RESUMO
BACKGROUND: The global burden of road injuries is known to follow complex geographical, temporal and demographic patterns. While health loss from road injuries is a major topic of global importance, there has been no recent comprehensive assessment that includes estimates for every age group, sex and country over recent years. METHODS: We used results from the Global Burden of Disease (GBD) 2017 study to report incidence, prevalence, years lived with disability, deaths, years of life lost and disability-adjusted life years for all locations in the GBD 2017 hierarchy from 1990 to 2017 for road injuries. Second, we measured mortality-to-incidence ratios by location. Third, we assessed the distribution of the natures of injury (eg, traumatic brain injury) that result from each road injury. RESULTS: Globally, 1 243 068 (95% uncertainty interval 1 191 889 to 1 276 940) people died from road injuries in 2017 out of 54 192 330 (47 381 583 to 61 645 891) new cases of road injuries. Age-standardised incidence rates of road injuries increased between 1990 and 2017, while mortality rates decreased. Regionally, age-standardised mortality rates decreased in all but two regions, South Asia and Southern Latin America, where rates did not change significantly. Nine of 21 GBD regions experienced significant increases in age-standardised incidence rates, while 10 experienced significant decreases and two experienced no significant change. CONCLUSIONS: While road injury mortality has improved in recent decades, there are worsening rates of incidence and significant geographical heterogeneity. These findings indicate that more research is needed to better understand how road injuries can be prevented.
Assuntos
Carga Global da Doença , Saúde Global , Ferimentos e Lesões , Acidentes de Trânsito , Ásia , Humanos , Morbidade , Mortalidade/tendências , Anos de Vida Ajustados por Qualidade de Vida , Ferimentos e Lesões/mortalidadeRESUMO
BACKGROUND: Genetic and nutritional factors play an important role in inflammatory response and diseases. CXCL10 is a critical biomarker that is involved in multiple inflammatory diseases, and elevated levels of CXCL10 have been associated with the development of several chronic and infectious diseases. In contrast, micronutrients can attenuate inflammatory responses. Single nucleotide polymorphisms in the pro-inflammatory cytokine genes such as IL-1ß at rs16944 contributed to a number of inflammatory disorders and may substantiate the convergance between chronic and infectious diseases. AIM: This study aims to identify the modifying effect of nutritional factors on the association between IL-1ß genotypes and CXCL10 levels. METHODS: Participants (N = 386) were healthy males and females from the Toronto Nutrigenomics and Health study recruited from the University of Toronto. Levels of micronutrients and inflammatory markers were measured in plasma. IL-1ß genotypes were extracted from the Affymetrix 6.0 SNP chip. RESULTS: CXCL10 levels were not different across different IL-1ß genotypes. Among those with the GA genotype, elevated CXCL10 levels were observed with higher than median ascorbic acid (ß = 0.004 ± 0.002, P = 0.047) or higher than median vitamin D status (ß = 0.003 ± 0.002, P = 0.044). Among participants with the AA genotype, subjects with low α-tocopherol status had elevated levels of CXCL10 (ß = -0.016 ± 0.007, P = 0.012). CONCLUSION: The association between IL-1ß rs16944 genotype and CXCL10 levels was modified by the levels of ascorbic acid, α-tocopherol and vitamin D. These findings may aid in understanding the combined effect of genetic and dietary factors in the development of various infectious and chronic diseases in which IL-1ß and CXCL10 may play an etiological role.
Assuntos
Quimiocina CXCL10/sangue , Interleucina-1beta/genética , Estado Nutricional , Polimorfismo de Nucleotídeo Único , Ácido Ascórbico/sangue , Biomarcadores/sangue , Canadá , Estudos Transversais , Feminino , Genótipo , Humanos , Inflamação/sangue , Masculino , Micronutrientes/sangue , Nutrigenômica , Vitamina D/sangue , Adulto Jovem , alfa-Tocoferol/sangueRESUMO
BACKGROUND: C-reactive protein (CRP) is an acute-phase reactant downstream of the pro-inflammatory cytokines released during influenza infection. However, the role of this inflammatory marker in influenza severity and complications is yet to be elucidated. OBJECTIVES: We aim to systematically review and evaluate the levels of CRP in severe and non-severe H1N1 influenza cases and assess its utility as a biomarker in predicting the severity of infection. METHODS: We conducted a comprehensive search in Ovid MEDLINE, Ovid MEDLINE (R) Epub ahead of Print, Embase and Embase Classic to identify human studies reporting measurements of CRP levels in patients infected with H1N1 influenza at various levels of disease severity. RESULTS: Our search identified ten studies eligible for inclusion in this systematic review. The results of the data analysis show that the average CRP levels upon diagnosis were significantly higher (P < 0.05) in patients who developed severe H1N1 influenza compared to their counterparts with a no severe disease. Furthermore, levels of CRP were associated with the degree of H1N1 severity. Subjects with H1N1-related pneumonia and patients who were hospitalized or died of the disease complications, respectively, had 1.4- and 2.5-fold significantly higher CRP levels (P < 0.05) than those with no severe disease outcome. CONCLUSION: CRP levels have been consistently shown to be significantly higher in H1N1 influenza patients who develop a severe disease outcome. The resuts of the present study suggest that serum CRP can be employed-in combination with other biomarkers-to predict the complications of H1N1 influenza.
