Preventive Effect of Depolymerized Sulfated Galactans from Eucheuma serra on Enterotoxigenic Escherichia coli-Caused Diarrhea via Modulating Intestinal Flora in Mice.

In this work, the preventive effect of depolymerized sulfated polysaccharides from Eucheuma serra (DESP) on bacterial diarrhea by regulating intestinal flora was investigated in vivo. Based on the enterotoxigenic Escherichia coli (ETEC)-infected mouse diarrhea model, DESP at doses ranging from 50 mg/kg to 200 mg/kg alleviated weight loss and decreased the diarrhea rate and diarrhea index. Serological tests showed that the levels of inflammation-related factors were effectively suppressed. Furthermore, the repaired intestinal mucosa was verified by morphology and pathological tissue section observations. Compared with the model group, the richness and diversity of the intestinal flora in the DESP group increased according to the 16S rRNA high-throughput sequencing of the gut microbiota. Specifically, Firmicutes and Actinobacteria increased, and Proteobacteria decreased after DESP administration. At the family level, DESP effectively improved the abundance of Lactobacillaceae, Bifidobacteriaceae, and Lachnospiraceae, while significantly inhibiting the growth of Enterobacteriaceae. Therefore, the antimicrobial diarrhea function of DESP may be related to the regulation of intestinal microbiota.

Pharmacological interventions for treating intrahepatic cholestasis of pregnancy.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder that can develop in pregnancy. It occurs when there is a build-up of bile acids in the maternal blood. It has been linked to adverse maternal and fetal/neonatal outcomes. As the pathophysiology is poorly understood, therapies have been largely empiric. As ICP is an uncommon condition (incidence less than 2% a year), many trials have been small. Synthesis, including recent larger trials, will provide more evidence to guide clinical practice. This review is an update of a review first published in 2001 and last updated in 2013. OBJECTIVES: To assess the effects of pharmacological interventions to treat women with intrahepatic cholestasis of pregnancy, on maternal, fetal and neonatal outcomes. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (13 December 2019), and reference lists of retrieved studies. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials, including cluster-randomised trials and trials published in abstract form only, that compared any drug with placebo or no treatment, or two drug intervention strategies, for women with a clinical diagnosis of intrahepatic cholestasis of pregnancy. DATA COLLECTION AND ANALYSIS: The review authors independently assessed trials for eligibility and risks of bias. We independently extracted data and checked these for accuracy. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 26 trials involving 2007 women. They were mostly at unclear to high risk of bias. They assessed nine different pharmacological interventions, resulting in 14 different comparisons. We judged two placebo-controlled trials of ursodeoxycholic acid (UDCA) in 715 women to be at low risk of bias. The ten different pharmacological interventions were: agents believed to detoxify bile acids (UCDA) and S-adenosylmethionine (SAMe); agents used to bind bile acids in the intestine (activated charcoal, guar gum, cholestyramine); Chinese herbal medicines (yinchenghao decoction (YCHD), salvia, Yiganling and Danxioling pill (DXLP)), and agents aimed to reduce bile acid production (dexamethasone) Compared with placebo, UDCA probably results in a small improvement in pruritus score measured on a 100 mm visual analogue scale (VAS) (mean difference (MD) -7.64 points, 95% confidence interval (CI) -9.69 to -5.60 points; 2 trials, 715 women; GRADE moderate certainty), where a score of zero indicates no itch and a score of 100 indicates severe itching. The evidence for fetal distress and stillbirth were uncertain, due to serious limitations in study design and imprecision (risk ratio (RR) 0.70, 95% CI 0.35 to 1.40; 6 trials, 944 women; RR 0.33, 95% CI 0.08 to 1.37; 6 trials, 955 women; GRADE very low certainty). We found very few differences for the other comparisons included in this review. There is insufficient evidence to indicate if SAMe, guar gum, activated charcoal, dexamethasone, cholestyramine, Salvia, Yinchenghao decoction, Danxioling and Yiganling, or Yiganling alone or in combination are effective in treating women with intrahepatic cholestasis of pregnancy. AUTHORS' CONCLUSIONS: When compared with placebo, UDCA administered to women with ICP probably shows a reduction in pruritus. However the size of the effect is small and for most pregnant women and clinicians, the reduction may fall below the minimum clinically worthwhile effect. The evidence was unclear for other adverse fetal outcomes, due to very low-certainty evidence. There is insufficient evidence to indicate that SAMe, guar gum, activated charcoal, dexamethasone, cholestyramine, YCHD, DXLP, Salvia, Yiganling alone or in combination are effective in treating women with cholestasis of pregnancy. There are no trials of the efficacy of topical emollients. Further high-quality trials of other interventions are needed in order to identify effective treatments for maternal itching and preventing adverse perinatal outcomes. It would also be helpful to identify those women who are mostly likely to respond to UDCA (for example, whether bile acid concentrations affect how women with ICP respond to treatment with UDCA).

