has been used as both a common seasoning and a traditional Chinese medicine. Sorghum vinegar is an excellent source of physiological substances with multiple health benefits. AIM OF THIS STUDY: To evaluate the antiplatelet aggregation activity of alditols and monosaccharides extracted from sorghum vinegar and analysis its mechanism. MATERIALS AND METHODS: Alditol and monosaccharide extract (AME) from sorghum vinegar was first evaluated for antiplatelet activity using the turbidimetric method. Blood was collected from healthy volunteer donors. The platelet aggregation was induced by arachidonic acid (AA), collagen, adenosine diphosphate (ADP) and thrombin in vitro. AME was divided into three experimental groups with the concentration were 0.10, 0.25 and 0.50 mg/mL. In order to determine the inhibitory activity of AME on COX1, TXS and TXA2 production experiments were conducted using the COX1, TXS and TXB2 EIA kit. Computational docking was used to find the docking pose of monosaccharides and alditols with COX1. RESULTS: AME showed significant induction of antiplatelet activity by arachidonic acid (AA), collagen, adenosine diphosphate (ADP) and thrombin in a concentration-dependent manner (p<0.05). AME (0.50 mg/mL) reduced the AA-induced aggregation rate to 10.35%±0.46%, which was comparable to acetylsalicylic acid (aspirin, ASA) (0.50 mg/mL, 6.35%±0.58%), a medical standard. Furthermore, AME strongly inhibited cyclooxygenase-1 (COX1) and thromboxane-A2 synthase (TXS), and subsequently attenuated thromboxane-A2 (TXA2) production. These findings indicated that AME attenuates platelet aggregation through the AA metabolism pathway. Computational docking showed that alditols (L-erythritol, L-arabitol, xylitol and D-sorbitol), monosaccharides (D-glucopyranose, D-fructofuranonse, D-xylopyranose, D-galactopyranose and D-ribose), ethyl glucoside and 3,4-(methylenedioxy) mandelic acid could dock directly into the active site of COX1. CONCLUSION: Alditols and monosaccharides from sorghum vinegar inhibit multiple steps in the platelet aggregation pathway, and may be beneficial for the treatment of cardiovascular diseases.

Digestive tolerance and postprandial glycaemic and insulinaemic responses after consumption of dairy desserts containing maltitol and fructo-oligosaccharides in adults.

BACKGROUND/OBJECTIVES: To evaluate the short-term digestive tolerance and glycaemic response of several associations of maltitol and short-chain fructo-oligosaccharides (scFOS) used to replace sugars (for example, dextrose) in foods. SUBJECTS/METHODS: Thirty-six healthy subjects aged 18-60 years were recruited for the study and 32 completed it. The subjects consumed six different mixtures of dextrose, maltitol and scFOS added in a chocolate dairy dessert at a dosage of 35 g. The test days were separated by 2-week washout periods. The subjects reported the intensity of four individual gastrointestinal (GI) symptoms, number of bowel movements and stool frequency for the 48 h following consumption of the dessert. A subgroup of 18 subjects also provided blood samples 2 h after intake to evaluate the postprandial glycaemic and insulinaemic responses. RESULTS: The composite score calculated from the intensity of flatulence, borborygmi, bloating and discomfort was significantly higher (P<0.0001) for all the desserts containing maltitol and/or scFOS than for the control dessert containing dextrose, but remains at the level of mild effects. The number of bowel movements was also slightly increased (P=0.0006) and the stools were softer (P=0.0045) for the first 24 h but not after (P=0.1373 and 0.5420, respectively). Blood glycaemic and insulinaemic responses were lower for all the sugar-free recipes containing maltitol and scFOS in comparison to the control one (P<0.0001). CONCLUSIONS: This study has shown that maltitol and scFOS can be used jointly when formulating sugar-free foods with the benefit to lower postprandial glycaemic response with only a small and transient increase in non-serious GI symptoms.

[Prevention of hepatic encephalopathy]. / Profilaxis de la encefalopatía hepática.

Hepatic encephalopathy (HE) is a frequent complication of cirrhosis which, in addition to producing a great social impact, deteriorates the quality of life of patients and is considered a sign of advanced liver disease and therefore a clinical indication for liver transplant evaluation. Patients who have had episodes of HE have a high risk of recurrence. Thus, after the HE episode resolves, it is recommended: control and prevention of precipitating factors (gastrointestinal bleeding, spontaneous bacterial peritonitis, use of diuretics with caution, avoid nervous system depressant medications), continued administration of non-absorbable disaccharides such as lactulose or lactitol, few or non-absorbable antibiotics such as rifaximin and assess the need for a liver transplant as the presence of a HE episode carries a poor prognosis in cirrhosis.

Evaluation of a sieve classification method for characterization of low-dose interactive mixtures.

This study investigated a sieve classification method for evaluating carrier materials and particle size fractions, which could be a valuable tool in the early development of pharmaceutical dosage forms containing low-dose interactive mixtures. When developing new products based on interactive mixtures, it is essential to ensure that the drug particles are successfully deagglomerated and have adhered to the carrier particles. In this study, the effect on the demixing potential (DP) of low-dose interactive mixtures was assessed for various carrier particle sizes and surface textures. The model drug used was sodium salicylate and the tested carriers were lactose, mannitol, and isomalt. The results showed that the lowest DPs, i.e. the most mechanically stable mixtures, were obtained with lactose. Furthermore, for interactive mixtures, small carrier particles and/or a narrow carrier particle size range are essential for obtaining a low DP and high homogeneity. Calculation of the DP provided a reliable estimate of the quality of the low-dose interactive mixtures used in this study.

Assessment of isomalt for colon-specific delivery and its comparison with lactulose.

Lactulose is used as a triggering substance in a unique colon-specific delivery technology called CODESTM. Colonic microflora degrades lactulose and forms short-chain fatty acids to activate the CODESTM system. However, lactulose has been reported to cause a Maillard-type reaction with substances containing primary or secondary amino groups that may produce carcinogenic compounds. Thus, the aim of this study was to look into the possibility to substitute lactulose with isomalt for fabrication of CODESTM. The in vitro degradation of both sugars before incorporating them into the CODESTM system was evaluated with the help of rat caecal microflora. The results showed that isomalt was less efficient with regard to its rate and extent of degradation into short-chain fatty acids by the microflora compared to lactulose. However, the in vitro dissolution study did not show a significant difference in the performance between lactulose and isomalt when they were incorporated separately in CODESTM. A similar result was also obtained in the in vivo study. Based on the above results, isomalt could be used as an alternative to lactulose for colonic delivery system utilizing the principles of CODESTM.