735 research outputs found
Vascular smooth muscle contraction in hypertension
Hypertension is a major risk factor for many common chronic diseases, such as heart failure, myocardial infarction, stroke, vascular dementia and chronic kidney disease. Pathophysiological mechanisms contributing to the development of hypertension include increased vascular resistance, determined in large part by reduced vascular diameter due to increased vascular contraction and arterial remodelling. These processes are regulated by complex interacting systems such as the renin angiotensin aldosterone system (RAAS), sympathetic nervous system, immune activation and oxidative stress, which influence vascular smooth muscle function. Vascular smooth muscle cells are highly plastic and in pathological conditions undergo phenotypic changes from a contractile to a proliferative state. Vascular smooth muscle contraction is triggered by an increase in intracellular free calcium concentration ([Ca2+]i), promoting actin-myosin cross-bridge formation. Growing evidence indicates that contraction is also regulated by calcium-independent mechanisms involving RhoA-Rho kinase (ROCK), protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) signaling, reactive oxygen species and reorganization of the actin cytoskeleton. Activation of immune/inflammatory pathways and noncoding RNAs are also emerging as important regulators of vascular function. Vascular smooth muscle cell [Ca2+]i, not only determines the contractile state but also influences activity of many calcium-dependent transcription factors and proteins thereby impacting the cellular phenotype and function. Perturbations in vascular smooth muscle cell signaling and altered function influence vascular reactivity and tone, important determinants of vascular resistance and blood pressure. Here we discuss mechanisms regulating vascular reactivity and contraction in physiological and pathophysiological conditions and highlight some new advances in the field, focusing specifically on hypertension
Vascular Biology of Superoxide-Generating NADPH Oxidase 5âImplications in Hypertension and Cardiovascular Disease
Significance: NADPH oxidases (Noxs), of which there are seven isoforms (Nox1â5, Duox1/Duox2), are professional oxidases functioning as reactive oxygen species (ROS)-generating enzymes. ROS are signaling molecules important in physiological processes. Increased ROS production and altered redox signaling in the vascular system have been implicated in the pathophysiology of cardiovascular diseases, including hypertension, and have been attributed, in part, to increased Nox activity.
Recent Advances: Nox1, Nox2, Nox4, and Nox5 are expressed and functionally active in human vascular cells. While Nox1, Nox2, and Nox4 have been well characterized in models of cardiovascular disease, little is known about Nox5. This may relate to the lack of experimental models because rodents lack NOX5. However, recent studies have advanced the field by (i) elucidating mechanisms of Nox5 regulation, (ii) identifying Nox5 variants, (iii) characterizing Nox5 expression, and (iv) discovering the Nox5 crystal structure. Moreover, studies in human Nox5-expressing mice have highlighted a putative role for Nox5 in cardiovascular disease.
Critical Issues: Although growing evidence indicates a role for Nox-derived ROS in cardiovascular (patho)physiology, the exact function of each isoform remains unclear. This is especially true for Nox5.
Future Directions: Future directions should focus on clinically relevant studies to discover the functional significance of Noxs, and Nox5 in particular, in human health and disease. Two important recent studies will impact future directions. First, Nox5 is the first Nox to be crystallized. Second, a genome-wide association study identified Nox5 as a novel blood pressure-associated gene. These discoveries, together with advancements in Nox5 biology and biochemistry, will facilitate discovery of drugs that selectively target Noxs to interfere in uncontrolled ROS generation
Systematic literature review of realistic simulators applied in educational robotics context
This paper presents a systematic literature review (SLR) about realistic simulators that can be applied in an educational robotics context. These simulators must include the simulation of actuators and sensors, the ability to simulate robots and their environment. During this systematic review of the literature, 559 articles were extracted from six different databases using the Population, Intervention, Comparison, Outcomes, Context (PICOC) method. After the selection process, 50 selected articles were included in this review. Several simulators were found and their features were also analyzed. As a result of this process, four realistic simulators were applied in the reviewâs referred context for two main reasons. The first reason is that these simulators have high fidelity in the robotsâ visual modeling due to the 3D rendering engines and the second reason is because they apply physics engines, allowing the robotâs interaction with the environment.info:eu-repo/semantics/publishedVersio
Vascular biology of superoxide-generating NADPH oxidase 5 (Nox5)- implications in hypertension and cardiovascular disease
