Administration Of Lactulose Research Articles

Coadministration of Lactulose with Probiotics Ameliorates Loperamide-Induced Constipation in Mice.

We evaluated the efficacy of mixtures of lactulose with probiotic strains to ameliorate constipation and to identify suitable probiotic strains. Constipation was induced in Institute of Cancer Research mice (6-week-old, male) by the administering loperamide (5 mg/kg, twice a day) orally for 5 days, whereas the control group was not treated. To evaluate the laxative effects of the lactulose-probiotic and lactulose-magnesium hydroxide mixtures, fecal parameters, the gastrointestinal (GI) transit ratio, and fecal short-chain fatty acid (SCFA) content were analyzed. The administration of lactulose and Bacillus licheniformis or Saccharomyces boulardii significantly improved stool number and water content, which were reduced by loperamide. The GI transit ratio was significantly increased compared with that of the control group. The combined administration of lactulose and probiotics (B. licheniformis or S. boulardii) increased total SCFA content, including that of acetate, more effectively compared with lactulose alone. Similarly, coadministration of lactulose and magnesium hydroxide improved the loperamide-induced changes in fecal parameters and GI transit as well as increased total SCFA content. Overall, the combination of lactulose and probiotics relieves the symptoms of constipation by increasing SCFA content and is more effective compared with lactulose alone.

Prebiotic prevents the development of gastrointestinal motility disorders caused by omeprazole

The synthetic disaccharide lactulose, consisting of fructose and galactose, after oral administration in an unchanged form reaches the lower part of the gastrointestinal tract, where under the action of normal flora it is broken down into short-chain fatty acids that stimulate colon motility. The effect of lactulose on gastrointestinal tract motility in the conditions of its long-term suppression by omeprazole has not been investigated. We studied the influence of lactulose on spontaneous and carbachol-stimulated gastric and colonic motility in rats treated with omeprazole for 28 days. The animals were divided into 3 groups. The first group of animals served as a control. The animals in the second group were administered omeprazole intraperitoneally at a dose of 14 mg/kg orally once a day for 28 days. The animals in the third group were simultaneously injected intraperitoneally with omeprazole and prebiotic lactulose at a dose of 0.2 g/kg orally once a day for 28 days. On the day after the last injections of drugs, we investigated the spontaneous and carbachol-stimulated contractions in the stomach and colon by the balloon graphic method. It was found that the frequency of spontaneous and stimulated contractions in the stomach and colon did not change significantly after 28 days of omeprazole treatment. The amplitude and index of spontaneous and carbachol-stimulated contractions in the stomach and colon were significantly weaker compared to the control. One day after the 28-day simultaneous administration of omeprazole and lactulose the amplitude and index of spontaneous and stimulated contractions in the stomach and colon increased compared with the group of rats treated with omeprazole alone. We concluded that the positive effect of lactulose on gastric and colon motility is a result of the prebiotic properties of lactulose which leads to the normalization of the microbiocenosis in the gastrointestinal tract and the elimination of the inflammatory process in it.

Correlation of lactulose-to-mannitol ratios in plasma and urine for intestinal permeability assessment in pigs.

The lactulose-to-mannitol ratio test is a test to assess the disorders associated with gut permeability. The test requires an oral administration of the mixture of lactulose and mannitol and urine collection. The urinary ratio of lactulose to mannitol is an indicator of intestinal permeability. Due to the complexity of urine collection in animal studies, plasma exposure ratios of lactulose to mannitol compared to their urinary concentration ratios were evaluated following an oral administration of the sugar mixture in pigs. 10 pigs were orally dosed with a solution of lactulose and mannitol mixture. Plasma samples were collected at predose, 10 and 30 minutes and 2, 4, and 6 hours postdosing, and cumulated urinary samples were collected at 6 hours for liquid chromatography-mass spectrometry analysis. The ratios of pharmacokinetic parameters of lactulose to mannitol and the plasma sugar ratios at a single time point or the mean values of several time points were compared to their urinary sugar ratios. The results revealed that the lactulose-to-mannitol ratios of AUC0-6h, AUCextrap, and Cmax were correlated to the urinary sugar ratios, and the plasma sugar ratios of a single time point at 2, 4, or 6 hours and the mean values of those time points were also appropriate to replace their urinary ratios in pigs. Following an oral administration of lactulose and mannitol mixture, blood collection, and assay can be an option for assessing intestinal permeability, especially in animal studies.

