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.
The low bioavailability of the anti‐migraine drug sumatriptan is partially caused by first‐pass hepatic metabolism. In this study, we analyzed the impact of the hepatic organic cation transporter ...OCT1 on sumatriptan cellular uptake, and of OCT1 polymorphisms on sumatriptan pharmacokinetics. OCT1 transported sumatriptan with high capacity and sumatriptan uptake into human hepatocytes was strongly inhibited by the OCT1 inhibitor MPP+. Sumatriptan uptake was not affected by the Met420del polymorphism, but was strongly reduced by Arg61Cys and Gly401Ser, and completely abolished by Gly465Arg and Cys88Arg. Plasma concentrations in humans with two deficient OCT1 alleles were 215% of those with fully active OCT1 (P = 0.0003). OCT1 also transported naratriptan, rizatriptan, and zolmitriptan, suggesting a possible impact of OCT1 polymorphisms on the pharmacokinetics of other triptans as well. In conclusion, OCT1 is a high‐capacity transporter of sumatriptan and polymorphisms causing OCT1 deficiency have similar effects on sumatriptan pharmacokinetics as those observed in subjects with liver impairment.
Imidacloprid (IMI) is an insecticide that interferes with the transmission of stimuli in the nervous system of insects. It is neurotoxic by mimicking nicotine through its binding to the nicotinic ...acetylcholine receptor. In this work, experiments comprising 96
h exposure followed by 48
h in clean medium were conducted to evaluate the toxicity of IMI to
Chironomus riparius and its potential recovery. Behavioural parameters and AChE activity were assessed. After 96
h exposure to IMI, AChE activity, and the behaviour parameters ventilation and locomotion were reduced. There were no signs of recovery after removal to clean water for 48
h.
Ventilation behaviour was the most sensitive parameter and the one with the highest correlation to AChE activity. Despite the possibility that IMI might be having an indirect effect on AChE activity, the behavioural endpoint showed a higher sensitivity than the biochemical response itself.
This work highlights the importance of linking parameters with ecological relevance at individual level (behavioural parameters) with biochemical responses, to unravel xenobiotics mode of action.
Fungi are known to occur ubiquitously in the environment. In the past years, the occurrence of filamentous fungi in the aquatic environment has been a subject of growing interest. This study ...describes the occurrence of various fungal genera in different drinking water sources being Penicillium and Trichoderma the most representative ones (30% and 17%, respectively). Also, 24 fungal species that have not been previously described in the aquatic environment are reported in this study, being once again the major species from the Penicillium genera. This study therefore contributes to the knowledge on the richness of fungi diversity in water. 68% of the described species were found to be able to grow at 30 °C but only Aspergillus fumigatus, Aspergillus viridinutans and Cunninghamella bertholletiae were able to grow at the higher temperature tested (42 °C). 66% of the species that were able to grow at 30 °C have spore sizes below 5 μm which enables them to cause breathing infections. These were therefore identified as potential pathogenic species.
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•This study contributes to knowledge on the richness of fungi diversity in water sources.•24 species are reported to occur in the aquatic environment for the first time.•Conidia size and growth at high temperatures were used to screen pathogenic species.•66% of the species are considered as potential pathogenic species.
In 2021, our research group published the prominent anticancer activity achieved through the successful combination of two redox centres (
-quinone/
-quinone or quinone/selenium-containing triazole) ...through a copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The combination of two naphthoquinoidal substrates towards a synergetic product was indicated, but not fully explored. Herein, we report the synthesis of 15 new quinone-based derivatives prepared from click chemistry reactions and their subsequent evaluation against nine cancer cell lines and the murine fibroblast line L929. Our strategy was based on the modification of the A-ring of
-naphthoquinones and subsequent conjugation with different
-quinoidal moieties. As anticipated, our study identified several compounds with IC
values below 0.5 µM in tumour cell lines. Some of the compounds described here also exhibited an excellent selectivity index and low cytotoxicity on L929, the control cell line. The antitumour evaluation of the compounds separately and in their conjugated form proved that the activity is strongly enhanced in the derivatives containing two redox centres. Thus, our study confirms the efficiency of using A-ring functionalized
-quinones coupled with
-quinones to obtain a diverse range of two redox centre compounds with potential applications against cancer cell lines. Here as well, it literally takes two for an efficient tango!
