Roux-En-Y Gastric Bypass (RYGB) Surgery during High Liquid Sucrose Diet Leads to Gut Microbiota-Related Systematic Alterations.

Roux-en-Y gastric bypass (RYGB) surgery has been proven successful in weight loss and improvement of co-morbidities associated with obesity. Chronic complications such as malabsorption of micronutrients in up to 50% of patients underline the need for additional therapeutic approaches. We investigated systemic RYGB surgery effects in a liquid sucrose diet-induced rat obesity model. After consuming a diet supplemented with high liquid sucrose for eight weeks, rats underwent RYGB or control sham surgery. RYGB, sham pair-fed, and sham ad libitum-fed groups further continued on the diet after recovery. Notable alterations were revealed in microbiota composition, inflammatory markers, feces, liver, and plasma metabolites, as well as in brain neuronal activity post-surgery. Higher fecal 4-aminobutyrate (GABA) correlated with higher Bacteroidota and Enterococcus abundances in RYGB animals, pointing towards the altered enteric nervous system (ENS) and gut signaling. Favorable C-reactive protein (CRP), serine, glycine, and 3-hydroxybutyrate plasma profiles in RYGB rats were suggestive of reverted obesity risk. The impact of liquid sucrose diet and caloric restriction mainly manifested in fatty acid changes in the liver. Our multi-modal approach reveals complex systemic changes after RYGB surgery and points towards potential therapeutic targets in the gut-brain system to mimic the surgery mode of action.

Behavioral and Metabolic Effects of a Calorie-Restricted Cafeteria Diet and Oleuropein Supplementation in Obese Male Rats.

Diet-induced obesity models are widely used to investigate dietary interventions for treating obesity. This study was aimed to test whether a dietary intervention based on a calorie-restricted cafeteria diet (CAF-R) and a polyphenolic compound (Oleuropein, OLE) supplementation modified sucrose intake, preference, and taste reactivity in cafeteria diet (CAF)-induced obese rats. CAF diet consists of high-energy, highly palatable human foods. Male rats fed standard chow (STD) or CAF diet were compared with obese rats fed CAF-R diet, alone or supplemented with an olive tree leaves extract (25 mg/kg*day) containing a 20.1% of OLE (CAF-RO). Biometric, food consumption, and serum parameters were measured. CAF diet increased body weight, food and energy consumption and obesity-associated metabolic parameters. CAF-R and CAF-RO diets significantly attenuated body weight gain and BMI, diminished food and energy intake and improved biochemical parameters such as triacylglycerides and insulin resistance which did not differ between CAF-RO and STD groups. The three cafeteria groups diminished sucrose intake and preference compared to STD group. CAF-RO also diminished the hedonic responses for the high sucrose concentrations compared with the other groups. These results indicate that CAF-R diet may be an efficient strategy to restore obesity-associated alterations, whilst OLE supplementation seems to have an additional beneficial effect on sweet taste function.

Acute Metabolic Responses to Glucose and Fructose Supplementation in Healthy Individuals: A Double-Blind Randomized Crossover Placebo-Controlled Trial.

The aim of this study was to investigate the impact of glucose (Glu), fructose (Fru), glucose and fructose (GluFru) and sucralose on blood glucose response in healthy individuals. Fifteen healthy individuals (five females, age of 25.4 ± 2.5 years, BMI of 23.7 ± 1.7 kg/m2 with a body mass (BM) of 76.3 ± 12.3 kg) participated in this double-blind randomized crossover placebo-controlled trial. Participants received a mixture of 300 mL of water with 1 g/kg BM of Glu, 1 g/kg BM of Fru, 0.5 g/kg BM of GluFru (each), and 0.2 g sucralose as a placebo. Peak BG values Glu were reached after 40 ± 13 min (peak BG: 141 ± 20 mg/dL), for Fru after 36 ± 22 min (peak BG: 98 ± 7 mg/dL), for GluFru after 29 ± 8 min (BG 128 ± 18 mg/dL), and sucralose after 34 ± 27 min (peak BG: 83 ± 5 mg/dL). Significant differences regarding the time until peak BG were found only between Glu and GluFru supplementation (p = 0.02). Peak blood glucose levels were significantly lower following the ingestion of Fru compared to the supplementation of Glu and GluFru (p < 0.0001) while Glu and GluFru supplementation showed no difference in peak values (p = 0.23). All conditions led to a significantly higher peak BG value compared to sucralose (p < 0.0001). Blood lactate increased in Glu (p = 0.002), Fru and GluFru (both p < 0.0001), whereas sucralose did not increase compared to the baseline (p = 0.051). Insulin levels were significantly higher in all conditions at peak compared to sucralose (p < 0.0001). The findings of this study prove the feasibility of combined carbohydrate supplementations for many applications in diabetic or healthy exercise cohorts.

