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INTRODUCTION: Leptospirosis and dengue are two significant public health concerns in tropical and subtropical regions, often resulting in severe forms of disease and fatality. This study addresses the pressing public health issues of leptospirosis and dengue in the Dakshina Kannada district of Karnataka, India. Both diseases pose significant health risks and are relatively understudied in this region, making it essential to investigate their prevalence and clinical presentations for targeted healthcare planning. AIM: The primary aim is to determine the frequency of leptospirosis and dengue among febrile illness cases to understand the epidemiological patterns and assess co-infection rates in Dakshina Kannada. METHOD: Between 2020 and 2021, serum samples suspected of leptospirosis were tested using IgM ELISA (n = 1629) and the Microscopic Agglutination Test (MAT) (n = 92) for leptospirosis, while dengue was tested using NS1Ag and IgM antibodies ELISA (n = 1415). Data were collected through medical records and patient interviews. Seasonal trends, gender, and age distributions were analyzed. RESULT: The study found a significant prevalence of leptospirosis (21 %) and dengue (10 %) among febrile illness cases in the study area, with a 1.3 % co-infection rate. Clinically, fever was common to both diseases, but leptospirosis also frequently exhibited symptoms such as abdominal pain, myalgia, and jaundice. MAT screening revealed a predominance of anti-leptospiral antibodies against the Djasiman, Pyrogenes, Hurstbridge, Hebdomadis, and Grippotyphosa serogroups in Dakshina Kannada. CONCLUSION: The study highlights the urgent need for focused public health interventions, improved diagnostic tools, and targeted epidemiological studies to manage these diseases. The findings underscore the necessity of enhancing diagnostic capabilities and public health awareness, particularly considering the significant health risks posed by leptospirosis and dengue in the region.
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A variety of methodologies have been used to explore heat transport enhancement, and the fin approach to inspect heat transfer characteristics is one such effective method. In a broad range of industrial applications, including heat exchangers and microchannel heat sinks, fins are often employed to improve heat transfer. Encouraged by this feature, the present research is concerned with the temperature distribution caused by convective and radiative mechanisms in an internal heat-generating porous longitudinal dovetail fin (DF). The Darcy formulation is considered for analyzing the velocity of the fluid passing through the fin, and the Rosseland approximation determines the radiation heat flux. The heat transfer problem of an inverted trapezoidal (dovetail) fin is governed by a second-order ordinary differential equation (ODE), and to simplify it to a dimensionless form, nondimensional terms are utilized. The generated ODE is numerically solved using the spectral collocation method (SCM) via a local linearization approach. The effect of different physical attributes on the dimensionless thermal field and heat flux is graphically illustrated. As a result, the temperature in the dovetail fin transmits in a decreasing manner for growing values of the porosity parameter. For elevated values of heat generation and the radiation-conduction parameter, the thermal profile of the fin displays increasing behavior, whereas an increment in the convection-conduction parameter downsizes the thermal dispersal. It is found that the SCM technique is very effective and more conveniently handles the nonlinear heat transfer equation. Furthermore, the temperature field results from the SCM-based solution are in very close accordance with the outcomes published in the literature.
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OBJECTIVE: Intima formation involves smooth muscle cell (SMC) proliferation and migration that ultimately drives arterial stenosis, thrombosis, and ischemia in atherosclerosis, hypertension, and arterial revascularization. Receptor for advanced glycation endproducts (RAGE) is a transmembrane signaling receptor implicated in diabetic renal and vascular complications, and post-injury intima formation, partly via Signal transducer and activator of transcription 3 (STAT3) activation. The metabolic super-regulator Adenosine monophosphate kinase (AMPK) inhibits SMC proliferation and intima formation. AMPK activation is promoted by liver kinase B1 (LKB1), and LKB1 inhibits STAT3 activation. Here, we tested the hypothesis that RAGE promotes arterial intima formation by modulating both LKB1 and AMPK. METHODS AND RESULTS: RAGE ligands (the calgranulin S100A11, and glycated albumin) suppressed AMPK activation in conjunction with increased proliferation and migration of cultured SMCs. These effects were inhibited both by RAGE deficiency and by prior AMPK activation. In SMCs, RAGE ligands decreased LKB1 activity. Moreover, knockdown of both LKB1 and AMPK were associated with increased STAT3 phosphorylation levels. In response to murine carotid artery ligation, expression of RAGE and S100A11 increased, whereas AMPK and LKB1 activity decreased in situ. Conversely, LKB1 and AMPK activity increased in situ, and neointima formation was attenuated in Rage(-/-) mice. CONCLUSION: The linkage of decreased LKB1 and AMPK activity with increased STAT3 in SMCs mediates the capacity of RAGE ligand-induced signaling to promote neointima formation in response to arterial injury.
