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Sample records for pathological systemic hypertension

  1. Physio-pathological effects of alcohol on the cardiovascular system: its role in hypertension and cardiovascular disease.

    PubMed

    Kawano, Yuhei

    2010-03-01

    Alcohol has complex effects on the cardiovascular system. The purpose of this article is to review physio-pathological effects of alcohol on cardiovascular and related systems and to describe its role in hypertension and cardiovascular disease. The relationship between alcohol and hypertension is well known, and a reduction in the alcohol intake is widely recommended in the management of hypertension. Moreover, alcohol has both pressor and depressor actions. The latter actions are clear in Oriental subjects, especially in those who show alcohol flush because of the genetic variation in aldehyde dehydrogenase activity. Repeated alcohol intake in the evening causes an elevation in daytime and a reduction in nighttime blood pressure (BP), with little change in the average 24-h BP in Japanese men. Thus, the hypertensive effect of alcohol seems to be overestimated by the measurement of casual BP during the day. Heavy alcohol intake seems to increase the risk of several cardiovascular diseases, such as hemorrhagic stroke, arrhythmia and heart failure. On the other hand, alcohol may act to prevent atherosclerosis and to decrease the risk of ischemic heart disease, mainly by increasing HDL cholesterol and inhibiting thrombus formation. A J- or U-shaped relationship has been observed between the level of alcohol intake and risk of cardiovascular mortality and total mortality. It is reasonable to reduce the alcohol intake to less than 30 ml per day for men and 15 ml per day for women in the management of hypertension. As a small amount of alcohol seems to be beneficial, abstinence from alcohol is not recommended to prevent cardiovascular disease.

  2. Modern Age Pathology of Pulmonary Arterial Hypertension

    PubMed Central

    Stacher, Elvira; Graham, Brian B.; Hunt, James M.; Gandjeva, Aneta; Groshong, Steve D.; McLaughlin, Vallerie V.; Jessup, Marsha; Grizzle, William E.; Aldred, Michaela A.; Cool, Carlyne D.

    2012-01-01

    Rationale: The impact of modern treatments of pulmonary arterial hypertension (PAH) on pulmonary vascular pathology remains unknown. Objectives: To assess the spectrum of pulmonary vascular remodeling in the modern era of PAH medication. Methods: Assessment of pulmonary vascular remodeling and inflammation in 62 PAH and 28 control explanted lungs systematically sampled. Measurements and Main Results: Intima and intima plus media fractional thicknesses of pulmonary arteries were increased in the PAH group versus the control lungs and correlated with pulmonary hemodynamic measurements. Despite a high variability of morphological measurements within a given PAH lung and among all PAH lungs, distinct pathological subphenotypes were detected in cohorts of PAH lungs. These included a subset of lungs lacking intima or, most prominently, media remodeling, which had similar numbers of profiles of plexiform lesions as those in lungs with more pronounced remodeling. Marked perivascular inflammation was present in a high number of PAH lungs and correlated with intima plus media remodeling. The number of profiles of plexiform lesions was significantly lower in lungs of male patients and those never treated with prostacyclin or its analogs. Conclusions: Our results indicate that multiple features of pulmonary vascular remodeling are present in patients treated with modern PAH therapies. Perivascular inflammation may have an important role in the processes of vascular remodeling, all of which may ultimately lead to increased pulmonary artery pressure. Moreover, our study provides a framework to interpret and design translational studies in PAH. PMID:22679007

  3. The immune system and hypertension.

    PubMed

    Singh, Madhu V; Chapleau, Mark W; Harwani, Sailesh C; Abboud, Francois M

    2014-08-01

    A powerful interaction between the autonomic and the immune systems plays a prominent role in the initiation and maintenance of hypertension and significantly contributes to cardiovascular pathology, end-organ damage and mortality. Studies have shown consistent association between hypertension, proinflammatory cytokines and the cells of the innate and adaptive immune systems. The sympathetic nervous system, a major determinant of hypertension, innervates the bone marrow, spleen and peripheral lymphatic system and is proinflammatory, whereas the parasympathetic nerve activity dampens the inflammatory response through α7-nicotinic acetylcholine receptors. The neuro-immune synapse is bidirectional as cytokines may enhance the sympathetic activity through their central nervous system action that in turn increases the mobilization, migration and infiltration of immune cells in the end organs. Kidneys may be infiltrated by immune cells and mesangial cells that may originate in the bone marrow and release inflammatory cytokines that cause renal damage. Hypertension is also accompanied by infiltration of the adventitia and perivascular adipose tissue by inflammatory immune cells including macrophages. Increased cytokine production induces myogenic and structural changes in the resistance vessels, causing elevated blood pressure. Cardiac hypertrophy in hypertension may result from the mechanical afterload and the inflammatory response to resident or migratory immune cells. Toll-like receptors on innate immune cells function as sterile injury detectors and initiate the inflammatory pathway. Finally, abnormalities of innate immune cells and the molecular determinants of their activation that include toll-like receptor, adrenergic, cholinergic and AT1 receptors can define the severity of inflammation in hypertension. These receptors are putative therapeutic targets.

  4. The Immune System in Hypertension

    ERIC Educational Resources Information Center

    Trott, Daniel W.; Harrison, David G.

    2014-01-01

    While hypertension has predominantly been attributed to perturbations of the vasculature, kidney, and central nervous system, research for almost 50 yr has shown that the immune system also contributes to this disease. Inflammatory cells accumulate in the kidneys and vasculature of humans and experimental animals with hypertension and likely…

  5. Molecular pathogenesis and current pathology of pulmonary hypertension.

    PubMed

    de Jesus Perez, Vinicio A

    2016-05-01

    Following its initial description over a century ago, pulmonary arterial hypertension (PAH) continues to challenge researchers committed to understanding its pathobiology and finding a cure. The last two decades have seen major developments in our understanding of the genetics and molecular basis of PAH that drive cells within the pulmonary vascular wall to produce obstructive vascular lesions; presently, the field of PAH research has taken numerous approaches to dissect the complex amalgam of genetic, molecular and inflammatory pathways that interact to initiate and drive disease progression. In this review, we discuss the current understanding of PAH pathology and the role that genetic factors and environmental influences share in the development of vascular lesions and abnormal cell function. We also discuss how animal models can assist in elucidating gene function and the study of novel therapeutics, while at the same time addressing the limitations of the most commonly used rodent models. Novel experimental approaches based on application of next generation sequencing, bioinformatics and epigenetics research are also discussed as these are now being actively used to facilitate the discovery of novel gene mutations and mechanisms that regulate gene expression in PAH. Finally, we touch on recent discoveries concerning the role of inflammation and immunity in PAH pathobiology and how they are being targeted with immunomodulatory agents. We conclude that the field of PAH research is actively expanding and the major challenge in the coming years is to develop a unified theory that incorporates genetic and mechanistic data to address viable areas for disease modifying drugs that can target key processes that regulate the evolution of vascular pathology of PAH.

  6. The immune system in hypertension.

    PubMed

    Trott, Daniel W; Harrison, David G

    2014-03-01

    While hypertension has predominantly been attributed to perturbations of the vasculature, kidney, and central nervous system, research for almost 50 yr has shown that the immune system also contributes to this disease. Inflammatory cells accumulate in the kidneys and vasculature of humans and experimental animals with hypertension and likely contribute to end-organ damage. We and others have shown that mice lacking adaptive immune cells, including recombinase-activating gene-deficient mice and rats and mice with severe combined immunodeficiency have blunted hypertension to stimuli such as ANG II, high salt, and norepinephrine. Adoptive transfer of T cells restores the blood pressure response to these stimuli. Agonistic antibodies to the ANG II receptor, produced by B cells, contribute to hypertension in experimental models of preeclampsia. The central nervous system seems important in immune cell activation, because lesions in the anteroventral third ventricle block hypertension and T cell activation in response to ANG II. Likewise, genetic manipulation of reactive oxygen species in the subfornical organ modulates both hypertension and immune cell activation. Current evidence indicates that the production of cytokines, including tumor necrosis factor-α, interleukin-17, and interleukin-6, contribute to hypertension, likely via effects on both the kidney and vasculature. In addition, the innate immune system also appears to contribute to hypertension. We propose a working hypothesis linking the sympathetic nervous system, immune cells, production of cytokines, and, ultimately, vascular and renal dysfunction, leading to the augmentation of hypertension. Studies of immune cell activation will clearly be useful in understanding this common yet complex disease.

  7. [Relevant issues in the pathology and pathobiology of pulmonary hypertension].

    PubMed

    Tuder, Rubin M; Archer, Stephen L; Dorfmüller, Peter; Erzurum, Serpil C; Guignabert, Christophe; Michelakis, Evangelos; Rabinovitch, Marlene; Schermuly, Ralph; Stenmark, Kurt R; Morrell, Nicholas W

    2014-10-01

    Knowledge of the pathobiology of pulmonary hypertension (PH) continues to accelerate. However, fundamental gaps remain in our understanding of the underlying pathological changes in pulmonary arteries and veins in the different forms of this syndrome. Although PH primarily affects the arteries, venous disease is increasingly recognized as an important entity. Moreover, prognosis in PH is determined largely by the status of the right ventricle, rather than the levels of pulmonary artery pressures. It is increasingly clear that although vasospasm plays a role, PH is an obstructive lung panvasculopathy. Disordered metabolism and mitochondrial structure, inflammation, and dysregulation of growth factors lead to a proliferative, apoptosis-resistant state. These abnormalities may be acquired, genetically mediated as a result of mutations in bone morphogenetic protein receptor-2 or activin-like kinase-1, or epigenetically inherited (as a result of epigenetic silencing of genes such as superoxide dismutase-2). There is a pressing need to better understand how the pathobiology leads to severe disease in some patients versus mild PH in others. Recent recognition of a potential role of acquired abnormalities of mitochondrial metabolism in the right ventricular myocytes and pulmonary vascular cells suggests new therapeutic approaches, diagnostic modalities, and biomarkers. Finally, dissection of the role of pulmonary inflammation in the initiation and promotion of PH has revealed a complex yet fascinating interplay with pulmonary vascular remodeling, promising to lead to novel therapeutics and diagnostics. Emerging concepts are also relevant to the pathobiology of PH, including a role for bone marrow and circulating progenitor cells and microribonucleic acids. Continued interest in the interface of the genetic basis of PH and cellular and molecular pathogenetic links should further expand our understanding of the disease. (J Am Coll Cardiol 2013;62:D4-12) a 2013 by the

  8. Relevant issues in the pathology and pathobiology of pulmonary hypertension.

    PubMed

    Tuder, Rubin M; Archer, Stephen L; Dorfmüller, Peter; Erzurum, Serpil C; Guignabert, Christophe; Michelakis, Evangelos; Rabinovitch, Marlene; Schermuly, Ralph; Stenmark, Kurt R; Morrell, Nicholas W

    2013-12-24

    Knowledge of the pathobiology of pulmonary hypertension (PH) continues to accelerate. However, fundamental gaps remain in our understanding of the underlying pathological changes in pulmonary arteries and veins in the different forms of this syndrome. Although PH primarily affects the arteries, venous disease is increasingly recognized as an important entity. Moreover, prognosis in PH is determined largely by the status of the right ventricle, rather than the levels of pulmonary artery pressures. It is increasingly clear that although vasospasm plays a role, PH is an obstructive lung panvasculopathy. Disordered metabolism and mitochondrial structure, inflammation, and dysregulation of growth factors lead to a proliferative, apoptosis-resistant state. These abnormalities may be acquired, genetically mediated as a result of mutations in bone morphogenetic protein receptor-2 or activin-like kinase-1, or epigenetically inherited (as a result of epigenetic silencing of genes such as superoxide dismutase-2). There is a pressing need to better understand how the pathobiology leads to severe disease in some patients versus mild PH in others. Recent recognition of a potential role of acquired abnormalities of mitochondrial metabolism in the right ventricular myocytes and pulmonary vascular cells suggests new therapeutic approaches, diagnostic modalities, and biomarkers. Finally, dissection of the role of pulmonary inflammation in the initiation and promotion of PH has revealed a complex yet fascinating interplay with pulmonary vascular remodeling, promising to lead to novel therapeutics and diagnostics. Emerging concepts are also relevant to the pathobiology of PH, including a role for bone marrow and circulating progenitor cells and microribonucleic acids. Continued interest in the interface of the genetic basis of PH and cellular and molecular pathogenetic links should further expand our understanding of the disease.

  9. The immune system in hypertension.

    PubMed

    Harrison, David G

    2014-01-01

    Hypertension is generally attributed to perturbations of the vasculature, the kidney, and the central nervous system. During the past several years, it has become apparent that cells of the innate and adaptive immune system also contribute to this disease. Macrophages and T cells accumulate in the kidneys and vasculature of humans and experimental animals with hypertension, and likely contribute to end-organ damage. We have shown that mice lacking lymphocytes, such as recombinase-activating gene-deficient (RAG-1(-/-)) mice, have blunted hypertension in response to angiotensin II, increased salt levels, and norepinephrine. Adoptive transfer of T cells restores the blood pressure response to these stimuli. Others have shown that mice with severe combined immunodeficiency have blunted hypertension in response to angiotensin II. Deletion of the RAG gene in Dahl salt-sensitive rats reduces the hypertensive response to salt feeding. The central nervous system seems to orchestrate immune cell activation. We produced lesions of the anteroventral third ventricle and showed that these block T cell activation in response to angiotensin II. Likewise, we showed that genetic manipulation of reactive oxygen species in the subfornical organ modulates both hypertension and T cell activation. Current evidence indicates that production of cytokines including tumor necrosis factor alpha, interleukin 17, and interleukin 6 contribute to hypertension, likely by promoting vasoconstriction, production of reactive oxygen species, and sodium reabsorption in the kidney. We propose a working hypothesis linking the sympathetic nervous system, immune cells, the production of cytokines, and ultimately vascular and renal dysfunction, leading to augmentation of hypertension.

  10. THE RENAL PATHOLOGY OF NUTRITIONAL HYPERTENSION IN RATS

    PubMed Central

    Calder, Royall M.

    1944-01-01

    Rats subsisting on a diet partially deficient in the heat-stable fractions of the vitamin B complex are known to experience a rise in blood pressure. The present study shows that after prolonged administration of this dietary, abnormal structural changes occur in the kidneys. The surface of this organ becomes finely granular. The afferent arterioles show degenerative changes, consisting of irregular subendothelial hyaline deposits which encroach on the lumen. The interlobular arteries undergo the same change, plus degeneration of the media; the lumen of these vessels is likewise compromised. Resultant, small, streak-like areas of ischemic atrophy occur in both cortex and medulla, with necrosis of the epithelial lining of the uriniferous tubules. The glomeruli are reduced in size, the number of their component loops decreased, their pattern simplified, and the capillary basement membrane thickened. In addition to these changes, kidneys from animals on a more profoundly deficient diet display numerous areas of hemorrhagic infiltration in the cortical and subcapsular regions. The possible identity of these lesions with those seen in essential hypertension in man is discussed. PMID:19871365

  11. Hypertension accelerates the progression of Alzheimer-like pathology in a mouse model of the disease.

    PubMed

    Cifuentes, Diana; Poittevin, Marine; Dere, Ekrem; Broquères-You, Dong; Bonnin, Philippe; Benessiano, Joëlle; Pocard, Marc; Mariani, Jean; Kubis, Nathalie; Merkulova-Rainon, Tatyana; Lévy, Bernard I

    2015-01-01

    Cerebrovascular impairment is frequent in patients with Alzheimer disease and is believed to influence clinical manifestation and severity of the disease. Cardiovascular risk factors, especially hypertension, have been associated with higher risk of developing Alzheimer disease. To investigate the mechanisms underlying the hypertension, Alzheimer disease cross talk, we established a mouse model of dual pathology by infusing hypertensive doses of angiotensin II into transgenic APPPS1 mice overexpressing mutated human amyloid precursor and presenilin 1 proteins. At 4.5 months, at the early stage of disease progression, only hypertensive APPPS1 mice presented impairment of temporal order memory performance in the episodic-like memory task. This cognitive deficit was associated with an increased number of cortical amyloid deposits (223±5 versus 207±5 plaques/mm(2); P<0.05) and a 2-fold increase in soluble amyloid levels in the brain and in plasma. Hypertensive APPPS1 mice presented several cerebrovascular alterations, including a 25% reduction in cerebral microvessel density and a 30% to 40% increase in cerebral vascular amyloid deposits, as well as a decrease in vascular endothelial growth factor A expression in the brain, compared with normotensive APPPS1 mice. Moreover, the brain levels of nitric oxide synthase 1 and 3 and the nitrite/nitrate levels were reduced in hypertensive APPPS1 mice (by 49%, 34%, and 33%, respectively, compared with wild-type mice; P<0.05). Our results indicate that hypertension accelerates the development of Alzheimer disease-related structural and functional alterations, partially through cerebral vasculature impairment and reduced nitric oxide production.

  12. Digital pathology and anatomic pathology laboratory information system integration to support digital pathology sign-out

    PubMed Central

    Guo, Huazhang; Birsa, Joe; Farahani, Navid; Hartman, Douglas J.; Piccoli, Anthony; O’Leary, Matthew; McHugh, Jeffrey; Nyman, Mark; Stratman, Curtis; Kvarnstrom, Vanja; Yousem, Samuel; Pantanowitz, Liron

    2016-01-01

    Background: The adoption of digital pathology offers benefits over labor-intensive, time-consuming, and error-prone manual processes. However, because most workflow and laboratory transactions are centered around the anatomical pathology laboratory information system (APLIS), adoption of digital pathology ideally requires integration with the APLIS. A digital pathology system (DPS) integrated with the APLIS was recently implemented at our institution for diagnostic use. We demonstrate how such integration supports digital workflow to sign-out anatomical pathology cases. Methods: Workflow begins when pathology cases get accessioned into the APLIS (CoPathPlus). Glass slides from these cases are then digitized (Omnyx VL120 scanner) and automatically uploaded into the DPS (Omnyx® Integrated Digital Pathology (IDP) software v.1.3). The APLIS transmits case data to the DPS via a publishing web service. The DPS associates scanned images with the correct case using barcode labels on slides and information received from the APLIS. When pathologists remotely open a case in the DPS, additional information (e.g. gross pathology details, prior cases) gets retrieved from the APLIS through a query web service. Results: Following validation of this integration, pathologists at our institution have signed out more than 1000 surgical pathology cases in a production environment. Integration between the APLIS and DPS enabled pathologists to review digital slides while simultaneously having access to pertinent case metadata. The introduction of a digital workflow eliminated costly manual tasks involving matching of glass slides and avoided delays waiting for glass slides to be delivered. Conclusion: Integrating the DPS and APLIS were instrumental for successfully implementing a digital solution at our institution for pathology sign-out. The integration streamlined our digital sign-out workflow, diminished the potential for human error related to matching slides, and improved the sign

  13. Pathological function of Ca2+-sensing receptor in pulmonary arterial hypertension.

    PubMed

    Yamamura, Aya

    2014-01-01

    Pulmonary arterial hypertension (PAH) is defined as an intractable disease characterized by a progressive elevation of pulmonary vascular resistance (PVR) and pulmonary arterial pressure (PAP), leading to right heart failure and premature death. The five-year survival rate after diagnosis is approximately 57%. Although extensive research has identified some factors associated with the cause of PAH, the etiology and pathogenesis remain unclear. In addition to Ca(2+) channel blockers (nifedipine, diltiazem), three categories of drug have been developed for the treatment of PAH based on the pathological mechanisms: prostacyclin and its analogues (epoprostenol, treprostinil, iloprost), endothelin receptor antagonists (bosentan, ambrisentan), and phosphodiesterase type 5 inhibitors (sildenafil, tadalafil). However, screening of novel types of drug acting on the signal pathway associated with the pathological mechanism underlying PAH is ongoing. We recently found that the extracellular Ca(2+)-sensing receptor (CaSR), which belongs to family C of the G protein-coupled receptor (GPCR) superfamily, is upregulated in pulmonary arterial smooth muscle cells (PASMCs) from patients with idiopathic PAH (IPAH). The upregulated CaSR is necessary for the enhanced Ca(2+) signaling and the augmented cell proliferation in PASMCs from IPAH patients. Most importantly, blockage of CaSR with an antagonist, NPS2143, prevents the development of pulmonary hypertension and right ventricular hypertrophy in animal models of pulmonary hypertension. The use of calcilytics, antagonists of CaSR, may be a novel therapeutic approach for PAH patients.

  14. Cardiac pathology in the hypertensive diabetic rat. Biventricular damage with right ventricular predominance.

    PubMed Central

    Fein, F. S.; Cho, S.; Zola, B. E.; Miller, B.; Factor, S. M.

    1989-01-01

    The hypertensive-diabetic rat is a new small animal model of cardiomyopathy characterized by ventricular damage. To determine the extent of pathology in this model, quantitation of light microscopic changes in hearts from 15 hypertensive-diabetic rats and 15 age-matched controls was performed. The fraction of myocardium involved by interstitial fibrosis, myocyte necrosis, replacement fibrosis, vascular sclerosis and perivascular fibrosis was computed separately for right and left ventricles. Spontaneously dying as well as deliberately killed hypertensive-diabetic rats were studied. Spontaneously dying animals had higher systolic blood pressures compared with rats killed deliberately. Body weights were lower and lung weights higher in the former group. Left and right ventricular necrosis and fibrosis were increased in spontaneously dying compared with deliberately killed rats. The degree of right ventricular necrosis and fibrosis paralleled that in the left ventricle, but was, unexpectedly, several times greater in magnitude. Thus, quantitative histology in the hypertensive-diabetic rat reveals more cardiac necrosis and fibrosis, in either ventricle, from spontaneously dying animals compared with deliberately killed rats. This damage, coupled with major functional alterations in the viable myocardium, may lead to congestive heart failure or arrhythmia. Images Figure 1 Figure 2 PMID:2719080

  15. The sympathetic nervous system in obesity hypertension.

    PubMed

    Lohmeier, Thomas E; Iliescu, Radu

    2013-08-01

    Abundant evidence supports a role of the sympathetic nervous system in the pathogenesis of obesity-related hypertension. However, the nature and temporal progression of mechanisms underlying this sympathetically mediated hypertension are incompletely understood. Recent technological advances allowing direct recordings of renal sympathetic nerve activity (RSNA) in conscious animals, together with direct suppression of RSNA by renal denervation and reflex-mediated global sympathetic inhibition in experimental animals and human subjects have been especially valuable in elucidating these mechanisms. These studies strongly support the concept that increased RSNA is the critical mechanism by which increased central sympathetic outflow initiates and maintains reductions in renal excretory function, causing obesity hypertension. Potential determinants of renal sympathoexcitation and the differential mechanisms mediating the effects of renal-specific versus reflex-mediated, global sympathetic inhibition on renal hemodynamics and cardiac autonomic function are discussed. These differential mechanisms may impact the efficacy of current device-based approaches for hypertension therapy.

  16. Mineralocorticoid hypertension

    PubMed Central

    Gupta, Vishal

    2011-01-01

    Hypertension affects about 10 – 25% of the population and is an important risk factor for cardiovascular and renal disease. The renin-angiotensin system is frequently implicated in the pathophysiology of hypertension, be it primary or secondary. The prevalence of primary aldosteronism increases with the severity of hypertension, from 2% in patients with grade 1 hypertension to 20% among resistant hypertensives. Mineralcorticoid hypertension includes a spectrum of disorders ranging from renin-producing pathologies (renin-secreting tumors, malignant hypertension, coarctation of aorta), aldosterone-producing pathologies (primary aldosteronism – Conns syndrome, familial hyperaldosteronism 1, 2, and 3), non-aldosterone mineralocorticoid producing pathologies (apparent mineralocorticoid excess syndrome, Liddle syndrome, deoxycorticosterone-secreting tumors, ectopic adrenocorticotropic hormones (ACTH) syndrome, congenitalvadrenal hyperplasia), and drugs with mineraocorticoid activity (locorice, carbenoxole therapy) to glucocorticoid receptor resistance syndromes. Clinical presentation includes hypertension with varying severity, hypokalemia, and alkalosis. Ratio of plasma aldosterone concentraion to plasma renin activity remains the best screening tool. Bilateral adrenal venous sampling is the best diagnostic test coupled with a CT scan. Treatment is either surgical (adrenelectomy) for unilateral adrenal disease versus medical therapy for idiopathic, ambiguous, or bilateral disease. Medical therapy focuses on blood pressure control and correction of hypokalemia using a combination of anti-hypertensives (calcium channel blockers, angiotensin converting enzyme inhibitors, or angiotensin receptor blockers) and potassium-raising therapies (mineralcorticoid receptor antagonist or potassium sparing diuretics). Direct aldosterone synthetase antagonists represent a promising future therapy. PMID:22145132

  17. Hypertension.

    PubMed

    Fitzgerald, Kara; Lepine, Todd

    2012-05-01

    Hypertension is responsible for roughly one-in-six adult deaths annually in the United States and is associated with five of the top nine causes of death.(1) Ten trillion dollars is the estimated annual cost worldwide of the direct and indirect effects of hypertension.(2,3) In the U.S. alone, costs estimated at almost $74 billion in 2009 placed a huge economic burden on the health care system.(4) The prevalence of hypertension increases with advancing age to the point where more than half of people 60 to 69 years of age and at least three-fourths of those 70 years of age and older are affected.(5) Most individuals with hypertension do not have it adequately controlled.(1,6) Medication noncompliance due to avoidance of side effects is suggested to be a primary factor.(6) The epidemic incidence of hypertension and its significant cost to society indicate that a well-tolerated, cost-effective approach to treatment is urgently needed.

  18. Treatment of pathological gambling - integrative systemic model.

    PubMed

    Mladenović, Ivica; Lažetić, Goran; Lečić-Toševski, Dušica; Dimitrijević, Ivan

    2015-03-01

    Pathological gambling was classified under impulse control disorders within the International Classification of Diseases (ICD-10) (WHO 1992), but the most recent Diagnostic and Statistical Manual, 5th edition (DSM-V), (APA 2013), has recognized pathological gambling as a first disorder within a new diagnostic category of behavioral addictions - Gambling disorder. Pathological gambling is a disorder in progression, and we hope that our experience in the treatment of pathological gambling in the Daily Hospital for Addictions at The Institute of Mental Health, through the original "Integrative - systemic model" would be of use to colleagues, dealing with this pathology. This model of treatment of pathological gambling is based on multi-systemic approach and it primarily represents an integration of family and cognitive-behavioral therapy, with traces of psychodynamic, existential and pharmacotherapy. The model is based on the book "Pathological gambling - with self-help manual" by Dr Mladenovic and Dr Lazetic, and has been designed in the form of a program that lasts 10 weeks in the intensive phase, and then continues for two years in the form of "extended treatment" ("After care"). The intensive phase is divided into three segments: educational, insight with initial changes and analysis of the achieved changes with the definition of plans and areas that need to be addressed in the extended treatment. "Extended treatment" lasts for two years in the form of group therapy, during which there is a second order change of the identified patient, but also of other family members. Pathological gambling has been treated in the form of systemic-family therapy for more than 10 years at the Institute of Mental Health (IMH), in Belgrade. For second year in a row the treatment is carried out by the modern "Integrative-systemic model". If abstinence from gambling witihin the period of one year after completion of the intensive phase of treatment is taken as the main criterion of

  19. Management of a child with pulmonary arterial hypertension presenting with systemic hypertension.

    PubMed

    Flores, Saul; Daily, Joshua; Pratap, Jayant Nick; Cash, Michelle C; Hirsch, Russel

    2016-02-01

    We describe the course and management of a 12-year-old girl with severe pulmonary arterial hypertension who initially presented with severe systemic hypertension. Successful therapy included pulmonary vasodilators and an atrial septostomy, while ensuring adequate maintenance of her systemic vascular resistance to maintain cardiac output. Clear understanding of the physiology and judicious medical management in patients with severe pulmonary arterial hypertension using extreme compensatory mechanisms is vitally important.

  20. Are the innate and adaptive immune systems setting hypertension on fire?

    PubMed

    Bomfim, Gisele F; Rodrigues, Fernanda Luciano; Carneiro, Fernando S

    2017-03-01

    Hypertension is the most common chronic cardiovascular disease and is associated with several pathological states, being an important cause of morbidity and mortality around the world. Low-grade inflammation plays a key role in hypertension and the innate and adaptive immune systems seem to contribute to hypertension development and maintenance. Hypertension is associated with vascular inflammation, increased vascular cytokines levels and infiltration of immune cells in the vasculature, kidneys and heart. However, the mechanisms that trigger inflammation and immune system activation in hypertension are completely unknown. Cells from the innate immune system express pattern recognition receptors (PRR), which detect conserved pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) that induce innate effector mechanisms to produce endogenous signals, such as inflammatory cytokines and chemokines, to alert the host about danger. Additionally, antigen-presenting cells (APC) act as sentinels that are activated by PAMPs and DAMPs to sense the presence of the antigen/neoantigen, which ensues the adaptive immune system activation. In this context, different lymphocyte types are activated and contribute to inflammation and end-organ damage in hypertension. This review will focus on experimental and clinical evidence demonstrating the contribution of the innate and adaptive immune systems to the development of hypertension.

  1. Effects of renin inhibition in systemic hypertension.

    PubMed

    Anderson, P W; Do, Y S; Schambelan, M; Horton, R; Boger, R S; Luther, R R; Hsueh, W A

    1990-12-01

    The effect of the direct renin inhibitor enalkiren (Abbott Laboratories) was examined in 8 healthy patients with essential hypertension. With an unrestricted sodium diet, plasma renin concentration was inhibited within 10 minutes by intravenous enalkiren and remained essentially undetectable for greater than or equal to 6 hours (11.9 +/- 4 to 1.0 +/- 0.6 ng angiotensin I/ml/hour, p less than 0.05). Mean arterial blood pressure declined gradually (108 +/- 5 to 84 +/- 4 mm Hg, p = 0.02), as did plasma aldosterone concentration (14.4 +/- 3.8 to 4.4 +/- 0.8 ng/dl, p = 0.03), whereas plasma immunoreactive active renin concentration increased progressively (35 +/- 14 to 160 +/- 60 pg/ml, p greater than 0.05). Urinary excretion of the stable metabolite of prostacyclin (6-keto-prostaglandin F1 alpha) decreased slightly, but not significantly (42 +/- 10 to 33 +/- 11 ng/g creatinine, p = 0.13). The addition of a diuretic decreased baseline blood pressure and increased baseline plasma renin and aldosterone values. Blood pressure responses to enalkiren were slightly (though not significantly) greater than those observed before diuretic administration. We conclude that enalkiren is effective in decreasing blood pressure and in inhibiting the renin system, without significantly altering urinary prostacyclin excretion, in patients with essential hypertension. These results suggest that the renin system contributes to the maintenance of elevated blood pressure in some patients with essential hypertension.

  2. CENTRAL NERVOUS MECHANISMS IN CIRCULATION REGULATION AND FUNCTIONAL DERANGEMENT (HYPERTENSION).

    DTIC Science & Technology

    BLOOD CIRCULATION, *CENTRAL NERVOUS SYSTEM, * HYPERTENSION , AUTONOMIC NERVOUS SYSTEM, ELECTROENCEPHALOGRAPHY, ELECTROPHYSIOLOGY, CHEMORECEPTORS...PERCEPTION, CARDIOVASCULAR SYSTEM, PATHOLOGY, REFLEXES, BEHAVIOR, BLOOD PRESSURE , ANOXIA, BRAIN, ITALY.

  3. [Systemic arterial hypertension in child and adolescent].

    PubMed

    Rosas-Peralta, Martín; Medina-Concebida, Luz Elena; Borrayo-Sánchez, Gabriela; Madrid-Miller, Alejandra; Ramírez-Arias, Erick; Pérez-Rodríguez, Gilberto

    2016-01-01

    The epidemic of childhood obesity, the risk of developing left ventricular hypertrophy, and evidence of the early development of atherosclerosis in children would make the detection of and intervention in childhood hypertension important to reduce long-term health risks; however, supporting data are lacking. Secondary hypertension is more common in preadolescent children, with most cases caused by renal disease. Primary or essential hypertension is more common in adolescents and has multiple risk factors, including obesity and a family history of hypertension. Evaluation involves a through history and physical examination, laboratory tests, and specialized studies. Management is multifaceted. Nonpharmacologic treatments include weight reduction, exercise, and dietary modifications. Although the evidence of first line therapy for hypertension is still controversial, the recommendations for pharmacologic treatment are based on symptomatic hypertension, evidence of end-organ damage, stage 2 of hypertension, or stage 1 of hypertension unresponsive to lifestyle modifications, and hypertension with diabetes mellitus where is the search for microalbuminuria justified.

  4. [Flexor tendon pulley system: anatomy, pathology, treatment].

    PubMed

    Moutet, F

    2003-02-01

    Flexor tendon pulley has been very early noticed and described. Terminology usually accepted recognizes 6 arcifom pulleys (A0 to A5) and 3 cruciform pulleys (C1 to C3). Anatomy and physiology of this flexor tendon gliding and reflection system at the level of the digital sheet are exposed. The integrity necessity of this system became obvious regarding the flexor tendons repair. Four main pathologies may be concerned: the trigger finger congenital or progressive, due to a chondroid metaplasia of the A1 pulley; tenosynovial ganglions arising at the weak point between A1 and A2 pulley; lesions of the flexor tendon sheet during traumatic lacerations or surgical repairs; quite experimental lesions creating isolated ruptures of one or several pulleys which occur during sport practice, especially high level rock climbing. The repair techniques are exposed to allow to graduate and hierarchy the reparation technique regarding the pathology. A2 and A4 repair is always indicated. The best reconstruction material is an extensor retinaculum graft. But its poor surface available often draws to use conventional palmaris longus free graft.

  5. Autonomic nervous system dysregulation in pediatric hypertension.

    PubMed

    Feber, Janusz; Ruzicka, Marcel; Geier, Pavel; Litwin, Mieczyslaw

    2014-05-01

    Historically, primary hypertension (HTN) has been prevalent typically in adults. Recent data however, suggests an increasing number of children diagnosed with primary HTN, mainly in the setting of obesity. One of the factors considered in the etiology of HTN is the autonomous nervous system, namely its dysregulation. In the past, the sympathetic nervous system (SNS) was regarded as a system engaged mostly in buffering major acute changes in blood pressure (BP), in response to physical and emotional stressors. Recent evidence suggests that the SNS plays a much broader role in the regulation of BP, including the development and maintenance of sustained HTN by a chronically elevated central sympathetic tone in adults and children with central/visceral obesity. Consequently, attempts have been made to reduce the SNS hyperactivity, in order to intervene early in the course of the disease and prevent HTN-related complications later in life.

  6. Endurance training in the spontaneously hypertensive rat: conversion of pathological into physiological cardiac hypertrophy.

