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Mechanisms and consequences of nutritional depletion in early lung cancerJagoe, Robert Thomas January 2000 (has links)
No description available.
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The clinical management of patients at increased risk of coronary heart diseaseHartwell, Debbie L. January 1998 (has links)
No description available.
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Effect of dietary fiber on the methanogen community in the hindgut of Lantang giltsCao, Z., Liang, J. B., Liao, X. D., Wright, A. D. G., Wu, Y. B., Yu, B. 07 April 2016 (has links)
The primary objective of this study was to investigate the effect of dietary fiber on methanogenic diversity and community composition in the hindgut of indigenous Chinese Lantang gilts to explain the unexpected findings reported earlier that Lantang gilts fed low-fiber diet (LFD) produced more methane than those fed high-fiber diet (HFD). In total, 12 Lantang gilts (58.7±0.37 kg) were randomly divided into two dietary groups (six replicates (pigs) per group) and fed either LFD (NDF=201.46 g/kg) or HFD (NDF=329.70 g/kg). Wheat bran was the main source of fiber for the LFD, whereas ground rice hull (mixture of rice hull and rice bran) was used for the HFD. Results showed that the methanogens in the hindgut of Lantang gilts belonged to four known species (
Methanobrevibacter ruminantium, Methanobrevibacter wolinii
,
Methanosphaera stadtmanae
and
Methanobrevibacter smithii
), with about 89% of the methanogens belonging to the genus
Methanobrevibacter
. The 16S ribosomal RNA (rRNA) gene copies of
Methanobrevibacter
were more than three times higher (
P
<0.05) for gilts fed LFD (3.31×10
9
copies/g dry matter (DM)) than gilts fed HFD (1.02×10
9
copies/g DM). No difference (
P
>0.05) was observed in 16S rRNA gene copies of
Fibrobacter succinogenes
between the two dietary groups, and 18S rRNA gene copies of anaerobic fungi in gilts fed LFD were lower than (
P
<0.05) those fed HFD. To better explain the effect of different fiber source on the methanogen community, a follow-up
in vitro
fermentation using a factorial design comprised of two inocula (prepared from hindgut content of gilts fed two diets differing in their dietary fiber)×four substrates (LFD, HFD, wheat bran, ground rice hull) was conducted. Results of the
in vitro
fermentation confirmed that the predominant methanogens belonged to the genus of
Methanobrevibacter
, and about 23% methanogens was found to be distantly related (90%) to
Thermogymnomonas acidicola. In vitro
fermentation also seems to suggest that fiber source did change the methanogens community. Although the density of
Methanobrevibacter
species was positively correlated with CH
4
production in both
in vivo
(
P
<0.01,
r
=0.737) and
in vitro
trials (
P
<0.05,
r
=0.854), which could partly explain the higher methane production from gilts fed LFD compared with those in the HFD group. Further investigation is needed to explain how the rice hull affected the methanogens and inhibited CH
4
emission from gilts fed HFD.
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The development of bone cholesterol delta¹³C values as a new source of palaeodietary information : models of its use in conjunction with bone collagen and apatite delta¹³C valuesJim, Susan January 2000 (has links)
No description available.
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Adherence to lifestyle modification recommendations in hypertensive patients at Parirenyatwa HospitalMakondo, Rulani January 2018 (has links)
Magister Public Health - MPH / Background: Hypertension (HTN) complications are one of the leading causes of disability and mortality worldwide, with increasing trends noted in Africa. The most neglected causes of uncontrolled HTN and its complications are unhealthy diets, excess alcohol consumption and physical inactivity. Adherence to recommended lifestyle modifications remains low in Zimbabwe. This study seeks to explore the factors influencing adherence to World Health Organisation (WHO) lifestyle modification recommendations in patients with hypertension at Parirenyatwa Hospital, Harare.
