Acute toxicity,percutaneous absorption and effects on hepatic mixed function oxidase activities of 2,4,4′-trichloro-2′-hydroxydiphenyl ether (Irgasan® DP300) and its chlorinated derivatives

Acute toxicity of 2,4,4-trichloro-2-hydroxydiphenyl ether (Irgasan^® DP300) (I) and its three chlorinated derivatives, 2,3,4,4-tetrachloro-2-hydroxydiphenyl ether (II), 2,4,4,5-tetrachloro-2-hydroxydiphenyl ether (III) and 2,3,4,4,5-pentachloro-2-hydroxydiphenyl ether (IV), in mice were examined by intraperitoneal injection. The LD₅₀ values of Irgasan DP300, II, III and IV were 1,090, 710, 650 and 430 mg/kg, respectively.The percutaneous absorptions of these tritiated compounds were also examined by the application on the backs of mice. The radioactivities in most tissues reached to the maximal levels at 12 h or 18 h after dosing, which corresponded to 11–76% of the maximal levels given by the oral administration (Kanetoshi et al. 1988a). These results show the high percutaneous absorbability of Irgasan DP300 and its chlorinated derivatives.The intraperitoneal administrations of III and IV to rats induced hepatic microsomal aminopyrine N-demethylase and aniline 4-hydroxylase activities similarly to phenobarbital. These chlorinated derivatives also increased cytochrome P-450 content, and the activities of aminopyrine N-demethylase and N-methylaniline N-demethylase in hepatic microsomes from mice. The extents of the increases were similar to those by phenobarbital and 3-methylcholanthrene.     

Mercury and chlorinated hydrocarbons in zoobenthos of Lake Päijänne,Finland

The average amounts of mercury, PCBs, and DDT (primarily DDE), found in macrozoobenthos, on the wet basis, in Lake Päijänne, Finland, for the time period 1972–1974, were 79 ng/g, 29 ng/g, and 8 ng/g, respectively. Lindane was found in negligible amounts in only 2% of the samples examined; aldrin was present in 10% of the samples; no dieldrin was detected. Mercury and PCB concentrations varied regionally in the lake. PCB and DDT concentrations were greater in the predatory bottom animals than in the herbivores or detritus feeders, and the amounts of chlorinated hydrocarbons were greater in profundal animals than in littoral animals. No significant correlation was apparent between the amount of residues found and the weight of the animal (e.g.Anodonta). A significant positive correlation was evident in the amounts of PCBs and DDT in most of the taxonomical groups.Spongilla lacustris andAnodonta piscinalis were excellent species for monitoring purposes.     

Urinary cadmium and N-acetyl-β-D-glucosaminidase excretion of inhabitants living in a cadmium-polluted area

Summary Urinary cadmium (Cd), N-acetyl--D-glucosaminidase (NAG), and creatinine levels were determined for 400 inhabitants living in Cd-polluted districts of Annaka City in Gunma Prefecture, Japan. The Cd pollution was mainly due to falling dust from a zinc smelter factory according to seasonal winds. The Cd-polluted areas were divided into five administrative districts around the factory. The geometric mean of the urinary Cd level of the inhabitants in the five districts, Nodono, Iwai, Ooya, Nakajyuku, and Itahana, were 2.95, 2.66, 2.45, 1.97, and 1.67 g/g creatinine, respectively. The geometric means for Nodono and Iwai are statistically larger than that for Itahana (P < 0.01). These results were well explained by the wind direction and proximity to the factory. In addition, a two-way analysis of variance on the urinary Cd level was made using place of residence and smoking habits. The effect was mainly due to the place of residence, and no interactions were found. There were statistically significant differences in NAG excretion among the five groups, but no difference could be found between two groups using a multiple comparison. Pearson's correlation coefficient between the logarithm of urinary Cd content and that of NAG was 0.203, but statistically significant (r = 0.462 without creatinine correction; P < 0.01). The present results indicate the association of urinary Cd and NAG levels in a Cd-exposed population whose geometric mean of urinary Cd content is about 2 g/g creatinine. We recommend a continuous survey of the minimum health effects of the Cd pollution using urinary levels of Cd and protein including NAG.     