Comparative impact of dietary carbohydrates on the liver transcriptome in two strains of mice.

Excessive long-term consumption of dietary carbohydrates, including glucose, sucrose, or fructose, has been shown to have significant impact on genome-wide gene expression, which likely results from changes in metabolic substrate flux. However, there has been no comprehensive study on the acute effects of individual sugars on the genome-wide gene expression that may reveal the genetic changes altering signaling pathways, subsequent metabolic processes, and ultimately physiological/pathological responses. Considering that gene expressions in response to acute carbohydrate ingestion might be different in nutrient sensitive and insensitive mammals, we conducted comparative studies of genome-wide gene expression by deep mRNA sequencing of the liver in nutrient sensitive C57BL/6J and nutrient insensitive BALB/cJ mice. Furthermore, to determine the temporal responses, we compared livers from mice in the fasted state and following ingestion of standard laboratory mouse chow supplemented with plain drinking water or water containing 20% glucose, sucrose, or fructose. Supplementation with these carbohydrates induced unique extents and temporal changes in gene expressions in a strain specific manner. Fructose and sucrose stimulated gene changes peaked at 3 h postprandial, whereas glucose effects peaked at 12 h and 6 h postprandial in C57BL/6J and BABL/cJ mice, respectively. Network analyses revealed that fructose changed genes were primarily involved in lipid metabolism and were more complex in C57BL/6J than in BALB/cJ mice. These data demonstrate that there are qualitative and antitative differences in the normal physiological responses of the liver between these two strains of mice and C57BL/6J is more sensitive to sugar intake than BALB/cJ.

Consuming sucrose solution promotes leptin resistance and site specifically modifies hypothalamic leptin signaling in rats.

Rats consuming 30% sucrose solution and a sucrose-free diet (LiqS) become leptin resistant, whereas rats consuming sucrose from a formulated diet (HS) remain leptin responsive. This study tested whether leptin resistance in LiqS rats extended beyond a failure to inhibit food intake and examined leptin responsiveness in the hypothalamus and hindbrain of rats offered HS, LiqS, or a sucrose-free diet (NS). Female LiqS Sprague-Dawley rats initially only partially compensated for the calories consumed as sucrose, but energy intake matched that of HS and NS rats when they were transferred to calorimetry cages. There was no effect of diet on energy expenditure, intrascapular brown fat tissue (IBAT) temperature, or fat pad weight. A peripheral injection of 2 mg of leptin/kg on day 23 or day 26 inhibited energy intake of HS and NS but not LiqS rats. Inhibition occurred earlier in HS rats than in NS rats and was associated with a smaller meal size. Leptin had no effect on energy expenditure but caused a transient rise in IBAT temperature of HS rats. Leptin increased the phosphorylation of signal transducer and activator of transcription 3 (pSTAT3) in the hindbrain and ventromedial hypothalamus of all rats. There was a minimal effect of leptin in the arcuate nucleus, and only the dorsomedial hypothalamus showed a correlation between pSTAT3 and leptin responsiveness. These data suggest that the primary response to leptin is inhibition of food intake and the pattern of sucrose consumption, rather than calories consumed as sucrose, causes leptin resistance associated with site-specific differences in hypothalamic leptin signaling.

Antidepressant Effect of Blue Light on Depressive Phenotype in Light-Deprived Male Rats.