    PubMed

    Garciarena, Carolina D; Pinilla, Oscar A; Nolly, Mariela B; Laguens, Ruben P; Escudero, Eduardo M; Cingolani, Horacio E; Ennis, Irene L

    2009-04-01

    The effect of endurance training (swimming 90 min/d for 5 days a week for 60 days) on cardiac hypertrophy was investigated in the spontaneously hypertensive rat (SHR). Sedentary SHRs (SHR-Cs) and normotensive Wistar rats were used as controls. Exercise training enhanced myocardial hypertrophy assessed by left ventricular weight/tibial length (228+/-7 versus 251+/-5 mg/cm in SHR-Cs and exercised SHRs [SHR-Es], respectively). Myocyte cross-sectional area increased approximately 40%, collagen volume fraction decreased approximately 50%, and capillary density increased approximately 45% in SHR-Es compared with SHR-Cs. The mRNA abundance of atrial natriuretic factor and myosin light chain 2 was decreased by the swimming routine (100+/-19% versus 41+/-10% and 100+/-8% versus 61+/-9% for atrial natriuretic factor and myosin light chain 2 in SHR-Cs and SHR-Es, respectively). The expression of sarcoplasmic reticulum Ca(2+) pump was significantly augmented, whereas that of Na(+)/Ca(2+) exchanger was unchanged (93+/-7% versus 167+/-8% and 158+/-13% versus 157+/-7%, sarcoplasmic reticulum Ca(2+) pump and Na(+)/Ca(2+) exchanger in SHR-Cs and SHR-Es, respectively; P<0.05). Endurance training inhibited apoptosis, as reflected by a decrease in caspase 3 activation and poly(ADP-ribose) polymerase-1 cleavage, and normalized calcineurin activity without inducing significant changes in the phosphatidylinositol 3-kinase/Akt pathway. The swimming routine improved midventricular shortening determined by echocardiography (32.4+/-0.9% versus 36.9+/-1.1% in SHR-Cs and SHR-Es, respectively; P<0.05) and decreased the left ventricular free wall thickness/left ventricular cavity radius toward an eccentric model of cardiac hypertrophy (0.59+/-0.02 versus 0.53+/-0.01 in SHR-Cs and SHR-Es, respectively; P<0.05). In conclusion, we present data demonstrating the effectiveness of endurance training to convert pathological into physiological hypertrophy improving cardiac performance. The reduction of

  7. [CHANGES OF CAROTID AND VERTEBRAL ARTERIES IN PATENTS WITH ARTERIAL HYPERTENSION AND HEPATOBILIARY PATHOLOGY].

    PubMed

    Polyakov, V Ya; Nikolaev, Yu A; Pegova, S V; Matsievskaya, T R; Obukhov, I V

    2016-01-01

    The study included 1172 patients (410 men and 762 women) at the mean age of 60.3 ± 10.4 years with grade I-II (stage I-II) arterial hypertension (AH) admitted to the clinic of Institute of Experimental Medicine. The patients were divided into 2 groups based on the results of clinical and laboratory diagnostics. Group 1 (n = 525) included patients with AH and hepatobiliary system (HBS) diseases, group 2 (n = 647) patients with AH without HBS diseases. The patients group 1 had a thicker intima-media complex of carotid arteries, higher peak systolic bloodflow rate in the internal and vertebral carotid arteries, more pronounced coiling of internal carotid arteries than patients of group 2. Patients with AH and HBS diseases exhibited correlation between bloodflow rate in external carotid arteries and atherogenicity coefficient. Duplex scanning of neck vessels of in patients with AH without HBS diseases revealed peculiar changes of the intima-media thickness and hemodynamically significant changes of the blood flow in the internal carotid arteries that may be of prognostic value in this nosological syntropy and require the personified approach to diagnostics, treatment, and prevention of these conditions.

  8. Systemic antioxidant properties of L-carnitine in two different models of arterial hypertension.

    PubMed

    Mate, Alfonso; Miguel-Carrasco, José L; Monserrat, María T; Vázquez, Carmen M

    2010-06-01

    In spite of a wide range of drugs being available in the market, treatment of arterial hypertension still remains a challenge, and new therapeutic strategies could be developed in order to improve the rate of success in controlling this disease. Since oxidative stress has gained importance in the last few years as one of the mechanisms involved in the origin and development of hypertension, and considering that L-carnitine (LC) is a useful compound in different pathologies characterized by increased oxidative status, the aim of the present study was to investigate the systemic antioxidant effect of LC and its correlation to blood pressure in two experimental models of hypertension: (1) spontaneously hypertensive rats (SHR) and (2) rats with hypertension induced by N(omega)-nitro-L-arginine methyl ester (L-NAME). Treatment with captopril was also performed in SHR in order to compare the antioxidant and antihypertensive effects of LC and captopril. The antioxidant defense capacity, in terms of antioxidant enzyme activity, glutathione system availability and plasma total antioxidant capacity, was measured in both animal models with or without an oral, chronic treatment with LC. All the antioxidant parameters studied were diminished in SHR and in L-NAME-treated animals, an alteration that was in general reversed after treatments with LC and captopril. In addition, LC produced a significant but not complete reduction of systolic and diastolic blood pressure levels in these two models of hypertension, whereas captopril was able to normalize blood pressure. Both LC and captopril prevented the reduction in nitric oxide (NO) levels observed in hypertensive animals. This suggests a decrease in the systemic oxidative stress and a higher availability of NO induced by LC in a similar way to captopril's effects, which could be relevant in the management of arterial hypertension eventually.

  9. [Hypertension].

    PubMed

    Ohishi, Mitsuru

    2014-04-01

    Hypertension is well known to one of the risk factors to reduce cognitive function, however, it is still unclear whether anti-hypertensive therapy is effective to prevent development of dementia or Alzheimer's disease. Epidemiological studies suggested antihypertensive therapy from the middle-age could reduce risk of dementia. The meta-analysis including HYVET also suggested blood pressure lowering from the elderly might be also effective to prevent development of dementia. The network meta-analysis and the cohort study using mega-data bank suggested ARB might be effective to prevent development of dementia or Alzheimer's disease compared to administration with other anti-hypertensive drugs. Although the further major clinical investigation is required, anti-hypertensive treatment might be useful to manage hypertensive patients with dementia.

  10. The sympathetic nervous system alterations in human hypertension.

    PubMed

    Grassi, Guido; Mark, Allyn; Esler, Murray

    2015-03-13

    Several articles have dealt with the importance and mechanisms of the sympathetic nervous system alterations in experimental animal models of hypertension. This review addresses the role of the sympathetic nervous system in the pathophysiology and therapy of human hypertension. We first discuss the strengths and limitations of various techniques for assessing the sympathetic nervous system in humans, with a focus on heart rate, plasma norepinephrine, microneurographic recording of sympathetic nerve traffic, and measurements of radiolabeled norepinephrine spillover. We then examine the evidence supporting the importance of neuroadrenergic factors as promoters and amplifiers of human hypertension. We expand on the role of the sympathetic nervous system in 2 increasingly common forms of secondary hypertension, namely hypertension associated with obesity and with renal disease. With this background, we examine interventions of sympathetic deactivation as a mode of antihypertensive treatment. Particular emphasis is given to the background and results of recent therapeutic approaches based on carotid baroreceptor stimulation and radiofrequency ablation of the renal nerves.

  11. Clinical and pathological characterisation of primary pulmonary hypertension in a dog.

    PubMed

    Glaus, T M; Soldati, G; Maurer, R; Ehrensperger, F

    2004-06-19

    Primary pulmonary hypertension was diagnosed in an eight-year-old labrador retriever on the basis of echocardiographic findings of severe right ventricular eccentric hypertrophy, abnormally high systolic and diastolic pulmonary arterial pressures calculated by applying the modified Bernoulli equation to the tricuspid and pulmonary insufficiency peak velocities, and the absence of any underlying disease known to cause secondary pulmonary hypertension. The clinical abnormalities developed gradually, from exercise intolerance starting early in life to terminal right-sided congestive heart failure. Consistent histopathological findings were severe intimal and medial thickening of small arteries and arterioles that led to vascular obliteration.

  12. [Arterial hypertension in females engaged into penal system work].

    PubMed

    Tagirova, M M; El'garov, A A; Shogenova, A B; Murtazov, A M

    2010-01-01

    The authors proved significant prevalence of arterial hypertension and atherosclerosis risk factors in women engaged into penal system work--so these values form cardiovascular risk caused by environmental parameters. Teveten and Nebilet were proved effective in the examinees with arterial hypertension.

  13. Theory of functional systems and human general pathology.

    PubMed

    Khitrov, N K; Saltykov, A B

    2003-07-01

    We analyze the role of the theory of functional systems for human general pathology and the necessity of integration of this theory with the concepts of pathological and ambivalent systems. Multiple (qualitatively heterogeneous) nature of system-forming factors and principle possibility of the formation of physiological, pathological, and ambivalent systems by the same factors are discussed. These theses broaden the application of the theory of functional systems as the fundamental basis for studies of informational mechanisms of vital activity under normal and pathological conditions.

  14. Apelin/APJ system: a promising therapy target for hypertension.

    PubMed

    Wu, Di; He, Lu; Chen, Linxi

    2014-10-01

    Apelin is a recently described endogenous peptide and its receptor APJ, is a member of the G protein-coupled receptors family. Apelin and APJ are widely distributed in central and peripheral tissues exert important biological effects on cardiovascular system. Recent studies have suggested that apelin/APJ system involves in decreasing the blood pressure and have a close relationship with hypertension, presumably, pathophysiology of hypertension as well. Such as, apelin/APJ system may be concerned in hyperfunction of the sympathetic nervous system, renin-angiotensin-aldosterone system, endothelial injury, excessive endothelin, sodium retention, vascular remodeling, insulin resistance elicit hypertension, as well as in hypertension-induced organ damaged. Meanwhile, on the ground of the variation of apelin level in hypertension therapeutic process and combining with the recently researches on APJ agonist and antagonist, we could infer that apelin/APJ system would be a promising therapeutic target for hypertension and other cardiovascular disease in the future. However, the role of apelin on these pathogenic conditions was not consistent, consequently, the contradictory role of apelin on these pathogenesis of hypertension would be discussed in this article.

  15. Neuropsychological profile of patients with primary systemic hypertension.

    PubMed

    Ostrosky-Solis, F; Mendoza, V U; Ardila, A

    2001-01-01

    Arterial hypertension represents a risk factor for cerebrovascular disease. It has been hypothesized that chronic hypertension may eventually result in small subcortical infarcts associated with some cognitive impairments. One hundred fourteen patients with primary systemic hypertension (PSH) and 114 matched subjects were selected. PSH patients were further divided in four groups depending upon the hypertension severity. In addition to the medical and laboratory exams, a neuropsychological evaluation was administered. The NEUROPSI neuropsychological test battery was used. An association between level of hypertension and cognitive impairment was observed. Most significant differences were observed in the following domains: Reading, executive functioning, constructional, and memory-recall. No differences were observed in orientation, memory-recognition, and language. Some neuropsychological functions appeared impaired even in the PSH group with the least risk factors. Cognitive evaluation may be important in cases of PSH not only to determine early subtle cognitive changes, but also for follow-up purposes, and to assess the efficacy of different therapeutic procedures.

  16. African Americans, hypertension and the renin angiotensin system

    PubMed Central

    Williams, Sandra F; Nicholas, Susanne B; Vaziri, Nosratola D; Norris, Keith C

    2014-01-01

    African Americans have exceptionally high rates of hypertension and hypertension related complications. It is commonly reported that the blood pressure lowering efficacy of renin angiotensin system (RAS) inhibitors is attenuated in African Americans due to a greater likelihood of having a low renin profile. Therefore these agents are often not recommended as initial therapy in African Americans with hypertension. However, the high prevalence of comorbid conditions, such as diabetes, cardiovascular and chronic kidney disease makes treatment with RAS inhibitors more compelling. Despite lower circulating renin levels and a less significant fall in blood pressure in response to RAS inhibitors in African Americans, numerous clinical trials support the efficacy of RAS inhibitors to improve clinical outcomes in this population, especially in those with hypertension and risk factors for cardiovascular and related diseases. Here, we discuss the rationale of RAS blockade as part of a comprehensive approach to attenuate the high rates of premature morbidity and mortality associated with hypertension among African Americans. PMID:25276290

  17. A Flexible, Open, Decentralized System for Digital Pathology Networks

    PubMed Central

    SMITH, David E.; KUMARAGURUPARAN, Gowri; CHERVENAK, Ann; LEWIS, Anne D.; HYDE, Dallas M.; KESSELMAN, Carl

    2014-01-01

    High-resolution digital imaging is enabling digital archiving and sharing of digitized microscopy slides and new methods for digital pathology. Collaborative research centers, outsourced medical services, and multi-site organizations stand to benefit from sharing pathology data in a digital pathology network. Yet significant technological challenges remain due to the large size and volume of digitized whole slide images. While information systems do exist for managing local pathology laboratories, they tend to be oriented toward narrow clinical use cases or offer closed ecosystems around proprietary formats. Few solutions exist for networking digital pathology operations. Here we present a system architecture and implementation of a digital pathology network and share results from a production system that federates major research centers. PMID:22941985

  18. Systemic Hypertension, Headache, and Ocular Hemodynamics: A New Hypothesis

    PubMed Central

    Gupta, Vinod Kumar

    2006-01-01

    The association between systemic hypertension and headache remains controversial and its pathophysiologic basis is uncertain. A rather characteristic early-morning pulsating headache is commonly seen in hypertensive patients, and a recent meta-analysis supports the link between these 2 entities. Epidemiologic evidence has paradoxically suggested a negative association between hypertension and headache. Unpredictable clinical association between severe hypertension and headache indicates that another cranial perfusion-related variable exerts a critical role. Neuroanatomically, head and neck pain primarily involves the ophthalmic division of the trigeminal nerve (V1). A link between systemic hypertension, pulsatile choroidal blood flow (CBF), and intraocular pressure (IOP) has been established. I propose that a trait ocular sympathetic hypofunction permits rapid episodic ocular choroidal overperfusion that stretches the ocular globe in the cohort of hypertensive patients with headache. Rapid distension of the pain-sensitive corneoscleral envelope can stimulate corneoscleral and iridial pain-sensitive V1 nerve endings and generate headache. Ocular tamponade function physiologically limits choroidal overperfusion. A higher basal IOP in some patients with moderate-to-severe hypertension may dampen pulsatile CBF and account for the negative epidemiologic link between sustained systemic hypertension and headache. Besides activation of the baroreceptor reflex, the association of hypalgesia with hypertension probably involves activation of the vasopressin-endorphin adaptive system consequent to mechanical stimulation of V1. The analogy between hypertensive headache and angle-closure glaucoma is rather limited because typical ocular and visual signs and symptoms of angle-closure glaucoma are not seen in hypertension-related headache. Hypertensive crises, including those associated with pheochromocytoma, are not accompanied by attacks of angle-closure glaucoma. Glaucoma is

  19. The brain melanocortin system, sympathetic control, and obesity hypertension.

    PubMed

    da Silva, Alexandre A; do Carmo, Jussara M; Wang, Zhen; Hall, John E

    2014-05-01

    Excess weight gain is the most significant, preventable cause of increased blood pressure (BP) in patients with primary (essential) hypertension and increases the risk for cardiovascular and renal diseases. In this review, we discuss the role of the brain melanocortin system in causing increased sympathetic activity in obesity and other forms of hypertension. In addition, we highlight potential mechanisms by which the brain melanocortin system modulates metabolic and cardiovascular functions.

  20. Aortic dilatation in children with systemic hypertension.

    PubMed

    Gupta-Malhotra, Monesha; Devereux, Richard B; Dave, Archana; Bell, Cynthia; Portman, Ronald; Milewicz, Diana

    2014-04-01

    The aim of the study was to determine the presence of aortic dilatation in hypertensive children, the prevalence of which is 4% to 10% in hypertensive adults. Prospectively enrolled multiethnic children, untreated for their hypertension, underwent an echocardiogram to exclude congenital heart disease and evaluate for end-organ damage and aortic size. The aorta was measured in the parasternal long-axis view at three levels: the sinus of Valsalva, supra-tubular junction, and the ascending aorta. Aortic dilatation was determined by z-score >2 at any one of the levels measured. Hypertension was defined as blood pressure above the 95th percentile based on the Fourth Working Group criteria confirmed by 24-hour ambulatory blood pressure monitoring. Among 142 consecutive hypertensive children (median age, 14 years; 45% females) aortic dilatation was detected in 2.8% (95% confidence interval, 1%-7%; median age, 16 years; 100% females). Children with aortic dilatation, when compared with those without, had significantly more aortic valve insufficiency (P = .005) and left ventricular hypertrophy (P = .018). Prevalence of aortic dilatation was 2.8% and was associated with significantly more aortic insufficiency and left ventricular hypertrophy in comparison to those without aortic dilatation.

  1. Aortic Dilatation in Children with Systemic Hypertension

    PubMed Central

    Gupta-Malhotra, Monesha; Devereux, Richard B.; Dave, Archana; Bell, Cynthia; Portman, Ronald; Milewicz, Diana

    2014-01-01

    Background The aim of the study was to determine presence of aortic dilatation in hypertensive children, the prevalence of which is 4–10% in hypertensive adults. Methods Prospectively enrolled multiethnic children untreated for their hypertension, underwent an echocardiogram to exclude congenital heart disease and evaluate for end-organ damage and aortic size. The aorta was measured in the parasternal long-axis view at 3 levels: the sinus of Valsalva, supra-tubular junction and the ascending aorta. Aortic dilatation was determined by z-score > 2 at any 1 of the levels measured. Hypertension was defined as blood pressure above the 95th percentile based on the Fourth Working Group criteria confirmed by 24-hour ambulatory blood pressure monitoring. Results Among 142 consecutive hypertensive children (median age 14 years, 45% females) aortic dilatation was detected in 2.8% (95% CI 1% to 7%, median age 16 years, 100% females). Children with aortic dilatation, when compared to those without, had significantly more aortic valve insufficiency (p = 0.005) and left ventricular hypertrophy (p = 0.018). Conclusions Prevalence of aortic dilatation was 2.8% and was associated with significantly more aortic insufficiency and left ventricular hypertrophy in comparison to those without aortic dilatation. PMID:24507486

  2. Thyroid and hypoxic moderation of systemic hypertension in the spontaneously hypertensive rat

    SciTech Connect

    Henley, W.N.; Tucker, A.; Tran, T.N.; Stager, J.M.

    1987-06-01

    The effect of altered thyroid metabolism on hypoxic moderation of hypertension was investigated, using three groups of spontaneously hypertensive rats: (1) surgically thyroidectomized (TX), (2) euthyroid (EU), and (3) TX with dietary hormone replacement (RPL). Each group was subdivided into hypoxic (H, 28 d at 3658 m simulated altitude) and normoxic (N, at 1525 m altitude). In all TX-H and TX-N rats, systolic blood pressure was attenuated. Thyroidectomy also decreased vessel responsiveness to KCl and isoproterenol, but hypoxia did not significantly change vessel responsiveness in either TX or EU rats. Vessels from RPL-N rats appeared to be euthyroid with respect to both isoproterenol and KCl responsiveness, while vessels from RPL-H showed a hyporesponsiveness characteristic of TX rats. It is argued that hypoxia and thyroidectomy mitigate systemic hypertension by different mechanisms. 24 references.

  3. The immune system: role in hypertension.

    PubMed

    Schiffrin, Ernesto L

    2013-05-01

    Over the past 20 years it has become recognized that low-grade inflammation plays a role in cardiovascular disease. More recently, participation of the innate and the adaptive immune response in mechanisms that contribute to inflammation in cardiovascular disease has been reported in atherosclerosis and hypertension. Different subsets of lymphocytes and their cytokines are involved in vascular remodelling and hypertensive renal disease as well as heart disease. Effector T cells including T-helper (Th) 1 (interferon-γ-producing) and Th2 lymphocytes (interleukin-4 producing), as well as Th17 (which produce interleukin-17), and T suppressor lymphocytes such as T regulatory cells, which express the transcription factor forkhead box P3, participate respectively as pro- and anti-inflammatory cells, and mediate effects of angiotensin II and mineralocorticoids. Involvement of immune mechanisms in cardiac, vascular, and renal changes in hypertension has been demonstrated in many experimental models, an example being the Dahl-salt sensitive rat and the spontaneously hypertensive rat. How activation of immunity is triggered remains unknown, but neoantigens could be generated by elevated blood pressure through damage-associated molecular pattern receptors or other mechanisms. When activated, Th1 may contribute to blood pressure elevation by affecting the kidney, vascular remodelling of blood vessels directly via effects of the cytokines produced, or through their effects on perivascular fat. T regulatory cells protect from blood pressure elevation acting on similar targets. These novel findings may open the way for new therapeutic approaches to improve outcomes in hypertension and cardiovascular disease in humans.

  4. THE SYMPATHETIC NERVOUS SYSTEM ALTERATIONS IN HUMAN HYPERTENSION

    PubMed Central

    Grassi, Guido; Mark, Allyn; Esler, Murray

    2015-01-01

    A number of articles have dealt with the importance and mechanisms of the sympathetic nervous system alterations in experimental animal models of hypertension. This review addresses the role of the sympathetic nervous system in the pathophysiology and therapy of human hypertension. We first discuss the strengths and limitations of various techniques for assessing the sympathetic nervous system in humans, with a focus on heart rate, plasma norepinephrine, microneurographic recording of sympathetic nerve traffic, and measurements of radiolabeled norepinephrine spillover. We then examine the evidence supporting the importance of neuroadrenergic factors as “promoters” and “amplifiers” of human hypertension. We expand on the role of the sympathetic nervous system in two increasingly common forms of secondary hypertension, namely hypertension associated with obesity and with renal disease. With this background, we examine interventions of sympathetic deactivation as a mode of antihypertensive treatment. Particular emphasis is given to the background and results of recent therapeutic approaches based on carotid baroreceptor stimulation and radiofrequency ablation of the renal nerves. PMID:25767284

  5. Think Small: Zebrafish as a Model System of Human Pathology

    PubMed Central

    Goldsmith, J. R.; Jobin, Christian

    2012-01-01

    Although human pathologies have mostly been modeled using higher mammal systems such as mice, the lower vertebrate zebrafish has gained tremendous attention as a model system. The advantages of zebrafish over classical vertebrate models are multifactorial and include high genetic and organ system homology to humans, high fecundity, external fertilization, ease of genetic manipulation, and transparency through early adulthood that enables powerful imaging modalities. This paper focuses on four areas of human pathology that were developed and/or advanced significantly in zebrafish in the last decade. These areas are (1) wound healing/restitution, (2) gastrointestinal diseases, (3) microbe-host interactions, and (4) genetic diseases and drug screens. Important biological processes and pathologies explored include wound-healing responses, pancreatic cancer, inflammatory bowel diseases, nonalcoholic fatty liver disease, and mycobacterium infection. The utility of zebrafish in screening for novel genes important in various pathologies such as polycystic kidney disease is also discussed. PMID:22701308

  6. Hypertension and hypertensive encephalopathy.

    PubMed

    Price, Raymond S; Kasner, Scott E

    2014-01-01

    The definition of hypertension has continuously evolved over the last 50 years. Hypertension is currently defined as a blood pressure greater than 140/90mmHg. One in every four people in the US has been diagnosed with hypertension. The prevalence of hypertension increases further with age, affecting 75% of people over the age of 70. Hypertension is by far the most common risk factor identified in stroke patients. Hypertension causes pathologic changes in the walls of small (diameter<300 microns) arteries and arterioles usually at short branches of major arteries, which may result in either ischemic stroke or intracerebral hemorrhage. Reduction of blood pressure with diuretics, β-blockers, calcium channel blockers, and angiotensin-converting enzyme (ACE) inhibitors have all been shown to markedly reduce the incidence of stroke. Hypertensive emergency is defined as a blood pressure greater than 180/120mmHg with end organ dysfunction, such as chest pain, shortness of breath, encephalopathy, or focal neurologic deficits. Hypertensive encephalopathy is believed to be caused by acute failure of cerebrovascular autoregulation. Hypertensive emergency is treated with intravenous antihypertensive agents to reduce blood pressure by 25% within the first hour. Selective inhibition of cerebrovascular blood vessel permeability for the treatment of hypertensive emergency is beginning early clinical trials.

  7. Therapy for Pulmonary Arterial Hypertension Associated with Systemic Sclerosis

    PubMed Central

    Mathai, Stephen C.; Hassoun, Paul M.

    2010-01-01

    Purpose of review Systemic sclerosis is commonly complicated by pulmonary arterial hypertension (PAH-SSc) and is a leading cause of death in this population. We will review existing challenges and recent advances in the treatment of this disease. Recent findings Traditionally employed outcome measures in pulmonary arterial hypertension research may not be applicable in PAH-SSc. Importantly, new therapies that target abnormal cellular proliferation in the pulmonary vasculature are currently under investigation and may be particularly relevant to PAH-SSc. Summary Pulmonary arterial hypertension complicating systemic sclerosis occurs commonly and portends a poor prognosis. However, recent advances in our understanding of the disease in the context of systemic sclerosis may lead to novel diagnostic and therapeutic strategies that will ultimately improve quality of life and survival in this population. PMID:19667994

  8. Pulmonary Arterial Hypertension-A Deadly Complication of Systemic Sclerosis

    PubMed Central

    Pankey, Edward A; Epps, Matthew; Nossaman, Bobby D; Hyman, Albert L; Kadowitz, Philip J

    2011-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease with limited therapeutic options. Moreover, when PAH occurs in patients diagnosed with systemic sclerosis, worse outcomes are observed. The purpose of this review is to discuss the etiologies of PAH found in the systemic sclerosis patient, limitations of current medical therapies, and, finally, potential therapies for patients with this combination. PMID:23626904

  9. Chronic Traumatic Encephalopathy Pathology in Multiple System Atrophy.

    PubMed

    Koga, Shunsuke; Dickson, Dennis W; Bieniek, Kevin F

    2016-10-01

    Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder associated with repetitive traumatic brain injury. Multiple system atrophy (MSA) is a Parkinsonian disorder that can result in repetitive falls with associated head trauma. We hypothesized that patients with neurodegenerative disorders like MSA could develop CTE pathology. Therefore, we assessed CTE pathology in 139 MSA cases in our brain bank. Sections from convexity cerebral cortices were screened by immunohistochemistry with anti-phospho-tau antibody. For cases with suggestive CTE pathology, further sections of basal forebrain and hippocampus were immunostained. Consensus criteria were used to make the diagnosis of CTE and aging-related tau astrogliopathy (ARTAG) was differentiated from CTE pathology. Pertinent clinical information was derived from the available records and online searches. Of the 139 MSA cases, 8 (6%) had CTE pathology and 10 (8%) had ARTAG pathology. All 8 cases with CTE were male and 4 of them had a documented history of contact sports. The median age at death in MSA with CTE was younger than in MSA without CTE or MSA with ARTAG (60, 67, and 74 years, respectively; p = 0.002). Even without a known history of contact sports or head trauma, a small subset of cases with MSA had CTE pathology.

  10. [Pulmonary arterial hypertension and BMP system abnormality].

    PubMed

    Otsuka, Fumio

    2008-11-01

    Genetic analysis has uncovered that familial and idiopathic pulmonary arterial hypertension (PAH) is linked to germline mutations in BMP type II receptor (BMPRII). PAH is characterized by enhanced remodeling of pulmonary arteries due to arterial smooth muscle cell proliferation. BMPRII mutations contribute to abnormal mitotic responses to BMP ligands in pulmonary artery smooth muscle cells. Unbalanced Smad signaling induced by BMP and TGFbeta is functionally involved in the pathogenesis of PAH. BMPRII mutations also increase the susceptibility of endothelial cell apoptosis. The combination of increased endothelial injury and impaired suppression of smooth muscle cell proliferation is critical for the cellular pathogenesis of PAH. However, the detailed molecular mechanism leading to severe vascular remodeling caused by BMPRII mutations has yet to be elucidated.

  11. Vascular lesions in systemic lupus erythematosus (SLE) with pulmonary hypertension.

    PubMed

    Wakaki, K; Koizumi, F; Fukase, M

    1984-05-01

    An autopsy case with SLE suffering from Raynaud's phenomenon and pulmonary hypertension was reported. Histological examinations revealed systemically marked fibrous intimal thickening of arteries and arterioles with or without thrombus throughout the whole body, especially of the pulmonary arteries and arterioles. Pulmonary arterial changes in the present case were compared with those in 52 autopsied cases with SLE without pulmonary hypertension, but there were no cases with such marked arterial changes as the present case. In addition, the incidence of pulmonary thrombosis was significantly higher in the cases with Raynaud's phenomenon than the cases without this phenomenon. However, the relation between pulmonary hypertension and Raynaud's phenomenon, pulmonary thrombosis, fibrous pericarditis, or type of lupus nephritis in SLE could not be clarified with a significant difference.

  12. A novel glass slide filing system for pathology slides.

    PubMed

    Tsai, Steve; Kartono, Francisca; Shitabata, Paul K

    2007-07-01

    The availability of a collection of microscope glass slides for review is essential in the study and practice of pathology. A common problem facing many pathologists is the lack of a well-organized filing system. We present a novel system that would be easily accessible, informative, protective, and portable.

  13. Expanding the spectrum of neuronal pathology in multiple system atrophy.

    PubMed

    Cykowski, Matthew D; Coon, Elizabeth A; Powell, Suzanne Z; Jenkins, Sarah M; Benarroch, Eduardo E; Low, Phillip A; Schmeichel, Ann M; Parisi, Joseph E

    2015-08-01

    Multiple system atrophy is a sporadic alpha-synucleinopathy that typically affects patients in their sixth decade of life and beyond. The defining clinical features of the disease include progressive autonomic failure, parkinsonism, and cerebellar ataxia leading to significant disability. Pathologically, multiple system atrophy is characterized by glial cytoplasmic inclusions containing filamentous alpha-synuclein. Neuronal inclusions also have been reported but remain less well defined. This study aimed to further define the spectrum of neuronal pathology in 35 patients with multiple system atrophy (20 male, 15 female; mean age at death 64.7 years; median disease duration 6.5 years, range 2.2 to 15.6 years). The morphologic type, topography, and frequencies of neuronal inclusions, including globular cytoplasmic (Lewy body-like) neuronal inclusions, were determined across a wide spectrum of brain regions. A correlation matrix of pathologic severity also was calculated between distinct anatomic regions of involvement (striatum, substantia nigra, olivary and pontine nuclei, hippocampus, forebrain and thalamus, anterior cingulate and neocortex, and white matter of cerebrum, cerebellum, and corpus callosum). The major finding was the identification of widespread neuronal inclusions in the majority of patients, not only in typical disease-associated regions (striatum, substantia nigra), but also within anterior cingulate cortex, amygdala, entorhinal cortex, basal forebrain and hypothalamus. Neuronal inclusion pathology appeared to follow a hierarchy of region-specific susceptibility, independent of the clinical phenotype, and the severity of pathology was duration-dependent. Neuronal inclusions also were identified in regions not previously implicated in the disease, such as within cerebellar roof nuclei. Lewy body-like inclusions in multiple system atrophy followed the stepwise anatomic progression of Lewy body-spectrum disease inclusion pathology in 25.7% of patients

  14. Hypertension

    MedlinePlus

    ... y Cuidadores Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ... Clinical Trials Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ...

  15. Angiotensin II, hypertension, and angiotensin II receptor antagonism: Roles in the behavioural and brain pathology of a mouse model of Alzheimer's disease.

    PubMed

    Wiesmann, Maximilian; Roelofs, Monica; van der Lugt, Robert; Heerschap, Arend; Kiliaan, Amanda J; Claassen, Jurgen Ahr

    2016-01-01

    Elevated angiotensin II causes hypertension and contributes to Alzheimer's disease by affecting cerebral blood flow. Angiotensin II receptor blockers may provide candidates to reduce (vascular) risk factors for Alzheimer's disease. We studied effects of two months of angiotensin II-induced hypertension on systolic blood pressure, and treatment with the angiotensin II receptor blockers, eprosartan mesylate, after one month of induced hypertension in wild-type C57bl/6j and AβPPswe/PS1ΔE9 (AβPP/PS1/Alzheimer's disease) mice. AβPP/PS1 showed higher systolic blood pressure than wild-type. Subsequent eprosartan mesylate treatment restored this elevated systolic blood pressure in all mice. Functional connectivity was decreased in angiotensin II-infused Alzheimer's disease and wild-type mice, and only 12 months of Alzheimer's disease mice showed impaired cerebral blood flow. Only angiotensin II-infused Alzheimer's disease mice exhibited decreased spatial learning in the Morris water maze. Altogether, angiotensin II-induced hypertension not only exacerbated Alzheimer's disease-like pathological changes such as impairment of cerebral blood flow, functional connectivity, and cognition only in Alzheimer's disease model mice, but it also induced decreased functional connectivity in wild-type mice. However, we could not detect hypertension-induced overexpression of Aβ nor increased neuroinflammation. Our findings suggest a link between midlife hypertension, decreased cerebral hemodynamics and connectivity in an Alzheimer's disease mouse model. Eprosartan mesylate treatment restored and beneficially affected cerebral blood flow and connectivity. This model could be used to investigate prevention/treatment strategies in early Alzheimer's disease.

  16. The therapeutic implications of diastolic time changes in systemic hypertension.

    PubMed

    Jawad, I A; Kinhal, V; Talmers, F; Weissler, A M; Boudoulas, H

    1985-06-01

    Twenty-five patients with chronic systemic hypertension were studied. Systolic time intervals and diastolic time were determined at baseline and after 12 weeks of therapy with nadolol, with or without bendroflumethiazide (treatment phase I), then after 12 weeks of therapy with hydralazine, bendroflumethiazide, or both (treatment phase II). Systolic, diastolic, and mean blood pressures were equally controlled after either treatment regimen. Heart rate was significantly slower after treatment phase I compared to baseline or after treatment phase II (p less than 0.001). Systolic time per minute was significantly shorter and diastolic time per beat and per minute were significantly longer after treatment phase I compared to baseline or after treatment phase II (p less than 0.001). Double and triple products decreased after either mode of therapy; however, these parameters were significantly lower after treatment phase I compared to treatment phase II (p less than 0.01). These changes in systolic and diastolic time and double and triple products may be of clinical significance during therapy of chronic systemic hypertension and may help explain the regression of left ventricular hypertrophy in patients with hypertension treated with sympathetic blocking agents.

  17. [Consensus on Systemic Arterial Hypertension In México].

    PubMed

    Rosas-Peralta, Martín; Palomo-Piñón, Silvia; Borrayo-Sánchez, Gabriela; Madrid-Miller, Alejandra; Almeida-Gutiérrez, Eduardo; Galván-Oseguera, Héctor; Magaña-Serrano, José Antonio; Saturno-Chiu, Guillermo; Ramírez-Arias, Erick; Santos-Martínez, Efrén; Díaz-Díaz, Enrique; Salgado-Pastor, Selene Janette; Morales-Mora, Gerardo; Medina-Concebida, Luz Elena; Mejía-Rodríguez, Oliva; Pérez-Ruiz, Claudia Elsa; Chapa-Mejía, Luis Raúl; Álvarez-Aguilar, Cleto; Pérez-Rodríguez, Gilberto; Castro-Martínez, María Guadalupe; López-Bárcena, Joaquín; Paniagua-Sierra, José Ramón

    2016-01-01

    This Consenso Nacional de Hipertensión Arterial Sistémica (National Consensus on Systemic Arterial Hypertension) brings together experiences and joint work of 79 specialists who have been in contact with the patient affected by systemic arterial hypertension. All concepts here presented were outlined on the basis of the real world practice of Mexican hypertensive population. The consensus was developed under strict methodological guidelines. The Delphi technique was applied in two rounds for the development of an appropriate statistical analysis of the concepts exposed by all the specialists, who posed key questions, later developed by the panel of experts of the Hospital de Cardiología, and specialists from the Centro Médico Nacional. Several angles of this illness are shown: detection, diagnosis, pathophysiology, classification, treatment and prevention. The evidence analysis was carried out using PRISMA method. More than 600 articles were reviewed, leaving only the most representative in the references. This document concludes with practical and useful recommendations for the three levels of health care of our country.

