Showing papers by "Rowett Research Institute published in 2002"
TL;DR: A better understanding of the microbial ecology of colonic butyrate-producing bacteria will help to explain the influence of diet uponbutyrate supply, and to suggest new approaches for optimising microbial activity in the large intestine.
Abstract: Butyrate arising from microbial fermentation is important for the energy metabolism and normal development of colonic epithelial cells and has a mainly protective role in relation to colonic disease. While certain dietary substrates such as resistant starch appear to be butyrogenic in the colon, it is not known to what extent these stimulate butyrate production directly, e.g. by promoting amylolytic species, or indirectly, e.g. through cross-feeding of fermentation products. Cultural and molecular studies indicate that the most numerous butyrate-producing bacteria found in human faeces are highly oxygen-sensitive anaerobes belonging to the Clostridial clusters IV and XIVa. These include many previously undescribed species related to Eubacterium, Roseburia, Faecalibacterium and Coprococcus whose distribution and metabolic characteristics are under investigation. A better understanding of the microbial ecology of colonic butyrate-producing bacteria will help to explain the influence of diet upon butyrate supply, and to suggest new approaches for optimising microbial activity in the large intestine.
1,143 citations
TL;DR: It is demonstrated that different functionally distinct groups of butyrate-producing bacteria are present in the human large intestine.
Abstract: Seven strains of Roseburia sp., Faecalibacterium prausnitzii, and Coprococcus sp. from the human gut that produce high levels of butyric acid in vitro were studied with respect to key butyrate pathway enzymes and fermentation patterns. Strains of Roseburia sp. and F. prausnitzii possessed butyryl coenzyme A (CoA):acetate-CoA transferase and acetate kinase activities, but butyrate kinase activity was not detectable either in growing or in stationary-phase cultures. Although unable to use acetate as a sole source of energy, these strains showed net utilization of acetate during growth on glucose. In contrast, Coprococcus sp. strain L2-50 is a net producer of acetate and possessed detectable butyrate kinase, acetate kinase, and butyryl-CoA:acetate-CoA transferase activities. These results demonstrate that different functionally distinct groups of butyrate-producing bacteria are present in the human large intestine.
579 citations
TL;DR: In this paper, nine commercial varieties of tomato (Rambo, Senior, Ramillete, Liso, Pera, Canario, Durina, Daniella and Remate) were analysed for their lycopene content, content of phenolic compounds and antioxidant capacity.
Abstract: Nine commercial varieties of tomato (Rambo, Senior, Ramillete, Liso, Pera, Canario, Durina, Daniella and Remate) produced in Spain were analysed for their lycopene content, content of phenolic compounds and antioxidant capacity. The phenolic compounds were characterised as flavonoids (quercetin, kaempferol and naringenin) and hydroxycinnamic acids (caffeic, chlorogenic, ferulic and p-coumaric acids). Antioxidant activity was measured using the DPPH and ABTS assays. The concentrations of lycopene and the various phenolic compounds as well as the antioxidant activity were significantly influenced by the tomato variety. Quercetin, the most abundant flavonoid, was found in concentrations ranging between 7.19 and 43.59 mg kg -1 fresh weight, while naringenin levels were lower than 12.55 mg kg -1 . The most abundant hydroxycinnamic acid was chlorogenic acid, with values ranging from 14 to 32 mg kg -1 fresh weight, followed by caffeic acid, while p-coumaric and ferulic acids showed similar concentrations lower than 5 mg kg -1 . The highest content of lycopene was found in Ramillete, Pera and Durina (>50 mg kg -1 fresh weight), while the concentration in the other varieties was between 50 and 30 mg kg -1 , with the exception of Liso (less than 20 mg kg 1 ). The antioxidant activity of tomato extracts varied with the tomato variety and the assay method used. Individual compounds found to be significantly related to antioxidant capacity were lycopene and ferulic and caffeic acids, but not quercetin and chlorogenic acid. Les tomates (Lycopersicum esculentum) sont consommees crues ou apres transformation et peuvent fournir une part significative des antioxydants totaux du regime alimentaire. Ceux-ci se trouvent principalement sous la forme de carotenes et de composes phenoliques. Parmi les carotenoides, les lycopenes predominent et sont responsables de la couleur rouge des tomates. L'objectif de cette etude est de determiner la teneur des flavonoides principaux, des acides hydroxycinnamiques et des lycopenes dans des varietes commerciales de tomates cultivees en Espagne et d'explorer la relation entre les concentrations de ces composes et l'activite antioxydante totale du fruit.
