| 1. |
- Lind, Lars, et al.
(författare)
-
Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)
- 2021
-
Ingår i: eLife. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
|
|
| 2. |
- Bixby, H., et al.
(författare)
-
Rising rural body-mass index is the main driver of the global obesity epidemic in adults
- 2019
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 569:7755, s. 260-4
-
Tidskriftsartikel (refereegranskat)abstract
- Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.
|
|
| 3. |
- Mishra, A, et al.
(författare)
-
Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
-
Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Taddei, C, et al.
(författare)
-
Repositioning of the global epicentre of non-optimal cholesterol
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
-
Tidskriftsartikel (refereegranskat)abstract
- High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
|
|
| 7. |
|
|
| 8. |
- Bergemalm, Daniel, 1977-, et al.
(författare)
-
Systemic Inflammation in Preclinical Ulcerative Colitis
- 2021
-
Ingår i: Gastroenterology. - : AGA Institute. - 0016-5085 .- 1528-0012. ; 161:5, s. 1526-1539.e9
-
Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Preclinical ulcerative colitis is poorly defined. We aimed to characterize the preclinical systemic inflammation in ulcerative colitis, using a comprehensive set of proteins.Methods: We obtained plasma samples biobanked from individuals who developed ulcerative colitis later in life (n = 72) and matched healthy controls (n = 140) within a population-based screening cohort. We measured 92 proteins related to inflammation using a proximity extension assay. The biologic relevance of these findings was validated in an inception cohort of patients with ulcerative colitis (n = 101) and healthy controls (n = 50). To examine the influence of genetic and environmental factors on these markers, a cohort of healthy twin siblings of patients with ulcerative colitis (n = 41) and matched healthy controls (n = 37) were explored.Results: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP-1) were up-regulated (P < .05) in preclinical ulcerative colitis compared with controls based on both univariate and multivariable models. Ingenuity Pathway Analyses identified several potential key regulators, including interleukin-1β, tumor necrosis factor, interferon-gamma, oncostatin M, nuclear factor-κB, interleukin-6, and interleukin-4. For validation, we built a multivariable model to predict disease in the inception cohort. The model discriminated treatment-naïve patients with ulcerative colitis from controls with leave-one-out cross-validation (area under the curve = 0.92). Consistently, MMP10, CXCL9, CXCL11, and MCP-1, but not CCL11 and SLAMF1, were significantly up-regulated among the healthy twin siblings, even though their relative abundances seemed higher in incident ulcerative colitis.Conclusions: A set of inflammatory proteins are up-regulated several years before a diagnosis of ulcerative colitis. These proteins were highly predictive of an ulcerative colitis diagnosis, and some seemed to be up-regulated already at exposure to genetic and environmental risk factors.
|
|
| 9. |
- Kariuki, Symon M., et al.
(författare)
-
Prevalence and factors associated with convulsive status epilepticus in Africans with epilepsy
- 2015
-
Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 84:18, s. 1838-1845
-
Tidskriftsartikel (refereegranskat)abstract
- Objective:We conducted a community survey to estimate the prevalence and describe the features, risk factors, and consequences of convulsive status epilepticus (CSE) among people with active convulsive epilepsy (ACE) identified in a multisite survey in Africa.Methods:We obtained clinical histories of CSE and neurologic examination data among 1,196 people with ACE identified from a population of 379,166 people in 3 sites: Agincourt, South Africa; Iganga-Mayuge, Uganda; and Kilifi, Kenya. We performed serologic assessment for the presence of antibodies to parasitic infections and HIV and determined adherence to antiepileptic drugs. Consequences of CSE were assessed using a questionnaire. Logistic regression was used to identify risk factors.Results:The adjusted prevalence of CSE in ACE among the general population across the 3 sites was 2.3 per 1,000, and differed with site (p < 0.0001). Over half (55%) of CSE occurred in febrile illnesses and focal seizures were present in 61%. Risk factors for CSE in ACE were neurologic impairments, acute encephalopathy, previous hospitalization, and presence of antibody titers to falciparum malaria and HIV; these differed across sites. Burns (15%), lack of education (49%), being single (77%), and unemployment (78%) were common in CSE; these differed across the 3 sites. Nine percent with and 10% without CSE died.Conclusions:CSE is common in people with ACE in Africa; most occurs with febrile illnesses, is untreated, and has focal features suggesting preventable risk factors. Effective prevention and the management of infections and neurologic impairments may reduce the burden of CSE in ACE.
|
|
| 10. |
- Dennis, Roger L. H., et al.