Mutagenicity of 4,4′-methylene-bis-(2-chloroaniline) “MOCA” and its N-acetyl derivatives in S. typhimurium

Summary 4,4-methylene-bis-(2-chloroaniline) (MOCA) and two identified urinary N-acetyl and N,N-diacetyl derivatives were tested in a Salmonella/mammalian microsome assay. No mutagenic activity was observed without rat liver S9 mix activation. In the presence of rat liver S9 mix, the chemicals were mutagens, but the mutagenicity of N-acetyl derivatives to strain TA 100 was reduced when compared to that of MOCA, and a greater amount of S9 was required to exhibit the mutagenicity of the N,N-diacetyl-MOCA. These data suggest that N-acetylation does not account for the mutagenic effectiveness of MOCA.     

Impact of ST-246® on ACAM2000™ smallpox vaccine reactogenicity, immunogenicity, and protective efficacy in immunodeficient mice

Although a highly effective vaccine against smallpox, vaccinia virus (VV) is not without adverse events, some of which can be life-threatening, particularly in immunocompromised individuals. We have recently demonstrated that the immunogenicity and protective efficacy of Dryvax^® in immunocompetent mice is preserved even when co-administered with ST-246, an orally bioavailable small-molecule inhibitor of orthopoxvirus egress and dissemination. In addition, ST-246 markedly reduced the reactogenicity of the smallpox vaccine ACAM2000 and the highly neurovirulent VV strain Western Reserve (VV-WR). Here, we evaluated the impact of ST-246 co-administration on ACAM2000 reactogenicity, immunogenicity, and protective efficacy in seven murine models of varying degrees of humoral and cellular immunodeficiency: BALB/c and B-cell deficient (JH-KO) mice depleted of CD4⁺ or CD8⁺ or both subsets of T cells. We observed that ST-246 reduced vaccine lesion severity and time to complete resolution in all of the immunodeficient models examined, except in those lacking both CD4⁺ and CD8⁺ T cells. Although VV-specific humoral responses were moderately reduced by ST-246 treatment, cellular responses were generally comparable or slightly enhanced at both 1 and 6 months post-vaccination. Most importantly, in those models in which vaccination given alone conferred protection against lethal VV challenge, similar levels of protection were observed at both time points when vaccination was given with ST-246. These data suggest that, with the exception of individuals with irreversible, combined CD4⁺ and CD8⁺ T-cell deficiency, ST-246 co-administered at the time of vaccination may help reduce vaccine reactogenicity—even in those lacking humoral immunity—without impeding the induction of protective immunity.     

Immunogenicity and safety of two monovalent rotavirus vaccines,ROTAVAC® and ROTAVAC 5D® in Zambian infants

Background and AimsROTAVAC® (frozen formulation stored at −20 °C) and ROTAVAC 5D® (liquid formulation stable at 2–8 °C) are rotavirus vaccines derived from the 116E human neonatal rotavirus strain, developed and licensed in India. This study evaluated and compared the safety and immunogenicity of these vaccines in an infant population in Zambia.MethodsWe conducted a phase 2b, open-label, randomized, controlled trial wherein 450 infants 6 to 8 weeks of age were randomized equally to receive three doses of ROTAVAC or ROTAVAC 5D, or two doses of ROTARIX®. Study vaccines were administered concomitantly with routine immunizations. Blood samples were collected pre-vaccination and 28 days after the last dose. Serum anti-rotavirus IgA antibodies were measured by ELISA, with WC3 and 89–12 rotavirus strains as viral lysates in the assays. The primary analysis was to assess non-inferiority of ROTAVAC 5D to ROTAVAC in terms of the geometric mean concentration (GMC) of serum IgA (WC3) antibodies. Seroresponse and seropositivity were also determined. Safety was evaluated as occurrence of immediate, solicited, unsolicited, and serious adverse events after each dose.ResultsThe study evaluated 388 infants in the per-protocol population. All three vaccines were well tolerated and immunogenic. The post-vaccination GMCs were 14.0 U/mL (95% CI: 10.4, 18.8) and 18.1 U/mL (95% CI: 13.7, 24.0) for the ROTAVAC and ROTAVAC 5D groups, respectively, yielding a ratio of 1.3 (95% CI: 0.9, 1.9), thus meeting the pre-set non-inferiority criteria. Solicited and unsolicited adverse events were similar across all study arms. No death or intussusception case was reported during study period.ConclusionsAmong Zambian infants, both ROTAVAC and ROTAVAC 5D were well tolerated and the immunogenicity of ROTAVAC 5D was non-inferior to that of ROTAVAC. These results are consistent with those observed in licensure trials in India and support use of these vaccines across wider geographical areas.     