Methodology: An analytic cross-sectional study design was utilized. 328 hypertensive patients aged at least 18, receiving care at Parirenyatwa Hospital were recruited into the study. A self-administered questionnaire was used to collect information on demographics, knowledge and adherence to WHO recommended lifestyle modifications from participants. Statistical Package for Social Scientists (SPSS) version 20 was used for data analysis. The Spearman test was used to test for linear correlation among variables and the 5-point Likert Scale was utilized to categorize the extent of practice of dietary and physical activity recommendations by WHO.
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Systems analysis of selenium accumulation in rice (Oryza sativa) and its regulation by O-acetylserine(thiol)lyase (OAS-TL) gene. / CUHK electronic theses & dissertations collectionJanuary 2012 (has links)
為滿足人類對微量元素硒的需求,在本研究中,我們進一步完善優化利用少硒化肥強化水稻的生物農業性狀,並且全面地檢測了富硒稻米中硒的生物有效性和生物利用度。首先,我們發現低濃度的亞硒酸鈉(2毫克/升)在提高水稻幼苗生長方面有顯著的成效。通過抽穗後葉面噴施亞硒酸鈉生產富硒稻米及調控低量的亞硒酸鈉(10.5克硒/公頃)能顯著增加水稻籽粒中硒含量高達51倍;同時,水稻產量也上調了1.24倍。此外,通過硒形態分析、體外胃腸消化和抗氧化實驗來評估,在富硒稻米中,硒的主要富集形態是硒代蛋氨酸;同時,富硒稻米具有明顯較高的抗氧化生物活性。這種富硒大米在人類補硒方面具有巨大潛力。 / 硒對植物生長的作用有兩方面,既有有利作用又有毒副作用。水稻種植應用低濃度的亞硒酸鈉能促進生長,而較高濃度的亞硒酸鈉則抑制生長。為詳細解釋這種兩面性影響機制,我們應用二維凝膠電泳(2-DE)結合基質輔助鐳射解吸離子化-飛行時間質譜(MALDI-TOF/TOF MS)進行蛋白質組學研究。將硒處理組與對照組水稻幼苗之間的凝膠圖像進行比較,確定了莖葉和根中分別有66和97個差異表達的蛋白質。基因聚類分析顯示,水稻的中心代謝,光合作用和氧化還原平衡高度受硒處理影響。低硒處理(2和6毫克/升亞硒酸鈉)啟動抗氧化系統,增強光合作用和初級代謝。而較高的硒處理(10毫克/升的亞硒酸鈉)則抑制光合作用和初級代謝。此項研究在未來生產富硒水稻方面具有指導性意義。 / 為了更好地瞭解水稻穀粒中硒富集的生物機制,我們應用2-DE結合MALDI-TOF/TOF MS及1-DE結合傅裏葉變換離子迴旋共振質譜(FTMS)進行了水稻穀粒的蛋白質組學研究。這項研究提供了最全面的稻米穀粒蛋白質表達圖譜。通過硒處理和對照之間的比較,62和250個差異表達的蛋白質分別被雙電離飛行時間質譜和傅裏葉變換質譜所鑒定。通過基因功能分類,在成熟的稻穀中,硫代謝,碳代謝,細胞的氧化還原調控,和種子的營養儲存過程中涉及的蛋白質受到硒富集的高度影響。此外,有6個蛋白被檢測具有含硒氨基酸片斷,這是高等植物中含硒蛋白的首次鑒定。 / 富硒水稻的基因工程能提高人類的補硒預期。因此,為獲得可以應用於基因工程改造的合適的水稻基因,我們通過在經典模型植物擬南芥中過表達水稻O-乙醯絲氨酸硫解酶(OASTL)的基因,包括在胞漿中表達的OASTLA基因、在質體中表的OASTLB基因和線粒體中表達的OASTLC基因,用以研究這些基因在轉基因植株中對硒富集的影響。在不同硒濃度處理下,與野生型植物相比,此三個基因均表達顯著提高轉基因植物中的硒含量。即時定量反轉錄PCR分析結果顯示,由於過表達的水稻OASTL基因,硒同化的整個代謝途徑被啟動,尤其是與半胱氨酸和蛋氨酸合成有關的基因被啟動,這可能就是引起更多的硒富集在轉基因植物裏的原因。此外,過表達水稻OASTL基因也啟動穀胱甘肽還原酶,這可能增強富硒轉基因植物的抗氧化系統從而提高抗逆性並增加產量。因此,OASTL基因在基因工程生產富硒稻米方面具有重要潛在價值。 / To fulfill the natural human needs of selenium (Se), I further improved the agronomic biofortification of rice (Oryza sativa) with less Se fertilizers and comprehensively evaluated Se bioaccessibility and bioavailability in the Se-enriched rice. Se-enriched rice grains were prepared by foliar application of selenite after rice heading. As compared with control, low amount of sodium selenite (10.5 g Se/ha) significantly increased Se content in rice grains by up to 51 times; at the same time, rice yield was also up-regulated by up to 1.24 times. Furthermore, by Se speciation analysis, in vitro gastrointestinal digestion and antioxidant assays, the Se-enriched rice grains contain readily absorbable selenomethionine as the major Se species and have significantly higher antioxidant bioactivities. This Se-enriched rice has enormous potential for Se supplementation in humans. / Se shows both beneficial and toxic effects on plant growth. Treatments with lower concentrations of sodium selenite enhanced the growth of rice seedlings, whereas higher concentrations of sodium selenite repressed seedling growth. To reveal the regulatory mechanisms underlying these