Assuntos
Proteína C-Reativa/análise , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/sangue , Biomarcadores/sangue , Humanos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Lyme disease or Lyme borreliosis (LB) is the commonest vector-borne disease in the North America. It is an inflammatory disease caused by the bacterium Borrelia burgdorferi. The role of the inflammatory processes mediated by prostaglandins (PGs), thromboxanes and leukotrienes (LTs) in LB severity and symptoms resolution is yet to be elucidated. OBJECTIVES: We aim to systematically review and evaluate the role of PGs and related lipid mediators in the induction and resolution of inflammation in LB. METHODS: We conducted a comprehensive search in PubMed, Ovid MEDLINE(R), Embase and Embase Classic to identify cell-culture, animal and human studies reporting the changes in PGs and related lipid mediators of inflammation during the course of LB. RESULTS: We identified 18 studies to be included into this systematic review. The selected reports consisted of seven cell-culture studies, seven animal studies, and four human studies (from three patient populations). Results from cell-culture and animal studies suggest that PGs and other lipid mediators of inflammation are elevated in LB and may contribute to disease development. The limited number of human studies showed that subjects with Lyme meningitis, Lyme arthritis (LA) and antibiotic-refractory LA had increased levels of an array of PGs and lipid mediators (e.g., LTB4, 8-isoPGF2α, and phospholipases A2 activity). Levels of these markers were significantly reduced following the treatment with antibiotics or non-steroidal anti-inflammatory drugs. CONCLUSION: Dysregulation of prostaglandins and related lipid mediators may play a role in the etiology of LB and persistence of inflammation that may lead to long-term complications. Further investigation into the precise levels of a wide range of PGs and related factors is critical as it may propose novel markers that can be used for early diagnosis.
Assuntos
Doença de Lyme/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Animais , Biomarcadores/metabolismo , Humanos , Prostaglandinas/metabolismo , Índice de Gravidade de DoençaRESUMO
The burden of premature death and health loss from ESRD is well described. Less is known regarding the burden of cardiovascular disease attributable to reduced GFR. We estimated the prevalence of reduced GFR categories 3, 4, and 5 (not on RRT) for 188 countries at six time points from 1990 to 2013. Relative risks of cardiovascular outcomes by three categories of reduced GFR were calculated by pooled random effects meta-analysis. Results are presented as deaths for outcomes of cardiovascular disease and ESRD and as disability-adjusted life years for outcomes of cardiovascular disease, GFR categories 3, 4, and 5, and ESRD. In 2013, reduced GFR was associated with 4% of deaths worldwide, or 2.2 million deaths (95% uncertainty interval [95% UI], 2.0 to 2.4 million). More than half of these attributable deaths were cardiovascular deaths (1.2 million; 95% UI, 1.1 to 1.4 million), whereas 0.96 million (95% UI, 0.81 to 1.0 million) were ESRD-related deaths. Compared with metabolic risk factors, reduced GFR ranked below high systolic BP, high body mass index, and high fasting plasma glucose, and similarly with high total cholesterol as a risk factor for disability-adjusted life years in both developed and developing world regions. In conclusion, by 2013, cardiovascular deaths attributed to reduced GFR outnumbered ESRD deaths throughout the world. Studies are needed to evaluate the benefit of early detection of CKD and treatment to decrease these deaths.
Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Taxa de Filtração Glomerular , Nefropatias/epidemiologia , Nefropatias/etiologia , Rim/fisiopatologia , Saúde Global , Humanos , Medição de Risco , Fatores de RiscoRESUMO
OBJECTIVES: We used findings from the Global Burden of Disease Study 2013 to report the burden of musculoskeletal disorders in the Eastern Mediterranean Region (EMR). METHODS: The burden of musculoskeletal disorders was calculated for the EMR's 22 countries between 1990 and 2013. A systematic analysis was performed on mortality and morbidity data to estimate prevalence, death, years of live lost, years lived with disability and disability-adjusted life years (DALYs). RESULTS: For musculoskeletal disorders, the crude DALYs rate per 100â 000 increased from 1297.1 (95% uncertainty interval (UI) 924.3-1703.4) in 1990 to 1606.0 (95% UI 1141.2-2130.4) in 2013. During 1990-2013, the total DALYs of musculoskeletal disorders increased by 105.2% in the EMR compared with a 58.0% increase in the rest of the world. The burden of musculoskeletal disorders as a proportion of total DALYs increased from 2.4% (95% UI 1.7-3.0) in 1990 to 4.7% (95% UI 3.6-5.8) in 2013. The range of point prevalence (per 1000) among the EMR countries was 28.2-136.0 for low back pain, 27.3-49.7 for neck pain, 9.7-37.3 for osteoarthritis (OA), 0.6-2.2 for rheumatoid arthritis and 0.1-0.8 for gout. Low back pain and neck pain had the highest burden in EMR countries. CONCLUSIONS: This study shows a high burden of musculoskeletal disorders, with a faster increase in EMR compared with the rest of the world. The reasons for this faster increase need to be explored. Our findings call for incorporating prevention and control programmes that should include improving health data, addressing risk factors, providing evidence-based care and community programmes to increase awareness.
