13 resultados para Liver fibrosis and carcinogenesis

em CentAUR: Central Archive University of Reading - UK


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The objective of this study was to determine the distribution of total selenium (Se) and of the proportion of total Se comprised as the selenized amino acids selenomethionine (SeMet) and selenocysteine (SeCys) within the post mortem tissues of lambs that were fed high dose selenized enriched yeast (SY), derived from a specific strain of Saccharomyces cerevisae CNCM (Collection Nationale de Culture de Micro-organism) I-3060. Thirty two Texel X Suffolk lambs (6.87 ± 0.23 kg BW) were offered both reconstituted milk replacer and a pelleted diet, both of which had been either supplemented with high SY (6.30 ± 0.18 mg Se/kg DM) or unsupplemented (0.13 ± 0.01 mg Se/kg of DM), depending on treatment designation, for a continuous period of 91 d. At enrollment and 28, 56 and 91 d following enrollment lambs were blood sampled. At the completion of the treatment period, five lambs from each treatment group were euthanased and samples of heart, liver, kidney and skeletal muscle (Longissimus Dorsi and Psoas Major) were retained for Se analysis. The inclusion of high SY increased (P < 0.001) whole blood Se concentration, reaching a maximum mean value of 815.2 ± 19.1 ng Se/mL compared with 217.8 ± 9.1 ng Se/mL in control animals. Tissue total Se concentrations were significantly (P < 0.001) higher in SY supplemented animals than in controls irrespective of tissue type; values were 26, 16, 8 and 3 times higher in skeletal muscle, liver, heart and kidney tissue of HSY lambs when compared to controls. however, the distribution of total Se and the proportions of total Se comprised as either SeMet or SeCys differed between tissue types. Selenocysteine was the predominant selenized amino acid in glandular tissues, such the liver and kidney. irrespective of treatment, although absolute values were markedly higher in HSY lambs. Conversely selenomethionine was the predominat selenized amino acid in cardiac and skeletal muscle (Longissimus Dorsi, and Psoas Major) tissues in HSY animals, although the same trend was not apparent for control lambs in which SeCys was the predominant selenized amino acid. It was concluded that there were increases in both whole blood and tissue total Se concentrations as a result of dietary supplementation with high dose of SY. Furthermore, distribution of total Se and Se species differed between both treatment designation and tissue type.

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The objective was to determine the concentration of total selenium (Se) and the proportion of total Se comprised as selenomethionine (SeMet) and selenocysteine (SeCys) in post mortem tissues of lambs in the six weeks period following the withdrawal of a diet containing high dose selenized yeast (SY), derived from a specific strain of Saccharomyces cerevisae CNCM (Collection Nationale de Culture de Micro-organism) I-3060. Thirty Texel x Suffolk lambs used in this study had previously received diets (91 days) containing either high dose SY (HSY; 6.30 mg Se/kg DM) or an unsupplemented control (C; 0.13 mg Se/kg DM). Following the period of supplementation all lambs were then offered a complete pelleted diet, without additional Se (0.15 mg Se/kg DM), for 42 days. At enrollment and 21 and 42 days later, five lambs from each treatment were blood sampled, euthanased and samples of heart, liver, kidney and skeletal muscle (Longissimus Dorsi and Psoas Major) tissue were retained. Total Se concentration in whole blood and tissues was significantly (P < 0.001) higher in HSY lambs at all time points that had previously received long term exposure to high dietary concentrations of SY. The distribution of total Se and the proportions of total Se comprised as SeMet and SeCys differed between tissues, treatment and time points. Total Se was greatest in HSY liver and kidney (22.64 and 18.96 mg Se/kg DM, respectively) and SeCys comprised the greatest proportion of total Se. Conversely, cardiac and skeletal muscle (Longissimus Dorsi and Psoas Major) tissues had lower total Se concentration (10.80, 7.02 and 7.82 mg Se/kg DM, respectively) and SeMet was the predominant selenized amino acid. Rates of Se clearance in HSY liver (307 µg Se/day) and kidney (238 µg Se/day) were higher compared with HSY cardiac tissue (120 µg Se/day) and skeletal muscle (20 µg Se/day). In conclusion differences in Se clearance rates were different between tissue types, reflecting the relative metabolic activity of each tissue, and appear to be dependant upon the proportions of total Se comprised as either SeMet or SeCys.