SAT-545 - Administration of Lactulose, Rifaximin, or combination therapy for hepatic encephalopathy is associated with a reduction in gastrointestinal cancers

SAT-545 - Administration of Lactulose, Rifaximin, or combination therapy for hepatic encephalopathy is associated with a reduction in gastrointestinal cancers

Portal Systemic Encephalopathy without Significant Changes of Chronic Liver Disease: A Case Report

Introduction: Determining the etiology of an encephalopathy can be challenging for the neurologists, especially when the preliminary investigations do not indicate any significant biochemical or other systemic abnormality. Portosystemic shunts maybe easily missed and may present as recurrent encephalopathy with elevated serum ammonia or cerebrospinal glutamate levels. These shunts maybe easily identified in the presence of overt chronic liver disease, but maybe easily missed in patients with cryptogenic liver disease or in congenital abnormalities of the intrahepatic vascular system without an associated chronic liver disease. Materials and Methods: The triple-phase computed tomography (CT) or contrast magnetic resonance imaging can demonstrate the extent of portal vein thrombosis, map the extent of the portosystemic collateral, and aid in planning the treatment in patients with difficult anatomy of the portosystemic collaterals. Treatment regimens for patients with portosystemic shunts manifesting as hyperammonemic encephalopathy include restriction of oral protein intake, lactulose administration, oral nonabsorbable antibiotics, closure of the endovascular shunt, or finally, liver transplant. We present a case of a 55-year-old female with seizure disorder presenting with recurrent episodes of encephalopathy with elevated serum ammonia without the overt signs of chronic liver disease with identification of portosystemic shunting on a triple-phase CT of the abdomen. Conclusion: Specialized investigations to identify the presence of portosystemic collaterals should be conducted in patients with cryptogenic encephalopathy with elevated serum ammonia.

A curious case of confusion

A curious case of confusion

Long-Term Lactulose Administration Improves Dysbiosis Induced by Antibiotic and C. difficile in the PathoGutTM SHIME Model.

Clostridioides difficile infection (CDI) is the leading cause of antibiotic-associated diarrhea and an important nosocomial infection with different severity degrees. Disruption of the gut microbiota by broad-spectrum antibiotics creates a proper environment for C. difficile colonization, proliferation, and clinical disease onset. Restoration of the gut microbial ecosystem through prebiotic interventions can constitute an effective complementary treatment of CDI. Using an adapted simulator of the human gut microbial ecosystem, the PathoGutTM SHIME, the effect of different long-term and repeated dose lactulose treatments was tested on C. difficile germination and growth in antibiotic-induced dysbiotic gut microbiota environments. The results showed that lactulose reduced the growth of viable C. difficile cells following clindamycin treatment, shifted the antibiotic-induced dysbiotic microbial community, and stimulated the production of health-promoting metabolites (especially butyrate). Recovery of the gut microenvironment by long-term lactulose administration following CDI was also linked to lactate production, decrease in pH and modulation of bile salt metabolism. At a structural level, lactulose showed a significant bifidogenic potential and restored key commensal members of the gut ecosystem such as Lactobacillaceae, Veillonellaceae and Lachnospiraceae. These results support further human intervention studies aiming to validate the in vitro beneficial effects of lactulose on gut microbiome recovery during antibiotic exposure and CDI.

S3430 Lactulose Works in the Large Bowel: But How Does It Improve Hepatic Encephalopathy in a Patient Without a Large Bowel?

