Experimental Periodontal Disease Triggers Coronary Endothelial Dysfunction in Middle-Aged Rats: Preventive Effect of a Prebiotic ß-Glucan.

This study was aimed to verify the hypothesis that periodontal disease contributes to endothelial dysfunction in the coronary arteries of middle-aged rats. Besides we evaluated the effects of a prebiotic (ß-glucan isolated from Saccharomyces cerevisiae) in preventing vascular dysfunction. The sample comprised young (sham and induced to periodontal disease) and middle-aged rats (sham, periodontal disease, sham-treated and periodontal disease-treated), at 12 and 57 weeks, respectively. The treated-groups received daily doses of ß-glucan (50 mg/kg) orally (gavage) for 4 weeks, and periodontal disease was induced in the last 2 weeks by ligature. A myograph system assessed vascular reactivity. The expression of endothelial nitric oxide synthase (eNOS), cyclooxygenase 1 (COX-1), COX-2, p47phox, gp91phox, NF-KB p65, p53, p21, and p16 was quantified by western blotting. Serum hydroperoxide production was measured by the ferrous oxidation-xylenol orange (FOX-2) assay method. Interleukin-1 beta (IL-1ß), IL-10, and tumor necrosis factor-alpha (TNF-α) levels were evaluated by spectroscopic ultraviolet-visible analysis. Periodontal disease in middle-aged rats was associated with reduced acetylcholine-induced relaxations of coronary artery rings affecting the endothelium-dependent hyperpolarization- and the nitric oxide-mediated relaxations. The endothelial dysfunction was related to eNOS downregulation, pronounced impairment of the EDH-mediated relaxation, increased IL-1ß and TNF-α proinflammatory cytokines, and also upregulation of NADPH oxidase and COXs, starting accumulate aging markers such as p53/p21 and the p16. Treatment with ß-glucan effectively reduced bone loss in periodontal disease and delayed endothelial dysfunction in the coronary artery. Our data show that yeast ß-glucan ingestion prevented oxidative stress and synthesis of proinflammatory marker and prevented eNOS reduction induced by periodontal disease in middle-aged rats. These results suggest that ß-glucan has a beneficial effect on the coronary vascular bed.

Endothelial Dysfunction and Thrombosis in Patients With COVID-19-Brief Report.

OBJECTIVE: Alveolar-capillary endothelial cells can be activated by severe acute respiratory syndrome coronavirus 2 infection leading to cytokine release. This could trigger endothelial dysfunction, pyroptosis, and thrombosis, which are the vascular changes, commonly referred to as coronavirus disease 2019 (COVID-19) endotheliopathy. Thus, this study aimed to identify tissue biomarkers associated with endothelial activation/dysfunction and the pyroptosis pathway in the lung samples of patients with COVID-19 and to compare them to pandemic influenza A virus H1N1 subtype 2009 and control cases. Approach and Results: Postmortem lung samples (COVID-19 group =6 cases; H1N1 group =10 cases, and control group =11 cases) were analyzed using immunohistochemistry and the following monoclonal primary antibodies: anti-IL (interleukin)-6, anti-TNF (tumor necrosis factor)-α, anti-ICAM-1 (intercellular adhesion molecule 1), and anticaspase-1. From the result, IL-6, TNF-α, ICAM-1, and caspase-1 showed higher tissue expression in the COVID-19 group than in the H1N1 and control groups. CONCLUSIONS: Our results demonstrated endothelial dysfunction and suggested the participation of the pyroptosis pathway in the pulmonary samples. These conditions might lead to systemic thrombotic events that could impair the clinical staff's efforts to avoid fatal outcomes. One of the health professionals' goals should be to identify the high risk of thrombosis patients early to block endotheliopathy and its consequences.

Echography analysis of musculoskeletal, heart and liver alterations associated with endothelial dysfunction in obese rats.

