39 research outputs found

    The Accumulation of People: Slavery and Capitalism in Southern Thought

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    The abolitionist movement in antebellum America provoked a frenzy of pro-slavery reaction. With the very foundation of their society under assault from the 1830s onward, southern planters, intellectuals and ministers penned countless speeches, essays, letters, and even poems in defense of bondage. Previously, the lack of a movement for immediate abolition gave slaveholders little reason to forcefully argue for the coerced labor of black people, but the rise of an energized opposition in Britain and America required ever more sophisticated justifications for the “peculiar institution.” The result was southern intellectuals began to justify slavery not only in terms of racial hierarchy or practical necessity, but also by critiquing the model of free labor offered by Northern abolitionists as an alternative. Through these critiques, southerners articulated an alternative vision of capitalism, one based on ostensibly more humane bound labor and the racial and social stability it maintained. However, I argue that this vision was fundamentally reactionary and situational. It was only articulated in response to attacks from British and northern abolitionists and, despite arguing for slavery universal superiority to wage labor, Southerners never advocated expanding it beyond the Southern, black population

    Broad-Spectrum Matrix Metalloproteinase Inhibition Curbs Inflammation and Liver Injury but Aggravates Experimental Liver Fibrosis in Mice

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    Background Liver fibrosis is characterized by excessive synthesis of extracellular matrix proteins, which prevails over their enzymatic degradation, primarily by matrix metalloproteinases (MMPs). The effect of pharmacological MMP inhibition on fibrogenesis, however, is largely unexplored. Inflammation is considered a prerequisite and important co-contributor to fibrosis and is, in part, mediated by tumor necrosis factor (TNF)-α-converting enzyme (TACE). We hypothesized that treatment with a broad-spectrum MMP and TACE-inhibitor (Marimastat) would ameliorate injury and inflammation, leading to decreased fibrogenesis during repeated hepatotoxin-induced liver injury.Methodology/Principal Findings Liver fibrosis was induced in mice by repeated carbon tetrachloride (CCl4) administration, during which the mice received either Marimastat or vehicle twice daily. A single dose of CCl4was administered to investigate acute liver injury in mice pretreated with Marimastat, mice deficient in Mmp9, or mice deficient in both TNF-α receptors. Liver injury was quantified by alanine aminotransferase (ALT) levels and confirmed by histology. Hepatic collagen was determined as hydroxyproline, and expression of fibrogenesis and fibrolysis-related transcripts was determined by quantitative reverse-transcription polymerase chain reaction. Marimastat-treated animals demonstrated significantly attenuated liver injury and inflammation but a 25% increase in collagen deposition. Transcripts related to fibrogenesis were significantly less upregulated compared to vehicle-treated animals, while MMP expression and activity analysis revealed efficient pharmacologic MMP-inhibition and decreased fibrolysis following Marimastat treatment. Marimastat pre-treatment significantly attenuated liver injury following acute CCl4-administration, whereas Mmp9 deficient animals demonstrated no protection. Mice deficient in both TNF-α receptors exhibited an 80% reduction of serum ALT, confirming the hepatoprotective effects of Marimastat via the TNF-signaling pathway.Conclusions/Significance Inhibition of MMP and TACE activity with Marimastat during chronic CCl4administration counterbalanced any beneficial anti-inflammatory effect, resulting in a positive balance of collagen deposition. Since effective inhibition of MMPs accelerates fibrosis progression, MMP inhibitors should be used with caution in patients with chronic liver diseases

    Cardiovascular disease, chronic kidney disease, and diabetes mortality burden of cardiometabolic risk factors from 1980 to 2010: A comparative risk assessment