SIGNIFICANCE: NADPH oxidases (Nox) of which there are 7 isoforms (Nox1-5, Duox1/Duox2) are professional oxidases functioning as ROS-generating enzymes. ROS are signaling molecules important in physiological processes. Increased ROS production and altered redox signaling in the vascular system have been implicated in the pathophysiology of cardiovascular diseases, including hypertension, and have been attributed, in part, to increased Nox activity. RECENT ADVANCES: Nox1,2,4,5 are expressed and functionally active in human vascular cells. While Nox1,2,4 have been well characterized in models of cardiovascular disease, little is known about Nox5. This may relate to the lack of experimental models because rodents lack NOX5. However, recent studies have advanced the field by i) elucidating mechanisms of Nox5 regulation, ii) identifying Nox5 variants, iii) characterizing Nox5 expression and iv) discovery of Nox5 crystal structure. Moreover, studies in human Nox5-expressing mice have highlighted a putative role for Nox5 in cardiovascular disease. CRITICAL ISSUES: Although growing evidence indicates a role for Nox-derived ROS in cardiovascular (patho)physiology, the exact function of each isoform remains unclear. This is especially true for Nox5. FUTURE DIRECTIONS: Future directions should focus on clinically-relevant studies to discover the functional significance of Noxs, and Nox5 in particular, in human health and disease. Two important recent studies will impact future directions. Firstly, Nox5 is the first Nox to be crystalized. Secondly GWAS identified Nox5 as a novel blood pressure-associated gene. These discoveries, together with advancements in Nox5 biology and
biochemistry, will facilitate discovery of drugs th
at selectively target Noxs to interfere with
uncontrolled ROS generation
Vascular smooth muscle contraction in hypertension
Hypertension is a major risk factor for many common chronic diseases, such as heart failure, myocardial infarction, stroke, vascular dementia, and chronic kidney disease. Pathophysiological mechanisms contributing to the development of hypertension include increased vascular resistance, determined in large part by reduced vascular diameter due to increased vascular contraction and arterial remodelling. These processes are regulated by complex-interacting systems such as the renin-angiotensin-aldosterone system, sympathetic nervous system, immune activation, and oxidative stress, which influence vascular smooth muscle function. Vascular smooth muscle cells are highly plastic and in pathological conditions undergo phenotypic changes from a contractile to a proliferative state. Vascular smooth muscle contraction is triggered by an increase in intracellular free calcium concentration ([Ca2+]i), promoting actinâmyosin cross-bridge formation. Growing evidence indicates that contraction is also regulated by calcium-independent mechanisms involving RhoA-Rho kinase, protein Kinase C and mitogen-activated protein kinase signalling, reactive oxygen species, and reorganization of the actin cytoskeleton. Activation of immune/inflammatory pathways and non-coding RNAs are also emerging as important regulators of vascular function. Vascular smooth muscle cell [Ca2+]i not only determines the contractile state but also influences activity of many calcium-dependent transcription factors and proteins thereby impacting the cellular phenotype and function. Perturbations in vascular smooth muscle cell signalling and altered function influence vascular reactivity and tone, important determinants of vascular resistance and blood pressure. Here, we discuss mechanisms regulating vascular reactivity and contraction in physiological and pathophysiological conditions and highlight some new advances in the field, focusing specifically on hypertension
Escorpiones venenosos encontrados en Corrientes y Chaco. CaracterĂsticas de la intoxicaciĂłn
Mediante el proyecto de Voluntariado Universitario âAlerta roja: escorpiones!â aprobado por la SPU, hemos realizado charlas, recorridas y trabajos de laboratorio en Corrientes y Chaco, alertando sobre la toxicidad de los escorpiones, la forma de reconocer especies tĂłxicas, medidas de prevenciĂłn y profilaxis. Asimismo se capturaron ejemplares para su identificaciĂłn y estudio posterior. Hemos encontrado las especies de escorpiones venenosos Tityus trivittatus y T. Confluens en Corrientes y Chaco, extraĂdo su veneno (promedio 0,26 y 0,21 mg por ejemplar respectivamente) y analizado la casuĂstica de accidentes particularmente en Puerto Vilelas (Chaco) encontrando que el 100 % referĂa dolor en el accidente, no requiriĂ©ndose en ninguno de los casos la derivaciĂłn a centros de mayor complejidad.
Assessment of Panoramic Radiomorphometric Indices of the Mandible in a Brazilian Population
The aim of this study was to evaluate radiomorphometric indices in dental panoramic radiographs in order to identify possible interrelationships between these indices and the sex and age of the patients analyzed. The study included 1287 digital panoramic radiographic images of patients that were grouped into five age groups (1â=âage 17â20; 2â=âage 21â35; 3â=âage 36â55; 4â=âage 56â69; 5â=âover age 70). Two indicesâcortical width at the gonion (GI) and below the mental foramen (MI)âwere measured bilaterally in all panoramic radiographs. Statistical analysis was performed with Kruskal-Wallis and Mann-Whitney tests (alphaâ=â0.05). Results for the indices measurements showed significant differences among patient age groups of both sexes, considering that groups 4 and 5 presented lower values for the cortical width of both indices. The present paper supports the role of sex- and age-related changes in mandibular radiomorphometric indices in identifying skeletal osteopenia
Hypertriglyceridemia Influences the Degree of Postprandial Lipemic Response in Patients with Metabolic Syndrome and Coronary Artery Disease: From the Cordioprev Study
Objective
To determine whether metabolic syndrome traits influence the postprandial lipemia response of coronary patients, and whether this influence depends on the number of MetS criteria.