BACKGROUND: Modern imaging plays a central role in the care of obese patients, and there is an integral focus on its use and accessibility in individuals who have alterations of various in various organs. The objective in this study was to perform an echographic analysis of musculoskeletal system disorders, endothelial dysfunction and the left ventricle (LV) in obese rats. METHODS: Sprague Dawley rats (250 ± 5 g) were obtained and divided into two groups: the control (C) group was fed with a standard diet, and the obese (Ob) group was fed hyper caloric diet with a high fructose-fat content for 4 months. Body weight, cholesterol, triglycerides, glucose, inflammatory cytokines and adhesion molecules (ICAM-1, VCAM-1) were measured. Additionally, two-dimensional echocardiography, abdominal ultrasound and musculoskeletal system studies were performed in the lower extremities. RESULTS: The body weight in the Ob group was increased compared to that in the control group, (p < 0.001); in addition, increased glucose, cholesterol and triglyceride concentrations (p < 0.05) as well as increased levels of the adhesion molecules ICAM-1 and, VCAM-1 (p < 0.01) were found in the Ob group vs the C group. On ultrasound, 75% of the Ob group presented fatty liver and distal joint abnormalities. CONCLUSION: Obese rats exhibit endothelial dysfunction and musculoskeletal changes, also, fatty liver and articular cysts in the posterior region of the distal lower- extremity joints.

Biochemical analysis of ectonucleotidases on primary rat vascular smooth muscle cells and in silico investigation of their role in vascular diseases.

Vascular smooth muscle cells (VSMCs) exhibit a high degree of plasticity when they undergo the progression from a normal to a disease condition, which makes them a potential target for evaluating early markers and for the development of new therapies. Purinergic signalling plays a key role in vascular tonus control, ATP being an inductor of vasoconstriction, whereas adenosine mediates a vasodilation effect antagonising the ATP actions. The control of extracellular ATP and adenosine levels is done by ectonucleotidases, which represent a potential target to be evaluated in the progression of cardiovascular diseases. In this study, we analysed the basal activity and expression of the ectonucleotidases in aortic rat VSMCs, and we further performed in silico analysis to determine the expression of those enzymes in conditions that mimicked vascular diseases. Cultured in vitro VSMCs showed a prominent expression of Entpd1 followed by Entpd2 and Nt5e (CD73) and very low levels of Entpd3. Slightly faster AMP hydrolysis was observed when compared to ATP and ADP nucleotides. In silico analysis showed that the ectonucleotidases were modulated after induction of conditions that can lead to vascular diseases such as, hypertensive and hypotensive mice models (Nt5e); exposition to high-fat (Entpd1 and Entpd2) or high-phosphate (Nt5e) diet; mechanical stretch (Entpd1, Entpd2 and Nt5e); and myocardial infarction (Entpd1). Our data show that VSMCs are able to efficiently metabolise the extracellular nucleotides generating adenosine. The modulation of Entpd1, Entdp2 and Nt5e in vascular diseases suggests these ectoenzymes as potential targets or markers to be investigated in future studies.

Underexpression of endothelial nitric oxide synthase leads to more severe pulmonary complex vascular lesions associated with HIV patients / La baja expresión de oxido nítrico sintetasa provoca mayor severidad en las lesiones vasculares complejas asociadas al VIH

Abstract Background: Despite increase in survival of human immunodeficiency virus (HIV) patients due to highly active antiretroviral therapy, non-infectious complications are still prevalent such as presentation of lung vasculopathy, even in asymptomatic patients. Endothelial nitric oxide synthase (eNOS) is necessary to produce nitric oxide that causes pulmonary endothelial vasodilation. Participation of this protein in the pulmonary circulation in HIV patients has not been elucidated. This work studied the presence and expression of eNOS in pulmonary complex vascular lesions associated with HIV (PCVL/HIV). Methods: In lung tissues from patients who died from complications of HIV, we used immunohistochemistry and immune chemiluminescence (imageJ) to determine the different degrees of expression of eNOS in PCVL-HIV in comparison with non-PCVL/HIV. Reagents used were anti-eNOS and an automated system. All data are presented as mean and standard deviation. Differences were analyzed with Wilcoxon; p < 0.05 was accepted as statistically significant. Results: In 57 tissues, the histological evidence of pulmonary vasculopathy was showed as different types (proliferative, obliterative, and plexiform) and severe presentation of vasculopathy than non-PCVL/HIV. A statistically significant decrease of eNOS was observed in all PCVL/HIV tissue samples. Conclusion: eNOS has a relevant role in the pathogenesis of pulmonary vasculopathy in acquired immunodeficiency syndrome patients. It is necessary to determine in the future the participation of eNOS and other mechanisms involved in PCVL/HIV.