  18. Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system.

    PubMed

    Mehta, Puja K; Griendling, Kathy K

    2007-01-01

    The renin-angiotensin system is a central component of the physiological and pathological responses of cardiovascular system. Its primary effector hormone, angiotensin II (ANG II), not only mediates immediate physiological effects of vasoconstriction and blood pressure regulation, but is also implicated in inflammation, endothelial dysfunction, atherosclerosis, hypertension, and congestive heart failure. The myriad effects of ANG II depend on time (acute vs. chronic) and on the cells/tissues upon which it acts. In addition to inducing G protein- and non-G protein-related signaling pathways, ANG II, via AT(1) receptors, carries out its functions via MAP kinases (ERK 1/2, JNK, p38MAPK), receptor tyrosine kinases [PDGF, EGFR, insulin receptor], and nonreceptor tyrosine kinases [Src, JAK/STAT, focal adhesion kinase (FAK)]. AT(1)R-mediated NAD(P)H oxidase activation leads to generation of reactive oxygen species, widely implicated in vascular inflammation and fibrosis. ANG II also promotes the association of scaffolding proteins, such as paxillin, talin, and p130Cas, leading to focal adhesion and extracellular matrix formation. These signaling cascades lead to contraction, smooth muscle cell growth, hypertrophy, and cell migration, events that contribute to normal vascular function, and to disease progression. This review focuses on the structure and function of AT(1) receptors and the major signaling mechanisms by which angiotensin influences cardiovascular physiology and pathology.

  19. Developmental and pathological angiogenesis in the central nervous system

    PubMed Central

    Vallon, Mario; Chang, Junlei; Zhang, Haijing

    2014-01-01

    Angiogenesis, the formation of new blood vessels from pre-existing vessels, in the central nervous system (CNS) is seen both as a normal physiological response as well as a pathological step in disease progression. Formation of the blood–brain barrier (BBB) is an essential step in physiological CNS angiogenesis. The BBB is regulated by a neurovascular unit (NVU) consisting of endothelial and perivascular cells as well as vascular astrocytes. The NVU plays a critical role in preventing entry of neurotoxic substances and regulation of blood flow in the CNS. In recent years, research on numerous acquired and hereditary disorders of the CNS has increasingly emphasized the role of angiogenesis in disease pathophysiology. Here, we discuss molecular mechanisms of CNS angiogenesis during embryogenesis as well as various pathological states including brain tumor formation, ischemic stroke, arteriovenous malformations, and neurodegenerative diseases. PMID:24760128

  20. Systemic and renal oxidative stress in the pathogenesis of hypertension: modulation of long-term control of arterial blood pressure by resveratrol

    PubMed Central

    Hamza, Shereen M.; Dyck, Jason R. B.

    2014-01-01

    Hypertension affects over 25% of the global population and is associated with grave and often fatal complications that affect many organ systems. Although great advancements have been made in the clinical assessment and treatment of hypertension, the cause of hypertension in over 90% of these patients is unknown, which hampers the development of targeted and more effective treatment. The etiology of hypertension involves multiple pathological processes and organ systems, however one unifying feature of all of these contributing factors is oxidative stress. Once the body's natural anti-oxidant defense mechanisms are overwhelmed, reactive oxygen species (ROS) begin to accumulate in the tissues. ROS play important roles in normal regulation of many physiological processes, however in excess they are detrimental and cause widespread cell and tissue damage as well as derangements in many physiological processes. Thus, control of oxidative stress has become an attractive target for pharmacotherapy to prevent and manage hypertension. Resveratrol (trans-3,5,4′-Trihydroxystilbene) is a naturally occurring polyphenol which has anti-oxidant effects in vivo. Many studies have shown anti-hypertensive effects of resveratrol in different pre-clinical models of hypertension, via a multitude of mechanisms that include its function as an anti-oxidant. However, results have been mixed and in some cases resveratrol has no effect on blood pressure. This may be due to the heavy emphasis on peripheral vasodilator effects of resveratrol and virtually no investigation of its potential renal effects. This is particularly troubling in the arena of hypertension, where it is well known and accepted that the kidney plays an essential role in the long term regulation of arterial pressure and a vital role in the initiation, development and maintenance of chronic hypertension. It is thus the focus of this review to discuss the potential of resveratrol as an anti-hypertensive treatment via

  1. Pulmonary hypertension in systemic lupus erythematosus: report of four cases and review of the literature

    SciTech Connect

    Perez, H.D.; Kramer, N.

    1981-08-01

    Pulmonary hypertension has been reported rarely in patients with systemic lupus erythematosus (SLE). During the past 31/2 yr we have observed pulmonary hypertension as a major clinical manifestation of their disease in four of 43 patients with well-documented SLE followed at out institution. Pulmonary hypertension could be attributed to underlying lung disease in three and was considered to be primary in the remaining patient. Neither hydralazine nor prednisone administration had any effect on the course of the pulmonary hypertension in these patients. The presence of pulmonary hypertension in the course of active SLE may be more common than previously recognized.

  2. Automated spoken dialogue system for hypertensive patient home management.

    PubMed

    Giorgino, Toni; Azzini, Ivano; Rognoni, Carla; Quaglini, Silvana; Stefanelli, Mario; Gretter, Roberto; Falavigna, Daniele

    2005-03-01

    Recent advances in automatic speech recognition and related technologies allow computers to carry on conversations by telephone. We developed an intelligent dialogue system that interacts with hypertensive patients to collect data about their health status. Patients thus avoid the inconvenience of traveling for frequent face to face visits to monitor the clinical variables they can easily measure at home; the physician is facilitated in acquiring patient information and cardiovascular risk, which is evaluated from the data according to noted guidelines. Controlled trials to assess the clinical efficacy are under way.

  3. Effect of Valsartan on Cerebellar Adrenomedullin System Dysregulation During Hypertension.

    PubMed

    Figueira, Leticia; Israel, Anita

    2017-02-01

    Adrenomedullin (AM) and its receptors components, calcitonin-receptor-like receptor (CRLR), and receptor activity-modifying protein (RAMP1, RAMP2, and RAMP3) are expressed in cerebellum. Cerebellar AM, AM binding sites and receptor components are altered during hypertension, suggesting a role for cerebellar AM in blood pressure regulation. Thus, we assessed the effect of valsartan, on AM and its receptor components expression in the cerebellar vermis of Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Additionally, we evaluated AM action on superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activity, and thiobarbituric acid reactive substances (TBARS) production in cerebellar vermis. Animals were treated with valsartan or vehicle for 11 days. Rats were sacrificed by decapitation; cerebellar vermis was dissected; and AM, CRLR, RAMP1, RAMP2, and RAMP3 expression was quantified by Western blot analysis. CAT, SOD, and GPx activity was determined spectrophotometrically and blood pressure by non-invasive plethysmography. We demonstrate that AM and RAMP2 expression was lower in cerebellum of SHR rats, while CRLR, RAMP1, and RAMP3 expression was higher than those of WKY rats. AM reduced cerebellar CAT, SOD, GPx activities, and TBARS production in WKY rats, but not in SHR rats. Valsartan reduced blood pressure and reversed the altered expression of AM and its receptors components, as well the loss of AM capacity to reduce antioxidant enzyme activity and TBARS production in SHR rats. These findings demonstrate that valsartan is able to reverse the dysregulation of cerebellar adrenomedullinergic system; and they suggest that altered AM system in the cerebellum could represent the primary abnormality leading to hypertension.

  4. [Radionuclide evaluation of the cardiovascular system in arterial hypertension].

    PubMed

    Oganesian, N M; Babaian, A S; Mikaelian, R S; Mnatsakanian, E L

    1986-08-01

    Proceeding from a study of the nature of changes in hemodynamics during development of hypertensive disease (HD) at its different stages it was shown that hemodynamic changes in 42.1% of the patients with Stage I-IIA HD were of hypertensive type, in the patients with Stage IIB-III HD normal and hypokinetic types of the blood circulation prevailed. After bicycle ergometry exercise the reactivity of the cardiovascular system was revealed more completely. The transition of one hemodynamic type into another and its detection acquired a great importance. The definition of the types of hemodynamics at rest and of effort was very important in terms of adequate antihypertensive therapy and the prediction of a subsequent course of disease. The most complete information on function of the cardiovascular system and myocardial contractility can be obtained with the help of radio-angiocardiography and radionuclide ventriculography. However in the absence of a gamma-chamber radiocardiography can provide necessary information on function of the cardiovascular system in case it is used in one and the same patient over time using bicycle ergometry testing.

  5. Metabolic syndrome, hypertension, and nervous system injury: Epidemiological correlates.

    PubMed

    Ricci, Giovanna; Pirillo, Isabel; Tomassoni, Daniele; Sirignano, Ascanio; Grappasonni, Iolanda

    2017-01-01

    Metabolic syndrome (MetS) is a common and complex disorder combining hypertension, obesity, dyslipidemia, and insulin resistance. MetS represents a risk factor for changes in cognitive functions in older age, and several studies have suggested that MetS may be linked to dementia. This article reviews the main evidences about the relationship between MetS and neurodegenerative disease. Starting from an epidemiological point of view, the article analyzes medico-social aspects related to MetS, considering the reduction of work capacity and the condition of disability that it involves. Some authors affirm that on the basis of current Italian legislation, it is possible to consider the syndrome as a disability. This is because all the diseases that make up MetS are high-risk clinical pathological conditions. For these reasons, a joint action is required to contain the incidence of MetS, the high social costs, and the loss of productivity related to the syndrome. In conclusion, healthcare initiatives could be adopted in order to increase the understanding of the pathogenic contributions of each element on MetS and how they can be modified. These actions will be useful to reduce healthcare costs and can lead to more effective prevention of metabolic disease, thus promoting good health.

  6. The dissociation of arterial hypertension and lupus glomerulonephritis in systemic lupus erythematosus.

    PubMed

    Petrin, J; Rozman, B; Dolenc, P; Logar, D; Bozic, B; Vizjak, A; Ferluga, D; Jezersek, P

    1993-06-01

    In spite of several articles questioning the general opinion that arterial hypertension in patients with systemic lupus erythematosus (SLE) is only the consequence of lupus glomerulonephritis (LGN), this still remains the usual pathophysiologic explanation. The purpose of this study was to explore the correlations between hypertension and LGN and to assess the importance of hypertension control for the prognosis of patients. A retrospective analysis of 173 patients with SLE over a period of 14 years was performed. For most of the patients, data were available from regular follow-up visits over an average of 6 years. Our results show a dissociation of hypertension and LGN and an association of hypertension and renal dysfunction. Severe hypertensive renal vascular lesions correlated well with a decrease of renal function. Successful treatment of hypertension is therefore essential in order to prevent deterioration of renal function in patients with LGN.

  7. Aspirin-sensitive asthma due to diffuse neuroendocrine system pathology.

    PubMed

    Evsyukova, Helen V

    2002-08-01

    Available clinical data on aspirin-sensitive asthma (ASA) indicate that ASA patients have certain disturbances in the nervous, endocrine, immune and other body systems. It has been found that such patients have a lower melatonin (MT) production in daytime, a pathology of the platelet membrane-receptor complex, and a pathological response to exogenic MT and acetylsalicylic acid. A hypothesis has been suggested in which ASA is considered as apudopathy caused by dysfunction of MT-producing cells. The decreased MT production and the disturbed cell sensitivity to MT lead to pathological changes in individual organs and functional systems. As a result, there is an enhanced lipid peroxidation, an excessive production of reactive oxygen radicals, and a reduced inhibitory action of MT on the 5-lipoxygenase and NO-synthase activities. The lower MT content also results in an intense aggregation of platelets, activating these cells and increasing the production of leukotrienes and nitric oxide. These changes disturb the pulmonary microcirculation, causing the bronchial obturation syndrome even in patient who do not take aspirin or other nonsteroidal anti-inflammatory drugs. The lower basic production of MT is also responsible for a lower content of its metabolite-endogenic acetylsalicylic acid, thereby increasing the sensitivity of melatonin-producing cells, in particular of platelets, to this acid. So, even minimal aspirin doses inhibit the activity of COX-1, which shunts the already abnormal metabolism of arachidonic acid. This, in turn, leads to a greater production of leukotrienes and, hence, to a severe course of the disease. This hypothesis has become the basis for a new pathogenetic approach to the treatment of ASA patients by correcting the melatonin content with peptide bioregulators--the epiphysis extracts--Epithalamin and Epiphamin.

  8. Diagnosis and Management of Pulmonary Hypertension in Systemic Sclerosis

    PubMed Central

    Sweiss, Nadera J.; Hushaw, Linda; Thenappan, Thenappan; Sawaqed, Ray; Machado, Roberto F.; Patel, Amit R.; Gomberg-Maitland, Mardi; Husain, Aliya N.

    2010-01-01

    Patients with systemic sclerosis (SSc) can develop pulmonary hypertension (PH; mean pulmonary artery pressure ≥ 25 mm Hg) caused by pulmonary arterial hypertension (PAH), left ventricular disease, or pulmonary fibrosis. PAH is a pulmonary vascular disease, the diagnosis of which requires pulmonary capillary wedge pressure less than 15 mm Hg, pulmonary vascular resistance greater than 3 Wood Units, and exclusion of thromboembolism and parenchymal lung disease. Molecular mechanisms underlying PAH-SSc include activation of inflammatory and fibrogenic pathways in the vasculature and right ventricle. Circulating autoantibodies trigger endothelial damage and fibroblast activation. PAH most commonly occurs as a late complication in patients with limited cutaneous disease and anticentromere antibodies. Although echocardiography is a useful screening tool, heart catheterization is required to diagnose PAH before initiating therapy. Prognosis and therapeutic response are worse in PAH-SSc than in other PAH categories (median survival, 1–3 y). Approved therapies include prostacyclins, endothelin antagonists, and phosphodiesterase type 5 inhibitors. Research is needed to define disease mechanisms and develop effective therapies. PMID:20425528

  9. Effects of Hypertension and Anti-Hypertensive Treatment on Amyloid-β (Aβ) Plaque Load and Aβ-Synthesizing and Aβ-Degrading Enzymes in Frontal Cortex.

    PubMed

    Ashby, Emma L; Miners, James S; Kehoe, Patrick G; Love, Seth

    2016-01-01

    Epidemiological data associate hypertension with a predisposition to Alzheimer's disease (AD), and a number of postmortem and in vivo studies also demonstrate that hypertension increases amyloid-β (Aβ) pathology. In contrast, anti-hypertensive medications reportedly improve cognition and decrease the risk of AD, while certain classes of anti-hypertensive drugs are associated with decreased AD-related pathology. We investigated the effects of hypertension and anti-hypertensive treatment on Aβ plaque load in postmortem frontal cortex in AD. Aβ load was significantly increased in hypertensive (n = 20) relative to normotensive cases (n = 62) and was also significantly higher in treated (n = 9) than untreated hypertensives (n = 11). We then looked into mechanisms by which hypertension and treatment might increase Aβ load, focusing on Aβ-synthesizing enzymes, β- and γ-secretase, and Aβ-degrading enzymes, angiotensin-converting enzyme (ACE), insulin-degrading enzyme (IDE) and neprilysin. ACE and IDE protein levels were significantly lower in hypertensive (n = 21) than normotensive cases (n = 64), perhaps translating to decreased Aβ catabolism in hypertensives. ACE level was significantly higher in treated (n = 9) than untreated hypertensives (n = 12), possibly reflecting feedback upregulation of the renin-angiotensin system. Prospective studies in larger cohorts stratified according to anti-hypertensive drug class are needed to confirm these initial findings and to elucidate the interactions between hypertension, anti-hypertensive treatments, and Aβ metabolism.

  10. Pulmonary vascular changes 22 years after single lung transplantation for pulmonary arterial hypertension: a case report with molecular and pathological analysis.

    PubMed

    Zhao, Yidan D; Peng, Jenny; Granton, Elise; Lin, Kathleen; Lu, Catherine; Wu, Licun; Machuca, Tiago; Waddell, Thomas K; Keshavjee, Shaf; de Perrot, Marc

    2015-12-01

    This study was undertaken to characterize the molecular and pathological mechanisms of pulmonary vascular remodeling in a patient who developed chronic lung allograft dysfunction and recurrent pulmonary hypertension (PH) 22 years after undergoing a right single lung transplantation for pulmonary arterial hypertension (PAH). Histopathologic examination of the explanted lungs at the time of retransplantation showed characteristics of diffuse vascular remodeling combined with features of acute and chronic thromboemboli and evidence of bronchiolitis obliterans in the right lung allograft. In contrast, the native left lung demonstrated pulmonary arterial changes in keeping with PAH associated with disseminated pulmonary ossification. Real-time polymerase chain reaction and Western blot-performed on the first lung allograft, the native lung, and the new donor lung-demonstrated increased expression of apoptotic-related gene and protein levels in the lung allograft compared with the native PAH lung and the donor lung. Localization of cell apoptosis determined by triple immunostaining for caspase 3, CD31, and smooth muscle actin was positive in the pulmonary endothelial cells but not the smooth muscle cells of the lung allograft, while no positive staining was detected for cell death in the native PAH lung. The presence of PH in the lung allograft 22 years after transplantation was associated with upregulation of apoptotic markers and evidence of apoptotic endothelial cell death compared with the native lung and donor lung.

  11. Targeting renin-angiotensin system in malignant hypertension in atypical hemolytic uremic syndrome

    PubMed Central

    Raghunathan, V.; Sethi, S. K.; Dragon-Durey, M. A.; Dhaliwal, M.; Raina, R.; Jha, P.; Bansal, S. B.; Kher, V.

    2017-01-01

    Hypertension is common in hemolytic uremic syndrome (HUS) and often difficult to control. Local renin-angiotensin activation is believed to be an important part of thrombotic microangiopathy, leading to a vicious cycle of progressive renal injury and intractable hypertension. This has been demonstrated in vitro via enhanced tissue factor expression on glomerular endothelial cells which is enhanced by angiotensin II. We report two pediatric cases of atypical HUS with severe refractory malignant hypertension, in which we targeted the renin-angiotensin system by using intravenous (IV) enalaprilat, oral aliskiren, and oral enalapril with quick and dramatic response of blood pressure. Both drugs, aliskiren and IV enalaprilat, were effective in controlling hypertension refractory to multiple antihypertensive medications. These appear to be promising alternatives in the treatment of severe atypical HUS-induced hypertension and hypertensive emergency. PMID:28356668

  12. Central nervous system dysfunction in obesity-induced hypertension.

    PubMed

    Head, Geoffrey A; Lim, Kyungjoon; Barzel, Benjamin; Burke, Sandra L; Davern, Pamela J

    2014-09-01

    The activation of the sympathetic nervous system is a major mechanism underlying both human and experimental models of obesity-related hypertension. While insulin and the adipokine leptin have long been thought to contribute to obesity-related neurogenic mechanisms, the evidence is now very strong that they play a major role, shown particularly in animal studies using selective receptor antagonists. There is not just maintenance of leptin's sympatho-excitatory actions as previously suggested but considerable amplification particularly in renal sympathetic nervous activity. Importantly, these changes are not dependent on short-term elevation or reduction in plasma leptin or insulin, but require some weeks to develop indicating a slow "neural adaptivity" within hypothalamic signalling. These effects can be carried across generations even when offspring are raised on a normal diet. A better understanding of the underlying mechanism should be a high research priority given the prevalence of obesity not just in the current population but also for future generations.

  13. [Obesity as pathology of adipocytes: number of cells, volume of arterial bloodstream,local pools of circulation in vivo, natriuretic peptides and arterial hypertension].

    PubMed

    Titov, V N; Dmitriev, V A

    2015-03-01

    The non-specific systemic biological reaction of arterial pressure from the level of organism. vasomotor center and proximal section of arterial bloodstream is appealed to compensate disorders of metabolism and microcirculation in distal section of arteries. This phenomenon occurs in several cases. The primarily local disorders of metabolism at autocrine level, physiological (aphysiological) death of cells, "littering" of intercellular medium become the cause of disorder of microcirculation in paracrin cenosises and deteriorate realization of biological functions of homeostasis, trophology, endoecology and adaptation. The local compensation of affected perfusion in paracrin cenosises at the expense of function of peripheral peristaltic pumps, redistribution of local bloodflow in biological reaction of endothelium-depended vaso-dilation has no possibility to eliminate disorders in realization of biological functions. The systemic increase of arterial pressure under absence of specific symptoms of symptomatic arterial hypertension is a test to detect disorder of biological functions of homeostasis, trophology, biological function of endoecology and adaptation. Allforms of arterial hypertension develop by common algorithm independently from causes of disorders of blood flow, microcirculation in distal section of arteries. The non-specific systemic compensation ofdisorders of metabolism from level of organism, in proximal section of arterial bloodstream always is the same one and results in aphysiological alterations in organs-targets. To comprehend etiological characteristics of common pathogenesis of arterial hypertension is possible in case of application of such technically complicated and still unclear in differential diagnostic of deranged functions modes of metabolomics.

  14. Regional cerebral blood flow in essential hypertension: data evaluation by a mapping system

    SciTech Connect

    Rodriguez, G.; Arvigo, F.; Marenco, S.; Nobili, F.; Romano, P.; Sandini, G.; Rosadini, G.

    1987-01-01

    Regional cerebral blood flow was studied by means of the 133Xe inhalation method in 26 untreated and 10 treated patients with essential hypertension. The untreated subjects were divided into newly and previously diagnosed groups to assess the relation between regional cerebral blood flow and the duration of hypertension. The overall flow reduction was more marked in the frontal and temporal regions in the previously diagnosed group, and this was attributed to pathological changes in the district served by the middle cerebral artery. Regional temporal lobe impairment was also noted in the newly diagnosed and treated subjects. A significant correlation was found between regional cerebral blood flow and mean arterial blood pressure.

  15. Role of angiotensin-converting enzyme 2 and angiotensin(1-7) in 17beta-oestradiol regulation of renal pathology in renal wrap hypertension in rats.

    PubMed

    Ji, Hong; Menini, Stefano; Zheng, Wei; Pesce, Carlo; Wu, Xie; Sandberg, Kathryn

    2008-05-01

    17beta-Oestradiol (E2)-mediated inhibition of angiotensin-converting enzyme (ACE) protects the E2-replete kidney from the progression of hypertensive renal disease. Angiotensin-converting enzyme 2 (ACE2), a homologue of ACE, counters the actions of ACE by catalysing the conversion of angiotensin II (Ang II) to angiotensin(1-7) [Ang(1-7)]. We investigated E2 regulation of ACE2 in the renal wrap (RW) model of hypertension in rats. After 6 weeks on a high-sodium diet (4% NaCl), the activity of ACE2 was reduced in the renal cortex by 31%, which was mirrored by similar decreases in ACE2 protein (30%) and mRNA expression (36%) in the ovariectomized RW rat (RW-OVX); E2 replacement prevented these effects. The RW-OVX rats exhibited greater renal injury, including 1.7-fold more tubulointerstitial fibrosis and 1.6-fold more glomerulosclerosis than E2-replete females (RW-Intact and RW-OVX+E2). Angiotensin(1-7) infusion prevented these exacerbating effects of ovariectomy on renal pathology; no differences in indicators of renal injury were observed between RW-OVX-Ang(1-7) and RW-Intact rats. These renal protective effects of Ang(1-7) infusion were not attributable to increased ACE2 activity or to changes in heart rate or body weight, since these parameters were unchanged by Ang(1-7) infusion. Furthermore, Ang(1-7) infusion did not attenuate renal injury by reducing mean arterial pressure (MAP), since infusion of the peptide did not lower MAP but rather caused a slight increase during a 6 week chronic treatment for Ang(1-7). These results suggest that E2-mediated upregulation of renal ACE2 and the consequent increased Ang(1-7) production contribute to E2-mediated protection from hypertensive renal disease. These findings have implications for E2-deficient women with hypertensive renal disease and suggest that therapeutics targeted towards increasing ACE2 activity and Ang(1-7) levels will be renal protective.

  16. Impaired Cardiac Autonomic Nervous System Function is Associated with Pediatric Hypertension Independent of Adiposity

    PubMed Central

    Ryder, Justin R.; O’Connell, Michael; Bosch, Tyler A.; Chow, Lisa; Rudser, Kyle D.; Dengel, Donald R.; Fox, Claudia K.; Steinberger, Julia; Kelly, Aaron S.

    2015-01-01

    Background We examined whether sympathetic nervous system activity influences hypertension status and systolic blood pressure (SBP) independent of adiposity in youth ranging from normal-weight to severe obesity. Methods We examined the association of heart rate variability (HRV) with hypertension status and SBP among youth (6-18 years old; n = 188; 103 female). Seated SBP was measured using an automated cuff. Pre-hypertension (SBP percentile≤90th-<95th) and hypertension (SBP percentile≤95th) were defined by age-, sex-, and height-norms. Autonomic nervous system activity was measured using HRV via SphygmoCorTM MM3 system and analyzed for time- and frequency-domains. Total body fat was measured via dual-energy X-ray absorptiometry. Results Logistic regression models demonstrated lower values in each time-domain HRV measure and larger LF:HF ratio to be significantly associated with higher odds of being pre-hypertensive/hypertensive (11-47% higher odds) independent of total body fat (p<0.05). In linear regression analysis, lower time-domain, but not frequency-domain, HRV measures were significantly associated with higher SBP independent of total body fat (p<0.05). Conclusion These data suggest that impaired cardiac autonomic nervous system function, at rest, is associated with higher odds of being pre-hypertensive/hypertensive and higher SBP which may be independent of adiposity in youth. PMID:26389821

  17. Systemic implementation strategies to improve hypertension: the Kaiser Permanente Southern California experience.

    PubMed

    Sim, John J; Handler, Joel; Jacobsen, Steven J; Kanter, Michael H

    2014-05-01

    The past decade has seen hypertension improving in the United States where control is approximately 50%. Kaiser Permanente has mirrored and exceeded these national advances in control. Integrated models of care such as Kaiser Permanente and the Veterans Administration health systems have demonstrated the greatest hypertension outcomes. We detail the story of Kaiser Permanente Southern California (KPSC) to illustrate the success that can be achieved with an integrated health system model that uses implementation, dissemination, and performance feedback approaches to chronic disease care. KPSC, with a large ethnically diverse population of more than 3.6 million, has used a stepwise approach to achieve control rates greater than 85% in those recognized with hypertension. This was accomplished through systemic implementations of specific strategies: (1) capturing hypertensive members into a hypertension registry; (2) standardization of blood pressure measurements; (3) drafting and disseminating an internal treatment algorithm that is evidence-based and is advocating of combination therapy; and (4) a multidisciplinary approach using medical assistants, nurses, and pharmacists as key stakeholders. The infrastructure, support, and involvement across all levels of the health system with rapid and continuous performance feedback have been pivotal in ensuring the follow-through and maintenance of these strategies. The KPSC hypertension program is continually evolving in these areas. With these high control rates and established infrastructure, they are positioned to take on different innovations and study models. Such potential projects are drafting strategies on resistant hypertension or addressing the concerns about overtreatment of hypertension.

  18. Hypertension guidelines and their effects on the health system

    PubMed Central

    Frank, Wilhelm; Konta, Brigitte

    2005-01-01

    Introduction Hypertension guidelines, which have existed for many years and primarily used in the USA, Canada and Great Britain, are now becoming an issue in Germany. Strong efforts are presently underway for a German version comparable to the guidelines developed for the mentioned countries. The development of guidelines is a part of the implementation system of guidelines in Germany. It covers the mode of operation of the AWMF (work community of the scientific medical subject companies) with the clearinghouse for guidelines (CLA) and the cooperation with the centre for medical quality (ÄZQ). In the HTA report the real use of the hypertension guidelines shall be investigated for Germany from the development trends and further possibilities of use according to a medical applicability. Economic issues and an optimisation of use are also discussed. Question The following questions shall be answered in particular: How much are the guidelines used concerning hypertension? Can effects (or their influence) be established on the medical procedures? Are there statements available about costs and cost effectiveness? Are there recommendations for further use? Methodology To answer these questions, a comprehensive literature search was done. No empirical investigation was carried out. From this enquiry 206 articles were checked in detail but not all of them were available in full text. Only those publications which directly dealt with high blood pressure guidelines or articles with a direct reference to the topic have been considered in the HTA report. Publications concerning screening or methods of prevention, medical studies of the hypertension syndrome without a direct reference to guidelines and publications concerned with putting guidelines into action were excluded. Results After an analysis of the selected literature addressing the topic of hypertension guidelines, it was evident that the use of these guidelines cannot be gathered from existing literature at the

  19. Computational Pathology

    PubMed Central

    Louis, David N.; Feldman, Michael; Carter, Alexis B.; Dighe, Anand S.; Pfeifer, John D.; Bry, Lynn; Almeida, Jonas S.; Saltz, Joel; Braun, Jonathan; Tomaszewski, John E.; Gilbertson, John R.; Sinard, John H.; Gerber, Georg K.; Galli, Stephen J.; Golden, Jeffrey A.; Becich, Michael J.

    2016-01-01

    Context We define the scope and needs within the new discipline of computational pathology, a discipline critical to the future of both the practice of pathology and, more broadly, medical practice in general. Objective To define the scope and needs of computational pathology. Data Sources A meeting was convened in Boston, Massachusetts, in July 2014 prior to the annual Association of Pathology Chairs meeting, and it was attended by a variety of pathologists, including individuals highly invested in pathology informatics as well as chairs of pathology departments. Conclusions The meeting made recommendations to promote computational pathology, including clearly defining the field and articulating its value propositions; asserting that the value propositions for health care systems must include means to incorporate robust computational approaches to implement data-driven methods that aid in guiding individual and population health care; leveraging computational pathology as a center for data interpretation in modern health care systems; stating that realizing the value proposition will require working with institutional administrations, other departments, and pathology colleagues; declaring that a robust pipeline should be fostered that trains and develops future computational pathologists, for those with both pathology and non-pathology backgrounds; and deciding that computational pathology should serve as a hub for data-related research in health care systems. The dissemination of these recommendations to pathology and bioinformatics departments should help facilitate the development of computational pathology. PMID:26098131

  20. Tuning pathological brain oscillations with neurofeedback: a systems neuroscience framework

    PubMed Central

    Ros, Tomas; J. Baars, Bernard; Lanius, Ruth A.; Vuilleumier, Patrik

    2014-01-01

    Neurofeedback (NFB) is emerging as a promising technique that enables self-regulation of ongoing brain oscillations. However, despite a rise in empirical evidence attesting to its clinical benefits, a solid theoretical basis is still lacking on the manner in which NFB is able to achieve these outcomes. The present work attempts to bring together various concepts from neurobiology, engineering, and dynamical systems so as to propose a contemporary theoretical framework for the mechanistic effects of NFB. The objective is to provide a firmly neurophysiological account of NFB, which goes beyond traditional behaviorist interpretations that attempt to explain psychological processes solely from a descriptive standpoint whilst treating the brain as a “black box”. To this end, we interlink evidence from experimental findings that encompass a broad range of intrinsic brain phenomena: starting from “bottom-up” mechanisms of neural synchronization, followed by “top-down” regulation of internal brain states, moving to dynamical systems plus control-theoretic principles, and concluding with activity-dependent as well as homeostatic forms of brain plasticity. In support of our framework, we examine the effects of NFB in several brain disorders, including attention-deficit hyperactivity (ADHD) and post-traumatic stress disorder (PTSD). In sum, it is argued that pathological oscillations emerge from an abnormal formation of brain-state attractor landscape(s). The central thesis put forward is that NFB tunes brain oscillations toward a homeostatic set-point which affords an optimal balance between network flexibility and stability (i.e., self-organised criticality (SOC)). PMID:25566028

  1. Tuning pathological brain oscillations with neurofeedback: a systems neuroscience framework.

    PubMed

    Ros, Tomas; J Baars, Bernard; Lanius, Ruth A; Vuilleumier, Patrik

    2014-01-01

    Neurofeedback (NFB) is emerging as a promising technique that enables self-regulation of ongoing brain oscillations. However, despite a rise in empirical evidence attesting to its clinical benefits, a solid theoretical basis is still lacking on the manner in which NFB is able to achieve these outcomes. The present work attempts to bring together various concepts from neurobiology, engineering, and dynamical systems so as to propose a contemporary theoretical framework for the mechanistic effects of NFB. The objective is to provide a firmly neurophysiological account of NFB, which goes beyond traditional behaviorist interpretations that attempt to explain psychological processes solely from a descriptive standpoint whilst treating the brain as a "black box". To this end, we interlink evidence from experimental findings that encompass a broad range of intrinsic brain phenomena: starting from "bottom-up" mechanisms of neural synchronization, followed by "top-down" regulation of internal brain states, moving to dynamical systems plus control-theoretic principles, and concluding with activity-dependent as well as homeostatic forms of brain plasticity. In support of our framework, we examine the effects of NFB in several brain disorders, including attention-deficit hyperactivity (ADHD) and post-traumatic stress disorder (PTSD). In sum, it is argued that pathological oscillations emerge from an abnormal formation of brain-state attractor landscape(s). The central thesis put forward is that NFB tunes brain oscillations toward a homeostatic set-point which affords an optimal balance between network flexibility and stability (i.e., self-organised criticality (SOC)).

  2. Abnormal thallium kinetics in postoperative coarctation of the aorta: evidence for diffuse hypertension-induced vascular pathology

    SciTech Connect

    Kimball, B.P.; Shurvell, B.L.; Mildenberger, R.R.; Houle, S.; McLaughlin, P.R.

    1986-03-01

    After operative correction of congenital coarctation of the aorta, patients continue to have excess cardiovascular mortality, including manifestations of ischemic heart disease. Previous morphologic studies support the concept of direct hypertensive vascular injury in these patients. To determine whether abnormalities of myocardial perfusion were present in an asymptomatic group of patients with coarctation repair, 18 men and 9 women with a mean age of 26 years (range 19 to 41) were studied between 2 and 25 years after operative correction. Stress electrocardiography and quantitative thallium imaging by a circumferential profile technique were used. These patients were compared with a normal group, statistically defined as having a less than 1% prevalence of significant obstructive coronary artery disease. The postoperative coarctation group demonstrated a reduction in global thallium redistribution in each view analyzed. As compared with findings in the control subjects, thallium washout in the anterior view (41.9 versus 48.6%, p = 0.02) and left anterior oblique projection (40.5 versus 48.2%, p = 0.007) was significantly diminished. Although the postoperative coarctation group had a lower thallium redistribution rate in the lateral view (41.4 versus 46.3%, p = 0.09) this difference did not reach statistical significance because of the intrinsic variability of this projection. Plots of the median percent thallium washout revealed independence from circumferential profile angle, indicating global abnormalities in perfusion. No correlation between clinical variables and thallium kinetics could be established, suggesting marked individual variability in the development of this vascular lesion. The observation of abnormal thallium kinetics in patients with coarctation repair may have consequences for long-term follow-up and therapy.