effects, a comparative proteomics study combining 2-dimensional gel electrophoresis (2-DE) and matrix assisted laser desorption ionization (MALDI)-tandem time of flight (TOF/TOF) mass spectrometry (MS) were performed. By comparison of gel images between Se treatments and control, 66 and 97 differentially expressed proteins were identified in shoot and root, respectively. Gene Ontology and Clustering analysis reveal primary metabolism, photosynthesis and redox homeostasis are the most highly affected biological processes by Se treatments. Lower Se treatments (2 and 6 mg/L sodium selenite) activated antioxidative system, enhanced photosynthesis and primary metabolism. However, higher Se treatment (10 mg/L sodium selenite) damaged photosynthesis apparatus, inhibited photosynthesis and primary metabolism. This study provided novel insights into Se response in rice at the proteome level, which are expected to be highly useful for dissecting the Se response pathways in higher plants and for producing of Se enriched rice cultivars in the future. / To better understand the regulatory mechanism under Se accumulation in rice grains, a comparative proteomics study using 2-DE coupled MALDI-TOF/TOF MS and 1-dimensional gel electrophoresis (1-DE) coupled liquid chromatography (LC) - Fourier transform-ion cyclotron resonance (FT-ICR) MS were carried out. By comparison of Se treatments and control, 62 and 250 differentially expressed proteins were identified by 2-DE/MALDI-TOF/TOF MS and 1-DE/LC-FT-ICR MS, respectively. By gene functional classification, proteins involved in the processes of sulfur metabolism, carbon metabolism, cell redox regulation, and seed nutritional storage were the most highly affected by Se accumulation in mature rice grains. In addition, there were 6 proteins identified to contain fragments of selenoamino acid modification, which was the first identification of selenoproteins in higher plants. / Genetic engineering of Se-enriched rice will have important implications for human health in Se deficient regions. Therefore, to acquire appropriate rice genes as candidates for bioengineering of Se-enriched rice cultivars, I overexpressed three of the rice O-Acetylserine(thiol)lyase (OASTL) genes encoding cytosolic OASTLA, plastic OASTLB and mitochondrial OASTLC, individually in the model plant Arabidopsis (Arabidopsis thaliana) to characterize the effects of Se accumulation in transgenic plants. The results showed that compared to the wild type plants, overexpression of all these genes significantly increased Se content in transgenic plants under treatments of different selenite concentrations. By real-time RT-PCR analysis, I found that the whole metabolic pathway of selenite assimilation was activated by overexpressing rice OASTL genes, especially the genes involved in cysteine and methionine biosynthesis, which may give rise to more Se accumulation in the transgenics. In addition, overexpression of rice OASTL genes also activated the antioxidative system by activating the glutathione reductase, which may be responsible for the increased biomass of Se-enriched transgenic plants. Therefore, OASTL genes could be good candidate for the future genetic engineering of Se-enriched rice. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Wang, Yudong. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 149-159). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / Declaration of Originality --- p.i / Acknowledgments --- p.ii / Abstract --- p.iii / 摘要 (Abstract in Chinese) --- p.v / List of Abbreviations --- p.vii / List of Figures --- p.x / List of Tables --- p.xi / Chapter Chapter 1: --- Introduction --- p.1 / Chapter 1.1. --- Implications of Se for human health and its metabolism in plants --- p.1 / Chapter 1.2. --- Systemic study of Se metabolism and regulation in rice --- p.3 / Chapter 1.3. --- Candidate genes for genetic engineering of Se-enriched rice --- p.4 / Chapter 1.4. --- Objectives of this project --- p.7 / Chapter Chapter 2: --- Generation of selenium-enriched rice with enhanced grain yield, selenium content and bioavailability through fertilization with selenite --- p.9 / Chapter 2.1. --- Introduction --- p.9 / Chapter 2.2. --- Materials and methods --- p.12 / Chapter 2.2.1. --- Reagents --- p.12 / Chapter 2.2.2. --- Plant materials and growth conditions --- p.12 / Chapter 2.2.3. --- Se speciation analysis --- p.14 / Chapter 2.2.4. --- Antioxidant assays --- p.16 / Chapter 2.2.5. --- Data analysis --- p.18 / Chapter 2.3. --- Results and discussion --- p.18 / Chapter 2.3.1. --- Effects of fertilization of selenite on the growth and Se content of rice seedlings --- p.18 / Chapter 2.3.2. --- Effects of fertilization of selenite on the antioxidant activity of rice seedlings --- p.19 / Chapter 2.3.3. --- Effect of fertilization of selenite on Se content in rice products --- p.20 / Chapter 2.3.4. --- Effect of fertilization of selenite on rice yield --- p.21 / Chapter 2.3.5. --- Analysis of Se bioaccessibility in Se-enriched rice grains --- p.22 / Chapter 2.3.6. --- Analysis of Se bioavailability in Se-enriched rice grains --- p.23 / Chapter 2.4. --- Conclusion --- p.24 / Chapter Chapter 3: --- Proteomics analysis reveals multiple regulatory mechanisms in response to selenium in rice --- p.37 / Chapter 3.1. --- Introduction --- p.37 / Chapter 3.2. --- Materials and methods --- p.39 / Chapter 3.2.1. --- Plant materials and growth conditions --- p.39 / Chapter 3.2.2. --- Physiological measurements --- p.40 / Chapter 3.2.3. --- Total protein extraction --- p.40 / Chapter 3.2.4. --- 2-DE separation, gel staining and image analysis --- p.40 / Chapter 3.2.5. --- Trypsin digestion, mass spectrometry and protein identification --- p.41 / Chapter 3.2.6. --- Protein functional classification and hierarchical cluster analysis --- p.43 / Chapter 3.2.7. --- Statistical analysis --- p.43 / Chapter 3.3. --- Results and discussion --- p.43 / Chapter 3.3.1. --- Effects of Se on rice seedlings --- p.43 / Chapter 3.3.2. --- Effects of Se on shoot and root proteomes of rice seedlings --- p.44 / Chapter 3.3.3. --- Gene ontology analysis of Se-responsive proteins --- p.46 / Chapter 3.3.4. --- Clustering analysis revealed the dynamics of functional protein groups under Se treatment --- p.47 / Chapter 3.3.5. --- Se treatment induced redox and stress related proteins --- p.48 / Chapter 3.3.6. --- Se-responsive proteins preferentially associated with primary metabolism and photosynthesis --- p.50 / Chapter 3.3.7. --- Post translational modifications involved in plant Se-response --- p.52 / Chapter 3.4. --- Conclusion --- p.53 / Chapter Chapter 4: --- Comparative proteomics