536 citations
TL;DR: The bacterial species diversity of three colonic tissue samples from elderly people was investigated by sequence analysis of randomly cloned eubacterial 16S rDNA, providing the first molecular information on the microbial diversity present in human colonic samples.
379 citations
TL;DR: A bioenergetic model is developed that predicts the feasibility of mammalian hibernation under different climatic conditions and predicts a pronounced northward range expansion of hibernating bats within the next 80 years.
Abstract: To predict the consequences of human-induced global climate change, we need to understand how climate is linked to biogeography. Energetic constraints are commonly invoked to explain animal distributions, and physiological parameters are known to vary along distributional gradients. But the causal nature of the links between climate and animal biogeography remain largely obscure. Here we develop a bioenergetic model that predicts the feasibility of mammalian hibernation under different climatic conditions. As an example, we use the well-quantified hibernation energetics of the little brown bat (Myotis lucifugus) to parameterize the model. Our model predicts pronounced effects of ambient temperature on total winter energy requirements, and a relatively narrow combination of hibernaculum temperatures and winter lengths permitting successful hibernation. Microhabitat and northern distribution limits of M. lucifugus are consistent with model predictions, suggesting that the thermal dependence of hibernation energetics constrains the biogeography of this species. Integrating projections of climate change into our model predicts a pronounced northward range expansion of hibernating bats within the next 80 years. Bioenergetics can provide the simple link between climate and biogeography needed to predict the consequences of climate change.
364 citations
TL;DR: There is little evidence to suggest that placental delivery of fatty acids limits normal fetal growth although the importance of the in utero supply may be to support post-natal development as most of the LCPUFA accumulated by the fetus is stored in the adipose tissue for use in early post- prenatal life.
320 citations
278 citations
TL;DR: B vitamins and homocysteine are associated with cognitive variation in old age and may prove relevant to the design of neuroprotective studies in late life.
249 citations
TL;DR: There is convincing evidence that folate modulates both DNA synthesis and repair and DNA hypomethylation with altered gene expression in vitro and the confounding effects of nutrient-gene interactions must be considered when interpreting evidence from human studies.
Abstract: Convincing evidence links folate deficiency with colorectal cancer incidence. Currently, it is believed that folate deficiency affects DNA stability principally through two potential pathways. 5,10-Methylenetetrahydrofolate donates a methyl group to uracil, converting it to thymine, which is used for DNA synthesis and repair. If folate is limited, imbalances in the DNA precursor pool occur, and uracil may be misincorporated into DNA. Subsequent misincorporation and repair may lead to double strand breaks, chromosomal damage and cancer. Moreover, folate affects gene expression by regulating cellular S-adenosylmethionine (SAM) levels. 5-Methyltetrahydrofolate serves as methyl donor in the remethylation of homocysteine to methionine, which in turn is converted to SAM. SAM methylates specific cytosines in DNA, and this regulates gene transcription. As a consequence of folate deficiency, cellular SAM is depleted, which in turn induces DNA hypomethylation and potentially induces proto-oncogene expression leading to cancer. Data from several model systems supporting these mechanisms are reviewed here. There is convincing evidence that folate modulates both DNA synthesis and repair and DNA hypomethylation with altered gene expression in vitro. The data from in vivo experiments in rodents is more difficult to interpret because of variations in the animal and experimental systems used and the influence of tissue specificity and folate metabolism. Most importantly, the confounding effects of nutrient-gene interactions, together with the identification of polymorphisms in key enzyme systems and the influence that these have on folate metabolism and DNA stability, must be considered when interpreting evidence from human studies.
