Instruct: Given a question, retrieve relevant passages that answer the question.
Query: amylase
AIMS/HYPOTHESIS: Dietary non-oil-seed pulses (chickpeas, beans, peas, lentils, etc.) are a good source of slowly digestible carbohydrate, fibre and vegetable protein and a valuable means of lowering the glycaemic-index (GI) of the diet. To assess the evidence that dietary pulses may benefit glycaemic control, we conducted a systematic review and meta-analysis of randomised controlled experimental trials investigating the effect of pulses, alone or as part of low-GI or high-fibre diets, on markers of glycaemic control in people with and without diabetes. METHODS: We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Library for relevant controlled trials of >or=7 days. Two independent reviewers (A. Esfahani and J. M. W. Wong) extracted information on study design, participants, treatments and outcomes. Data were pooled using the generic inverse variance method and expressed as standardised mean differences (SMD) with 95% CIs. Heterogeneity was assessed by chi (2) and quantified by I (2). Meta-regression models identified independent predictors of effects. RESULTS: A total of 41 trials (39 reports) were included. Pulses alone (11 trials) lowered fasting blood glucose (FBG) (-0.82, 95% CI -1.36 to -0.27) and insulin (-0.49, 95% CI -0.93 to -0.04). Pulses in low-GI diets (19 trials) lowered glycosylated blood proteins (GP), measured as HbA(1c) or fructosamine (-0.28, 95% CI -0.42 to -0.14). Finally, pulses in high-fibre diets (11 trials) lowered FBG (-0.32, 95% CI -0.49 to -0.15) and GP (-0.27, 95% CI -0.45 to -0.09). Inter-study heterogeneity was high and unexplained for most outcomes, with benefits modified or predicted by diabetes status, pulse type, dose, physical form, duration of follow-up, study quality, macronutrient profile of background diets, feeding control and design. CONCLUSIONS/INTERPRETATION: Pooled analyses demonstrated that pulses, alone or in low-GI or high-fibre diets, improve markers of longer term glycaemic control in humans, with the extent of the improvements subject to significant inter-study heterogeneity. There is a need for further large, well-designed trials.
Eisenberg's helical hydrophobic moment (less than mu H greater than) algorithm was applied to the analysis of the primary structure of amphipathic alpha-helical peptide hormones and an optimal method for identifying other peptides of this class determined. We quantitate and compare known amphipathic helical peptide hormones with a second group of peptides with proven nonamphipathic properties and determine the best method of distinguishing between them. The respective means of the maximum 11 residue less than mu H greater than for the amphipathic helical and control peptides were 0.46 (+/-/-0.07) and 0.33 (0.07) (P + 0.004). To better reflect the amphipathic potential of the entire peptide, the percent of 11 residue segments in each peptide above a particular less than mu H greater than was plotted vs less than mu H greater than. The resulting curves are referred to as HM-C. The mean HM-C (of the two groups) was highly significantly different such that the HM-C method was superior to others in its ability to distinguish amphipathic from nonamphipathic peptides. Several potential new members of this structural class were identified using this approach. Molecular modeling of a portion of one of these, prolactin inhibitory factor, reveals a strongly amphipathic alpha helix at residues 4-21. This computer-based method may enable rapid identification of peptides of the amphipathic alpha-helix class.
OBJECTIVE: Secretory immunoglobulin A (SIgA) acts as the first line of adaptive humoral immune defense at mucosal surfaces. A lack of SIgA or the inability to produce antigen-specific SIgA can lead to an increased risk of infections. Dietary intake may improve mucosal immunity by accelerating SIgA secretion. This study investigated the effect of dietary intake of Agaricus bisporus white button mushroom (WBM) on salivary IgA (sIgA) secretion in healthy subjects. METHODS: Twenty-four healthy volunteers were randomly assigned to a normal daily diet (control group) or a normal diet with WBM. The subjects in the active group (n = 12, 41.4 ± 11.3 y old) consumed 100 g of blanched WBM daily with their normal diet for 1 wk, whereas those in the control group consumed their normal diet (n = 12, 43.5 ± 12.5 y old) without WBM. Saliva was collected before and after commencement of the study and every week thereafter for 3 wk. Saliva flow rate, sIgA concentration, and osmolality were determined and the sIgA:osmolality ratio and the sIgA secretion rate were calculated. RESULTS: There was no significant difference between pre- and postdietary mushroom intakes for all indices in the control group (P > 0.05). In contrast, the mean sIgA secretion rate increased significantly at weeks 1 and 2 by 53% and 56%, respectively, compared with that at week 0 (P < 0.0005) in the WBM intake group and then returned to a baseline level at week 3. Changes in sIgA secretion rate over the intervention period were greater in the WBM group than in the control group without WBM. In both groups, no significant changes in osmolality and saliva IgG were noted. There was, however, a significant increase in the sIgA:osmolality ratio (P < 0.0012), confirming the postdietary WBM-induced sIgA increase. CONCLUSION: The dietary intake of A. bisporus WBM significantly accelerates sIgA secretion, thereby indicating its potential health benefits for improving mucosal immunity. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.