Assuntos
Artrite Reumatoide/epidemiologia , Carga Global da Doença , Gota/epidemiologia , Dor Lombar/epidemiologia , Cervicalgia/epidemiologia , Osteoartrite/epidemiologia , Adulto , África do Norte/epidemiologia , Idoso , Djibuti/epidemiologia , Feminino , Humanos , Masculino , Região do Mediterrâneo/epidemiologia , Pessoa de Meia-Idade , Oriente Médio/epidemiologia , Mortalidade , Doenças Musculoesqueléticas/epidemiologia , Prevalência , Anos de Vida Ajustados por Qualidade de Vida , Somália/epidemiologiaRESUMO
AIMS: Low serum 25-hydroxyvitamin-D (25(OH)D) concentrations are associated with insulin resistance, ß-cell dysfunction and type 2 diabetes. We conducted a 24-week double-blind, randomized, placebo-controlled trial to examine the effect of 28 000 IU of vitamin D3 once weekly on plasma glucose after a 2 hour-75 g oral glucose tolerance test (2hrPC glucose), insulin sensitivity and ß-cell function. STUDY DESIGN AND METHODS: A total of 71 participants with serum 25(OH)D ≤65 nmol/L, impaired fasting glucose and elevated glycated hemoglobin were randomly assigned to receive 28 000 IU of vitamin D3 (VitD; n = 35) or placebo (n = 36) in cheese once weekly for 24 weeks. The primary outcome was the change in 2hPC glucose. Secondary outcomes were fasting glucose, fasting and postprandial insulin, indices of insulin sensitivity and ß-cell function, glycated hemoglobin and lipid profile. Participants underwent an oral glucose tolerance test to determine 2hPC glucose. RESULTS: Mean baseline serum 25(OH)D was 48.1 and 47.6 nmol/L in the VitD and placebo groups, respectively. Serum 25(OH)D significantly increased to 98.7 nmol/L (51 nmol/L increase; P < .0001) in the VitD group. No significant differences in fasting ( P = .42) or 2hPC glucose ( P = .55) or other indices of glucose metabolism, including ß-cell function and insulin sensitivity, were observed between groups. A subgroup analysis of individuals with 25(OH)D < 50 nmol/L and prediabetes did not change these results. The VitD group exhibited a significant reduction in LDL cholesterol (-0.27 vs 0.01 mmol/L, P = .03). CONCLUSION: Weekly doses of vitamin D3 in individuals with suboptimal vitamin D levels who were at risk for type 2 diabetes did not improve oral glucose tolerance or markers of glycaemic status.
Assuntos
Glicemia/metabolismo , Colecalciferol/uso terapêutico , Resistência à Insulina , Estado Pré-Diabético/metabolismo , Deficiência de Vitamina D/tratamento farmacológico , Vitaminas/uso terapêutico , Adulto , LDL-Colesterol/metabolismo , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/metabolismo , Suplementos Nutricionais , Método Duplo-Cego , Jejum , Feminino , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/metabolismo , Humanos , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial , Estado Pré-Diabético/epidemiologia , Risco , Vitamina D/análogos & derivados , Vitamina D/metabolismo , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/metabolismoRESUMO
BACKGROUND: The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age-sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. METHODS: We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. FINDINGS: Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6-6·6), from 65·3 years (65·0-65·6) in 1990 to 71·5 years (71·0-71·9) in 2013, HALE at birth rose by 5·4 years (4·9-5·8), from 56·9 years (54·5-59·1) to 62·3 years (59·7-64·8), total DALYs fell by 3·6% (0·3-7·4), and age-standardised DALY rates per 100â000 people fell by 26·7% (24·6-29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non-communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. INTERPRETATION: Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition--in which increasing sociodemographic status brings structured change in disease burden--is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions. FUNDING: Bill & Melinda Gates Foundation.