247 citations
225 citations
TL;DR: Assessment of the effect of a blockade of estrogen synthesis on bone turnover markers in 42 normal women randomly assigned to groups receiving the potent aromatase inhibitor letrozole or placebo for 6 months indicates that in late postmenopausal women even the low serum estrogen levels present exert a restraining effect on Bone turnover.
Abstract: Although median levels of bone turnover are increased in postmenopausal women, it is unclear whether the low circulating levels of endogenous estrogen exert a regulatory role on these levels. This issue was evaluated by assessing the effect of a blockade of estrogen synthesis on bone turnover markers in 42 normal women (mean age +/- SD, 69 +/- 5 years) randomly assigned to groups receiving the potent aromatase inhibitor letrozole or placebo for 6 months. Letrozole treatment reduced serum estrone (E1) and estradiol (E2) to near undetectable levels (p < 0.0001). This treatment did not affect bone formation markers but, as compared with the placebo group, increased bone resorption markers (urine 24-h pyridinoline [PYD] by 13.3% [p < 0.05] and 24-h urine deoxypyridinoline [DPD] by 14.2% [p < 0.05]) and decreased serum parathyroid hormone (PTH) by 22% (p = 0.002). These data indicate that in late postmenopausal women even the low serum estrogen levels present exert a restraining effect on bone turnover and support the concept that variations in these low levels may contribute to differences in their rate of bone loss.
TL;DR: It is demonstrated that there is a poor association between resting metabolic rate (RMR) and daily energy expenditure (DEE) measured using the doubly labeled water (DLW) method at the level of species and the link between energetics and aging across species is reconcilable within the framework of the "free-radical damage hypothesis" and the "disposable soma hypothesis".
Abstract: The idea that aging should be linked to energy expenditure has a long history that can be traced to the late 1800s and the industrial revolution. Machines that are run fast wear out more quickly, so the notion was born that humans and animals might experience similar fates: the faster they live (expressed as greater energy expenditure), the sooner they die. Evidence supporting the rate-of-living theory was gleaned from the scaling of resting metabolism and life span as functions of body mass. The product of these factors yields a mass-invariant term, equivalent to the amount of living. There are at least four problems with this evidence, which are summarized and reviewed in this communication: 1) life span is a poor measure of aging, 2) resting metabolism is a poor measure of energy expenditure, 3) the effects are confounded by body mass and 4) the comparisons made are not phylogenetically independent. We demonstrate that there is a poor association between resting metabolic rate (RMR) and daily energy expenditure (DEE) measured using the doubly labeled water (DLW) method at the level of species. Nevertheless, the scaling relation between DEE and body mass still has the same scaling exponent as the RMR and body mass relationship. Thus, if we use DEE rather than RMR in the analysis, the rate-of-living ideas are still supported. Data for 13 species of small mammal were obtained, where energy demands by DLW and longevity were reliably known. In these species, there was a strong negative relationship between residual longevity and residual DEE, both with the effects of body mass removed (r 2 = 0.763, F = 32.1, P < 0.001). Hence, the association of energy demands and life span is not attributed to the confounding effects of body size. We subjected these latter data to an analysis that extracts phylogenetically independent contrasts, and the relationship remained significant (r2 = 0.815, F = 39.74, P < 0.001). Small mammals that live fast really do die young. However, there are very large differences between species in the amounts of living that each enjoy and these disparities are even greater when other taxa are included in the comparisons. Such differences are incompatible with the rate-of-living theory. However, the link between energetics and aging across species is reconcilable within the framework of the free-radical damage hypothesis and the disposable soma hypothesis. Within species one might anticipate the rate-of-living model would be more appropriate. We reviewed data generated from three different sources to evaluate whether this were so, studies in which metabolic rate is experimentally increased and impacts on life span followed, studies of caloric restriction and studies where links between natural variation in metabolism and life span are sought. This review reveals that there might be contrasting effects of resting and nonresting energy expenditure on aging, with increases in the former being protective and increases in the latter being harmful.
