Both the aging of the population and the increase in noncommunicable diseases may influence the progression and outcomes culminating in death, changing the evolution of ischemic heart diseases (IHDs) ...and their associated causes. Using the multiple causes of death method could help understand the magnitude of these relationships and enable better targeting of investments in health.
To evaluate the mortality from IHD in Brazil between 2006 and 2020 using the method of multiple causes and identify differences in the distribution pattern of IHD mortality by sex and geographic region.
Based on information extracted from death certificates (DCs) obtained from the database of the Department of Informatics of the Unified Health System (DATASUS), we used the multiple causes method to analyze the causes of death associated with IHD when IHD was defined as the underlying cause of death (UC) and the causes of death listed as the UC when IHD was recorded in any other lines of the DC, from 2006 to 2020, in Brazil. Subsequently, the proportion of these causes of death and differences between sexes and geographic regions were evaluated, with statistical relevance analyzed using the chi-square test, and the dependence between factors illustrated using stacked bar charts and small-world network graphs.
When IHD was listed as the UC of death, the most frequent associated causes of death were, in descending order of frequency, acute myocardial infarction (AMI), arterial hypertension (AH), chronic ischemic heart disease (CHID), heart failure (HF), and diabetes mellitus (DM). When IHD was mentioned in any line of the DC, the most frequent UCs of death were AMI followed by DM, CIHD, chronic obstructive pulmonary disease (COPD), stroke, dyslipidemia, and, in the year 2020, COVID-19. The most frequent cause of death in women were DM as the UC and associated cause of death, AH as the UC, and CIHD and Alzheimer's disease as associated causes of death, while the most frequent causes of death in men were substance dependence as the UC and associated cause of death, and cancer as an associated cause of death. The most frequent causes of death were DM and stroke in the North and Northeast, dyslipidemia and obesity in the Midwest, Alzheimer's disease in the South and Southeast, and atherosclerotic heart disease (AHD) and COPD in the South.
Several diseases - including AMI, AH, CIHD, HF, and DM - were the most frequent associated causes of death when IHD was recorded as the UC. In contrast, AMI, DM, CIHD, COPD, and stroke were the most frequent UCs when IHD was listed as an associated cause of death. The degree of these associations varied between sexes and geographic regions.
Pathologic heart conditions, particularly heart failure (HF) and ischemia-reperfusion (I/R) injury, are characterized by sustained elevation of plasma and interstitial catecholamine levels, as well ...as by the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Despite the continuous and extensive research on catecholamines since the early years of the XX(th) century, the mechanisms underlying catecholamine-induced cardiotoxicity are still not fully elucidated. The role of catecholamines in HF, stress cardiomyopathy, I/R injury, ageing, stress, and pheochromocytoma will be thoroughly discussed. Furthermore and although the noxious effects resulting from catecholamine excess have traditionally been linked to adrenoceptors, in fact, several evidences indicate that oxidative stress and the oxidation of catecholamines can have important roles in catecholamine-induced cardiotoxicity. Accordingly, the reactive intermediates formed during catecholamine oxidation have been associated with cardiac toxicity, both in in vitro and in vivo studies. An insight into the influence of ROS, RNS, and catecholamine oxidation products on several heart diseases and their clinical course will be provided. In addition, the source and type of oxidant species formed in some heart pathologies will be referred. In this review a special focus will be given to the research of cardiac pathologies where catecholamines and oxidative stress are involved. An integrated vision of these matters is required and will be provided along this review, namely how the concomitant surge of catecholamines and ROS occurs and how they can be interconnected. The concomitant presence of these factors can elicit peculiar and not fully characterized responses on the heart. We will approach the existing data with new perspectives as they can help explaining several controversial results regarding cardiovascular diseases and the redox ability of catecholamines.
Use of organic–inorganic hybrid sol–gel thin films is recently reported among the most promising approaches for the replacement of chromate based pre-treatment methods for high strength structural ...aluminium parts.
To be applied in the aerospace industry, pre-treatments have to meet the demanding requirements and must be compatible to state of the art paint systems. The addition of inhibitive species is desirable for the active corrosion protection and the prevention of sub-surface migration at defect sites of the coating.
In the present work hybrid films were produced by the controllable sol–gel route. Corrosion inhibitors were incorporated to the coatings in order to provide active protective effect. The barrier properties and the active corrosion protection on AA2024-T3 have been studied by Electrochemical Impedance Spectroscopy and Scanning Vibrating Electrode Technique. The obtained results were proven by conventional accelerated tests such as neutral salt spray test confirming validity of the mentioned electrochemical techniques for the evaluation of protection efficiency of hybrid sol–gel films.