Resumen Antecedentes: A pesar del incremento en la sobrevivencia del paciente con virus de inmunodeficiencia humana (VIH) debido al uso del tratamiento antiretroviral altamente efectivo, las complicaciones no infecciosas siguen ocasionando vasculopatía pulmonar, aun en pacientes asintomáticos. La óxido nítrico sintetasa (ONSe) es necesaria para la producción de óxido nítrico la cual provoca vasodilatación pulmonar. La participación de esta proteína en la circulación pulmonar en los pacientes con VIH aún no se ha dilucidado. Este trabajo estudia la presencia y la expresión de ONSe en las lesiones vasculares pulmonares complejas asociadas al VIH (LVPC/VIH). Métodos: En tejidos pulmonares de pacientes que fallecieron por complicaciones del VIH, se utilizó inmunohistoquímica e inmunoquimioluminescencia (imageJ) para determinar los diferentes grados de expresión de la ONSe en LVPC/VIH. Los reactivos utilizados son anti-ONSe en sistema automatizado. Todos los datos son presentados en media y desviación estándar. Las diferencias son analizadas con la prueba de Wilcoxon; se aceptó como estadísticamente significativa una p < 0.05. Resultados: En 57 pacientes, la histología de la vasculopatía pulmonar mostró diferentes tipos (proliferativo, obliterativo y plexiforme) además de varias presentaciones de vasculopatía en tejidos no-LVPC/VIH. Se observó diferencia estadística en la disminución de ONSe en todos los tejidos LVPC/VIH. Conclusiones: La ONSe tiene un papel relevante en la patogénesis de la vasculopatía pulmonar en el VIH. Es necesario determinar en el futuro la participación de ONSe y otros mecanismos involucrados en LVPC/VIH.

Hypertensive Mediated Organ Damage and Hypertension Management. How to Assess Beneficial Effects of Antihypertensive Treatments?

The presence of hypertensive mediated organ damage is related to increased vascular risk and mortality and its prevention should be a therapeutic target and a surrogate marker of in/adequate blood pressure control. In old adult hypertensive patients the therapeutic target should be to prevent major cardiovascular events, but in young hypertensive subjects the focus should be pointed on preventing the development of hypertensive mediated organ damage, since most of the hard events are preceded by functional and structural tissues injury. Hypertension Guidelines of the European Society of Cardiology and European Society of Hypertension recognizes that some variables like electrocardiographic or echocardiographic left ventricle hypertrophy, chronic kidney disease or advance retinopathy, all considered as hypertensive mediated organ damage, may be modifiers of cardiovascular risk estimated by the SCORE system, and for that reason they should be screened in hypertensive patients. It is well known the problem of limited health systems financial resources in many low and even median income countries which precludes the possibilities of generalizing the search for hypertension mediated organ damage in all hypertensive patients. In these scenario the recommendation to perform a detailed screening should be critically evaluated. Some questions remained unanswered: the screening generalization of hypertensive mediated organ damage should modify the cardiovascular risk score of the patients, if its presence could modify the therapeutic approach, and as a consequence, if the treatment adjustment should prolong life expectancy and ameliorate the quality of life.

Underexpression of endothelial nitric oxide synthase leads to more severe pulmonary complex vascular lesions associated with HIV patients.