TL;DR: A single oral ingestion of O. formigenes by adult volunteers was, for the first time, shown to result in reduced urinary oxalate excretion following administration of anOxalate load, the recovery of oxalATE-degrading activity in feces, and prolonged retention of colonization.
Abstract: Oxalate degradation by the anaerobic bacterium Oxalobacter formigenes is important for human health, helping to prevent hyperoxaluria and disorders such as the development of kidney stones. Oxalate-degrading activity cannot be detected in the gut flora of some individuals, possibly because Oxalobacter is susceptible to commonly used antimicrobials. Here, clarithromycin, doxycycline, and some other antibiotics inhibited oxalate degradation by two human strains of O. formigenes. These strains varied in their response to gut environmental factors, including exposure to gastric acidity and bile salts. O. formigenes strains established oxalate breakdown in fermentors which were preinoculated with fecal bacteria from individuals lacking oxalate-degrading activity. Reducing the concentration of oxalate in the medium reduced the numbers of O. formigenes bacteria. Oxalate degradation was established and maintained at dilution rates comparable to colonic transit times in healthy individuals. A single oral ingestion of O. formigenes by adult volunteers was, for the first time, shown to result in (i) reduced urinary oxalate excretion following administration of an oxalate load, (ii) the recovery of oxalate-degrading activity in feces, and (iii) prolonged retention of colonization.
TL;DR: Lean men appear able to tolerate a considerable negative energy balance, induced by exercise, over 7 days without invoking compensatory increases in EI, according to the modified FLEX method.
Abstract: Objective: To assess the effect of graded increases in exercised-induced energy expenditure (EE) on appetite, energy intake (EI), total daily EE and body weight in men living in their normal environment and consuming their usual diets. Design: Within-subject, repeated measures design. Six men (mean (s.d.) age 31.0 (5.0) y; weight 75.1 (15.96) kg; height 1.79 (0.10) m; body mass index (BMI) 23.3(2.4) kg/m2), were each studied three times during a 9 day protocol, corresponding to prescriptions of no exercise, (control) (Nex; 0 MJ/day), medium exercise level (Mex; ∼1.6 MJ/day) and high exercise level (Hex; ∼3.2 MJ/day). On days 1–2 subjects were given a medium fat (MF) maintenance diet (1.6 × resting metabolic rate (RMR)). Measurements: On days 3–9 subjects self-recorded dietary intake using a food diary and self-weighed intake. EE was assessed by continual heart rate monitoring, using the modified FLEX method. Subjects' HR (heart rate) was individually calibrated against submaximal VO2 during incremental exercise tests at the beginning and end of each 9 day study period. Respiratory exchange was measured by indirect calorimetry. Subjects completed hourly hunger ratings during waking hours to record subjective sensations of hunger and appetite. Body weight was measured daily. Results: EE amounted to 11.7, 12.9 and 16.8 MJ/day (F(2,10)=48.26; P<0.001 (s.e.d=0.55)) on the Nex, Mex and Hex treatments, respectively. The corresponding values for EI were 11.6, 11.8 and 11.8 MJ/day (F(2,10)=0.10; P=0.910 (s.e.d.=0.10)), respectively. There were no treatment effects on hunger, appetite or body weight, but there was evidence of weight loss on the Hex treatment. Conclusion: Increasing EE did not lead to compensation of EI over 7 days. However, total daily EE tended to decrease over time on the two exercise treatments. Lean men appear able to tolerate a considerable negative energy balance, induced by exercise, over 7 days without invoking compensatory increases in EI.