analysis of selenium responses in selenium-enriched rice grains --- p.79 / Chapter 4.1. --- Introduction --- p.79 / Chapter 4.2. --- Materials and methods --- p.82 / Chapter 4.2.1. --- Plant materials and growth conditions --- p.82 / Chapter 4.2.2. --- Total protein extraction --- p.83 / Chapter 4.2.3. --- 2-DE separation, gel staining and image analysis --- p.83 / Chapter 4.2.4. --- Trypsin digestion, mass spectrometry and protein identification --- p.84 / Chapter 4.2.5. --- Preparative SDS-PAGE separation and trypsin digestion --- p.85 / Chapter 4.2.6. --- NanoLC-FT-ICR MS and protein identification --- p.86 / Chapter 4.2.7. --- Label-free quantitation of identified proteins --- p.87 / Chapter 4.2.8. --- Functional classification of Se-responsive proteins --- p.87 / Chapter 4.3. --- Results and discussion --- p.88 / Chapter 4.3.1. --- Effects of foliar application of selenite in rice grain production --- p.88 / Chapter 4.3.2. --- 2-DE/MALDI-TOF/TOF MS analysis of Se-enriched rice grains --- p.89 / Chapter 4.3.3. --- Label-free 1-DE/LC-FT-ICR-MS analysis of Se-enriched rice grains --- p.89 / Chapter 4.3.4. --- Gene ontology analysis of rice grain proteome and Se-responsive proteins --- p.90 / Chapter 4.3.5. --- Sulfur metabolism were highly repressed in Se-enriched rice --- p.91 / Chapter 4.3.6. --- Proteins involved in redox regulation were induced in Se-enriched rice --- p.92 / Chapter 4.3.7. --- Se-responsive proteins are preferentially associated with carbon metabolism --- p.93 / Chapter 4.3.8. --- Proteins involved in seed nutritional storage --- p.95 / Chapter 4.4. --- Conclusion --- p.97 / Chapter Chapter 5: --- Overexpressing rice O-Acetylserine(thiol)lyase Genes Enhances Selenium Accumulation in Arabidopsis --- p.123 / Chapter 5.1. --- Introduction --- p.123 / Chapter 5.2. --- Materials and methods --- p.126 / Chapter 5.2.1. --- DNA constructs --- p.126 / Chapter 5.2.2. --- Transient gene expression and subcellular localization --- p.127 / Chapter 5.2.3. --- Arabidopsis plant transformation and growth --- p.127 / Chapter 5.2.4. --- Selenium treatment and physiological measurements --- p.127 / Chapter 5.2.5. --- Total Se content assay --- p.127 / Chapter 5.2.6. --- RT-PCR analysis --- p.128 / Chapter 5.3. --- Results and discussion --- p.128 / Chapter 5.3.1. --- Phenotypes of OASTL-transgenic Arabidopsis --- p.128 / Chapter 5.3.2. --- Se accumulated in OASTL-transgenic Arabidopsis under Se treatment --- p.129 / Chapter 5.3.3. --- Overexpression of rice OASTL genes activated Se assimilation pathways --- p.130 / Chapter 5.3.4. --- ATSAT genes were highly expressed in OASTL-transgenics --- p.132 / Chapter 5.3.5. --- Overexpression of rice OASTL genes activated the antioxidative system --- p.133 / Chapter 5.3.6. --- Methionine synthesis was enhanced in OASTL-transgenics --- p.134 / Chapter 5.4. --- Conclusion --- p.134 / Chapter Chapter 6: --- Conclusion --- p.146 / References --- p.149 / Chapter Appendix I: --- Publications --- p.160
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Treatment of adult obesityGarcia-Lago, Erica January 2013 (has links)
As rates of obesity have increased this disease has become a common problem that physicians are faced with treating. This paper aims to review the different options for patients and determine the best treatments for obesity.