Introduction: Lactulose is a non-absorbable disaccharide which acts in the large bowel, and is commonly used in the treatment of hepatic encephalopathy. We present an interesting case of altered mental status due to hepatic encephalopathy successfully managed with lactulose in a patient with history of total colectomy. Case Description/Methods: A 67-year-old male with non-alcoholic cirrhosis and inflammatory bowel disease (IBD) post total proctocolectomy with a continent ileostomy known as a “Kock-pouch” (K-pouch) presented to the hospital with flu like symptoms and altered mental status. He was subsequently found to be positive for COVID-19. At the time of initial evaluation, the patient was obtunded with an elevated ammonia level of 91 umol/L. Colorectal surgery was consulted as the patient was not able to empty his K-pouch. Recently, he complained of inability to catheterize and with bleeding from the stoma. Initial catheterization with a Water’s tube yielded 400 cc of effluent. Nasogastric tube was placed through which he was receiving lactulose 30 mg q8 hours. The patient’s mental status improved within 24 hours. The patient ultimately underwent flexible pouchoscopy with endoscopic dilation and placement of a 22 French mushroom catheter for decompression of the K-pouch. Discussion: Lactulose is a non-absorbable disaccharide composed of galactose and fructose. The small intestine does not have the enzymes required to breakdown lactulose so it reaches the large bowel in its original form. In the large bowel, it is metabolized by colonic bacteria into monosaccharides and then to volatile fatty acids, hydrogen and methane. Lactulose decreases both the production and absorption of ammonia mainly through the presence of gut bacteria. The question arises as to how lactulose decreased ammonia levels in this patient without a large bowel. One proposed mechanism is the translocation of bacteria normally found in the large bowel to the small intestine. Small Intestinal Bacterial Overgrowth (SIBO), is a condition causing an increased number of bacteria in the small intestine. Patients with IBD and structural abnormalities are at increased risk of developing SIBO. Lactulose is commonly used in the diagnosis through the administration of lactulose and subsequent measurements of hydrogen and methane gas in expired air. This condition, in our patient with history of ulcerative colitis and colectomy, is a proposed mechanism of the efficacy of lactulose in the treatment of hepatic encephalopathy.

Co-Administration of Lactulose Crystals with Amoxicillin Followed by Prolonged Lactulose Treatment Promotes Recovery of the Human Gut Microbiome In Vitro.

The validated SHIME model was used to assess the effect of repeated administration of two different lactulose dosages (5 g/d and 10 g/d) on the human gut microbiome during and following amoxicillin–clavulanic acid treatment. First, antibiotic treatment strongly decreased Bifidobacteriaceae levels from 54.4% to 0.6% and from 23.8% to 2.3% in the simulated proximal and distal colon, respectively, coinciding with a marked reduction in butyrate concentrations. Treatment with lactulose enhanced acetate and lactate levels during antibiotic treatment, likely through lactulose fermentation by Lachnospiraceae and Lactobacillaceae. One week after cessation of antibiotic treatment, Bifidobacteriaceae levels re-increased to 20.4% and 7.6% in the proximal and distal colon of the 5 g lactulose/d co-administered unit, as compared with 1.0% and 2.2% in the antibiotic-treated unit, and were even further stimulated upon extension of lactulose administration. Marked butyrogenic effects were observed upon prolonged lactulose supplementation, suggesting the establishment of cross-feeding interactions between Bifidobacteriaceae and butyrate producers. Furthermore, a limited Enterobacteriaceae outgrowth following antibiotic treatment was observed upon dosing with 10 g lactulose/d, indicating inhibition of pathogenic colonization by lactulose following antibiotic therapy. Overall, lactulose seems to be an interesting candidate for limiting the detrimental effects of amoxicillin–clavulanic acid on the human gut microbiome, though further studies are warranted to confirm these findings.

Local and Systemic Effects of Green Coffee Extract (Coffea canephora) in Animal Model of Colorectal Carcinogenesis

ObjectivesEvaluate the local and systemic effects of aqueous extract of green coffee (GCE) in colorectal carcinogenesis (CRC) induced in rats. MethodsAdult Wistar rats (n = 48) were divided into two groups (C and T, n = 24). Group T was induced to CRC with 1,2-dimethylhydrazine (55 mg/kg, subcutaneously, weekly) for 5 weeks, and during this period all animals received standard AIN93-M diet. From week 6 to 15, the animals were divided into 4 groups (n = 12): C (healthy control fed AIN93-M diet), T (CRC- induced, fed AIN93-M diet), CGC (healthy control, fed AIN93-M diet + GCE), TGC (CRC-induced, fed AIN93-M diet + GCE). At 10th week, the pre-neoplastic lesions were evaluated in 4 rats from each group. The remaining rats (n = 8) were feed their experimental diet until the 15th week. In the last week, 24 h-urine collection was performed for intestinal permeability analysis using lactulose (100 mg/kg) and mannitol (50 mg/kg) administration. Afterwards, blood samples were collected to the analyses of plasma cytokines (TNF-alpha, interleukins IL-6, 10 and 12) and total antioxidant capacity (TAC). Large intestine content was collected for pH and secretory immunoglobulin A (sIgA) analyses. The microscopic lesions were evaluated in the colorectal mucosa. ResultsTGC group had the highest aberrant crypt foci (ACF) count, 51% higher compared to the T group. Intestinal permeability was increased in the T group. There was no significant difference in the quantification of cytokines TNF-alpha, IL-6, 10 and 12. Both TGC and T showed high values of TAC. Intestinal pH was significantly higher in CGC group compared to TGC. There was no significant difference in the quantification of sIgA between groups. The reduction of malignant neoplastic changes was 42% and of benign changes was 66% and there was a reduction of 33.33% and 20% of hyperplasia and dysplasia, respectively, in TGC compared with T group. ConclusionsGCE was beneficial for intestinal permeability and controlled the development of neoplasms in the colorectal mucosa, without interfering with systemic inflammation, reinforcing that GCE reduces the risk of developing the CRC. Funding SourcesThis study was financed by CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) and FAPES (Fundação de Amparo à Pesquisa e Inovação do Espírito Santo), Brazil.