TL;DR: It is concluded that freshly picked, fresh commercial, and frozen raspberries all contain similar levels of phytochemicals and antioxidants per serving.
Abstract: Scottish-grown red raspberries are a rich source of vitamin C and phenolics, most notably, the anthocyanins cyanidin-3-sophoroside, cyanidin-3-(2(G)-glucosylrutinoside), and cyanidin-3-glucoside, and two ellagitannins, sanguiin H-6 and lambertianin C, which are present together with trace levels of flavonols, ellagic acid, and hydroxycinnamates. The antioxidant capacity of the fresh fruit and the levels of vitamin C and phenolics were not affected by freezing. When fruit were stored at 4 degrees C for 3 days and then at 18 degrees C for 24 h, mimicking the route fresh fruit takes after harvest to the supermarket and onto the consumer's table, anthocyanin levels were unaffected while vitamin C levels declined and those of elligitannins increased, and overall, there was no effect on the antioxidant capacity of the fruit. It is concluded, therefore, that freshly picked, fresh commercial, and frozen raspberries all contain similar levels of phytochemicals and antioxidants per serving.
TL;DR: Markedly increasing EE through exercise produced significant but partial compensations in EI (∼33% of EE due to exercise) but accurate adjustments of El to acute increases in EE are likely to take weeks rather than days.
Abstract: Aim: We assessed the effect of graded increases in exercised-induced energy expenditure (EE) on appetite, daily energy intake (EI), total daily EE and body weight in six lean women using a within-subject, repeated measures design. Method: Subjects were each studied three times during 7 day treatments, corresponding to no-exercise (control; Nex; 0 MJ/day), medium exercise level (Mex; ∼1.9 MJ/day) and high exercise level (Hex; ∼3.4 MJ/day), with 2 day maintenance beforehand. Subjects self-weighed ad libitum food intake. EE was assessed by continual heart rate monitoring. During waking hours subjects recorded hourly sensations of hunger and appetite. Results: EE amounted to 9.2, 11.0 and 12.1 MJ/day (F (2, 10)=5.67; P=0.023 (s.e.d.=0.87)) on the Nex, Mex and Hex treatments, respectively. The corresponding values for EI were 8.9, 9.2 and 10.0 MJ/day (F (2, 10)=4.80; P=0.035 (s.e.d.=0.36)). There were very weak treatment effects on hunger. Weight loss was significantly different from zero on the Mex and Hex treatments. Conclusion: Markedly increasing EE through exercise produced significant but partial compensations in EI (∼33% of EE due to exercise). Accurate adjustments of El to acute increases in EE are likely to take weeks rather than days.
TL;DR: It is proposed that the two strains from faeces be classified as a new genus and species, Anaerostipes caccae, which represents a new subline within the Clostridium coccoides group of organisms.
TL;DR: The historical background to Se is described, followed by details of the dietary sources of Se and Se status in different parts of the world, together with the clinical effects of Se deficiency and toxicity.
Abstract: In the past 30 years, it has been recognized that dietary selenium (Se) is essential for the normal function of many of the systems of the body. Furthermore, low Se intake can have deleterious effects on several aspects of human and animal health. The importance of Se is characterized in its role as a constituent of several key antioxidant and redox enzyme families. Most of the effects of Se are probably mediated by selenoproteins, which have the micronutrient covalently incorporated into the protein. The purpose of this review is to examine basic mechanisms by which Se regulates cell growth, gene transcription, cell signaling, and cell death. We start with the historical background to Se. The synthesis and function of selenoproteins are described, followed by details of the dietary sources of Se and Se status in different parts of the world, together with the clinical effects of Se deficiency and toxicity. We consider some aspects of the molecular mechanisms by which Se modulates cell growth, intracellular signaling, and gene transcription.
TL;DR: Investigation of uterine, fetal, and uteroplacental metabolism in ewes offered a high or moderate dietary intake indicates that increased fetal glucose clearance and/or insulin sensitivity may be operating as compensatory mechanisms to preserve normal fetal metabolism while fetal growth is sacrificed.
