Modulation Of The Catalytic Activity Of Porphyrins By Lipid- And Surfactant-containing Nanostructures

The structural factors modulating porphyrin activity encompass pyrrole and equatorial ligands, as well as the central metal and the number and structure of their axial ligands. Of equal importance is the microenvironment provided by apoproteins, solvents and membranes. Porphyrins are often used to construct supramolecular structures with different applications. The modulation of activity of the porphyrins has been frequently achieved by mimicking nature, i.e., by the provision of different microenvironments for these molecules. The association of porphyrins to surfactant- and lipid-containing nanostructures has changed the activity of these compounds to mimic different enzymes such as SOD, cytochrome P450, peroxidases and others. In determined conditions, the reactive forms of the porphyrins are high-valence states of oxo-metal-π cations and oxo-metal produced by the reaction with peroxides and peracids. 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Transgenic rat with overproduction of ubiquitous angiotensin-(1-7) presents neuroprotection in a model of ischemia and reperfusion

Recent studies showed that angiotensin-(1-7) has cerebroprotective actions in stroke. In the present study, we aim to test whether tissue overexpression of Angiotensin-(1-7), mainly in the brain provides neuroprotection in a model of ischemia/reperfusion by bilateral common carotid arteries occlusion/reperfusion (BCCAo/R). Evaluation of neurological deficit scores and bilateral asymmetry test (BAT) were performed seven days after transient BCCAo/R in transgenic rats (TG-7371) overexpressing Angiotensin-(1-7) and Sprague-Dawley (SD) rats. To assess blood-brain barrier (BBB) permeability Evans blue dye (EB) was intravenously injected. Cytokine levels were quantified in the whole brain through Elisa assay and oxidative stress was measured 7 days after ischemia. The expression of AT(1) and Mas receptors and inducible nitric oxide synthase (iNOS) was evaluated by RT-PCR. Neurological deficits were observed in both SD-BCCAo/R and TG-BCCAo/R, contrasting to sham-operated groups. However, TG-BCCAo/R showed a significant lower neurological score and latency in BAT when compared with SD-BCCAo/R. BBB integrity in TG-BCCAo/R was improved, since these animals showed lower extravasation of EB than SD-BCCAo/R. Interestingly, TG-BCCAo/R presented lower levels of pro-inflammatory cytokines when compared to SD-BCCAo/R. Levels of IL-10 were higher in SD-BCCAo/R than in SD control and even higher in TG-BCCAo/R. TG-BCCAo/R animals presented decreased levels of TBARS and increase in SOD activity and GSH levels when compared to SD sham rats. RT-PCR results showed higher levels of AT(1) receptor and iNOS in SD-BCCAo/R compared to TG-BCCAo/R, but no difference was observed for Mas receptor. The present study shows that lifetime increase in cerebral expression of an Ang-(1-7)-producing fusion protein induces neuroprotection in experimental global cerebral ischemia and reperfusion, reassuring that, pharmacological strategies leading to increase in Ang-(1-7) can be an additional tool for stroke therapy

A study of the distribution of chitosan onto and within a paper sheet using a fluorescent chitosan derivative

International audienceA fluorescent chitosan derivative was deposited layer-by-layer onto conventional paper sheets and its distribution, in terms of both spreading and penetration, was assessed by SEM observations and emission measurements. The results showed that, on the one hand the surface distribution was highly homogeneous and, on the other hand, the penetration of chitosan within the paper pores ceased after a three layer deposit, beyond which any additional coating only produced an increase in its overall thickness and film-forming aptitude. These results show that this modified chitosan can be used as probe to optimize and understand the mechanism of the deposition of chitosan onto paper and other substrates

Increased circulating angiotensin-(1-7) protects white adipose tissue against development of a proinflammatory state stimulated by high-fat diet

INTRODUCTION: The aim of the present study was to evaluate the effect of a transgenic-induced chronic increase of Ang-(1-7) on the expression of inflammatory markers in adipose tissue and the metabolic profile in rats treated with high-fat diet. Research Design and Methods Transgenic rats expressing a Ang-(1-7)-producing fusion protein (TGR L-3292) and Sprague Dawley (SD) control rats 4weeks old were treated for 8weeks with high-fat diet. Food intake and body weight were measured once a week. Glucose-tolerance and insulin sensitivity tests were performed one week before the sacrifice. At end of experiment plasma lipids concentrations were measured in TGR and SD rats. Adipose tissue were weighted and corrected by the body weight. Proinflammatory markers in adipose tissue were analyzed using Western-blotting, real time-PCR and immunohistochemistry. RESULTS: High-fat diet TGR rats presented increased HDL cholesterol levels and decreased abdominal fat mass, without changes in food intake. In addition, rats with increased Ang-(1-7) levels had lower body weight. Molecular analysis revealed decreased IL-1β and COX-2 in adipose tissue. CONCLUSIONS: Taken together, these results show that chronic high circulating angiotensin-(1-7) levels protect against metabolic stress induced by high-fat diet decreasing the proinflammatory profile of adipose tissue

The burden of mental disorders, substance use disorders and self-harm among young people in Europe, 1990–2019: Findings from the Global Burden of Disease Study 2019