  3. Obesity-induced hypertension: role of sympathetic nervous system, leptin, and melanocortins.

    PubMed

    Hall, John E; da Silva, Alexandre A; do Carmo, Jussara M; Dubinion, John; Hamza, Shereen; Munusamy, Shankar; Smith, Grant; Stec, David E

    2010-06-04

    Excess weight gain contributes to increased blood pressure in most patients with essential hypertension. Although the mechanisms of obesity hypertension are not fully understood, increased renal sodium reabsorption and impaired pressure natriuresis play key roles. Several mechanisms contribute to altered kidney function and hypertension in obesity, including activation of the sympathetic nervous system, which appears to be mediated in part by increased levels of the adipocyte-derived hormone leptin, stimulation of pro-opiomelanocortin neurons, and subsequent activation of central nervous system melanocortin 4 receptors.

  4. The Renin Angiotensin Aldosterone System in Obesity and Hypertension: Roles in the Cardiorenal Metabolic Syndrome.

    PubMed

    Cabandugama, Peminda K; Gardner, Michael J; Sowers, James R

    2017-01-01

    In the United States, more than 50 million people have blood pressure at or above 120/80 mm Hg. All components of cardiorenal metabolic syndrome (CRS) are linked to metabolic abnormalities and obesity. A major driver for CRS is obesity. Current estimates show that many of those with hypertension and CRS show some degree of systemic and cardiovascular insulin resistance. Several pathophysiologic factors participate in the link between hypertension and CRS. This article updates recent literature with a focus on the function of insulin resistance, obesity, and renin angiotensin aldosterone system-mediated oxidative stress on endothelial dysfunction and the pathogenesis of hypertension.

  5. Pulmonary hypertension, systemic lupus erythematosus, and the contraceptive pill: another report.

    PubMed

    Miller, M H

    1987-02-01

    I report the case of a woman with systemic lupus erythematosus who had pulmonary hypertension unassociated with chronic interstitial lung disease or pulmonary emboli. She had started taking the contraceptive pill seven months previously.

  6. Pulmonary hypertension

    MedlinePlus

    Pulmonary arterial hypertension; Sporadic primary pulmonary hypertension; Familial primary pulmonary hypertension; Idiopathic pulmonary arterial hypertension; Primary pulmonary hypertension; PPH; Secondary pulmonary ...

  7. Development of an electronic breast pathology database in a community health system

    PubMed Central

    Nelson, Heidi D.; Weerasinghe, Roshanthi; Martel, Maritza; Bifulco, Carlo; Assur, Ted; Elmore, Joann G.; Weaver, Donald L.

    2014-01-01

    Background: Health care systems rely on electronic patient data, yet access to breast tissue pathology results continues to depend on interpreting dictated free-text reports. Objective: The objective was to develop a method to electronically search and categorize pathologic diagnoses of patients’ breast tissue specimens from dictated free-text pathology reports in a large health system for multiple users including clinicians. Design: A database integrating existing patient-level administrative and clinical information for breast cancer screening and diagnostic services and a web-based application for comprehensive searching of pathology reports were developed by a health system team led by pathologists. The Breast Pathology Assessment Tool and Hierarchy for Diagnosis (BPATH-Dx) provided search terms and guided electronic transcription of diagnoses from text fields on breast pathology clinical reports to standardized categories. Approach: Breast pathology encounters in the pathology database were matched with administrative data for 7332 women with breast tissue specimens obtained from an initial procedure in the health system from January 1, 2008 to December 31, 2011. Sequential queries of the pathology text based on BPATH-Dx categorized biopsies according to their worst pathological diagnosis, as is standard practice. Diagnoses ranged from invasive breast cancer (23.3%), carcinoma in situ (7.8%), atypical lesions (6.39%), proliferative lesions without atypia (27.9%), and nonproliferative lesions (34.7%), and were further classified into subcategories. A random sample of 5% of reports that were manually reviewed indicated 97.5% agreement. Conclusions: Sequential queries of free-text pathology reports guided by a standardized assessment tool in conjunction with a web-based search application provide an efficient and reproducible approach to accessing nonmalignant breast pathology diagnoses. This method advances the use of pathology data and electronic health

  8. 77 FR 59941 - Prospective Grant of Exclusive License: Terahertz Scanning Systems for Cancer Pathology

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-01

    ... Systems for Cancer Pathology AGENCY: National Institutes of Health, Public Health Service, HHS. ACTION... systems for cancer pathology. Upon the expiration or termination of the exclusive evaluation option... therefore potentially suitable for medical applications such as cancer diagnosis of living subjects...

  9. Study of nanosensor systems for hypertension associated cerebrovascular and cardiovascular disorders

    NASA Astrophysics Data System (ADS)

    Ramasamy, Mouli; Varadan, Vijay K.

    2015-04-01

    Hypertension and hypertension associated cerebrovascular and cardiovascular diseases are on a rise. At-least 970 million people in the world and Seventy percent of the American adults are affected by high blood pressure, also known as hypertension. Even though blood pressure monitoring systems are readily available, the number of people being affected has been increasing. Most of the blood pressure monitoring systems require cumbersome approaches. Even the noninvasive techniques have not lowered the number of people affected nor did at-least increase the user base of these systems. Uncontrolled or untreated hypertension may lead to various cerebrovascular disorders including stroke, hypertensive crisis, lacunar infarcts intracerebral damage, microaneurysm, and cardiovascular disorders including heart failure, myocardial infraction, and ischemic heart disease. Hypertension is rated as the one of the most important causes of premature death in spite of the technical advances in biomedical technology. This paper briefs a review of the widely adopted blood pressure monitoring methods, research techniques, and finally, proposes a concept of implementing nanosensors and wireless communication for real time non-invasive blood pressure monitoring.

  10. [Theory of functional systems: postulates and principles of human body construction in health and pathology].

    PubMed

    Sudakov, K V

    2007-01-01

    It is shown that many functional systems with different level of organization harmoniously interact in healthy humans and animals. Early stress discoordinates information links of functional systems which can be easily corrected by nonpharmacological methods. Long-term and intensive stress disturbs mechanisms of self-regulation of the weakest functional systems. This converts a pathological process to a molecular tissue level. Principles of systemic functional human organization in pathology and compensation of impaired functions are considered.

  11. [The role of the immune system in the pathogenesis of hypertension].

    PubMed

    Leibowitz, Avshalom; Grossman, Ehud

    2014-01-01

    Inflammation plays an important role in the pathogenesis of hypertension. Innate and adaptive immune response may contribute to this process. The mechanisms implicating immune response in hypertension are still elusive. To date, the evidence originates in three major areas of data: cytokine production, central nervous system (CNS) stimulation and kidney damage. The cytokine microenvironment can become proinflammatory and propagate low-grade inflammation, which may contribute to vascular injury and end-organ damage in hypertension. In addition, stimulation of the CNS by some stimuli (e.g. angiotensin II) causes mild hypertension that may modulate peripheral immune responses leading to aggravation of blood pressure elevation. The immune response can induce kidney injury and also interfere with sodium excretion, further contributing to elevation of blood pressure.

  12. Pulmonary hypertension in systemic lupus erythematosus: a systematic review and analysis of 642 cases in Chinese population.

    PubMed

    Xia, Y K; Tu, S H; Hu, Y H; Wang, Y; Chen, Z; Day, H T; Ross, K

    2013-05-01

    Pulmonary hypertension (PH) is an increasingly recognized complication of systemic lupus erythematosus (SLE). To develop a more comprehensive understanding of the clinical and pathological characteristics of pulmonary hypertension associated with systemic lupus erythematosus (PH/SLE) in the Chinese population, a systematic review of the literature up to 2012 was conducted. Six hundred and forty-two Chinese PH/SLE cases from 22 studies were identified as well documented and further analyzed. Transthoracic echocardiography (TTE), X-ray, electrocardiogram and right heart catheterization (RHC) were performed to diagnose PH in SLE patients. The mean age of subjects was 35.5 years, the male to female ratio was 1:14, and the mean duration of SLE when PH was diagnosed was 10.7 years. The prevalence of PH in SLE was 2.8-23.3 %. Symptoms were usually nonspecific, and the observed clinical characteristics include Raynaud's phenomenon (41.4 %), serous effusion (27.7 %), positive RNP (51.5 %) and positive ACL (46.6 %). Gold standard RHC is strongly recommended, especially for those who had resting pulmonary arterial systolic pressure >30 mmHg on TTE with the aforementioned clinical characteristics. Corticosteroids, immunosuppressants and vasodilators were the most common medications employed in treatment. Early identification and standard PH treatment with intensive SLE treatment can improve the prognosis.

  13. [The influence of structural and functional disorders in cardiovascular and renal systems and metabolic disturbances on perinatal outcomes in pregnant women with chronic arterial hypertension].

    PubMed

    Padyganova, A V; Chicherina, E N

    2014-01-01

    We studied the influence of structural and functional disorders in cardiovascular and renal system and metabolic disturbances on perinatal outcomes in pregnant women with chronic arterial hypertension. The study included 100 women with these pathologies and 30 patients with physiological pregnancy. Comprehensive evaluation of the cardiovascular system, metabolic status, and perinatal outcomes was undertaken. The results indicate that atherogenic dyslipidemia is significantly associated with the reduction of body mass while glomerular filtration rate, concentric and eccentric left ventricular hypertrophy with the decrease of both weight and height of the newborns.

  14. [INFLUENCE OF THE INTRA-ABDOMINAL HYPERTENSION ON THE BLOOD COAGULATION SYSTEM (EXPERIMENTAL STUDY)].

    PubMed

    Turgunov, Y; Matyushko, D; Nurbekov, A; Kaliyeva, D; Alibekov, A

    2016-07-01

    The analysis of the influence of the intra-abdominal hypertension on the blood coagulation system by carrying out an experimental research with laboratory animals is presented in article. After simulating intra-abdominal hypertension with different degree and exposition we made the laboratory research of blood coagulation system (fibrinogen, PTI, SFMC, APTT) and ELISA research on the concentration of the modern marker of thrombozis - D-dimer. The results in article clearly demonstrate that there is a direct linear dependence of level of fibrinogen and SFMC on degree of intra-abdominal hypertension, and the multidirectional changes of indicators with increase of intra-abdominal hypertension duration - towards hypercoagulation for 3-12 hours, and then by 24 o'clock - in the opposite direction towards hypocoagulation. Perhaps, it is explained with development of organ dysfunction and a coagulopathy of consumption. Indicator D-dimer has also direct linear dependence on the intra-abdominal hypertension level with contents peak at 3 hour exposition, and at all intra-abdominal hypertension levels, more than 2-fold rise of D-dimer level is statistically significant.

  15. Prevalence of chronic obstructive pulmonary disease among patients with systemic arterial hypertension without respiratory symptoms

    PubMed Central

    Rabahi, Marcelo Fouad; Pereira, Sheila Alves; Silva Júnior, José Laerte Rodrigues; de Rezende, Aline Pacheco; Castro da Costa, Adeliane; de Sousa Corrêa, Krislainy; Conde, Marcus Barreto

    2015-01-01

    Background The diagnosis of chronic obstructive pulmonary disease (COPD) is often delayed until later stages of the disease. The purpose of the present study was to determine the prevalence of COPD among adults on treatment for systemic arterial hypertension independently of the presence of respiratory symptoms. Methods This cross-sectional study included adults aged ≥40 years with tobacco/occupational exposure and systemic arterial hypertension diagnosed at three Primary Health Care facilities in Goiania, Brazil. Patients were evaluated using a standardized respiratory questionnaire and spirometry. COPD prevalence was measured considering the value of forced vital capacity and/or forced expiratory volume in 1 second <0.70. Results Of a total of 570 subjects, 316 (55%) met inclusion criteria and were invited to participate. Two hundred and thirty-three (73.7%) patients with arterial hypertension reported at least one respiratory symptom, while 83 (26.3%) reported no respiratory symptoms; 41 (17.6%) patients with arterial hypertension and at least one respiratory symptom, and 10 (12%) patients with arterial hypertension but no respiratory symptoms were diagnosed with COPD (P=0.24). The prevalence of COPD in people with no previous COPD diagnosis was greater among those with no respiratory symptoms (100%) than among those with respiratory symptoms (56.1%) (P=0.01). Conclusion Our findings suggest that regardless of the presence of respiratory symptoms, individuals aged ≥40 years with tobacco/occupational exposure and arterial hypertension may benefit from spirometric evaluation. PMID:26257517

  16. Hypoactivation of reward motivational system in patients with newly diagnosed hypertension grade I-II.

    PubMed

    Aftanas, L I; Brak, I V; Gilinskaya, O M; Korenek, V V; Pavlov, S V; Reva, N V

    2014-08-01

    In patients with newly diagnosed untreated grade I-II hypertension, EEG oscillations were recorded under conditions activation of the two basic motivational systems, defensive motivational system and positive reinforcement system, evoked by recall of personally meaningful emotional events. The 64-channel EEG and cardiovascular reactivity (beat-by-beat technology) were simultaneously recorded. At rest, hypertensive patients had significantly reduced platelet serotonin concentrations in comparison with healthy individuals. The patients experiencing emotional activation were characterized by significantly lower intensity of positive emotions associated with more pronounced suppression of EEG activity in the delta (2-4 Hz) and theta (ranges of frequency 4-6 and 6-8 Hz) oscillators in the parieto-occipital cortex (zones P and PO) in both hemispheres of the brain. The findings attest to insufficient function of the brain serotonin system and hypoactivation of the reward/reinforcement system in patients with primary hypertension.

  17. [Systemic arterial hypertension in the elderly. Recommendations for clinical practice].

    PubMed

    Rosas-Peralta, Martín; Borrayo-Sánchez, Gabriela; Madrid-Miller, Alejandra; Ramírez-Arias, Erick; Pérez-Rodríguez, Gilberto

    2016-01-01

    Hypertension is common in people aged 65 and older. In those aged 70 and older, hypertension is more poorly controlled than in those whose age is between 60 and 69 years. The number of trials available concerning the elderly population is limited; therefore, strong recommendations on blood pressure (BP) goals are limited. The American College of Cardiology has recently published a consensus report of management of hypertension in the elderly population. This review presents an overview of that consensus report and reviews specific studies that provide some novel findings regarding BP goals and the progression of nephropathy. In general, the evidence strongly supports a BP goal < 150/80 mm Hg for the elderly with scant data in those aged 80 and older. However, it was decided to set the goal < 140/90 mm Hg, unless the patient cannot tolerate it, and then try to achieve 140-145 mm Hg. Diuretics and calcium antagonists are the most efficient treatment; however, most patients will require two or more drugs to achieve such goals.

  18. Is immune system-related hypertension associated with ovarian hormone deficiency?

    PubMed Central

    Sandberg, Kathryn; Ji, Hong; Einstein, Gillian; Au, April; Hay, Meredith

    2017-01-01

    The immune system is known to contribute to the development of high blood pressure in males. However, the role of the immune system in the development of high blood pressure in females and the role of ovarian hormones has only recently begun to be studied. In animal studies, both the sex of the host and the T cell are critical biological determinants of susceptibility and resistance to hypertension induced by angiotensin II. In women, natural menopause is known to result in significant changes in the expression of genes regulating the immune system. Likewise, in animal models, ovariectomy results in hypertension and an upregulation in T-cell tumour necrosis factor-α-related genes. Oestrogen replacement results in decreases in inflammatory genes in the brain regions involved in blood pressure regulation. Together, these studies suggest that the response of the adaptive immune system to ovarian hormone deficiency is a significant contributor to hypertension in women. PMID:26419911

  19. Whole-Organism Cellular Pathology: A Systems Approach to Phenomics.

    PubMed

    Cheng, K C; Katz, S R; Lin, A Y; Xin, X; Ding, Y

    2016-01-01

    Phenotype is defined as the state of an organism resulting from interactions between genes, environment, disease, molecular mechanisms, and chance. The purpose of the emerging field of phenomics is to systematically determine and measure phenotypes across biology for the sake of understanding. Phenotypes can affect more than one cell type and life stage, so ideal phenotyping would include the state of every cell type within the context of both tissue architecture and the whole organism at each life stage. In medicine, high-resolution anatomic assessment of phenotype is obtained from histology. Histology's interpretative power, codified by Virchow as cellular pathology, is derived from its ability to discern diagnostic and characteristic cellular changes in diseased tissues. Cellular pathology is observed in every major human disease and relies on the ability of histology to detect cellular change in any cell type due to unbiased pan-cellular staining, even in optically opaque tissues. Our laboratory has shown that histology is far more sensitive than stereomicroscopy for detecting phenotypes in zebrafish mutants. Those studies have also shown that more complete sampling, greater consistency in sample orientation, and the inclusion of phenotypes extending over longer length scales would provide greater coverage of common phenotypes. We are developing technical approaches to achieve an ideal detection of cellular pathology using an improved form of X-ray microtomography that retains the strengths and addresses the weaknesses of histology as a screening tool. We are using zebrafish as a vertebrate model based on the overlaps between zebrafish and mammalian tissue architecture, and a body size small enough to allow whole-organism, volumetric imaging at cellular resolution. Automation of whole-organism phenotyping would greatly increase the value of phenomics. Potential societal benefits would include reduction in the cost of drug development, a reduction in the

  20. Systemic Mastocytosis Complicated by Non-Cirrhotic Portal Hypertension and Variceal Bleeding

    PubMed Central

    McCarty, Thomas R.; Hung, Adelina; Mohanty, Arpan

    2017-01-01

    Systemic mastocytosis is a myeloproliferative disorder characterized by extracutaneous involvement of at least one organ. Although rare, infiltration of inflammatory mast cells within the portal vein may lead to obstruction of the sinusoids resulting in non-cirrhotic portal hypertension. We present a patient with known history of systemic mastocytosis with bone marrow involvement presenting with new-onset esophageal variceal bleeding. Although systemic mastocytosis is uncommon, the subsequent development of hepatic involvement and non-cirrhotic portal hypertension are discussed. Further highlighted is a lack of organization guidelines and the potential for gastrointestinal and hepatic screening of mastocytosis patients with known extracutaneous involvement. PMID:28286795

  1. System of polarization phasometry of polycrystalline blood plasma networks in mammary gland pathology diagnostics

    NASA Astrophysics Data System (ADS)

    Zabolotna, Natalia I.; Oliinychenko, Bogdan P.; Radchenko, Kostiantyn O.; Krasnoshchoka, Anastasiia K.; Shcherba, Olga K.

    2015-09-01

    The polarizing phase meter system of polycrystalline networks of human blood plasma which is used for the mammary gland pathology diagnostics was proposed in this paper. Increasing the accuracy of the phase value determination was achieved using a combination of low coherent source of radiation and circularly polarized probing of biological object. Thus, high informativity of polarizing phase meter system for the diagnosis of breast pathology using the phase mapping of the human blood plasma films were determined, thereafter statistical, correlational, fractal structure analysis of the obtained phase maps was carried out and the quantitative criterias of the phase diagnostics and differentiation of the breast pathological conditions were determined too.

  2. [Proteomic analysis of exhaled breath condensate for diagnosis of pathologies of the respiratory system].

    PubMed

    Kononikhin, A S; Fedorchenko, K Yu; Ryabokon, A M; Starodubtseva, N L; Popov, I A; Zavialova, M G; Anaev, E C; Chuchalin, A G; Varfolomeev, S D; Nikolaev, E N

    2015-01-01

    Study of the proteomic composition of exhaled breath condensate (EBC), is a promising non-invasive method for the diagnosis of the respiratory tract diseases in patients. In this study the EBC proteomic composition of the 79 donors, including patients with different pathologies of the respiratory system has been investigated. Cytoskeletal keratins type II (1, 2, 3, 4, 5, 6) and cytoskeletal keratins the type I (9, 10, 14, 15, 16) were invariant for all samples. Analyzing the frequency of occurrence of proteins in different groups of examined patients, several categories of protein have been recognized: found in all pathologies (Dermcidin, Alpha-1-microglobulin, SHROOM3), found in several pathologies (CSTA, LCN1, JUP, PIP, TXN), and specific for a single pathology (PRDX1, Annexin A1/A2). The EBC analysis by HPLC-MS/MS can be used to identify potential protein markers characteristic for pathologies such as chronic obstructive pulmonary disease (PRDX1) and pneumonia (Annexin A1/A2).

  3. Portal hypertension.

    PubMed

    Garcia-Tsao, G

    2001-05-01

    Portal hypertension is the main complication of cirrhosis and is responsible for its most common complications: variceal hemorrhage, ascites, and portosystemic encephalopathy. Portal hypertension is the result of increased intrahepatic resistance and increased portal venous inflow, which in turn is the result of splanchnic vasodilatation. Vasodilatation (splanchnic and systemic) and hyperdynamic circulation are hemodynamic abnormalities typical of cirrhosis and portal hypertension. Gastroesophageal varices result almost solely from portal hypertension, although the hyperdynamic circulation contributes to variceal growth and hemorrhage. Ascites results from sinusoidal hypertension and sodium retention, which is, in turn, secondary to vasodilatation and activation of neurohumoral systems. The hepatorenal syndrome represents the result of extreme vasodilatation with an extreme decrease in effective blood volume that leads to maximal activation of vasoconstrictive systems, renal vasoconstriction, and renal failure. Spontaneous bacterial peritonitis is a potentially lethal infection of ascites that occurs in the absence of a local source of infection. Portosystemic encephalopathy is a consequence of both portal hypertension (shunting of blood through portosystemic collaterals) and hepatic insufficiency that result in the accumulation of neurotoxins in the brain. This paper reviews the recent advances in the pathophysiology and management of the complications of portal hypertension.

  4. Portal hypertension.

    PubMed

    Garcia-Tsao, Guadalupe

    2003-05-01

    Portal hypertension, the main complication of cirrhosis, is responsible for its most common complications: variceal hemorrhage, ascites, and portosystemic encephalopathy. Portal hypertension is the result of increased intrahepatic resistance and increased portal venous inflow. Vasodilatation (splanchnic and systemic) and the hyperdynamic circulation are hemodynamic abnormalities typical of cirrhosis and portal hypertension. Gastroesophageal varices result almost solely from portal hypertension, although the hyperdynamic circulation contributes to variceal growth and hemorrhage. Ascites results from sinusoidal hypertension and sodium retention, which, in turn, is secondary to vasodilatation and activation of neurohumoral systems. The hepatorenal syndrome represents the result of extreme vasodilatation, with an extreme decrease in effective blood volume that leads to maximal activation of vasoconstrictive systems, renal vasoconstriction, and renal failure. Spontaneous bacterial peritonitis is a potentially lethal infection of ascites that occurs in the absence of a local source of infection. Portosystemic encephalopathy is a consequence of both portal hypertension (shunting of blood through portosystemic collaterals) and hepatic insufficiency that result in the accumulation of neurotoxins in the brain. This review covers the recent advances in the pathophysiology and management of the complications of portal hypertension.

  5. Epigenetic Modifications in Essential Hypertension.

    PubMed

    Wise, Ingrid A; Charchar, Fadi J

    2016-03-25

    Essential hypertension (EH) is a complex, polygenic condition with no single causative agent. Despite advances in our understanding of the pathophysiology of EH, hypertension remains one of the world's leading public health problems. Furthermore, there is increasing evidence that epigenetic modifications are as important as genetic predisposition in the development of EH. Indeed, a complex and interactive genetic and environmental system exists to determine an individual's risk of EH. Epigenetics refers to all heritable changes to the regulation of gene expression as well as chromatin remodelling, without involvement of nucleotide sequence changes. Epigenetic modification is recognized as an essential process in biology, but is now being investigated for its role in the development of specific pathologic conditions, including EH. Epigenetic research will provide insights into the pathogenesis of blood pressure regulation that cannot be explained by classic Mendelian inheritance. This review concentrates on epigenetic modifications to DNA structure, including the influence of non-coding RNAs on hypertension development.

  6. Severe biventricular hypertrophy mimicking infiltrative cardiomyopathy in old man with pulmonary stenosis and systemic hypertension.

    PubMed

    Efe, Süleyman Çağan; Kahveci, Gokhan; Bakal, Ruken Bengi; Akpinar, Suzan Hatipoğlu; Unkun, Tuba; Ozdemir, Nihal

    2015-01-01

    Hypertrophic biventricular cardiomyopathy is a rare finding and generally caused by systemic infiltrative diseases. Its association with pulmonary stenosis in same patient is even rarer. We report a case report of male patient with biventricular hypertrophy coexisting with pulmonary valve stenosis and systemic hypertension.

  7. [Peculiarities of cardiovascular system pathology depending on psychological profile in patients of senior age groups].

    PubMed

    Prokhorenko, I O

    2013-01-01

    Interrelations between peculiarities of psychological profile of patients of senior age groups (according to Cattel), level of stress hormones in blood and background pathology of cardiovascular system were studied. Levels of catecholamine and corticosteroids in dynamics, rate of magnesium in erythrocytes and calcium in plaques of coronary arteries as well as fats, Holter ECG, daily profiles of blood pressure, vasomotor function of endothelium and microcirculation were analysed. It is established that stress hormones indirectly determine original form of stress reaction depending on patients' psychological profile. This contributes to the development of one or another form of cardiovascular system pathology. Excessive alcohol intake also promotes progression of cardiovascular system pathology. Depression, being a reflection of disbalance of stress hormones levels, can be used as a marker of unfavourable course of cardiovascular pathology.

  8. Oligodendrogenesis in the normal and pathological central nervous system

    PubMed Central

    El Waly, Bilal; Macchi, Magali; Cayre, Myriam; Durbec, Pascale

    2014-01-01

    Oligodendrocytes (OLGs) are generated late in development and myelination is thus a tardive event in the brain developmental process. It is however maintained whole life long at lower rate, and myelin sheath is crucial for proper signal transmission and neuronal survival. Unfortunately, OLGs present a high susceptibility to oxidative stress, thus demyelination often takes place secondary to diverse brain lesions or pathologies. OLGs can also be the target of immune attacks, leading to primary demyelination lesions. Following oligodendrocytic death, spontaneous remyelination may occur to a certain extent. In this review, we will mainly focus on the adult brain and on the two main sources of progenitor cells that contribute to oligodendrogenesis: parenchymal oligodendrocyte precursor cells (OPCs) and subventricular zone (SVZ)-derived progenitors. We will shortly come back on the main steps of oligodendrogenesis in the postnatal and adult brain, and summarize the key factors involved in the determination of oligodendrocytic fate. We will then shed light on the main causes of demyelination in the adult brain and present the animal models that have been developed to get insight on the demyelination/remyelination process. Finally, we will synthetize the results of studies searching for factors able to modulate spontaneous myelin repair. PMID:24971048

  9. [Selective portal-systemic shunts for bleeding portal hypertension].

    PubMed

    Orozco, H; Mercado, M A; Takahashi, T; García-Tsao, G; Guevara, L; Hernandez-Ortiz, J; Tielve, M

    1990-07-01

    At the beginning of the seventies, we began to perform regularly selective shunts for the treatment of portal hypertension. In a 15 year period, 177 patients (155 with liver cirrhosis) were operated with three kinds of selective shunts: 128 with a Warren shunt, 29 with an end to end renosplenic shunt and 20 with a splenocaval shunt. 167 cases were operated in an elective fashion. The 15 years global operative mortality, was 14.4%. Operative mortality of the Child A patients, was 11.6%. Survival for the Child A group was 74.6% at 1 year, 68.2% at 5 years and 64.6% at 15 years. Incapacitating encephalopathy was observed in 6.9%, rebleeding 6.2% and shunt thrombosis in 6.2%. Portal vein alterations in the postoperative period were observed: in 13.3% a reduction in diameter ocurred and in 20.5%, thrombosis was recorded. It is concluded that when feasible, the selective shunts are the treatment of choice for portal hypertension in those patients with good liver function.

  10. [Clinical guidelines for detection, prevention, diagnosis and treatment of systemic arterial hypertension in Mexico (2008)].

    PubMed

    Rosas, Martín; Pastelín, Gustavo; Vargas-Alarcón, Gilberto; Martínez-Reding, Jesús; Lomelí, Catalina; Mendoza-González, Celso; Lorenzo, José Antonio; Méndez, Arturo; Franco, Martha; Sánchez-Lozada, Laura Gabriela; Verdejo, Juan; Sánchez, Noé; Ruiz, Rocío; Férez-Santander, Sergio Mario; Attie, Fause

    2008-01-01

    The multidisciplinary Institutional Committee of experts in Systemic Arterial Hypertension from the National Institute of Cardiology "Ignacio Chávez" presents its update (2008) of "Guidelines and Recommendations" for the early detection, control, treatment and prevention of Hypertension. The boarding tries to be simple and realistic for all that physicians whom have to face the hypertensive population in their clinical practice. The information is based in the most recent scientific evidence. These guides are principally directed to hypertensive population of emergent countries like Mexico. It is emphasized preventive health measures, the importance of the no pharmacological actions, such as good nutrition, exercise and changes in life style, (which ideally it must begin from very early ages). "We suggest that the changes in the style of life must be vigorous, continuous and systematized, with a real reinforcing by part of all the organisms related to the health education for all population (federal and private social organisms). It is the most important way to confront and prevent this pandemic of chronic diseases". In this new edition the authors amplifies the information and importance on the matter. The preventive cardiology must contribute in multidisciplinary entailment. Based mainly on national data and the international scientific publications, we developed our own system of classification and risk stratification for the carrying people with hypertension, Called HTM (Arterial Hypertension in Mexico) index. Its principal of purpose this index is to keep in mind that the current approach of hypertension must be always multidisciplinary. The institutional committee of experts reviewed with rigorous methodology under the principles of the evidence-based medicine, both, national and international medical literature, with the purpose of adapting the concepts and guidelines for a better control and treatment of hypertension in Mexico. This work group recognizes

  11. Response of the adrenergic system in the cadmium-induced hypertensive rat

    SciTech Connect

    Revis, N.W.; Major, T.C.; Horton, C.Y.

    1983-01-01

    Previous investigators, using an in vitro system, have shown that cadmium inhibits neuronal uptake of norepinephrine (NE). The current studies were performed to determine if the adrenergic system is altered in the cadmium-induced hypertensive rat. The results show that the Fischer and Sprague-Dawley rats develop hypertension, whereas the Wistar normotensive and Wistar hypertensive rats develop hypotension when exposed to 5 ppm of cadmium via drinking water. Results from these studies also show that in the cadmium-induced hypertensive rat, plasma NE is significantly elevated and that plasma clearance of (/sup 3/H)NE is significantly reduced. However, the changes in NE metabolism observed in the hypertensive rats were also observed in hypotensive rats. Furthermore in the Wistar strain, renal artery cadmium levels were significantly higher than observed in the other two strains. The authors suggest that the direction of change in blood following cadmium treatment is associated with both the plasma level of norepinephrine and the arterial level of cadmium.

  12. Sympathetic‐mediated activation versus suppression of the immune system: consequences for hypertension

    PubMed Central

    Case, Adam J.

    2016-01-01

    Abstract It is generally well‐accepted that the immune system is a significant contributor in the pathogenesis of hypertension. Specifically, activated and pro‐inflammatory T‐lymphocytes located primarily in the vasculature and kidneys appear to have a causal role in exacerbating elevated blood pressure. It has been proposed that increased sympathetic nerve activity and noradrenaline outflow associated with hypertension may be primary contributors to the initial activation of the immune system early in the disease progression. However, it has been repeatedly demonstrated in many different human and experimental diseases that sympathoexcitation is immunosuppressive in nature. Moreover, human hypertensive patients have demonstrated increased susceptibility to secondary immune insults like infections. Thus, it is plausible, and perhaps even likely, that in diseases like hypertension, specific immune cells are activated by increased noradrenaline, while others are in fact suppressed. We propose a model in which this differential regulation is based upon activation status of the immune cell as well as the resident organ. With this, the concept of global immunosuppression is obfuscated as a viable target for hypertension treatment, and we put forth the concept of focused organ‐specific immunotherapy as an alternative option. PMID:26830047

  13. Aging in blood vessels. Medicinal agents FOR systemic arterial hypertension in the elderly.

    PubMed

    Rubio-Ruiz, María Esther; Pérez-Torres, Israel; Soto, María Elena; Pastelín, Gustavo; Guarner-Lans, Verónica

    2014-11-01

    Aging impairs blood vessel function and leads to cardiovascular disease. The mechanisms underlying the age-related endothelial, smooth muscle and extracellular matrix vascular dysfunction are discussed. Vascular dysfunction is caused by: (1) Oxidative stress enhancement. (2) Reduction of nitric oxide (NO) bioavailability, by diminished NO synthesis and/or augmented NO scavenging. (3) Production of vasoconstrictor/vasodilator factor imbalances. (4) Low-grade pro-inflammatory environment. (5) Impaired angiogenesis. (6) Endothelial cell senescence. The aging process in vascular smooth muscle is characterized by: (1) Altered replicating potential. (2) Change in cellular phenotype. (3) Changes in responsiveness to contracting and relaxing mediators. (4) Changes in intracellular signaling functions. Systemic arterial hypertension is an age-dependent disorder, and almost half of the elderly human population is hypertensive. The influence of hypertension on the aging cardiovascular system has been studied in models of hypertensive rats. Treatment for hypertension is recommended in the elderly. Lifestyle modifications, natural compounds and hormone therapies are useful for initial stages and as supporting treatment with medication but evidence from clinical trials in this population is needed. Since all antihypertensive agents can lower blood pressure in the elderly, therapy should be based on its potential side effects and drug interactions.

  14. Renal Denervation Improves the Baroreflex and GABA System in Chronic Kidney Disease-induced Hypertension

    PubMed Central

    Chen, Hsin-Hung; Cheng, Pei-Wen; Ho, Wen-Yu; Lu, Pei-Jung; Lai, Chi-Cheng; Tseng, Yang-Ming; Fang, Hua-Chang; Sun, Gwo-Ching; Hsiao, Michael; Liu, Chun-Peng; Tseng, Ching-Jiunn

    2016-01-01

    Hypertensive rats with chronic kidney disease (CKD) exhibit enhanced gamma-aminobutyric acid (GABA)B receptor function and regulation within the nucleus tractus solitarii (NTS). For CKD with hypertension, renal denervation (RD) interrupts the afferent renal sympathetic nerves, which are connecting to the NTS. The objective of the present study was to investigate how RD improves CKD-induced hypertension. Rats underwent 5/6 nephrectomy for 8 weeks, which induced CKD and hypertension. RD was induced by applying phenol to surround the renal artery in CKD. RD improved blood pressure (BP) by lowering sympathetic nerve activity and markedly restored the baroreflex response in CKD. The GABAB receptor expression was increased in the NTS of CKD; moreover, the central GABA levels were reduced in the cerebrospinal fluid, and the peripheral GABA levels were increased in the serum. RD restored the glutamic acid decarboxylase activity in the NTS in CKD, similar to the effect observed for central treatment with baclofen, and the systemic administration of gabapentin reduced BP. RD slightly improved renal function and cardiac load in CKD. RD may improve CKD-induced hypertension by modulating the baroreflex response, improving GABA system dysfunction and preventing the development and reducing the severity of cardiorenal syndrome type 4 in CKD rats. PMID:27917928

  15. [Considerations about mechanisms of acupuncture therapy for improving hypertension by regulating immune system].