We investigated the effect of resistant starch (RS) on markers of colonic protein metabolism. Eleven subjects participated in a randomized crossover study in which they consumed either high-RS (39 +/- 3 g/d, -chi +/- SEM) or low-RS (5 +/- 0.4 g/d) diets for 3 wk. All other macronutrients were kept constant. During the high-RS diet daily excretion of fecal nitrogen increased from 1.84 +/- 0.15 to 2.86 +/- 0.42 g/d (P < 0.01) and excretion of fecal phenols fell from 9.2 +/- 1.4 to 5.3 +/- 0.8 mg/d (P < 0.01). Fecal concentrations of ammonia decreased from 397 +/- 33 to 278 +/- 49 microgram/g (P < 0.01) and phenols decreased from 69 +/- 8 to 39 +/- 10 microgram/g (P < 0.001). Daily output of urinary ammonia, urea, phenols, and total nitrogen did not change significantly, but pH decreased from 6.4 +/- 0.1 to 6.2 +/- 0.1 (P < 0.05) during the high-RS period. These results suggest that RS significantly attenuates the accumulation of potentially harmful byproducts of protein fermentation in the human colon.
OBJECTIVE: Update of the Hohenheim consensus on monosodium glutamate from 1997: Summary and evaluation of recent knowledge with respect to physiology and safety of monosodium glutamate. DESIGN: Experts from a range of relevant disciplines received and considered a series of questions related to aspects of the topic. SETTING: University of Hohenheim, Stuttgart, Germany. METHOD: The experts met and discussed the questions and arrived at a consensus. CONCLUSION: Total intake of glutamate from food in European countries is generally stable and ranged from 5 to 12 g/day (free: ca. 1 g, protein-bound: ca. 10 g, added as flavor: ca. 0.4 g). L-Glutamate (GLU) from all sources is mainly used as energy fuel in enterocytes. A maximum intake of 6.000 [corrected] mg/kg body weight is regarded as safe. The general use of glutamate salts (monosodium-L-glutamate and others) as food additive can, thus, be regarded as harmless for the whole population. Even in unphysiologically high doses GLU will not trespass into fetal circulation. Further research work should, however, be done concerning the effects of high doses of a bolus supply at presence of an impaired blood brain barrier function. In situations with decreased appetite (e.g., elderly persons) palatability can be improved by low dose use of monosodium-L-glutamate.
In this study, solid fermentation of steamed black soybean with various GRAS (Generally recognized as safe) filamentious-fungi including Aspergillus awamori, Aspergillus oryzae BCRC 30222, Aspergillus sojae BCRC 30103, Rhizopus azygosporus BCRC 31158 and Rhizopus sp. No. 2 was performed. Mutagenicity and antimutagenicity of the methanol extracts of unfermented and fermented steamed black soybeans against 4-nitroquinoline-N-oxide (4-NQO), a direct mutagen and Benzo[a]pyrene (B[a]P), an indirect mutagen, on Salmonella Typhimurium TA100 and TA 98, were examined. The methanol extracts of unfermented and fermented steamed black soybeans show no mutagenic activity for either test strains at the doses tested. The extracts inhibited mutagenesis by either 4-NQO or B[a]P in S. Typhimurium TA100 and TA98. Fermentation with fungi also enhanced the antimutagenic effect of black soybean while the antimutagenic effect of the fermented black soybeans extract varied with the starter organism, mutagen, and test strain of S. Typhimurium examined. Generally, the extracts of A. awamori-fermented black soybean exhibited the highest antimutagenic effect. With strain TA100, the inhibitory effects of 5.0 mg of A. awamori-fermented black soybean extract per plate on the mutagenic effects of 4-NQO and B[a]P were 92% and 89%, respectively, while the corresponding rates for extract of unfermented were 41% and 63%, respectively. With strain 98, the inhibition rates were 94 and 81% for the fermented bean extract and 58% and 44% for the unfermented bean extracts. Testing of extracts prepared from black soybean by A. awamori at temperatures 25, 30 and 35 degrees C and for times of 1-5 days revealed that, generally, the extract prepared from beans fermented at 30 degrees C for 3 days exhibited the greatest inhibition against the mutagenic effects of 4-NQO and B[a]P.