Background: Despite increase in survival of human immunodeficiency virus (HIV) patients due to highly active antiretroviral therapy, non-infectious complications are still prevalent such as presentation of lung vasculopathy, even in asymptomatic patients. Endothelial nitric oxide synthase (eNOS) is necessary to produce nitric oxide that causes pulmonary endothelial vasodilation. Participation of this protein in the pulmonary circulation in HIV patients has not been elucidated. This work studied the presence and expression of eNOS in pulmonary complex vascular lesions associated with HIV (PCVL/HIV). Methods: In lung tissues from patients who died from complications of HIV, we used immunohistochemistry and immune chemiluminescence (imageJ) to determine the different degrees of expression of eNOS in PCVL-HIV in comparison with non-PCVL/HIV. Reagents used were anti-eNOS and an automated system. All data are presented as mean and standard deviation. Differences were analyzed with Wilcoxon; p < 0.05 was accepted as statistically significant. Results: In 57 tissues, the histological evidence of pulmonary vasculopathy was showed as different types (proliferative, obliterative, and plexiform) and severe presentation of vasculopathy than non-PCVL/HIV. A statistically significant decrease of eNOS was observed in all PCVL/HIV tissue samples. Conclusion: eNOS has a relevant role in the pathogenesis of pulmonary vasculopathy in acquired immunodeficiency syndrome patients. It is necessary to determine in the future the participation of eNOS and other mechanisms involved in PCVL/HIV.

Antecedentes: A pesar del incremento en la sobrevivencia del paciente con virus de inmunodeficiencia humana (VIH) debido al uso del tratamiento antiretroviral altamente efectivo, las complicaciones no infecciosas siguen ocasionando vasculopatía pulmonar, aun en pacientes asintomáticos. La óxido nítrico sintetasa (ONSe) es necesaria para la producción de óxido nítrico la cual provoca vasodilatación pulmonar. La participación de esta proteína en la circulación pulmonar en los pacientes con VIH aún no se ha dilucidado. Este trabajo estudia la presencia y la expresión de ONSe en las lesiones vasculares pulmonares complejas asociadas al VIH (LVPC/VIH). Métodos: En tejidos pulmonares de pacientes que fallecieron por complicaciones del VIH, se utilizó inmunohistoquímica e inmunoquimioluminescencia (imageJ) para determinar los diferentes grados de expresión de la ONSe en LVPC/VIH. Los reactivos utilizados son anti-ONSe en sistema automatizado. Todos los datos son presentados en media y desviación estándar. Las diferencias son analizadas con la prueba de Wilcoxon; se aceptó como estadísticamente significativa una p < 0.05. Resultados: En 57 pacientes, la histología de la vasculopatía pulmonar mostró diferentes tipos (proliferativo, obliterativo y plexiforme) además de varias presentaciones de vasculopatía en tejidos no-LVPC/VIH. Se observó diferencia estadística en la disminución de ONSe en todos los tejidos LVPC/VIH. Conclusiones: La ONSe tiene un papel relevante en la patogénesis de la vasculopatía pulmonar en el VIH. Es necesario determinar en el futuro la participación de ONSe y otros mecanismos involucrados en LVPC/VIH.

Blood flow restriction impairs the inflammatory adaptations of strength training in overweight men: a clinical randomized trial.

The aim of this study was to evaluate the impact of high-intensity strength training (ST) or low-intensity strength training with blood flow restriction (ST-BFR) on monocyte subsets, the expression of C-C chemokine receptor 5 (CCR5), and CD16 on monocytes, and tumor necrosis factor alpha (TNF-α) production of overweight men. Thirty overweight men were randomly assigned to conventional ST or ST-BFR. Both groups performed exercises of knee extension and biceps curl with equal volume (3 sessions/week) over 8 weeks, and the peripheral frequency of monocytes (CD14+CD16-, classical monocytes; CD14+CD16+, intermediate monocytes; CD14-CD16+, nonclassical monocytes), the mean fluorescence intensity (MFI) of CCR5 and CD16 on CD14+ monocytes; and the production of TNF-α by lipopolysaccharide (LPS)-stimulated cells were quantified. Eight weeks of ST increased the frequency of CD14+CD16- monocytes (p = 0.04) and reduced the percentage of CD14-CD16+ (p = 0.02) and the production of TNF-α by LPS-stimulated cells (p = 0.03). The MFI of CD16 on CD14+ monocytes decreased after the ST intervention (p = 0.02). No difference in monocyte subsets, CCR5 or CD16 expression, and TNF-α production were identified after ST-BFR intervention (p > 0.05). The adoption of ST promotes anti-inflammatory effects on monocyte subsets of overweight men, but this effect was lost when BFR was adopted. Novelty High-intensity strength training reduces the production of TNF-α and the peripheral frequency of CD16+ monocytes in overweight men. Blood flow restriction method blunts the strength training adaptations on monocyte subsets and pro-inflammatory TNF-α production in overweight men.