Blue light has been previously reported to play a salient role in the treatment of seasonal affective disorder. The present study aimed to investigate whether blue light had antidepressant effect on light-deprivation-induced depression model, and the underlying visual neural mechanism. Blue light mitigated depression-like behaviors induced by light deprivation as measured by elevated sucrose preference and reduced immobility time. Blue light enhanced melanopsin expression and light responses in the retina. We also found the upregulation of serotonin and brain derived neurotrophic factor expression in the c-fos-positive areas of rats treated with blue light compared with those maintained in darkness. The species gap between nocturnal albino (Sprague-Dawley rat) and diurnal pigmented animals (human) might have influenced extrapolating data to humans. Blue light has antidepressant effect on light-deprived Sprague-Dawley rats, which might be related to activating the serotonergic system and neurotrophic activity via the retinoraphe and retinoamygdala pathways. Blue light is the effective component of light therapy for treatment of depression.

Response of Soybean Root to Phosphorus Deficiency under Sucrose Feeding: Insight from Morphological and Metabolome Characterizations.

Phosphorus (P) is one the least available essential plant macronutrients in soils that is a major constraint on plant growth. Soybean (Glycine max L.) production is often limited due to low P availability. The better management of P deficiency requires improvement of soybean's P use efficiency. Sugars are implicated in P starvation responses, and a complete understanding of the role of sucrose together with P in coordinating P starvation responses is missing in soybean. This study explored global metabolomic changes in previously screened low-P-tolerant (Liaodou, L13) and low-P-sensitive (Tiefeng 3, T3) soybean genotypes by liquid chromatography coupled mass spectrometry. We also studied the root morphological response to sucrose application (1%) in P-starved soybean genotypes against normal P supply. Root morphology in L13 genotype has significantly improved P starvation responses as compared to the T3 genotype. Exogenous sucrose application greatly affected root length, root volume, and root surface area in L13 genotype while low-P-sensitive genotype, i.e., T3, only responded by increasing number of lateral roots. Root : shoot ratio increased after sucrose treatment regardless of P conditions, in both genotypes. T3 showed a relatively higher number of differentially accumulated metabolites between P-starved and normal P conditions as compared to L13 genotype. Common metabolites accumulated under the influence of sucrose were 5-O-methylembelin, D-glucuronic acid, and N-acetyl-L-phenylalanine. We have discussed the possible roles of the pathways associated with these metabolites. The differentially accumulated metabolites between both genotypes under the influence of sucrose are also discussed. These results are important to further explore the role of sucrose in the observed pathways. Especially, our results are relevant to formulate strategies for improving P efficiency of soybean genotypes with different P efficiencies.

Association of Dietary Change during Pregnancy with Large-for-Gestational Age Births: A Prospective Observational Study.

Being born with large birthweight is considered as a risk of non-communicable diseases later in life. However, it is not fully understood what kind of maternal dietary intake during pregnancy affect large birthweight. Therefore, we examined the association of dietary intakes and its changes during pregnancy with large-for-gestational-age (LGA) births in Japanese pregnant women. In the prospective study, 245 pregnant women who visited Kyoto Medical Center were enrolled. Nutrition survey using brief-type self-administered diet history questionnaire (BDHQ) at all trimester was completed in 171 pregnant women. Based on birthweight and gestational age, participants were divided into three groups, such as small-for-gestational-age (<10th, SGA, n=17), appropriate-for-gestational-age (≥10th and <90th, AGA, n=144), and LGA (≥90th, n=10) groups. Compared with those without LGA births, mothers with LGA births showed: 1) greater weight gain during pregnancy (LGA: 14.0±3.2 kg, AGA: 9.9±3.9 kg, SGA: 8.4±3.1 kg, p<0.05); 2) higher energy intake throughout pregnancy (LGA: 310±368 kcal, AGA: 7±490 kcal, SGA: -97±293 kcal, ptrend<0.05); 3) larger changes in plant oil and sucrose consumptions from the 1st to 2nd trimester, probably due to the results of greater consumption of bread, Western confectionery, Japanese confectionery, and mayonnaise and dressing during the same period (ptrend<0.05, respectively). Our results suggest that higher energy intake throughout pregnancy, as well as greater consumption of plant oil and sucrose from the first to second trimester could be associated with LGA births.

Fetal expression of genes related to metabolic function is impacted by supplementation of ground beef and sucrose during gestation in a swine model.