Modalities that are considered include dietary treatment, exercise, pharmacologic treatment, and weight loss surgery. This study compares reduced calorie diets, low fat diets, low glycemic index/load diets, the Mediterranean diet, and low carbohydrate diets. The validity of exercise as an effective prescription for
obesity is evaluated and debunked. Pharmacologic treatments that are contrasted include those drug therapies that are currently approved by the United States Food and Drug Administration for the long-term treatment of obesity.
Those are orlistat, lorcaserin and phentermine/topiramate. The surgical treatments reviewed include vertical banded gastroplasty, adjustable gastric banding, Roux-en Y gastric bypass, biliopancreatic diversion, and biliopancreatic diversion with duodenal switch. After a comprehensive review of the literature the conclusion reached was that treatment for obesity should begin with the least invasive options and those that have the least potential for harm. That is, diet should be a first course of action. Among diets a Mediterranean diet or another culturally adapted low glycemic index/load diet is best. However, more studies are needed to determine how to translate the diets for different cultures and individual tastes. When diets are unable to produce enough weight loss, pharmacologic treatments are considered. Among them, lorcaserin and
phentermine/topiramate do not have enough long-term studies to warrant a strong recommendation as of the publishing of this paper. The only other option available, orlistat, comes with many uncomfortable gastrointestinal side effects, so it is also not an ideal option. In addition, orlistat does not produce the amount
of weight loss that is seen with surgical procedures. Patients and physicians considering surgical treatment for obesity will find that the best option is laparoscopic adjustable gastric banding.
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Effects of dietary energy level and tanniniferous Acacia Karroo leaf meal level of supplementation at finisher stage on performance and carcass characteristics of ross 308 broiler chickens.Nakalebe, Papali Mary 01 October 2010 (has links)
Thesis (M.Sc) (Agriculture) --University of Limpopo,2009. / The study was conducted to determine the effect of dietary energy level and tanniniferous Acacia karroo leaf meal level of supplementation at finisher stage on performance and carcass characteristics of male and female Ross 308 broiler chickens. Three hundred and sixty, 21-day old male and female broiler chickens were assigned to twelve treatments with three replications of ten birds in a 2 (sex) x 3 (dietary energy level) x 3 (tanniniferous Acacia karroo leaf meal level) factorial, complete randomized design. Supplementation with Acacia karroo leaf meal had no effect on diet intake, digestibility and live weight of broiler chickens. However, supplementation with 9 and 12 g of Acacia karroo leaf meal per kg DM feed reduced fat pad weights in male broiler chickens by 26 and 29 percentage points, respectively. Similarly, supplementation with 9 and 12 g of Acacia karroo leaf meal per kg DM feed reduced fat pad weights in female chickens by 26 percentage points. These reductions were achieved without any significant reduction in feed intake and digestibility. However, the physiological explanation for this effect is not clear and it, thus, merits further investigation. / National Research Foundation.
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Dietary habits and prevalence of obesity among type 2 diabetes patients seen at Scott Hospital, Morija, LesothoAdebayo, Francis Opeyemi 29 May 2010 (has links)
Thesis (M Med (Family Medicine))--University of Limpopo (Medunsa Campus), 2010. / Introduction: Diabetes Mellitus still remains an important non- communicable disease globally. The burden of the disease continues to rise even in the sub-Saharan Africa.
Aim: The study aimed to assess and describe the dietary practices and the prevalence of obesity among type 2 diabetic patients seen at Scott Hospital.