Altered Intestinal Production of Volatile Fatty Acids in Dogs Triggered by Lactulose and Psyllium Treatment.

The intestinal microbiome of dogs can be influenced by a number of factors such as non-starch polysaccharides as well as some non-digestible oligo- and disaccharides. These molecules are only decomposed by intestinal anaerobic microbial fermentation, resulting in the formation of volatile fatty acids (VFAs), which play a central role in maintaining the balance of the intestinal flora and affecting the health status of the host organism. In the present study, the effects of lactulose and psyllium husk (Plantago ovata) were investigated regarding their influence on concentrations of various VFAs produced by the canine intestinal microbiome. Thirty dogs were kept on a standard diet for 15 days, during which time half of the animals received oral lactulose once a day, while the other group was given a psyllium-supplemented diet (in 0.67 and in 0.2 g/kg body weight concentrations, respectively). On days 0, 5, 10 and 15 of the experiment, feces were sampled from the rectum, and the concentration of each VFA was determined by GC-MS (gas chromatography–mass spectrometry). Lactulose administration caused a significant increase in the total VFA concentration of the feces on days 10 and 15 of the experiment (p = 0.035 and p < 0.001, respectively); however, in the case of psyllium supplementation, the concentration of VFAs showed a significant elevation only on day 15 (p = 0.003). Concentrations of acetate and propionate increased significantly on days 5, 10 and 15 after lactulose treatment (p = 0.044, p = 0.048 and p < 0.001, respectively). Following psyllium administration, intestinal acetate, propionate and n-butyrate production were stimulated on day 15, as indicated by the fecal VFA levels (p = 0.002, p = 0.035 and p = 0.02, respectively). It can be concluded that both lactulose and psyllium are suitable for enhancing the synthesis of VFAs in the intestines of dogs. Increased acetate and propionate concentrations were observed following the administration of both supplements; however, elevated n-butyrate production was found only after psyllium treatment, suggesting that the applied prebiotics may exert slightly different effects in the hindgut of dogs. These findings can be also of great importance regarding the treatment and management of patients suffering from intestinal disorders as well as hepatic encephalopathy due to portosystemic shunt.

Gut integrity and duodenal enteropathogen burden in undernourished children with environmental enteric dysfunction.

Environmental enteric dysfunction (EED) is a subclinical condition of intestinal inflammation, barrier dysfunction and malabsorption associated with growth faltering in children living in poverty. This study explores association of altered duodenal permeability (lactulose, rhamnose and their ratio) with higher burden of enteropathogen in the duodenal aspirate, altered histopathological findings and higher morbidity (diarrhea) that is collectively associated with linear growth faltering in children living in EED endemic setting. In a longitudinal birth cohort, 51 controls (WHZ > 0, HAZ > −1.0) and 63 cases (WHZ< -2.0, refractory to nutritional intervention) were recruited. Anthropometry and morbidity were recorded on monthly bases up to 24 months of age. Dual sugar assay of urine collected after oral administration of lactulose and rhamnose was assessed in 96 children from both the groups. Duodenal histopathology (n = 63) and enteropathogen analysis of aspirate via Taqman array card (n = 60) was assessed in only cases. Giardia was the most frequent pathogen and was associated with raised L:R ratio (p = 0.068). Gastric microscopy was more sensitive than duodenal aspirate in H. pylori detection. Microscopically confirmed H. pylori negatively correlated with HAZ at 24 months (r = −0.313, p = 0.013). Regarding histopathological parameters, goblet cell reduction significantly correlated with decline in dual sugar excretion (p< 0.05). Between cases and controls, there were no significant differences in the median (25th, 75th percentile) of urinary concentrations (μg/ml) of lactulose [27.0 (11.50, 59.50) for cases vs. 38.0 (12.0, 61.0) for controls], rhamnose [66.0 (28.0, 178.0) vs. 86.5 (29.5, 190.5)] and L:R ratio [0.47 (0.24, 0.90) vs. 0.51 (0.31, 0.71)] respectively. In multivariable regression model, 31% of variability in HAZ at 24 months of age among cases and controls was explained by final model including dual sugars. In conclusion, enteropathogen burden is associated with altered histopathological features and intestinal permeability. In cases and controls living in settings of endemic enteropathy, intestinal permeability test may predict linear growth. However, for adoption as a screening tool for EED, further validation is required due to its complex intestinal pathophysiology.

