Aluminum exposure at human dietary levels promotes vascular dysfunction and increases blood pressure in rats: a concerted action of NAD(P)H oxidase and COX-2

Abstract Aluminum (Al) is a non-essential metal and a significant environmental contaminant and is associated with a number of human diseases including cardiovascular disease. We investigated the effects of Al exposure at doses similar to human dietary levels on the cardiovascular system over a 60 day period. Wistar male rats were divided into two major groups and received orally: 1) Low aluminum level − rats were subdivided and treated for 60 days as follows: a) Untreated − ultrapure water; b) AlCl3 at a dose of 8.3 mg/kg bw for 60 days, representing human Al exposure by diet; and 2) High aluminum level − rats were subdivided and treated for 42 days as follows: C) Untreated − ultrapure water; d) AlCl3 at 100 mg/kg bw for 42 days, representing a high level of human exposure to Al. Effects on systolic blood pressure (SBP) and vascular function of aortic and mesenteric resistance arteries (MRA) were studied. Endothelium and smooth muscle integrity were evaluated by concentration-response curves to acetylcholine (ACh) and sodium nitroprusside. Vasoconstrictor responses to phenylephrine (Phe) in the presence and absence of endothelium and in the presence of the NOS inhibitor L-NAME, the potassium channels blocker TEA, the NAD(P)H oxidase inhibitor apocynin, superoxide dismutase (SOD), the non-selective COX inhibitor indomethacin and the selective COX-2 inhibitor NS 398 were analyzed. Vascular reactive oxygen species (ROS), lipid peroxidation and total antioxidant capacity, were measured. The mRNA expressions of eNOS, NAD(P)H oxidase 1 and 2, SOD1, COX-2 and thromboxane A2 receptor (TXA-2 R) were also investigated. Al exposure at human dietary levels impaired the cardiovascular system and these effects were almost the same as Al exposure at much higher levels. Al increased SBP, decreased ACh-induced relaxation, increased response to Phe, decreased endothelial modulation of vasoconstrictor responses, the bioavailability of nitric oxide (NO), the involvement of potassium channels on vascular responses, as well as increased ROS production from NAD(P)H oxidase and contractile prostanoids mainly from COX-2 in both aorta and mesenteric arteries. Al exposure increased vascular ROS production and lipid peroxidation as well as altered the antioxidant status in aorta and MRA. Al decreased vascular eNOS and SOD1 mRNA levels and increased the NAD(P)H oxidase 1, COX-2 and TXA-2 R mRNA levels. Our results point to an excess of ROS mainly from NAD(P)H oxidase after Al exposure and the increased vascular prostanoids from COX-2 acting in concert to decrease NO bioavailability, thus inducing vascular dysfunction and increasing blood pressure. Therefore, 60-day chronic exposure to Al, which reflects common human dietary Al intake, appears to pose a risk for the cardiovascular system

Análise comparativa da função respiratória de indivíduos hígidos em solo e na água

A mensuração da função respiratória oferece informações essenciais para caracterizar anormalidades pulmonares. A pressão hidrostática da água atua no tórax submerso de diversas formas, causando alterações no sistema respiratório. O objetivo deste estudo foi analisar comparativamente variáveis que avaliam a função respiratória - volume minuto (Vmin), volume corrente (Vc), capacidade vital (Cvital) e frequência respiratória (FR) - de voluntárias no solo e com o tórax submerso em piscina terapêutica aquecida. A função respiratória de 30 voluntárias saudáveis (20,9±2,1 anos; 1,64±0,07 m; 58,8±9,2 kg; índice de massa corporal 21,78±2,63 kg/m²) foi avaliada por meio de ventilômetro em solo e aos 1 e 20 minutos de imersão, com água ao nível dos ombros, em posição sentada. Após 20 minutos de imersão, foi registrado aumento estatisticamente significativo no Vmin (p=0,015) e Vc (p=0,027); e uma redução estatisticamente significativa (p=0,016) na Cvital 1 minuto após imersão, em relação aos valores obtidos em solo. O maior tempo de imersão alterou assim os valores obtidos em solo, com exceção da Cvital, que sofreu alteração significativa desde o primeiro minuto de imersão. Não foram encontradas diferenças significativas entre os valores obtidos após 1 e 20 minutos na água. O estudo permite concluir que a imersão do tórax em piscina aquecida provocou aumento no Vmin e Vc e diminuição na Cvital de voluntárias saudáveis.Measuring respiratory function provides essential information to assess pulmonary changes. Effects of water hydrostatic pressure on the submerged chest cause changes in the respiratory system. The purpose here was to compare respiratory function variables - minute volume (MV), tidal volume (TV), vital capacity (Vitalc), and respiratory rate (RR) - on the ground and with chest submerged in water. Respiratory function of 30 healthy female volunteers (mean age 20.93 ± 2.11; weight 58.8±9.2 kg; body mass index 21.78±2.63 kg/m²) was assessed by spirometry on the ground, and 1 and 20 minutes after immersion in warm water at shoulder level in the sitting position. As compared to ground levels, statistically significant increases were found in MV (p=0.015) and TV (p=0.027) 20 minutes after immersion, as well as a significant decrease (p=0.016) in Vitalc one minute after immersion. Longer time immersion has thus altered values obtained on ground, except for Vitalc, which showed significant reduction on the first minute after chest immersion. Comparison between variable values obtained 1 and 20 minutes in water showed no significant difference. It may thus be said that chest submersion in warm water caused an increase in MV and VT and a decrease in Vitalc of healthy subjects