Advanced glycation end products (AGEs) are a heterogeneous, complex group of compounds that are formed when reducing sugar reacts in a non-enzymatic way with amino acids in proteins and other macromolecules. This occurs both exogenously (in food) and endogenously (in humans) with greater concentrations found in older adults. While higher AGEs occur in both healthy older adults and those with chronic diseases, research is progressing to both quantify AGEs in food and in people, and to identify mechanisms that would explain why some human tissues are damaged, and others are not. In the last twenty years, there has been increased evidence that AGEs could be implicated in the development of chronic degenerative diseases of aging, such as cardiovascular disease, Alzheimer’s disease and with complications of diabetes mellitus. Results of several studies in animal models and humans show that the restriction of dietary AGEs has positive effects on wound healing, insulin resistance and cardiovascular diseases. Recently, the effect of restriction in AGEs intake has been reported to increase the lifespan in animal models. This paper will summarize the work that has been published for both food AGEs and in vivo AGEs and their relation with aging, as well as provide suggestions for future research.
Fenugreek, maple syrup and the urine of maple syrup urine disease (MSUD) patients all share a characteristic odour originating from a common component, sotolone. Ingestion of fenugreek by mothers during labour resulted in a maple syrup-like odour in their newborn infants, leading to a false suspicion of MSUD.
Background Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine with keto-enol tautomerase activity, rises rapidly in response to inflammation, and is elevated in many chronic diseases. Isothiocyanates, such as sulforaphane from broccoli, are very potent inactivators of MIF tautomerase activity. A simple rapid method for determining this activity in tissues and body fluids may therefore be valuable for assessing severity of inflammation and efficacy of intervention. Methods Existing spectrophotometric assays of MIF, based on conversion of methyl L-dopachrome to methyl 5,6-dihydroxyindole-2-carboxylate and associated loss of absorption at 475 nm, lack sensitivity. Assay sensitivity and efficiency were markedly improved by reducing the nonenzymatic rate, by lowering pH to 6.2, replacing phosphate (which catalyzes the reaction) with Bis-Tris buffer, and converting to a microtiter plate format. Results A structure-potency study of MIF tautomerase inactivation by isothiocyanates showed that sulforaphane, benzyl, n-hexyl, and phenethyl isothiocyanates were especially potent. MIF tautomerase could be readily quantified in human urine concentrated by ultrafiltration. This activity comprised: (i) a heat-labile, sulforaphane-inactivated macromolecular fraction (presumably MIF) that was concentrated during ultrafiltration; (ii) a flow-through fraction, with constant activity during filtration, that was heat-stable, and insensitive to sulforaphane. Administration of the sulforaphane precursor glucoraphanin to human volunteers almost completely abolished urinary tautomerase activity, which was recovered over many hours. Conclusions A simple, rapid, quantitative MIF tautomerase assay has been developed as a potential biomarker for assessing inflammatory severity and effectiveness of intervention. Impact An improved assay for measuring MIF tautomerase activity and its applications are described.