Lactulose Improves Neurological Outcomes by Repressing Harmful Bacteria and Regulating Inflammatory Reactions in Mice After Stroke.

Background and ObjectiveGut microbiota dysbiosis following stroke affects the recovery of neurological function. Administration of prebiotics to counteract post-stroke dysbiosis may be a potential therapeutic strategy to improve neurological function. We aim to observe the effect of lactulose on neurological function outcomes, gut microbiota composition, and plasma metabolites in mice after stroke.MethodsMale C57BL/6 mice (20–25 g) were randomly divided into three groups: healthy control, photothrombotic stroke + triple-distilled water, and photothrombotic stroke + lactulose. After 14 consecutive days of lactulose administration, feces, plasma, and organs were collected. 16S rDNA sequencing, plasma untargeted metabolomics, qPCR, flow cytometry and Elisa were performed.ResultsLactulose supplementation significantly improved the functional outcome of stroke, downregulated inflammatory reaction, and increased anti-inflammatory factors in both the brain and gut. In addition, lactulose supplementation repaired intestinal barrier injury, improved gut microbiota dysbiosis, and partially amended metabolic disorder after stroke.ConclusionLactulose promotes functional outcomes after stroke in mice, which may be attributable to repressing harmful bacteria, and metabolic disorder, repairing gut barrier disruption, and reducing inflammatory reactions after stroke.

Hyperammonemia in patients receiving valproic acid in the hospital setting: A retrospective review.

IntroductionValproic acid (VPA) is widely used for the treatment of epilepsy, migraine, and a variety of psychiatric conditions. The reported incidences of hyperammonemia induced by VPA use is variable. The purpose of this study is to evaluate the incidence of VPA-induced hyperammonemia in the general adult inpatient population.MethodsAdult patients who received at least 1 dose of VPA and derivatives between June 1, 2017 to December 31, 2017 were included. Patients were excluded if they did not have VPA administered during their inpatient stay or if they had elevated ammonia levels (>33 μmol/L) prior to initiation of VPA. Patients with a confirmed diagnosis of liver cirrhosis were also excluded. The primary endpoint was the incidence of hyperammonemia. Secondary outcomes included symptoms of hyperammonemia, diagnosis of VPA-induced hyperammonemia, and treatment of VPA-induced hyperammonemia.ResultsA total of 162 patients were included in this study. A total of 33 (20.4%) patients were identified as having the primary outcome of hyperammonemia; 26 (16.0%) patients had symptoms of hyperammonemia, and 13 (8.0%) patients were diagnosed with VPA-induced hyperammonemia. Treatment modalities included administration of lactulose, levocarnitine, discontinuing VPA, or decreasing the VPA dose.DiscussionThe administration of VPA in the general adult inpatient population resulted in a 20.4% incidence of hyperammonemia, with a lower rate of diagnosed VPA-induced hyperammonemia. Clinicians should be encouraged to obtain ammonia levels in patients receiving VPA if symptoms of altered mental status or encephalopathy develop.