Urinary excretion of in vivo ¹³C-labelled milk oligosaccharides in breastfed infants

Recent observations indicate that human milk oligosaccharides (HMO) are involved in a variety of physiological processes in infants. Their metabolic fate, however, is virtually unknown. We investigated metabolic aspects in infants after endogenous 13C-labelling of HMO. An oral bolus of natural and 13C-labelled galactose (Gal; 23 g Gal+4 g 13C-Gal) was given to ten lactating women. Aliquots of milk at each nursing as well as breath samples from the mothers and urine from their infants were collected over 36 h. The 13C-enrichment of HMO and their renal excretion was determined by isotope ratio-MS; characterisation was achieved by fast atom bombardment-MS. After the Gal bolus was given, an immediate 13C-enrichment in milk and in infants' urine was observed which lasted 36 h. Mass spectrometric analysis of 13C-enriched urinary fractions confirmed the excretion of a variety of neutral and acidic HMO without metabolic modification of their structures. Components with glucose split off at the reducing end were also detectable. Quantitative data regarding the infants' intake of lacto-N-tetraose and its monofucosylated derivative lacto-N-fucopentaose II ranged from 50 to 160 mg with each suckling, respectively; renal excretion of both components varied between 1 and 3 mg/d. Since the intake of individual HMO by the infants was in the range of several hundred mg per suckling, i.e. several g/d, and some of these components were excreted in mg amounts as intact HMO with the infants' urine, not only local but also systemic effects might be expected.     

Urinary excretion of phthalate metabolites,phenols and parabens in rural and urban Danish mother–child pairs

Some phthalates, parabens and phenols have shown adverse endocrine disrupting effects in animal studies and are also suspected to be involved in human reproductive problems. However, knowledge about exposure sources and biomonitoring data in different subsets of populations are still scarce. Thus, in this study first morning urine samples were collected from 6 to 11 years Danish children and their mothers. The content of seven parabens, nine phenols and metabolites of eight different phthalates were analysed by LC–MS/MS. Two parabens, six phenols and metabolites from six phthalate diesters were measurable in more than 50%, 75% and 90% of the participants, respectively. Thus the children and their mothers were generally exposed simultaneously to a range of phthalates, phenols and parabens. In general, the levels were low but for several of the compounds extreme creatinine adjusted concentrations 100–500-fold higher than the median level were seen in some participants. Children were significantly higher exposed to bisphenol A (BPA) and some of the phthalates (DiBP, DnBP, BBzP, DEHP and DiNP) than their mothers, whereas mothers were higher exposed to compounds related to cosmetics and personal care products such as parabens (MeP, EtP and n-PrP), benzophenone-3, triclosan and diethyl phthalate. However, a very high correlation between mothers and their children was observed for all chemicals. A high individual exposure to one chemical was often associated with a high exposure to other of the chemicals and the possibility of combination effects of multiple simultaneous exposures cannot be excluded.     