Background Dietary exposure to the cyanotoxin BMAA is suspected to be the cause of amyotrophic lateral sclerosis in the Western Pacific Islands. In Europe and North America, this toxin has been identified in the marine environment of amyotrophic lateral sclerosis clusters but, to date, only few dietary exposures have been described. Objectives We aimed at identifying cluster(s) of amyotrophic lateral sclerosis in the Hérault district, a coastal district from Southern France, and to search, in the identified area(s), for the existence of a potential dietary source of BMAA. Methods A spatio-temporal cluster analysis was performed in the district, considering all incident amyotrophic lateral sclerosis cases identified from 1994 to 2009 by our expert center. We investigated the cluster area with serial collections of oysters and mussels that were subsequently analyzed blind for BMAA concentrations. Results We found one significant amyotrophic lateral sclerosis cluster (p = 0.0024), surrounding the Thau lagoon, the most important area of shellfish production and consumption along the French Mediterranean coast. BMAA was identified in mussels (1.8 µg/g to 6.0 µg/g) and oysters (0.6 µg/g to 1.6 µg/g). The highest concentrations of BMAA were measured during summer when the highest picocyanobacteria abundances were recorded. Conclusions While it is not possible to ascertain a direct link between shellfish consumption and the existence of this ALS cluster, these results add new data to the potential association of BMAA with sporadic amyotrophic lateral sclerosis, one of the most severe neurodegenerative disorder.
Previous studies on healthy subjects have shown that the intake of 6 g Cinnamomum cassia reduces postprandial glucose and that the intake of 3 g C. cassia reduces insulin response, without affecting postprandial glucose concentrations. Coumarin, which may damage the liver, is present in C. cassia, but not in Cinnamomum zeylanicum. The aim of the present study was to study the effect of C. zeylanicum on postprandial concentrations of plasma glucose, insulin, glycaemic index (GI) and insulinaemic index (GII) in subjects with impaired glucose tolerance (IGT). A total of ten subjects with IGT were assessed in a crossover trial. A standard 75 g oral glucose tolerance test (OGTT) was administered together with placebo or C. zeylanicum capsules. Finger-prick capillary blood samples were taken for glucose measurements and venous blood for insulin measurements, before and at 15, 30, 45, 60, 90, 120, 150 and 180 min after the start of the OGTT. The ingestion of 6 g C. zeylanicum had no significant effect on glucose level, insulin response, GI or GII. Ingestion of C. zeylanicum does not affect postprandial plasma glucose or insulin levels in human subjects. The Federal Institute for Risk Assessment in Europe has suggested the replacement of C. cassia by C. zeylanicum or the use of aqueous extracts of C. cassia to lower coumarin exposure. However, the positive effects seen with C. cassia in subjects with poor glycaemic control would then be lost.
The effectiveness of high-temperature, short holding time (HTST) pasteurization and homogenization with respect to inactivation of Mycobacterium avium subsp. paratuberculosis was evaluated quantitatively. This allowed a detailed determination of inactivation kinetics. High concentrations of feces from cows with clinical symptoms of Johne's disease were used to contaminate raw milk in order to realistically mimic possible incidents most closely. Final M. avium subsp. paratuberculosis concentrations varying from 102 to 3.5 × 105 cells per ml raw milk were used. Heat treatments including industrial HTST were simulated on a pilot scale with 22 different time-temperature combinations, including 60 to 90°C at holding (mean residence) times of 6 to 15 s. Following 72°C and a holding time of 6 s, 70°C for 10 and 15 s, or under more stringent conditions, no viable M. avium subsp. paratuberculosis cells were recovered, resulting in >4.2- to >7.1-fold reductions, depending on the original inoculum concentrations. Inactivation kinetic modeling of 69 quantitative data points yielded an Ea of 305,635 J/mol and an lnk0 of 107.2, corresponding to a D value of 1.2 s at 72°C and a Z value of 7.7°C. Homogenization did not significantly affect the inactivation. The conclusion can be drawn that HTST pasteurization conditions equal to 15 s at ≥72°C result in a more-than-sevenfold reduction of M. avium subsp. paratuberculosis.
