Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Circulating renin-angiotensin system and catecholamines in childhood: is there a role for birthweight?

There have been only a few reports on the sympathoadrenal and renin-angiotensin systems in children of small gestational age. The purpose of the present study was to investigate plasma levels of ACE (angiotensin-converting enzyme) activity, angiotensin and catecholamines in 8- to 13-year-old children and to determine whether there are correlations between the components of these systems with both birthweight and BP (blood pressure) levels. This clinical study included 66 children (35 boys and 31 girls) in two groups: those born at term with an appropriate birthweight [AGA (appropriate-for-gestational age) group, n = 31] and those born at term but with a small birthweight for gestational age [SGA (small-for-gestational age) group, n = 35]. Concentrations of angiotensin, catecholamines and ACE activity were determined in plasma. Circulating noradrenaline levels were significantly elevated in SGA girls compared with AGA girls (P = 0.036). In addition, angiotensin 11 and ACE activity were higher in SGA boys (P = 0.024 and P = 0.050 respectively). There was a significant association of the circulating levels of both angiotensin 11 and ACE activity with BP levels in our study population. Although the underlying mechanisms that link restricted fetal growth with later cardiovascular events are not fully understood, the findings in the present study support the link between low birthweight and overactivity of both sympathoadrenal and renin-angiotensin systems into later childhood

Desigualdade, pobreza e condições de saúde e nutrição na infância no Nordeste brasileiro

Estudo transversal, envolvendo 2.001 crianças das áreas rural e urbana de dez municípios da Bahia, Brasil. Avalia-se a relação entre os gradientes da desigualdade e os fatores do ambiente familiar, de saúde e nutrição, utilizando-se a regressão logística multinomial multivariada. As crianças do tercil intermediário das condições de vida e aquelas do tercil mais pobre têm chances significantes e crescentes de viverem na área rural, em domicílio chefiado pela mulher, ter o pai desempregado, mãe com baixa escolaridade, de dormir com mais de uma pessoa na mesma cama, déficit linear grave e consumir retinol abaixo da mediana. A existência de mais de uma criança no domicílio, ser portadora de déficit ponderal e ter o consumo de lipídeo abaixo da mediana foram eventos também significantes para as crianças mais pobres. A anemia foi identificada entre as crianças do tercil intermediário. A desigualdade expõe as crianças a chances crescentes de inadequado estado de saúde e nutrição. Políticas de saúde podem implementar medidas emergenciais no sentido de minimizar os males impostos pela desigualdade à saúde e nutrição na infância

Seleção de prioridades para programas de saúde, nutrição e alimentação: um exemplo no estado da Bahia Selection of priorities for health and nutrition programs: an example in the state of Bahia

OBJETIVOS: entre 1996 e 1998 foram implantadas três políticas públicas na área de saúde materno-infantil: Programa de Redução da Mortalidade Infantil (PRMI), Programa Comunidade Solidária (PCS) e Incentivo de Combate às Carências Nutricionais (ICCN). Este estudo teve como objetivo comparar a metodologia empregada para selecionar os municípios prioritários nestas três políticas públicas. MÉTODOS: os índices e indicadores estatísticos, bem como as bases de dados que deram origem aos mesmos, as suas variáveis independentes e dependentes e a modelagem estatística, foram analisados a partir de sua descrição nas publicações oficiais. Foi usado como exemplo o estado da Bahia e a construção da base cartográfica ocorreu pela digitalização do contorno dos municípios, diretamente na tela do programa Epi-Map. RESULTADOS: pode-se observar que parâmetros distintos e diferentes bases de dados foram empregados para a construção dos três diferentes índices analisados. Como resultado final dentre os 111 municípios selecionados pelo PRMI, os 96 escolhidos pelo PCS e os 100 considerados prioritários dentro do ICCN, verificou-se que houve superposição em apenas 28. CONCLUSÕES: no caso destas três políticas públicas, implantadas quase simultaneamente no estado da Bahia, envolvendo um volume considerável de recursos, em menos do que 28% dos casos ocorreu o que se pode chamar de focalização e convergência, elementos considerados essenciais para a otimização do investimento dos recursos públicos em políticas sociais.<br>OBJECTIVES: between 1996 and 1998 three public policies in the area of maternal and child health were implemented: Program to Reduce Infant Mortality (PRIM), Community Solidarity Program (CSP) and Incentive to Combat Nutritional Deficiencies (ICND). The objective of this study was to compare the methodology used to select priorities and to choose municipalities for these three public policies. METHODS: the indexes and statistical indicators, as well as the databases from which they originated, the independent and dependent variables and statistical models employed were analyzed, based on the description available in official publications. The state of Bahia was chosen as an example, and the construction of the cartographic database was performed directly on the screen, with the software Epi-Map. RESULTS: one could observe that different parameters and distinct databases were used to construct each one of the indexes analyzed. As a final result, there was an agreement in only 28 of the 111 municipalities chosen by PRIM, the 96 selected by CSP and the 100 considered priorities by the ICND. CONCLUSIONS: in the case of these three social programs, implemented almost simultaneously in the state of Bahia, involved considerable investments of funds, focusing and targeting, which are key elements for the optimization of public spending in social policies, occurred in only less than 28% of the cases