Methods: A descriptive cross- sectional study was conducted among type 2 diabetic patients at Scott Hospital, Morija, Lesotho. A simple random sample of 50 participants was selected and each completed an interviewer administered questionnaire. The administration of the questionnaire was done by the researcher and a research assistant. Socio- demographic characteristics of the participants were obtained, anthropometric measurements were height and weight of each participant with subsequent determination of the BMI. Dietary intake was assessed using questions from a modified food frequency questionnaire of 16 food groups that reflect the commonest food items available.
Results: The results showed that 86% (43/50) of the participants were females and 14% (7/50) were males with a female: male ratio of 6:1.
The majority (72%) were above age 50 years and with regards to educational status, 62% had primary school education as the highest level attained. Four percent (4%) had no formal education. Fifty percent (50%) of the participants were unemployed.
The mean weight of the participants was 84.22 ± 13.51 kg and the mean height was 157.76 ± 6.10 cm. The mean BMI was 33.97 ± 4.99 kg/m².
Seventy-eight percent (38/50) of the participants were obese, and 14% (7/50) of the participants who were females, were morbidly obese with BMIs ≥ 40kg/m². The prevalence of obesity when stratified by gender showed that 57% (4/7) of male participants and 81% (35/43) of female participants were obese.
According to the dietary assessments, food groups with the highest reported consumption per unit per month were; maize meals, breakfast-cereals and bread respectively.
Conclusion: The study showed a predominantly female and elderly population of type 2 diabetics at Scott Hospital, Morija, Lesotho.
The prevalence of obesity was high (78%) among the participants and this further supports the view that obesity is a major risk factor for type 2 diabetes.
Reported dietary intake showed a higher consumption of carbohydrates and a very low intake of dietary fibre as represented by legumes.
Keywords: Type 2 diabetes mellitus, dietary habits and obesity.
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Using dietary strategies to explore mechanisms of hepatic toxicity caused by 3,3',4,4',5-Pentachlorobiphenyl (PCB 126) in an animal modelLai, Ian Kwan-Tai 01 July 2011 (has links)
This doctoral dissertation work strived to contribute to the ever expanding knowledge about the mechanisms of polychlorinated biphenyl (PCB) toxicity using dietary strategies. PCBs are a family of persistent environmental pollutants with a wide range of toxicity. The toxicity of PCBs is largely dependent on the congener's chlorination pattern. Of particular interest to this work was 3,3',4,4',5-pentachlorobiphenyl (PCB 126), the most potent of the dioxin-like PCB congeners. I hypothesized that in vivo PCB 126 toxicity will be ameliorated by dietary selenium supplementation, lowered dietary copper, and dietary N-acetylcysteine (NAC) supplementation.
Dioxin-like PCBs are known for diminishing hepatic selenium and selenium-dependent glutathione peroxidase (SeGPx), an antioxidant enzyme. In the first study, PCB 126 caused a dose-dependent decrease in hepatic selenium and SeGPx. Supplemental dietary selenium significantly increased hepatic selenium and SeGPx, and decreased incidence of apoptosis in these rats. The results from this study support that selenium plays a protective role, and differences in liver injuries of these rats may be reflected in their selenium status.
The dose-dependent increase in hepatic copper caused by PCB 126 was a subject of interest and concern in the next study. Lowering dietary copper levels without negatively affecting the function of the essential antioxidant enzyme copper zinc superoxide dismutase did not result in reduction of PCB 126-induced toxicity. Copper metabolism was unlikely a main target of PCB 126 toxicity as increasing dietary copper did not significantly increase hepatic copper levels. Hepatic copper is highly regulated and likely does not play a significant role in PCB 126-induced toxicity.
The effectiveness of NAC on restoring glutathione status and reducing PCB 126 toxicity was tested in the final study. While NAC did not restore glutathione status, NAC supplemented rats had significantly reduced severity of PCB 126-induced liver status. The results of this study are consistent with the theory that NAC has a glutathione-independent effect in improving mitochondrial energy metabolism. It also suggests that PCB 126-induced mitochondrial metabolic disruption of the liver is of greater concern than oxidative stress.
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