(författare)
-
Butterflies of European islands : the implications of the geography and ecology of rarity and endemicity for conservation
- 2008
-
Ingår i: Journal of Insect Conservation. - : Springer Science and Business Media LLC. - 1366-638X .- 1572-9753. ; 12:3-4, s. 205-236
-
Tidskriftsartikel (refereegranskat)abstract
- Depending on their faunal content islands can function as important ‘vehicles’ for conservation. In this study, we examine data on 440 butterfly species over 564 European islands in 10 island groups. To determine the status of the butterfly fauna, we have adopted two approaches, island-focused and species-focused, examined using principal components analysis and regression modelling.In the former, we relate species richness, rarity and endemicity to island geography (area, elevation, isolation and location in latitude and longitude); in the latter, species occurrence on islands is examined in relation to distribution, range, range boundaries, and altitudinal limits on the continent as well as species’ ecology (number of"/> host plants) and morphology (wing expanse). Species on islands are also assessed for their status on the continental mainland, their distributional dynamics (extinctions, distribution changes) and conservation status (Red Data Book, European Habitat Directive, Species of European Conservation Concern and Bern Convention listing.Unexpectedly, we find that a large fraction of the European butterfly species is found on the islands (63.4%; 59% on small islands) comprising some 6.2% of the land area of Europe. Although species occurring on the islands tend, on the whole, to have lower conservation status and are not declining over Europe, 45 species are endemics restricted to the islands. Species richness shows only a weak locational pattern and is related as expected to isolation from the continental source and island area; but, both rarity and endemicity have distinctive geographical bias to southern Europe, on islands now under increasing pressure from climate change and increasingly intensive human exploitation. The vulnerability of species on islands is emphasised in the relationship of island occurrence (% occurrence and presence/absence of species on any island) with continental distributions. A large proportion of the variation (84%) is accounted by continental distribution, the southern range limit and lower altitudinal limit. Most species (69%) occur on very few islands (\5%). In view of ongoing species dynamics on islands, migrations and extinctions of species, island repositories of species depend in large part on conservation of butterflies at continental sources. The unique faunas and rare species on islands also depend on appropriate concern being given to the island faunas. Conservation of European islands is thus a two-way process, sustaining sources and conserving island refuges. Residuals from the regressions (islands with more or fewer species, rare and endemic species; species occurring more or less frequently than expected on islands) provide warning signals of regions and islands deserving immediate attention.
|
|
| 11. |
- Grieshop, Karl, 1986-, et al.
(författare)
-
Dominance reversals : the resolution of genetic conflict and maintenance of genetic variation
- 2024
-
Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - 0962-8452 .- 1471-2954. ; 291:2018
-
Forskningsöversikt (refereegranskat)abstract
- Beneficial reversals of dominance reduce the costs of genetic trade-offs and can enable selection to maintain genetic variation for fitness. Beneficial dominance reversals are characterized by the beneficial allele for a given context (e.g. habitat, developmental stage, trait or sex) being dominant in that context but recessive where deleterious. This context dependence at least partially mitigates the fitness consequence of heterozygotes carrying one non-beneficial allele for their context and can result in balancing selection that maintains alternative alleles. Dominance reversals are theoretically plausible and are supported by mounting empirical evidence. Here, we highlight the importance of beneficial dominance reversals as a mechanism for the mitigation of genetic conflict and review the theory and empirical evidence for them. We identify some areas in need of further research and development and outline three methods that could facilitate the identification of antagonistic genetic variation (dominance ordination, allele-specific expression and allele-specific ATAC-Seq (assay for transposase-accessible chromatin with sequencing)). There is ample scope for the development of new empirical methods as well as reanalysis of existing data through the lens of dominance reversals. A greater focus on this topic will expand our understanding of the mechanisms that resolve genetic conflict and whether they maintain genetic variation.
|
|
| 12. |
- Guimaraes, Drielle D., et al.