Background: Rice can be a major source of inorganic arsenic (Asi) for many sub-populations. Rice products are also used as ingredients in prepared foods, some of which may not be obviously rice based. Organic brown rice syrup (OBRS) is used as a sweetener in organic food products as an alternative to high-fructose corn syrup. We hypothesized that OBRS introduces As into these products. Objective: We determined the concentration and speciation of As in commercially available brown rice syrups and in products containing OBRS, including toddler formula, cereal/energy bars, and high-energy foods used by endurance athletes. Methods: We used inductively coupled plasma mass spectrometry (ICP-MS) and ion chromatography coupled to ICP-MS to determine total As (Astotal) concentrations and As speciation in products purchased via the Internet or in stores in the Hanover, New Hampshire, area. Discussion: We found that OBRS can contain high concentrations of Asi and dimethyl-arsenate (DMA). An “organic” toddler milk formula containing OBRS as the primary ingredient had Astotal concentrations up to six times the U.S. Environmental Protection Agency safe drinking water limit. Cereal bars and high-energy foods containing OBRS also had higher As concentrations than equivalent products that did not contain OBRS. Asi was the main As species in most food products tested in this study. Conclusions: There are currently no U.S. regulations applicable to As in food, but our findings suggest that the OBRS products we evaluated may introduce significant concentrations of Asi into an individual’s diet. Thus, we conclude that there is an urgent need for regulatory limits on As in food.
Beta-glucans are a heterogeneous group of natural polysaccharides mostly investigated for their immunological effects. Due to the low systemic availability of oral preparations, it has been thought that only parenterally applied beta-glucans can modulate the immune system. However, several in vivo and in vitro investigations have revealed that orally applied beta-glucans also exert such effects. Various receptor interactions, explaining possible mode of actions, have been detected. The effects mainly depend on the source and structure of the beta-glucans. In the meantime, several human clinical trials with dietary insoluble yeast beta-glucans have been performed. The results confirm the previous findings of in vivo studies. The results of all studies taken together clearly indicate that oral intake of insoluble yeast beta-glucans is safe and has an immune strengthening effect.
BACKGROUND: Low postprandial blood glucose is associated with low risk of metabolic diseases. A meal's ability to diminish the glucose response to carbohydrates eaten during the following meal is known as the "second-meal effect" (SME). The reduced glycemia elicited by low-glycemic-index (LGI) foods consumed during the first meal has been suggested as the main mechanism for SME. However, LGI foods often increase colonic fermentation because of the presence of fiber and resistant starch. OBJECTIVE: The objective was to study the SME of greater fermentation of high-glycemic-index (HGI) and LGI carbohydrates eaten during a previous meal. DESIGN: Ten healthy volunteers ate 3 breakfast test meals consisting of sponge cakes made with rapidly digestible, nonfermentable amylopectin starch plus cellulose (HGI meal), amylopectin starch plus the fermentable disaccharide lactulose (HGI-Lac meal), or slowly digestible, partly fermentable amylose starch plus cellulose (LGI meal). Five hours later, subjects were fed the same standard lunch containing 93 g available carbohydrates. Blood was collected for measurement of glucose, insulin, and nonesterified fatty acids (NEFAs). Breath hydrogen was measured as a marker of colonic fermentation. Postlunch gastric emptying was measured by using ultrasonography. RESULTS: Both the HGI-Lac and LGI meals improved glucose tolerance at lunch. In the case of the HGI-Lac meal, this effect was concomitant with low NEFA concentrations and delayed gastric emptying. CONCLUSION: Fermentable carbohydrates, independent of their effect on a food's glycemic index, have the potential to regulate postprandial responses to a second meal by reducing NEFA competition for glucose disposal and, to a minor extent, by affecting intestinal motility.
Celiac disease (CD) is a gluten-dependent immune-mediated disease with a prevalence in the general population estimated between 0.3% and 1.2%. Large-scale epidemiological studies have shown that only 10-20% of cases of CD are identified on the basis of clinical findings and that laboratory tests are crucial to identify subjects with subtle or atypical symptoms. The correct choice and clinical use of these diagnostic tools may enable accurate diagnosis and early recognition of silent CD cases. In this review, we have considered some relevant aspects related to the laboratory diagnosis of CD and, more extensively, of gluten intolerance, such as the best combination of tests for early and accurate diagnosis, the diagnostic role of new tests for detecting antibodies against neoepitopes produced by the transglutaminase-gliadin complex, the forms of non-celiac gluten intolerance (gluten sensitivity), and the use and significance of measuring cytokines in CD.