To determine the effects of maternal supplementation on the mRNA abundance of genes associated with metabolic function in fetal muscle and liver, pregnant sows (Landrace × Yorkshire; initial body weight (BW) 221.58 ± 33.26 kg; n = 21) fed a complete gestation diet (corn-soybean meal based diet, CSM) were randomly assigned to 1 of 4 isocaloric supplementation treatments: control (CON, 378 g/d CSM, n = 5), sucrose (SUGAR, 255 g/d crystalized sugar, n = 5), cooked ground beef (BEEF, 330 g/d n = 6), or BEEF + SUGAR (B+S, 165 g/d cooked ground beef and 129 g/d crystalized sugar, n = 5), from days 40 to 110 of gestation. Sows were euthanized on day 111 of gestation. Two male and 2 female fetuses of median BW were selected from each litter, and samples of the longissimus dorsi muscle and liver were collected. Relative transcript level was quantified via qPCR with HPRT1 as the reference gene for both muscle and liver samples. The following genes were selected and analyzed in the muscle: IGF1R, IGF2, IGF2R, GYS-1, IRS-1, INSR, SREBP-1C, and LEPR; while the following were analyzed in the liver: IGF2, IGF2R, FBFase, G6PC, PC, PCK1, FGF21, and LIPC. No effect of fetal sex by maternal treatment interaction was observed in mRNA abundance of any of the genes evaluated (P > 0.11). In muscle, the maternal nutritional treatment influenced (P = 0.02) IGF2 mRNA abundance, with B+S and SUGAR fetuses having lower abundance than CON, which was not different from BEEF. Additionally, SREBP-1 mRNA abundance was greater (P < 0.01) for B+S compared with CON, BEEF, or SUGAR fetuses; and females tended (P = 0.06) to have an increased abundance of SREBP-1 than males. In fetal liver, IGF2R mRNA abundance was greater (P = 0.01) for CON and BEEF than SUGAR and B+S; while FBPase mRNA abundance was greater (P = 0.03) for B+S compared with the other groups. In addition, maternal nutritional tended (P = 0.06) to influence LIPC mRNA abundance, with increased abundance in CON compared with SUGAR and B+S. These data indicate limited changes in transcript abundance due to substitution of supplemental sugar by ground beef during mid to late gestation. However, the differential expression of FBPase and SREBP-1c in response to the simultaneous supplementation of sucrose and ground beef warrants further investigations, since these genes may play important roles in determining the offspring susceptibility to metabolic diseases.

Characteristics of Patients Who Achieve Serum Phosphorus Control on Sucroferric Oxyhydroxide or Sevelamer Carbonate: A post hoc Analysis of a Phase 3 Study.

INTRODUCTION: Control of hyperphosphatemia in patients on dialysis remains a major challenge. OBJECTIVE: This study evaluated predictors of serum phosphorus (sP) control among dialysis patients treated with noncalcium, oral phosphate binder therapy in a phase 3 clinical trial. METHODS: Post hoc analyses were performed using data for patients with hyperphosphatemia who received 52 weeks of treatment with sucroferric oxyhydroxide (SFOH) or sevelamer carbonate (sevelamer). Patients were categorized into those who achieved sP control (n = 302; defined as sP ≤ 5.5 mg/dL at week 52), and those with uncontrolled sP (n = 195; sP >5.5 mg/dL at week 52). Because SFOH and sevelamer have previously demonstrated similar effects on chronic kidney disease-mineral-bone disorder parameters in this study, the treatment groups were pooled. RESULTS: Average age at baseline was higher among sP-controlled versus sP-uncontrolled patients (56.9 vs. 53.4 years; p = 0.005). Baseline sP levels were significantly lower among sP-controlled versus sP-uncontrolled patients (7.30 vs. 7.85 mg/dL; p < 0.001), and sP reductions from baseline were significantly greater in the sP-controlled group (-2.89 vs. -0.99 mg/dL at week 52; p < 0.001). Logistic regression analysis identified higher baseline sP levels (odds ratio [OR] = 0.86, 95% confidence interval [CI]: 0.765-0.960), no concomitant active vitamin D therapy use (OR = 0.51, 95% CI: 0.328-0.804), and higher body mass index at baseline (OR = 0.96, 95% CI: 0.937-0.992) as significant predictors of uncontrolled sP. CONCLUSION: This analysis indicates that sP control may be more challenging in younger patients with high sP levels. Closer monitoring and management of serum phosphorus levels may be required in this population.