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The objective was to determine the concentration of total selenium (Se) and the proportion of total Se comprised as selenomethionine (SeMet) and selenocysteine (SeCys) in post mortem tissues of beef cattle offered diets containing graded additions of selenized enriched yeast (SY) [Saccharomyces cerevisae CNCM I-3060]), or sodium selenite (SS). Oxidative stability and tissue glutathione peroxidase (GSH-Px) activity of edible muscle tissue were assessed 10 d post-mortem. Thirty two beef cattle were offered, for a period of 112 d, a total mixed ration which had either been supplemented with SY (0, 0.15 or 0.35 mg Se/kg DM) or SS (0.15 mg Se/kg DM). At enrollment (0 d) and at 28, 56, 84 and 112 d following enrollment, blood samples were taken for Se and Se species determination, as well as whole blood GSH-Px activity. At the end of the study beef cattle were euthanized and samples of heart, liver, kidney, and skeletal muscle (LM and psoas major) were retained for Se and Se species determination. Tissue GSH-Px activity and thiobarbituric acid reactive substances (TBARS) were determined in skeletal muscle tissue (LM only). The incorporation into the diet of ascending concentrations of Se as SY increased whole blood total Se and the proportion of total Se comprised as SeMet, as well as GSH-Px activity. There was also a dose dependant response to the graded addition of SY on total Se and proportion of total Se as SeMet in all tissues and GSH-Px activity in skeletal muscle tissue. Furthermore, total Se concentration of whole blood and tissues was greater in those animals offered SY when compared with those receiving a comparable dose of SS, indicating an improvement in Se availability and tissue Se retention. Likewise, GSH-Px activity in whole blood and LM was greater in those animals offered SY when compared with those receiving a comparable dose of SS. However, these increases in tissue total Se and GSH-Px activity appeared to have little or no effect in meat oxidative stability.

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The objective was to determine the concentration of total selenium (Se) and the proportion of total Se comprised as selenomethionine (SeMet) and selenocysteine (SeCys), as well as meat quality in terms of oxidative stability in post mortem tissues of lambs offered diets with an increasing dose rate of selenized enriched yeast (SY), or sodium selenite (SS). Fifty lambs were offered, for a period of 112 d, a total mixed ration which had either been supplemented with SY (0, 0.11, 0.21 or 0.31 mg/kg DM to give total Se contents of 0.19, 0.3, 0.4 and 0.5 mg Se/kg DM for treatments T1, T2, T3 and T4, respectively) or SS (0.11 mg/kg DM to give 0.3 mg Se/kg DM total Se [T5]). At enrolment and at 28, 56, 84 and 112 d following enrolment, blood samples were taken for Se and Se species determination, as well as glutathione peroxidase (GSH-Px) activity. At the end of the study lambs were euthanased and samples of heart, liver, kidney, and skeletal muscle were retained for Se and Se species determination. Tissue GSH-Px activity and thiobarbituric acid reactive substances (TBARS) were determined in Longissimus Thoracis. The incorporation into the diet of ascending concentrations of Se as SY increased whole blood total Se and the proportion of total Se comprised as SeMet, and erythrocyte GSH-Px activity. Comparable doses of SS supplementation did not result in significant differences between these parameters. With the exception of kidney tissue, all other tissues showed a dose dependant response to increasing concentrations of dietary SY, such that total Se and SeMet increased. Selenium content of Psoas Major was higher in animals fed SY when compared to a similar dose of SS, indicating improvements in Se availability and retention. There were no significant treatment effects on meat quality assessments GHS-Px and TBARS, reflecting the lack of difference in the proportion of total Se that was comprised as SeCys. However, oxidative stability improved marginally with ascending tissue Se content, providing an indication of a linear dose response whereby TBARS improved with ascending SY inclusion.