    PubMed

    Yu, Zheng; Wu, Qiao-Feng; Liang, Fan-Rong

    2014-08-01

    Essential hypertension (EH) is a very common clinical disorder affecting the patient's health. Accumulating evidence indicates that immunological factors play an important role in the pathogenesis of hypertension. In the present paper, the authors introduce 1) progress of researches on the pathogenesis of hypertension from cellular immune and body fluid immune (multiple immuno-humoral factors); 2) effects of acupuncture intervention on natural killer cell activity, exercise-induced immunosuppression, circulating inflammatory factor levels and balance of cytokines; 3) blood-pressure reduction effect of acupuncture intervention by lowering circulating TNF-alpha, IL-6, matrix metalloproteinases-9, angiotensin convertase and endothelin levels, and up-regulating serum opioid peptide content, etc. to decrease inflammatory injury of the cardiovascular system. Many researches have demonstrated that acupuncture may have a positive role in improving EH in clinical practice, which may be associated with its regulative effect on immune system, but its mechanism has not been fully elucidated.

  16. [Systemic immunological response in children with chronic gingivitis and gastro-intestinal pathology].

    PubMed

    Romanenko, E G

    2014-01-01

    Study of the immune system mechanisms in chronic catarrhal gingivitis in children with gastrointestinal pathology was performed in 102 children (49 with chronic gastritis and duodenitis and 53 with no signs of gastrointestinal pathology). Forty-eight children with healthy periodontium constituted control group. Generalized chronic catarrhal gingivitis in children with gastroduodenal pathology is characterized by intense humoral response by simultaneous T-cell immunity suppression. Detection of high serum titers of circulating immune complexes in patients with chronic catarrhal gingivitis suggests a role of immune response in the pathogenesis of periodontal disease increases with concomitant diseases of the upper gastrointestinal tract.

  17. Responsiveness of the renin-aldosterone system during exercise in young patients with essential hypertension.

    PubMed

    Pedersen, E B; Kornerup, H J; Larsen, J S

    1981-10-01

    The effect of exercise of gradually increased intensity, i.e. 75 W for 20 min followed by 100 W for 20 min, on plasma renin concentration (PRC) and plasma aldosterone concentration (PAC) was studied in young patients with essential hypertension and normotensive control subjects. During exercise without previous sodium loading PRC and PAC increased to the same degree in both hypertensives and normotensives during light exercise; PRC increased further significantly in the normotensives (63 to 72 microIU/ml (medians), P less than 0.01) but not in the hypertensives (46 to 51 microIU/ml) during heavy exercise. PRC and PAC were significantly correlated during both 75 W (rho = 0.633, P less than 0.05) and 100 W (rho = 0.635, P less than 0.05) exercise in the normotensives, but not in the hypertensives. During exercise after loading with 500 ml sodium chloride (0.85 mol/l) PRC and PAC increased in both hypertensives (28 to 42 microIU/ml, P less than 0.01; 0.11 to 0.53 nmol/l, P less than 0.01) and normotensives (22 to 33 microIU/ml, P less than 0.02; 0.12 to 0.34 nmol/l, P less than 0.01), although to a considerably lower degree than without previous loading. PRC and PAC were, however, significantly higher in the hypertensive than in the normotensive group after exercise. It is suggested that the responsiveness of the renin-aldosterone system is abnormal during exercise in young patients with mild essential hypertension, both without and with previous intravenous sodium loading.

  18. [The influence of carbon dioxide baths differing in the total mineralization levels on the functional state of the cardiovascular system of the patients presenting with hypertensive disease associated with coronary heart disease].

    PubMed

    L'vova, N V; Tupitsyna, Iu Iu; Badalov, N G; Krasnikov, V E; Lebedeva, O D

    2013-01-01

    The results of the study on the influence of carbon dioxide baths differing in the total mineralization levels on the clinical course of hypertensive disease associated with coronary heart disease and on various functional systems of the body. The data obtained provide an insight into the role of salt concentrations (10 and 20 g/l) in carbon dioxide bath water (1.2 g/l) applied for the traditional treatment of the patients with hypertensive disease associated with concomitant coronary heart disease and musculoskeletal pathology. Highly mineralized bath water has a greater influence on the functional state of the cardiovascular system by causing a more pronounced decrease in peripheral vascular resistance and hypotensive effect. Baths with a salt concentration of 20 g/l markedly reduced pain and had anti-inflammatory effect in the patients with pathology of support and locomotor organs.

  19. Transcatheter therapy for aortic coarctation with severe systemic hypertension during pregnancy.

    PubMed

    Assaidi, Anass; Sbragia, Pascal; Fraisse, Alain

    2013-10-01

    Aortic coarctation is an unusual cause of hypertension during pregnancy and its management is not clarified. We report transcatheter balloon dilatation and stenting for native aortic coarctation in a 22-year-old pregnant woman with severe and uncontrolled systemic hypertension. Arterial blood pressure could be successfully controlled with medical treatment during the rest of the pregnancy and the patient underwent uneventful delivery. No adverse events or recoarctation was observed during 24 months clinical follow-up. In conclusion, native aortic coarctation can be successfully treated during pregnancy with transcatheter therapy. More experience is needed to confirm the safety and efficacy of such management.

  20. The role of renin-angiotensin aldosterone system related micro-ribonucleic acids in hypertension

    PubMed Central

    Wang, Hui-Bo; Yang, Jun

    2015-01-01

    Micro-ribonucleic acids (miRNAs) are small (21-25 nucleotide) single-stranded, evolutionarily conserved non-protein-coding RNAs, which control diverse cellular functions by interacting with the 3’ untranslated region of specific target messenger RNAs at the post-transcriptional level. Research shows that an aberrant expression profile of miRNAs has been linked to a series of diseases, including hypertension. In the past few decades, it has been demonstrated that excessive activation of the renin-angiotensin aldosterone system (RAAS) involves in the pathogenesis of hypertension. This article reviews the latest insights in the identification of RAAS-correlative miRNAs and the potential mechanisms for their roles in hypertension. PMID:26446323

  1. Would Virchow be a systems biologist? A discourse on the philosophy of science with implications for pathological research.

    PubMed

    Stenzinger, Albrecht; Klauschen, Frederick; Wittschieber, Daniel; Weichert, Wilko; Denkert, Carsten; Dietel, Manfred; Roller, Claudio

    2010-06-01

    Research in pathology spans from merely descriptive work to functional studies, "-omics" approaches and, more recently, systems biology. The work presented here aims at placing pathological research into an epistemological context. Aided by Rudolf Virchow, we give an overview on the philosophy of science including the Wiener Kreis, Popper, Kuhn, Fleck and Rheinberger and demonstrate their implications for routine diagnostics and science in pathology. A focus is on the fields of "-omics" and systems pathology.

  2. The endocannabinoid system in normal and pathological brain ageing.

    PubMed

    Bilkei-Gorzo, Andras

    2012-12-05

    The role of endocannabinoids as inhibitory retrograde transmitters is now widely known and intensively studied. However, endocannabinoids also influence neuronal activity by exerting neuroprotective effects and regulating glial responses. This review centres around this less-studied area, focusing on the cellular and molecular mechanisms underlying the protective effect of the cannabinoid system in brain ageing. The progression of ageing is largely determined by the balance between detrimental, pro-ageing, largely stochastic processes, and the activity of the homeostatic defence system. Experimental evidence suggests that the cannabinoid system is part of the latter system. Cannabinoids as regulators of mitochondrial activity, as anti-oxidants and as modulators of clearance processes protect neurons on the molecular level. On the cellular level, the cannabinoid system regulates the expression of brain-derived neurotrophic factor and neurogenesis. Neuroinflammatory processes contributing to the progression of normal brain ageing and to the pathogenesis of neurodegenerative diseases are suppressed by cannabinoids, suggesting that they may also influence the ageing process on the system level. In good agreement with the hypothesized beneficial role of cannabinoid system activity against brain ageing, it was shown that animals lacking CB1 receptors show early onset of learning deficits associated with age-related histological and molecular changes. In preclinical models of neurodegenerative disorders, cannabinoids show beneficial effects, but the clinical evidence regarding their efficacy as therapeutic tools is either inconclusive or still missing.

  3. Reactive oxygen species and the central nervous system in salt-sensitive hypertension: possible relationship with obesity-induced hypertension.

    PubMed

    Ando, Katsuyuki; Fujita, Megumi

    2012-01-01

    1. There are multiple and complex mechanisms of salt-induced hypertension; however, central sympathoexcitation plays an important role. In addition, the production of reactive oxygen species (ROS) is increased in salt-sensitive hypertensive humans and animals. Thus, we hypothesized that brain ROS overproduction may increase blood pressure (BP) by central sympathostimulation. 2. Recently, we demonstrated that ROS levels were elevated in the hypothalamus of salt-sensitive hypertensive animals. Moreover, intracerebroventricular anti-oxidants suppressed BP and renal sympathetic nerve activity more in salt-sensitive than non-salt-sensitive hypertensive rats. Thus, brain ROS overproduction increased BP through central sympathoexcitation in salt-sensitive hypertension. 3. Salt sensitivity of BP is enhanced in obesity and metabolic syndrome. Interestingly, it is also suggested that, in obesity-induced hypertension models, increases in BP are caused by brain ROS-induced central sympathoexcitation. 4. Recent studies suggest that increased ROS production in the brain and central sympathoexcitation may share a common pathway that increases BP in both salt- and obesity-induced hypertension.

  4. Portal hypertension.

    PubMed

    Garcia-Tsao, Guadalupe

    2002-05-01

    Portal hypertension is the main complication of cirrhosis and is responsible for its most common complications: variceal hemorrhage, ascites, and portosystemic encephalopathy. Portal hypertension is the result of increased intrahepatic resistance and increased portal venous inflow. Vasodilatation (splanchnic and systemic) and the hyperdynamic circulation are hemodynamic abnormalities typical of cirrhosis and portal hypertension. Gastroesophageal varices result almost solely from portal hypertension, although the hyperdynamic circulation contributes to variceal growth and hemorrhage. Ascites results from sinusoidal hypertension and sodium retention, which is in turn secondary to vasodilatation and activation of neurohumoral systems. Hepatic hydrothorax results from the passage of ascites across the diaphragm and into the pleural space. The hepatorenal syndrome represents the result of extreme vasodilatation with an extreme decrease in effective blood volume that leads to maximal activation of vasoconstrictive systems, renal vasoconstriction, and renal failure. Spontaneous bacterial peritonitis is a potentially lethal infection of ascites that occurs in the absence of a local source of infection. Portosystemic encephalopathy is a consequence of both portal hypertension (shunting of blood through portosystemic collaterals) and hepatic insufficiency resulting in the accumulation of neurotoxins in the brain.

  5. Effect of postural stimulation on systemic hemodynamics and sympathetic nervous activity in systemic hypertension.

    PubMed

    Izzo, J L; Sander, E; Larrabee, P S

    1990-02-01

    The contributions of the carotid sinus and cardiopulmonary baroreflexes to the interindividual variation in sympathetic nervous system activation caused by postural adaptation were indirectly assessed in 68 mild hypertensive subjects. Supine and upright plasma norepinephrine (NE), blood pressure (cuff) and cardiac output (acetylene rebreathing) were measured. Mean arterial pressure (MAP), carotid sinus pressure, stroke volume and systemic vascular resistance were calculated. Stroke volume was assumed to be proportional to the degree of stretch of cardiac mechanoreceptors, carotid sinus MAP was assumed to be proportional to carotid sinus stretch and plasma NE to reflect sympathetic nervous activity. Plasma NE correlated inversely with stroke volume (r = -0.62, p less than 10(-14] and estimated carotid sinus MAP (r = -0.33, p less than 0.0002) and positively with systemic vascular resistance (r = 0.59, p less than 10(-10]. Holding systemic vascular resistance constant by partial regression, the inverse relation between plasma NE and stroke volume remained (partial r = -0.36, p less than 0.02). Multiple linear regression yielded the equation: plasma NE (pg/ml) = 720 + 4.3 age - 5.1 stroke volume (ml) - 1.0 carotid sinus MAP (mm Hg). Substituting mean supine and upright values for stroke volume and carotid sinus MAP in this equation, it can be roughly estimated that changes in stroke volume account for as much as 60% of the postural variation in plasma NE in hypertensives, whereas only 15% of this variation is caused by changes in carotid sinus pressure. These findings suggest that cardiopulmonary baroreflexes are primary activators of the sympathetic nervous system during postural adaptation.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Portal-systemic encephalopathy in two patients without liver cirrhosis and portal hypertension.

    PubMed

    K C, Sudhamshu; Matsutani, Shoichi; Maruyama, Hitoshi; Fukamachi, Tadahiro; Nomoto, Hiromasa; Akiike, Taro; Ebara, Masaaki; Saisho, Hiromitsu

    2002-06-01

    The portal-systemic venous shunt is uncommon in patients without portal hypertension. We present two cases of portal-systemic encephalopathy due to extrahepatic shunt without liver cirrhosis and portal hypertension. Two women in their seventies were admitted to our hospital because of recurrent episodes of altered sensorium, drowsiness, slurred speech, disorientation, asterexis and high blood ammonia levels. There was no history of abdominal surgery or abdominal trauma. Clinical examination revealed no signs of portal hypertension or stigmata of chronic liver diseases. Brain CT and MRI scanning were unremarkable except for a high intensity signal in the basal ganglia on T1 weighted MRI images. Laboratory tests were almost normal except for the hyperammonemia occurring on several occasions. There was no evidence of liver cirrhosis by imaging. However, color Doppler showed an extra-hepatic shunt in both patients and pulsed Doppler showed decreased velocity and volume of the portal venous flow. These sonographic findings were confirmed during percutaneous transhepatic portography (PTP). Portal pressures measured during PTP were 9 and 11 mmHg. Needle biopsy ruled out idiopathic portal hypertension and liver cirrhosis. The diagnosis was portal systemic encephalopathy due to extra-hepatic portosystemic venous shunting. Both patients were treated by embolization of the shunting vessel with metallic coils.

  7. Ultrasound of the digital flexor system: Normal and pathological findings☆

    PubMed Central

    Bianchi, S.; Martinoli, C.; de Gautard, R.; Gaignot, C.

    2007-01-01

    Recent improvements in ultrasound (US) software and hardware have markedly increased the role of this imaging modality in the evaluation of the musculoskeletal system. US is currently one of the main imaging tools used to diagnose and assess most tendon, muscle, and ligament disorders. Compared with magnetic resonance imaging, US is much less expensive; it has no contraindications and is also widely available. Diseases affecting the digital flexor system (DFS) require early diagnosis if treatment is expected to limit functional impairment of the hand. US scans performed with high-resolution, broad-band transducers allows superb visualization of the flexor tendons of the hand and the annular digital pulleys. In addition, dynamic US can be used to assess movement of the tendon within the pulleys during passive or active joint movements. This article examines the anatomy and US appearance of the normal DFS and reviews the US findings associated with the most common disorders affecting it. PMID:23396583

  8. Dual-Use Telemedicine Support System for Pathology.

    DTIC Science & Technology

    1998-12-01

    revolutionary tool for pathologists employing digital technology which eliminates the inherent limitations of traditional microscopy . " Lensless microscopy ...telepathology, lensless microscopy , imaging system 4 0m .. . Unclassified Unclassified Unclassified Limited DTIC QUALITy INSPETD 4 Grant No. DMIT7-94-J-4500...tower. Both integrate the patented " lensless microscopy " with lensed full-color imaging (U.S. Patent 4,777,525). During the development of the TSS, a

  9. Novel Therapeutic Targets for Phosphodiesterase 5 Inhibitors: current state-of-the-art on systemic arterial hypertension and atherosclerosis.

    PubMed

    Vasquez, Elisardo C; Gava, Agata L; Graceli, Jones B; Balarini, Camille M; Campagnaro, Bianca P; Pereira, Thiago Melo C; Meyrelles, Silvana S

    2016-01-01

    The usefulness of selective inhibitors of phosphodiesterase 5 (PDE5) is well known, first for the treatment of male erectile dysfunction and more recently for pulmonary hypertension. The discovery that PDE5 is present in the systemic artery endothelium and smooth muscle cells led investigators to test the extra sexual effects of sildenafil, the first and most investigated PDE5 inhibitor, in diseases affecting the systemic arteries. Cumulative data from experimental and clinical studies have revealed beneficial effects of sildenafil on systemic arterial hypertension and its target organs, such as the heart, kidneys and vasculature. An important effect of sildenafil is reduction of hypertension and improvement of endothelial function in experimental models of hypertension and hypertensive subjects. Interestingly, in angiotensin-dependent hypertension, its beneficial effects on endothelial and kidney dysfunctions seem to at least in part be caused by its ability to decrease the levels of angiotensin II and increase angiotensin 1-7, in addition to improving nitric oxide bioavailability and diminishing reactive oxygen species. Another remarkable finding on the effects of sildenafil comes from studies in apolipoprotein E knockout mice, a model of atherosclerosis that closely resembles human atherosclerotic disease. In this review, we focus on the promising beneficial effects of sildenafil for treating systemic high blood pressure, especially resistant hypertension, and the endothelial dysfunction that is present in hypertension and atherosclerosis.

  10. [The (putative) pathological impact of fibromyalgia on the orofacial system].

    PubMed

    de Baat, C; Gerritsen, A E; de Baat-Ananta, M; de Baat, P

    2016-03-01

    Fibromyalgia is a syndrome without apparent aetiology, characterised by pain, fatigue, memory disorders, mood disorders, and sleep disturbances. The syndrome is considered to be one of the rheumatic diseases. In the general population, the prevalence varies from 2 to 8%, with a women-men ratio of about 2:1. Suspicion of fibromyalgia arises when a patient has pain at multiple locations that cannot be attributed to trauma or inflammation, and when the pain is especially musculoskeletal. Primary management includes explaining the syndrome and offering reassurance. In addition, one can also attempt to increase mobility, avoid overloading, and improve physical condition and the level of activity, and to activate problem-solving skills. Subsequently, behavioural therapy and pharmacotherapy may be considered. The most important manifestations of fibromyalgia in the orofacial and occlusal system seem to be temporomandibular dysfunction, headache, xerostomia, hyposalivation, burning mouth and dysgeusia. However, with respect to the precise relation of fibromyalgia with the orofacial system, much needs to be elucidated.

  11. [Involvement of Syk in pathology of systemic autoimmune disease].

    PubMed

    Iwata, Shigeru; Yamaoka, Kunihiro; Niiro, Hiroaki; Nakano, Kazuhisa; Wang, Sheau-Pey; Saito, Kazuyoshi; Akashi, Koichi; Tanaka, Yoshiya

    2012-01-01

    Biological products have proven its high efficacy on autoimmune disease such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Meanwhile, small molecular drugs have attracted attention over the years because of its availability of oral administration and cost effectiveness. Spleen tyrosine kinase (Syk) is a 72 kDa protein tyrosine kinase widely expressed on cells that are involved in the immune system and inflammation such as B cells, T cells, macrophages and synovial fibroblast. Syk is involved in intracellular signaling of the multi-chain immune receptors, including B cell receptor (BCR), ζchain of T-cell receptor (TCR), FcR and integrins, which contains the immune-receptor tyrosine-based activation motif (ITAM). Recently, Syk inhibitor fostamatinib has exerted potent therapeutic efficacy against autoimmune and allergic diseases such as rheumatoid arthritis (RA), bronchial asthma and thrombocytopenic purpura (ITP). Moreover, Syk blockade prevented the development of skin and kidney lesions in lupus-prone mice, however the mechanism of action is unclear. We have revealed that Syk-mediated BCR-signaling is prerequisite for optimal induction of toll-like receptor (TLR)-9, thereby allowing efficient propagation of CD40- and TLR9- signaling in human B cells. These results indicate that inhibition of Syk have a potential to regulate B-cell mediated inflammatory diseases such as SLE. We here document the in vitro and in vivo effects of a Syk inhibitor for the treatment of autoimmune diseases, mainly in RA and SLE.

  12. Robust Central Nervous System Pathology in Transgenic Mice following Peripheral Injection of α-Synuclein Fibrils.

    PubMed

    Ayers, Jacob I; Brooks, Mieu M; Rutherford, Nicola J; Howard, Jasie K; Sorrentino, Zachary A; Riffe, Cara J; Giasson, Benoit I

    2017-01-15

    Misfolded α-synuclein (αS) is hypothesized to spread throughout the central nervous system (CNS) by neuronal connectivity leading to widespread pathology. Increasing evidence indicates that it also has the potential to invade the CNS via peripheral nerves in a prion-like manner. On the basis of the effectiveness following peripheral routes of prion administration, we extend our previous studies of CNS neuroinvasion in M83 αS transgenic mice following hind limb muscle (intramuscular [i.m.]) injection of αS fibrils by comparing various peripheral sites of inoculations with different αS protein preparations. Following intravenous injection in the tail veins of homozygous M83 transgenic (M83(+/+)) mice, robust αS pathology was observed in the CNS without the development of motor impairments within the time frame examined. Intraperitoneal (i.p.) injections of αS fibrils in hemizygous M83 transgenic (M83(+/-)) mice resulted in CNS αS pathology associated with paralysis. Interestingly, injection with soluble, nonaggregated αS resulted in paralysis and pathology in only a subset of mice, whereas soluble Δ71-82 αS, human βS, and keyhole limpet hemocyanin (KLH) control proteins induced no symptoms or pathology. Intraperitoneal injection of αS fibrils also induced CNS αS pathology in another αS transgenic mouse line (M20), albeit less robustly in these mice. In comparison, i.m. injection of αS fibrils was more efficient in inducing CNS αS pathology in M83 mice than i.p. or tail vein injections. Furthermore, i.m. injection of soluble, nonaggregated αS in M83(+/-) mice also induced paralysis and CNS αS pathology, although less efficiently. These results further demonstrate the prion-like characteristics of αS and reveal its efficiency to invade the CNS via multiple routes of peripheral administration.

  13. The systemic pathology of cerebral malaria in African children.

    PubMed

    Milner, Danny A; Whitten, Richard O; Kamiza, Steve; Carr, Richard; Liomba, George; Dzamalala, Charles; Seydel, Karl B; Molyneux, Malcolm E; Taylor, Terrie E

    2014-01-01

    Pediatric cerebral malaria carries a high mortality rate in sub-Saharan Africa. We present our systematic analysis of the descriptive and quantitative histopathology of all organs sampled from a series of 103 autopsies performed between 1996 and 2010 in Blantyre, Malawi on pediatric cerebral malaria patients and control patients (without coma, or without malaria infection) who were clinically well characterized prior to death. We found brain swelling in all cerebral malaria patients and the majority of controls. The histopathology in patients with sequestration of parasites in the brain demonstrated two patterns: (a) the "classic" appearance (i.e., ring hemorrhages, dense sequestration, and extra-erythrocytic pigment) which was associated with evidence of systemic activation of coagulation and (b) the "sequestration only" appearance associated with shorter duration of illness and higher total burden of parasites in all organs including the spleen. Sequestration of parasites was most intense in the gastrointestinal tract in all parasitemic patients (those with cerebral malarial and those without).

  14. The role of the sympathetic nervous system in obesity-related hypertension.

    PubMed

    da Silva, Alexandre A; do Carmo, Jussara; Dubinion, John; Hall, John E

    2009-06-01

    Obesity is recognized as a major health problem throughout the world. Excess weight is a major cause of increased blood pressure in most patients with essential hypertension and greatly increases the risk for diabetes, cardiovascular diseases, and end-stage renal disease. Although the mechanisms by which obesity raises blood pressure are not completely understood, increased renal sodium reabsorption, impaired pressure natriuresis, and volume expansion appear to play important roles. Several potential mechanisms have been suggested to contribute to altered kidney function and hypertension in obesity, including activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system, as well as physical compression of the kidneys, especially when visceral obesity is present. Activation of the sympathetic nervous system in obesity may be due, in part, to hyperleptinemia and other factors secreted by adipocytes and the gastrointestinal tract, activation of the central nervous system melanocortin pathway, and baroreceptor dysfunction.

  15. Successful Pregnancy Following Assisted Reproduction in Woman With Systemic Lupus Erythematosus and Hypertension: A Case Report.

    PubMed

    de Macedo, José Fernando; de Macedo, Gustavo Capinzaiki; Campos, Luciana Aparecida; Baltatu, Ovidiu Constantin

    2015-09-01

    Patients with systemic lupus erythematosus have a poor prognosis of pregnancy, since it is associated with significant maternal and fetal morbidity, including spontaneous miscarriage, pre-eclampsia, intrauterine growth restriction, fetal death and pre-term delivery. We report a case with successful pregnancy in a patient with systemic lupus erythematosus and hypertension. A 39-year-old nulliparous woman presented with systemic lupus erythematosus with antinuclear and antiphospholipid antibodies, hypertension and recurrent pregnancy loss presented for assisted reproduction. The patient responded well to enoxaparin and prednisone during both assisted reproduction and prenatal treatment. This case report indicates that prescription of immunosuppressant and blood thinners can be safely recommended throughout the whole prenatal period in patients with systemic lupus erythematosus. Enoxaparin and prednisone may be prescribed concurrently during pregnancy.

  16. Sympathetic nervous system in obesity-related hypertension: mechanisms and clinical implications.

    PubMed

    Kalil, Graziela Z; Haynes, William G

    2012-01-01

    Obesity markedly increases the risk of hypertension and cardiovascular disease, which may be related to activation of the sympathetic nervous system (SNS). Sympathetic overactivity directly and indirectly contributes to blood pressure (BP) elevation in obesity, including stimulation of the renin-angiotensin-aldosterone system (RAAS). The adipocyte-derived peptide leptin suppresses appetite, increases thermogenesis, but also raises SNS activity and BP. Obese individuals exhibit hyperleptinemia but are resistant to its appetite-suppressing actions. Interestingly, animal models of obesity exhibit preserved sympathoexcitatory and pressor actions of leptin, despite resistance to its anorexic and metabolic actions, suggesting selective leptin resistance. Disturbance of intracellular signaling at specific hypothalamic neural networks appears to underlie selective leptin resistance. Delineation of these pathways should lead to novel approaches to treatment. In the meantime, treatment of obesity-hypertension has relied on antihypertensive drugs. Although sympathetic blockade is mechanistically attractive in obesity-hypertension, in practice its effects are disappointing because of adverse metabolic effects and inferior outcomes. On the basis of subgroup analyses of obese patients in large randomized clinical trials, drugs such as diuretics and RAAS blockers appear superior in preventing cardiovascular events in obesity--hypertension. An underused alternative approach to obesity-hypertension is induction of weight loss, which reduces circulating leptin and insulin, partially reverses resistance to these hormones, decreases sympathetic activation and improves BP and other risk factors. Though weight loss induced by lifestyle is often modest and transient, carefully selected pharmacological weight loss therapies can produce substantial and sustained antihypertensive effects additive to lifestyle interventions.

  17. Electrocardiogram-based scoring system for predicting secondary pulmonary hypertension: A cross-sectional study

    PubMed Central

    Palamaner Subash Shantha, Ghanshyam; Patel, Nimesh Kirit; Boruah, Pranjal; Nanavaty, Sukrut; Chandran, Sindu; Sethi, Arjinder; Sheth, Jignesh

    2014-01-01

    Objectives In this study, we have developed an electrocardiogram-based scoring system to predict secondary pulmonary hypertension. Design A cross-sectional study. Setting Single tertiary-care hospital in Scranton, Pennsylvania, USA. Participants Five hundred and fifty-two consecutive patients undergoing right heart catheterization between 2006 and 2009. Main outcome measures Surface electrocardiogram was assessed for R-wave in lead V1 ≥ 6mm, R-wave in V6 ≤ 3mm, S-wave in V6 ≥ 3mm, right atrial enlargement, right axis deviation and left atrial enlargement. Pulmonary hypertension was defined as mean pulmonary artery pressure ≥25 mmHg, determined by right heart catheterization. Results A total of 297 (54%) patients in the study cohort had pulmonary hypertension. In total, 332 patients from the study cohort formed the development cohort and the remaining 220 patients formed the validation cohort. In the development cohort, based on log odds ratios of association, RAE, LAE, RAD, R-wave in V1 ≥ 6 mm were assigned scores of 5, 2, 2 and 1, respectively, to form a 10-point scoring system “Scranton PHT (SP) score”. SP scores of 5 points and 7 points in DC showed C-statistic of 0.83 and 0.89, respectively, for discriminating pulmonary hypertension. C-statistic for RAE alone was significantly lower compared to an SP score of 7 (0.83 vs. 0.89, P = 0.021). The reliability of SP score in the validation cohort was acceptable. Conclusion SP score provides a good point-of-care tool to predict pulmonary hypertension in patients with clinical suspicion of it. PMID:25396053

  18. Statins and Renin Angiotensin System Inhibitors Dose-Dependently Protect Hypertensive Patients against Dialysis Risk

    PubMed Central

    Wu, Szu-Yuan

    2016-01-01

    Background Taiwan has the highest renal disease incidence and prevalence in the world. We evaluated the association of statin and renin–angiotensin system inhibitor (RASI) use with dialysis risk in hypertensive patients. Methods Of 248,797 patients who received a hypertension diagnosis in Taiwan during 2001–2012, our cohort contained 110,829 hypertensive patients: 44,764 who used RASIs alone; 7,606 who used statins alone; 27,836 who used both RASIs and statins; and 33,716 who used neither RASIs or statins. We adjusted for the following factors to reduce selection bias by using propensity scores (PSs): age; sex; comorbidities; urbanization level; monthly income; and use of nonstatin lipid-lowering drugs, metformin, aspirin, antihypertensives, diuretics, and beta and calcium channel blockers. The statin and RASI use index dates were considered the hypertension confirmation dates. To examine the dose–response relationship, we categorized only statin or RASI use into four groups in each cohort: <28 (nonusers), 28–90, 91–365, and >365 cumulative defined daily doses (cDDDs). Results In the main model, PS-adjusted hazard ratios (aHRs; 95% confidence intervals [CIs]) for dialysis risk were 0.57 (0.50–0.65), 0.72 (0.53–0.98), and 0.47 (0.41–0.54) in the only RASI, only statin, and RASI + statin users, respectively. RASIs dose-dependently reduced dialysis risk in most subgroups and in the main model. RASI use significantly reduced dialysis risk in most subgroups, regardless of comorbidities or other drug use (P < 0.001). Statins at >365 cDDDs protected hypertensive patients against dialysis risk in the main model (aHR = 0.62, 95% CI: 0.54–0.71), regardless of whether a high cDDD of RASIs, metformin, or aspirin was used. Conclusion Statins and RASIs independently have a significant dose-dependent protective effect against dialysis risk in hypertensive patients. The combination of statins and RASIs can additively protect hypertensive patients against dialysis

  19. Non-Newtonian flow of pathological bile in the biliary system: experimental investigation and CFD simulations

    NASA Astrophysics Data System (ADS)

    Kuchumov, Alex G.; Gilev, Valeriy; Popov, Vitaliy; Samartsev, Vladimir; Gavrilov, Vasiliy

    2014-02-01

    The paper presents an experimental study of pathological human bile taken from the gallbladder and bile ducts. The flow dependences were obtained for different types of bile from patients with the same pathology, but of different age and sex. The parameters of the Casson's and Carreau's equations were found for bile samples. Results on the hysteretic bile behavior at loading-unloading tests are also presented, which proved that the pathologic bile is a non-Newtonian thixotropic liquid. The viscosity of the gallbladder bile was shown to be higher compared to the duct bile. It was found that at higher shear stress the pathological bile behaves like Newtonian fluid, which is explained by reorientation of structural components. Moreover, some pathological bile flow in the biliary system CFD simulations were performed. The velocity and pressure distributions as well as flow rates in the biliary segments during the gallbladder refilling and emptying phases are obtained. The results of CFD simulations can be used for surgeons to assess the patient's condition and choose an adequate treatment.

  20. A pathogenic role of complement in arterial hypertension and hypertensive end organ damage.

    PubMed

    Wenzel, Ulrich O; Bode, Marlies; Köhl, Jörg; Ehmke, Heimo

    2017-03-01

    The self-amplifying cascade of messenger and effector molecules of the complement system serves as a powerful danger-sensing system that protects the host from a hostile microbial environment, while maintaining proper tissue and organ function through effective clearance of altered or dying cells. As an important effector arm of innate immunity, it also plays important roles in the regulation of adaptive immunity. Innate and adaptive immune responses have been identified as crucial players in the pathogenesis of arterial hypertension and hypertensive end organ damage. In line with this view, complement activation may drive the pathology of hypertension and hypertensive injury through its impact on innate and adaptive immune responses. It is well known that complement activation can cause tissue inflammation and injury and complement-inhibitory drugs are effective treatments for several inflammatory diseases. In addition to these proinflammatory properties, complement cleavage fragments of C3 and C5 can exert anti-inflammatory effects that dampen the inflammatory response to injury. Recent experimental data strongly support a role for complement in arterial hypertension. The remarkably similar clinical and histopathological features of malignant nephrosclerosis and atypical hemolytic uremic syndrome, which is driven by complement activation, suggest a role for complement also in the development of malignant nephrosclerosis. Herein, we will review canonical and noncanonical pathways of complement activation as the framework to understand the multiple roles of complement in arterial hypertension and hypertensive end organ damage.

  1. Improved hypertension control using a surveillance system in a neighborhood health center.

    PubMed

    Smith, D A; Schnall, P L

    1980-07-01

    The Dr. Martin Luther King, Jr., Health Center has developed a simple inexpensive McBee Card Surveillance System for following approximately 2,000 registered patients with hypertension. The system has been in use for the past two years by three health teams. On a quarterly basis teams and physicians are given reports on the percentage of their hypertensive patients with controlled blood pressure (bp) (bp less than or equal to 140/90 for patients younger than 50; bp less than or equal to 160/95 for 50 or older). In addition, patients not seen in the past 4 months are identified for follow-up by family health workers. During the 2-year period that the system has been in operation, the three teams have increased their percentage of patients under control by 50%. Of 929 patients with hypertension, 411 were controlled at the inception of the study and 617 were controlled 2 years later. Such a simple surveillance and self-evaluaton system is readily applicable to all ambulatory care settings.

  2. [Pulmonary involvement in systemic sclerosis. Alveolitis, fibrosis and pulmonar arterial hypertension].

    PubMed

    Navarro, Carmen

    2006-11-01

    Pulmonary involvement in systemic sclerosis. Alveolitis, fibrosis and pulmonar arterial hypertension Lung disease is present in most of the patients with systemic sclerosis and is now the most important cause of mortality. Interstitial lung disease and pulmonary hypertension are, so far, the main disorders found and both are difficult to detect at the earliest stages. However, diagnostic tools such as immunological test, lung function test, high resolution CT, bronchoalveolar lavage, echocardiography, right-side cardiac catheterization, or lung biopsy are necessary to accurately evaluate the clinical status and allow to improve the management organ-specific ad hoc. Progress in immunological and vascular therapies as well as other emergence drugs offer new expectations to scleroderma patients.