Ly6C+ Inflammatory Monocyte Differentiation Partially Mediates Hyperhomocysteinemia-Induced Vascular Dysfunction in Type 2 Diabetic db/db Mice.

OBJECTIVE: Hyperhomocysteinemia (HHcy) is a potent risk factor for diabetic cardiovascular diseases. We have previously reported that hyperhomocysteinemia potentiates type 1 diabetes mellitus-induced inflammatory monocyte differentiation, vascular dysfunction, and atherosclerosis. However, the effects of hyperhomocysteinemia on vascular inflammation in type 2 diabetes mellitus (T2DM) and the underlying mechanism are unknown. Approach and Results: Here, we demonstrate that hyperhomocysteinemia was induced by a high methionine diet in control mice (homocysteine 129 µmol/L), which was further worsened in T2DM db/db mice (homocysteine 180 µmol/L) with aggravated insulin intolerance. Hyperhomocysteinemia potentiated T2DM-induced mononuclear cell, monocyte, inflammatory monocyte (CD11b+Ly6C+), and M1 macrophage differentiation in periphery and aorta, which were rescued by folic acid-based homocysteine-lowering therapy. Moreover, hyperhomocysteinemia exacerbated T2DM-impaired endothelial-dependent aortic relaxation to acetylcholine. Finally, transfusion of bone marrow cells depleted for Ly6C by Ly6c shRNA transduction improved insulin intolerance and endothelial-dependent aortic relaxation in hyperhomocysteinemia+T2DM mice. CONCLUSIONS: Hyperhomocysteinemia potentiated systemic and vessel wall inflammation and vascular dysfunction partially via inflammatory monocyte subset induction in T2DM. Inflammatory monocyte may be a novel therapeutic target for insulin resistance, inflammation, and cardiovascular complications in hyperhomocysteinemia+T2DM.

Antiplatelet agents for preventing vaso-occlusive events in people with sickle cell disease: a systematic review.

BACKGROUND: Sickle cell disease (SCD) is the most common hemoglobinopathy, occurring worldwide, and vaso-occlusive events (VOEs) are its paramount, hallmark clinical manifestation. Evidence exists that platelets play an important role in generating VOEs. OBJECTIVE: To assess the clinical benefits and harms of antiplatelet agents for preventing VOEs in patients with SCD. METHODS: We conducted searches of the Cochrane Central Register of Controlled Trials (CENTRAL; up to 2018, issue 3 of 12), PubMed/MEDLINE (up to April 20, 2018), and the Excerpta Medica database (EMBASE; from 1980 to week 16 of 2018). We also searched the Latin American and Caribbean Health Sciences Literature (LILACS) database, the US Food and Drug Administration (FDA) website, the European Medicines Agency (EMA) website, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), and www.ClinicalTrials.gov. We checked the bibliographies of included studies and any relevant systematic reviews. Our systematic review included randomized clinical trials (RCTs) conducted in people who had SCD without VOEs at trial entry. Eligible trials compared a single or combination treatment regimen (with each treatment classified as a conventional or nonconventional antiplatelet agent) with conventional care, placebo, or another regimen. No restrictions were placed on the route of administration, dose, frequency, or duration of treatment. We selected RCTs, assessed the risk for bias, and extracted data in a duplicate and independent fashion. We estimated risk ratios for dichotomous outcomes and mean differences for continuous outcomes. We also subjected our analyses to a random-effects model, and Trial Sequential Analysis (TSA) was used. We used the grading of recommendations, assessment, development, and evaluation (GRADE) approach to assess the overall quality of data for each individual outcome. RESULTS: We identified 5 RCTs (N=747) that met our criteria. Of these, 4 trials were multicenter and multinational. The trials included patients of all ages and assessed prasugrel, ticagrelor, crizanlizumab, and aspirin vs either placebo or no intervention. The most frequent route of administration was oral. The trials were small and carried a high risk for bias, given that pharmaceutical companies sponsored 4 of them. None of the trials reported information on quality of life. No meta-analysis was performed owing to heterogeneity in the ages of the participants and in the interventions. No single trial showed evidence of certainty regarding all-cause mortality. One trial showed uncertainty in comparing prasugrel vs placebo for preventing VOEs in patients younger than 18 years (relative risk [RR], 0.92; 95% CI, 0.80 to 1.06; low quality of evidence). TSA for this outcome suggested that a new trial should be conducted. One trial found a difference in the size effect of uncomplicated VOEs, favoring high-dose crizanlizumab vs placebo (mean difference, -1.50; 95% CI, -2.61 to -0.39; very low quality of evidence). No difference in VOEs was found in studies that compared either ticagrelor in children or prasugrel in adults vs placebo. The overall incidence of harms in any intervention did not differ from that in the control. CONCLUSIONS: The current evidence does not support or reject the use of any antiplatelet agent for preventing VOEs in people with SCD. This conclusion was based on small RCTs that carried a high risk for bias. No conclusive evidence exists regarding relevant clinical outcomes because the evidence is limited and of very low quality.