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The expression of two metallothionein genes (Mt-I and Mt-II) in the liver, kidney, and gonad of bank voles collected at four metal-contaminated sites (Cd, Zn, Pb, and Fe) were measured using the quantitative real-time PCR method (QPCR). Relative Mt gene expression was calculated by applying a normalization factor (NF) using the expression of two housekeeping genes, ribosomal 18S and beta-actin. Relative Mt expression in tissues of animals from contaminated sites was up to 54.8-fold higher than those from the reference site for Mt-I and up to 91.6-fold higher for Mt-II. Mt-II gene expression in the livers of bank voles from contaminated sites was higher than Mt-I gene expression. Inversely, Mt-II expression in the kidneys of voles was lower than Mt-I expression. Positive correlations between cadmium levels in the tissues and Mt-I were obtained in all studied tissues. Zinc, which undergoes homeostatic regulation, correlated positively with both Mt-I and Mt-II gene expression only in the kidney. Results showed that animals living in chronically contaminated environments intensively activate detoxifying mechanisms such as metallothionein expression. This is the first time that QPCR techniques to measure MT gene expression have been applied to assess the impact of environmental metal pollution on field collected bank voles.

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The expression of two metallothionein genes (Mt-I and Mt-II) in the liver, kidney, and gonad of bank voles collected at four metal-contaminated sites (Cd, Zn, Pb, and Fe) were measured using the quantitative real-time PCR method (QPCR). Relative Mt gene expression was calculated by applying a normalization factor (NF) using the expression of two housekeeping genes, ribosomal 18S and beta-actin. Relative Mt expression in tissues of animals from contaminated sites was up to 54.8-fold higher than those from the reference site for Mt-I and up to 91.6-fold higher for Mt-II. Mt-II gene expression in the livers of bank voles from contaminated sites was higher than Mt-I gene expression. Inversely, Mt-II expression in the kidneys of voles was lower than Mt-I expression. Positive correlations between cadmium levels in the tissues and Mt-I were obtained in all studied tissues. Zinc, which undergoes homeostatic regulation, correlated positively with both Mt-I and Mt-II gene expression only in the kidney. Results showed that animals living in chronically contaminated environments intensively activate detoxifying mechanisms such as metallothionein expression. This is the first time that QPCR techniques to measure MT gene expression have been applied to assess the impact of environmental metal pollution on field collected bank voles.

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Regular consumption of green tea polyphenols (GTP) is thought to reduce the risk of cardiovascular disease (CVD) but has also been associated with liver toxicity. The present trial aimed to assess the safety and potential CVD health beneficial effects of daily GTP consumption. We conducted a placebo-controlled parallel study to evaluate the chronic effects of GTP on liver function and CVD risk biomarkers in healthy men. Volunteers (treatment: n = 17, BMI 26.7 +/- 3.3 kg/m(2), age 41 +/- 9 y; placebo, n = 16, BMI 25.4 +/- 3.3 kg/m(2), age 40 +/- 10 y) consumed for 3 wk 6 capsules per day (2 before each principal meal) containing green tea extracts (equivalent to 714 mg/d GTP) or placebo. At the beginning and end of the intervention period, we collected blood samples from fasting subjects and measured vascular tone using Laser Doppler lontophoresis. Biomarkers of liver function and CVD risk (including blood pressure, plasma lipids, and asymmetric dimethylarginine) were unaffected by GTP consumption. After treatment, the ratio of total:HDL cholesterol was significantly reduced in participants taking GTP capsules compared with baseline. Endothelial-dependent and -independent vascular reactivity did not significantly differ between treatments. In conclusion, the present data suggests that the daily consumption of high doses of GTP by healthy men for 3 wk is safe but without effects on CVD risk biomarkers other than the total:HDL cholesterol ratio. J. Nutr. 139: 58-62, 2009.