The addition of inhibitors to sol–gel coatings in most cases leads to an improvement of the active corrosion protection but on the other hand it may negatively influences the barrier properties of the films. Therefore, encapsulation of the inhibiting compounds is beneficial in order to combine the good barrier function of the coating with the corrosion mitigating effect of the inhibitors.
Over the last decades there has been a change in biomedical research with the search for single genes, transcripts, proteins, or metabolites being substituted by the coverage of the entire genome, ...transcriptome, proteome, and metabolome with the "omics" approaches. The emergence of metabolomics, defined as the comprehensive analysis of all metabolites in a system, is still recent compared to other "omics" fields, but its particular features and the improvement of both analytical techniques and pattern recognition methods has contributed greatly to its increasingly use. The feasibility of metabolomics for biomarker discovery is supported by the assumption that metabolites are important players in biological systems and that diseases cause disruption of biochemical pathways, which are not new concepts. In fact, metabolomics, meaning the parallel assessment of multiple metabolites, has been shown to have benefits in various clinical areas. Compared to classical diagnostic approaches and conventional clinical biomarkers, metabolomics offers potential advantages in sensitivity and specificity. Despite its potential, metabolomics still retains several intrinsic limitations which have a great impact on its widespread implementation - these limitations in biological and experimental measurements. This review will provide an insight to the characteristics, strengths, limitations, and recent advances in metabolomics, always keeping in mind its potential application in clinical/ health areas as a biomarker discovery tool.
Piperazine compounds as drugs of abuse Arbo, M.D; Bastos, M.L; Carmo, H.F
Drug and alcohol dependence,
05/2012, Letnik:
122, Številka:
3
Journal Article
Recenzirano
Abstract Synthetic drugs are among the most commonly abused drugs in the world. This abuse is widespread among young people, especially in the dance club and rave scenes. Over the last several years, ...piperazine derived drugs have appeared, mainly available via the internet, and sold as ecstasy pills or under the names of“ Frenzy”,“ Bliss”,“ Charge”,“ Herbal ecstasy”,“ A2”,“ Legal X” and“ Legal E”. Although in the market piperazine designer drugs have the reputation of being safe, several experimental and epidemiological studies indicate risks for humans. Piperazine designer drugs can be divided into two classes, the benzylpiperazines such as N-benzylpiperazine (BZP) and its methylenedioxy analogue 1-(3,4-methylenedioxybenzyl)piperazine (MDBP), and the phenylpiperazines such as 1-(3-chlorophenyl)piperazine (mCPP), 1-(3-trifluoromethylphenyl)piperazine (TFMPP), and 1-(4-methoxyphenyl)piperazine (MeOPP). Toxicokinetic properties, including metabolic pathways, actions and effects in animals and humans, with some hypothesis of mechanism of action, and analytical approaches for the identification of these drugs are summarized in this review.
Chagas disease is caused by the protozoan Trypanosoma cruzi, affecting around 8 million people worldwide. After host cell invasion, the infective trypomastigote form remains 2-4 hours inside acidic ...phagolysosomes to differentiate into replicative amastigote form. In vitro acidic-pH-induced axenic amastigogenesis was used here to study this step of the parasite life cycle. After three hours of trypomastigote incubation in amastigogenesis promoting acidic medium (pH 5.0) or control physiological pH (7.4) medium samples were subjected to three rounds of centrifugation followed by ultrafiltration of the supernatants. The resulting exoproteome samples were trypsin digested and analysed by nano flow liquid chromatography coupled to tandem mass spectrometry. Computational protein identification searches yielded 271 and 483 protein groups in the exoproteome at pH 7.4 and pH 5.0, respectively, with 180 common proteins between both conditions. The total amount and diversity of proteins released by parasites almost doubled upon acidic incubation compared to control. Overall, 76.5% of proteins were predicted to be secreted by classical or non-classical pathways and 35.1% of these proteins have predicted transmembrane domains. Classical secretory pathway analysis showed an increased number of mucins and mucin-associated surface proteins after acidic incubation. However, the number of released trans-sialidases and surface GP63 peptidases was higher at pH 7.4. Trans-sialidases and mucins are anchored to the membrane and exhibit an enzyme-substrate relationship. In general, mucins are glycoproteins with immunomodulatory functions in Chagas disease, present mainly in the epimastigote and trypomastigote surfaces and could be enzymatically cleaved and released in the phagolysosome during amastigogenesis. Moreover, evidence for flagella discard during amastigogenesis are addressed. This study provides the first comparative analysis of the exoproteome during amastigogenesis, and the presented data evidence the dynamism of its profile in response to acidic pH-induced differentiation.