Effects of Resistance and Combined training on Vascular Function in Type 2 Diabetes: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Cardiovascular disease (CVD) is the main cause of mortality in type 2 diabetes (T2D). Exercise can reduce the risk factors associated with CVD in T2D patients. However, research evaluating its beneficial effects in these patients has used different measurement protocols and types of exercise, complicating comparison. AIM: To assess the effects of resistance training (RT) and combined training (CT) on the vascular function of T2D patients. METHODS: A database search (MEDLINE, Scopus, and Web of Science) was performed to identify relevant articles that were published up to August 2017. Only original studies evaluating the effects of RT or CT interventions on vascular function in T2D patients were included. The articles were reviewed independently by at least three reviewers. The Cochrane guidelines were used to assess the methodological quality of the studies. Fourteen studies were finally included. Two studies only used RT and twelve studies used CT as intervention strategy. RESULTS AND CONCLUSIONS: The results show that resistance training is a useful means for primary treatment of vascular diseases and maintenance of vascular function in T2D patients. However, more studies are necessary to gain full knowledge of the beneficial effects and to identify tailored exercise plans to optimize these benefits. The information provided in this review may help to improve current treatment of vascular diseases in T2D patients and to design future studies.

Chronic thromboembolic and pulmonary arterial hypertension share right ventricular and pulmonary artery CMR features.

BACKGROUND: Cardiac magnetic resonance (CMR) imaging has gained importance in pulmonary hypertension (PH) and studies have demonstrated its use as a surrogate marker and in following treatment of these patients. The pathophysiology of PH differs between pulmonary arterial hypertension (PAH, group 1) and chronic thromboembolic PH (CTEPH, group 4). OBJECTIVES: The present study tested the hypothesis that PAH and CTEPH display different characteristics on CMR imaging. METHODS: 46 patients were evaluated for pulmonary vascular disease in the French National Reference Center for PH (23 PAH and 23 CTEPH matched for age and gender). All patients had the right heart catheterization (RHC) and CMR imaging performed within 48h. CMR imaging was performed on a 1.5 T scanner. RESULTS: PAH and CTEPH had similar body surface area and similar invasive hemodynamics, including mean pulmonary arterial pressure, cardiac index, pulmonary vascular resistance and right atrial pressure. PAH and CTEPH had similar CMR data. Right ventricular (RV) morphology and function and pulmonary artery (PA) data were also similar. CONCLUSION: Age- and sex-matched PAH and CTEPH patients displayed similar values of the CMR indices of RV and PA morphology and function, suggesting that the RV-PA responses are similar in both groups, mostly related to the overall increase in after load.