  3. Hypertension and Angiotensin System Inhibitors in Patients with Metastatic Renal Cell Carcinoma

    PubMed Central

    Derosa, Lisa; Izzedine, Hassane; Albiges, Laurence; Escudier, Bernard

    2016-01-01

    Arterial hypertension (HTN) is a class effect of anti-vascular endothelial growth factor (VEGF) therapies, including the monoclonal antibody bevacizumab. Data are conflicting regarding the role of the renin-angiotensin system on angiogenesis and recent data suggest that the use of angiotensin system inhibitors (ASIs; angiotensin receptor blockers or angiotensin-converting enzyme inhibitors) is associated with improved survival in metastatic renal cell carcinoma (mRCC), particularly when used with VEGF targeted therapies. The aim of this review is to discuss the available treatment options for mRCC and associated incidence of hypertension as well as summarize the known data about ASIs use and mRCC. Additionally, given that the optimal management of HTN remains unclear, we will focus on prevention strategies and propose potential therapeutic approaches. PMID:27994768

  4. Pulmonary Vascular Impedance in Chronic Pulmonary Hypertension.

    DTIC Science & Technology

    PULMONARY HYPERTENSION , *PULMONARY BLOOD CIRCULATION, BLOOD CIRCULATION, LUNG, PATHOLOGY, VASCULAR DISEASES, ARTERIES, OBSTRUCTION(PHYSIOLOGY...EMBOLISM, HISTOLOGY, DOGS, LABORATORY ANIMALS, BLOOD PRESSURE , EXPERIMENTAL DATA, PHYSIOLOGY.

  5. Processing system of jaws tomograms for pathology identification and surgical guide modeling

    SciTech Connect

    Putrik, M. B. Ivanov, V. Yu.; Lavrentyeva, Yu. E.

    2015-11-17

    The aim of the study is to create an image processing system, which allows dentists to find pathological resorption and to build surgical guide surface automatically. X-rays images of jaws from cone beam tomography or spiral computed tomography are the initial data for processing. One patient’s examination always includes up to 600 images (or tomograms), that’s why the development of processing system for fast automation search of pathologies is necessary. X-rays images can be useful not for only illness diagnostic but for treatment planning too. We have studied the case of dental implantation – for successful surgical manipulations surgical guides are used. We have created a processing system that automatically builds jaw and teeth boundaries on the x-ray image. After this step, obtained teeth boundaries used for surgical guide surface modeling and jaw boundaries limit the area for further pathologies search. Criterion for the presence of pathological resorption zones inside the limited area is based on statistical investigation. After described actions, it is possible to manufacture surgical guide using 3D printer and apply it in surgical operation.

  6. Processing system of jaws tomograms for pathology identification and surgical guide modeling

    NASA Astrophysics Data System (ADS)

    Putrik, M. B.; Lavrentyeva, Yu. E.; Ivanov, V. Yu.

    2015-11-01

    The aim of the study is to create an image processing system, which allows dentists to find pathological resorption and to build surgical guide surface automatically. X-rays images of jaws from cone beam tomography or spiral computed tomography are the initial data for processing. One patient's examination always includes up to 600 images (or tomograms), that's why the development of processing system for fast automation search of pathologies is necessary. X-rays images can be useful not for only illness diagnostic but for treatment planning too. We have studied the case of dental implantation - for successful surgical manipulations surgical guides are used. We have created a processing system that automatically builds jaw and teeth boundaries on the x-ray image. After this step, obtained teeth boundaries used for surgical guide surface modeling and jaw boundaries limit the area for further pathologies search. Criterion for the presence of pathological resorption zones inside the limited area is based on statistical investigation. After described actions, it is possible to manufacture surgical guide using 3D printer and apply it in surgical operation.

  7. [Systemic arterial hypertension in México. A consensus to mitigate its comorbidities].

    PubMed

    Pérez-Rodríguez, Gilberto

    2016-01-01

    Given that systemic arterial hypertension (SAH) is the most common illness presented by the adults who come to primary care in México, in this supplement a group of cardiologists, as well as other specialists, from the Instituto Mexicano del Seguro Social (IMSS) offer a systematic review, a critical analysis, and a national consensus of guidelines as a frame of reference to the daily clinical practice in order to mitigate SAH in México.

  8. Intussusception Presenting with Malignant Hypertension and Lethargy

    PubMed Central

    de Vries, Andra; Ashtiani, Nilou; Ahmadi, Nazanin; Bakx, Roel; de Vaate, Annelies Walrave-bij; Bökenkamp, Arend

    2013-01-01

    The most common cause of malignant hypertension in children is renal or renovascular pathology. The combination with lethargy suggests a diagnosis of hypertensive crisis with hypertensive encephalopathy. Here, we present a case of severe hypertension with lethargy as the sole presenting symptoms of ileocecal intussusception. Both normalized following surgical repositioning. We conclude that malignant hypertension and lethargy can be presenting symptoms of intussusception. PMID:23914204

  9. Systemic delivery of β-blockers via transdermal route for hypertension

    PubMed Central

    Ahad, Abdul; Al-Jenoobi, Fahad I.; Al-Mohizea, Abdullah M.; Akhtar, Naseem; Raish, Mohammad; Aqil, Mohd.

    2014-01-01

    Hypertension is the most common cardiovascular disease worldwide. Moreover, management of hypertension requires long-term treatment that may result in poor patient compliance with conventional dosage forms due to greater frequency of drug administration. Although there is availability of a plethora of therapeutically effective antihypertensive molecules, inadequate patient welfare is observed; this arguably presents an opportunity to deliver antihypertensive agents through a different route. Ever since the transdermal drug delivery came into existence, it has offered great advantages including non-invasiveness, prolonged therapeutic effect, reduced side effects, improved bioavailability, better patient compliance and easy termination of drug therapy. Attempts were made to develop the transdermal therapeutic system for various antihypertensive agents, including β-blockers, an important antihypertensive class. β-blockers are potent, highly effective in the management of hypertension and other heart ailments by blocking the effects of normal amounts of adrenaline in the heart and blood vessels. The shortcomings associated with β-blockers such as more frequent dose administration, extensive first pass metabolism and variable bioavailability, make them an ideal candidate for transdermal therapeutic systems. The present article gives a brief view of different β-blockers formulated as transdermal therapeutic system in detail to enhance the bioavailability as well as to improve patient compliance. Constant improvement in this field holds promise for the long-term success in technologically advanced transdermal dosage forms being commercialized sooner rather than later. PMID:26702253

  10. Systemic delivery of β-blockers via transdermal route for hypertension.

    PubMed

    Ahad, Abdul; Al-Jenoobi, Fahad I; Al-Mohizea, Abdullah M; Akhtar, Naseem; Raish, Mohammad; Aqil, Mohd

    2015-11-01

    Hypertension is the most common cardiovascular disease worldwide. Moreover, management of hypertension requires long-term treatment that may result in poor patient compliance with conventional dosage forms due to greater frequency of drug administration. Although there is availability of a plethora of therapeutically effective antihypertensive molecules, inadequate patient welfare is observed; this arguably presents an opportunity to deliver antihypertensive agents through a different route. Ever since the transdermal drug delivery came into existence, it has offered great advantages including non-invasiveness, prolonged therapeutic effect, reduced side effects, improved bioavailability, better patient compliance and easy termination of drug therapy. Attempts were made to develop the transdermal therapeutic system for various antihypertensive agents, including β-blockers, an important antihypertensive class. β-blockers are potent, highly effective in the management of hypertension and other heart ailments by blocking the effects of normal amounts of adrenaline in the heart and blood vessels. The shortcomings associated with β-blockers such as more frequent dose administration, extensive first pass metabolism and variable bioavailability, make them an ideal candidate for transdermal therapeutic systems. The present article gives a brief view of different β-blockers formulated as transdermal therapeutic system in detail to enhance the bioavailability as well as to improve patient compliance. Constant improvement in this field holds promise for the long-term success in technologically advanced transdermal dosage forms being commercialized sooner rather than later.

  11. Systemic mastocytosis: A rare cause of non-cirrhotic portal hypertension

    PubMed Central

    Martins, Cláudio; Teixeira, Cristina; Ribeiro, Suzane; Trabulo, Daniel; Cardoso, Cláudia; Mangualde, João; Freire, Ricardo; Gamito, Élia; Alves, Ana Luísa; Cremers, Isabelle; Alves, Cecília; Neves, Anabela; Oliveira, Ana Paula

    2016-01-01

    Mastocytosis is a clonal neoplastic disorder of the mast cells (MC) that can be limited to the skin (cutaneous mastocytosis) or involve one or more extracutaneous organs (systemic mastocytosis). The clinical manifestations of mastocytosis are heterogeneous ranging from indolent disease with a long-term survival to a highly aggressive neoplasm with survival of about 6 mo. Although liver involvement in aggressive systemic mastocytosis (ASM) is relatively common, the development of portal hypertension with or without cirrhosis is rare. We report a case of ASM without skin involvement in a 72-year-old caucasian male who presented with non-cirrhotic portal hypertension based on clinical, analytical, imagiological and endoscopic findings. Given the hematological picture, the correct diagnosis was established based on ancillary tests for MC using bone marrow aspirates and biopsy. Extensive involvement of the liver and gastrointestinal tract was histologically documented. The disease progressed rapidly and severe pancytopenia and recurrent upper gastrointestinal bleeding became the dominant problem. This case illustrates the challenge in establishing a diagnosis of ASM especially when the clinical picture is atypical and without skin involvement. Gastroenterologists should consider infiltrative disease, particularly systemic mastocytosis, as a differential diagnosis in a clinical case of portal hypertension of unknown etiology. PMID:27605890

  12. Critical comparison of 31 commercially available digital slide systems in pathology.

    PubMed

    Rojo, Marcial García; García, Gloria Bueno; Mateos, Carlos Peces; García, Jesús González; Vicente, Manuel Carbajo

    2006-10-01

    Advances in new technologies for complete slide digitization in pathology have allowed the appearance of a wide spectrum of technologic solutions for whole-slide scanning, which have been classified into motorized microscopes and scanners. This article describes technical aspects of 31 different digital microscopy systems. The most relevant characteristics of the scanning devices are described, including the cameras used, the speed of digitization, and the image quality. Other aspects, such as the file format, the compression techniques, and the solutions for visualization of digital slides, (including diagnosis-aided tools) are also considered. Most of the systems evaluated allow a high-resolution digitization of the whole slide within about 1 hour using a x40 objective. The image quality of the current virtual microscopy systems is suitable for clinical, educational, and research purposes. The efficient use of digital microscopy by means of image analysis systems can offer important benefits to pathology departments.

  13. Neuroinflammation and oxidative stress in rostral ventrolateral medulla contribute to neurogenic hypertension induced by systemic inflammation

    PubMed Central

    2012-01-01

    Background In addition to systemic inflammation, neuroinflammation in the brain, which enhances sympathetic drive, plays a significant role in cardiovascular diseases, including hypertension. Oxidative stress in rostral ventrolateral medulla (RVLM) that augments sympathetic outflow to blood vessels is involved in neural mechanism of hypertension. We investigated whether neuroinflammation and oxidative stress in RVLM contribute to hypertension following chronic systemic inflammation. Methods In normotensive Sprague-Dawley rats, systemic inflammation was induced by infusion of Escherichia coli lipopolysaccharide (LPS) into the peritoneal cavity via an osmotic minipump. Systemic arterial pressure and heart rate were measured under conscious conditions by the non-invasive tail-cuff method. The level of the inflammatory markers in plasma or RVLM was analyzed by ELISA. Protein expression was evaluated by Western blot or immunohistochemistry. Tissue level of superoxide anion (O2·-) in RVLM was determined using the oxidation-sensitive fluorescent probe dihydroethidium. Pharmacological agents were delivered either via infusion into the cisterna magna with an osmotic minipump or microinjection bilaterally into RVLM. Results Intraperitoneal infusion of LPS (1.2 mg/kg/day) for 14 days promoted sustained hypertension and induced a significant increase in plasma level of C-reactive protein, tumor necrosis factor-α (TNF-α), or interleukin-1β (IL-1β). This LPS-induced systemic inflammation was accompanied by activation of microglia, augmentation of IL-1β, IL-6, or TNF-α protein expression, and O2·- production in RVLM, all of which were blunted by intracisternal infusion of a cycloxygenase-2 (COX-2) inhibitor, NS398; an inhibitor of microglial activation, minocycline; or a cytokine synthesis inhibitor, pentoxifylline. Neuroinflammation in RVLM was also associated with a COX-2-dependent downregulation of endothelial nitric oxide synthase and an upregulation of

  14. Sympathetic Nervous System, Hypertension, Obesity and Metabolic Syndrome.

    PubMed

    Seravalle, Gino; Grassi, Guido

    2016-09-01

    Experimental and clinical studies have clearly shown the role of the sympathetic nervous system in the pathophysiology of several cardiovascular and non-cardiovascular diseases. This short review will be aimed at focusing and discussing the new information collected on two specific clinical conditions such as obesity and metabolic syndrome. The paper will briefly describe the four main mechanisms that represent the common link between these two pathophysiological conditions and that through the sympathetic nervous system contribute to increase the cardiovascular risk.

  15. Oral pathology.

    PubMed

    Niemiec, Brook A

    2008-05-01

    Oral disease is exceedingly common in small animal patients. In addition, there is a very wide variety of pathologies that are encountered within the oral cavity. These conditions often cause significant pain and/or localized and systemic infection; however, the majority of these conditions have little to no obvious clinical signs. Therefore, diagnosis is not typically made until late in the disease course. Knowledge of these diseases will better equip the practitioner to effectively treat them. This article covers the more common forms of oral pathology in the dog and cat, excluding periodontal disease, which is covered in its own chapter. The various pathologies are presented in graphic form, and the etiology, clinical signs, recommended diagnostic tests, and treatment options are discussed. Pathologies that are covered include: persistent deciduous teeth, fractured teeth, intrinsically stained teeth, feline tooth resorption, caries, oral neoplasia, eosinophilic granuloma complex, lymphoplasmacytic gingivostomatitis, enamel hypoplasia, and "missing" teeth.

  16. Content based sub-image retrieval system for high resolution pathology images using salient interest points.

    PubMed

    Mehta, Neville; Alomari, Raja' S; Chaudhary, Vipin

    2009-01-01

    Content-based image retrieval systems for digital pathology require sub-image retrieval rather than the whole image retrieval for the system to be of clinical use. Digital pathology images are huge in size and thus the pathologist is interested in retrieving specific structures from the whole images in the database along with the previous diagnosis of the retrieved sub-image. We propose a content-based sub-image retrieval system (sCBIR) framework for high resolution digital pathology images. We utilize scale-invariant feature extraction and present an efficient and robust searching mechanism for indexing the images as well as for query execution of sub-image retrieval. We present a working sCBIR system and show results of testing our system on a set of queries for specific structures of interest for pathologists in clinical use. The outcomes of the sCBIR system are compared to manual search and there is an 80% match in the top five searches.

  17. Clinical integration of picture archiving and communication systems with pathology and hospital information system in oncology.

    PubMed

    Duncan, Lisa D; Gray, Keith; Lewis, James M; Bell, John L; Bigge, Jeremy; McKinney, J Mark

    2010-09-01

    The complexity of our current healthcare delivery system has become an impediment to communication among caregivers resulting in fragmentation of patient care. To address these issues, many hospitals are implementing processes to facilitate clinical integration in an effort to improve patient care and safety. Clinical informatics, including image storage in a Picture Archiving and Communication System (PACS), represents a tool whereby clinical integration can be accomplished. In this study, we obtained intraoperative photographs of 19 cases to document clinical stage, extent of disease, disease recurrence, reconstruction/grafting, intraoperative findings not identified by preoperative imaging, and site verification as part of the Universal Protocol. Photographs from all cases were stored and viewed in PACS. Images from many of the cases were presented at our interdepartmental cancer conferences. The stored images improved communication among caregivers and preserved pertinent intraoperative findings in the patients' electronic medical record. In the future, pathology, gastroenterology, pulmonology, dermatology, and cardiology are just a few other subspecialties which could accomplish image storage in PACS. Multidisciplinary image storage in a PACS epitomizes the concept of clinical integration and its goal of improving patient care.

  18. Hypertension in Sub-Saharan Africa: A Contextual View of Patterns of Disease, Best Management, and Systems Issues.

    PubMed

    Nulu, Shanti; Aronow, Wilbert S; Frishman, William H

    2016-01-01

    Sub-Saharan Africa (SSA) bears the highest burden of both communicable and noncommunicable disease and has the weakest health systems. Much attention is directed toward a rising burden of chronic disease in the setting of epidemiologic transition and urbanization. Indeed, the highest prevalence of hypertension globally is in the World Health Organization's African region at 46% of adults aged 25 and above. And while hypertension in SSA is common, its prevalence varies significantly between urban and rural settings. Although there is evidence for epidemiologic transition in urban areas, there is also evidence of static levels of hypertension within rural areas, which comprise more than 70% of the population of SSA. Furthermore, overall cardiovascular (CV) risk in rural areas remains low. The mean age of hypertensives in SSA is approximately 30s to 40s, burdening those at peak productivity. Complications of hypertension are frequent, given the poor levels of awareness and treatment (<10%) of hypertension on the continent. Such complications include primarily stroke and hypertensive heart disease, as ischemic heart disease is uncommon. Mortality associated with these complications is high, with in-hospital mortality from 2 different sites reported as around 20%. The overall burden of hypertension is likely to be more related to poor access and availability of health systems and is representative of a looming crisis in health care delivery. The best approaches to population-wide treatment are those that utilize CV risk prediction for those with stage 1 hypertension, whereas treatment is generally indicated for all those with stage 2 or greater hypertension, especially in light of the high burden of stroke in SSA. Current guidelines recommend first-line drug therapy with a diuretic or calcium channel blocker. Despite these recommendations, the major obstacles to hypertension treatment are systemic and include the availability and cost of medications, the adequacy of

  19. Development of a servo pump system for in vivo loading of pathological pulmonary artery impedance on the right ventricle of normal rats.

    PubMed

    Fukumitsu, Masafumi; Kawada, Toru; Shimizu, Shuji; Turner, Michael J; Uemura, Kazunori; Sugimachi, Masaru

    2016-04-15

    Pulmonary artery (PA) impedance provides detailed information on right ventricular (RV) afterload in pulmonary hypertension (PH). This study aimed to examine PA impedance in a rat model of monocrotaline-induced PH (MCT-PH) and to develop an experimental system for in vivo loading of pathological PA impedance on the RV of normal rats. PA impedance was quantified in normal (n= 10) and MCT-PH rats (n= 10) using a three-element Windkessel (3-WK) model. Compared with normal rats, MCT-PH rats had higher characteristic impedance (ZC) and peripheral pulmonary resistance (RP) (ZC: 0.121 ± 0.039 vs. 0.053 ± 0.017 mmHg·min·ml(-1), P< 0.001; RP: 0.581 ± 0.334 vs. 0.252 ± 0.105 mmHg·min·ml(-1), P= 0.013) and lower pulmonary artery compliance (CP) (0.242 ± 0.131 vs. 0.700 ± 0.186 ml/mmHg, P< 0.001). In another group of 10 normal rats, a computer-controlled servo pump was connected to the left PA for loading PA impedance with parameters in pathological ranges designed by the 3-WK model. Activation of the servo pump decreased the error of measured vs. target PA impedance (modulus: from 0.047 ± 0.020 without pump activation to 0.019 ± 0.007 with pump activation,P< 0.001; phase: 0.085 ± 0.028 to 0.043 ± 0.012 radians,P< 0.001). In conclusion, MCT-PH increases ZC and RP and decreases CP Our servo pump system, which is capable of imposing arbitrary PA impedance with pathological parameters, may offer a unique opportunity to delineate the pathological significance of PA impedance in PH.

  20. Intracranial hypertension with delayed puberty: a rare presentation of juvenile onset systemic lupus erythematosus.

    PubMed

    Mathew, M; Cherian, A

    2012-01-01

    An adolescent boy presented with headache, bilateral papilloedema, growth retardation and absent secondary sexual characteristics. The diagnosis of intracranial hypertension was confirmed by increased intracranial pressure and normal neuroimaging of the brain except for partial empty sella and prominent perioptic cerebrospinal fluid (CSF) spaces. Evaluation showed an erythrocyte sedimentation rate of 150 mm/hr, positive antinuclear antibody, anti-dsDNA and antiribosomal P protein. Renal biopsy revealed diffuse segmental proliferative lupus nephritis (LN) class IV-S (A), which confirmed the diagnosis of systemic lupus erythematosus (SLE). Treatment of LN with intravenous pulse methylprednisolone and cyclophosphamide normalised the patient's CSF pressure and symptoms. In cases of intracranial hypertension, SLE must be considered. Growth retardation and absence of secondary sexual characteristics could coexist and may be presenting features of SLE. These manifestations point to advanced grades of LN, which could be asymptomatic and may be missed without a renal biopsy.

  1. Therapeutic potential of targeting the renin angiotensin system in portal hypertension

    PubMed Central

    Herath, Chandana B; Grace, Josephine A; Angus, Peter W

    2013-01-01

    Portal hypertension is responsible for the bulk of the morbidity and mortality in patients with cirrhosis. Drug therapy to reduce portal pressure involves targeting two vascular beds. The first approach is to reduce intra hepatic vascular tone induced by the activity of powerful vasocontrictors such as angiotensin II, endothelin-1 and the sympathetic system and mediated via contraction of perisinusoidal myofibroblasts and pervascular smooth muscle cells. The second approach is to reduce mesenteric and portal blood flow. Non-selective β-blockers are widely used and have been shown to prolong patient survival and reduce oesophageal variceal bleeding in advanced cirrhosis. However many patients are unable to tolerate these drugs and they are ineffective in a significant proportion of patients. Unfortunately there are no other drug therapies that have proven efficacy in the treatment of portal hypertension and prevention of variceal bleeding. This review briefly outlines current therapeutic approaches to the management of portal hypertension, and the evidence supporting the role of the renin angiotensin system (RAS) and the use of RAS blockers in this condition. It will also outline recent advances in RAS research that could lead to the development of new treatments focusing in particular on the recently discovered “alternate axis” of the RAS. PMID:23596549

  2. Muscle contracture emulating system for studying artificially induced pathological gait in intact individuals.

    PubMed

    Olensek, Andrej; Matjacic, Zlatko; Bajd, Tadej

    2005-11-01

    When studying pathological gait it is important to correctly identify primary gait anomalies originating from damage to the central nervous and musculoskeletal system and separate them from compensatory changes of gait pattern, which is often challenging due to the lack of knowledge related to biomechanics of pathological gait. A mechanical system consisting of specially designed trousers, special shoe arrangement, and elastic ropes attached to selected locations on the trousers and shoes is proposed to allow emulation of muscle contractures of soleus (SOL) and gastrocnemius (GAS) muscles and both SOL-GAS. The main objective of this study was to evaluate and compare gait variability as recorded in normal gait and when being constrained with the proposed system. Six neurologically and orthopedically intact volunteers walked along a 7-m walkway while gait kinematics and kinetics were recorded using VICON motion analysis system and two AMTI forceplates. Statistical analysis of coefficient of variation of kinematics and kinetics as recorded in normal walking and during the most constrained SOL-GAS condition showed comparable gait variability. Inspection of resulting group averaged gait patterns revealed considerable resemblance to a selected clinical example of spastic diplegia, indicating that the proposed mechanical system potentially represents a novel method for studying emulated pathological gait arising from artificially induced muscle contractures in neurologically intact individuals.

  3. [State of the dopamine system activity, as one of factors for the development of arterial hypertension and obesity].

    PubMed

    Lyzogub, V H; Dolynna, O V; Bogdan, T V; Sobol', V O

    2012-01-01

    The discovery of 5 subtypes of dopamine receptors revealed their important role in development of arterial hypertension and obesity. Reduce of their functional activity or number with age conduces to the increase of tone of the sympathetic nervous system, dyspoiesis of leptin, hyperphagia, development of obesity and arterial hypertension. Prescription of dopamine agonists conduces to reduction of in, normalization of leptin, diminishing of appetite and body mass, decrease of blood pressure. Combination of arterial hypertension and obesity is recommended to determine dopamine excretion and to appoint dopamine agonists at level of < 600 nmol/24 hours.

  4. Assessing the role of optometrists in the control of systemic hypertension in Saudi Arabia.

    PubMed

    Osuagwu, Uchechukwu L; Ogbuehi, Kelechi C; Almubrad, Turki M

    2013-01-01

    The low level of awareness, treatment, and control of systemic hypertension is a global problem, but it is much more serious in Saudi Arabia. This study examines the contribution made by Saudi optometrists in detection and management of patients with systemic hypertension. We surveyed a sample of 250 optometrists practicing in Saudi Arabia to evaluate the level of knowledge and awareness of their role in combating systemic hypertension. A 48.4% response rate was obtained from practicing optometrists. Of those responding, optometrists were very positive towards the use of blood pressure (BP) monitors in optometric practice on a routine basis. Forty-six percent of the optometrists had access to a BP monitor, and about 93% of these respondents actually used the monitors during clinic consultations. Automated monitors were the most common (54%). Fifty-one percent and 49% of the optometrists reported that they did routinely question their patients about high BP and about their current BP medications, respectively. The less frequently asked question concerned the cholesterol level of the patient (21%). The tests most widely used by the optometrists while examining hypertensive patients was direct ophthalmoscopy with red free filter (56%) and the least was binocular indirect ophthalmoscopy (21%). Optometrists were more likely to refer patients suspected of systemic hypertension on the basis of elevated BP (74%) and presence of retinal hemorrhages (72%), but were less likely to refer patients with changes in arteriolar reflex (41%). The opinions were very positive towards the routine monitoring of BP within the Saudi optometry profession, as optometrists indicated that they had time within an eye examination to measure BP, it was financially rewarding (56% of respondents), and patients appreciated it (64% of respondents). Despite half of the optometrists having access to BP monitors (predominantly automated devices), many of the optometrists were unsure if they were

  5. Cervical Spondylosis and Hypertension

    PubMed Central

    Peng, Baogan; Pang, Xiaodong; Li, Duanming; Yang, Hong

    2015-01-01

    Abstract Cervical spondylosis and hypertension are all common diseases, but the relationship between them has never been studied. Patients with cervical spondylosis are often accompanied with vertigo. Anterior cervical discectomy and fusion is an effective method of treatment for cervical spondylosis with cervical vertigo that is unresponsive to conservative therapy. We report 2 patients of cervical spondylosis with concomitant cervical vertigo and hypertension who were treated successfully with anterior cervical discectomy and fusion. Stimulation of sympathetic nerve fibers in pathologically degenerative disc could produce sympathetic excitation, and induce a sympathetic reflex to cause cervical vertigo and hypertension. In addition, chronic neck pain could contribute to hypertension development through sympathetic arousal and failure of normal homeostatic pain regulatory mechanisms. Cervical spondylosis may be one of the causes of secondary hypertension. Early treatment for resolution of symptoms of cervical spondylosis may have a beneficial impact on cardiovascular disease risk in patients with cervical spondylosis. PMID:25761188

  6. Pulmonary hypertension in congenital shunts.

    PubMed

    Beghetti, Maurice; Tissot, Cecile

    2010-10-01

    Pulmonary arterial hypertension frequently arises in patients with congenital heart disease. The vast majority present with congenital cardiac shunts. Initially these may manifest as left-to-right (i.e. systemic-to-pulmonary) shunts. The natural history of disease progression involves vascular remodeling and dysfunction that lead to increased pulmonary vascular resistance and, finally, to the development of Eisenmenger's syndrome, which is the most advanced form. The anatomical, pathological and structural abnormalities occurring in the pulmonary circulation of these patients are, to some extent, similar to those observed in other forms of pulmonary arterial hypertension. This understanding has recently led to significant changes in the management of Eisenmenger's syndrome, with the introduction of treatment specifically targeting pulmonary vascular disease. Early closure of the cardiac shunt remains the best way of preventing pulmonary vascular lesions. However, it is still not clear which preoperative parameters predict safe and successful repair, though hemodynamic evaluation is still routinely used for assessment. Postoperative pulmonary hypertension, both in the immediate period after surgical repair and during long-term follow-up, remains a real therapeutic challenge. The clinical situation of a single ventricle with Fontan circulation also presents difficulties when pulmonary vascular lesions are present. This article reviews pulmonary hypertension associated with congenital shunts and discusses a number of the specific problems encountered.

  7. Quantitative analysis of retinal changes in hypertension

    NASA Astrophysics Data System (ADS)

    Giansanti, Roberto; Boemi, Massimo; Fumelli, Paolo; Passerini, Giorgio; Zingaretti, Primo

    1995-05-01

    Arterial hypertension is a high prevalence disease in Western countries and it is associated with increased risk for cardiovascular accidents. Retinal vessel changes are common findings in patients suffering from long-standing hypertensive disease. Morphological evaluations of the fundus oculi represent a fundamental tool for the clinical approach to the patient with hypertension. A qualitative analysis of the retinal lesions is usually performed and this implies severe limitations both in the classification of the different degrees of the pathology and in the follow-up of the disease. A diagnostic system based on a quantitative analysis of the retinal changes could overcome these problems. Our computerized approach was intended for this scope. The paper concentrates on the results and the implications of a computerized approach to the automatic extraction of numerical indexes describing morphological details of the fundus oculi. A previously developed image processing and recognition system, documented elsewhere and briefly described here, was successfully tested in pre-clinical experiments and applied in the evaluation of normal as well as of pathological fundus. The software system was developed to extract indexes such as caliber and path of vessels, local tortuosity of arteries and arterioles, positions and angles of crossings between two vessels. The reliability of the results, justified by their low variability, makes feasible the standardization of quantitative parameters to be used both in the diagnosis and in the prognosis of hypertension, and also allows prospective studies based upon them.

  8. Pathological Diagnosis of Gastric Cancers with a Novel Computerized Analysis System

    PubMed Central

    Oikawa, Kosuke; Saito, Akira; Kiyuna, Tomoharu; Graf, Hans Peter; Cosatto, Eric; Kuroda, Masahiko

    2017-01-01

    Background: Recent studies of molecular biology have provided great advances for diagnostic molecular pathology. Automated diagnostic systems with computerized scanning for sampled cells in fluids or smears are now widely utilized. Automated analysis of tissue sections is, however, very difficult because they exhibit a complex mixture of overlapping malignant tumor cells, benign host-derived cells, and extracellular materials. Thus, traditional histological diagnosis is still the most powerful method for diagnosis of diseases. Methods: We have developed a novel computer-assisted pathology system for rapid, automated histological analysis of hematoxylin and eosin (H and E)-stained sections. It is a multistage recognition system patterned after methods that human pathologists use for diagnosis but harnessing machine learning and image analysis. The system first analyzes an entire H and E-stained section (tissue) at low resolution to search suspicious areas for cancer and then the selected areas are analyzed at high resolution to confirm the initial suspicion. Results: After training the pathology system with gastric tissues samples, we examined its performance using other 1905 gastric tissues. The system's accuracy in detecting malignancies was shown to be almost equal to that of conventional diagnosis by expert pathologists. Conclusions: Our novel computerized analysis system provides a support for histological diagnosis, which is useful for screening and quality control. We consider that it could be extended to be applicable to many other carcinomas after learning normal and malignant forms of various tissues. Furthermore, we expect it to contribute to the development of more objective grading systems, immunohistochemical staining systems, and fluorescent-stained image analysis systems.

  9. Relevance of Immune-Sympathetic Nervous System Interplay for the Development of Hypertension.

    PubMed

    Winklewski, Pawel J; Radkowski, Marek; Demkow, Urszula

    2016-01-01

    Historically, the sympathetic nervous system (SNS) has been mostly associated with the 'fight or flight' response and the regulation of cardiovascular function. However, evidence over the past 30 years suggests that SNS may also influence the function of immune cells. In this review we describe the basic research being done in the area of SNS regulation of immune function. Further, we show that the SNS-immune interplay during circadian rhythm may modulate the robustness of the inflammatory response, critical for survival during periods of increased activity. Finally, new concepts of a close relationship between these systems in the pathogenesis of hypertension are discussed.

  10. [Features of systemic hemostasis in arterial hypertension with vibration disease in accordance with vibration type].

    PubMed

    Gerasimenko, O N; Chachibaia, É K

    2014-01-01

    Study covered systemic hemostasis in 69 males aged 47.6 +/- 2.1 years with 1 stage arterial hypertension and 1 stage vibration disease, exposed to various types of occupational vibration at work. Those exposed to bump vibration demonstrated an increase in platelets aggregation with all aggregation inductors, if compared to reference values, increased generaton and activity of von Willebrand factor, moderately depressed fibrinolysis system with increased serum content of fibrin and fibrinogen degradation products and decreased anticoagulation factors activity. Those exposed to rotation vibration demonstrated less changes.

  11. A computer-aided diagnosis system to detect pathologies in temporal subtraction images of chest radiographs

    NASA Astrophysics Data System (ADS)

    Looper, Jared; Harrison, Melanie; Armato, Samuel G.

    2016-03-01

    Radiologists often compare sequential radiographs to identify areas of pathologic change; however, this process is prone to error, as human anatomy can obscure the regions of change, causing the radiologists to overlook pathology. Temporal subtraction (TS) images can provide enhanced visualization of regions of change in sequential radiographs and allow radiologists to better detect areas of change in radiographs. Not all areas of change shown in TS images, however, are actual pathology. The purpose of this study was to create a computer-aided diagnostic (CAD) system that identifies which regions of change are caused by pathology and which are caused by misregistration of the radiographs used to create the TS image. The dataset used in this study contained 120 images with 74 pathologic regions on 54 images outlined by an experienced radiologist. High and low ("light" and "dark") gray-level candidate regions were extracted from the images using gray-level thresholding. Then, sampling techniques were used to address the class imbalance problem between "true" and "false" candidate regions. Next, the datasets of light candidate regions, dark candidate regions, and the combined set of light and dark candidate regions were used as training and testing data for classifiers by using five-fold cross validation. Of the classifiers tested (support vector machines, discriminant analyses, logistic regression, and k-nearest neighbors), the support vector machine on the combined candidates using synthetic minority oversampling technique (SMOTE) performed best with an area under the receiver operating characteristic curve value of 0.85, a sensitivity of 85%, and a specificity of 84%.

  12. [Outstanding problems of normal and pathological morphology of the diffuse endocrine system].

    PubMed

    Iaglov, V V; Iaglova, N V

    2011-01-01

    The diffuse endocrine system (DES)--a mosaic-cellular endoepithelial gland--is the biggest part of the human endocrine system. Scientists used to consider cells of DES as neuroectodermal. According to modem data cells of DES are different cytogenetic types because they develop from the different embryonic blastophyllum. So that any hormone-active tumors originated from DES of the digestive, respiratory and urogenital system shouldn't be considered as neuroendocrinal tumors. The basic problems of DES morphology and pathology are the creation of scientifically substantiated histogenetic classification of DES tumors.

  13. All cognitive systems but speed and visuospatial functions reduce the effect of CSF pathology on other systems.

    PubMed

    Rolstad, Sindre; Berg, Anne I; Zetterberg, Henrik; Johansson, Boo; Wallin, Anders

    2012-11-01

    The concept of reserve can be conceived as differences in the ability to compensate for pathology by recruiting additional or alternative networks. The purpose of this study was to examine whether certain cognitive systems may compensate for the effect of CSF amyloid beta 42 (Aβ42) and total tau (T-tau) on other cognitive systems. Five hundred and nine participants underwent neuropsychological examination and lumbar puncture. Multiple regression was performed with interaction terms to test whether a cognitive system reduced the impact of CSF pathology on other systems. All cognitive systems except speed and visuospatial functions were associated with reduced effects of T-tau and Aβ42 on semantic memory, working memory and visuospatial abilities. The burden of Aβ42 was reduced more often than that of T-tau. Our results suggest that most cognitive systems may be beneficial to maintenance of cognitive performance despite CSF burden. The results support the notion of cognitive reserve.

