Farmacologia e toxicologia do ácido ascórbico: uma revisão

L-Ascorbic acid (AA) or vitamin C is a six carbon cetolactone, structurally related to glucose and other hexoses. The major sources of AA are citrus fruits, strawberry, melon, green pepper, potato, tomato and leafy green vegetables. AA interferes with a broad spectrum of oxidation-reduction reactions, acting in at least 10 enzymatic systems. In this way, vitamin C influences the synthesis of collagen, carnitine, and neurotransmitters; the transformation of cholesterol into bile acids; biotransformation of xenobiotics substances; absorption of iron; and formation and scavenging of oxygen free radicals. AA is used as food addictive because of its antioxidant properties.Therapeutically, it is used as nutritional supplement during scurvy. Human beings and other primates, as well as guinea pigs and some species of bats are mammals that are unable to synthesize AA; thus, they need AA in the diet to prevent scurvy. Rats are able to synthesize AA using glucose, through intermediary formation of D-glucuronic acid, L-gulonic acid and gulonolactone.Homo sapiens lack the hepatic enzyme gulonolactone oxidase, which catalyses the last reaction of the biosynthesis pathway (L-gulonolactone conversion to ascorbic acid). The functions of central nervous, immune, and cardiovascular systems, and the periodontal tissue, as well as the detoxification function of the liver, are negatively influenced by vitamin C deficiency. In this way, it has been described several benefits of vitamin supplement ingestion, as decreasing of LDL cholesterol, including mega doses that can reach as much as 18g daily. Although there have been raised many literatures about vitamin C use in a wide variety of diseases, there is a lack of clinical efficiency of mega doses; besides, some side effects can come up, as diarrhea and oxalate stones in the kidneys. However, the ideal daily intake of vitamin C is still unknown. This happen because the recommended daily intake is based in a single role of AA, the scurvy prevention. Daily ingestion of AA should be the same quantity excreted or destroyed by oxidation, taking into consideration AA actions on the enzymatic systems. Actually, vitamin C is necessary for health in little quantities and is harmful in large doses. It happens because the cells are always walking a balance between oxidation and reduction processes, and AA in great quantities assume oxidative characteristics, interfering in this balance. Although the existence of several evidences indicating AA toxicity in large doses, there are some authors who believe that the ingestion of large doses is safe, but they admit that the disposable data are very contradictory.O L–ácido ascórbico (AA) ou vitamina C, é uma cetolactona de 6 carbonos, estruturalmente relacionada com a glicose e outras hexoses. As fontes de AA na ieta são as frutas cítricas, morango, melão, pimentão verde, repolho, batata, tomate e vegetais de folhas verdes. O AA atua em reações de oxi-redução em pelo menos 10 sistemas enzimáticos. Dessa maneira, a vitamina C tem influência na síntese do colágeno, carnitina e neurotransmissores; transformação de colesterol em ácidos biliares; biotransformação de xenobióticos; absorção do ferro; formação e neutralização de radicais livres de oxigênio. Por suas propriedades antioxidantes, o AA é usado como aditivo alimentar. Terapeuticamente, é usado como suplemento nutricional durante estados de deficiência da vitamina, que é o caso do escorbuto. Os seres humanos e outros primatas, bem como as cobaias e alguns tipos de morcegos são os únicos mamíferos conhecidos incapazes de sintetizar o AA; em consequência, necessitam da vitamina C na dieta para a prevenção do escorbuto. O rato sintetiza o ácido ascórbico a partir da glicose, através da formação intermediária de ácido D-glicurônico, ácido L-gulônico e L-gulonolactona. O homem não possui a enzima hepática gulonolactona oxidase, que fez a última reação da via de síntese, que é a conversão da L-gulonolactona em ácido L-ascórbico. As funções do sistema nervoso, imune e cardiovascular, o tecido periodontal assim como a função de detoxificação do fígado são negativamente influenciados pela deficiência de vitamina C. Assim, têm sido relatados vários benefícios da ingestão de suplementos da vitamina, inclusive de megadoses que podem alcançar até 18g diárias, como diminuição do colesterol LDL. Apesar de ter surgido uma extensa literatura a respeito da aplicação da vitamina C em uma grande variedade de doenças, há uma falta de eficácia clinica das megadoses, além de alguns efeitos colaterais que podem surgir, como diarreia e cálculos de oxalato nos rins. No entanto, a dose diária ideal de vitamina C ainda é desconhecida. Isso porque a dose diária recomendada atualmente baseia-se em uma única função do AA, a de evitar o escorbuto. A ingestão diária de AA deve ser igual à quantidade excretada ou destruída pela oxidação, levando em conta os sistemas enzimáticos nos quais a vitamina atua. Na verdade, a vitamina C é necessária para a saúde em pequenas quantidades e danosa em grandes doses. Isso acontece porque as células estão em constante manutenção de seus processos de oxidação e redução, e o AA em grande quantidade assume características oxidativas, interferindo então neste equilíbrio. Apesar de várias evidências indicando a toxicidade do AA em altas doses, também há autores que afirmam que a ingestão de grandes doses de vitamina C é segura, apesar de admitir que os dados disponíveis são muito contraditórios.