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Proteínas Quinasas Activadas por AMP/metabolismo , Traumatismos de las Arterias Carótidas/enzimología , Hígado/enzimología , Músculo Liso Vascular/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Receptores Inmunológicos/metabolismo , Proteínas Quinasas Activadas por AMP/genética , Animales , Arterias Carótidas/metabolismo , Arterias Carótidas/patología , Traumatismos de las Arterias Carótidas/genética , Traumatismos de las Arterias Carótidas/patología , Bovinos , Movimiento Celular , Proliferación Celular , Células Cultivadas , Modelos Animales de Enfermedad , Regulación hacia Abajo , Activación Enzimática , Técnicas de Silenciamiento del Gen , Productos Finales de Glicación Avanzada , Ligandos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Músculo Liso Vascular/patología , Neointima , Fosforilación , Proteína Fosfatasa 2/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Receptor para Productos Finales de Glicación Avanzada , Receptores Inmunológicos/deficiencia , Receptores Inmunológicos/genética , Proteínas S100/metabolismo , Factor de Transcripción STAT3/metabolismo , Albúmina Sérica/metabolismo , Transducción de Señal , Albúmina Sérica GlicadaRESUMEN
Mammalian cytosolic sulfotransferases (SULTs) catalyze the sulfation of xenobiotics as well as numerous endogenous molecules. The major aryl (phenol) SULT in rat liver, rSULT1A1, has been used extensively as a model enzyme for understanding the catalytic function of SULTs. Previous studies showed that purified rSULT1A1 displays significant catalytic changes in the presence of GSSG and other oxidants. In the present study, the effects of diamide [1,1'-azobis(N,N-dimethylformamide)] and tert-butyl hydroperoxide (TBHP) on the activity of rSULT1A1 in rat hepatic slices were compared with the effects of these oxidants on a homogeneous preparation of the enzyme. Precision-cut hepatic slices were incubated with 10 µM 7-hydroxycoumarin (7-HC) in the presence of varied concentrations of either diamide or TBHP. Analysis of the 7-hydroxycoumarin sulfate released into the incubation medium indicated that both oxidants significantly increased the sulfation of 7-HC, and this occurred at optimal concentrations of 5 and 10 µM, respectively. Cellular GSH and GSSG levels in the hepatic slices were not significantly altered from control values at these concentrations of diamide and TBHP. Exposure of homogeneous rSULT1A1 to diamide or TBHP also increased the rate of sulfation of 7-HC, although the optimal concentrations of diamide and TBHP were lower (50- and 100-fold, respectively) than those required for effects with the hepatic slices. These results indicate that both diamide and TBHP may modify the rSULT1A1 in intact cells in a manner similar to that observed with the homogeneous purified enzyme.