(författare)
-
Dietary Nitrate Reduces Blood Pressure in Rats With Angiotensin II-Induced Hypertension via Mechanisms That Involve Reduction of Sympathetic Hyperactivity
- 2019
-
Ingår i: Hypertension. - : Lippincott Williams & Wilkins. - 0194-911X .- 1524-4563. ; 73:4, s. 839-848
-
Tidskriftsartikel (refereegranskat)abstract
- Several experimental and clinical studies have shown that dietary nitrate supplementation can increase nitric oxide bioavailability. In the oral cavity, commensal bacteria reduce nitrate to nitrite, which is subsequently absorbed into the circulation where reduction to nitric oxide by enzymatic systems occur. Although it is well-known that boosting the nitrate-nitrite-nitric oxide pathway can improve cardiovascular, renal, and metabolic functions and that sympathoexcitation contributes to the development of the same disorders, the potential effects of dietary nitrate on sympathetic activity remain to be elucidated. In this study, we hypothesized that treatment with inorganic nitrate could prevent the increase in sympathetic nerve activity in an experimental model of Ang II (angiotensin II)-induced hypertension. Multiple in vivo approaches were combined, that is, Wistar rats orally treated with the nitric oxide synthase inhibitor L-NAME (N(G)-nitro-L-arginine methyl ester, 0.5 g/L) and implanted with subcutaneous osmotic minipump for continuous delivery of Ang II (120 ng/kg per minute; 14 days). Simultaneously, rats were supplemented with sodium nitrate (10 mmol/L) or placebo (sodium chloride; 10 mmol/L) in the drinking water. Blood pressure, heart rate, and renal sympathetic nerve activity were recorded. In placebo-treated rats, Ang II+ L-NAME treatment-induced arterial hypertension, which was linked with reduced spontaneous baroreflex sensitivity and increased renal sympathetic nerve activity, as well as upregulation of AT 1 Rs (Ang II type-1 receptors) in the rostral ventrolateral medulla. Supplementation with nitrate normalized the expression of AT 1 Rs in rostral ventrolateral medulla and reduced sympathetic nerve activity, which was associated with attenuated development of hypertension. In conclusion, chronic dietary nitrate supplementation blunted the development of hypertension via mechanisms that involve reduction of sympathetic outflow.
|
|
| 13. |
- Jendzurski, John R., et al.
(författare)
-
Image quality testing : Selection of images for assessing test subject input
- 2014
-
Ingår i: International Journal on Smart Sensing and Intelligent Systems. - 1178-5608. ; 7:5, s. 110-113
-
Tidskriftsartikel (refereegranskat)abstract
- Determining image quality is dependent to some degree on human interpretation. Although entirely subjective methods of evaluating image quality may be adequate for consumer applications, they are not acceptable for security and safety applications where operator interpretation may lead to missing a threat or finding threats where they do not exist. Therefore, methods must be developed to ensure that the imagery used in security and safety applications are of sufficient quality to allow the operator to perform his job accurately and efficiently. NIST has developed a method to quantify the capability of imagers to provide images of sufficient quality to allow humans to perform specific perception-based tasks. A one-time humanperception based step is required that results in perception coefficients that are combined with lab-measured objective image quality indicators (IQIs) to calculate image quality. This work uses a d′ evaluation method to examine the performance of test subjects in the human-perception based step, which was identification of a fire hazard in a set of grey-scale infrared images.
|
|
| 14. |
- Kariuki, Symon M., et al.