How to improve adherence the captors of phosphorus on hemodialysis: Experience in real life with sucroferric oxyhydroxide.

INTRODUCTION: The lack of adherence to phosphate -binders (PB) is the most important factor in not achieving the objectives of serum phosphorus (sP). Studies in the real-world population are needed to understand the influence of PBs on adherence and how to modify it. METHODS: Prospective study conducted during 3 months in usual clinical practice. Out of 105 hemodialysis patients, 57 were switched to SFOH and 48 maintained their baseline treatment (control group). sP levels and the percentage of patients with sP levels <5mg/dl were compared. Adherence before and after introduction of SFOH, number of pills of PB, preferences in the administration mode and side effects were analyzed. RESULTS: The percentage of patients with controlled sP (<5mg/dl) increased significantly in the SFOH users' group (62.1-92.9%, p<0.001), but not in the control group (83-83.3%, p=NS). The average of daily tablets decreased significantly in the SFOH group (7.2-2.3 comp, p<0.001), but not in the control group (5.6-5.6, p=NS) and 100% of the patients used only one PB in SFOH group. The use of SFOH increased the adherence according to the SMAQ questionnaire (57.8-84.3%; OR 13.1, p<0.001). The possibility to choose the preferred mode of administration (split-swallowing 89% compared to chewing 11%), improved the acceptance (44.7-78%). 14% of the patients experienced side effects and in 5.2% SFOH was discontinued for this reason. CONCLUSIONS: SFOH controlled serum sP in 93% of patients, 100% in monotherapy, and with fewer tablets. The exploration and adaptation of preferences in the mode of administration influenced the acceptance of the drug by the patient and, probably, the future adherence.

Involvement of mTOR-related signaling in antidepressant effects of Sophoraflavanone G on chronically stressed mice.

SophoraflavanoneG (SG), an important prenylated flavonoid isolated from Sophoraalopecuroides.L, is effective for many illnesses. The present study was designed to investigate whether the compound could reverse depressive-like symptoms and investigate its possible mechanisms. Chronic Unpredictable Mild Stress (CUMS) mice were treated with fluoxetine and SG. The immobility time in forced swimming test (FST) and tail suspension test (TST) were recorded. The levels of pro-inflammatory cytokines and neurotransmitters in the hippocampus were evaluated. Furthermore, the protein expressions of PI3K, AKT, mTOR, p70S6K, BDNF, and Trkb in hippocampus were detected. Rapamycin, the selective mTOR inhibitor, was used to estimate the potential mechanism. As a result, after 7 days of SG treatment, the immobility time in FST and TST was declined obviously. The levels of IL-6, IL-1ß, and TNF-α in the hippocampus were significantly reduced, and the quantity of 5-HT and NE was raised considerably in SG-treated group compared with the CUMS-exposed group. Additionally, SG could up-regulate the expressions of PI3K, AKT, mTOR, 70S6K, BDNF, and Trkb. The blockade of mammalian target of rapamycin signaling blunted the antidepressant effect and reversed the up-regulation of BDNF expression caused by SG. These findings suggested that SG treatment alleviated depressive-like symptoms via mTOR-mediated BDNF/Trkb signaling.

Iron kinetics following treatment with sucroferric oxyhydroxide or ferric citrate in healthy rats and models of anaemia, iron overload or inflammation.

BACKGROUND: The iron-based phosphate binders, sucroferric oxyhydroxide (SFOH) and ferric citrate (FC), effectively lower serum phosphorus in clinical studies, but gastrointestinal iron absorption from these agents appears to differ. We compared iron uptake and tissue accumulation during treatment with SFOH or FC using experimental rat models. METHODS: Iron uptake was evaluated during an 8-h period following oral administration of SFOH, FC, ferrous sulphate (oral iron supplement) or control (methylcellulose vehicle) in rat models of anaemia, iron overload and inflammation. A 13-week study evaluated the effects of SFOH and FC on iron accumulation in different organs. RESULTS: In the pharmacokinetic experiments, there was a minimal increase in serum iron with SFOH versus control during the 8-h post-treatment period in the iron overload and inflammation rat models, whereas a moderate increase was observed in the anaemia model. Significantly greater increases (P < 0.05) in serum iron were observed with FC versus SFOH in the rat models of anaemia and inflammation. In the 13-week iron accumulation study, total liver iron content was significantly higher in rats receiving FC versus SFOH (P < 0.01), whereas liver iron content did not differ between rats in the SFOH and control groups. CONCLUSIONS: Iron uptake was higher from FC versus SFOH following a single dose in anaemia, iron overload and inflammation rat models and 13 weeks of treatment in normal rats. These observations likely relate to different physicochemical properties of SFOH and FC and suggest distinct mechanisms of iron absorption from these two phosphate binders.