  14. Respiratory system involvement in antineutrophil cytoplasmic-associated systemic vasculitides: clinical, pathological, radiological and therapeutic considerations.

    PubMed

    Pesci, Alberto; Manganelli, Paolo

    2007-01-01

    Wegener's granulomatosis (WG), microscopic polyangiitis (MPA) and Churg- Strauss syndrome (CSS) are small-vessel vasculitides that, because of their frequent association with antineutrophil cytoplasmic antibodies (ANCA), are usually referred to as ANCA-associated systemic vasculitides (AASV). The diagnosis of AASV is made on the basis of clinical findings, biopsy of an involved organ and the presence of ANCA in the serum. Lung disease is a very common and important clinical feature of AASV. In WG, almost all patients have either upper airway or lower respiratory tract disease. Solitary or multiple nodules, frequently cavitated, and masses are the most common findings on chest radiography. Asthma is a cardinal symptom of CSS, often preceded by allergic rhinitis. Pulmonary transient and patchy alveolar infiltrates are the most common radiographic findings. In MPA, diffuse alveolar haemorrhage as a result of alveolar capillaritis is the most frequent manifestation of respiratory involvement, and is clinically expressed as haemoptysis, respiratory distress and anaemia. However, diffuse alveolar haemorrhage may also be subclinical and should be suspected when a chest radiograph demonstrates new unexplained bilateral alveolar infiltrates in the context of falling haemoglobin levels. Normal and high-resolution CT have a higher sensitivity than chest radiography for demonstrating airway, parenchymal and pleural lesions. However, many of these radiological findings are nonspecific and, therefore, their interpretation must take into account all clinical, laboratory and pathological data. Therapy of AASV is commonly divided into two phases: an initial 'remission induction' phase, in which more intensive immunosuppressant therapy is used to control disease activity, and a 'maintenance' phase, which uses less intensive therapy, for maintaining disease remission while lowering the risk of adverse effects of immunosuppressant drugs. In patients with AASV refractory to standard

  15. Advancing the Assessment of Personality Pathology With the Cognitive-Affective Processing System.

    PubMed

    Huprich, Steven K; Nelson, Sharon M

    2015-01-01

    The Cognitive-Affective Processing System (CAPS) is a dynamic and expansive model of personality proposed by Mischel and Shoda (1995) that incorporates dispositional and processing frameworks by considering the interaction of the individual and the situation, and the patterns of variation that result. These patterns of cognition, affect, and behavior are generally defined through the use of if … then statements, and provide a rich understanding of the individual across varying levels of assessment. In this article, we describe the CAPS model and articulate ways in which it can be applied to conceptualizing and assessing personality pathology. We suggest that the CAPS model is an ideal framework that integrates a number of current theories of personality pathology, and simultaneously overcomes a number of limits that have been empirically identified in the past.

  16. Small G proteins in the cardiovascular system: physiological and pathological aspects.

    PubMed

    Loirand, Gervaise; Sauzeau, Vincent; Pacaud, Pierre

    2013-10-01

    Small G proteins exist in eukaryotes from yeast to human and constitute the Ras superfamily comprising more than 100 members. This superfamily is structurally classified into five families: the Ras, Rho, Rab, Arf, and Ran families that control a wide variety of cell and biological functions through highly coordinated regulation processes. Increasing evidence has accumulated to identify small G proteins and their regulators as key players of the cardiovascular physiology that control a large panel of cardiac (heart rhythm, contraction, hypertrophy) and vascular functions (angiogenesis, vascular permeability, vasoconstriction). Indeed, basal Ras protein activity is required for homeostatic functions in physiological conditions, but sustained overactivation of Ras proteins or spatiotemporal dysregulation of Ras signaling pathways has pathological consequences in the cardiovascular system. The primary object of this review is to provide a comprehensive overview of the current progress in our understanding of the role of small G proteins and their regulators in cardiovascular physiology and pathologies.

  17. A Multilayer Perceptron Based Smart Pathological Brain Detection System by Fractional Fourier Entropy.

    PubMed

    Zhang, Yudong; Sun, Yi; Phillips, Preetha; Liu, Ge; Zhou, Xingxing; Wang, Shuihua

    2016-07-01

    This work aims at developing a novel pathological brain detection system (PBDS) to assist neuroradiologists to interpret magnetic resonance (MR) brain images. We simplify this problem as recognizing pathological brains from healthy brains. First, 12 fractional Fourier entropy (FRFE) features were extracted from each brain image. Next, we submit those features to a multi-layer perceptron (MLP) classifier. Two improvements were proposed for MLP. One improvement is the pruning technique that determines the optimal hidden neuron number. We compared three pruning techniques: dynamic pruning (DP), Bayesian detection boundaries (BDB), and Kappa coefficient (KC). The other improvement is to use the adaptive real-coded biogeography-based optimization (ARCBBO) to train the biases and weights of MLP. The experiments showed that the proposed FRFE + KC-MLP + ARCBBO achieved an average accuracy of 99.53 % based on 10 repetitions of K-fold cross validation, which was better than 11 recent PBDS methods.

  18. Associations between proteinuria, systemic hypertension and glomerular filtration rate in dogs with renal and non-renal diseases.

    PubMed

    Wehner, A; Hartmann, K; Hirschberger, J

    2008-02-02

    Proteinuria and systemic hypertension are well recognised risk factors in chronic renal failure (CRF). They are consequences of renal disease but also lead to a further loss of functional kidney tissue. The objectives of this study were to investigate the associations between proteinuria, systemic hypertension and glomerular filtration rate (GFR) in dogs with naturally occurring renal and non-renal diseases, and to determine whether proteinuria and hypertension were associated with shorter survival times in dogs with CRF. Measurements of exogenous creatinine plasma clearance (ECPC), urine protein:creatinine ratio (UPC), and Doppler sonographic measurements of systolic blood pressure (SBP) were made in 60 dogs with various diseases. There was a weak but significant inverse correlation between UPC and ECPC, a significant inverse correlation between SBP and ECPC and a weak but significant positive correlation between UPC and SBP. Some of the dogs with CRF were proteinuric and almost all were hypertensive. Neoplasia was commonly associated with proteinuria in the dogs with a normal ECPC. CRF was the most common cause leading to hypertension. In the dogs with CRF, hypertension and marked proteinuria were associated with significantly shorter survival times.

  19. Evaluation of modified Kumar and Kalra myelopathy scoring system in sub-axial spinal pathologies

    PubMed Central

    Mehrotra, Anant; Srivastava, Arun; Sahu, Rabi N.; Kumar, Raj

    2016-01-01

    Background: Various pathologies affect the spine, but these lesions present with more or less similar clinical profile. The present functional scoring systems are inadequate and insensitive to changes in neurological status of the patient. Objective: Our study aims to assess the modified Kumar and Kalra (K and K) scoring system in patients with pathologies in the sub-axial spine. Materials and Methods: A total of 78 consecutive patients from the period of January 2009 to June 2010 were prospectively included in the study. These patients were operated by the senior author at our institute. The mean Modified Japanese Orthopaedic Association (MJOA) score and the mean modified K and K score were calculated in the preoperative, at the time of discharge (post-surgery), and at 3 months and 6 months follow-up. Results: There were 57 male (73.01%) patients and 21 female patients (26.92%), with the mean age of presentation of 39.20 years (±14.12 years) and a range of 9-75 years. Out of the total 78 patients, 60 patients had pathology in the cervical spine (sub-axial spine) and 18 patients had pathology in the dorsal spine. Majority of the patients had motor and sensory symptoms. The mean preoperative modified K and K score was 17.38 (±3.18) and the mean preoperative MJOA score was 11.21 (±2.12). The K and K score was able to predict the correct outcome in 70 patients (89.74%), whereas the MJOA score was able to predict correctly in 62 patients (79.49%). Conclusion: The modified K and K score has a better predictive value than the MJOA score. PMID:27695541

  20. Phases in development of an interactive mobile phone-based system to support self-management of hypertension

    PubMed Central

    Hallberg, Inger; Taft, Charles; Ranerup, Agneta; Bengtsson, Ulrika; Hoffmann, Mikael; Höfer, Stefan; Kasperowski, Dick; Mäkitalo, Åsa; Lundin, Mona; Ring, Lena; Rosenqvist, Ulf; Kjellgren, Karin

    2014-01-01

    Hypertension is a significant risk factor for heart disease and stroke worldwide. Effective treatment regimens exist; however, treatment adherence rates are poor (30%–50%). Improving self-management may be a way to increase adherence to treatment. The purpose of this paper is to describe the phases in the development and preliminary evaluation of an interactive mobile phone-based system aimed at supporting patients in self-managing their hypertension. A person-centered and participatory framework emphasizing patient involvement was used. An interdisciplinary group of researchers, patients with hypertension, and health care professionals who were specialized in hypertension care designed and developed a set of questions and motivational messages for use in an interactive mobile phone-based system. Guided by the US Food and Drug Administration framework for the development of patient-reported outcome measures, the development and evaluation process comprised three major development phases (1, defining; 2, adjusting; 3, confirming the conceptual framework and delivery system) and two evaluation and refinement phases (4, collecting, analyzing, interpreting data; 5, evaluating the self-management system in clinical practice). Evaluation of new mobile health systems in a structured manner is important to understand how various factors affect the development process from both a technical and human perspective. Forthcoming analyses will evaluate the effectiveness and utility of the mobile phone-based system in supporting the self-management of hypertension. PMID:24910510

  1. Phases in development of an interactive mobile phone-based system to support self-management of hypertension.

    PubMed

    Hallberg, Inger; Taft, Charles; Ranerup, Agneta; Bengtsson, Ulrika; Hoffmann, Mikael; Höfer, Stefan; Kasperowski, Dick; Mäkitalo, Asa; Lundin, Mona; Ring, Lena; Rosenqvist, Ulf; Kjellgren, Karin

    2014-01-01

    Hypertension is a significant risk factor for heart disease and stroke worldwide. Effective treatment regimens exist; however, treatment adherence rates are poor (30%-50%). Improving self-management may be a way to increase adherence to treatment. The purpose of this paper is to describe the phases in the development and preliminary evaluation of an interactive mobile phone-based system aimed at supporting patients in self-managing their hypertension. A person-centered and participatory framework emphasizing patient involvement was used. An interdisciplinary group of researchers, patients with hypertension, and health care professionals who were specialized in hypertension care designed and developed a set of questions and motivational messages for use in an interactive mobile phone-based system. Guided by the US Food and Drug Administration framework for the development of patient-reported outcome measures, the development and evaluation process comprised three major development phases (1, defining; 2, adjusting; 3, confirming the conceptual framework and delivery system) and two evaluation and refinement phases (4, collecting, analyzing, interpreting data; 5, evaluating the self-management system in clinical practice). Evaluation of new mobile health systems in a structured manner is important to understand how various factors affect the development process from both a technical and human perspective. Forthcoming analyses will evaluate the effectiveness and utility of the mobile phone-based system in supporting the self-management of hypertension.

  2. Secondary Hypertension

    MedlinePlus

    Secondary hypertension Overview By Mayo Clinic Staff Secondary hypertension (secondary high blood pressure) is high blood pressure that's caused by another medical condition. Secondary hypertension can be caused by conditions that affect your ...

  3. The apelinergic system: the role played in human physiology and pathology and potential therapeutic applications.

    PubMed

    Ladeiras-Lopes, Ricardo; Ferreira-Martins, João; Leite-Moreira, Adelino F

    2008-05-01

    Apelin is a recently discovered peptide, identified as an endogenous ligand of receptor APJ. Apelin and receptor APJ are expressed in a wide variety of tissues including heart, brain, kidneys and lungs. Their interaction may have relevant pathophysiologic effects in those tissues. In fact, the last decade has been rich in illustrating the possible roles played by apelin in human physiology, namely as a regulating peptide of cardiovascular, hypothalamus-hypophysis, gastrointestinal, and immune systems. The possible involvement of apelin in the pathogenesis of high prevalence conditions and comorbidities - such as hypertension, heart failure, and Diabetes Mellitus Type 2 (T2DM) - rank it as a likely therapeutic target to be investigated in the future. The present paper is an overview of apelin physiologic effects and presents the possible role played by this peptide in the pathogenesis of a number of conditions as well as the therapeutic implications that might, therefore, be investigated.

  4. Dawn of the digital diagnosis assisting system, can it open a new age for pathology?

    NASA Astrophysics Data System (ADS)

    Saito, Akira; Cosatto, Eric; Kiyuna, Tomoharu; Sakamoto, Michiie

    2013-03-01

    Digital pathology is developing based on the improvement and popularization of WSI (whole slide imaging) scanners. WSI scanners are widely expected to be used as the next generation microscope for diagnosis; however, their usage is currently mostly limited to education and archiving. Indeed, there are still many hindrances in using WSI scanners for diagnosis (not research purpose), two of the main reasons being the perceived high cost and small gain in productivity obtained by switching from the microscope to a WSI system and the lack of WSI standardization. We believe that a key factor for advancing digital pathology is the creation of computer assisted diagnosis systems (CAD). Such systems require high-resolution digitization of slides and provide a clear added value to the often costly conversion to WSI. We (NEC Corporation) are creating a CAD system, named e-Pathologist ®. This system is currently used at independent pathology labs for quality control (QC/QA), double-checking pathologists diagnosis and preventing missed cancers. At the end of 2012, about 80,000 slides, 200,000 tissues of gastric and colorectal samples will have been analyzed by e-Pathologist ®. Through the development of e-Pathologist ®, it has become clear that a computer program should be inspired by the pathologist diagnosis process, yet it should not be a mere copy or simulation of it. Indeed pathologists often approach the diagnosis of slides in a "holistic" manner, examining them at various magnifications, panning and zooming in a seemingly haphazard way that they often have a hard time to precisely describe. Hence there has been no clear recipe emerging from numerous interviews with pathologists on how to exactly computer code a diagnosis expert system. Instead, we focused on extracting a small set of histopathological features that were consistently indicated as important by the pathologists and then let the computer figure out how to interpret in a quantitative way the presence or

  5. Evidences of Polymorphism Associated with Circadian System and Risk of Pathologies: A Review of the Literature

    PubMed Central

    Valenzuela, F. J.; Vera, J.; Venegas, C.; Muñoz, S.; Oyarce, S.; Muñoz, K.; Lagunas, C.

    2016-01-01

    The circadian system is a supraphysiological system that modulates different biological functions such as metabolism, sleep-wake, cellular proliferation, and body temperature. Different chronodisruptors have been identified, such as shift work, feeding time, long days, and stress. The environmental changes and our modern lifestyle can alter the circadian system and increase the risk of developing pathologies such as cancer, preeclampsia, diabetes, and mood disorder. This system is organized by transcriptional/tranductional feedback loops of clock genes Clock, Bmal1, Per1–3, and Cry1-2. How molecular components of the clock are able to influence the development of diseases and their risk relation with genetic components of polymorphism of clock genes is unknown. This research describes different genetic variations in the population and how these are associated with risk of cancer, metabolic diseases such as diabetes, obesity, and dyslipidemias, and also mood disorders such as depression, bipolar disease, excessive alcohol intake, and infertility. Finally, these findings will need to be implemented and evaluated at the level of genetic interaction and how the environment factors trigger the expression of these pathologies will be examined. PMID:27313610

  6. New drug therapies interfering with the renin-angiotensin-aldosterone system for resistant hypertension.

    PubMed

    Monge, Matthieu; Lorthioir, Aurélien; Bobrie, Guillaume; Azizi, Michel

    2013-12-01

    There is a persistent need for the development of new antihypertensive drugs, because the control of blood pressure is still not achievable in a significant proportion of hypertensive patients. Since the approval in 2007 of aliskiren, no other new antihypertensive based on new mechanism(s) of action have been approved. In fact, the development of promising novel drugs has been stopped for safety, efficacy or marketing reasons. Despite these difficulties, the pipeline is not dry and different new antihypertensive strategies targeting the renin-angiotensin-aldosterone pathway, are in clinical development stage. The dual angiotensin II receptor-neprilysin inhibitor LCZ696, a single molecule synthetized by cocrystallisation of valsartan and the neprilysin inhibitor prodrug AHU377 is in development for resistant hypertension and for heart failure. Daglutril is a dual neprylisin-endothelin converting enzyme inhibitor which was shown to decrease BP in patients with type 2 diabetic nephropathy. Aldosterone synthase inhibitors and the third and fourth generation non-steroidal dihydropyridine based mineralocorticoid receptors blockers are new ways to target the multiple noxious effects of aldosterone in the kidney, vessels and heart. Centrally acting aminopeptidase A inhibitors block brain angiotensin III formation, one of the main effector peptides of the brain renin angiotensin system. However, a long time will be still necessary to evaluate extensively the efficacy and safety of these new approaches. In the mean time, using appropriate and personalized daily doses of available drugs, decreasing physician inertia, improving treatment adherence, improving access to healthcare and reducing treatment costs remain major objectives to reduce the incidence of resistant hypertension.

  7. Vasopressors induce passive pulmonary hypertension by blood redistribution from systemic to pulmonary circulation.

    PubMed

    Jiang, Chunling; Qian, Hong; Luo, Shuhua; Lin, Jing; Yu, Jerry; Li, Yajiao; An, Qi; Luo, Nanfu; Du, Lei

    2017-05-01

    Vasopressors are widely used in resuscitation, ventricular failure, and sepsis, and often induce pulmonary hypertension with undefined mechanisms. We hypothesize that vasopressor-induced pulmonary hypertension is caused by increased pulmonary blood volume and tested this hypothesis in dogs under general anesthesia. In normal hearts (model 1), phenylephrine (2.5 μg/kg/min) transiently increased right but decreased left cardiac output, associated with increased pulmonary blood volume (63% ± 11.8, P = 0.007) and pressures in the left atrium, pulmonary capillary, and pulmonary artery. However, the trans-pulmonary gradient and pulmonary vascular resistance remained stable. These changes were absent after decreasing blood volume or during right cardiac dysfunction to reduce pulmonary blood volume (model 2). During double-ventricle bypass (model 3), phenylephrine (1, 2.5 and 10 μg/kg/min) only slightly induced pulmonary vasoconstriction. Vasopressin (1U and 2U) dose-dependently increased pulmonary artery pressure (52 ± 8.4 and 71 ± 10.3%), but did not cause pulmonary vasoconstriction in normally beating hearts (model 1). Pulmonary artery and left atrial pressures increased during left ventricle dysfunction (model 4), and further increased after phenylephrine injection by 31 ± 5.6 and 43 ± 7.5%, respectively. In conclusion, vasopressors increased blood volume in the lung with minimal pulmonary vasoconstriction. Thus, this pulmonary hypertension is similar to the hemodynamic pattern observed in left heart diseases and is passive, due to redistribution of blood from systemic to pulmonary circulation. Understanding the underlying mechanisms may improve clinical management of patients who are taking vasopressors, especially those with coexisting heart disease.

  8. Association of gene polymorphisms in RANKL/RANK/OPG system with hypertension and blood pressure in Chinese women.

    PubMed

    Duan, P; Wang, Z-M; Liu, J; Wang, L-N; Yang, Z; Tu, P

    2015-12-01

    Recent studies have revealed that the receptor activator of nuclear factor-kappa B ligand/RANK/osteoprotegerin (RANKL/RANK/OPG) system has an important role in vascular calcification, which is contributory to various cardiovascular diseases and intimately linked to the regulation of blood pressure. Therefore, we performed a case-control study to investigate the associations of 21 single-nucleotide polymorphisms (SNPs) in the TNFSF11, TNFRSF11A and TNFRSF11B genes in the RANKL/RANK/OPG system with hypertension and blood pressure in post-menopausal Chinese women. In this study, 503 hypertensive patients and 509 normal controls were recruited. Genotyping was performed using the high-throughput Sequenom genotyping platform. The results showed that two SNPs (rs6567270 and rs4603673) in the TNFRSF11A were associated with hypertension (P=0.010 and P=0.013, respectively) and systolic blood pressure (P=0.024 and P=0.023, respectively). One SNP (rs9646629) in the TNFRSF11A showed significant association with diastolic blood pressure (P=0.031). The results of this study suggest that TNFRSF11A but not TNFSF11 and TNFRSF11B genetic variation is associated with hypertension and blood pressure in Chinese women. The findings provide additional support for the genetic role of RANKL/RANK/OPG system in hypertension and blood pressure regulation.

  9. Hypertension: issues in control and resistance.

    PubMed

    Wofford, Marion R; Minor, Deborah S

    2009-10-01

    Hypertension remains uncontrolled in more than 50% of treated patients. Barriers to hypertension control include those that are patient-related, physician-related, and related to the health system. Identification of uncontrolled hypertension, pseudoresistant hyper-tension, and resistant hypertension require thoughtful attention to accurate blood pressure measurement, lifestyle factors, evaluation for secondary causes of hypertension, and proper treatment. Recent guidelines emphasize the importance of aggressive treatment and referral to hypertension specialists for patients with resistant hypertension, defined as blood pressure that remains above goal despite the use of three appropriate anti-hypertensive agents.

  10. Pediatric respiratory and systemic effects of chronic air pollution exposure: nose, lung, heart, and brain pathology.

    PubMed

    Calderón-Garcidueñas, Lilian; Franco-Lira, Maricela; Torres-Jardón, Ricardo; Henriquez-Roldán, Carlos; Barragán-Mejía, Gerardo; Valencia-Salazar, Gildardo; González-Maciel, Angelica; Reynoso-Robles, Rafael; Villarreal-Calderón, Rafael; Reed, William

    2007-01-01

    Exposures to particulate matter and gaseous air pollutants have been associated with respiratory tract inflammation, disruption of the nasal respiratory and olfactory barriers, systemic inflammation, production of mediators of inflammation capable of reaching the brain and systemic circulation of particulate matter. Mexico City (MC) residents are exposed to significant amounts of ozone, particulate matter and associated lipopolysaccharides. MC dogs exhibit brain inflammation and an acceleration of Alzheimer's-like pathology, suggesting that the brain is adversely affected by air pollutants. MC children, adolescents and adults have a significant upregulation of cyclooxygenase-2 (COX2) and interleukin-1beta (IL-1beta) in olfactory bulb and frontal cortex, as well as neuronal and astrocytic accumulation of the 42 amino acid form of beta -amyloid peptide (Abeta 42), including diffuse amyloid plaques in frontal cortex. The pathogenesis of Alzheimer's disease (AD) is characterized by brain inflammation and the accumulation of Abeta 42, which precede the appearance of neuritic plaques and neurofibrillary tangles, the pathological hallmarks of AD. Our findings of nasal barrier disruption, systemic inflammation, and the upregulation of COX2 and IL-1beta expression and Abeta 42 accumulation in brain suggests that sustained exposures to significant concentrations of air pollutants such as particulate matter could be a risk factor for AD and other neurodegenerative diseases.

  11. NADPH Oxidases in Vascular Pathology

    PubMed Central

    Konior, Anna; Schramm, Agata; Czesnikiewicz-Guzik, Marta

    2014-01-01

    Abstract Significance: Reactive oxygen species (ROS) play a critical role in vascular disease. While there are many possible sources of ROS, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases play a central role. They are a source of “kindling radicals,” which affect other enzymes, such as nitric oxide synthase endothelial nitric oxide synthase or xanthine oxidase. This is important, as risk factors for atherosclerosis (hypertension, diabetes, hypercholesterolemia, and smoking) regulate the expression and activity of NADPH oxidases in the vessel wall. Recent Advances: There are seven isoforms in mammals: Nox1, Nox2, Nox3, Nox4, Nox5, Duox1 and Duox2. Nox1, Nox2, Nox4, and Nox5 are expressed in endothelium, vascular smooth muscle cells, fibroblasts, or perivascular adipocytes. Other homologues have not been found or are expressed at very low levels; their roles have not been established. Nox1/Nox2 promote the development of endothelial dysfunction, hypertension, and inflammation. Nox4 may have a role in protecting the vasculature during stress; however, when its activity is increased, it may be detrimental. Calcium-dependent Nox5 has been implicated in oxidative damage in human atherosclerosis. Critical Issues: NADPH oxidase-derived ROS play a role in vascular pathology as well as in the maintenance of normal physiological vascular function. We also discuss recently elucidated mechanisms such as the role of NADPH oxidases in vascular protection, vascular inflammation, pulmonary hypertension, tumor angiogenesis, and central nervous system regulation of vascular function and hypertension. Future Directions: Understanding the role of individual oxidases and interactions between homologues in vascular disease is critical for efficient pharmacological regulation of vascular NADPH oxidases in both the laboratory and clinical practice. Antioxid. Redox Signal. 20, 2794–2814. PMID:24180474

  12. CT features and pathologic characteristics of IgG4-related systemic disease of submandibular gland.

    PubMed

    Wang, Zhiwei; Feng, Ruie; Chen, Yu; Duan, Miao; Wang, Man; Jin, Zhengyu; Rumboldt, Zoran; Zhang, Zhuhua

    2015-01-01

    The submandibular gland is one of the most frequently affected salivary gland in IgG4-related systemic disease, usually demonstrate homogeneous attenuation on CT imaging as reported, but without much pathological comparison of many cases. This article is to investigate and analyze the typical CT findings and pathologic characteristics of IgG4-related systemic disease (IgG4-RSD) of submandibular gland. A retrospective analysis of the preoperative CT findings in patients with IgG4-RSD of submandibular glands who underwent surgical resection between January 2010 and February 2014 was performed. Twenty patients (16 women) were identified, with a mean age of 58.1±10.2 years. All patients presented with painless submandibular gland swelling. Diffuse gland enlargement, with clear margins and homogeneous density, was found on non-enhanced CT scans in all cases. There were no calcifications or stones within the involved glands. Based on contrast-enhanced CT appearance the patients could be divided into two groups: 11 cases showed homogeneous gland enhancement; and multiple hyperenhancing foci, with a crazy-paving pattern, were detected in 9 cases, which were in consistent with the pathologic findings. The maximum submandibular gland diameter on transverse images was significantly larger (P=0.008) in patients with crazy-paving appearance (32±4 mm) compared to patients with homogeneous enhancement (28±3 mm). It is concluded that the submandibular glands with IgG4-RSD can be characterized by either homogenous appearance or crazy-paving pattern on contrast-enhanced CT imaging.

  13. Renin angiotensin aldosterone system altered in resistant hypertension in Sub-Saharan African diabetes patients without evidence of primary hyperaldosteronism

    PubMed Central

    Edinga-Melenge, Bertille Elodie; Ama Moor, Vicky J; Nansseu, Jobert Richie N; Nguetse Djoumessi, Romance; Mengnjo, Michel K; Katte, Jean-Claude; Noubiap, Jean Jacques N

    2017-01-01

    Background The renin-angiotensin-aldosterone system may be altered in patients with resistant hypertension. This study aimed to evaluate the relation between renin-angiotensin-aldosterone system activity and resistant hypertension in Cameroonian diabetes patients with resistant hypertension. Methods We carried out a case-control study including 19 diabetes patients with resistant hypertension and 19 diabetes patients with controlled hypertension matched to cases according to age, sex and duration of hypertension since diagnosis. After collection of data, fasting blood was collected for measurement of sodium, potassium, chloride, active renin and plasma aldosterone of which the aldosterone-renin ratio was derived to assess the activity of renin-angiotensin-aldosterone system. Then, each participant received 2000 ml infusion of saline solution after which plasma aldosterone was re-assayed. Results Potassium levels were lower among cases compared to controls (mean: (4.10 ± 0.63 mmol/l vs. 4.47 ± 0.58 mmol/l), though nonsignificant (p = 0.065). Active renin, plasma aldosterone both before and after the dynamic test and aldosterone-renin ratio were comparable between cases and controls (all p values > 0.05). Plasma aldosterone significantly decreased after the dynamic test in both groups (p < 0.001), but no participant exhibited a post-test value>280 pmol/l. We found a significant negative correlation between potassium ion and plasma aldosterone (ρ = −0.324; p = 0.047), the other correlations being weak and unsignificant. Conclusion Although this study failed to show an association between RH and primary hyperaldosteronism in our context, there was a hyperactivity of renin-angiotensin-aldosterone system. Moreover, this study confirms the importance of potassium dosage when screening the renin-angiotensin-aldosterone system. PMID:28321294

  14. Physiological and pathological roles of tissue plasminogen activator and its inhibitor neuroserpin in the nervous system

    PubMed Central

    Lee, Tet Woo; Tsang, Vicky W. K.; Birch, Nigel P.

    2015-01-01

    Although its roles in the vascular space are most well-known, tissue plasminogen activator (tPA) is widely expressed in the developing and adult nervous system, where its activity is believed to be regulated by neuroserpin, a predominantly brain-specific member of the serpin family of protease inhibitors. In the normal physiological state, tPA has been shown to play roles in the development and plasticity of the nervous system. Ischemic damage, however, may lead to excess tPA activity in the brain and this is believed to contribute to neurodegeneration. In this article, we briefly review the physiological and pathological roles of tPA in the nervous system, which includes neuronal migration, axonal growth, synaptic plasticity, neuroprotection and neurodegeneration, as well as a contribution to neurological disease. We summarize tPA's multiple mechanisms of action and also highlight the contributions of the inhibitor neuroserpin to these processes. PMID:26528129

  15. Speech input system for meat inspection and pathological coding used thereby

    NASA Astrophysics Data System (ADS)

    Abe, Shozo

    Meat inspection is one of exclusive and important jobs of veterinarians though it is not well known in general. As the inspection should be conducted skillfully during a series of continuous operations in a slaughter house, development of automatic inspecting systems has been required for a long time. We employed a hand-free speech input system to record the inspecting data because inspecters have to use their both hands to treat the internals of catles and check their health conditions by necked eyes. The data collected by the inspectors are transfered to a speech recognizer and then stored as controlable data of each catle inspected. Control of terms such as pathological conditions to be input and their coding are also important in this speech input system and practical examples are shown.

  16. Lung tissues in systemic sclerosis have gene expression patterns unique to pulmonary fibrosis and pulmonary hypertension

    PubMed Central

    Hsu, Eileen; Shi, Haiwen; Jordan, Rick M.; Lyons-Weiler, James; Pilewski, Joseph M.; Feghali-Bostwick, Carol A.

    2010-01-01

    Objective Pulmonary complications in systemic sclerosis (SSc), including pulmonary fibrosis (PF) and pulmonary arterial hypertension (PAH), are the leading cause of mortality. We compared the molecular fingerprint of SSc lung tissues and matching primary lung fibroblasts to those of normal donors, and patients with idiopathic pulmonary fibrosis (IPF) and idiopathic pulmonary arterial hypertension (IPAH). Methods Lung tissues were obtained from 33 patients with SSc who underwent lung transplantation. Tissues and cells from a subgroup of SSc patients with predominantly PF or PAH were compared to those from normal donors, patients with IPF, or IPAH. Microarray data was analyzed using Efficiency Analysis for determination of optimal data processing methods. Real time PCR and immunohistochemistry were used to confirm differential levels of mRNA and protein, respectively. Results We identified a consensus of 242 and 335 genes that were differentially expressed in lungs and primary fibroblasts, respectively. Enriched function groups in SSc-PF and IPF lungs included fibrosis, insulin-like growth factor signaling and caveolin-mediated endocytosis. Functional groups shared by SSc-PAH and IPAH lungs included antigen presentation, chemokine activity, and IL-17 signaling. Conclusion Using microarray analysis on carefully phenotyped SSc and comparator lung tissues, we demonstrated distinct molecular profiles in tissues and fibroblasts of patients with SSc-associated lung disease compared to idiopathic forms of lung disease. Unique molecular signatures were generated that are disease- (SSc) and phenotype- (PF vs PAH) specific. These signatures provide new insights into pathogenesis and potential therapeutic targets for SSc lung disease. PMID:21360508

  17. A nanostructured genosensor for the early diagnosis of systemic arterial hypertension.

    PubMed

    Rolim, Thalita; Cancino, Juliana; Zucolotto, Valtencir

    2015-02-01

    The rapid progress of nanomedicine, especially in areas related to medical imaging and diagnostics, has motivated the development of new nanomaterials that can be combined with biological materials for specific medical applications. One such area of research involves the detection of specific DNA sequences for the early diagnosis of genetic diseases, using nanoparticles-containing genosensors. Typical genosensors devices are based on the use of sensing electrodes - biorecognition platforms - containing immobilized capture DNA probes capable of hybridizing with specific target DNA sequences. In this paper we show that upon an appropriate design of the biorecognition platform, efficient sandwich-type genosensors based upon DNA-AuNPs nanocomplexes can be efficiently applied to the detection of a Systemic Arterial Hypertension (SAH) polymorphism located in intron 16 of the Angiotensin-converter enzyme (ACE) gene. Since SAH is intimately related to heart diseases, especially blood hypertension, its early detection is of great biomedical interest. The biorecognition platforms were assembled using mixed self-assembled monolayers (SAMmix), which provided the immobilization of organized architectures with molecular control. Detection of the DNA target sequence at concentrations down to 1 nM was carried out using electrochemical impedance spectroscopy (EIS). We show that the use of EIS combined with specific nanobiocomplexes represents an efficient method for the unambiguous detection of complementary DNA hybridization for preventative nanomedicine applications.