Abstract: To establish physiological mechanisms for fetal growth restriction in pregnant adolescent ewes we studied uterine, fetal, and uteroplacental metabolism in ewes offered a high (n = 12) or moderate (...
TL;DR: The dose-response curves indicate that the comet assay and HPLC are equally efficient at detecting induced damage, and it is reasonable to assess oxidative stress by any of these methods.
Abstract: Two studies have been performed to clarify the relationship between different markers of oxidative DNA damage commonly employed in molecular epidemiological studies. In the first, 8-Oxo-7,8-dihydroguanine (8-oxoGua) was induced in DNA of HeLa cells by treatment with different concentrations of photosensitizer Ro 19-8022 together with visible light. 8-OxoGua was estimated by the comet assay (alkaline single cell gel electrophoresis) with formamidopyrimidine DNA glycosylase and by HPLC with electrochemical detection. The dose-response curves indicate that the comet assay and HPLC are equally efficient at detecting induced damage. Background levels of 8-oxoGua in HeLa cells were 0.92 +/- 0.22 per 10(6) guanines by the comet assay and 2.09 +/- 0.13 per 10(6) guanines by HPLC. The second study was a small human trial, in which lymphocytes were collected for analysis of background levels of 8-oxoGua, as well as overnight and 24 h urine samples for measurement of excreted 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) by ELISA. The mean level of 8-oxoGua in lymphocytes was determined as 1.33 +/- 0.21 per 10(6) guanines by the comet assay and 3.72 +/- 1.06 per 10(6) guanines by HPLC. A strong correlation was seen between overnight and 24 h urinary 8-oxodGuo (r = 0.93, P < 0.01). Overnight urinary 8-oxodGuo concentrations correlated with 8-oxoGua in lymphocytes measured by HPLC (r = 0.85, P < 0.05) or by the comet assay (r = 0.86, P < 0.05), although individual values from HPLC and the comet assay did not correlate with each other. It is reasonable to assess oxidative stress by any of these methods.
TL;DR: A new syndrome with recurrent infections, inflammation, and hyperzincaemia associated with excessively high plasma concentrations of calprotectin is reported, which encompasses a pathological role for dysregulation of two members of the large S100 protein family.
TL;DR: A case-control study of two functional polymorphisms in MTHFR, dietary folate intake and breast cancer finds patterns in risk with regard to genotype and folate combinations are broadly similar those reported for colorectal neoplasia.
TL;DR: These studies indicate that removal of nucleus may lead to further disc degeneration and indicate the material properties required for an implant material and provide a reasonable model for human lumbar intervertebral discs.
TL;DR: Findings indicate that CLA elicits mainly proapoptotic effects in human breast tumor cells through both p53‐dependent and p 53‐independent pathways, according to cell type.
Abstract: SPECIFIC AIMSConjugated linoleic acid (CLA) inhibits mammary tumorigenesis in animals and attenuates animal and human cancer cell proliferation. The aim of this study was a detailed determination of the modulatory effect of CLA on the expression (mRNA and protein) of major proto-oncogenes that regulate cell proliferation and apoptosis in benign (MCF-10A) and malignant (estrogen receptor positive MCF-7 and negative, MDA-MB-231) mammary tumor cells.PRINCIPAL FINDINGS1. CLA mix differentially regulates expression of p53 and p21WAF1/CIP1 and bcl-2 mRNA in MCF-7, MBA-MD-231, and MCF-10A cellsThe three cell lines were grown to subconfluence under standard culture conditions in 75 cm2 flasks and treated with varying concentrations of CLA (a 50:50 mix of 9-cis, trans-11, and trans-10, cis-12 isomers) for 24 h. Total RNA and protein was extracted and subjected to Northern, Western, and ELISA using standard procedures to determine changes in gene expression (mRNA and protein) of the above-mentioned oncogenes.Northe...