Protocolo de manejo de suspeita de infecção viral de vias respiratórias em pacientes com neoplasia hematológica do serviço de hematologia e transplante de medula óssea do Hospital Universitário Walter Cantídio (HUWC)

Infecção respiratória viral é causa significativa de morbi-mortalidade em paciente com doenças hematológicas. Deve ser suspeitado sempre que houver sintomas como coriza, obstrução nasal, odinofagia, tosse e dispnéia e deve-se seguir à identificação viral, quando possível. Os casos podem ser classificados como possível, provável ou confirmado. E observando-se o risco de progressão da infecção para vias aéreas inferiores, o diagnóstico deve ser precoce e as medidas terapêuticas específicas aos vírus bem como medidas de controle da infecção no ambiente hospitalar devem ser prontamente tomadas. O presente trabalho visa descrever um protocolo de manejo da infecção viral de vias respiratórias em pacientes com neoplasia hematológica dentro do Serviço de Hematologia e Transplante de medula do Hospital Universitário Walter Cantídio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP

Measuring universal health coverage based on an index of effective coverage of health services in 204 countries and territories, 1990–2019 : A systematic analysis for the Global Burden of Disease Study 2019

Background Achieving universal health coverage (UHC) involves all people receiving the health services they need, of high quality, without experiencing financial hardship. Making progress towards UHC is a policy priority for both countries and global institutions, as highlighted by the agenda of the UN Sustainable Development Goals (SDGs) and WHO's Thirteenth General Programme of Work (GPW13). Measuring effective coverage at the health-system level is important for understanding whether health services are aligned with countries' health profiles and are of sufficient quality to produce health gains for populations of all ages. Methods Based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we assessed UHC effective coverage for 204 countries and territories from 1990 to 2019. Drawing from a measurement framework developed through WHO's GPW13 consultation, we mapped 23 effective coverage indicators to a matrix representing health service types (eg, promotion, prevention, and treatment) and five population-age groups spanning from reproductive and newborn to older adults (≥65 years). Effective coverage indicators were based on intervention coverage or outcome-based measures such as mortality-to-incidence ratios to approximate access to quality care; outcome-based measures were transformed to values on a scale of 0–100 based on the 2·5th and 97·5th percentile of location-year values. We constructed the UHC effective coverage index by weighting each effective coverage indicator relative to its associated potential health gains, as measured by disability-adjusted life-years for each location-year and population-age group. For three tests of validity (content, known-groups, and convergent), UHC effective coverage index performance was generally better than that of other UHC service coverage indices from WHO (ie, the current metric for SDG indicator 3.8.1 on UHC service coverage), the World Bank, and GBD 2017. We quantified frontiers of UHC effective coverage performance on the basis of pooled health spending per capita, representing UHC effective coverage index levels achieved in 2019 relative to country-level government health spending, prepaid private expenditures, and development assistance for health. To assess current trajectories towards the GPW13 UHC billion target—1 billion more people benefiting from UHC by 2023—we estimated additional population equivalents with UHC effective coverage from 2018 to 2023. Findings Globally, performance on the UHC effective coverage index improved from 45·8 (95% uncertainty interval 44·2–47·5) in 1990 to 60·3 (58·7–61·9) in 2019, yet country-level UHC effective coverage in 2019 still spanned from 95 or higher in Japan and Iceland to lower than 25 in Somalia and the Central African Republic. Since 2010, sub-Saharan Africa showed accelerated gains on the UHC effective coverage index (at an average increase of 2·6% [1·9–3·3] per year up to 2019); by contrast, most other GBD super-regions had slowed rates of progress in 2010–2019 relative to 1990–2010. Many countries showed lagging performance on effective coverage indicators for non-communicable diseases relative to those for communicable diseases and maternal and child health, despite non-communicable diseases accounting for a greater proportion of potential health gains in 2019, suggesting that many health systems are not keeping pace with the rising non-communicable disease burden and associated population health needs. In 2019, the UHC effective coverage index was associated with pooled health spending per capita (r=0·79), although countries across the development spectrum had much lower UHC effective coverage than is potentially achievable relative to their health spending. Under maximum efficiency of translating health spending into UHC effective coverage performance, countries would need to reach $1398 pooled health spending per capita (US$ adjusted for purchasing power parity) in order to achieve 80 on the UHC effective coverage index. From 2018 to 2023, an estimated 388·9 million (358·6–421·3) more population equivalents would have UHC effective coverage, falling well short of the GPW13 target of 1 billion more people benefiting from UHC during this time. Current projections point to an estimated 3·1 billion (3·0–3·2) population equivalents still lacking UHC effective coverage in 2023, with nearly a third (968·1 million [903·5–1040·3]) residing in south Asia. Interpretation The present study demonstrates the utility of measuring effective coverage and its role in supporting improved health outcomes for all people—the ultimate goal of UHC and its achievement. Global ambitions to accelerate progress on UHC service coverage are increasingly unlikely unless concerted action on non-communicable diseases occurs and countries can better translate health spending into improved performance. Focusing on effective coverage and accounting for the world's evolving health needs lays the groundwork for better understanding how close—or how far—all populations are in benefiting from UHC