Recurrent noncirrhotic hyperammonemia causing acute metabolic encephalopathy in a patient with a continent ileocecal pouch: a case report

IntroductionAcute encephalopathy, while a common presentation in the emergency department, is typically caused by a variety of metabolic, vascular, infectious, structural, or psychiatric etiologies. Among metabolic causes, hyperammonemia is relatively common and typically occurs in the setting of cirrhosis or liver dysfunction. However, noncirrhotic hyperammonemia is a rare occurrence and poses unique challenges for clinicians.Case presentationHere we report a rare case of a 50-year-old Caucasian female with history of bladder cancer status post chemotherapy, radical cystectomy, and ileocecal diversion who presented to the emergency department with severe altered mental status, combativeness, and a 3-day history of decreased urine output. Her laboratory tests were notable for hyperammonemia up to 289 μmol/L, hypokalemia, and hyperchloremic nonanion gap metabolic acidosis; her liver function tests were normal. Urine cultures were positive for Enterococcus faecium. Computed tomography imaging showed an intact ileoceal urinary diversion with chronic ileolithiasis. Upon administration of appropriate antibiotics, lactulose, and potassium citrate, she experienced rapid resolution of her encephalopathy and a significant reduction in hyperammonemia. Her hyperchloremic metabolic acidosis persisted, but her hypokalemia had resolved.ConclusionThis case is an example of one of the unique consequences of urinary diversions. Urothelial tissue is typically impermeable to urinary solutes. However, when bowel segments are used, abnormal absorption of solutes occurs, including exchange of urinary chloride for serum bicarbonate, leading to a persistent hyperchloremic nonanion gap metabolic acidosis. In addition, overproduction of ammonia from urea-producing organisms can lead to abnormal absorption into the blood and subsequent oversaturation of hepatic metabolic capacity with consequent hyperammonemic encephalopathy. Although this is a rare case, prompt identification and treatment of these metabolic abnormalities is critical to prevent severe central nervous system complications such as altered mental status, coma, and even death in patients with urinary diversions.

Minimal portosystemic encephalopathy: A new nosological entity in patients with hereditary haemorrhagic telangiectasia

Background. Portosystemic shunts in Hereditary Haemorrhagic Telangiectasia (HHT) are often overlooked by conventional imaging although they could reduce hepatic clearance of gut-derived toxins.Aims. To evaluate, the presence of subclinical neurological alterations (SNAs), that we named “minimal portosystemic encephalopathy” (mPSE) in HHT patients without advanced liver disease (ALD).Methods. In this cross sectional study, consecutive HHT outpatients were firstly screened by critical flicker frequency (CFF) test (abnormal ≤39Hz), and the simplified animal naming test (S-ANT1) (abnormal <15) was used to confirm the diagnosis of mPSE. Furthermore, we evaluated the effect of lactulose administration on mPSE. Multi-slice CT, cerebral dynamic magnetic resonance, laboratory analyses and transient elastography were also used.Results. None of the 37 enrolled patients showed portosystemic shunts at imaging techniques. However, 33 patients had normal CFF values (CFF-) and 4 displayed CFF alterations (37.0±0.7Hz, CFF+). The S-ANT1 confirmed an impaired neurological performance (10.2±2.8) in CFF+ patients thus confirming the presence of mPSE. Noteworthy, lactulose administration determined a CFF increase (39.1±0.4Hz) and S-ANT1 normalization in these patients. Neither mPSE- nor mPSE+ patients had ALD and showed similar demographic, clinical and laboratory parameters. Finally, no mPSE+ patient showed radiologically-detectable brain vascular malformations or other brain abnormalities at imaging.Conclusions. HHT patients represent a human model of mPSE secondary to portosystemic shunts escaping radiological detection. mPSE evaluation should be incorporated in HHT surveillance protocols since it can affect both health-related/social aspects and pharmacokinetics of orally administered drugs with a narrow therapeutic index and high hepatic first-pass uptake.

Effects of spray-dried bovine plasma protein in milk replacers fed at a high plane of nutrition on performance, intestinal permeability, and morbidity of Holstein calves