Endoplasmic reticulum stress impairs cardiomyocyte contractility through JNK-dependent upregulation of BNIP3

Disruption of endoplasmic reticulum (ER) homeostasis is a common feature of cardiac diseases. However, the signaling events involved in ER stress-induced cardiac dysfunction are still elusive. Here, we uncovered a mechanism by which disruption of ER homeostasis impairs cardiac contractility.We found that ER stress is associated with activation of JNK and upregulation of BNIP3 in a post-myocardial infarction (MI) model of cardiac dysfunction. Of interest, 4-week treatment of MI rats with the chemical ER chaperone 4-phenylbutyrate (4PBA) prevented both activation of JNK and upregulation of BNIP3, and improved cardiac contractility. We showed that disruption of ER homeostasis by treating adult rat cardiomyocytes in culture with tunicamycin leads to contractile dysfunction through JNK signaling pathway. Upon ER stress JNK upregulates BNIP3 in a FOXO3a-dependent manner. Further supporting a BNIP3 mechanism for ER stress-induced deterioration of cardiac function, siRNA-mediated BNIP3 knockdown mitigated ER stress-induced cardiomyocyte dysfunction by reestablishing sarcoplasmic reticulum Ca content.Collectively, our data identify JNK-dependent upregulation of BNIP3 as a critical process involved in ER stress-induced cardiomyocyte contractile dysfunction and highlight 4PBA as a potential intervention to counteract ER stress-mediated BNIP3 upregulation in failing hearts

Cardiac and pulmonary arterial remodeling after sinoaortic denervation in normotensive rats

Blood pressure variability (BPV) and baroreflex dysfunction may contribute to end-organ damage process. We investigated the effects of baroreceptor deficit (10 weeks after sinoaortic denervation - SAD) on hemodynamic alterations, cardiac and pulmonary remodeling. Cardiac function and morphology of male Wistar intact rats (C) and SAD rats (SAD) (n = 8/group) were assessed by echocardiography and collagen quantification. BP was directly recorded. Ventricular hypertrophy was quantified by the ratio of left ventricular weight (LVW) and right ventricular weight (RVW) to body weight (BW). BPV was quantified in the time and frequency domains. The atrial natriuretic peptide (ANP), alpha-skeletal actin (alpha-skelectal), collagen type I and type III genes mRNA expression were evaluated by RT-PCR. SAD did not change BP, but increased BPV (11 +/- 0.49 vs. 5 +/- 0.3 mm Hg). As expected, baroreflex was reduced in SAD. Pulmonary artery acceleration time was reduced in SAD. In addition, SAD impaired diastolic function in both LV (6.8 +/- 0.26 vs. 5.02 +/- 0.21 mm Hg) and RV (5.1 +/- 0.21 vs. 4.2 +/- 0.12 mm Hg). SAD increased LVW/BW in 9% and RVW/BW in 20%, and augmented total collagen (3.8-fold in LV, 2.7-fold in RV, and 3.35-fold in pulmonary artery). Also, SAD increased type I (similar to 6-fold) and III (similar to 5-fold) collagen gene expression. Denervation increased ANP expression in LV (75%), in RV (74%) and increased a-skelectal expression in LV (300%) and in RV (546%). Baroreflex function impairment by SAD, despite not changing BP, induced important adjustments in cardiac structure and pulmonary hypertension. These changes may indicate that isolated baroreflex dysfunction can modulate target tissue damage. (C) 2011 Elsevier B.V. All rights reserved.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Fundacao Zerbini-Sao PauloFundacao ZerbiniSao Paul

Effects of des-Arg⁹-bradykinin (DABK) and angiotensin II (ANG II) vascular smooth muscle cells (VSMC) growth.

<p>[A] Aortic VSMC from Wistar rats treated with ANG II and/or DABK at low concentration (0.1 nM) in the presence or not of losartan (LOS – 10 µM), des-arg9-leu8-bradykinin (DAL – 10 µM) and TIRON (1 mM). Bar graph shows PCNA expression normalized against the housekeeping protein β-actin. Results are represented as mean±SEM of 4 experiments. *P<0.05 vs Vehicle. [B] Aortic VSMC from Wistar rats with ANG II at high concentration (100 nM) in the presence or not of losartan (LOS – 10 µM), des-arg9-leu8-bradykinin (DAL – 10 µM). Bar graph shows PCNA expression normalized against the housekeeping protein β-actin. Results are expressed as mean±SEM of 5 experiments. *P<0.05 vs vehicle. [C] [H3] leucine incorporation in VSMC treated with ANG II and/or DABK at low concentration (0.1 nM) in the presence or not of losartan (LOS – 10 µM) and des-arg9-leu8-bradykinin (DAL – 10 µM) and VSMC treated with ANG II at high concentration (100 nM). Results are expressed as mean±SEM of 3 experiments and *P<0.05 vs vehicle.</p