Browsing by Subject "Cholesterol"

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    Anaemia, haemoglobin level and cause-specific mortality in people with and without diabetes
    (Public Library of Science, 2012) Kengne, Andre Pascal; Czernichow, Sébastien; Hamer, Mark; Batty, G David; Stamatakis, Emmanuel
    BACKGROUND: Both anaemia and cardiovascular disease (CVD) are common in people with diabetes. While individually both characteristics are known to raise mortality risk, their combined influence has yet to be quantified. In this pooling project, we examined the combined impact of baseline haemoglobin levels and existing CVD on all-cause and CVD mortality in people with diabetes. We draw comparison of these effects with those apparent in diabetes-free individuals. Methods/Principal FINDINGS: A combined analyses of 7 UK population-based cohorts resulted in 26,480 study members. There were 946 participants with physician-diagnosed diabetes, 2227 with anaemia [haemoglobin<13 g/dl (men) or <12 (women)], 2592 with existing CVD (stroke, ischaemic heart disease), and 21,396 with none of the conditions. Across diabetes and anaemia subgroups, and using diabetes-free, non-anaemic participants as the referent group, the adjusted hazard ratios (HR) were 1.46 (95% CI: 1.30-1.63) for anaemia, 1.67 (1.45-1.92) for diabetes, and 2.10 (1.55-2.85) for diabetes and anaemia combined. Across combined diabetes, anaemia and CVD subgroups, and compared with non-anaemic, diabetes-free and CVD-free participants, HR (95% CI) for all-cause mortality were 1.49 (1.32-1.69) anaemia, 1.60 (1.46-1.76) for existing CVD, and 1.66 (1.39-1.97) for diabetes alone. Equivalents were 2.13 (1.48-3.07) for anaemia and diabetes, 2.68 (2.14-3.36) for diabetes and existing CVD, and 3.25 (1.88-5.62) for the three combined. Patterns were similar for CVD mortality. Conclusions/Significance Individually, anaemia and CVD confer similar mortality risks in people with diabetes, and are excessively fatal in combination. Screening for anaemia would identify vulnerable diabetic patients whose outcomes can potentially be improved.
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    Anti-retroviral therapy increases the prevalence of dyslipidemia in South African HIV-infected patients
    (Public Library of Science, 2016) Dave, Joel A; Levitt, Naomi S; Ross, Ian L; Lacerda, Miguel; Maartens, Gary; Blom, Dirk
    Purpose Data on the prevalence of dyslipidaemia and associated risk factors in HIV-infected patients from sub-Saharan Africa is sparse. We performed a cross-sectional analysis in a cohort of HIV-infected South African adults. METHODS: We studied HIV-infected patients who were either antiretroviral therapy (ART)-naive or receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-based or protease inhibitor (PI)-based ART. Evaluation included fasting lipograms, oral glucose tolerance tests and clinical anthropometry. Dyslipidemia was defined using the NCEP ATPIII guidelines. RESULTS: The median age of the participants was 34 years (range 19-68 years) and 78% were women. The prevalence of dyslipidemia in 406 ART-naive and 551 participants on ART was 90.0% and 85%, respectively. Low HDL-cholesterol (HDLC) was the most common abnormality [290/406 (71%) ART-naïve and 237/551 (43%) ART- participants]. Participants on ART had higher triglycerides (TG), total cholesterol (TC), LDL-cholesterol (LDLC) and HDLC than the ART-naïve group. Severe dyslipidaemia, (LDLC> 4.9 mmol/L or TG >5.0 mmol/L) was present in <5% of participants. In multivariate analyses there were complex associations between age, gender, type and duration of ART and body composition and LDLC, HDLC and TG, which differed between ART-naïve and ART-participants. CONCLUSION: Participants on ART had higher TG, TC, LDLC and HDLC than those who were ART-naïve but severe lipid abnormalities requiring evaluation and treatment were uncommon.