Assuntos
Doença Crônica/epidemiologia , Doenças Transmissíveis/epidemiologia , Saúde Global/estatística & dados numéricos , Transição Epidemiológica , Expectativa de Vida , Ferimentos e Lesões/epidemiologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade Prematura , Anos de Vida Ajustados por Qualidade de Vida , Fatores SocioeconômicosRESUMO
BACKGROUND: The fifth Millennium Development Goal (MDG 5) established the goal of a 75% reduction in the maternal mortality ratio (MMR; number of maternal deaths per 100,000 livebirths) between 1990 and 2015. We aimed to measure levels and track trends in maternal mortality, the key causes contributing to maternal death, and timing of maternal death with respect to delivery. METHODS: We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to analyse a database of data for 7065 site-years and estimate the number of maternal deaths from all causes in 188 countries between 1990 and 2013. We estimated the number of pregnancy-related deaths caused by HIV on the basis of a systematic review of the relative risk of dying during pregnancy for HIV-positive women compared with HIV-negative women. We also estimated the fraction of these deaths aggravated by pregnancy on the basis of a systematic review. To estimate the numbers of maternal deaths due to nine different causes, we identified 61 sources from a systematic review and 943 site-years of vital registration data. We also did a systematic review of reports about the timing of maternal death, identifying 142 sources to use in our analysis. We developed estimates for each country for 1990-2013 using Bayesian meta-regression. We estimated 95% uncertainty intervals (UIs) for all values. FINDINGS: 292,982 (95% UI 261,017-327,792) maternal deaths occurred in 2013, compared with 376,034 (343,483-407,574) in 1990. The global annual rate of change in the MMR was -0·3% (-1·1 to 0·6) from 1990 to 2003, and -2·7% (-3·9 to -1·5) from 2003 to 2013, with evidence of continued acceleration. MMRs reduced consistently in south, east, and southeast Asia between 1990 and 2013, but maternal deaths increased in much of sub-Saharan Africa during the 1990s. 2070 (1290-2866) maternal deaths were related to HIV in 2013, 0·4% (0·2-0·6) of the global total. MMR was highest in the oldest age groups in both 1990 and 2013. In 2013, most deaths occurred intrapartum or postpartum. Causes varied by region and between 1990 and 2013. We recorded substantial variation in the MMR by country in 2013, from 956·8 (685·1-1262·8) in South Sudan to 2·4 (1·6-3·6) in Iceland. INTERPRETATION: Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015. Accelerated reductions since the Millennium Declaration in 2000 coincide with increased development assistance for maternal, newborn, and child health. Setting of targets and associated interventions for after 2015 will need careful consideration of regions that are making slow progress, such as west and central Africa. FUNDING: Bill & Melinda Gates Foundation.
Assuntos
Saúde Global/tendências , Mortalidade Materna/tendências , Distribuição por Idade , Causas de Morte/tendências , Feminino , Saúde Global/estatística & dados numéricos , Infecções por HIV/mortalidade , Humanos , Modelos Estatísticos , Objetivos Organizacionais , Gravidez , Complicações Infecciosas na Gravidez/mortalidade , Fatores de Risco , Fatores Socioeconômicos , Fatores de TempoRESUMO
BACKGROUND: The Arab world has a set of historical, geopolitical, social, cultural, and economic characteristics and has been involved in several wars that have affected the burden of disease. Moreover, financial and human resources vary widely across the region. We aimed to examine the burden of diseases and injuries in the Arab world for 1990, 2005, and 2010 using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010). METHODS: We divided the 22 countries of the Arab League into three categories according to their gross national income: low-income countries (LICs; Comoros, Djibouti, Mauritania, Yemen, and Somalia), middle-income countries (MICs; Algeria, Egypt, Iraq, Jordan, Lebanon, Libya, Morocco, occupied Palestinian territory, Sudan, Syria, and Tunisia), and high-income countries (HICs; Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates). For the whole Arab world, each income group, and each individual country, we estimated causes of death, disability-adjusted life years (DALYs), DALY-attributable risk factors, years of life lived with disability (YLDs), years of life lost due to premature mortality (YLLs), and life expectancy by age and sex for 1990, 2005, and 2010. FINDINGS: Ischaemic heart disease was the top cause of death in the Arab world in 2010 (contributing to 14·3% of deaths), replacing lower respiratory infections, which were the leading cause of death in 1990 (11·0%). Lower respiratory infections contributed to the highest proportion of DALYs overall (6·0%), and in female indivduals (6·1%), but ischaemic heart disease was the leading cause of DALYs in male individuals (6·0%). DALYs from non-communicable diseases--especially ischaemic heart disease, mental disorders such as depression and anxiety, musculoskeletal disorders including low back pain and neck pain, diabetes, and cirrhosis--increased since 1990. Major depressive disorder was ranked first as a cause of YLDs in 1990, 2005, and 2010, and lower respiratory infections remained the leading cause of YLLs in 2010 (9·2%). The burden from HIV/AIDS also increased substantially, specifically in LICs and MICs, and road injuries continued to rank highly as a cause of death and DALYs, especially in HICs. Deaths due to suboptimal breastfeeding declined from sixth place in 1990 to tenth place in 2010, and childhood underweight declined from fifth to 11th place. INTERPRETATION: Since 1990, premature death and disability caused by communicable, newborn, nutritional, and maternal disorders (with the exception of HIV/AIDS) has decreased in the Arab world--although these disorders do still persist in LICs--whereas the burden of non-communicable diseases and injuries has increased. The changes in the burden of disease will challenge already stretched human and financial resources because many Arab countries are now dealing with both non-communicable and infectious diseases. A road map for health in the Arab world is urgently needed. FUNDING: Bill & Melinda Gates Foundation.