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Background The gut and immune system form a complex integrated structure that has evolved to provide effective digestion and defence against ingested toxins and pathogenic bacteria. However, great variation exists in what is considered normal healthy gut and immune function. Thus, whilst it is possible to measure many aspects of digestion and immunity, it is more difficult to interpret the benefits to individuals of variation within what is considered to be a normal range. Nevertheless, it is important to set standards for optimal function for use both by the consumer, industry and those concerned with the public health. The digestive tract is most frequently the object of functional and health claims and a large market already exists for gut-functional foods worldwide. Aim To define normal function of the gut and immune system and describe available methods of measuring it. Results We have defined normal bowel habit and transit time, identified their role as risk factors for disease and how they may be measured. Similarly, we have tried to define what is a healthy gut flora in terms of the dominant genera and their metabolism and listed the many, varied and novel methods for determining these parameters. It has proved less easy to provide boundaries for what constitutes optimal or improved gastric emptying, gut motility, nutrient and water absorption and the function of organs such as the liver, gallbladder and pancreas. The many tests of these functions are described. We have discussed gastrointestinal well being. Sensations arising from the gut can be both pleasant and unpleasant. However, the characteristics of well being are ill defined and merge imperceptibly from acceptable to unacceptable, a state that is subjective. Nevertheless, we feel this is an important area for future work and method development. The immune system is even more difficult to make quantitative judgements about. When it is defective, then clinical problems ensure, but this is an uncommon state. The innate and adaptive immune systems work synergistically together and comprise many cellular and humoral factors. The adaptive system is extremely sophisticated and between the two arms of immunity there is great redundancy, which provides robust defences. New aspects of immune function are discovered regularly. It is not clear whether immune function can be "improved". Measuring aspects of immune function is possible but there is no one test that will define either the status or functional capacity of the immune system. Human studies are often limited by the ability to sample only blood or secretions such as saliva but it should be remembered that only 2% of lymphocytes circulate at any given time, which limits interpretation of data. We recommend assessing the functional capacity of the immune system by: measuring specific cell functions ex vivo, measuring in vivo responses to challenge, e. g. change in antibody in blood or response to antigens, determining the incidence and severity of infection in target populations during naturally occurring episodes or in response to attenuated pathogens.

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The objective of this study was to determine the concentration of total selenium (Se) and proportions of total Se comprised as selenomethionine (SeMet) and selenocysteine (SeCys) in the tissues of female turkeys offered diets containing graded additions of selenized-enriched yeast (SY), or sodium selenite (SS). Oxidative stability and tissue glutathione peroxidase (GSH-Px) activity of breast and thigh muscle were assessed at 0 and 10 days post mortem. A total of 216 female turkey poults were enrolled in the study. A total of 24 birds were euthanized at the start of the study and samples of blood, breast, thigh, heart, liver, kidney and gizzard were collected for determination of total Se. Remaining birds were blocked by live weight and randomly allocated to one of four dietary treatments(n548 birds/treatment) that differed either in Se source (SY v. SS) or dose (Con [0.2 mg/kg total Se], SY-L and SS-L [0.3mg/kg total Se as SY and SS, respectively] and SY-H [0.45mg total Se/kg]). Following 42 and 84 days of treatment 24 birds per treatment were euthanized and samples of blood, breast, thigh, heart, liver, kidney and gizzard were retained for determination of total Se and the proportion of total Se comprised as SeMet or SeCys. Whole blood GSH-Px activity was determined at each time point. Tissue GSH-Px activity and thiobarbituric acid reactive substances were determined in breast and thigh tissue at the end of the study. There were responses (P,0.001) in all tissues to the graded addition of dietary Se, although rates of accumulation were highest in birds offered SY. There were notable differences between tissue types and treatments in the distribution of SeMet and SeCys, and the activity of tissue and erythrocyte GSH-Px (P,0.05). SeCys was the predominant form of Se in visceral tissue and SeMet the predominant form in breast tissue. SeCys contents were greater in thigh when compared with breast tissue. Muscle tissue GSH-Px activities mirrored SeCys contents. Despite treatment differences in tissue GSH-Px activity, there were no effects of treatment on any meat quality parameter.