Hemorrhagic cystitis (HC) is the major dose-limiting adverse effect of the clinical use ifosfamide (IFOS). The incidence of this side effect can be as high as 75%. Mesna has been used to reduce the ...risk of HC, although 5% of patients who get IFOS treatment may still suffer from HC. In previous studies, our group demonstrated that α-phellandrene (α-PHE) possesses anti-inflammatory activity, which opens the door for its study in the attenuation of HC. The objective of this study was to investigate the potential uroprotective effect of the α-PHE in the mouse model of IFOS-induced HC. In order to analyze the reduction of the urothelial damage, the bladder wet weight, hemoglobin content, and the Evans blue dye extravasation from the bladder matrix were evaluated. To investigate the involvement of neutrophil migration and lipid peroxidation and involvement of enzymatic and endogenous non-enzymatic antioxidants, the tissue markers myeloperoxidase (MPO), malondialdehyde, nitrite/nitrate (NOx), superoxide dismutase (SOD), and reduced glutathione (GSH) were evaluated. TNF-α and IL-1β were measured by ELISA immunoassay technique. The results show that pretreatment with α-PHE significantly reduced urothelial damage that was accompanied by a decrease in the activity of MPO, MDA, and NOx levels and prevention of the depletion of SOD and GSH in bladder tissues. In the assessment of cytokines, α-PHE was able to significantly reduce TNF-α level. However, it does not affect the activities of IL-1β. These data confirm that α-PHE exerts potent anti-inflammatory properties and demonstrates that α-PHE represents a promising therapeutic option for this pathological condition.
This work describes the state of the art of electrochemical devices for the detection of an important class of neurotransmitters: the catecholamines. This class of biogenic amines includes dopamine, ...noradrenaline (also called norepinephrine) and adrenaline (also called epinephrine).
Researchers have focused on the role of catecholamine molecules within the human body because they are involved in many important biological functions and are commonly associated with several diseases, such as Alzheimer's and Parkinson. Furthermore, the release of catecholamines as a consequence of induced stimulus is an important indicator of reward-related behaviors, such as food, drink, sex and drug addiction. Thus, the development of simple, fast and sensitive electroanalytical methodologies for the determination of catecholamines is currently needed in clinical and biomedical fields, as they have the potential to serve as clinically relevant biomarkers for specific disease states or to monitor treatment efficacy.
Currently, three main strategies have used by researchers to detect catecholamine molecules, namely: the use electrochemical materials in combination with, for example, HPLC or FIA, the incorporation of new materials/layers on the sensor surfaces (Tables 1–7) and in vivo detection, manly by using FSCV at CFMEs (Section 10). The developed methodologies were able not only to accurately detect catecholamines at relevant concentration levels, but to do so in the presence of co-existing interferences in samples detected (ascorbate, for example).
This review examines the progress made in electrochemical sensors for the selective detection of catecholamines in the last 15 years, with special focus on highly innovative features introduced by nanotechnology. As the literature in rather extensive, we try to simplify this work by summarizing and grouping electrochemical sensors according to the manner their substrates were chemically modified. We also discuss the current and future of electrochemical sensors for catecholamines in terms of the analytical performance of the devices and emerging applications.
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•Review about electrochemical sensors and biosensorst for detection of catecholamines.•Determination of NTs can be a powerful tool as biomarkers for several diseases.•Special focus on the detection of catecholamines using nanomaterials.•Critical comparison of the analytical parameters of the different groups of sensors.
The pace of discovery of potentially actionable pharmacogenetic variants has increased dramatically in recent years. However, the implementation of this new knowledge for individualized patient care ...has been slow. The Pharmacogenomics Research Network (PGRN) Translational Pharmacogenetics Program seeks to identify barriers and develop real‐world solutions to implementation of evidence‐based pharmacogenetic tests in diverse health‐care settings. Dissemination of the resulting toolbox of “implementation best practices” will prove useful to a broad audience.
Clinical Pharmacology & Therapeutics (2013); 94 2, 207–210. doi:10.1038/clpt.2013.59
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