Assuntos
Mundo Árabe , Nível de Saúde , Ferimentos e Lesões/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Causas de Morte/tendências , Criança , Pré-Escolar , Doenças Transmissíveis/epidemiologia , Pessoas com Deficiência/estatística & dados numéricos , Feminino , Humanos , Renda , Lactente , Recém-Nascido , Expectativa de Vida/tendências , Masculino , Pessoa de Meia-Idade , Oriente Médio/epidemiologia , Mortalidade Prematura/tendências , Isquemia Miocárdica/epidemiologia , Anos de Vida Ajustados por Qualidade de Vida , Infecções Respiratórias/epidemiologia , Fatores de Risco , Distribuição por Sexo , Adulto JovemRESUMO
PURPOSE: The purpose of this study was to assess safety of the traditional antidiabetic extracts of either S. purpurea or its lead active principle, morroniside at the transcriptional level. The overarching objective was to profile and validate transcriptional changes in the cytochrome P450 family of genes, in response to treatment with S. purpurea ethanolic extract or its lead active, morroniside. METHODS: Transcriptional activity was profiled using a 19K human cDNA microarray in C2BBe1 cells, clone of Caco-2 intestinal cells, which are a model of first-pass metabolism (1, 2). Cells were treated with S. purpurea extract for 4 and 24 hrs, as well as the pure compound morroniside for 4 hrs, to determine their effects. RESULTS: No evidence of cytochrome P450 transcriptome regulation or of transcriptional activation of other diabetes relevant mRNA was detected after rigorous quantitative-PCR validation of microarray results. CONCLUSION: Our data do not support a transcriptional mechanism of action for either S. purpurea extract or its lead active, morroniside. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
Assuntos
Sistema Enzimático do Citocromo P-450/genética , Glicosídeos/toxicidade , Extratos Vegetais/toxicidade , Sarraceniaceae/química , Células CACO-2 , DNA Complementar/genética , Glicosídeos/isolamento & purificação , Humanos , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/toxicidade , Indígenas Norte-Americanos , Medicina Tradicional , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Extratos Vegetais/isolamento & purificação , Reação em Cadeia da Polimerase , Quebeque , RNA Mensageiro/metabolismo , Fatores de TempoRESUMO
Vitamin D affects gene expression, but its downstream effects on the proteome are unclear. Hormonal contraceptives (HC), which affect vitamin D metabolism and have widespread effects on the plasma proteome, may confound the association between vitamin D and the proteome. We determined whether HC use modified the association between 25-hydroxyvitamin D (25D) and a panel of 54 high-abundance plasma proteins. Cross-sectional analyses were conducted in healthy, nonsmoking female HC users (n = 216), female HC nonusers (n = 502), and men (n = 301) from Toronto, Canada. Plasma 25D was measured by HPLC-MS/MS, and proteins were measured by LC-multiple-reaction-monitoring (MRM)-MS. The 54 proteins clustered into four distinct proteomic profiles. A positive association was observed between Profile 1, containing positive acute phase proteins, and 25D. In female HC users, a J-shaped association existed between Profile 1 and 25D, but no associations existed in female HC nonusers and men. Twelve proteins were individually associated with 25D in female HC users, but only two were associated with 25D in female HC nonusers and no associations were observed in men. After accounting for hormone dose, only three proteins were associated with 25D. In summary, HC use is an important confounder of the association between circulating 25D and numerous plasma proteins.
Assuntos
Proteínas Sanguíneas/metabolismo , Anticoncepcionais Orais Hormonais/uso terapêutico , Vitamina D/análogos & derivados , Adulto , Sudeste Asiático/etnologia , Proteínas Sanguíneas/análise , Canadá , Análise por Conglomerados , Anticoncepcionais Orais Hormonais/administração & dosagem , Estudos Transversais , Feminino , Humanos , Masculino , Fumar/sangue , Espectrometria de Massas em Tandem , Vitamina D/sangue , População Branca , Adulto JovemRESUMO
OBJECTIVES: The relationship between vitamin D and cardiometabolic disease risk across ethnic groups is unclear, and it is not known whether the use of hormonal contraceptives (HCs), which affect vitamin D metabolism and are also associated with cardiometabolic disease risk, modifies this relationship. Our objectives were to determine the prevalence of vitamin D deficiency (plasma 25-hydroxyvitamin D [25(OH)D] < 30 nmol/L) to assess seasonal variation in concentrations of 25(OH)D, and to examine whether 25(OH)D is associated with cardiometabolic biomarkers across ethnic groups and across men, female HC nonusers, and female HC users in an ethnically diverse population of young adults living in Canada. METHODS: The study population consisted of Caucasian, East Asian, and South Asian individuals (n = 1384, 69% female) aged 20-29 years. Participants provided overnight fasting blood samples, from which plasma 25(OH)D and cardiometabolic biomarkers were measured. Vitamin D status distributions were compared using χ(2) tests, and analysis of covariance (ANCOVA) was used to examine seasonal variations in 25(OH)D, as well as the association between 25(OH)D and cardiometabolic biomarkers, across groups. RESULTS: Plasma 25(OH)D concentrations fluctuated seasonally among Caucasians and East Asians and across men, female HC nonusers, and female HC users, but they remained low year-round in South Asians, half of whom were vitamin D deficient. Vitamin D deficiency was associated with higher insulin, homeostasis model assessment-estimated insulin resistance (HOMA-IR), and homeostasis model assessment (HOMA)-beta among Caucasians and East Asians and among men and female HC nonusers and with higher triglycerides among men only. No biomarkers were associated with 25(OH)D among South Asians and female HC users, although nonsignificant trends were observed for higher markers of glycemic dysregulation in those who were vitamin D deficient in both groups. CONCLUSIONS: Vitamin D deficiency varies between ethnic groups and is particularly high among South Asians, and it is associated with biomarkers of glycemic dysregulation; however, HC use among women may attenuate this association. Given the widespread use of HCs by women throughout the world, a better understanding of the extent to which these medications may modify the relationship between vitamin D and processes related to disease is warranted.