Therapeutic Uses of Red Macroalgae.

Red Seaweed "Rhodophyta" are an important group of macroalgae that include approximately 7000 species. They are a rich source of structurally diverse bioactive constituents, including protein, sulfated polysaccharides, pigments, polyunsaturated fatty acids, vitamins, minerals, and phenolic compounds with nutritional, medical, and industrial importance. Polysaccharides are the main components in the cell wall of red algae and represent about 40-50% of the dry weight, which are extensively utilized in industry and pharmaceutical compounds, due to their thickening and gelling properties. The hydrocolloids galactans carrageenans and agars are the main red seaweed cell wall polysaccharides, which had broad-spectrum therapeutic characters. Generally, the chemical contents of seaweed are different according to the algal species, growth stage, environment, and external conditions, e.g., the temperature of the water, light intensity, nutrient concentrations in the ecosystem. Economically, they can be recommended as a substitute source for natural ingredients that contribute to a broad range of bioactivities like cancer therapy, anti-inflammatory agents, and acetylcholinesterase inhibitory. This review touches on the main points of the pharmaceutical applications of red seaweed, as well as the exploitation of their specific compounds and secondary metabolites with vital roles.

A whey/guar "preload" improves postprandial glycaemia and glycated haemoglobin levels in type 2 diabetes: A 12-week, single-blind, randomized, placebo-controlled trial.

AIMS: To evaluate the effects of 12 weeks of treatment with a whey/guar preload on gastric emptying, postprandial glycaemia and glycated haemoglobin (HbA1c) levels in people with type 2 diabetes (T2DM). MATERIALS AND METHODS: A total of 79 people with T2DM, managed on diet or metformin (HbA1c 49 ± 0.7 mmol/mol [6.6 ± 0.1%]), were randomized, in single-blind fashion, to receive 150 mL flavoured preloads, containing either 17 g whey protein plus 5 g guar (n = 37) or flavoured placebo (n = 42), 15 minutes before two meals, each day for 12 weeks. Blood glucose and gastric emptying (breath test) were measured before and after a mashed potato meal at baseline (without preload), and after the preload at the beginning (week 1) and end (week 12) of treatment. HbA1c levels, energy intake, weight and body composition were also evaluated. RESULTS: Gastric emptying was slower (P < 0.01) and postprandial blood glucose levels lower (P < 0.05) with the whey/guar preload compared to placebo preload, and the magnitude of reduction in glycaemia was related to the rate of gastric emptying at both week 1 (r = -0.54, P < 0.001) and week 12 (r = -0.54, P < 0.0001). At the end of treatment, there was a 1 mmol/mol [0.1%] reduction in HbA1c in the whey/guar group compared to the placebo group (49 ± 1.0 mmol/mol [6.6 ± 0.05%] vs. 50 ± 0.8 mmol/mol [6.7 ± 0.05%]; P < 0.05). There were no differences in energy intake, body weight, or lean or fat mass between the groups. CONCLUSIONS: In patients with well-controlled T2DM, 12 weeks' treatment with a low-dose whey/guar preload, taken twice daily before meals, had sustained effects of slowing gastric emptying and reducing postprandial blood glucose, which were associated with a modest reduction in HbA1c, without causing weight gain.

Sulfated fucans and a sulfated galactan from sea urchins as potent inhibitors of selectin-dependent hematogenous metastasis.

Metastasis is responsible for the majority of cancer-associated deaths, though only a very small number of tumor cells are able to efficiently complete all the steps of that process. Tumor cell survival in the bloodstream is one of the limiting aspects of the metastatic cascade. The formation of tumor cell-platelet complexes that promote tumor cell survival is facilitated by the binding of P-selectin on activated platelets to sialyl Lewis-containing oligosaccharides on the surface of tumor cells. Inhibition of this interaction has been shown to attenuate metastasis. Heparin is a potent selectin inhibitor and is capable to block platelet-tumor cell complex formation, thereby attenuating metastasis. Similarly, other sulfated polysaccharides isolated from marine invertebrates attenuate metastasis by a P-selectin-mediated mechanism. In this work, we investigated the selectin-dependent antimetastatic activity of sea urchin sulfated polysaccharides with slight structural differences: a sulfated fucan from Strongylocentrotus franciscanus; a sulfated fucan from Strongylocentrotus droebachiensis; and a sulfated galactan from Echinometra lucunter. The results demonstrate that these fucans and the galactan have different antiselectin activities despite being very similar molecules. Therefore, they may be interesting tools for studies on the structure-function relationship or even for future treatments.

Dietary Fermentable Fibers Attenuate Chronic Kidney Disease in Mice by Protecting the Intestinal Barrier.