TL;DR: Whether animal feeding studies for establishing the safety of GM feedstuffs for the target animals and whether they are always necessary to establish the safety for the consumer of products of animals fed GM material are considered.
TL;DR: The data demonstrate that quercetin-4'-glucoside, which is a major flavonol in onions, undergoes rapid and extensive metabolism in the intestine, and this appears not to be associated with transport across the gut wall into the blood stream.
Abstract: Epidemiological studies suggest that consumption of flavonol-rich diets decreases the risk of developing heart disease and certain cancers. Recent studies have detected flavonol conjugates in blood and urine following various dietary interventions. To assess to what extent flavonols also accumulate in tissues, where they might be expected to exert anti-carcinogenic and anti-atherogenic effects, [2-(14)C]quercetin-4'-glucoside was synthesized and fed to rats. After 60 min, 93.6% of the ingested radioactivity was recovered from the intestine, incorporated into 18 metabolites that had undergone deglycosylation followed by varying degrees of glucuronidation, methylation, and/or sulfation. [(14)C]Quercetin, the aglycon of the radiolabeled substrate, was present in the intestine and in trace amounts in the liver but was not detected in the plasma and kidneys. The original [2-(14)C]quercetin-4'-glucoside was detected exclusively in the intestine, where it accounted for only 26.2% of the radioactivity. The remainder of the recovered radioactivity was located mainly in the plasma, liver, and kidneys as (14)C-labeled metabolites. However, compared to the quantities in the gastrointestinal tract, the levels of metabolites in plasma and body tissues were very low, indicating only limited absorption into the blood stream. The data demonstrate that quercetin-4'-glucoside, which is a major flavonol in onions, undergoes rapid and extensive metabolism in the intestine, and this appears not to be associated to any extent with transport across the gut wall into the blood stream.
TL;DR: The incidence of conjugative transposons (CTns) and the antibiotic resistance genes they carry has not been well studied among the dense, diverse anaerobic microbial population inhabiting the gastrointestinal tract of humans and animals.
Abstract: There is huge potential for genetic exchange to occur within the dense, diverse anaerobic microbial population inhabiting the gastrointestinal tract (GIT) of humans and animals. However, the incidence of conjugative transposons (CTns) and the antibiotic resistance genes they carry has not been well studied among this population. Since any incoming bacteria, including pathogens, can access this reservoir of genes, this oversight would appear to be an important one. Recent evidence has shown that anaerobic bacteria native to the rumen or hindgut harbour both novel antibiotic resistance genes and novel conjugative transposons. These CTns, and previously characterized CTns, can be transferred to a wide range of commensal bacteria under laboratory and in vivo conditions. The main evidence that gene transfer occurs widely in vivo between GIT bacteria, and between GIT bacteria and pathogenic bacteria, is that identical resistance genes are present in diverse bacterial species from different hosts.
TL;DR: Melatonin may act on the human fetus via the MT1 receptor subtype at a number of discrete brain sites through binding to the leptomeninges, cerebellum, thalamus, hypothalamus, and brainstem.
Abstract: The purpose of this study was to identify sites of action of melatonin in the human fetal brain by in vitro autoradiography and in situ hybridization. Specific, guanosine triphosphate (GTP) sensitive, binding of 2-[(125)I]iodomelatonin was localized to the leptomeninges, cerebellum, thalamus, hypothalamus, and brainstem. In the hypothalalmus, specific binding was present in the suprachiasmatic nuclei (SCN) as well as the arcuate, ventromedial and mammillary nuclei. In the brainstem specific binding was present in the cranial nerve nuclei including the oculomotor nuclei, the trochlear nuclei, the motor and sensory trigeminal nuclei, the facial nuclei, and the cochlear nuclei. The localization of MT1 receptor subtype gene expression as determined by in situ hybridization matched the localization of 2-[(125)I]iodomelatonin binding. No MT2 receptor subtype gene expression was detected using this technique. Thus, melatonin may act on the human fetus via the MT1 receptor subtype at a number of discrete brain sites. A major site of action of melatonin in both fetal and adult mammals is the pars tuberalis of the pituitary gland. However, no 2-[(125)I]iodomelatonin binding or melatonin receptor gene expression was detected in the pituitary gland in the present study, indicating that the pituitary, particularly the pars tuberalis, is not a site of action of melatonin in the human fetus.