Effects of a novel heat-treated protein and carbohydrate supplement on feed consumption, milk production, and cheese yield in early-lactation dairy cows.

Protein is an expensive component of the dairy cow diet, and overfeeding protein can have adverse economic and environmental impacts. Our objective was to maintain milk production and components while decreasing dietary crude protein (CP) through use of a heat-treated, rumen-resistant sugar amino acid complex (SAAC) as the Schiff base, as an addition to low-protein diets. Dietary treatments included a negative control [NC, 146 g of CP/kg of dry matter (DM)], a positive control (PC, 163 g of CP/kg of DM), and the NC supplemented with SAAC in lieu of some barley grain (SAAD, 151 g of CP/kg of DM). Diets were fed to 30 multiparous Holstein-Friesian dairy cows for the first 50 d postpartum. Dry matter intake (DMI) was determined daily. Milk yield and content of fat, protein, lactose, and casein were recorded weekly from wk 2 to 7 of lactation. The fixed effects of treatment, week, treatment × week, month of calving, and BCS at calving, and a random effect of cow, were analyzed using the MIXED procedure of SAS (SAS Institute Inc., Cary, NC). The SAAD treatment had greater energy-corrected milk yield than did NC. The PC treatment had greater DMI than did NC, and SAAD tended to have greater DMI than did NC. We found significant treatment effects for fat percentage and yield. The NC and SAAD treatments had higher fat percentages than did PC, and SAAD had a higher fat yield than did the NC and PC treatments. Treatment effects were found for casein yield and percentage. We discovered a treatment effect for protein percentage and yield. The PC treatment had higher protein percentage than did NC and SAAD. The PC treatment had a higher protein yield than did NC, and analysis revealed no difference in protein yield between PC and SAAD. The SAAD treatment had higher total milk solids than did the NC treatment. Lactose yield tended to be higher in PC than in NC, and no differences were found between PC and NC and SAAD treatments. The PC treatment had a higher casein percentage than did NC and SAAD; however, the SAAD and PC treatments had higher casein yields than did NC. The PC treatment had a higher casein:fat ratio than did the NC and SAAD treatments. The NC and SAAD treatments had higher Cheddar cheese yields than did PC. We found no treatment × week interactions for any parameter. Supplementing low-protein dairy cow diets with a heat-treated, rumen-resistant SAAC caused beneficial effects by improving milk components and increasing cheese yield to levels similar to those found when feeding expensive and environmentally damaging high-protein diets.

Changes in serum albumin and other nutritional markers when using sucroferric oxyhydroxide as phosphate binder among hemodialysis patients: a historical cohort study.

BACKGROUND: Elevated serum phosphorus concentrations are common among maintenance hemodialysis patients. Protein is a major source of dietary phosphate, but restriction of protein intake can result in hypoalbuminemia and protein-energy wasting. We hypothesized that sucroferric oxyhydroxide (SO), a potent phosphate binder with a low pill burden, may reduce serum phosphorus levels in hemodialysis patients with hypoalbuminemia without adversely impacting albumin levels or dietary intake of protein. METHODS: We retrospectively examined de-identified data from 79 adult, in-center hemodialysis patients with baseline hypoalbuminemia (≤ 3.5 g/dL) switched to SO as part of routine clinical care for at least 1 year. Temporal changes (3-month intervals from baseline through Q4) in phosphate binder pill burden, serum phosphorous levels, nutritional markers, and equilibrated Kt/V were analyzed. Data from a matched reference group of non-hypoalbuminemic patients (N = 79) switched to SO were also examined. RESULTS: SO therapy was associated with a mean reduction of 45.7 and 45.1% in daily phosphate binder pill burden, and a mean reduction of 0.4 mg/dL and 0.51 mg/dL in serum phosphorus levels for the hypoalbuminemic and non-hypoalbuminemic patients, respectively. Hypoalbuminemic patients demonstrated significant increases in mean serum albumin levels from 3.50 mg/dL at baseline to 3.69, 3.74, 3.70, and 3.69 mg/dL during Q1 through Q4, respectively (P < 0.0001), whereas serum albumin levels remained unchanged in the non-hypoalbuminemic group. CONCLUSIONS: Both hypoalbuminemic and non-hypoalbuminemic patients switching to SO exhibited significant reductions in serum phosphorus concentrations and daily phosphate binder pill burden. Among hypoalbuminemic patients, the initiation of SO therapy was also associated with increases in serum albumin, suggesting therapy may have allowed patients to increase their dietary intake of protein.