Assuntos
Povo Asiático , Doenças Cardiovasculares/etiologia , Anticoncepcionais/farmacologia , Doenças Metabólicas/etiologia , Deficiência de Vitamina D/complicações , Vitamina D/análogos & derivados , População Branca , Adulto , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Feminino , Intolerância à Glucose/sangue , Intolerância à Glucose/complicações , Intolerância à Glucose/etnologia , Humanos , Masculino , Doenças Metabólicas/sangue , Prevalência , Fatores de Risco , Estações do Ano , Fatores Sexuais , Triglicerídeos/sangue , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/etnologia , Adulto JovemRESUMO
BACKGROUND: Chronic kidney disease is an important risk factor for death and cardiovascular-related morbidity, but estimates to date of its prevalence in Canada have generally been extrapolated from the prevalence of end-stage renal disease. We used direct measures of kidney function collected from a nationally representative survey population to estimate the prevalence of chronic kidney disease among Canadian adults. METHODS: We examined data for 3689 adult participants of cycle 1 of the Canadian Health Measures Survey (2007-2009) for the presence of chronic kidney disease. We also calculated the age-standardized prevalence of cardiovascular risk factors by chronic kidney disease group. We cross-tabulated the estimated glomerular filtration rate (eGFR) with albuminuria status. RESULTS: The prevalence of chronic kidney disease during the period 2007-2009 was 12.5%, representing about 3 million Canadian adults. The estimated prevalence of stage 3-5 disease was 3.1% (0.73 million adults) and albuminuria 10.3% (2.4 million adults). The prevalence of diabetes, hypertension and hypertriglyceridemia were all significantly higher among adults with chronic kidney disease than among those without it. The prevalence of albuminuria was high, even among those whose eGFR was 90 mL/min per 1.73 m(2) or greater (10.1%) and those without diabetes or hypertension (9.3%). Awareness of kidney dysfunction among adults with stage 3-5 chronic kidney disease was low (12.0%). INTERPRETATION: The prevalence of kidney dysfunction was substantial in the survey population, including individuals without hypertension or diabetes, conditions most likely to prompt screening for kidney dysfunction. These findings highlight the potential for missed opportunities for early intervention and secondary prevention of chronic kidney disease.
Assuntos
Insuficiência Renal Crônica/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Albuminúria/epidemiologia , Canadá/epidemiologia , Comorbidade , Creatinina/urina , Diabetes Mellitus/epidemiologia , Feminino , Taxa de Filtração Glomerular , Inquéritos Epidemiológicos , Humanos , Hipertensão/epidemiologia , Hipertrigliceridemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fatores Sexuais , Adulto JovemRESUMO
INTRODUCTION: Vitamin D may modulate cardiometabolic disease risk, although the relationship has not been investigated in the general Canadian population. Understanding this relationship may inform public health strategies to curb the incidence of cardiometabolic disease in Canada and elsewhere. The objectives of this study were to examine the association between vitamin D and traditional and novel biomarkers of cardiometabolic disease and to describe the extent of the month-to-month fluctuations of vitamin D in the Canadian population. METHODS: We examined the association between plasma 25-hydroxyvitamin D and a range of cardiometabolic risk biomarkers in participants (n = 1,928; age range, 16-79 years) from the Canadian Health Measures Survey. We conducted linear regressions analyses (adjusted for sex, waist circumference, physical activity, hormone use, and season) to assess the relationship between 25-hydroxyvitamin D and biomarkers of dysglycemia, dyslipidemia, and inflammation in the study population. We repeated analyses stratified by sex, and we evaluated monthly fluctuations in 25-hydroxyvitamin D in men and women. RESULTS: We observed wide month-to-month variations in 25-hydroxyvitamin D; fluctuations were more pronounced in men. Plasma 25-hydroxyvitamin D was inversely associated with insulin, insulin resistance, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and the ratio of total to high-density lipoprotein cholesterol but not with fasting glucose, apolipoprotein A1, apolipoprotein B, C-reactive protein, fibrinogen, or homocysteine. This pattern varied between men and women. CONCLUSION: Vitamin D may modulate various metabolic processes and may influence cardiometabolic disease risk in Canadians. These findings may have public health implications when recommending vitamin D for the prevention of cardiometabolic disease and related conditions.