Metabolic Changes Induced by High-Fat Meal Evoke Different Microvascular Responses in Accordance with Adiposity Status.

BACKGROUND: Frequently, ingestion of lipids exceeds our daily requirements and constantly exposes humans to circulating lipid overload which may lead to endothelial dysfunction (ED), the earliest marker of atherosclerosis. Nailfold videocapillaroscopy (NVC) technique can detect ED on microcirculation. Using NVC, we aimed to demonstrate if metabolic alterations evoked by high-fat meals can act differently on microvascular endothelial reactivity in lean and women with obesity. METHODS: Women, aged between 19 and 40 years, were allocated to control group (CG) and with obesity group (OBG) and were subjected to blood analysis for determination of glucose, total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) and NVC evaluation at fasting and 30, 60, 120, and 180-min after high-fat meal ingestion. NVC technique evaluated microvascular reactivity through the following variables: red blood cell velocity (RBCV) at rest and after 1-min ischemia (maximal red blood cell velocity, RBCVmax) and time taken to reach it (TRBCVmax). A P value ≤0.05 was considered significant. RESULTS: High-fat meal promoted a two-phase response in both groups: one until 60-min, associated with glucose and insulin levels, and the other after 120-min, associated with TG levels. Significant differences between groups were observed concerning insulin and HDL-c concentrations only at fasting and TC, TG, and LDL-c levels in all-time points. Regarding microvascular reactivity, RBCV, RBCVmax, and TRBCVmax were significantly different in OBG at 30-min compared to baseline. RBCVmax and TRBCVmax were significantly different in CG at 30-min and 60-min comparing to fasting. In all-time points, OBG presented RBCV, RBCVmax , and TRBCVmax significantly different in comparison to CG. CONCLUSION: High-fat meal worsened ED on microcirculation in women with obesity and induced impairment of endothelial function in lean ones, reinforcing the association between high-fat meal and atherosclerosis.

The Placenta in Neonatal Encephalopathy: A Case-Control Study.

OBJECTIVE: We assessed whether specific histologic placental lesions were associated with risk for neonatal encephalopathy, a strong predictor of death or cerebral palsy. STUDY DESIGN: Case-control study of singletons with gestational ages ≥35 weeks. Data were abstracted from a prospectively collected database of consecutive births at a hospital in which placental samples from specified sites are collected and stored for all inborn infants. Placentas of infants with neonatal encephalopathy were compared with randomly selected control infants (ratio of 1:3). Placental histologic slides were read by a single experienced perinatal pathologist unaware of case status, using internationally recommended definitions and terminology. Findings were grouped into inflammatory, maternal, or fetal vascular malperfusion (FVM) and other lesions. RESULTS: Placental samples were available for 73 of 87 (84%) cases and 253 of 261 (97%) controls. Delivery complications and gross placental abnormalities were more common in cases, of whom 4 died. Inflammation and maternal vascular malperfusion did not differ, and findings consistent with global FVM were more frequent in case (20%) than control (7%) placentas (P = .001). There was a trend toward more segmental FVM and high-grade FVM (fetal thrombotic vasculopathy) among cases. Some type of FVM was observed in 24% of placentas with neonatal encephalopathy. In infants with both neonatal encephalopathy and placental FVM, more often than in infants with neonatal encephalopathy without FVM, electronic fetal monitoring tracings were considered possibly or definitely abnormal (P = .028). CONCLUSIONS: Vascular malperfusion of subacute or chronic origin on the fetal side of the placenta was associated with increased risk of neonatal encephalopathy.

Phenotypic Variability in a Mexican Mestizo Family with Retinal Vasculopathy with Cerebral Leukodystrophy and TREX1 Mutation p.V235Gfs*6.