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    Association of serum leptin and adiponectin with anthropomorphic indices of obesity, blood lipids and insulin resistance in a Sub-Saharan African population
    (2016) Ayina, Clarisse Noël A; Noubiap, Jean Jacques N; Etoundi Ngoa, Laurent Serge; Boudou, Philippe; Gautier, Jean François; Mengnjo, Michel Karngong; Mbanya, Jean Claude; Sobngwi, Eugène
    Abstract Background There is little data on the metabolic effects of adipokines in sub-Saharan African populations. This study aimed to explore the potential relationship of leptin and adiponectin, with obesity, plasma lipids and insulin resistance in a Cameroonian population. Methods We enrolled 167 men and 309 women aged ≥18 years from the general population in Cameroon. Data were collected on waist circumference (WC), body mass index (BMI), waist-to-hip ratio (WHR), body fat (BF%), fasting blood glucose, plasma lipids, adiponectin, leptin, insulin and homeostasis model for assessment of insulin resistance (HOMA-IR). Pearson’s correlation and multiple stepwise linear regression analyses were used to determine correlates of leptin and adiponectin serum levels. Results The prevalence of obesity was higher in women compared to men (p < 0.0001), and Central obesity which is more prevalent particularly in women (WC = 42.4 %, WHR = 42.3 %), is almost for 90 % comparable to %BF (42.7 %). Adiponectin negatively with BMI (r = −0.294, p < 0.0001), WC (r = −0.294, p < 0.0001), %BF (r = −0.122, p = 0.028), WHR (r = −0.143, p = 0.009), triglycerides (r = −0.141, p = 0.011), HOMA-IR (r = −0.145, p = 0.027) and insulin (r = −0.130, p = 0.048). Leptin positively correlated with BMI (r = 0.628), WC (r = 0.530), BF% (r = 0.720), (all p < 0.0001); with DBP (r = 0.112, p = 0.043), total cholesterol (r = 0.324, p < 0.0001), LDL-cholesterol (r = 0.298, p < 0.0001), insulin (r = 0.320, p < 0.001 and HOMA-IR (r = 0.272, p < 0.0001). In multiple stepwise regression analysis, adiponectin was negatively associated with WC (β = −0.38, p = 0.001) and BF% (β = 0.33, p < 0.0001), while leptin was positively associated with BF% (β = 0.60, p < 0.0001), total cholesterol (β = 0.11, p = 0.02) and HOMA-IR (β = 0.11, p = 0.02). When controlled for gender, HOMA-IR was found significantly associated to adiponectin (β = 0.13, p = 0.046), but not BF%, while the association previously found between leptin and HOMA-IR disappeared; BMI and WC were significantly associated with leptin (β = 0.18, p = 0.04 & β = 0.19, p = 0.02 respectively). Conclusion This study, which includes a population who was not receiving potentially confounding medications, confirms the associations previously observed of adiponectin with reduced adiposity especially central adiposity and improved insulin sensitivity. Confirmatory associations were also observed between leptin and obesity, blood lipids and insulin resistance for the first time in an African population. Gender was significant covariate interacting with insulin sensitivity/insulin resistance and obesity indexes associations in this population.
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    Chylomicron remnant metabolism in familial dyslipidemias studied with a remnant-like emulsion breath test
    (2001)
    We have developed a stable isotope breath test for the assessment of chylomicron remnant metabolism and report the results from the breath test in human subjects selected for disorders of chylomicron or remnant metabolism. In type I hyperlipemia, the phenotype is extreme hypertriglyceridemia due to a lack of lipoprotein lipase activity, which causes the failure of remnant formation. The type III dyslipidemia phenotype is caused by the inefficient removal of chylomicron remnants from plasma, generally because of homozygosity for apolipoprotein E2 alleles. The breath test was predicted to be abnormal in type III hyperlipemia, whereas a priori in type I hyperlipemia defective remnant clearance was not anticipated. Subjects were injected with lipid emulsions prepared with a composition similar to normal chylomicron remnants. The emulsions contained cholesteryl ester incorporating the stable nonradioactive isotope
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    Comparative assessment of absolute cardiovascular disease risk characterization from non-laboratory-based risk assessment in South African populations
    (BioMed Central, 2013-07-24) Gaziano, Thomas A; Pandya, Ankur; Steyn, Krisela; Levitt, Naomi; Mollentze, Willie; Joubert, Gina; Walsh, Corinna M; Motala, Ayesha A; Kruger, Annamarie; Schutte, Aletta E; Naidoo, Datshana P; Prakaschandra, Dorcas R; Laubscher, Ria