Background: Chronic kidney disease (CKD) is a worldwide health problem. Although the pathogenesis of CKD is still unclear, recent studies suggest that systemic inflammation caused by a dysregulated microflora and an impaired intestinal barrier is involved in CKD development. Objective: We investigated the effects of the fermentable dietary fibers (DFs), unmodified guar gum (GG), and partially hydrolyzed GG (PHGG) (i.e., substances with distinct viscosity characteristics) on CKD development, with a particular focus on colonic tight junction (TJ) barriers in mice. Methods: Male 7-wk-old ICR mice were fed an AIN-93G diet that contained 0.25% adenine for 2 wk to induce CKD. Mice fed adenine were then divided into 3 groups and fed the unsupplemented diet (CKD) or a diet containing 10% PHGG (CKD+PHGG) or GG (CKD+GG) for 3 wk. Control (CON) mice were fed an AIN-93G diet without adenine throughout the 5-wk experiment. Plasma urea concentration; the colonic TJ proteins zonula occludens (ZO) 1, ZO2, occludin, junctional adhesion molecule A (JAMA), and claudin isoforms; renal inflammatory cytokines tumor necrosis factor α (Tnfa), interleukin (Il ) 1ß (Il1b), and Il6; and cecal short-chain fatty acids (SCFAs) and microflora were analyzed. Results: Compared with the CON, CKD+PHGG, and CKD+GG groups, the CKD group had a 2.2- to 4.4-fold higher plasma urea concentration and greater expression of inflammatory cytokine genes in the kidney, including Tnfa (4.4- to 48-fold), Il1b (4.6- to 56-fold), and Il6 (8.8- to 115-fold). The CON, CKD+PHGG, and CKD+GG groups had greater expression of colonic TJ proteins including ZO1 (2.9- to 3.7-fold), ZO2 (3.4- to 4.3-fold), occludin (3.0- to 3.3-fold), JAMA (4.4- to 5.4-fold), and claudin 7 (2.1- to 2.6-fold) and higher cecal SCFA (1.8- to 3.5-fold) and Lactobacillus (2.7- to 4.0-fold) concentrations than the CKD group. Conclusion: Supplemental feeding with fermentable DFs, such as GG and PHGG, might be effective for the prevention or management of CKD by restoring colonic barrier integrity and microflora composition, as shown in mice.

A proof-of-concept study to evaluate the efficacy and safety of BTI320 on post-prandial hyperglycaemia in Chinese subjects with pre-diabetes.

BACKGROUND: Galactomannan(s) are plant-derived fiber shown to reduce post-prandial blood glucose by delaying intestinal absorption of carbohydrates and slowing down gastric emptying. We examined glucose-lowering effects of BTI320, a propriety fractionated mannan(s) administered as a chewable tablet before meal in a proof-of-concept study in Chinese subjects with prediabetes. METHODS: Sixty Chinese adults aged 18-70 years with either impaired fasting glucose, impaired glucose tolerance, or glycated haemoglobin 5.7-6.4% (39-46 mmol/mol), were randomly assigned in 2:2:1 ratio to either BTI320 8 g (high dose), BTI320 4 g (low dose) or matching-placebo three times daily before meal for 16 weeks. The primary endpoint was change in fructosamine in subjects treated with BTI320 compared with placebo from baseline to week 4. Indices of glycaemic variability based on continuous glucose monitoring (CGM) and standard meal tolerance test were explored in secondary analyses. RESULTS: Of 60 subjects randomized, 3 subjects discontinued study treatment prematurely. In intention-to-treat analysis, no significant differences in change in serum fructosamine between low or high dose BTI320 and placebo were observed. Using random effect models, adjusted for variability by meals, treatment with low dose BTI320 was associated with reduction in 1-h (p < 0.01), 2-h (p = 0.01) and 3-h (p = 0.02) post-prandial incremental glucose area-under-curve and post-meal maximum glucose (p = 0.03) compared with placebo. Subjects receiving low dose BTI320 had greater body weight reduction than placebo group. CONCLUSIONS: BTI320 did not change fructosamine levels compared with placebo. BTI320 reduced glycaemic variability based on CGM indices. TRIAL REGISTRATION: The study was registered at www.clinicaltrials.gov , reference number NCT02358668 (9 February 2015).

Potential of two delivery systems for nisin topical application to dental plaque biofilms in dogs.