Inhibition of nitric oxide in LPS-stimulated macrophages of young and senescent mice by δ-tocotrienol and quercetin

Background

Changes in immune function believed to contribute to a variety of age-related diseases have been associated with increased production of nitric oxide (NO). We have recently reported that proteasome inhibitors (dexamethasone, mevinolin, quercetin, δ-tocotrienol, and riboflavin) can inhibit lipopolysaccharide (LPS)-induced NO production in vitro by RAW 264.7 cells and by thioglycolate-elicited peritoneal macrophages derived from four strains of mice (C57BL/6, BALB/c, LMP7/MECL-1^-/- and PPAR-α^-/- knockout mice). The present study was carried out in order to further explore the potential effects of diet supplementation with naturally-occurring inhibitors (δ-tocotrienol and quercetin) on LPS-stimulated production of NO, TNF-α, and other pro-inflammatory cytokines involved in the ageing process. Young (4-week-old) and senescent mice (42-week old) were fed control diet with or without quercetin (100 ppm), δ-tocotrienol (100 ppm), or dexamethasone (10 ppm; included as positive control for suppression of inflammation) for 4 weeks. At the end of feeding period, thioglycolate-elicited peritoneal macrophages were collected, stimulated with LPS, LPS plus interferon-β (IFN-β), or LPS plus interferon-γ (IFN-γ), and inflammatory responses assessed as measured by production of NO and TNF-α, mRNA reduction for TNF-α, and iNOS genes, and microarray analysis.

Results

Thioglycolate-elicited peritoneal macrophages prepared after four weeks of feeding, and then challenged with LPS (10 ng or 100 ng) resulted in increases of 55% and 73%, respectively in the production of NO of 46-week-old compared to 8-week-old mice fed control diet alone (respective control groups), without affecting the secretion of TNF-α among these two groups. However, macrophages obtained after feeding with quercetin, δ-tocotrienol, and dexamethasone significantly inhibited (30% to 60%; P < 0.02) the LPS-stimulated NO production, compared to respective control groups. There was a 2-fold increase in the production of NO, when LPS-stimulated macrophages of quercetin, δ-tocotrienol, or dexamethasone were also treated with IFN-β or IFN-γ compared to respective control groups. We also demonstrated that NO levels and iNOS mRNA expression levels were significantly higher in LPS-stimulated macrophages from senescent (0.69 vs 0.41; P < 0.05), compared to young mice. In contrast, age did not appear to impact levels of TNF-α protein or mRNA expression levels (0.38 vs 0.35) in LPS-stimulated macrophages. The histological analyses of livers of control groups showed lesions of peliosis and microvesicular steatosis, and treated groups showed Councilman body, and small or large lymphoplasmacytic clusters.

Conclusions

The present results demonstrated that quercetin and δ-tocotrienols inhibit the LPS-induced NO production in vivo. The microarray DNA analyses, followed by pathway analyses indicated that quercetin or δ-tocotrienol inhibit several LPS-induced expression of several ageing and pro-inflammatory genes (IL-1β, IL-1α, IL-6, TNF-α, IL-12, iNOS, VCAM1, ICAM1, COX2, IL-1RA, TRAF1 and CD40). The NF-κB pathway regulates the production of NO and inhibits the pro-inflammatory cytokines involved in normal and ageing process. These ex vivo results confirmed the earlier in vitro findings. The present findings of inhibition of NO production by quercetin and δ-tocotrienol may be of clinical significance treating several inflammatory diseases, including ageing process.     

The Impact of the Concentration and Dose of Palatinjt® in Foods and Diets on Energy Value

Selenium concentration and bioavailability were assessed in a common Mato Grosso urban regional diet (RUDMT), using 52 Wistar male weanling rats, weighing 56.2 ± 1.4 g. Thirty-two rats were fed a casein diet that was free of selenium, vitamin E and methionine and contained anti-oxidant-free oil for a 30 day period in order to induce a selenium deficiency. The remaining rats were fed on a casein diet, forming control group I, with 0.10μg of selenium per gram of diet. After selenium deficiency had been established, 24 rats were divided into three groups which were fed on three different diets for 25 days: (i) RUDMT group, with 0.02 μg of selenium per gram of diet; (ii) control group II, with 0.10μg of selenium per gram of diet; and (iii) pair-feeding group, with 0.04 μg of selenium per gram of diet. During this latter period, the control group I without depletion continued to be fed on the casein diet with 0.10 μg of selenium per gram of diet. Apparent selenium absorption, selenium concentration and the enzymatic activity of the glutathione peroxidase (GSH Px) in plasma, liver and kidney were determined in order to assess the selenium bioavailability. The RUDMT group showed low selenium bioavailability than the control groups. The low concentration of selenium and other components in the RUDMT diet might have contributed to this result.     