Materials and Methods
1002 coronary artery disease patients from the CORDIOPREV study were submitted to an oral fat load test meal with 0.7 g fat/kg body weight (12% saturated fatty acids, 10% polyunsaturated fatty acids, 43% monounsaturated fatty acids), 10% protein and 25% carbohydrates. Serial blood test analyzing lipid fractions were drawn at 0, 1, 2, 3 and 4 hours during the postprandial state. Total and incremental area under the curves of the different postprandial parameters were calculated following the trapezoid rule to assess the magnitude of change during the postprandial state
Results
Postprandial lipemia response was directly related to the presence of metabolic syndrome. We found a positive association between the number of metabolic syndrome criteria and the response of postprandial plasma triglycerides (p<0.001), area under the curve of triglycerides (p<0.001) and incremental area under the curve of triglycerides (p<0.001). However, the influence of them on postprandial triglycerides remained statistically significant only in those patients without basal hypertriglyceridemia. Interestingly, in stepwise multiple linear regression analysis with the AUC of triglycerides as the dependent variable, only fasting triglycerides, fasting glucose and waist circumference appeared as significant independent (P<0.05) contributors. The multiple lineal regression (R) was 0.77, and fasting triglycerides showed the greatest effect on AUC of triglycerides with a standardized coefficient of 0.75.
Conclusions
Fasting triglycerides are the major contributors to the postprandial triglycerides levels. MetS influences the postprandial response of lipids in patients with coronary heart disease, particularly in non-hypertriglyceridemic patients
Influence of Obesity and Metabolic Disease on Carotid Atherosclerosis in Patients with Coronary Artery Disease (CordioPrev Study)
Background
Recent data suggest that the presence of associated metabolic abnormalities may be
important modifiers of the association of obesity with a poorer prognosis in coronary heart
disease. We determined the influence of isolated overweight and obesity on carotid intima
media thickness (IMT-CC), and also assessed whether this influence was determined by
the presence of metabolic abnormalities.
Methods
1002 participants from the CordioPrev study were studied at entry. We determined their
metabolic phenotypes and performed carotid ultrasound assessment. We evaluated the
influence of obesity, overweight and metabolic phenotypes on the IMT-CC.
Results
Metabolically sick participants (defined by the presence of two or more metabolic abnormalities)
showed a greater IMT-CC than metabolically healthy individuals (p = 4 * 10â6). Overweight
and normal weight patients who were metabolically healthy showed a lower IMT-CC
than the metabolically abnormal groups (all p<0.05). When we evaluated only body weight
(without considering metabolic phenotypes), overweight or obese patients did not differsignificantly from normal-weight patients in their IMT-CC (p = 0.077). However, obesity was
a determinant of IMT-CC when compared to the composite group of normal weight and
overweight patients (all not obese).
Conclusions
In coronary patients, a metabolically abnormal phenotype is associated with a greater IMTCC,
and may be linked to a higher risk of suffering new cardiovascular events. The protection
conferred in the IMT-CC by the absence of metabolic abnormality may be blunted by
the presence of obesit
Hepatic insulin resistance both in prediabetic and diabetic patients determines postprandial lipoprotein metabolism: from the CORDIOPREV study
Background/aims: Previous evidences have shown the presence of a prolonged and exaggerated postprandial
response in type 2 diabetes mellitus (T2DM) and its relation with an increase of cardiovascular risk. However, the
response in prediabetes population has not been established. The objective was to analyze the degree of postprandial
lipemia response in the CORDIOPREV clinical trial (NCT00924937) according to the diabetic status.
Methods: 1002 patients were submitted to an oral fat load test meal (OFTT) with 0.7 g fat/kg body weight [12 %
saturated fatty acids (SFA), 10 % polyunsaturated fatty acids (PUFA), 43 % monounsaturated fatty acids (MUFA), 10 %
protein and 25 % carbohydrates]. Serial blood test analyzing lipid fractions were drawn at 0, 1, 2, 3 and 4 h during
postprandial state. Postprandial triglycerides (TG) concentration at any point >2.5 mmol/L (220 mg/dL) has been
established as undesirable response. We explored the dynamic response in 57 non-diabetic, 364 prediabetic and 581
type 2 diabetic patients. Additionally, the postprandial response was evaluated according to basal insulin resistance
subgroups in patients non-diabetic and diabetic without pharmacological treatment (N = 642).
Results: Prevalence of undesirable postprandial TG was 35 % in non-diabetic, 48 % in prediabetic and 59 % in diabetic
subgroup, respectively (p < 0.001). Interestingly, prediabetic patients displayed higher plasma TG and large triacylglycerol-
rich lipoproteins (TRLs-TG) postprandial response compared with those non-diabetic patients (p < 0.001
and p = 0.003 respectively). Moreover, the area under the curve (AUC) of TG and AUC of TRLs-TG was greater in the
prediabetic group compared with non-diabetic patients (p < 0.001 and p < 0.005 respectively). Patients with liver
insulin resistance (liver-IR) showed higher postprandial response of TG compared with those patients with muscle-IR
or without any insulin-resistance respectively (p < 0.001).
Conclusions: Our findings demonstrate that prediabetic patients show a lower phenotypic flexibility after external
aggression, such as OFTT compared with nondiabetic patients. The postprandial response increases progressively
according to non-diabetic, prediabetic and type 2 diabetic state and it is higher in patients with liver insulin-resistance.
To identify this subgroup of patients is important to treat more intensively in order to avoid future cardiometabolic
complications
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