    Background: All rigorous primary cardiovascular disease (CVD) prevention guidelines recommend absolute CVD risk scores to identify high- and low-risk patients, but laboratory testing can be impractical in low- and middle-income countries. The purpose of this study was to compare the ranking performance of a simple, non-laboratory-based risk score to laboratory-based scores in various South African populations. Methods: We calculated and compared 10-year CVD (or coronary heart disease (CHD)) risk for 14,772 adults from thirteen cross-sectional South African populations (data collected from 1987 to 2009). Risk characterization performance for the non-laboratory-based score was assessed by comparing rankings of risk with six laboratory-based scores (three versions of Framingham risk, SCORE for high- and low-risk countries, and CUORE) using Spearman rank correlation and percent of population equivalently characterized as ‘high’ or ‘low’ risk. Total 10-year non-laboratory-based risk of CVD death was also calculated for a representative cross-section from the 1998 South African Demographic Health Survey (DHS, n = 9,379) to estimate the national burden of CVD mortality risk. Results: Spearman correlation coefficients for the non-laboratory-based score with the laboratory-based scores ranged from 0.88 to 0.986. Using conventional thresholds for CVD risk (10% to 20% 10-year CVD risk), 90% to 92% of men and 94% to 97% of women were equivalently characterized as ‘high’ or ‘low’ risk using the non-laboratory-based and Framingham (2008) CVD risk score. These results were robust across the six risk scores evaluated and the thirteen cross-sectional datasets, with few exceptions (lower agreement between the non-laboratory-based and Framingham (1991) CHD risk scores). Approximately 18% of adults in the DHS population were characterized as ‘high CVD risk’ (10-year CVD death risk >20%) using the non-laboratory-based score. Conclusions: We found a high level of correlation between a simple, non-laboratory-based CVD risk score and commonly-used laboratory-based risk scores. The burden of CVD mortality risk was high for men and women in South Africa. The policy and clinical implications are that fast, low-cost screening tools can lead to similar risk assessment results compared to time- and resource-intensive approaches. Until setting-specific cohort studies can derive and validate country-specific risk scores, non-laboratory-based CVD risk assessment could be an effective and efficient primary CVD screening approach in South Africa.
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    A high burden of hypertension in the urban black population of Cape Town: the cardiovascular risk in Black South Africans (CRIBSA) study
    (Public Library of Science, 2013) Peer, Nasheeta; Steyn, Krisela; Lombard, Carl; Gwebushe, Nomonde; Levitt, Naomi
    Objective To determine the prevalence, associations and management of hypertension in the 25-74-year-old urban black population of Cape Town and examine the change between 1990 and 2008/09 in 25-64-year-olds. METHODS: In 2008/09, a representative cross-sectional sample, stratified for age and sex, was randomly selected from the same townships sampled in 1990. Cardiovascular disease risk factors were determined by administered questionnaires, clinical measurements and fasting biochemical analyses. Logistic regression models evaluated the associations with hypertension. RESULTS: There were 1099 participants, 392 men and 707 women (response rate 86%) in 2008/09. Age-standardised hypertension prevalence was 38.9% (95% confidence interval (CI): 35.6-42.3) with similar rates in men and women. Among 25-64-year-olds, hypertension prevalence was significantly higher in 2008/09 (35.6%, 95% CI: 32.3-39.0) than in 1990 (21.6%, 95% CI: 18.6-24.9). In 2008/09, hypertension odds increased with older age, family history of hypertension, higher body mass index, problematic alcohol intake, physical inactivity and urbanisation. Among hypertensive participants, significantly more women than men were detected (69.5% vs. 32.7%), treated (55.7% vs. 21.9%) and controlled (32.4% vs. 10.4%) in 2008/09. There were minimal changes from 1990 except for improved control in 25-64-year-old women (1990∶14.1% vs. 2008/09∶31.5%). CONCLUSIONS: The high and rising hypertension burden in this population, its association with modifiable risk factors and the sub-optimal care provided highlight the urgent need to prioritise hypertension management. Innovative solutions with efficient and cost-effective healthcare delivery as well as population-based strategies are required.