Identification of a Novel Oligosaccharide in Maple Syrup as a Potential Alternative Saccharide for Diabetes Mellitus Patients.

The incidence of diabetes mellitus (DM) is increasing rapidly and is associated with changes in dietary habits. Although restrictions in the use of sweeteners may prevent the development of DM, this might reduce the quality of life of patients with DM. Therefore, there has been a great deal of research into alternative sweeteners. In the search for such sweeteners, we analyzed the carbohydrate content of maple syrup and identified a novel oligosaccharide composed of fructose and glucose, linked at the C-4 of glucose and the C-6 of fructose. This oligosaccharide inhibited the release of fructose from sucrose by invertase (IC50: 1.17 mmol/L) and the decomposition of maltose by α-(1-4) glucosidase (IC50: 1.72 mmol/L). In addition, when orally administered together with sucrose to rats with DM, the subsequent plasma glucose concentrations were significantly lower than if the rats had been administered sucrose alone, without having any effect on the insulin concentration. These findings suggest that this novel oligosaccharide might represent a useful alternative sweetener for inclusion in the diet of patients with DM and may also have therapeutic benefits.

Risk of reduced intestinal absorption of myo-inositol caused by D-chiro-inositol or by glucose transporter inhibitors.

Background: D-chiro-inositol (DCI) and glucose transporter inhibitors may inhibit myo-inositol (MI) transporters, and the aim is to clinically evaluate their effect on MI absorption. Research design and methods: Fasting 18 healthy volunteers received orally 6000 mg MI, 6000 mg MI with 1000 mg DCI, and 6000 mg MI with SelectSIEVE® Apple PCQ and Sorbitol, Maltodextrin and Sucralose (PCQ-SMS), in three different phases with a washout period of 7 days. At each phase, blood samples were collected before administration, and every 60 minutes until 540 minutes after administration. MI plasma levels (µmol/L) were quantified by gas chromatography-mass spectrometry; maximum plasma concentration (Cmax), time to reach it (Tmax), and the area under the time-concentration curve of MI (AUC 0-540) were evaluated. Results: The Cmax of MI alone (Tmax = 180min) was 1.29-fold higher than those of MI with DCI (Tmax = 180min) (p < 0.001) and 1.69-fold higher than those of MI with PCQ-SMS (Tmax = 240min) (p < 0.001). The AUC 0-540 was reduced by 19.09% in MI plus DCI (p = 0.0118) and by 31.8% in MI plus PCQ-SMS (p < 0.001) as compared to MI alone. Conclusions: DCI, glucose transporter inhibitors and sugars, such as sorbitol and maltodextrin, seem to inhibit MI absorption, decreasing MI plasma concentration as compared to MI alone.

Procedural pain reduction strategies in paediatric nuclear medicine.