Background: Mental health is a public health issue for European young people, with great heterogeneity in resource allocation. Representative population-based studies are needed. The Global Burden of Disease (GBD) Study 2019 provides internationally comparable information on trends in the health status of populations and changes in the leading causes of disease burden over time. Methods: Prevalence, incidence, Years Lived with Disability (YLDs) and Years of Life Lost (YLLs) from mental disorders (MDs), substance use disorders (SUDs) and self-harm were estimated for young people aged 10-24 years in 31 European countries. Rates per 100,000 population, percentage changes in 1990-2019, 95% Uncertainty Intervals (UIs), and correlations with Sociodemographic Index (SDI), were estimated. Findings: In 2019, rates per 100,000 population were 16,983 (95% UI 12,823 – 21,630) for MDs, 3,891 (3,020 - 4,905) for SUDs, and 89·1 (63·8 - 123·1) for self-harm. In terms of disability, anxiety contributed to 647·3 (432–912·3) YLDs, while in terms of premature death, self-harm contributed to 319·6 (248·9–412·8) YLLs, per 100,000 population. Over the 30 years studied, YLDs increased in eating disorders (14·9%;9·4-20·1) and drug use disorders (16·9%;8·9-26·3), and decreased in idiopathic developmental intellectual disability (–29·1%;23·8-38·5). YLLs decreased in self-harm (–27·9%;38·3-18·7). Variations were found by sex, age-group and country. The burden of SUDs and self-harm was higher in countries with lower SDI, MDs were associated with SUDs. Interpretation: Mental health conditions represent an important burden among young people living in Europe. National policies should strengthen mental health, with a specific focus on young people. Funding: The Bill and Melinda Gates Foundation © 2022 The Author(s

The burden of mental disorders, substance use disorders and self-harm among young people in Europe, 1990–2019: Findings from the Global Burden of Disease Study 2019

Background: Mental health is a public health issue for European young people, with great heterogeneity in resource allocation. Representative population-based studies are needed. The Global Burden of Disease (GBD) Study 2019 provides internationally comparable information on trends in the health status of populations and changes in the leading causes of disease burden over time. Methods: Prevalence, incidence, Years Lived with Disability (YLDs) and Years of Life Lost (YLLs) from mental disorders (MDs), substance use disorders (SUDs) and self-harm were estimated for young people aged 10-24 years in 31 European countries. Rates per 100,000 population, percentage changes in 1990-2019, 95% Uncertainty Intervals (UIs), and correlations with Sociodemographic Index (SDI), were estimated. Findings: In 2019, rates per 100,000 population were 16,983 (95% UI 12,823 – 21,630) for MDs, 3,891 (3,020 - 4,905) for SUDs, and 89·1 (63·8 - 123·1) for self-harm. In terms of disability, anxiety contributed to 647·3 (432–912·3) YLDs, while in terms of premature death, self-harm contributed to 319·6 (248·9–412·8) YLLs, per 100,000 population. Over the 30 years studied, YLDs increased in eating disorders (14·9%;9·4-20·1) and drug use disorders (16·9%;8·9-26·3), and decreased in idiopathic developmental intellectual disability (–29·1%;23·8-38·5). YLLs decreased in self-harm (–27·9%;38·3-18·7). Variations were found by sex, age-group and country. The burden of SUDs and self-harm was higher in countries with lower SDI, MDs were associated with SUDs. Interpretation: Mental health conditions represent an important burden among young people living in Europe. National policies should strengthen mental health, with a specific focus on young people. Funding: The Bill and Melinda Gates Foundation © 2022 The Author(s

The burden of injury in Central, Eastern, and Western European sub-region: a systematic analysis from the Global Burden of Disease 2019 Study

Background: Injury remains a major concern to public health in the European region. Previous iterations of the Global Burden of Disease (GBD) study showed wide variation in injury death and disability adjusted life year (DALY) rates across Europe, indicating injury inequality gaps between sub-regions and countries. The objectives of this study were to: 1) compare GBD 2019 estimates on injury mortality and DALYs across European sub-regions and countries by cause-of-injury category and sex; 2) examine changes in injury DALY rates over a 20 year-period by cause-of-injury category, sub-region and country; and 3) assess inequalities in injury mortality and DALY rates across the countries. Methods: We performed a secondary database descriptive study using the GBD 2019 results on injuries in 44 European countries from 2000 to 2019. Inequality in DALY rates between these countries was assessed by calculating the DALY rate ratio between the highest-ranking country and lowest-ranking country in each year. Results: In 2019, in Eastern Europe 80 [95% uncertainty interval (UI): 71 to 89] people per 100,000 died from injuries; twice as high compared to Central Europe (38 injury deaths per 100,000; 95% UI 34 to 42) and three times as high compared to Western Europe (27 injury deaths per 100,000; 95%UI 25 to 28). The injury DALY rates showed less pronounced differences between Eastern (5129 DALYs per 100,000; 95% UI: 4547 to 5864), Central (2940 DALYs per 100,000; 95% UI: 2452 to 3546) and Western Europe (1782 DALYs per 100,000; 95% UI: 1523 to 2115). Injury DALY rate was lowest in Italy (1489 DALYs per 100,000) and highest in Ukraine (5553 DALYs per 100,000). The difference in injury DALY rates by country was larger for males compared to females. The DALY rate ratio was highest in 2005, with DALY rate in the lowest-ranking country (Russian Federation) 6.0 times higher compared to the highest-ranking country (Malta). After 2005, the DALY rate ratio between the lowest- and the highest-ranking country gradually decreased to 3.7 in 2019. Conclusions: Injury mortality and DALY rates were highest in Eastern Europe and lowest in Western Europe, although differences in injury DALY rates declined rapidly, particularly in the past decade. The injury DALY rate ratio of highest- and lowest-ranking country declined from 2005 onwards, indicating declining inequalities in injuries between European countries. © 2022, The Author(s)