Evaluation of Cuprimine® and Syprine® for decorporation of radioisotopes of cesium, cobalt, iridium and strontium

Cuprimine? and Syprine? are therapeutics approved by the USFDA to treat copper overload in Wilson Disease (a genetic defect in copper transport) by chelation and accelerated excretion of internally-deposited copper. These oral therapeutics are based on the respective active ingredients D-penicillamine (DPA) and N,N'-bis (2-aminoethyl) -1,2-ethanediamine dihydrochloride (Trien). Cuprimine is considered the primary treatment, although physicians are increasingly turning to Syprine as a first-line therapy. Both drugs exhibit oral systemic activity and low toxicity; their biological effects and safety are established. Previous in vivo studies using a rodent animal model established the decorporation potential of Cuprimine and Syprine for (60)Co and (210)Po. Currently these studies are being expanded to evaluate the in vivo decorporation efficacy of these drugs for several additional radionuclides. In this report, results of this investigation are discussed using the radionuclides (137)Cs, (60)Co, (192)Ir and (85)Sr. Short-term 48-h pilot studies were undertaken to evaluate DPA and Trien for their in vivo decorporation potential using male Wistar-Han rats. In these studies, a radionuclide solution was administered to the animals by intravenous (IV) injection, followed by a single IV dose of either DPA or Trien. Control animals received the radionuclide alone. Results show effective decorporation of (60)Co by DPA within the time frame evaluated. DPA and Trien were also modestly effective in decorporation of (137)Cs and (85)Sr, respectively. The study did not find DPA or Trien effective for decorporation of (192)Ir. Based on these encouraging findings, further studies to evaluate the dose-response profiles and timing of the chelator administration post exposure to radionuclides are warranted.     

Decreased excretion of thioethers in urine of smokers after the use of β-carotene

Summary Epidemiologic studies have demonstrated an inverse relation between vitamin A intake and lung cancer rate. There is strong evidence that the provitamin A, -carotene, plays a more important role in the protective effect than vitamin A itself. The anticarcinogenic properties of -carotene have so far been attributed to its scavenger properties in deactivating or trapping reactive chemical species such as singlet oxygen and certain organic free radicals. Smoking results in increased excretion of detoxification products of electrophilic agents (mercapturic acids) in urine. Since reactive electrophilic intermediates are involved in carcinogenesis, we performed a double-blind, placebo-controlled intervention trial to investigate whether the intake of -carotene by smokers would affect urinary thioether excretion. Before the intervention the -carotene group (n = 62) and the placebo group (n = 61) had similar thioether excretion levels in urine (4.2 vs 4.3mmolSH/molcreatinine). During the intervention (20 mg -carotene daily for 14 weeks) the placebo group showed a 12% increase, whereas the -carotene group showed a 5% decrease (P=0.004). After the intervention the -carotene group had a 15% lower thioether excretion level than the placebo group (4.1 vs 4.7 mmol SH/mol creatinine; P=0.0017). Our study shows that urinary thioether excretion varies considerably over time, and that smokers have a decreased excretion of thioethers in urine after the use of -carotene. This latter observation suggests a role of -carotene in the detoxification of tobacco smoke constituents. Our observations warrant further studies on the involvement of -carotene in the generation and detoxification of electrophilic intermediates.     

Predicting urinary creatinine excretion and its usefulness to identify incomplete 24 h urine collections