BACKGROUND: Vinegar reduces postprandial glycemia (PPG) in healthy adults. This study investigated the vinegar dosage (10 vs. 20 g), timing (during mealtime vs. 5 h before meal) and application (acetic acid as vinegar vs. neutralized salt) for reducing PPG. METHODS: Four randomized crossover trials were conducted in adults (n = 9-10/trial) with type 2 diabetes (1 trial) or without diabetes (3 trials). All trials followed the same protocol: a standardized meal the evening prior to testing, an overnight fast ( 1 10 h) and 2-hour glucose testing following consumption of a bagel and juice test meal (3 trials) or dextrose solution (1 trial). For each trial, PPG was compared between treatments using area-under-the-curve calculations 120 min after the meal. RESULTS: Two teaspoons of vinegar ( 10 g) effectively reduced PPG, and this effect was most pronounced when vinegar was ingested during mealtime as compared to 5 h before the meal. Vinegar did not alter PPG when ingested with monosaccharides, suggesting that the antiglycemic action of vinegar is related to the digestion of carbohydrates. Finally, sodium acetate did not alter PPG, indicating that acetate salts lack antiglycemic properties. CONCLUSIONS: The antiglycemic properties of vinegar are evident when small amounts of vinegar are ingested with meals composed of complex carbohydrates. In these situations, vinegar attenuated PPG by 20% compared to placebo. 2009 S. Karger AG, Basel.
Almond (Prunus dulcis[Mill.] D.A. Webb) skins have been proposed as a source of bioactive polyphenols. In this article, the phenolic composition and antioxidant activity of almond skins obtained from different processes (blanching [freeze-drying], blanching + drying, and roasting) were studied. A total of 31 phenolic compounds corresponding to flavan-3-ols (33% to 56% of the total of phenolic compounds identified), flavonol glycosides (9% to 36%), hydroxybenzoic acids and aldehydes (6% to 26%), flavonol aglycones (1.7% to 18%), flavanone glycosides (3% to 7.7%), flavanone aglycones (0.69% to 5.4%), hydroxycinnamic acids (0.65% to 2.6%), and dihydroflavonol aglycones (0% to 2.8%) were determined in the skins from 3 different varieties of almonds. The total contents of phenolic compounds identified were significantly (P < 0.05) higher (around 2-fold) in the roasted samples than in the blanched almonds (freeze-dried). Industrial drying (oven drying) of the blanched almond skins produced an increase (< 2-fold) in the contents of phenolic compounds, although the results were only statistically significant (P < 0.05) for some samples. The antioxidant activity (ORAC values) was higher for the roasted samples (0.803 to 1.08 mmol Trolox/g), followed by the samples subjected to blanching + drying (0.398 to 0.575 mmol Trolox/g) and then the blanched (freeze-dried) samples (0.331 to 0.451 mmol Trolox/g). Roasting is the most suitable type of industrial processing of almonds to obtain almond skin extracts with the greatest antioxidant capacity.
Prunes are used by folks as a remedy of various diseases including hepatitis. A clinical trial was designed to see the effects of prunes (Prunus domestica) on liver function. 166 healthy volunteers were divided into three groups randomly. Either three (about 11.43g) or six (23g approx.) prunes were soaked in a glass of water (250ml) overnight. Each subject from two test groups was asked to drink prune juice & eat whole fruit(single or double dose of prunes) as well, early in the morning, daily for 8 weeks; whereas each subject from control group was given a glass of water to drink. Blood samples were taken at week 0 and week 8 for chemical analysis. There was significant reduction of serum alanine transaminase (p 0.048) and serum alkaline phosphatase (p 0.017) by the lower dose of prunes. There was no change in serum aspartate transaminase and bilirubin. Alteration in liver function by use of prunes may have clinical relevance in appropriate cases and prunes might prove beneficial in hepatic disease.
An increased risk of breast cancer has been observed in women who consume "very well-done" meats. Heterocyclic amines are mutagenic and carcinogenic pyrolysis products formed during high temperature cooking of meats. In the present study, human milk samples were analyzed for PhIP, one of the most abundant dietary heterocyclic amine. A protocol was developed with a mixed-mode cation exchange sorbent for the extraction of heterocyclic amines from milk. Milk samples were acquired from healthy Canadian women. With LC/MS analysis and the method of isotope dilution for quantification, levels of PhIP were determined in human milk samples. PhIP was detected in 9 of the 11 milk samples, at levels as high as 59 pg/mL (ppt). No PhIP was detected in the milk of the vegetarian donor. Detection of PhIP in milk indicates that ductal mammary epithelial cells are directly exposed to this carcinogen, suggesting that heterocyclic amines are possible human mammary carcinogens.