(författare)
-
Electroencephalographic features of convulsive epilepsy in Africa : A multicentre study of prevalence, pattern and associated factors
- 2016
-
Ingår i: Clinical Neurophysiology. - : Elsevier BV. - 1388-2457 .- 1872-8952. ; 127:2, s. 1099-1107
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: We investigated the prevalence and pattern of electroencephalographic (EEG) features of epilepsy and the associated factors in Africans with active convulsive epilepsy (ACE).Methods: We characterized electroencephalographic features and determined associated factors in a sample of people with ACE in five African sites. Mixed-effects modified Poisson regression model was used to determine factors associated with abnormal EEGs.Results: Recordings were performed on 1426 people of whom 751 (53%) had abnormal EEGs, being an adjusted prevalence of 2.7 (95% confidence interval (95% CI), 2.5–2.9) per 1000. 52% of the abnormal EEG had focal features (75% with temporal lobeinvolvement). The frequency and pattern of changes differed with site. Abnormal EEGs were associated with adverse perinatal events (risk ratio (RR) = 1.19 (95% CI, 1.07–1.33)), cognitive impairments (RR = 1.50 (95% CI, 1.30–1.73)), use of anti-epilepticdrugs (RR = 1.25 (95% CI, 1.05–1.49)), focal seizures (RR = 1.09 (95% CI, 1.00–1.19)) and seizure frequency (RR = 1.18 (95% CI, 1.10–1.26) for daily seizures; RR = 1.22 (95% CI, 1.10–1.35) for weekly seizures and RR = 1.15 (95% CI, 1.03–1.28) for monthly seizures)).Conclusions: EEG abnormalities are common in Africans with epilepsy and are associated with preventable risk factors.Significance: EEG is helpful in identifying focal epilepsy in Africa, where timing of focal aetiologies is problematic and there is a lack of neuroimaging services.
|
|
| 15. |
- Lundberg, Jon O., et al.
(författare)
-
Nitrate and nitrite in biology, nutrition and therapeutics
- 2009
-
Ingår i: Nature Chemical Biology. - : Springer Science and Business Media LLC. - 1552-4450 .- 1552-4469. ; 5:12, s. 865-869
-
Tidskriftsartikel (refereegranskat)abstract
- Inorganic nitrate and nitrite from endogenous or dietary sources are metabolized in vivo to nitric oxide (NO) and other bioactive nitrogen oxides. The nitrate-nitrite-NO pathway is emerging as an important mediator of blood flow regulation, cell signaling, energetics and tissue responses to hypoxia. The latest advances in our understanding of the biochemistry, physiology and therapeutics of nitrate, nitrite and NO were discussed during a recent 2-day meeting at the Nobel Forum, Karolinska Institutet in Stockholm.
|
|
| 16. |
- Ngugi, Anthony K., et al.
(författare)
-
Prevalence of active convulsive epilepsy in sub-Saharan Africa and associated risk factors : cross-sectional and case-control studies
- 2013
-
Ingår i: Lancet Neurology. - 1474-4422 .- 1474-4465. ; 12:3, s. 253-263
-
Tidskriftsartikel (refereegranskat)abstract
- Background The prevalence of epilepsy in sub-Saharan Africa seems to be higher than in other parts of the world, but estimates vary substantially for unknown reasons. We assessed the prevalence and risk factors of active convulsive epilepsy across five centres in this region. Methods We did large population-based cross-sectional and case-control studies in five Health and Demographic Surveillance System centres: Kilifi, Kenya (Dec 3, 2007-July 31, 2008); Agincourt, South Africa (Aug 4, 2008-Feb 27, 2009); Iganga-Mayuge, Uganda (Feb 2, 2009-Oct 30, 2009); Ifakara, Tanzania (May 4, 2009-Dec 31, 2009); and Kintampo, Ghana (Aug 2, 2010-April 29, 2011). We used a three-stage screening process to identify people with active convulsive epilepsy. Prevalence was estimated as the ratio of confirmed cases to the population screened and was adjusted for sensitivity and attrition between stages. For each case, an age-matched control individual was randomly selected from the relevant centre's census database. Fieldworkers masked to the status of the person they were interviewing administered questionnaires to individuals with active convulsive epilepsy and control individuals to assess sociodemographic variables