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Arilsulfotransferasa/metabolismo , Dimetilformamida/análogos & derivados , Hígado/enzimología , Oxidantes/farmacología , terc-Butilhidroperóxido/farmacología , Animales , Arilsulfotransferasa/química , Arilsulfotransferasa/genética , Supervivencia Celular/efectos de los fármacos , Dimetilformamida/farmacología , Glutatión/metabolismo , Técnicas In Vitro , Cinética , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Concentración Osmolar , Oxidación-Reducción , Estrés Oxidativo , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes/agonistas , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Umbeliferonas/metabolismoRESUMEN
BACKGROUND AND HYPOTHESIS: Interleukin (IL)-10 is an anti-inflammatory cytokine. Nox1 is a mitogenic oxidase (p65-mox). The objective of this study was to test a hypothesis that IL-10 deficiency would cause vascular remodeling via the upregulation of Nox1. METHODS AND RESULTS: Recombinant adeno-associated virus (AAV) carrying short hairpin small interference RNA for Nox1 (AAV.Nox1shRNA) was constructed for in-vivo-specific inhibition of Nox1. Three groups of IL-10 gene knockout (IL-10KO) mice and three groups of wild-type mice were used. Three groups of each strain received intravenous delivery of AAV.Nox1shRNA, AAV with scrambled shRNA, and PBS, respectively. Animals were euthanized at 3 weeks after gene delivery. IL-10KO increased Nox1 protein expression, NADPH oxidase activity, and superoxide production in aortas. IL-10KO also resulted in a significant decrease in aortic medial thickness, a loss of smooth muscle cells (SMCs), and an increase in vascular collagen deposition, indicating vascular remodeling. The IL-10KO induced increases in NADPH oxidase activity and superoxide production, and vascular remodeling were abolished by silencing of Nox1 (p65-mox), suggesting that these effects may be mediated by the upregulation of Nox1. In addition, IL-10KO increased endothelin-1 levels in plasma and aortas, and this effect was partially blocked by silencing of Nox1. RNA interference silencing of Nox1 obliterated the IL-10KO-induced increases in IL-6 expression in aortas, superoxide production, and matrix metalloproteinase-9 activity in aortic SMCs, and SMC migration. CONCLUSION: IL-10 is essential for the maintenance of normal vasculature, as IL-10 deficiency resulted in vascular damage and remodeling. The IL-10KO-induced vascular structure damage may be mediated by the upregulation of Nox1.
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Interleucina-10/genética , NADH NADPH Oxidorreductasas/genética , NADPH Oxidasas/genética , Regulación hacia Arriba , Animales , Aorta/patología , Movimiento Celular , Endotelina-1/genética , Endotelio Vascular/patología , Eliminación de Gen , Silenciador del Gen , Técnicas de Transferencia de Gen , Humanos , Metaloproteinasa 9 de la Matriz/genética , Ratones , Ratones Noqueados , Miocitos del Músculo Liso/citología , NADPH Oxidasa 1 , Interferencia de ARNRESUMEN
Endothelin (ET)-1 stimulates nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and increases superoxide production in some cells such as vascular smooth muscle cells. Here, we reported that ET1 inhibited NADPH oxidase activity, superoxide generation, and cell proliferation in human abdominal aortic endothelial cells (HAAECs) via the ETB1-Pyk2-Rac1-Nox1 pathway. Superoxide production was determined by assessing ethidium fluorescence using flow cytometry in HAAECs exposed to ET1 (10-30 nm) at different time intervals. ET1 significantly decreased superoxide production in HAAECs in the presence of NG-nitro-L-arginine methyl ester, indicating that ET1 suppressed superoxide generation independent of nitric oxide synthase. ET1 significantly attenuated NADPH oxidase activity and cell proliferation, which could be abolished by silence of Nox1 gene, suggesting that ET1-induced inhibition of NADPH oxidase activity was mediated by Nox1. Furthermore, RNA interference silence of ETB1 receptors significantly increased NADPH oxidase activity, and blocked the inhibitory effect of ET1 on NADPH oxidase activity. Activation of ETB1 receptors by ET1 suppressed protein phosphorylation of pyk2 (Y402) and Rac1, suggesting that ET1 inhibited NADPH oxidase activity via ETB1-Pyk2-Rac1 pathway. Indeed, inhibition of Pyk2 by AG-17 abolished ET1-induced suppression of NADPH oxidase activity. ET1 also attenuated angiotensin II-induced activation of NADPH oxidase and cell proliferation. This study demonstrated, for the first time, that ET1, via ETB1, inhibited NADPH oxidase activity in HAAECs by suppressing the Pyk2-Rac1-Nox1 pathway. This finding reveals a novel function of ETB1 receptors in regulating endothelial NADPH oxidase activity, superoxide production, and cell proliferation, opening a new avenue for understanding the role of ETB1 receptors in protecting endothelial cells.