Measuring universal health coverage based on an index of effective coverage of health services in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background Achieving universal health coverage (UHC) involves all people receiving the health services they need, of high quality, without experiencing financial hardship. Making progress towards UHC is a policy priority for both countries and global institutions, as highlighted by the agenda of the UN Sustainable Development Goals (SDGs) and WHO's Thirteenth General Programme of Work (GPW13). Measuring effective coverage at the health-system level is important for understanding whether health services are aligned with countries' health profiles and are of sufficient quality to produce health gains for populations of all ages. Methods Based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we assessed UHC effective coverage for 204 countries and territories from 1990 to 2019. Drawing from a measurement framework developed through WHO's GPW13 consultation, we mapped 23 effective coverage indicators to a matrix representing health service types (eg, promotion, prevention, and treatment) and five population-age groups spanning from reproductive and newborn to older adults (≥65 years). Effective coverage indicators were based on intervention coverage or outcome-based measures such as mortality-to-incidence ratios to approximate access to quality care; outcome-based measures were transformed to values on a scale of 0–100 based on the 2·5th and 97·5th percentile of location-year values. We constructed the UHC effective coverage index by weighting each effective coverage indicator relative to its associated potential health gains, as measured by disability-adjusted life-years for each location-year and population-age group. For three tests of validity (content, known-groups, and convergent), UHC effective coverage index performance was generally better than that of other UHC service coverage indices from WHO (ie, the current metric for SDG indicator 3.8.1 on UHC service coverage), the World Bank, and GBD 2017. We quantified frontiers of UHC effective coverage performance on the basis of pooled health spending per capita, representing UHC effective coverage index levels achieved in 2019 relative to country-level government health spending, prepaid private expenditures, and development assistance for health. To assess current trajectories towards the GPW13 UHC billion target—1 billion more people benefiting from UHC by 2023—we estimated additional population equivalents with UHC effective coverage from 2018 to 2023. Findings Globally, performance on the UHC effective coverage index improved from 45·8 (95% uncertainty interval 44·2–47·5) in 1990 to 60·3 (58·7–61·9) in 2019, yet country-level UHC effective coverage in 2019 still spanned from 95 or higher in Japan and Iceland to lower than 25 in Somalia and the Central African Republic. Since 2010, sub-Saharan Africa showed accelerated gains on the UHC effective coverage index (at an average increase of 2·6% [1·9–3·3] per year up to 2019); by contrast, most other GBD super-regions had slowed rates of progress in 2010–2019 relative to 1990–2010. Many countries showed lagging performance on effective coverage indicators for non-communicable diseases relative to those for communicable diseases and maternal and child health, despite non-communicable diseases accounting for a greater proportion of potential health gains in 2019, suggesting that many health systems are not keeping pace with the rising non-communicable disease burden and associated population health needs. In 2019, the UHC effective coverage index was associated with pooled health spending per capita (r=0·79), although countries across the development spectrum had much lower UHC effective coverage than is potentially achievable relative to their health spending. Under maximum efficiency of translating health spending into UHC effective coverage performance, countries would need to reach $1398 pooled health spending per capita (US$ adjusted for purchasing power parity) in order to achieve 80 on the UHC effective coverage index. From 2018 to 2023, an estimated 388·9 million (358·6–421·3) more population equivalents would have UHC effective coverage, falling well short of the GPW13 target of 1 billion more people benefiting from UHC during this time. Current projections point to an estimated 3·1 billion (3·0–3·2) population equivalents still lacking UHC effective coverage in 2023, with nearly a third (968·1 million [903·5–1040·3]) residing in south Asia. Interpretation The present study demonstrates the utility of measuring effective coverage and its role in supporting improved health outcomes for all people—the ultimate goal of UHC and its achievement. Global ambitions to accelerate progress on UHC service coverage are increasingly unlikely unless concerted action on non-communicable diseases occurs and countries can better translate health spending into improved performance. Focusing on effective coverage and accounting for the world's evolving health needs lays the groundwork for better understanding how close—or how far—all populations are in benefiting from UHC