BACKGROUND: Retinal vasculopathy with cerebral leukodystrophy (RVCL) is an adult-onset, autosomal dominant disease involving microvessels of the brain and eye resulting in central nervous system degeneration with visual disturbances, stroke, motor impairment, and cognitive decline. Frameshift mutations at the C-terminus of TREX1 gene are the molecular cause of this disorder. OBJECTIVES: The objective of this study is to present the different clinical manifestations of RVCL in three-related patients and to investigate the presence of TREX1 mutation in the extended genealogy. METHODS: Multidisciplinary testing was performed in three related patients. Based on their family history, the study was extended to 34 relatives from the same small community. Neurological evaluation, sequencing of TREX1, and presymptomatic diagnosis were offered to all participants. RESULTS: The patients exhibited the heterozygous TREX1 mutation p.V235Gfs*6, but with phenotypic variability. In addition, 15 relatives were identified as pre-manifest mutation carriers. The remaining participants did not carry the mutation. CONCLUSIONS: This is the figrst report of a large Mexican genealogy with RVCL, where the same TREX1 mutation causes a variation in organ involvement and clinical progression. The early identification and follow-up of individuals at risk may help provide insights into the basis for this variability in presentation.

Muscular and Vascular Issues Induced by Prolonged Standing With Different Work-Rest Cycles With Active or Passive Breaks.

OBJECTIVE: The aim of this study was to evaluate the long-lasting motor, behavioral, physiological, and perceptual effects of prolonged standing work in three work-rest cycle conditions including passive or active rest breaks. BACKGROUND: Muscle fatigue has been evidenced after prolonged standing work through physiological and neuromotor measures. It has been postulated that muscle fatigue induced by prolonged work could be attenuated by appropriate scheduling of work and rest periods. However, investigations in this domain remain limited. METHOD: Thirty participants simulated standing work for 5 hr with work-rest cycles of short, medium, or long standing periods including passive or active breaks. Lower-leg muscle twitch force (MTF), muscle oxygenation, lower-leg volume, postural stability, force control, and discomfort perception were quantified on 2 days. RESULTS: Prolonged standing induced significant changes in all measures immediately after 5 hr of work, indicating a detrimental effect in long-lasting muscle fatigue, performance, discomfort, and vascular aspects. Differences in the measures were not significant between work cycles and/or break type. CONCLUSION: Similar physiological and motor alterations were induced by prolonged standing. The absence of difference in the effects induced by the tested work-rest cycles suggests that simply altering the work-rest cycle may not be sufficient to counteract the effects of mainly static standing work. Finally, standing for 3 hr or more shows clear detrimental effects. APPLICATION: Prolonged standing is likely to contribute to musculoskeletal and vascular symptoms. A limitation to less than 3 hr of mostly static standing in occupational activities could avoid alterations leading to these symptoms.

Developmental programming of vascular dysfunction by prenatal and postnatal zinc deficiency in male and female rats.

Micronutrient malnutrition during intrauterine and postnatal growth may program cardiovascular diseases in adulthood. We examined whether moderate zinc restriction in male and female rats throughout fetal life, lactation and/or postweaning growth induces alterations that can predispose to the onset of vascular dysfunction in adulthood. Female Wistar rats were fed low- or control zinc diets from pregnancy to offspring weaning. After weaning, offspring were fed either a low- or a control zinc diet until 81 days. We evaluated systolic blood pressure (SBP), thoracic aorta morphology, nitric oxide (NO) system and vascular reactivity in 6- and/or 81-day-old offspring. At day 6, zinc-deficient male and female offspring showed a decrease in aortic NO synthase (NOS) activity accompanied by an increase in oxidative stress. Zinc-deficient 81-day-old male rats exhibited an increase in collagen deposition in tunica media, as well as lower activity of endothelial NOS (eNOS) that could not be reversed with an adequate zinc diet during postweaning life. Zinc deficiency programmed a reduction in eNOS protein expression and higher SBP only in males. Adult zinc-deficient rats of both sexes showed reduced vasodilator response dependent on eNOS activity and impaired aortic vasoconstrictor response to angiotensin-II associated with alterations in intracellular calcium mobilization. Female rats were less sensitive to the effects of zinc deficiency and exhibited higher eNOS activity and/or expression than males, without alterations in SBP or aortic histology. This work strengthens the importance of a balanced intake of micronutrients during perinatal growth to ensure adequate vascular function in adult life.