BACKGROUND: Periodontal disease (PD) is caused by the development of a microbial biofilm (dental plaque) in the periodontium, affecting approximately 80% of dogs. Several bacterial species present in the canine oral cavity can be implicated in the development of this disease, including Enterococcus spp. To decrease antibiotic administration, a possible control strategy for dog's enterococcal PD may involve the use of the antimicrobial peptide (AMP) nisin. Nisin's inhibitory activity was evaluated against a collection of previously characterized enterococci obtained from the oral cavity of dogs with PD (n = 20), as well as the potential of a guar-gum gel and a veterinary toothpaste as topical delivery systems for this AMP. The Minimum Inhibitory (MIC) and Bactericidal Concentrations (MBC) and the Minimum Biofilm Eradication (MBEC) and Inhibitory Concentrations (MBIC) were determined for nisin and for the supplemented guar-gum gel. For the supplemented veterinary toothpaste an agar-well diffusion assay was used to evaluate its inhibitory potential. RESULTS: Nisin was effective against all isolates. Independently of being or not incorporated in the guar-gum gel, its inhibitory activity on biofilms was higher, with MBIC (12.46 ± 5.16 and 13.60 ± 4.31 µg/mL, respectively) and MBEC values (21.87 ± 11.33 and 42.34 ± 16.61 µg/mL) being lower than MIC (24.61 ± 4.64 and 14.90 ± 4.10 µg/mL) and MBC (63.09 ± 13.22 and 66.63 ± 19.55 µg/mL) values. The supplemented toothpaste was also effective, showing inhibitory activity against 95% of the isolates. CONCLUSIONS: The inhibitory ability of nisin when incorporated in the two delivery systems was maintained or increased, demonstrating the potential of these supplemented vehicles to be applied to PD control in dogs.

Potential Usefulness of a Wakame/Carob Functional Snack for the Treatment of Several Aspects of Metabolic Syndrome: From In Vitro to In Vivo Studies.

Metabolic syndrome (MetS) greatly increases the risk of cardiovascular diseases and type 2 diabetes mellitus. The aim of this study was to evaluate the efficacy of functional snacks containing a combination of wakame (W) and carob pod (CP) flours in reducing markers associated with MetS. The mechanisms of action underlying these effects were also evaluated. In vitro approaches were carried out in mature 3T3-L1 adipocytes and RAW 264.7 macrophages treated with different doses of extracts from W, CP, or a combination of both. Furthermore, an in vivo experiment was conducted in rats with MetS treated with normal-caloric diets containing different snack formulations with combinations of 1/50 (snack A) or 1/5 of wakame/carob (snack B). In vitro experiments results indicated that both W and CP had delipidating effects, but only the latter induced anti-inflammatory and anti-hypertensive effects. As far as the in vivo study is concerned, snack B was ineffective and snack A showed an anti-hypertensive effect in rats with MetS. The present study shows for the first time the in vitro efficacy of a W and CP combination as an anti-inflammatory, delipidating, and anti-hypertensive tool, and its potential usefulness in treating MetS.

Functional Components of Carob Fruit: Linking the Chemical and Biological Space.

The contribution of natural products to the drug-discovery pipeline has been remarkable since they have served as a rich source for drug development and discovery. Natural products have adapted, during the course of evolution, optimum chemical scaffolds against a wide variety of diseases, including cancer and diabetes. Advances in high-throughput screening assays, assisted by the continuous development on the instrumentation's capabilities and omics, have resulted in charting a large chemical and biological space of drug-like compounds, originating from natural sources. Herein, we attempt to integrate the information on the chemical composition and the associated biological impact of carob fruit in regards to human health. The beneficial and health-promoting effects of carob along with the clinical trials and the drug formulations derived from carob's natural components are presented in this review.

Acute effects of a dietary non-starch polysaccharide supplement on cognitive performance in healthy middle-aged adults.

OBJECTIVE: Certain plant polysaccharides may provide psychological health benefits. The aim of this study was to evaluate whether they can acutely improve mood and cognitive function. METHOD: In a randomized, double-blind, placebo-controlled, between subjects design trial, 73 middle-aged adults consumed 4 g of a proprietary mixture of non-starch polysaccharides (NSPs) (Ambrotose® complex), a rice flour placebo, or a sucrose control. Participants completed testing at baseline and 30 minutes post-consumption. Acute effects of consumption on mood, cognition, and blood glucose were evaluated during mental tests designed to induce mental fatigue. RESULTS: Significant improvement in recognition and working memory performance was observed in the group that consumed NSP compared with placebo or sucrose. Improvements in memory performance following NSP intake were independent of changes in blood glucose. DISCUSSION: This is the first report of acute behavioural improvement following plant polysaccharide intake in healthy middle-aged adults under conditions of mental fatigue. The findings suggest that certain NSP may enhance memory performance through mechanisms other than elevated blood glucose.

A CE-Marked Drug Used for Localized Adiposity Reduction: A 4-Year Experience.