Tegumentary leishmaniasis and coinfections other than HIV

<div><p>Background</p><p>Tegumentary leishmaniasis (TL) is a disease of skin and/or mucosal tissues caused by <i>Leishmania</i> parasites. TL patients may concurrently carry other pathogens, which may influence the clinical outcome of TL.</p><p>Methodology and principal findings</p><p>This review focuses on the frequency of TL coinfections in human populations, interactions between <i>Leishmania</i> and other pathogens in animal models and human subjects, and implications of TL coinfections for clinical practice. For the purpose of this review, TL is defined as all forms of cutaneous (localised, disseminated, or diffuse) and mucocutaneous leishmaniasis. Human immunodeficiency virus (HIV) coinfection, superinfection with skin bacteria, and skin manifestations of visceral leishmaniasis are not included. We searched MEDLINE and other databases and included 73 records: 21 experimental studies in animals and 52 studies about human subjects (mainly cross-sectional and case studies). Several reports describe the frequency of <i>Trypanosoma cruzi</i> coinfection in TL patients in Argentina (about 41%) and the frequency of helminthiasis in TL patients in Brazil (15% to 88%). Different hypotheses have been explored about mechanisms of interaction between different microorganisms, but no clear answers emerge. Such interactions may involve innate immunity coupled with regulatory networks that affect quality and quantity of acquired immune responses. Diagnostic problems may occur when concurrent infections cause similar lesions (e.g., TL and leprosy), when different pathogens are present in the same lesions (e.g., <i>Leishmania</i> and <i>Sporothrix schenckii</i>), or when similarities between phylogenetically close pathogens affect accuracy of diagnostic tests (e.g., serology for leishmaniasis and Chagas disease). Some coinfections (e.g., helminthiasis) appear to reduce the effectiveness of antileishmanial treatment, and drug combinations may cause cumulative adverse effects.</p><p>Conclusions and significance</p><p>In patients with TL, coinfection is frequent, it can lead to diagnostic errors and delays, and it can influence the effectiveness and safety of treatment. More research is needed to unravel how coinfections interfere with the pathogenesis of TL.</p></div

Dietary Egg White Hydrolysate Prevents Male Reproductive Dysfunction after Long-Term Exposure to Aluminum in Rats

Aluminum (Al) is a non-essential metal omnipresent in human life and is considered an environmental toxicant. Al increases reactive oxygen production and triggers immune responses, contributing to chronic systemic inflammation development. Here, we have tested whether an egg white hydrolysate (EWH) with potential bioactive properties can protect against changes in reproductive function in rats exposed to long-term Al dietary levels at high and low doses. Male Wistar rats received orally: low aluminum level group—AlCl3 at 8.3 mg/kg b.w. for 60 days with or without EWH (1 g/kg/day); high aluminum level group—AlCl3 at 100 mg/kg b.w. for 42 days with or without EWH (1 g/kg/day). The co-administration of EWH prevented the increased Al deposition surrounding the germinative cells, reducing inflammation and oxidative stress in the reproductive organs. Furthermore, the daily supplementation with EWH maintained sperm production and sperm quality similar to those found in control animals, even after Al exposure at a high dietary contamination level. Altogether, our results suggest that EWH could be used as a protective agent against impairment in the reproductive system produced after long-term exposure to Al at low or high human dietary levels.</jats:p