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    Lipoprotein lipase activity is decreased in a large cohort of patients with coronary artery disease and is associated with changes in lipids and lipoproteins
    (1999) Hockman, Dorit; Henderson,Howard E; Hockman, Dorit; Kastelein, John P; Zwinderman, Aeilko H; Gagné, Eric; Jukema, J Wouter; Reymer, Paul W A; Groenemeyer, Björn E; Hockman, Dorit; Lie, Kong I; Bruschke, Albert V G; Hayden, Michael R; Jansen, Hans
    Lipoprotein lipase (LPL) is crucial in the hydrolysis of triglycerides (TG) in TG-rich lipoproteins in the formation of HDL particles. As both these lipoproteins play an important role in the pathogenesis of atherosclerotic vascular disease, we sought to assess the relationship between post-heparin LPL (PH-LPL) activity and lipids and lipoproteins in a large, well-defined cohort of Dutch males with coronary artery disease (CAD). These subjects were drawn from the REGRESS study, totaled 730 in number and were evaluated against 75 healthy, normolipidemic male controls. Fasting mean PH-LPL activity in the CAD subjects was 108 46 mU/ml, compared to 138 44 mU/ml in controls (P < 0.0001). When these patients were divided into activity quartiles, those in the lowest versus the highest quartile had higher levels of TG (P < 0.001), VLDLc and VLDL-TG (P = 0.001). Conversely, levels of TC, LDL, and HDLc were lower in these patients (P = 0.001, P = 0.02, and P = 0.001, respectively). Also, in this cohort PH-LPL relationships with lipids and lipoproteins were not altered by apoE genotypes. The frequency of common mutations in the LPL gene associated with partial LPL deficiency (N291S and D9N carriers) in the lowest quartile for LPL activity was more than double the frequency in the highest quartile (12.0% vs. 5.0%; P = 0.006). By contrast, the frequency of the S447X LPL variant rose from 11.5% in the lowest to 18.3% (P = 0.006) in the highest quartile. This study, in a large cohort of CAD patients, has shown that PH-LPL activity is decreased (22%; P = 0.001) when compared to controls; that the D9N and N291S, and S447X LPL variants are genetic determinants, respectively, in CAD patients of low and high LPL PH-LPL activities; and that PH-LPL activity is strongly associated with changes in lipids and lipoproteins.
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    Low carbohydrate versus isoenergetic balanced diets for reducing weight and cardiovascular risk: a systematic review and meta-analysis
    (Public Library of Science, 2014) Naude, Celeste E; Schoonees, Anel; Senekal, Marjanne; Young, Taryn; Garner, Paul; Volmink, Jimmy
    BACKGROUND: Some popular weight loss diets restricting carbohydrates (CHO) claim to be more effective, and have additional health benefits in preventing cardiovascular disease compared to balanced weight loss diets. Methods and FINDINGS: We compared the effects of low CHO and isoenergetic balanced weight loss diets in overweight and obese adults assessed in randomised controlled trials (minimum follow-up of 12 weeks), and summarised the effects on weight, as well as cardiovascular and diabetes risk. Dietary criteria were derived from existing macronutrient recommendations. We searched Medline, EMBASE and CENTRAL (19 March 2014). Analysis was stratified by outcomes at 3-6 months and 1-2 years, and participants with diabetes were analysed separately. We evaluated dietary adherence and used GRADE to assess the quality of evidence. We calculated mean differences (MD) and performed random-effects meta-analysis. Nineteen trials were included (n = 3209); 3 had adequate allocation concealment. In non-diabetic participants, our analysis showed little or no difference in mean weight loss in the two groups at 3-6 months (MD 0.74 kg, 95%CI −1.49 to 0.01 kg; I 2  = 53%; n = 1745, 14 trials; moderate quality evidence) and 1-2 years (MD 0.48 kg, 95%CI −1.44 kg to 0.49 kg; I 2  = 12%; n = 1025; 7 trials, moderate quality evidence). Furthermore, little or no difference was detected at 3-6 months and 1-2 years for blood pressure, LDL, HDL and total cholesterol, triglycerides and fasting blood glucose (>914 participants). In diabetic participants, findings showed a similar pattern. CONCLUSIONS: Trials show weight loss in the short-term irrespective of whether the diet is low CHO or balanced. There is probably little or no difference in weight loss and changes in cardiovascular risk factors up to two years of follow-up when overweight and obese adults, with or without type 2 diabetes, are randomised to low CHO diets and isoenergetic balanced weight loss diets.