Assuntos
Doenças Cardiovasculares/sangue , Síndrome Metabólica/sangue , Medição de Risco/tendências , Vitamina D/análogos & derivados , Vitamina D/sangue , Adolescente , Adulto , Idoso , Antropometria , Biomarcadores/sangue , Canadá/epidemiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Exercício Físico/fisiologia , Feminino , Humanos , Modelos Lineares , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Fatores Sexuais , Adulto JovemRESUMO
Fatty acids (FA) represent a diverse class of molecules known to regulate inflammatory pathways. Therefore enzymes that regulate FA metabolism are attractive candidates to better understand the relationship between FA and inflammation. Stearoyl-CoA desaturase 1 (SCD1) is rate limiting for the conversion of saturated FA (SFA) to monounsaturated FA (MUFA). Evidence suggests that SCD1 activity may be positively associated with inflammation. Moreover, genetic variation in SCD1 may alter enzyme activity; however, it is unknown whether this affects inflammatory status. The goal of this study was to examine the relationships between plasma FA, SCD1 activity, and SCD1 polymorphisms with C-reactive protein (CRP) levels in young adults. SFA, MUFA, and CRP were measured in fasted plasma samples from European (n=279, 198 female and 81 male) and Asian (n=249, 179 female and 70 male) subjects, 20-29 years old. Circulating levels of palmitic (16:0), palmitoleic (16:1), stearic (18:0), and oleic acids (18:1) were measured by gas chromatography and SCD1 activity was estimated by the ratio of product to precursor (16:1/16:0; 18:1/18:0). Positive associations were identified between CRP levels and 16:0 (p<2.0×10(-4)), 16:1 (p<0.05), and the SCD1 index (18:1/18:0; p<6.0×10(-3)) in European and Asian females, while 18:0 was inversely associated with CRP (p<2.0×10(-4)) in both groups. Ten single nucleotide polymorphisms (SNPs) in SCD1 were genotyped in all subjects. One SNP (rs2060792) was associated (p<0.05) with 16:0 and 18:0 levels in females of European descent. This same SNP was also associated with CRP levels in both groups of females (p<0.05). Overall, SCD1 activity and genetic variation have an important role in modulating the relationship between FA and inflammation in young adults.
Assuntos
Ácidos Graxos/sangue , Ácidos Graxos/metabolismo , Inflamação/metabolismo , Estearoil-CoA Dessaturase/genética , Estearoil-CoA Dessaturase/metabolismo , Adulto , Proteína C-Reativa/análise , Ácidos Graxos/imunologia , Ácidos Graxos Monoinsaturados/sangue , Feminino , Variação Genética , Genótipo , Humanos , Inflamação/imunologia , Metabolismo dos Lipídeos/genética , Masculino , Ácido Oleico/sangue , Ácido Palmítico/sangue , Polimorfismo de Nucleotídeo Único , Ácidos Esteáricos/sangue , Adulto JovemRESUMO
Oxidative stress develops as a result of an imbalance between the production and accumulation of reactive species and the body's ability to manage them using exogenous and endogenous antioxidants. Exogenous antioxidants obtained from the diet, including vitamin C, vitamin E, and carotenoids, have important roles in preventing and reducing oxidative stress. Individual genetic variation affecting proteins involved in the uptake, utilization and metabolism of these antioxidants may alter their serum levels, exposure to target cells and subsequent contribution to the extent of oxidative stress. Endogenous antioxidants include the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, paraoxanase, and glutathione S-transferase. These enzymes metabolize reactive species and their by-products, reducing oxidative stress. Variation in the genes coding these enzymes may impact their enzymatic antioxidant activity and, thus, the levels of reactive species, oxidative stress, and risk of disease development. Oxidative stress may contribute to the development of chronic disease, including osteoporosis, type 2 diabetes, neurodegenerative diseases, cardiovascular disease, and cancer. Indeed, polymorphisms in most of the genes that code for antioxidant enzymes have been associated with several types of cancer, although inconsistent findings between studies have been reported. These inconsistencies may, in part, be explained by interactions with the environment, such as modification by diet. In this review, we highlight some of the recent studies in the field of nutrigenetics, which have examined interactions between diet, genetic variation in antioxidant enzymes, and oxidative stress.
Assuntos
Antioxidantes/administração & dosagem , Dieta , Variação Genética , Promoção da Saúde , Estresse Oxidativo , Oxirredutases/genética , Animais , Antioxidantes/metabolismo , Arildialquilfosfatase/genética , Arildialquilfosfatase/metabolismo , Dieta/efeitos adversos , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Promoção da Saúde/tendências , Humanos , Nutrigenômica/tendências , Oxirredutases/metabolismo , Medicina de Precisão/tendências , Medicina Preventiva/tendênciasRESUMO
Canadian Aboriginals, like others globally, suffer from disproportionately high rates of diabetes. A comprehensive evidence-based approach was therefore developed to study potential antidiabetic medicinal plants stemming from Canadian Aboriginal Traditional Medicine to provide culturally adapted complementary and alternative treatment options. Key elements of pathophysiology of diabetes and of related contemporary drug therapy are presented to highlight relevant cellular and molecular targets for medicinal plants. Potential antidiabetic plants were identified using a novel ethnobotanical method based on a set of diabetes symptoms. The most promising species were screened for primary (glucose-lowering) and secondary (toxicity, drug interactions, complications) antidiabetic activity by using a comprehensive platform of in vitro cell-based and cell-free bioassays. The most active species were studied further for their mechanism of action and their active principles identified though bioassay-guided fractionation. Biological activity of key species was confirmed in animal models of diabetes. These in vitro and in vivo findings are the basis for evidence-based prioritization of antidiabetic plants. In parallel, plants were also prioritized by Cree Elders and healers according to their Traditional Medicine paradigm. This case study highlights the convergence of modern science and Traditional Medicine while providing a model that can be adapted to other Aboriginal realities worldwide.