BACKGROUND: In paediatric nuclear medicine, the majority of the scans require intravenous (IV) access to deliver the radiotracers. Children and parents often cite procedural pain as the most distressing part of their child's hospitalization. In our department, various pain management strategies including physical and psychological distraction methods and pharmacological intervention have been implemented to reduce procedural pain. OBJECTIVE: The purpose of this study was to evaluate and compare different pain reduction strategies used in our paediatric nuclear medicine department. MATERIALS AND METHODS: The charts of 196 children (114 female) were reviewed retrospectively (median age: 8 months; interquartile range [IQR]: 33.1). Children were categorized into five groups: (1) Maxilene (topical liposomal lidocaine; n=50), (2) Pain Ease (vapocoolant; n=69), (3) oral sucrose (n=48), (4) Maxilene and Pain Ease combined (n=10), and (5) no pharmacological/adjuvant intervention (n=19). Physical and psychological distraction were used in all patients. Therefore, Group 5 only received physical and psychological strategies. Physical methods included supportive positioning, deep breathing, temperature considerations, massage pressure or vibration and neonatal development strategies (e.g., non-nutritive sucking, facilitated tucking, swaddling, rocking). Psychological strategies included education, distraction with movies, books or storytelling, and relaxation techniques. The pain perceived by the children after the IV access was compared in these five groups. Two types of pain assessment were used in this study: self-reporting pain scale and behavioural observational pain rating scale. Pain was reported on a scale of 1 to 10. The average pain score was also compared between patients who had one or two attempts for IV access and those who had more than two attempts. RESULTS: The average pain score was 2.8 (mean±standard error [SE]=0.4) in Maxilene, 2.1 (SE=0.3) in Pain Ease, 2.7 (SE=0.3) in sucrose, 1.6 (SE=0.5) in combined Maxilene and Pain Ease and 3.4 (SE=0.6) in "no pharmacology/adjuvant" groups. There was no statistically significant difference between the four pharmacology groups of Maxilene, Pain Ease, sucrose and no pharmacology/adjuvant intervention group. However, the pain score was significantly reduced in patients who received both Maxilene and Pain Ease combined compared with the patients who didn't have any pharmacological/adjuvant intervention (P=0.041). The average pain was 2.2 (SE=0.1) with one attempt at IV access, 3.0 (SE=0.5) with two attempts and 5.1 (SE=0.9) with three attempts. CONCLUSION: A combination of two pharmacological/adjuvant interventions may be more effective in reducing procedural pain compared with a single intervention. A comprehensive pain management program should consider all available interventions - pharmacological, adjuvant, physical and psychological. Further randomized clinical trials are needed to evaluate if a combination of two or more methods of pharmacological and adjuvant interventions are more effective to reduce procedural pain compared with only one method.

Combination of Clinically Utilized Kappa-Opioid Receptor Agonist Nalfurafine With Low-Dose Naltrexone Reduces Excessive Alcohol Drinking in Male and Female Mice.

BACKGROUND: Nalfurafine is the first clinically approved kappa-opioid receptor (KOP-r) agonist as an antipruritus drug with few side effects in humans (e.g., sedation, depression, and dysphoria). No study, however, has been done using nalfurafine on alcohol drinking in rodents or humans. METHODS: We investigated whether nalfurafine alone or in combination with mu-opioid receptor (MOP-r) antagonist naltrexone changed excessive alcohol drinking in male and female C57BL/6J (B6) mice subjected to a chronic intermittent-access drinking paradigm (2-bottle choice, 24-hour access every other day) for 3 weeks. Neuronal proopiomelanocortin enhancer (nPE) knockout mice with brain-specific deficiency of beta-endorphin (endogenous ligand of MOP-r) were used as a genetic control for the naltrexone effects. RESULTS: Single administration of nalfurafine decreased alcohol intake and preference in both male and female B6 mice in a dose-dependent manner. Pretreatment with nor-BNI (a selective KOP-r antagonist) blocked the nalfurafine effect on alcohol drinking, indicating a KOP-r-mediated mechanism. Pharmacological effects of a 5-dosing nalfurafine regimen were further evaluated: The repeated nalfurafine administrations decreased alcohol consumption without showing any blunted effects, suggesting nalfurafine did not develop a tolerance after the multidosing regimen tested. Nalfurafine did not produce any sedation (spontaneous locomotor activity), anhedonia-like (sucrose preference test), anxiety-like (elevated plus maze test), or dysphoria-like (conditioned place aversion test) behaviors, suggesting that nalfurafine had few side effects. Investigating synergistic effects between low-dose naltrexone and nalfurafine, we found that single combinations of nalfurafine and naltrexone, at doses lower than individual effective dose, profoundly decreased excessive alcohol intake in both sexes. The effect of nalfurafine on decreasing alcohol consumption was confirmed in nPE-/- mice, suggesting independent mechanisms by which nalfurafine and naltrexone reduced alcohol drinking. CONCLUSION: The clinically utilized KOP-r agonist nalfurafine in combination with low-dose naltrexone has potential in alcoholism treatment.