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    Metabolic syndrome and fatal outcomes in the post-stroke event: a 5-year cohort study in Cameroon
    (Public Library of Science, 2013) Balti, Eric Vounsia; Kengne, André Pascal; Fokouo, Jean Valentin Fogha; Nouthé, Brice Enid; Sobngwi, Eugene
    Background and Purpose: Determinants of post-acute stroke outcomes in Africa have been less investigated. We assessed the association of metabolic syndrome (MetS) and insulin resistance with post-stroke mortality in patients with first-ever-in-lifetime stroke in the capital city of Cameroon (sub-Saharan Africa). METHODS: Patients with an acute first-stroke event (n = 57) were recruited between May and October 2006, and followed for 5 years for mortality outcome. MetS definition was based on the Joint Interim Statement 2009, insulin sensitivity/resistance assessed via glucose-to-insulin ratio, quantitative insulin sensitivity check index and homeostatic model assessment. RESULTS: Overall, 24 (42%) patients deceased during follow-up. The prevalence of MetS was higher in patients who died after 28 days, 1 year and 5 years from any cause or cardiovascular-related causes (all p≤ 0.040). MetS was associated with an increased overall mortality both after 1 year (39% vs. 9%) and 5 years of follow-up (55% vs. 26%, p  = 0.022). Similarly, fatal events due to cardiovascular-related conditions were more frequent in the presence of MetS both 1 year (37% vs. 9%) and 5 years after the first-ever-in-lifetime stroke (43% vs. 13%, p  = 0.017). Unlike biochemical measures of insulin sensitivity and resistance (non-significant), in age- and sex-adjusted Cox models, MetS was associated with hazard ratio (95% CI) of 2.63 (1.03-6.73) and 3.54 (1.00-12.56) respectively for all-cause and cardiovascular mortality 5 years after stroke onset. CONCLUSION: The Joint Interim Statement 2009 definition of MetS may aid the identification of a subgroup of black African stroke patients who may benefit from intensification of risk factor management.
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    Osteoprotegerin in relation to insulin resistance and blood lipids in sub-Saharan African women with and without abdominal obesity
    (2015) Ayina Ayina, Clarisse Noël; Sobngwi, Eugène; Essouma, Mickael; Noubiap, Jean Jacques N; Boudou, Philippe; Etoundi Ngoa, Laurent Serge; Gautier, Jean François
    BackgroundOsteoprotegerin (OPG), a soluble member of the tumor necrosis factor receptor superfamily that inhibits bone resorption, has been suggested as a potential marker of cardiovascular risk. This study aimed to assess the relationship between insulin resistance, lipid profile and OPG levels in obese and non-obese sub-Saharan African women.MethodsSixty obese (44) and non-obese (16) volunteer women aged 18 to 40years were recruited in this cross-sectional study. Their clinical (age, height, weight, waist circumference, systolic and diastolic blood pressures) and biochemical parameters (fasting blood glucose, total cholesterol, high density lipoprotein-cholesterol (HDL-C)) were measured using standard methods. Insulin levels were measured using an electrochemiluminescence immunoassay, while OPG levels were measured using the ELISA technique. Low density lipoprotein-cholesterol (LDL-C), body mass index (BMI) and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) were calculated using standard methods. Abdominal obesity was defined as a waist circumference ≥ 80cm.ResultsOPG levels were higher in obese than in normal subjects, though the difference was not significant (p = 0.9). BMI, waist circumference, percent body fat and systolic blood pressure were significantly higher in obese than in non-obese subjects (p < 0.05). In these subjects, only age significantly correlated with OPG levels (r = 0.831, p = 0.003), while none of the anthropometric nor metabolic parameter did, even after adjustment for age. In obese subjects, OPG levels fairly correlated with HDL-C (r = 0.298, p = 0.058), and significantly correlated with HOMA-IR (r = −0.438, p = 0.018). After adjustment for age, OPG levels remained negatively correlated to HOMA-IR (r = −0.516, p = 0.020) and LDL-C (r = −0.535, p = 0.015) and positively correlated to HDL-C (r = 0.615, p = 0.004). In multiple linear regression analysis, age was a main determinant of OPG levels in non-obese (β = 0.647, p = 0.006) and obese (β = 0.356, p = 0.044) women. HDL-C was also associated to OPG levels in obese women (β = 0.535, p = 0.009).ConclusionThe positive correlation of OPG with HDL-C and HOMA-IR, and its negative correlation with LDL-C suggest that it may be a marker of insulin sensitivity/resistance and atherogenic risk in obese African women.