RESUMO
Recent evidence indicates that genetic variation in fatty acid desaturases 1 and 2 (FADS1 and FADS2) is associated with changes in plasma fatty acid profiles; however, the association with altered desaturase activity has not been examined in different ethnic populations. The present study examined whether genetic variation in the FADS gene cluster regulates desaturase activity in two populations of young Canadian adults (Caucasian and Asian) and whether altered desaturase activity was reflected in both n-3 and n-6 fatty acid profiles. FADS1 and FADS2 were genotyped in a random subset of participants (Caucasian, n=78; Asian, n=69) from the Toronto Nutrigenomics and Health study using MALDI-TOF mass spectrometry, and plasma fatty acids were measured by gas chromatography. Desaturase activities were estimated using the following fatty acid ratios: γ-linoleic acid to linoleic acid (GLA:LA), arachidonic acid to linoleic acid (AA:LA), arachidonic acid to dihomo-γ-linoleic acid (AA:DGLA), and eicosapentaneoic acid to α-linolenic acid (EPA:ALA). Nineteen single nucleotide polymorphisms (SNPs) were examined, and several SNPs (9 in Caucasians and 8 in Asians) were associated with various desaturase activities. The most significant association detected was between the FADS1 rs174547 SNP and AA:LA in both Caucasians (p=4.0 × 10(-8)) and Asians (p=5.0 × 10(-5)). Although the minor allele for this SNP differed between Caucasians (T) and Asians (C), carriers of the C allele had a lower desaturase activity than carriers of the T allele in both groups. To determine whether rs174547 was a dominant SNP in the FADS gene cluster, we constructed an additional model which included this SNP as a covariate. Only one SNP (rs498793 in FADS2) remained associated with the EPA:ALA ratio (p=1.1 × 10(-5)) in Asians. This study shows that genetic variation in the FADS gene cluster (in particular rs174547) can alter desaturase activity in subjects of Caucasians and Asian descent.
Assuntos
Povo Asiático/genética , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Dessaturases/metabolismo , Polimorfismo de Nucleotídeo Único/genética , População Branca/genética , Dessaturase de Ácido Graxo Delta-5 , Ativação Enzimática/genética , Ácidos Graxos Dessaturases/sangue , Ácidos Graxos/sangue , Feminino , Regulação Enzimológica da Expressão Gênica , Frequência do Gene/genética , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Adulto JovemRESUMO
BACKGROUND: Type 2 diabetes mellitus (T2DM) has been linked to a state of pre-clinical chronic inflammation resulting from abnormalities in the innate immune pathway. Serum levels of pro-inflammatory cytokines and acute-phase proteins, collectively known as 'inflammatory network', are elevated in the pre-, or early, stages of T2DM and increase with disease progression. Genetic variation can affect the innate immune response to certain environmental factors, and may, therefore, determine an individual's lifetime risk of disease. METHODS: We conducted a cross-sectional study in 6,720 subjects from the Twins UK Registry to evaluate the association between 18 single nucleotide polymorphisms (SNPs) in five genes (TLR4, IL1A, IL6, TNFA, and CRP) along the innate immunity-related inflammatory pathway and biomarkers of predisposition to T2DM [fasting insulin and glucose, HDL- and LDL- cholesterols, triglycerides (TGs), amyloid-A, sensitive C-reactive protein (sCRP) and vitamin D binding protein (VDBP) and body mass index (BMI)]. RESULTS: Of 18 the SNPs examined for their association with nine metabolic phenotypes of interest, six were significantly associated with five metabolic phenotypes (Bonferroni correction, P ≤ 0.0027). Fasting insulin was associated with SNPs in IL6 and TNFA, serum HDL-C with variants of TNFA and CRP and serum sCRP level with SNPs in CRP. Cross-correlation analysis among the different metabolic factors related to risk of T2DM showed several significant associations. For example, BMI was directly correlated with glucose (r = 0.11), insulin (r = 0.15), sCRP (r = 0.23), LDL-C (r = 0.067) and TGs (r = 0.18) but inversely with HDL-C (r = -0.14). sCRP was also positively correlated (P < 0.0001) with insulin (r = 0.17), amyloid-A (r = 0.39), TGs (r = 0.26), and VDBP (r = 0.36) but inversely with HDL-C (r = -0.12). CONCLUSION: Genetic variants in the innate immunity pathway and its related inflammatory cascade is associated with some metabolic risk factors for T2DM; an observation that may provide a rationale for further studying their role as biomarkers for disease early risk prediction.