and historical risk factors (perinatal events, head injuries, and diet). Blood samples were taken from a randomly selected subgroup of 300 participants with epilepsy and 300 control individuals from each centre and were screened for antibodies to Toxocara canis, Toxoplasma gondii, Onchocerca volvulus, Plasmodium falciparum, Taenia solium, and HIV. We estimated odds ratios (ORs) with logistic regression, adjusted for age, sex, education, employment, and marital status. Results 586 607 residents in the study areas were screened in stage one, of whom 1711 were diagnosed as having active convulsive epilepsy. Prevalence adjusted for attrition and sensitivity varied between sites: 7.8 per 1000 people (95% CI 7.5-8.2) in Kilifi, 7.0 (6.2-7.4) in Agincourt, 10.3 (9.5-11.1) in Iganga-Mayuge, 14.8 (13.8-15.4) in Ifakara, and 10.1 (9.5-10.7) in Kintampo. The 1711 individuals with the disorder and 2032 control individuals were given questionnaires. In children (aged <18 years), the greatest relative increases in prevalence were associated with difficulties feeding, crying, or breathing after birth (OR 10.23, 95% CI 5 85-1788; p<0.0001); abnormal antenatal periods (2.15, 1.53-3.02; p<0.0001); and head injury (1.97, 1.28-3.03; p=0.002). In adults (aged >= 18 years), the disorder was significantly associated with admission to hospital with malaria or fever (2.28, 1.06-4.92; p=0.036), exposure to T canis (1.74, 1.27-2.40; p=0.0006), exposure to T gondii (1.39, 1.05-1.84; p=0.021), and exposure to 0 volvulus (2.23, 1.56-3.19; p<0.0001). Hypertension (2.13, 1.08-4.20; p=0.029) and exposure to T solium (7.03, 2.06-24.00; p=0.002) were risk factors for adult-onset disease. Interpretation The prevalence of active convulsive epilepsy varies in sub-Saharan Africa and that the variation is probably a result of differences in risk factors. Programmes to control parasitic diseases and interventions to improve antenatal and perinatal care could substantially reduce the prevalence of epilepsy in this region.
|
|
| 17. |
- Porpino, Suenia K. P., et al.
(författare)
-
Nitric oxide generation by the organic nitrate NDBP attenuates oxidative stress and angiotensin II-mediated hypertension
- 2016
-
Ingår i: British Journal of Pharmacology. - : Wiley. - 0007-1188 .- 1476-5381. ; 173:14, s. 2290-2302
-
Tidskriftsartikel (refereegranskat)abstract
- Background and PurposeNO deficiency and oxidative stress are crucially involved in the development or progression of cardiovascular disease, including hypertension and stroke. We have previously demonstrated that acute treatment with the newly discovered organic nitrate, 2-nitrate-1,3-dibuthoxypropan (NDBP), is associated with NO-like effects in the vasculature. This study aimed to further characterize the mechanism(s) and to elucidate the therapeutic potential in a model of hypertension and oxidative stress. Experimental ApproachA combination of ex vivo, in vitro and in vivo approaches was used to assess the effects of NDBP on vascular reactivity, NO release, NADPH oxidase activity and in a model of hypertension. Key ResultsEx vivo vascular studies demonstrated NDBP-mediated vasorelaxation in mesenteric resistance arteries, which was devoid of tolerance. In vitro studies using liver and kidney homogenates revealed dose-dependent and sustained NO generation by NDBP, which was attenuated by the xanthine oxidase inhibitor febuxostat. In addition, NDBP reduced NADPH oxidase activity in the liver and prevented angiotensin II-induced activation of NADPH oxidase in the kidney. In vivo studies showed that NDBP halted the progression of hypertension in mice with chronic angiotensin II infusion. This was associated with attenuated cardiac hypertrophy, and reduced NADPH oxidase-derived oxidative stress and fibrosis in the kidney and heart. Conclusion and ImplicationsThe novel organic nitrate NDBP halts the progression of angiotensin II-mediated hypertension. Mechanistically, our findings suggest that NDBP treatment is associated with sustained NO release and attenuated activity of NADPH oxidase, which to some extent requires functional xanthine oxidase.
|
|