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    Rising diabetes prevalence among urban-dwelling black South Africans
    (Public Library of Science, 2012) Peer, Nasheeta; Steyn, Krisela; Lombard, Carl; Lambert, Estelle V; Vythilingum, Bavanisha; Levitt, Naomi S
    Objective: To examine the prevalence of and the association of psychosocial risk factors with diabetes in 25-74-year-old black Africans in Cape Town in 2008/09 and to compare the prevalence with a 1990 study. Research Design and METHODS: A randomly selected cross-sectional sample had oral glucose tolerance tests. The prevalence of diabetes (1998 WHO criteria), other cardiovascular risk factors and psychosocial measures, including sense of coherence (SOC), locus of control and adverse life events, were determined. The comparison of diabetes prevalence between this and a 1990 study used the 1985 WHO diabetes criteria. RESULTS: There were 1099 participants, 392 men and 707 women (response rate 86%). The age-standardised (SEGI) prevalence of diabetes was 13.1% (95% confidence interval (CI) 11.0-15.1), impaired glucose tolerance (IGT) 11.2% (9.2-13.1) and impaired fasting glycaemia 1.2% (0.6-1.9). Diabetes prevalence peaked in 65-74-year-olds (38.6%). Among diabetic participants, 57.9% were known and 38.6% treated. Using 1985 WHO criteria, age-standardised diabetes prevalence was higher by 53% in 2008/09 (12.2% (10.2-14.2)) compared to 1990 (8.0% (5.8-10.3)) and IGT by 67% (2008/09: 11.7% (9.8-13.7); 1990: 7.0% (4.9-9.1)). In women, older age (OR: 1.05, 95%CI: 1.03-1.08, p<0.001), diabetes family history (OR: 3.13, 95%CI: 1.92-5.12, p<0.001), higher BMI (OR: 1.44, 95%CI: 1.20-1.82, p = 0.001), better quality housing (OR: 2.08, 95%CI: 1.01-3.04, p = 0.047) and a lower SOC score (≤40) was positively associated with diabetes (OR: 2.57, 95%CI: 1.37-4.80, p = 0.003). Diabetes was not associated with the other psychosocial measures in women or with any psychosocial measure in men. Only older age (OR: 1.05, 95%CI: 1.02-1.08, p = 0.002) and higher BMI (OR: 1.10, 95%CI: 1.04-1.18, p = 0.003) were significantly associated with diabetes in men. CONCLUSIONS: The current high prevalence of diabetes in urban-dwelling South Africans, and the likelihood of further rises given the high rates of IGT and obesity, is concerning. Multi-facetted diabetes prevention strategies are essential to address this burden.
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    The role of scavenger receptor B1 in infection with Mycobacterium tuberculosis in a murine model
    (Public Library of Science, 2009) Schäfer, Georgia; Guler, Reto; Murray, Graeme; Brombacher, Frank; Brown, Gordon D
    BACKGROUND: The interaction between Mycobacterium tuberculosis (Mtb) and host cells is complex and far from being understood. The role of the different receptor(s) implicated in the recognition of Mtb in particular remains poorly defined, and those that have been found to have activity in vitro were subsequently shown to be redundant in vivo . Methods and FINDINGS: To identify novel receptors involved in the recognition of Mtb, we screened a macrophage cDNA library and identified scavenger receptor B class 1 (SR-B1) as a receptor for mycobacteria. SR-B1 has been well-described as a lipoprotein receptor which mediates both the selective uptake of cholesteryl esters and the efflux of cholesterol, and has also recently been implicated in the recognition of other pathogens. We show here that mycobacteria can bind directly to SR-B1 on transfected cells, and that this interaction could be inhibited in the presence of a specific antibody to SR-B1, serum or LDL. We define a variety of macrophage populations, including alveolar macrophages, that express this receptor, however, no differences in the recognition and response to mycobacteria were observed in macrophages isolated from SR-B1 −/− or wild type mice in vitro . Moreover, when wild type and SR-B1 −/− animals were infected with a low dose of Mtb (100 CFU/mouse) there were no alterations in survival, bacterial burdens, granuloma formation or cytokine production in the lung. However, significant reduction in the production of TNF, IFNγ, and IL10 were observed in SR-B1 −/− mice following infection with a high dose of Mtb (1000 CFU/mouse), which marginally affected the size of inflammatory foci but did not influence bacterial burdens. Deficiency of SR-B1 also had no effect on resistance to disease under conditions of varying dietary cholesterol. We did observe, however, that the presence of high levels of cholesterol in the diet significantly enhanced the bacterial burdens in the lung, but this was independent of SR-B1. CONCLUSION: SR-B1 is involved in mycobacterial recognition, but this receptor plays only a minor role in anti-mycobacterial immunity in vivo . Like many other receptors for these pathogens, the loss of SR-B1 can be functionally compensated for under normal conditions.