BACKGROUND: Injectable fat-reducing therapies are not an alternative to liposuction. Rather, they may be best suited for patients who are unwilling or unable to undergo surgical reduction of small collections of fat, and for patients who desire touchups for liposuction-induced irregularities. OBJECTIVES: The authors report their 4-year experience with a novel injectable CE-marked drug, used in an off-label manner. METHODS: Between October 2009 and November 2013, 186 patients were treated by injection of an adipocitolytic solution in 1 of 4 private Italian aesthetic facilities, by 1 of 4 independent physicians. Treated areas included the neck, hips/saddlebags, abdomen/love handles, inner thighs, and buffalo hump. Complications and side effects were documented. RESULTS: All patients experienced mild to moderate swelling and reddening of the skin, which resolved 3 to 5 days after injection. No major complications or side effects occurred, such as necrosis. Rates of transient events were as follows: hematoma, 1.61%; paresthesia, 1.07%; and ecchymosis, 6.45%. Pruritus was reported by 21.5% of patients, which began 3 to 7 days following injection. Subcutaneous nodules were noted in 1.61% and resolved within 4 months of injection. A transitory "unusual sensation" was reported by 12.9% of patients, which lasted up to 2 months after final injection. CONCLUSIONS: Results demonstrate that this CE-marked agent appears to be effective and safe for medical treatment of fat reduction.

Carob pod insoluble fiber exerts anti-atherosclerotic effects in rabbits through sirtuin-1 and peroxisome proliferator-activated receptor-γ coactivator-1α.

The aim of this study was to evaluate the potential effects of an insoluble dietary fiber from carob pod (IFC) (1 g ⋅ kg(-1) ⋅ d(-1) in the diet) on alterations associated with atherosclerosis in rabbits with dyslipidemia. Male New Zealand rabbits (n = 30) were fed the following diets for 8 wk: 1) a control diet (SF412; Panlab) as a control group representing normal conditions; 2) a control supplemented with 0.5% cholesterol + 14% coconut oil (DL) (SF302; Panlab) for 8 wk as a dyslipidemic group; and 3) a control containing 0.5% cholesterol + 14% coconut oil plus IFC (1 g ⋅ kg(-1) ⋅ d(-1)) (DL+IFC) for 8 wk. IFC was administered in a pellet mixed with the DL diet. The DL-fed group developed mixed dyslipidemia and atherosclerotic lesions, which were associated with endothelial dysfunction, inflammation, and fibrosis. Furthermore, sirtuin-1 (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) protein expression in the aorta were reduced to 77% and 63% of the control group, respectively (P < 0.05), in these rabbits. Administration of IFC to DL-fed rabbits reduced the size of the aortic lesion significantly (DL, 15.2% and DL+IFC, 2.6%) and normalized acetylcholine-induced relaxation (maximal response: control, 89.3%; DL, 61.6%; DL+IFC, 87.1%; P < 0.05) and endothelial nitric oxide synthase expression (DL, 52% and DL+IFC, 104% of the control group). IFC administration to DL-fed rabbits also reduced cluster of differentiation 36 (DL, 148% and DL+IFC, 104% of the control group; P < 0.05), plasminogen activator inhibitor-1 (DL, 141% and DL+IFC, 107% of the control group), tumor necrosis factor-α (DL, 166% and DL+IFC, 120% of the control group), vascular cell adhesion molecule-1 (DL, 153% and DL+IFC, 110% of the control group), transforming growth factor-ß (DL, 173% and DL+IFC, 99% of the control group), and collagen I (DL, 157% and DL+IFC, 112% of the control group) in the aorta. These effects were accompanied by an enhancement of SIRT1 and PGC-1α (160% and 121% of the control group, respectively; P < 0.05) vascular expression. In summary, we demonstrated for the first time, to our knowledge, that administration of IFC reduces the development of atherosclerosis in rabbits. This effect seems to be related to an improvement in endothelial function and a reduction of inflammation and fibrosis, most probably as a consequence of the reduction of serum concentrations of cholesterol and triglycerides. Increased expression of aortic SIRT1 and PGC-1α could play an important role in the observed effects of IFC in rabbits with dyslipidemia.

High-viscosity dietary fibers reduce adiposity and decrease hepatic steatosis in rats fed a high-fat diet.