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The objective of this study was to determine the concentration of total selenium (Se) and the proportions of total Se comprised as selenomethionine (SeMet) and selenocysteine (SeCys) in the post mortem tissues of female pheasants (Phasianus Colchicus Torquator) offered diets containing graded additions of selenized enriched yeast (SY) or sodium selenite (SS). Thiobarbituric acid reactive substances (TBARS) and tissue glutathione peroxidase (GSH-Px) activity of breast (Pectoralis Major) were assessed at 0 and 5 d post-mortem. A total of 216 female pheasant chicks were enrolled onto the study. 24 birds were euthanased at the start of the study and samples of blood, breast muscle, leg muscle (Peroneus Longus and M. Gastrocnemius), heart, liver, kidney and gizzard collected for determination of total Se. Remaining birds were blocked by live weight and randomly allocated to one of four dietary treatments (n=48 birds/treatment) that either differed in Se source (SY vs. SS) or dose (Con [0.2 mg total Se/kg], SY-L and SS-L [0.3 mg/kg total Se as SY and SS, respectively], and SY-H [0.45 mg total Se/kg]). Following 42 and 91 days of treatment 24 birds/treatment were euthanased and samples of blood, breast muscle, leg muscle, heart, liver, kidney and gizzard retained for determination of total Se and the proportion of total Se comprised as SeMet or SeCys. Whole blood GSH-Px activity was determined at each time point. Tissue GSH-Px activity and TBARS were determined in breast tissue at the end of the study. There were positive responses (P<0.001) in both blood and tissues to the graded addition of SY to the diet but the same responses were not apparent in the blood and tissues of selenite supplemented birds receiving comparable doses. Although there were differences between tissue types in the distribution of SeMet and SeCys there were few differences between treatments. There were effects of treatment on erythrocyte GSH-Px activity (P = 0.012) with values being higher in treatments SY-H and SS-L when compared to the negative control and treatment SY-L. There were no effects of treatment on tissue GSH-Px activity which is reflected in the overall lack of any treatment effects on TBARS.

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Several bis-malonatooxidovanadium(IV) complexes of the general type [M(2)(H2(O))(n)][VO(mal)(2)(H(2)O)] (where M = Li(1), Na(2), K(3), Cs(4) and NH4(5); n = 3.5, 1, 3, 1 and 1, respectively) were isolated in good yield and high purity. These complexes were fully characterized by various physicochemical techniques (elemental analysis, UV- Vis, IR, EPR, CV, etc.) complexes 1, 2 and 3 were structurally characterized by single crystal X- ray diffraction technique. In vivo antidiabetic properties of bis- malonato complexes 1, 2, 3 and 5 have been studied using Streptozotocin induced diabetic rats. Significant lowering of blood sugar level has been noticed. At the same time these complexes were found to regulate secondary pathophysiological complications like liver damage and lowering of the total antioxidant status (TAS) in diabetic rats. Results of these study are expected to a expand the possibility of designing new oxidovanadium(IV) complexes of O, O chelating ligands with significant antidiabetic properties

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Cardiac hypertrophy is associated with hypertrophic growth of cardiac myocytes and increased fibrosis. Much is known of the stimuli which promote myocyte hypertrophy and the changes associated with the response, but the links between the two are largely unknown. Using subtractive hybridization, we identified three genes which are acutely (<1 h) upregulated in neonatal rat ventricular myocytes exposed to the alpha-adrenergic agonist, phenylephrine. One represented connective tissue growth factor (CTGF) which is implicated in fibrosis and promotes hypertrophy in other cells. We further examined the expression of CTGF mRNA and protein in cardiac myocytes using quantitative PCR and immunoblotting, confirming that phenylephrine increased CTGF mRNA (maximal within 1 h) and protein (increased over 4 - 24 h). Endothelin-1 promoted a greater, though transient, increase in CTGF mRNA, but the increase in CTGF protein was sustained over 8 h. Neither agonist increased CTGF mRNA in cardiac non-myocytes. By increasing the expression of CTGF in cardiac myocytes, hypertrophic agonists such as phenylephrine and endothelin-1 may promote fibrosis. CTGF may also propagate the hypertrophic response initiated by these agonists.