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    Simvastatin enhances protection against Listeria monocytogenes infection in mice by counteracting Listeria-induced phagosomal escape
    (Public Library of Science, 2013) Parihar, Suraj P; Guler, Reto; Lang, Dirk M; Suzuki, Harukazu; Marais, A David; Brombacher, Frank
    Statins are well-known cholesterol lowering drugs targeting HMG-CoA-reductase, reducing the risk of coronary disorders and hypercholesterolemia. Statins are also involved in immunomodulation, which might influence the outcome of bacterial infection. Hence, a possible effect of statin treatment on Listeriosis was explored in mice. Statin treatment prior to subsequent L. monocytogenes infection strikingly reduced bacterial burden in liver and spleen (up to 100-fold) and reduced histopathological lesions. Statin-treatment in infected macrophages resulted in increased IL-12p40 and TNF-α and up to 4-fold reduced bacterial burden within 6 hours post infection, demonstrating a direct effect of statins on limiting bacterial growth in macrophages. Bacterial uptake was normal investigated in microbeads and GFP-expressing Listeria experiments by confocal microscopy. However, intracellular membrane-bound cholesterol level was decreased, as analyzed by cholesterol-dependent filipin staining and cellular lipid extraction. Mevalonate supplementation restored statin-inhibited cholesterol biosynthesis and reverted bacterial growth in Listeria monocytogenes but not in listeriolysin O (LLO)-deficient Listeria . Together, these results suggest that statin pretreatment increases protection against L. monocytogenes infection by reducing membrane cholesterol in macrophages and thereby preventing effectivity of the cholesterol-dependent LLO-mediated phagosomal escape of bacteria.
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    The social patterning of risk factors for noncommunicable diseases in five countries: evidence from the modeling the epidemiologic transition study (METS)
    (2016) Stringhini, Silvia; Forrester, Terrence E; Plange-Rhule, Jacob; Lambert, Estelle V; Viswanathan, Bharathi; Riesen, Walter; Korte, Wolfgang; Levitt, Naomi; Tong, Liping; Dugas, Lara R; Shoham, David; Durazo-Arvizu, Ramon A; Luke, Amy; Bovet, Pascal
    Abstract Background Associations between socioeconomic status (SES) and risk factors for noncommunicable diseases (NCD-RFs) may differ in populations at different stages of the epidemiological transition. We assessed the social patterning of NCD-RFs in a study including populations with different levels of socioeconomic development. Methods Data on SES, smoking, physical activity, body mass index, blood pressure, cholesterol and glucose were available from the Modeling the Epidemiologic Transition Study (METS), with about 500 participants aged 25–45 in each of five sites (Ghana, South Africa, Jamaica, Seychelles, United States). Results The prevalence of NCD-RFs differed between these populations from five countries (e.g., lower prevalence of smoking, obesity and hypertension in rural Ghana) and by sex (e.g., higher prevalence of smoking and physical activity in men and of obesity in women in most populations). Smoking and physical activity were associated with low SES in most populations. The associations of SES with obesity, hypertension, cholesterol and elevated blood glucose differed by population, sex, and SES indicator. For example, the prevalence of elevated blood glucose tended to be associated with low education, but not with wealth, in Seychelles and USA. The association of SES with obesity and cholesterol was direct in some populations but inverse in others. Conclusions In conclusion, the distribution of NCD-RFs was socially patterned in these populations at different stages of the epidemiological transition, but associations between SES and NCD-RFs differed substantially according to risk factor, population, sex, and SES indicator. These findings emphasize the need to assess and integrate the social patterning of NCD-RFs in NCD prevention and control programs in LMICs.