Viscous dietary fiber consumption lowers the postprandial glucose curve and may decrease obesity and associated comorbidities such as insulin resistance and fatty liver. We determined the effect of 2 viscous fibers, one fermentable and one not, on the development of adiposity, fatty liver, and metabolic flexibility in a model of diet-induced obesity. Rats were fed a normal-fat (NF) diet (26% energy from fat), a high-fat diet (60% energy from fat), each containing 5% fiber as cellulose (CL; nonviscous and nonfermentable), or 5% of 1 of 2 highly viscous fibers-hydroxypropyl methylcellulose (HPMC; nonfermentable) or guar gum (GG; fermentable). After 10 wk, fat mass percentage in the NF (18.0%; P = 0.03) and GG groups (17.0%; P < 0.01) was lower than the CL group (20.7%). The epididymal fat pad weight of the NF (3.9 g; P = 0.04), HPMC (3.9 g; P = 0.03), and GG groups (3.6 g; P < 0.01) was also lower than the CL group (5.0 g). The HPMC (0.11 g/g liver) and GG (0.092 g/g liver) groups had lower liver lipid concentrations compared with the CL group (0.14 g/g liver). Fat mass percentage, epididymal fat pad weight, and liver lipid concentration were not different among the NF, HPMC, and GG groups. The respiratory quotient was higher during the transition from the diet-deprived to fed state in the GG group (P = 0.002) and tended to be higher in the HPMC group (P = 0.06) compared with the CL group, suggesting a quicker shift from fatty acid (FA) to carbohydrate oxidation. The HPMC group [15.1 nmol/(mg ⋅ h)] had higher ex vivo palmitate oxidation in muscle compared with the GG [11.7 nmol/(mg ⋅ h); P = 0.04] and CL groups [10.8 nmol/(mg ⋅ h); P < 0.01], implying a higher capacity to oxidize FAs. Viscous fibers can reduce the adiposity and hepatic steatosis that accompany a high-fat diet, and increase metabolic flexibility, regardless of fermentability.

Activity, reduced toxicity, and scale-up synthesis of amphotericin B-conjugated polysaccharide.

Amphotericin B (AMB) arabinogalactan (AG) conjugate was synthesized by the conjugation of AMB to oxidized AG by reductive amination. The conjugate was evaluated for in vitro antifungal activity and in vivo toxicity. Optimization of the conjugation process was investigated using large batches of 100 g, which are 20 times larger than previously reported for AMB-AG conjugation. The efficacy of AMB-AG conjugates was studied as a function of reaction conditions and time, aldehyde/reducing agent mole ratio, and purification procedure. The most potent AMB-AG conjugate having low minimal inhibitory concentration (MIC) and high maximal tolerated dose (MTD) was obtained following reduction with NaBH4 at 1:2 mol ratio (AG units/NaBH4) at 25 °C for 24 h. AMB-AG conjugate prepared under these conditions demonstrated MIC of 0.5 mg/L (equiv of AMB) in Candida albicans, and an MTD of 60 mg/kg (equiv of AMB) in mice, while AMB clinical formulation (Fungizone) demonstrated high toxicity (MTD = 3 mg/kg). These findings confirm the simplicity and reproducibility of the conjugation allowing this method to be applied on larger scale production.

Partially hydrolyzed guar gum accelerates colonic transit time and improves symptoms in adults with chronic constipation.

BACKGROUND AND AIM: Partially hydrolyzed guar gum (PHGG) is a water-soluble, non-gelling dietary fiber with a wide range of uses in clinical nutrition. The aim of this prospective study was to investigate the effect of guar gum on colonic transit time (CTT) and symptoms of chronic constipation. METHODS: We enrolled patients fulfilling Rome III criteria for chronic constipation. CTT was measured before and at the end of treatment. After a 2-week run-in period, patients received 5 mg PHGG daily for 4 weeks. During study period, patients kept daily symptoms, stool and laxative usage diaries. They also recorded their symptom-related satisfaction weekly and treatment adverse events. RESULTS: Forty-nine patients received treatment; 39 (80 %) completed the study. Treatment significantly reduced colon transit time, from 57.28 ± 39.25 to 45.63 ± 37.27 h (p = 0.026), a reduction more prominent in slow transit patients (from 85.50 ± 27.75 to 63.65 ± 38.11 h, p = 0.016). Overall, the weekly number of complete spontaneous and spontaneous bowel movements increased significantly (p < 0.001); the latter correlated significantly with the acceleration of CTT in the overall population and in slow transit patients (B = 0.382; p = 0.016 and B = 0.483; p = 0.023, respectively). In addition, the number of bowel movements with straining decreased (p < 0.001) and stool form improved (p < 0.001), while days with laxative intake and days with abdominal pain decreased (p = 0.001 and p = 0.027, respectively). CONCLUSION: Four-week PHGG use accelerates colon transit time in patients with chronic constipation, especially in those with slow transit, and improves many of their symptoms including frequency of bowel movements.

Improvement of the metabolic syndrome profile by soluble fibre - guar gum - in patients with type 2 diabetes: a randomised clinical trial.