Studies using 24?h urine collections need to incorporate ways to validate the completeness of the urine samples. Models to predict urinary creatinine excretion (UCE) have been developed for this purpose; however, information on their usefulness to identify incomplete urine collections is limited. We aimed to develop a model for predicting UCE and to assess the performance of a creatinine index using para-aminobenzoic acid (PABA) as a reference. Data were taken from the European Food Consumption Validation study comprising two non-consecutive 24?h urine collections from 600 subjects in five European countries. Data from one collection were used to build a multiple linear regression model to predict UCE, and data from the other collection were used for performance testing of a creatinine index-based strategy to identify incomplete collections. Multiple linear regression (n 458) of UCE showed a significant positive association for body weight (β?=?0·07), the interaction term sex?×?weight (β?=?0·09, reference women) and protein intake (β?=?0·02). A significant negative association was found for age (β?=?-?0·09) and sex (β?=?-?3·14, reference women). An index of observed-to-predicted creatinine resulted in a sensitivity to identify incomplete collections of 0·06 (95?% CI 0·01, 0·20) and 0·11 (95?% CI 0·03, 0·22) in men and women, respectively. Specificity was 0·97 (95?% CI 0·97, 0·98) in men and 0·98 (95?% CI 0·98, 0·99) in women. The present study shows that UCE can be predicted from weight, age and sex. However, the results revealed that a creatinine index based on these predictions is not sufficiently sensitive to exclude incomplete 24?h urine collections.     

Effects of a soluble dietary fibre NUTRIOSE? on colonic fermentation and excretion rates in rats

The resistant dextrin NUTRIOSE®, developed from starch, is expected to act as a prebiotic. The aim of this study was to determine the effects of NUTRIOSE® on cecal parameters, short-chain fatty acid (SCFA) concentrations, and fecal excretion in rats. In an initial experiment, twenty-four male Fischer F344 rats were randomly assigned to one of the following four treatments for 14 days: G0 (control diet), G2.5 (control diet + 2.5% of dextrin), G5 (control diet + 5% of dextrin), and G10 (control diet + 10% of dextrin). After 14 days, total cecal weight, cecal content, and cecal wall weight were significantly increased in G5 and G10 compared to G0. At the same time, cecal pH was significantly lower in G10 compared to G0. Total SCFA concentration was significantly higher in G10 than in G5, G2.5, and G0, and significantly higher in G5 than in G0. Acetate, butyrate, and propionate concentrations were significantly increased in G5 and G10 compared to the controls. In a second trial based on a similar design, eighteen male Fischer F344 rats were treated with a control diet supplemented with 5% of dextrin or 5% of fructo-oligosaccharide. The results obtained with NUTRIOSE® were similar to those obtained with the fructo-oligosaccharide. In a third experiment, two groups of 5 Fischer F344 rats were orally treated with 100 and 1,000 mg/kg NUTRIOSE®, respectively, and from 18% to 25% of the dextrin was excreted in the feces. The results of these three studies show that the consumption of NUTRIOSE®, by its effects on total cecal weight, cecal content, cecal wall weight, pH, and SCFA production, could induce healthy benefits since these effects are reported to be prebiotic effects.     

CpG 1018® adjuvant enhances Tdap immune responses against Bordetella pertussis in mice

Bordetella pertussis is the causative agent of whooping cough (pertussis), a severe respiratory disease that can be fatal, particularly in infants. Despite high vaccine coverage, pertussis remains a problem because the currently used DTaP and Tdap vaccines do not completely prevent infection or transmission. It is well established that the alum adjuvant is a potential weakness of the acellular vaccines because the immunity provided by it is short-term. We aimed to evaluate the potential of CpG 1018® adjuvant to improve antibody responses and enhance protection against B. pertussis challenge in a murine model. A titrated range of Tdap vaccine doses were evaluated in order to best identify the adjuvant capability of CpG 1018. Antibody responses to pertussis toxin (PT), filamentous hemagglutinin (FHA), or the whole bacterium were increased due to the inclusion of CpG 1018. In B. pertussis intranasal challenge studies, we observed improved protection and bacterial clearance from the lower respiratory tract due to adding CpG 1018 to 1/20th the human dose of Tdap. Further, we determined that Tdap and Tdap + CpG 1018 were both capable of facilitating clearance of strains that do not express pertactin (PRN^-), which are rising in prevalence. Functional phenotyping of antibodies revealed that the inclusion of CpG 1018 induced more bacterial opsonization and antibodies of the Th1 phenotype (IgG2a and IgG2b). This study demonstrates the potential of adding CpG 1018 to Tdap to improve immunogenicity and protection against B. pertussis compared to the conventional, alum-only adjuvanted Tdap vaccine.     