AIMS: Various spices display insulin-potentiating activity in vitro, and in particular, cinnamon spice and its phenolic extracts have been shown to exhibit these capabilities. In vivo study shows that cinnamon may have beneficial effects on glucose homeostasis; therefore the aim of this study was to further investigate this phenomenon in humans. METHODS: Seven lean healthy male volunteers, aged 26 +/- 1 years, body mass index 24.5 +/- 0.3 kg/m(2) (mean +/- s.e.m.), underwent three oral glucose tolerance tests (OGTT) supplemented with either a 5 g placebo (OGTT(control)), 5 g of cinnamon (OGTT(cin)), or 5 g of cinnamon taken 12 h before (OGTT(cin12hpre)) in a randomized-crossover design. RESULTS: Cinnamon ingestion reduced total plasma glucose responses (AUC) to oral glucose ingestion [-13% and -10% for OGTT(cin) (p < 0.05) and OGTT(cin12hpre) (p < 0.05), respectively], as well as improving insulin sensitivity as assessed by insulin sensitivity index measures based on Matsuda's model in both OGTT(cin) (p < 0.05) and OGTT(cin12hpre) (p < 0.05) trials compared with OGTT(control). CONCLUSIONS: These data illustrate that cinnamon spice supplementation may be important to in vivo glycaemic control and insulin sensitivity in humans, and not only are its effects immediate, they also appear to be sustained for 12 h.
There is growing interest in the potential health benefits of tea, including the antimutagenic properties. Four varieties of white tea, which represent the least processed form of tea, were shown to have marked antimutagenic activity in the Salmonella assay, particularly in the presence of S9. The most active of these teas, Exotica China white tea, was significantly more effective than Premium green tea (Dragonwell special grade) against 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and four other heterocyclic amine mutagens, namely 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline (4,8-DiMeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). Mechanism studies were performed using rat liver S9 in assays for methoxyresorufin O-demethylase (MROD), a marker for the enzyme cytochrome P4501A2 that activates heterocyclic amines, as well as Salmonella assays with the direct-acting mutagen 2-hydroxyamino-3-methylimidazo[4,5-f]quinoline (N-hydroxy-IQ). White tea at low concentrations in the assay inhibited MROD activity, and attenuated the mutagenic activity of N-hydroxy-IQ in the absence of S9. Nine of the major constituents found in green tea also were detected in white tea, including high levels of epigallocatechin-3-gallate (EGCG) and several other polyphenols. When these major constituents were mixed to produce "artificial" teas, according to their relative levels in white and green teas, the complete tea exhibited higher antimutagenic potency compared with the corresponding artificial tea. The results suggest that the greater inhibitory potency of white versus green tea in the Salmonella assay might be related to the relative levels of the nine major constituents, perhaps acting synergistically with other (minor) constituents, to inhibit mutagen activation as well as "scavenging" the reactive intermediate(s).
Salmonella enterica is one of the most common causes of foodborne illness in the United States. Although salmonellosis is usually self-limiting, severe infections typically require antimicrobial treatment, and ceftriaxone, an extended-spectrum cephalosporin (ESC), is commonly used in both adults and children. Surveillance conducted by the National Antimicrobial Resistance Monitoring System (NARMS) has shown a recent increase in ESC resistance among Salmonella Heidelberg isolated from food animals at slaughter, retail meat, and humans. ESC resistance among Salmonella in the United States is usually mediated by a plasmid-encoded bla(CMY) β-lactamase. In 2009, we identified 47 ESC-resistant bla(CMY)-positive Heidelberg isolates from humans (n=18), food animals at slaughter (n=16), and retail meats (n=13) associated with a spike in the prevalence of this serovar. Almost 90% (26/29) of the animal and meat isolates were isolated from chicken carcasses or retail chicken meat. We screened NARMS isolates for the presence of bla(CMY), determined whether the gene was plasmid-encoded, examined pulsed-field gel electrophoresis patterns to assess the genetic diversities of the isolates, and categorized the bla(CMY) plasmids by plasmid incompatibility groups and plasmid multi-locus sequence typing (pMLST). All 47 bla(CMY) genes were found to be plasmid encoded. Incompatibility/replicon typing demonstrated that 41 were IncI1 plasmids, 40 of which only conferred bla(CMY)-associated resistance. Six were IncA/C plasmids that carried additional resistance genes. pMLST of the IncI1-bla(CMY) plasmids showed that 27 (65.8%) were sequence type (ST) 12, the most common ST among bla(CMY)-IncI1 plasmids from Heidelberg isolated from humans. Ten plasmids had a new ST profile, ST66, a type very similar to ST12. This work showed that the 2009 increase in ESC resistance among Salmonella Heidelberg was caused mainly by the dissemination of bla(CMY) on IncI1 and IncA/C plasmids in a variety of genetic backgrounds, and is likely not the result of clonal expansion.