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    Background: High blood pressure, blood glucose, serum cholesterol, and BMI are risk factors for cardiovascular diseases and some of these factors also increase the risk of chronic kidney disease and diabetes. We estimated mortality from cardiovascular diseases, chronic kidney disease, and diabetes that was attributable to these four cardiometabolic risk factors for all countries and regions from 1980 to 2010. Methods: We used data for exposure to risk factors by country, age group, and sex from pooled analyses of population-based health surveys. We obtained relative risks for the effects of risk factors on cause-specific mortality from meta-analyses of large prospective studies. We calculated the population attributable fractions for each risk factor alone, and for the combination of all risk factors, accounting for multicausality and for mediation of the effects of BMI by the other three risks. We calculated attributable deaths by multiplying the cause-specific population attributable fractions by the number of disease-specific deaths. We obtained cause-specific mortality from the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We propagated the uncertainties of all the inputs to the final estimates. Findings: In 2010, high blood pressure was the leading risk factor for deaths due to cardiovascular diseases, chronic kidney disease, and diabetes in every region, causing more than 40% of worldwide deaths from these diseases; high BMI and glucose were each responsible for about 15% of deaths, and high cholesterol for more than 10%. After accounting for multicausality, 63% (10·8 million deaths, 95% CI 10·1-11·5) of deaths from these diseases in 2010 were attributable to the combined effect of these four metabolic risk factors, compared with 67% (7·1 million deaths, 6·6-7·6) in 1980. The mortality burden of high BMI and glucose nearly doubled from 1980 to 2010. At the country level, age-standardised death rates from these diseases attributable to the combined effects of these four risk factors surpassed 925 deaths per 100 000 for men in Belarus, Kazakhstan, and Mongolia, but were less than 130 deaths per 100 000 for women and less than 200 for men in some high-income countries including Australia, Canada, France, Japan, the Netherlands, Singapore, South Korea, and Spain. Interpretation: The salient features of the cardiometabolic disease and risk factor epidemic at the beginning of the 21st century are high blood pressure and an increasing effect of obesity and diabetes. The mortality burden of cardiometabolic risk factors has shifted from high-income to low-income and middle-income countries. Lowering cardiometabolic risks through dietary, behavioural, and pharmacological interventions should be a part of the global response to non-communicable diseases. Funding: UK Medical Research Council, US National Institutes of Health. © 2014 Elsevier Ltd

    National, regional, and global trends in body-mass index since 1980: Systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9·1 million participants

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    Excess bodyweight is a major public health concern. However, few worldwide comparative analyses of long-term trends of body-mass index (BMI) have been done, and none have used recent national health examination surveys. We estimated worldwide trends in population mean BMI. We estimated trends and their uncertainties of mean BMI for adults 20 years and older in 199 countries and territories. We obtained data from published and unpublished health examination surveys and epidemiological studies (960 country-years and 9·1 million participants). For each sex, we used a Bayesian hierarchical model to estimate mean BMI by age, country, and year, accounting for whether a study was nationally representative. Between 1980 and 2008, mean BMI worldwide increased by 0·4 kg/m2 per decade (95 uncertainty interval 0·2-0·6, posterior probability of being a true increase >0·999) for men and 0·5 kg/m2 per decade (0·3-0·7, posterior probability >0·999) for women. National BMI change for women ranged from non-significant decreases in 19 countries to increases of more than 2·0 kg/m2 per decade (posterior probabilities >0·99) in nine countries in Oceania. Male BMI increased in all but eight countries, by more than 2 kg/m2 per decade in Nauru and Cook Islands (posterior probabilities >0·999). Male and female BMIs in 2008 were highest in some Oceania countries, reaching 33·9 kg/m2 (32·8-35·0) for men and 35·0 kg/m2 (33·6-36·3) for women in Nauru. Female BMI was lowest in Bangladesh (20·5 kg/m2, 19·8-21·3) and male BMI in Democratic Republic of the Congo 19·9 kg/m2 (18·2-21·5), with BMI less than 21·5 kg/m2 for both sexes in a few countries in sub-Saharan Africa, and east, south, and southeast Asia. The USA had the highest BMI of high-income countries. In 2008, an estimated 1·46 billion adults (1·41-1·51 billion) worldwide had BMI of 25 kg/m2 or greater, of these 205 million men (193-217 million) and 297 million women (280-315 million) were obese. Globally, mean BMI has increased since 1980. The trends since 1980, and mean population BMI in 2008, varied substantially between nations. Interventions and policies that can curb or reverse the increase, and mitigate the health effects of high BMI by targeting its metabolic mediators, are needed in most countries. Bill Melinda Gates Foundation and WHO
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