TL;DR: It is demonstrated that different methodologies and different substrate concentrations provide an explanation for different apparent rates of ruminal NH3 production reported in different studies and identifies a diverse range of hyper-ammonia-producing bacteria in the rumen of sheep.
Abstract: Excessive NH(3) production in the rumen is a major nutritional inefficiency in ruminant animals. Experiments were undertaken to compare the rates of NH(3) production from different substrates in ruminal fluid in vitro and to assess the role of asaccharolytic bacteria in NH(3) production. Ruminal fluid was taken from four rumen-fistulated sheep receiving a mixed hay-concentrate diet. The calculated rate of NH(3) production from Trypticase varied from 1.8 to 19.7 nmol mg of protein(-1) min(-1) depending on the substrate, its concentration, and the method used. Monensin (5 micro M) inhibited NH(3) production from proteins, peptides, and amino acids by an average of 28% with substrate at 2 mg/ml, compared to 48% with substrate at 20 mg/ml (P = 0.011). Of the total bacterial population, 1.4% grew on Trypticase alone, of which 93% was eliminated by 5 micro M monensin. Many fewer bacteria (0.002% of the total) grew on amino acids alone. Nineteen isolates capable of growth on Trypticase were obtained from four sheep. 16S ribosomal DNA and traditional identification methods indicated the bacteria fell into six groups. All were sensitive to monensin, and all except one group (group III, similar to Atopobium minutum), produced NH(3) at >250 nmol min(-1) mg of protein(-1), depending on the medium, as determined by a batch culture method. All isolates had exopeptidase activity, but only group III had an apparent dipeptidyl peptidase I activity. Groups I, II, and IV were most closely related to asaccharolytic ruminal and oral Clostridium and Eubacterium spp. Group V comprised one isolate, similar to Desulfomonas piger (formerly Desulfovibrio pigra). Group VI was 95% similar to Acidaminococcus fermentans. Growth of the Atopobium- and Desulfomonas-like isolates was enhanced by sugars, while growth of groups I, II, and V was significantly depressed by sugars. This study therefore demonstrates that different methodologies and different substrate concentrations provide an explanation for different apparent rates of ruminal NH(3) production reported in different studies and identifies a diverse range of hyper-ammonia-producing bacteria in the rumen of sheep.
TL;DR: Results indicate that hydroxytyrosol is the only significant antioxidant phenolic in olive oil and may be the major component accounting for its beneficial properties.
Abstract: Hydroxytyrosol, tyrosol and caffeic acid effects on hydrogen peroxide-induced DNA damage, hydroperoxide generation and redox enzyme gene expression were studied in oxidative-stress-sensitive human prostate cells (PC3). Hydroxytyrosol led to lower levels of hydroperoxides, DNA damage, and mRNA levels of classic glutathione peroxidase (GPx) for all the studied concentrations. Only hydroxytyrosol was effective at low concentrations (10 microm). Tyrosol reduced DNA oxidation only at high (>50 microm) concentrations and increased hydroperoxides, GPx and phospholipid hydroperoxide GPx mRNA levels. Caffeic acid elicited effects between those of the other two phenolics. Results indicate that hydroxytyrosol is the only significant antioxidant phenolic in olive oil and may be the major component accounting for its beneficial properties. Tyrosol appeared to exhibit pro-oxidant effects (only at high concentrations) and caffeic acid was neutral. Both number and position of hydroxyl groups appear to play a role in the cellular effects of hydroxytyrosol.