A diet rich in fibre seems to protect against the metabolic syndrome (MetS), but there is scarce information about the role of fibre intake in patients with the MetS and diabetes. The aim of the present study was to evaluate the effects of soluble fibre from partially hydrolysed guar gum (PHGG) on the MetS and cardiovascular risk factors in patients with type 2 diabetes. In the present randomised controlled clinical trial, forty-four patients with type 2 diabetes (males 38·6 %, age 62 (SD 9) years, diabetes duration 14·2 (SD 9·6) years) and the MetS underwent clinical, laboratory and dietary evaluations at baseline, 4 and 6 weeks. All patients followed their usual diet and the intervention group (n 23) received an additional 10 g/d of PHGG. In the intervention group, waist circumference (WC), glycated Hb (HbA1c), 24 h urinary albumin excretion (UAE) and serum trans-fatty acids (FA) were reduced in comparison with baseline after 4 and 6 weeks: WC 103·5 (SD 9·5) to 102·1 (SD 10) to 102·3 (SD 9·7) cm; HbA1c 6·88 (SD 0·99) to 6·64 (SD 0·94) to 6·57 (SD 0·84) %; 24 h UAE 6·8 (interquartile range 3·0-17·5) to 4·5 (interquartile range 3·0-10·5) to 6·2 (interquartile range 3·0-9·5) mg; trans-FA 71 (interquartile range 46-137) to 67 (interquartile range 48-98) to 57 (interquartile range 30-110) mg/l (P< 0·05 for all). The only change in the control group was weight reduction: 77·0 (SD 13·5) to 76·2 (SD 13·3) to 76·1 (SD 13·4) kg (P= 0·005). Other MetS components (blood pressure, TAG, HDL-cholesterol, fasting plasma glucose), total and LDL-cholesterol, C-reactive protein and endothelin-1 did not change in either group. In patients with type 2 diabetes and the MetS, the addition of PHGG to the usual diet improved cardiovascular and metabolic profiles by reducing WC, HbA1c, UAE and trans-FA.

Interventions for treating cholestasis in pregnancy.

BACKGROUND: Obstetric cholestasis has been linked to adverse maternal and fetal/neonatal outcomes. As the pathophysiology is poorly understood, therapies have been empiric. The first version of this review, published in 2001, and including nine randomised controlled trials involving 227 women, concluded that there was insufficient evidence to recommend any of the interventions alone or in combination. This is the first update. OBJECTIVES: To evaluate the effectiveness and safety of therapeutic and delivery interventions in women with cholestasis of pregnancy. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (20 February 2013) and reference lists of identified studies. SELECTION CRITERIA: Randomised controlled trials that compared two intervention strategies for women with a clinical diagnosis of obstetric cholestasis. DATA COLLECTION AND ANALYSIS: The review authors independently assessed trials for eligibility and risk of bias. We independently extracted data and checked these for accuracy. MAIN RESULTS: We included 21 trials with a total of 1197 women. They were mostly at moderate to high risk of bias. They assessed 11 different interventions resulting in 15 different comparisons.Compared with placebo, ursodeoxycholic acid (UDCA) showed improvement in pruritus in five (228 women) out of seven trials. There were no significant differences in instances of fetal distress in the UDCA groups compared with placebo (average risk ratio (RR) 0.67; 95% confidence interval (CI) 0.22 to 2.02; five trials, 304 women; random-effects analysis: T² = 0.74; I² = 48%). There were significantly fewer total preterm births with UDCA (RR 0.46; 95% CI 0.28 to 0.73; two trials, 179 women). The difference for spontaneous preterm births was not significant (RR 0.99; 95% CI 0.41 to 2.36, two trials, 109 women).Two trials (48 women) reported lower (better) pruritus scores for S-adenosylmethionine (SAMe) compared with placebo, while two other trials of 34 women reported no significant differences between groups.UDCA was more effective in improving pruritus than either SAMe (four trials; 133 women) or cholestyramine (one trial; 84 women), as was combined UDCA+SAMe when compared with placebo (one trial; 16 women) and SAMe alone (two trials; 68 women). However, combined UDCA+SAMe was no more effective than UDCA alone in regard to pruritus improvement (one trial; 53 women) and two trials (80 women) reported data were insufficient to draw any conclusions from. In one trial comparing UDCA and dexamethasone (83 women), a significant improvement with UDCA was seen only in a subgroup of women with severe obstetric cholestasis (23 women).Danxiaoling significantly improved pruritus in comparison to Yiganling. No significant differences were seen in pruritus improvement with other interventions.Eight trials reported fetal or neonatal deaths, with two deaths reported overall (both in the placebo groups).Women receiving UDCA and cholestyramine experienced nausea, vomiting and diarrhoea. Guar gum caused mild abdominal distress, diarrhoea and flatulence during the first days of treatment. Women found charcoal suspension unpleasant to swallow. Dexamethasone caused nausea, dizziness and stomach pain in one woman.One trial (62 women) looked at the timing of delivery intervention. There were no stillbirths or neonatal deaths in 'early delivery' or the 'await spontaneous labour' group. There were no significant differences in the rates of caesarean section, meconium passage or admission to neonatal intensive care unit between the two groups. AUTHORS' CONCLUSIONS: Different approaches to assessing and reporting pruritus precluded pooling of trials comparing the effects of UDCA versus placebo on pruritus, but examination of individual trials suggests that UDCA significantly improves pruritus, albeit by a small amount. Fewer instances of fetal distress/asphyxial events were seen in the UDCA groups when compared with placebo but the difference was not statistically significant. Large trials of UDCA to determine fetal benefits or risks are needed.A single trial was too small to rule in or out a clinically important effect of early term delivery on caesarean section.There is insufficient evidence to indicate that SAMe, guar gum, activated charcoal, dexamethasone, cholestyramine, Salvia, Yinchenghao decoction (YCHD), Danxioling and Yiganling, or Yiganling alone or in combination are effective in treating women with cholestasis of pregnancy.