We previously reported that chickens infected with the avian adenovirus SMAM-1 developed a unique syndrome characterized by excessive intra-abdominal fat deposition accompanied by paradoxically low serum cholesterol and triglyceride levels. There have been no previous reports of avian adenoviruses infecting humans. We screened the serum of 52 humans with obesity in Bombay, India, for antibodies against SMAM-1 virus using the agar gel precipitation test (AGPT) method. Bodyweights and serum cholesterol and triglyceride levels were compared in SMAM-1-positive (P-AGPT) and SMAM-1-negative (N-AGPT) groups. Ten subjects were positive for antibodies to SMAM-1, and 42 subjects did not have antibodies. The P-AGPT group had a significantly higher bodyweight (p < 0.02) and body mass index (p < 0.001) (95.1 +/- 2.1 kg and 35.3 +/- 1.5 kg/m2, respectively) compared with the N-AGPT group (80.1 +/- 0.6 kg and 30.7 +/- 0.6 kg/m2, respectively). Also, the P-AGPT group had significantly lower serum cholesterol (p < 0.02) and triglyceride (p < 0.001) values (4.65 mmol/L and 1.45 mmol/L, respectively) compared with the N-AGPT group (5.51 mmol/L and 2.44 mmol/L, respectively). Two subjects positive for SMAM-1 antibodies had antibodies against each others' serum, suggesting the presence of antigens in one or both. When these two serum samples were inoculated into chicken embryos, macroscopic lesions compatible with SMAM-1 infection developed. The inoculation of serum from N-AGPT subjects did not produce such lesions. The presence of increased obesity, antibodies to SMAM-1, reduced levels of blood lipids, and viremia that produces a typical infection in chicken embryos suggests that SMAM-1, or a serologically similar human virus, may be involved in the cause of obesity in some humans.
Aromatase cytochrome P450 is the only enzyme in vertebrates known to catalyse the biosynthesis of all oestrogens from androgens1–3. Aromatase inhibitors therefore constitute a front-line therapy for oestrogen-dependent breast cancer3,4. In a three-step process, each step requiring 1 mol of O2, 1 mol of NADPH, and coupling with its redox partner cytochrome P450 reductase, aromatase converts androstenedione, testosterone and 16α-hydroxytestosterone to oestrone, 17β-oestradiol and 17β,16α-oestriol, respectively1–3. The first two steps are C19-methyl hydroxylation steps, and the third involves the aromatization of the steroid A-ring, unique to aromatase. Whereas most P450s are not highly substrate selective, it is the hallmark androgenic specificity that sets aromatase apart. The structure of this enzyme of the endoplasmic reticulum membrane has remained unknown for decades, hindering elucidation of the biochemical mechanism. Here we present the crystal structure of human placental aromatase, the only natural mammalian, full-length P450 and P450 in hormone biosynthetic pathways to be crystallized so far. Unlike the active sites of many microsomal P450s that metabolize drugs and xenobiotics, aromatase has an androgen-specific cleft that binds the androstenedione molecule snugly. Hydrophobic and polar residues exquisitely complement the steroid backbone. The locations of catalytically important residues shed light on the reaction mechanism. The relative juxtaposition of the hydrophobic amino-terminal region and the opening to the catalytic cleft shows why membrane anchoring is necessary for the lipophilic substrates to gain access to the active site. The molecular basis for the enzyme’s androgenic specificity and unique catalytic mechanism can be used for developing next-generation aromatase inhibitors.