Paraquat dichloride (methyl viologen; PQ) is an effective and widely used herbicide that has a proven safety record when appropriately applied to eliminate weeds. However, over the last decades, ...there have been numerous fatalities, mainly caused by accidental or voluntary ingestion. PQ poisoning is an extremely frustrating condition to manage clinically, due to the elevated morbidity and mortality observed so far and due to the lack of effective treatments to be used in humans. PQ mainly accumulates in the lung (pulmonary concentrations can be 6 to 10 times higher than those in the plasma), where it is retained even when blood levels start to decrease. The pulmonary effects can be explained by the participation of the polyamine transport system abundantly expressed in the membrane of alveolar cells type I, II, and Clara cells. Further downstream at the toxicodynamic level, the main molecular mechanism of PQ toxicity is based on redox cycling and intracellular oxidative stress generation. With this review we aimed to collect and describe the most pertinent and significant findings published in established scientific publications since the discovery of PQ, focusing on the most recent developments related to PQ lung toxicity and their relevance to the treatment of human poisonings. Considerable space is also dedicated to techniques for prognosis prediction, since these could allow development of rigorous clinical protocols that may produce comparable data for the evaluation of proposed therapies.
Display omitted
Cancer is a disease with a high mortality rate characterized by uncontrolled proliferation of abnormal cells. The hallmarks of cancer evidence the acquired cells characteristics that ...promote the growth of malignant tumours, including genomic instability and mutations, the ability to evade cellular death and the capacity of sustaining proliferative signalization. Poly(ADP-ribose) polymerase-1 (PARP1) is a protein that plays key roles in cellular regulation, namely in DNA damage repair and cell survival. The inhibition of PARP1 promotes cellular death in cells with homologous recombination deficiency, and therefore, the interest in PARP protein has been rising as a target for anticancer therapies. There are already some PARP1 inhibitors approved by Food and Drug Administration (FDA), such as Olaparib and Niraparib. The last compound presents in its structure an indazole core. In fact, pyrazoles and indazoles have been raising interest due to their various medicinal properties, namely, anticancer activity. Derivatives of these compounds have been studied as inhibitors of PARP1 and presented promising results. Therefore, this review aims to address the importance of PARP1 in cell regulation and its role in cancer. Moreover, it intends to report a comprehensive literature review of PARP1 inhibitors, containing the pyrazole and indazole scaffolds, published in the last fifteen years, focusing on structure–activity relationship aspects, thus providing important insights for the design of novel and more effective PARP1 inhibitors.
In this work, layered double hydroxide (LDH) conversion films were grown on aluminium alloy 2024 substrates. The effect of experimental conditions on the growth of LDH conversion films, including ...concentration of reactants and presence of corrosion inhibitor, was investigated. The protective performance provided by LDH films was assessed by electrochemical impedance spectroscopy (EIS), and rationalised in terms of structural and morphological characteristics surveyed by X-ray diffraction (XRD) and scanning electron microscopy (SEM), respectively. The results show that corrosion protection increases when corrosion inhibitors (vanadates) are intercalated in LDHs and dilute solutions of Zn2+ are used to grow LDHs.
In the present work corrosion inhibition in microdefects of protective coatings on magnesium alloy was studied by SVET (scanning vibrating electrode technique) and SIET (scanning ion-selective ...electrode technique) in 0.05
M NaCl. Mg
2+- and pH-selective microelectrodes were developed to be used by SIET. The microelectrodes were characterized from the standpoint of properties important for corrosion applications, aiming at the reliable functioning during measurements. The combination of SVET and SIET demonstrated to be a useful approach to investigate the inhibition of corrosion processes in microdefects on coated AZ31. In this paper the corrosion inhibiting properties of 1,2,4,-triazole, F
− and Ce
3+ on AZ31 alloy were analyzed. According to the results, 1,2,4-triazole in concentration of 0.01
M showed the highest inhibition efficiency among the studied inhibitors and was able to prevent the increase of pH in the corroding defects, by keeping the corrosion activity on a very low level during the tested immersion period.
PDF