Role of PHGG as a dietary fiber: a review article.

AIM: Functional and metabolic effects of dietary fiber are recognized by the scientific, clinical and nutritional experts. Dietary fiber plays a very significant role in modifying the intestinal microbiota, exerting prebiotic effects such as stimulating the growth and/or function of beneficial intestinal microorganisms. Changes in the gut microbiota composition are classically considered as one of the many factors involved in the pathogenesis of either inflammatory bowel disease or irritable bowel syndrome. The use of particular food products with a prebiotic effect has thus been tested in clinical trials with the objective to improve the clinical activity and well-being of patients with such disorders. Partially Hydrolyzed Guar Gum (PHGG) is a natural dietary fiber (Benefibra™, Novartis CH Italy): it is a white powder, water-soluble, colorless and transparent in water solution and almost tasteless. PHGG is stable and soluble at various pH levels commonly found in foods as well as resistant to heat, acid, salt, high pressure and digestive enzymes. Low viscosity of PHGG provides a distinct advantage for the use of fiber in enteral feeding products to be administered through feeding tubes. It has been studied in adults, both healthy volunteers and patients, in different disorders such as constipation, irritable bowel syndrome (IBS), enteral nutrition, small intestine bacterial overgrowth (SIBO) and, very recently, in children suffering from functional abdominal pain according to the Rome III Criteria definition for functional gastrointestinal disorders (FGIDs). This review takes stock of the situation concerning what is known to date on PHGG as dietary fiber, in order to give the health care professionals, such as gastroenterologists, dieticians and general practitioners, a complete overview on its intrinsic characteristics, preclinical and clinical evaluations, uses in different situations as supportive therapy in the management of the main intestinal functional disorders both in adults and in children. METHODS: All the papers on PHGG, published from the early 1990s of the Last Century to the Year 2013, have been considered. All types of publications have been included. PubMed, Medline, Ovid were the main sources adopted for data retrieving. RESULTS: PHGG has been studied in both animals and humans; its safety is well known and several clinical uses are well established. Concerning the modulation of metabolism in human, very little has been done to date and the studies have been focused, for the most part, on the functional diseases: PHGG has been proved to be useful in treating both IBS -C and D symptoms, not only in adults but also in children; data on constipation are relatively scarce and what can be deduced from the Literature is that the high concentration of fiber gives the PHGG the possibility of being used effectively in acceptable dosages (up to 22 g/day) even in situations such as chronic constipation. The use in clinical nutrition has revealed the flexibility of the compound which, owing to its peculiar characteristics, does not gel and remains liquid, PHGG can be used successfully in patients in enteral nutrition lowering the incidence of diarrhea. New open horizons can be glimpsed for SIBO treatment, lowering or maximizing the antibiotics use. CONCLUSION: Not all the fibers are the same: this is a fact. Promoting the specific knowledge of their characteristics is very important if healthcare professionals want to give their patients the best options for functional gastrointestinal disorders or nutritional needs. PHGG (Benefiber™ Novartis CH) has been proved to be safe and effective in promoting gut health.

Immunomodulatory and anti-inflammatory and anticancer activities of porphyran, a sulfated galactan.

Seaweeds are high in bioactive chemicals frequently used to treat human illnesses. Porphyran is a polysaccharide found in the red seaweeds of the genus Porphyra. Porphyran has been discovered to have immunomodulatory, anti-inflammatory activity, and anti-cancer effects via boosting immunity and targeting important apoptotic molecules, making them potential chemotherapeutic or chemopreventive drugs. Polysaccharide-mediated dynamic control of apoptosis and autophagy in cancer has been a viable treatment with low cytotoxicity with high efficacy. Thus, comprehending the influence of porphyran on human health and their molecular mechanisms would open up a new paradigm in cancer therapies. Also, the importance of apoptotic/autophagy modulating porphyran in cancer therapy has been highlighted as the future direction of improved nano-formulation for improved clinical efficacy. This review focuses on the current research into porphyran's anti-cancer efficacy and putative mechanisms of action through apoptosis and autophagy in various cancers, as well as its potential chemotherapeutic treatment in near future.