Unprecedented synthesis, in vitro and in vivo anti-cancer evaluation of novel triazolonaphthalimide derivatives

An efficient synthesis method for fusing triazole ring onto the naphthalimide core was described. The anti-cancer activities of the generated triazolonaphthalimide derivatives were evaluated with five cancer cell lines. The compounds generally displayed higher potency than amonafide. 4d,4e carrying two amino side chains showed the strongest cytotoxicities. N-oxide 5, a prodrug of 4a, was designed and synthesized. The agent was expected to be activated under the hypoxic condition in tumor tissue. Compared with 4a, 5 manifested much lower cytotoxicity both in cancer cell lines and human normal cells in the in?vitro assays. However, N-oxide 5 performed potent anti-cancer activity in?vivo using S-180 sarcoma bearing mice. All the results suggested that 5 was a promising anti-cancer agent.     

Energy value of a low-digestible carbohydrate, NUTRIOSE® FB, and its impact on magnesium, calcium and zinc apparent absorption and retention in healthy young men

Summary Background Long-term consumption of imbalanced diets, poor in dietary fibres, resulted in the prevalence of several nutritional pathologies. However, low digestible carbohydrates (LDC) have many beneficial effects, especially on energy intake, digestive physiology, and mineral absorption. Aim of the study To determine the digestive effects of a LDC, called NUTRIOSE^® FB, its metabolisable energy (ME) value, and its effects on mineral absorption in humans. Methods Ten healthy young men were fed for 31 d periods a maintenance diet supplemented with either dextrose or the LDC at a level of 100 g DM/d, in six equal doses per d according to a cross-over design. After a 20 d adaptation period, food intake was determined for 11 days using the duplicate meal method, and faeces and urine were collected for 10 d for further analyses. Results Ingestion of the LDC did not cause severe digestive disorders, except excessive gas emission, and flatulence and slight abdominal pain in some subjects for intakes above 50 g DM/d. Wet and dry stool outputs increased by 45 and 70%, respectively (P<0.02). In vitro enzymatic digestibility of the LDC was 15 (SD 1.5) %, and 9.2 (SD 8.3) % of the LDC was excreted in faeces (P<0.001). The ME value of the LDC was 14.1 (SD 2.3) kJ/g DM, that is 14 % less than the tabulated values of sucrose and starch. Its net energy value (NEV), estimated using three prediction equations, was 8.7, 8.9, and 11.4 kJ/g DM. Ingestion of the LDC significantly increased the relative apparent absorption of Mg, and Mg retention by 67% and 31 mg/d, respectively, tended to increase Ca apparent absorption (P=0.110) and Ca retention (P=0.059), but did not significantly alter Zn parameters. Conclusion NUTRIOSE^® FB can be used as a bulking agent, and substituted up to 50 g/d for usual maltodextrins without causing digestive disorders in healthy subjects. It would reduce intestinal transit disorders and energy intake, and improve magnesium and calcium absorption and retention. Funding The study was funded by the Roquette Frères company, which also supplied the experimental products.     

Updated bioavailability and 48 h excretion profile of flavan-3-ols from green tea in humans

Green tea is a popular beverage, prepared with infusion of unfermented dried leaves of Camellia sinensis, and is one of the most relevant sources of polyphenolic compounds in the human diet. This study reports green tea flavan-3-ol absorption, metabolism and complete urinary excretion up to 48?h in 20 healthy volunteers. Urinary and tea samples were analysed by high-performance liquid chromatography coupled with tandem mass spectrometry. Green tea contained monomeric flavan-3-ols and proanthocyanidins with a total polyphenol content of 728?μmol. A total of 41 metabolites were identified in urines, all present in conjugated forms. Among these, six colonic metabolites of green tea flavan-3-ols were identified for the first time after green tea consumption in humans. The average 48?h bioavailability was close to 62%, major contributors being microbial metabolites. Some volunteer showed a 100% absorption/excretion, whereas some others were unable to efficiently absorb/excrete this class of flavonoids. This suggests that colonic ring fission metabolism could be relevant in the putative bioactivity of green tea polyphenols.