Spray-dried plasma protein (SDP) has been shown to improve growth and intestinal function in young calves when included in milk replacers (MR) fed at conventional rates. Use of an SDP and wheat protein blend to replace a portion of whey protein has been shown to perform similarly to using an all-whey protein control MR. However, a trend in the dairy industry is to feed calves for greater rates of growth during the preweaning period. The purpose of this study was to determine the effects of increasing amounts of SDP inclusion in MR on growth and health of calves fed at a high plane of nutrition. Young (<7 d) Holstein calves were offered starter and assigned to 1 of 5 MR treatments: an all-milk protein (whey) control MR (0SDP, n = 26) or MR containing 5% SDP (5SDP, n = 20), 7.5% SDP (7.5SDP, n = 14), 10% SDP (10SDP, n = 20), or 12% of an approximate 1:1 SDP plus wheat protein blend (PW, n = 17). All MR were formulated to contain 26% CP and 16% fat and were fed at a maximum rate of 1 kg of powder (as fed) from d 8 to 36. Amounts of MR powder were decreased by 25%/wk from d 37 to weaning at d 57. Thereafter, calves were provided only starter feed until the end of the study at d 63. On d 4, 15, 36, and 57, intestinal permeability was assessed via oral administration of lactulose and d-mannitol followed by analysis of lactulose and mannitol in blood at 60 min after administration. Increasing SDP led to a small linear decrease in MR consumed. There was a tendency for a positive linear relationship between increasing SDP and average daily gain of body weight, and SDP had mixed effects on body frame variables. Increasing SDP tended to increase fecal scores and increased the amount of fluid therapy given. Diet had no effect on intestinal permeability. Increasing SDP led to an increase in serum total cholesterol and serum urea N and tended to have a quadratic effect on serum glucose concentration on d 36. Calves fed PW tended to have increased withers height, increased intestinal permeability on d 36, and an increased likelihood of being medicated for any reason or being medicated for respiratory illness, but growth and health were not different from the control diet otherwise. Feeding PW led to an increase in serum total cholesterol and tended to lead to increased serum glucose concentration on d 36. Results of this study indicate that SDP can be included at up to 10% as fed in the MR of calves fed at a high plane of nutrition (1 kg/d of MR powder, as fed) with improvements in average daily gain. Additionally, a 1:1 SDP plus wheat protein blend can be used at 12% inclusion with no difference in most health and growth parameters.

Prebiotic Lactulose Ameliorates the Cognitive Deficit in Alzheimer's Disease Mouse Model through Macroautophagy and Chaperone-Mediated Autophagy Pathways.

Lactulose, as a prebiotic, can be utilized by human gut microbiota and stimulate their growth. Although microbiota modulation has become an emerging approach to manage many diseases and can be achieved by the administration of prebiotics, fewer investigations have been carried out on the therapeutic mechanism of lactulose. Two trehalose analogs, lactulose and melibiose, were identified as having a neuroprotective effect in polyglutamine and Parkinson disease models. In this study, we examined lactulose and melibiose in a mouse primary hippocampal neuronal culture under the toxicity of oligomeric Aβ25-35. Lactulose was further tested in vivo because its effective concentration is lower than that of melibiose. Lactulose and trehalose were applied individually to mice before a bilateral intrahippocampal CA1 injection of oligomeric Aβ25-35. The administration of lactulose and trehalose attenuated the short-term memory and the learning retrieval of Alzheimer's disease (AD) mice. From a pathological analysis, we found that the pretreatment of lactulose and trehalose decreased neuroinflammation and increased the levels of the autophagic pathways. These results suggest that the neuroprotective effects of both lactulose and trehalose are achieved through anti-inflammation and autophagy. In addition, lactulose was better than trehalose in the enhancement of the synaptic protein expression level in AD mice. Therefore, lactulose could potentially be developed into a preventive and/or therapeutic disaccharide for AD.

Clinical investigation in non-liver cirrhosis portosystemic shunt encephalopathy-four case series.

We reported here four cases presenting with disturbance of consciousness over long periods of time and hyperammonemia. Two patients were on maintenance hemodialysis. Contrast-enhanced computed tomography (CT) of abdomen and balloon-occluded retrograde contrast venography revealed existence of a non-cirrhotic portosystemic shunt. Conservative treatment such as intravenous branched-chain amino acid administration and oral lactulose administration had only a modest effect in all patients. Improvements in symptoms were observed following the occlusion of the shunt path in three patients. Measurements of ammonia values would be the most important test for screening, but changes in Fischer’s ratio or indocyanine green (ICG) test values were also correlated with clinical symptoms. Neurologists should keep in mind the possibility of non-cirrhotic portosystemic shunts when they encounter patients with disturbance of consciousness. They should also remember that occlusion of the shunt pathway is an effective treatment.

Prevention of hepatic encephalopathy by administration of rifaximin and lactulose in patients with liver cirrhosis undergoing placement of a transjugular intrahepatic portosystemic shunt (TIPS): a multicentre randomised, double blind, placebo controlled trial (PEARL trial)

IntroductionCirrhotic patients with portal hypertension can suffer from variceal bleeding or refractory ascites and can benefit from a transjugular intrahepatic portosystemic shunt (TIPS). Post-TIPS hepatic encephalopathy (HE) is a common...