  18. Fatal postoperative systemic pulmonary hypertension in benfluorex-induced valvular heart disease surgery

    PubMed Central

    Baufreton, Christophe; Bruneval, Patrick; Rousselet, Marie-Christine; Ennezat, Pierre-Vladimir; Fouquet, Olivier; Giraud, Raphael; Banfi, Carlo

    2017-01-01

    Abstract Rationale: Drug-induced valvular heart disease (DI-VHD) remains an under-recognized entity. Patient concerns: This report describes a heart valve replacement which was complicated by intractable systemic pulmonary arterial hypertension in a 61-year-old female with severe restrictive mitral and aortic disease. The diagnosis of valvular disease was preceded by a history of unexplained respiratory distress. The patient had been exposed to benfluorex for 6.5 years. Diagnoses: The diagnostic procedure documented specific drug-induced valvular fibrosis. Interventions: Surgical mitral and aortic valve replacement was performed. Outcomes: Heart valve replacement was postoperatively complicated by unanticipated disproportionate pulmonary hypertension. This issue was fatal despite intensive care including prolonged extracorporeal life support. Lessons: Benfluorex is a fenfluramine derivative which has been marketed between 1976 and 2009. Although norfenfluramine is the common active and toxic metabolite of all fenfluramine derivatives, the valvular and pulmonary arterial toxicity of benfluorex was much less known than that of fenfluramine and dexfenfluramine. The vast majority of benfluorex-induced valvular heart disease remains misdiagnosed as hypothetical rheumatic fever due to similarities between both etiologies. Better recognition of DI-VHD is likely to improve patient outcome. PMID:28079786

  19. The Circadian Timing System: A Recent Addition in the Physiological Mechanisms Underlying Pathological and Aging Processes

    PubMed Central

    Arellanes-Licea, Elvira; Caldelas, Ivette; De Ita-Pérez, Dalia; Díaz-Muñoz, Mauricio

    2014-01-01

    Experimental findings and clinical observations have strengthened the association between physio-pathologic aspects of several diseases, as well as aging process, with the occurrence and control of circadian rhythms. The circadian system is composed by a principal pacemaker in the suprachiasmatic nucleus (SNC) which is in coordination with a number of peripheral circadian oscillators. Many pathological entities such as metabolic syndrome, cancer and cardiovascular events are strongly connected with a disruptive condition of the circadian cycle. Inadequate circadian physiology can be elicited by genetic defects (mutations in clock genes or circadian control genes) or physiological deficiencies (desynchronization between SCN and peripheral oscillators). In this review, we focus on the most recent experimental findings regarding molecular defects in the molecular circadian clock and the altered coordination in the circadian system that are related with clinical conditions such as metabolic diseases, cancer predisposition and physiological deficiencies associated to jet-lag and shiftwork schedules. Implications in the aging process will be also reviewed. PMID:25489492

  20. Role of the sympathetic nervous system in cold-induced hypertension in rats.

    PubMed

    Papanek, P E; Wood, C E; Fregly, M J

    1991-07-01

    Hypertension develops in rats exposed chronically to cold [6 +/- 2 degrees C (SE)] and includes both an elevation of mean arterial pressure and cardiac hypertrophy. Previous studies suggest that cold-exposed animals, at least initially, have a large sustained increase in the activity of their sympathetic nervous system, suggesting a failure of the baroreceptor system to provide sufficient negative feedback to the central nervous system. The present study was designed to investigate whether alterations in the activity of the sympathetic nervous system, including the baroreceptor reflex, occur during exposure to cold and whether they contribute to cold-induced hypertension. Twenty male rats were prepared with indwelling catheters in the femoral artery and vein. Ten of the rats were exposed to cold (6 +/- 2 degrees C) chronically, while the remaining 10 were kept at 26 +/- 2 degrees C. Withdrawal of arterial blood samples (less than 5 ml/kg), measurement of direct arterial pressures, and measurement of baroreflex function were carried out at 0800 h at intervals throughout the experiment. Norepinephrine and epinephrine concentrations in plasma were also determined at intervals throughout the experiment. Systolic, diastolic, and mean blood pressures of cold-exposed rats were increased to levels significantly above those of controls. The sensitivity of the baroreflex (delta heart period/delta mean arterial pressure) was decreased in the cold-treated group. The concentration of norepinephrine in plasma increased after 24 h of exposure to cold and remained elevated throughout the experiment, whereas the concentration of epinephrine in plasma increased initially but returned to control levels after 19 days of exposure to cold.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Splanchnic-aortic inflammatory axis in experimental portal hypertension

    PubMed Central

    Aller, Maria-Angeles; de las Heras, Natalia; Nava, Maria-Paz; Regadera, Javier; Arias, Jaime; Lahera, Vicente

    2013-01-01

    Splanchnic and systemic low-grade inflammation has been proposed to be a consequence of long-term prehepatic portal hypertension. This experimental model causes minimal alternations in the liver, thus making a more selective study possible for the pathological changes characteristic of prehepatic portal hypertension. Low-grade splanchnic inflammation after long-term triple partial portal vein ligation could be associated with liver steatosis and portal hypertensive intestinal vasculopathy. In fact, we have previously shown that prehepatic portal hypertension in the rat induces liver steatosis and changes in lipid and carbohydrate metabolism similar to those produced in chronic inflammatory conditions described in metabolic syndrome in humans. Dysbiosis and bacterial translocation in this experimental model suggest the existence of a portal hypertensive intestinal microbiome implicated in both the splanchnic and systemic alterations related to prehepatic portal hypertension. Among the systemic impairments, aortopathy characterized by oxidative stress, increased levels of proinflammatory cytokines and profibrogenic mediators stand out. In this experimental model of long-term triple portal vein ligated-rats, the abdominal aortic proinflammatory response could be attributed to oxidative stress. Thus, the increased aortic reduced-nicotinamide-adenine dinucleotide phosphate [NAD(P)H] oxidase activity could be associated with reactive oxygen species production and promote aortic inflammation. Also, oxidative stress mediated by NAD(P)H oxidase has been associated with risk factors for inflammation and atherosclerosis. The splanchnic and systemic pathology that is produced in the long term after triple partial portal vein ligation in the rat reinforces the validity of this experimental model to study the chronic low-grade inflammatory response induced by prehepatic portal hypertension. PMID:24307792

  2. Association of systemic hypertension with renal injury in dogs with induced renal failure.

    PubMed

    Finco, Delmar R

    2004-01-01

    Systemic hypertension is hypothesized to cause renal injury to dogs. This study was performed on dogs with surgically induced renal failure to determine whether hypertension was associated with altered renal function or morphology. Mean arterial pressure (MAP), heart rate (HR), systolic arterial pressure (SAP), and diastolic arterial pressure (DAP) were measured before and after surgery. Glomerular filtration rate (GFR) and urine protein:creatinine ratios (UPC) were measured at 1, 12, 24, 36, and 56-69 weeks after surgery, and renal histology was evaluated terminally. The mean of weekly MAP, SAP, and DAP measurements for each dog over the 1st 26 weeks was used to rank dogs on the basis of MAP, SAP, or DAP values. A statistically significant association was found between systemic arterial pressure ranking and ranked measures of adverse renal responses. When dogs were divided into higher pressure and lower pressure groups on the basis of SAP, group 1 (higher pressure, n = 9) compared with group 2 (lower pressure, n = 10) had significantly lower GFR values at 36 and 56-69 weeks; higher UPC values at 12 and 56-69 weeks; and higher kidney lesion scores for mesangial matrix, tubule damage, and fibrosis. When dogs were divided on MAP and DAP values, group 1 compared with group 2 had significantly lower GFR values at 12, 24, 36, and 56-69 weeks; higher UPC values at 12 and 56-69 weeks; and higher kidney lesion scores for mesangial matrix, tubule damage, fibrosis, and cell infiltrate. These results demonstrate an association between increased systemic arterial pressure and renal injury. Results from this study might apply to dogs with some types of naturally occurring renal failure.

  3. [Comparative pathology of the microcirculatory bed].

    PubMed

    Strukov, A I; Vorob'eva, A A

    1976-11-01

    This paper presents an analysis of publications, mostly by Soviet authores, on clinical studies and morphological examinations of the microcirculatory bed in different pathology. It is concluded that the microcirculatory bed should be regarded as an integral system responding to the pathological effects by a local and general reaction of its structural components and by changing the rheological properties of blood. Two types of changes develop in the microcirculatory system -- sterotyped ones, typical for extreme states (various kinds of shock, hypertensive crisis, stress situations), and those specific for certain diseases (diabetes melitus, essential hypertension, athersclerosis, collagenoses, etc.). In all the above diseases the pathological process affects the functional structures of microcirculation that undergo a rearrangement in accordance with the requirements of the body. In the initial period of the disease this re-arrangement is of a compensatory nature and passes ahead of the clinical manifestations. A comparison of the pictutrs obtained by biomicroscopy of the bulbconjunctiva of the eye and of other mucosae with film preparations of the serosae demonstrates their complete similarity. Therefore, the method of biomicroscopy of the eyeball and of the mucosae as a method reflecting the state of microcirculation in the body as a whole should become an integral part of the clinical examination of patients.

  4. Therapeutic perspectives in hypertension: novel means for renin-angiotensin-aldosterone system modulation and emerging device-based approaches.

    PubMed

    Unger, Thomas; Paulis, Ludovit; Sica, Domenic A

    2011-11-01

    The conventional antihypertensive therapies including renin-angiotensin-aldosterone system antagonists (converting enzyme inhibitors, receptor blockers, renin inhibitors, and mineralocorticoid receptor blockers), diuretics, β-blockers, and calcium channel blockers are variably successful in achieving the challenging target blood pressure values in hypertensive patients. Difficult to treat hypertension is still a commonly observed problem world-wide. A number of drugs are considered to be used as novel therapies for hypertension. Renalase supplementation, vasopeptidase inhibitors, endothelin antagonists, and especially aldosterone antagonists (aldosterone synthase inhibitors and novel selective mineralocorticoid receptor blockers) are considered an option in resistant hypertension. In addition, the aldosterone antagonists as well as (pro)renin receptor blockers or AT(2) receptor agonists might attenuate end-organ damage. This array of medications has now been complemented by a number of new approaches of non-pharmacological strategies including vaccination, genomic interference, controlled breathing, baroreflex activation, and probably most successfully renal denervation techniques. However, the progress on innovative therapies seems to be slow and the problem of resistant hypertension and proper blood pressure control appears to be still persisting. Therefore the regimens of currently available drugs are being fine-tuned, resulting in the establishment of several novel fixed-dose combinations including triple combinations with the aim to facilitate proper blood pressure control. It remains an exciting question which approach will confer the best blood pressure control and risk reduction in this tricky disease.

  5. Exercise Training Improves the Altered Renin-Angiotensin System in the Rostral Ventrolateral Medulla of Hypertensive Rats

    PubMed Central

    Ren, Chang-zhen; Yang, Ya-Hong; Sun, Jia-cen; Wu, Zhao-Tang; Zhang, Ru-Wen; Shen, Du; Wang, Yang-Kai

    2016-01-01

    The imbalance between angiotensin II (Ang II) and angiotensin 1–7 (Ang 1–7) in the brain has been reported to contribute to cardiovascular dysfunction in hypertension. Exercise training (ExT) is beneficial to hypertension and the mechanism is unclear. This study was aimed to determine if ExT improves hypertension via adjusting renin angiotensin system in cardiovascular centers including the rostral ventrolateral medulla (RVLM). Spontaneously hypertensive rats (SHR, 8 weeks old) were subjected to low-intensity ExT or kept sedentary (Sed) for 12 weeks. Blood pressure elevation coupled with increase in age was significantly decreased in SHR received ExT compared with Sed. The results in vivo showed that ExT significantly reduced or increased the cardiovascular responses to central application of sarthran (antagonist of Ang II) or A779 (antagonist of Ang 1–7), respectively. The protein expression of the Ang II acting receptor AT1R and the Ang 1–7 acting receptor Mas in the RVLM was significantly reduced and elevated in SHR following ExT, respectively. Moreover, production of reactive oxygen species in the RVLM was significantly decreased in SHR following ExT. The current data suggest that ExT improves hypertension via improving the balance of Ang II and Ang 1–7 and antioxidative stress at the level of RVLM. PMID:26881037

  6. RecutClub.com: An Open Source, Whole Slide Image-based Pathology Education System

    PubMed Central

    Christensen, Paul A.; Lee, Nathan E.; Thrall, Michael J.; Powell, Suzanne Z.; Chevez-Barrios, Patricia; Long, S. Wesley

    2017-01-01

    Background: Our institution's pathology unknown conferences provide educational cases for our residents. However, the cases have not been previously available digitally, have not been collated for postconference review, and were not accessible to a wider audience. Our objective was to create an inexpensive whole slide image (WSI) education suite to address these limitations and improve the education of pathology trainees. Materials and Methods: We surveyed residents regarding their preference between four unique WSI systems. We then scanned weekly unknown conference cases and study set cases and uploaded them to our custom built WSI viewer located at RecutClub.com. We measured site utilization and conference participation. Results: Residents preferred our OpenLayers WSI implementation to Ventana Virtuoso, Google Maps API, and OpenSlide. Over 16 months, we uploaded 1366 cases from 77 conferences and ten study sets, occupying 793.5 GB of cloud storage. Based on resident evaluations, the interface was easy to use and demonstrated minimal latency. Residents are able to review cases from home and from their mobile devices. Worldwide, 955 unique IP addresses from 52 countries have viewed cases in our site. Conclusions: We implemented a low-cost, publicly available repository of WSI slides for resident education. Our trainees are very satisfied with the freedom to preview either the glass slides or WSI and review the WSI postconference. Both local users and worldwide users actively and repeatedly view cases in our study set. PMID:28382224

  7. Comparison of the diagnostic utility of digital pathology systems for telemicrobiology

    PubMed Central

    Rhoads, Daniel D.; Habib-Bein, Nadia F.; Hariri, Rahman S.; Hartman, Douglas J.; Monaco, Sara E.; Lesniak, Andrew; Duboy, Jon; Salama, Mohamed El-Sayed; Pantanowitz, Liron

    2016-01-01

    Introduction: Telemicrobiology is a growing component of clinical microbiology informatics. However, few studies have been performed to assess the diagnostic utility of telemicroscopy systems in evaluating infectious agents. Objective: Evaluate multiple contemporary digital pathology platforms for use in diagnostic telemicrobiology. Materials and Methods: A mix of thirty cases that included viral, bacterial, fungal, and parasitological findings were evaluated by four experts using ×40 whole slide imaging (WSI) scans, ×83 oil-immersion WSI scans, ×100 oil-immersion WSI scans, digital photomicrographs, and glass slides. Results: The ×83 WSI, ×100 WSI, and photomicrograph interpretations were not significantly different in quality and accuracy when compared to glass slide interpretations. The ×40 WSI interpretations were of lower quality and were more likely to be incorrect when compared to glass slide interpretations. Conclusions: In this study, high magnification, oil-immersion digital pathology platforms are better suited to support telemicrobiology applications and yield interpretations on par with glass slide evaluations. PMID:27076988

  8. Successful treatment with bosentan for pulmonary hypertension and reduced peripheral circulation in juvenile systemic sclerosis.

    PubMed

    Shimizu, Masaki; Hashida, Yoko; Ueno, Kazuyuki; Yokoyama, Tadafumi; Nakayama, Yuko; Saito, Takekatsu; Ohta, Kunio; Takehara, Kazuhiko; Yachie, Akihiro

    2011-10-01

    Pulmonary arterial hypertension (PAH) when associated with systemic sclerosis (SSc) (SSc-PAH) is one of the leading causes of mortality and is found in 10-15% of adult patients with SSc. The ET receptor antagonist bosentan has been shown to be effective in the treatment of adult patients with SSc-PAH. Furthermore, it has been shown that bosentan ameliorates decreased skin perfusion and digital ulceration secondary to SSc. However, the effectiveness and safety of bosentan for treatment of juvenile SSc still remains unclear. We describe a case of juvenile SSc-PAH successfully treated with bosentan. The present case shows that bosentan ameliorated PAH and peripheral circulation as evaluated by cold stress thermography. No bosentan-related adverse events such as liver dysfunction were observed. Prospective randomized trials are required to validate the effectiveness of bosentan for patients with juvenile SSc; however, bosentan might be useful for the management of patients with juvenile SSc.

  9. Factors Influencing the Selection of Speech Pathology as a Career: A Qualitative Analysis Utilising the Systems Theory Framework

    ERIC Educational Resources Information Center

    Byrne, Nicole

    2007-01-01

    Factors identified by 16 participants during in-depth interviews as influencing selection of speech pathology as a career were described using the Systems Theory Framework (STF, Patton & McMahon, 2006). Participants were highly likely to identify factors from the individual and social systems, but not the environmental-societal system, of the STF…

  10. Techno economic systems and excessive consumption: a political economy of 'pathological' gambling.

    PubMed

    Reith, Gerda

    2013-12-01

    This article argues that gambling is a paradigmatic form of consumption that captures the intensified logic at the heart of late modern capitalist societies. As well as a site of intensified consumption, it claims that gambling has also become the location of what has been described as a new form of 'social pathology' related to excess play. Drawing on Castells' (1996) notion of techno-economic systems, it explores the ways that intersections between technology, capital and states have generated the conditions for this situation, and critiques the unequal distribution of gambling environments that result. It argues that, while the products of these systems are consumed on a global scale, the risks associated with them tend to be articulated in bio-psychological discourses of 'pathology' which are typical of certain types of knowledge that have salience in neo-liberal societies, and which work to conceal wider structural relationships. We argue that a deeper understanding of the political and cultural economy of gambling environments is necessary, and provide a synoptic overview of the conditions upon which gambling expansion is based. This perspective highlights parallels with the wider global economy of finance capital, as well as the significance of intensified consumption, of which gambling is an exemplary instance. It also reveals the existence of a geo-political dispersal of 'harms', conceived as deteriorations of financial, temporal and social relationships, which disproportionately affect vulnerable social groups. From this, we urge an understanding of commercial gambling based on a critique of the wider social body of gambling environments within techno economic systems, rather than the (flawed) individual bodies within them.

  11. Food Insecurity and Self-Reported Hypertension Among Hispanic, Black, and White Adults in 12 States, Behavioral Risk Factor Surveillance System, 2009

    PubMed Central

    Njai, Rashid S.; Siegel, Paul Z.

    2014-01-01

    Food insecurity is positively linked to risk of hypertension; however, it is not known whether this relationship persists after adjustment for socioeconomic position (SEP). We examined the association between food insecurity and self-reported hypertension among adults aged 35 or older (N = 58,677) in 12 states that asked the food insecurity question in their 2009 Behavioral Risk Factor Surveillance System questionnaire. After adjusting for SEP, hypertension was more common among adults reporting food insecurity (adjusted prevalence ratio, 1.27; 95% confidence interval, 1.19–1.36). Our study found a positive relationship between food insecurity and hypertension after adjusting for SEP and other characteristics. PMID:25232748

  12. Food insecurity and self-reported hypertension among Hispanic, black, and white adults in 12 states, Behavioral Risk Factor Surveillance System, 2009.

    PubMed

    Irving, Shalon M; Njai, Rashid S; Siegel, Paul Z

    2014-09-18

    Food insecurity is positively linked to risk of hypertension; however, it is not known whether this relationship persists after adjustment for socioeconomic position (SEP). We examined the association between food insecurity and self-reported hypertension among adults aged 35 or older (N = 58,677) in 12 states that asked the food insecurity question in their 2009 Behavioral Risk Factor Surveillance System questionnaire. After adjusting for SEP, hypertension was more common among adults reporting food insecurity (adjusted prevalence ratio, 1.27; 95% confidence interval, 1.19-1.36). Our study found a positive relationship between food insecurity and hypertension after adjusting for SEP and other characteristics.

  13. Supporting the self-management of hypertension: Patients' experiences of using a mobile phone-based system.

    PubMed

    Hallberg, I; Ranerup, A; Kjellgren, K

    2016-02-01

    Globally, hypertension is poorly controlled and its treatment consists mainly of preventive behavior, adherence to treatment and risk-factor management. The aim of this study was to explore patients' experiences of an interactive mobile phone-based system designed to support the self-management of hypertension. Forty-nine patients were interviewed about their experiences of using the self-management system for 8 weeks regarding: (i) daily answers on self-report questions concerning lifestyle, well-being, symptoms, medication intake and side effects; (ii) results of home blood-pressure measurements; (iii) reminders and motivational messages; and (iv) access to a web-based platform for visualization of the self-reports. The audio-recorded interviews were analyzed using qualitative thematic analysis. The patients considered the self-management system relevant for the follow-up of hypertension and found it easy to use, but some provided insight into issues for improvement. They felt that using the system offered benefits, for example, increasing their participation during follow-up consultations; they further perceived that it helped them gain understanding of the interplay between blood pressure and daily life, which resulted in increased motivation to follow treatment. Increased awareness of the importance of adhering to prescribed treatment may be a way to minimize the cardiovascular risks of hypertension.

  14. Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin–angiotensin system and proinflammatory cytokines in hypertension

    SciTech Connect

    Su, Qing; Qin, Da-Nian; Wang, Fu-Xin; Ren, Jun; Li, Hong-Bao; Zhang, Meng; Yang, Qing; Miao, Yu-Wang; Yu, Xiao-Jing; Qi, Jie; Zhu, Zhiming; Zhu, Guo-Qing; Kang, Yu-Ming

    2014-04-15

    Aims: To explore whether reactive oxygen species (ROS) scavenger (tempol) in the hypothalamic paraventricular nucleus (PVN) attenuates renin–angiotensin system (RAS) and proinflammatory cytokines (PICs), and decreases the blood pressure and sympathetic activity in angiotensin II (ANG II)-induced hypertension. Methods and results: Male Sprague–Dawley rats were infused intravenously with ANG II (10 ng/kg per min) or normal saline (NS) for 4 weeks. These rats were treated with bilateral PVN infusion of oxygen free radical scavenger tempol (TEMP, 20 μg/h) or vehicle (artificial cerebrospinal fluid, aCSF) for 4 weeks. ANG II infusion resulted in increased mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). These ANG II-infused rats also had higher levels of gp91{sup phox} (a subunit of NAD(P)H oxidase), angiotensin-converting enzyme (ACE), and interleukin-1beta (IL-1β) in the PVN than the control animals. Treatment with PVN infusion of TEMP attenuated the overexpression of gp91{sup phox}, ACE and IL-1β within the PVN, and decreased sympathetic activity and MAP in ANG II-infused rats. Conclusion: These findings suggest that ANG II infusion induces elevated PICs and oxidative stress in the PVN, which contribute to the sympathoexcitation in hypertension. Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin–angiotensin system, proinflammatory cytokines and oxidative stress in ANG II-induced hypertension. - Highlights: • The effect of chronic inhibiting PVN superoxide on hypertension was investigated. • ANG II infusion induced increased proinflammatory cytokines and superoxide in PVN. • ANG II infusion resulted in oxidative stress, sympathoexcitation and hypertension. • Chronic inhibiting PVN superoxide attenuates RAS and cytokines in hypertension.

  15. Chronomodulated drug delivery system of urapidil for the treatment of hypertension

    PubMed Central

    Chaudhary, Sona S.; Patel, Hetal K.; Parejiya, Punit B.; Shelat, Pragna K.

    2015-01-01

    Introduction: Hypertension is a disease which shows circadian rhythm in the pattern of two peaks, one in the evening at about 7pm and other in the early morning between 4 am to 8 am. Conventional therapies are incapable to target those time points when actually the symptoms get worsened. To achieve drug release at two time points, chronomodulated delivery system may offer greater benefits. Materials and methods: The chronomodulated system comprised of dual approach; immediate release granules (IRG) and pulsatile release mini-tablets (PRM) filled in the hard gelatin capsule. The mini-tablets were coated using Eudragit S-100 which provided the lag time. To achieve the desired release, various parameters like coating duration and coat thickness were studied. The immediate release granules were evaluated for micromeritical properties and drug release, while mini-tablets were evaluated for various parameters such as hardness, thickness, friability, weight variation, drug content, and disintegration time and in-vitro drug release. Compatibility of drug-excipient was checked by fourier transform infrared spectroscopy and Differential scanning calorimetry studies and pellets morphology was done by Scanning electron microscopy studies. Results: The in-vitro release profile suggested that immediate release granules gives drug release within 20 min at the time of evening attack while the programmed pulsatile release was achieved from coated mini-tablets after a lag time of 9hrs, which was consistent with the demand of drug during early morning hour attack. Pellets found to be spherical in shape with smooth surface. Moreover compatibility studies illustrated no deleterious reaction between drug and polymers used in the study. Conclusions: The dual approach of developed chronomodulated formulation found to be satisfactory in the treatment of hypertension. PMID:25838996

  16. Nonselective Blocking of the Sympathetic Nervous System Decreases Detrusor Overactivity in Spontaneously Hypertensive Rats

    PubMed Central

    Kim, Khae-Hawn; Jin, Long-Hu; Choo, Gwoan-Youb; Lee, Hun-Jae; Choi, Bo-Hwa; Kwak, Jiyeon; Yoon, Sang-Min; Park, Chang-Shin; Lee, Tack

    2012-01-01

    The involuntary dual control systems of the autonomic nervous system (ANS) in the bladder of awake spontaneously hypertensive rats (SHRs) were investigated through simultaneous registrations of intravesical and intraabdominal pressures to observe detrusor overactivity (DO) objectively as a core symptom of an overactive bladder. SHRs (n = 6) showed the features of overactive bladder syndrome during urodynamic study, especially DO during the filling phase. After injection of the nonselective sympathetic blocking agent labetalol, DO disappeared in 3 of 6 SHRs (50%). DO frequency decreased from 0.98 ± 0.22 min−1 to 0.28 ± 0.19 min−1 (p < 0.01), and DO pressure decreased from 3.82 ± 0.57 cm H2O to 1.90 ± 0.86 cm H2O (p < 0.05). This suggests that the DO originating from the overactive parasympathetic nervous system is attenuated by the nonselective blocking of the sympathetic nervous system. The detailed mechanism behind this result is still not known, but parasympathetic overactivity seems to require overactive sympathetic nervous system activity in a kind of balance between these two systems. These findings are consistent with recent clinical findings suggesting that patients with idiopathic overactive bladder may have ANS dysfunction, particularly a sympathetic dysfunction. The search for newer and better drugs than the current anticholinergic drugs as the mainstay for overactive bladder will be fueled by our research on these sympathetic mechanisms. Further studies of this principle are required. PMID:22606029

  17. [Heme oxygenase and carbon monoxide in the physiology and pathology of the cardiovascular system].

    PubMed

    Bełtowski, Jerzy; Jamroz, Anna; Borkowska, Ewelina

    2004-03-03

    Heme oxygenase (HO) degrades heme to carbon monoxide (CO), ferrous ions, and the bile pigment biliverdin, which is subsequently reduced to the other important bile pigment, bilirubin, by biliverdin reductase. Fe2+ liberated from the heme molecule upregulates ferritin production, and bile pigments are potent endogenous antioxidants. The HO enzyme exists in three isophorms: HO-1 is expressed at low levels under physiological conditions, but is induced by numerous factors, including oxidative stress, inflammation, nitric oxide, an elevated level of substrate, and hypoxia. HO-2 is a constitutive enzyme involved in the baseline production of CO in the cardiovascular and nervous systems, whereas HO-3 is also ubiquitously expressed, but possesses low catalytic activity. Like nitric oxide, CO activates soluble guanylate cyclase and elevates cGMP in target tissues, which dilates blood vessels. It also does this by directly activating potassium channels in vascular smooth muscle cells. In addition, CO inhibits platelet aggregation and proliferation of vascular smooth muscle cells, inhibits apoptosis, and stimulates angiogenesis. Both deficiency, and excess of HO-1 may be involved in the pathogenesis of arterial hypertension. Induction of HO-1 attenuates atherosclerosis and myocardial ischemia-reperfusion injury. Pharmacological and genetic induction of HO-1 as well as the delivery of exogenous CO are promising therapeutic strategies for the treatment of cardiovascular diseases.

  18. Does the choice of display system influence perception and visibility of clinically relevant features in digital pathology images?

    NASA Astrophysics Data System (ADS)

    Kimpe, Tom; Rostang, Johan; Avanaki, Ali; Espig, Kathryn; Xthona, Albert; Cocuranu, Ioan; Parwani, Anil V.; Pantanowitz, Liron

    2014-03-01

    Digital pathology systems typically consist of a slide scanner, processing software, visualization software, and finally a workstation with display for visualization of the digital slide images. This paper studies whether digital pathology images can look different when presenting them on different display systems, and whether these visual differences can result in different perceived contrast of clinically relevant features. By analyzing a set of four digital pathology images of different subspecialties on three different display systems, it was concluded that pathology images look different when visualized on different display systems. The importance of these visual differences is elucidated when they are located in areas of the digital slide that contain clinically relevant features. Based on a calculation of dE2000 differences between background and clinically relevant features, it was clear that perceived contrast of clinically relevant features is influenced by the choice of display system. Furthermore, it seems that the specific calibration target chosen for the display system has an important effect on the perceived contrast of clinically relevant features. Preliminary results suggest that calibrating to DICOM GSDF calibration performed slightly worse than sRGB, while a new experimental calibration target CSDF performed better than both DICOM GSDF and sRGB. This result is promising as it suggests that further research work could lead to better definition of an optimized calibration target for digital pathology images resulting in a positive effect on clinical performance.

  19. Arteriovenous fistula and forward hypertension in the portal circulation.

    PubMed

    Pasternak, B M; Cohen, H

    1978-05-01

    The notorious predilection for rupture of splenic artery aneurysms in women of childbearing age is once more stressed by this case report. Although such ruptures usually result in a catastrophic interabdominal bleeding, in rare instances they lead to the formation of an arteriovenous fistula and consequent portal hypertension. Arterialization of the portal vein results in a progressive development of intrinsic hepatic morphologic changes and hepatoportal sclerosis, which further elevate the pressure in the portal system. This combination of pathophysiologic hemodynamic features closely resembles the original concept of Banti. He postulated that portal hypertension began with pathologic changes within the spleen which were associated with an increased blood flow through this organ. This led to increased flow and pressure in the portal venous system and ultimately cumulated in cirrhosis of the liver. This concept of the pathophysiology of portal hypertension has been universally abandoned, but it could serve as a model of the sequelae of an arteriovenous communication within the portal system.

  20. [A system of digital analysis for the diagnosis of vascular pathologies of the fundus oculi].

    PubMed

    Branchevskiĭ, S L; Gavrilova, N A; Il'iasova, N Iu; Khramov, A G

    2003-01-01

    A diagnostic tools' set was worked out for the digital analysis of eye-fundus images; it comprises a retinophot and a digital camera adapted to it as well as a computer system and a special soft. A new mathematical model of a fragment of the ocular main microcirculation vessel and the below related global diagnostic parameters of the vascular system were elaborated: mean diameter, deviation from linearity, image acutance, fluctuations' amplitude for thickness and route, and sinuosity of thickness and route. The system of eye-fundus image processing provides for precising a nature of changes in vascular thickness along the route and for assessing the local diameter by using the vascular profile; it can also be used for determining the angle of vessels' branching. A set of expert diagnostic etalons was set up for vascular pathologies of the eye fundus and an appropriate database was created. The advantages of the designed system are: the possibility to use it comprehensively in clinical practice, less time needed to make and to analyze the eye-fundus images, a higher accuracy in determining the local vascular diameter, the possibility to perform simultaneously an analysis of diagnostic signs of retinal vessels on the basis of using a radically new approach towards assessing the vascular system ("tracing-type isolation of segments"), a higher diagnostic efficiency, the possibility to perform the differential diagnosis and the capability of preserving data without any limitations by volume and store duration time.

  1. Effect of noisy stimulation on neurobiological sensitization systems and its role for normal and pathological physiology

    NASA Astrophysics Data System (ADS)

    Huber, Martin; Braun, Hans; Krieg, J.\\:Urgen-Christian

    2004-03-01

    Sensitization is discussed as an important phenomenon playing a role in normal physiology but also with respect to the initiation and progression of a variety of neuropsychiatric disorders such as epilepsia, substance-related disorders or recurrent affective disorders. The relevance to understand the dynamics of sensitization phenomena is emphasized by recent findings that even single stimulations can induce longlasting changes in biological systems. To address specific questions associated with the sensitization dynamics, we use a computational approach and develop simple but physiologically-plausible models. In the present study we examine the effect of noisy stimulation on sensitization development in the model. We consider sub- and suprathresold stimulations with varying noise intensities and determine as response measures the (i) absolute number of stimulus-induced sensitzations and (ii) the temporal relsation of stimulus-sensitization coupling. The findings indicate that stochastic effects including stochastic resonance might well contribute to the physiology of sensitization mechanisms under both nomal and pathological conditions.

  2. [Fundamentals of interferon system function in pathology and molecular biological peculiarities of interferon production].

    PubMed

    Spivak, M Ia; Didenko, L F; Lazarenko, L M; Zholobak, N M

    2008-01-01

    Molecular biological peculiarities of interferon system function in PV-infected persons have been found. It is evident that the interferon production, anti-inflammatory cytokines and their receptors and also defensines play an important role in the mechanism of virus interaction with sensitive cells of macroorganism with development of pathological process. The new conception of expediency for the use of interferons and their inducers as the polyfunctional regulators with a broad spectrum of activity for the treatment of PV-infected patients was suggested. Patents for the method of treatment of PV-infected patients were obtained. New inducers of interferon as well as recombinant IFN-alpha-2b was developed. Our results were introduced in the medical practice.

  3. Pathology of the Nervous System in Von Hippel-Lindau Disease

    PubMed Central

    Alomari, Ahmed K.

    2015-01-01

    Von Hippel-Lindau (VHL) disease is a tumor syndrome that frequently involves the central nervous system (CNS). It is caused by germline mutation of the VHL gene. Subsequent VHL inactivation in selected cells is followed by numerous well-characterized molecular consequences, in particular, activation and stabilization of hypoxia-inducible factors HIF1 and HIF2. The link between VHL gene inactivation and tumorigenesis remains poorly understood. Hemangioblastomas are the most common manifestation in the CNS; however, CNS invasion by VHL disease-associated endolymphatic sac tumors or metastatic renal cancer also occur, and their differentiation from primary hemangioblastoma may be challenging. Finally, in this review, we present recent morphologic insights on the developmental concept of VHL tumorigenesis which is best explained by pathologic persistence of temporary embryonic progenitor cells. PMID:28326266

  4. Pathology of the Nervous System in Von Hippel-Lindau Disease.

    PubMed

    Vortmeyer, Alexander O; Alomari, Ahmed K

    2015-01-01

    Von Hippel-Lindau (VHL) disease is a tumor syndrome that frequently involves the central nervous system (CNS). It is caused by germline mutation of the VHL gene. Subsequent VHL inactivation in selected cells is followed by numerous well-characterized molecular consequences, in particular, activation and stabilization of hypoxia-inducible factors HIF1 and HIF2. The link between VHL gene inactivation and tumorigenesis remains poorly understood. Hemangioblastomas are the most common manifestation in the CNS; however, CNS invasion by VHL disease-associated endolymphatic sac tumors or metastatic renal cancer also occur, and their differentiation from primary hemangioblastoma may be challenging. Finally, in this review, we present recent morphologic insights on the developmental concept of VHL tumorigenesis which is best explained by pathologic persistence of temporary embryonic progenitor cells.

  5. CD74 Deficiency Mitigates Systemic Lupus Erythematosus-like Autoimmunity and Pathological Findings in Mice.

    PubMed

    Zhou, Yi; Chen, Huimei; Liu, Li; Yu, Xueqing; Sukhova, Galina K; Yang, Min; Zhang, Lijun; Kyttaris, Vasileios C; Tsokos, George C; Stillman, Isaac E; Ichimura, Takaharu; Bonventre, Joseph V; Libby, Peter; Shi, Guo-Ping

    2017-04-01

    CD74 mediates MHC class-II antigenic peptide loading and presentation and plays an important role in the pathogenesis of autoimmune diseases, including systemic lupus erythematosus. C57BL/6 Fas(lpr) mice that develop spontaneous lupus-like autoimmunity and pathology showed elevated CD74 expression in the inflammatory cell infiltrates and the adjacent tubular epithelial cells (TECs) in kidneys affected by lupus nephritis but negligible levels in kidneys from age-matched wild-type mice. The inflammatory cytokine IFN-γ or IL-6 induced CD74 expression in kidney TECs in vitro. The presence of kidney TECs from Fas(lpr) mice, rather than from wild-type mice, produced significantly stronger histones, dsDNA, and ribonucleoprotein-Smith Ag complex-induced CD4(+) T cell activation. Splenocytes from CD74-deficient Fas(lpr)Cd74(-/-) mice had muted responses in a MLR and to the autoantigen histones. Compared with Fas(lpr)Cd74(+/+) mice, Fas(lpr)Cd74(-/-) mice had reduced kidney and spleen sizes, splenic activated T cells and B cells, serum IgG and autoantibodies, urine albumin/creatinine ratio, kidney Periodic acid-Schiff score, IgG and C3 deposition, and serum IL-6 and IL-17A levels, but serum IL-2 and TGF-β levels were increased. Study of chronic graft-versus-host C57BL/6 mice that received donor splenocytes from B6.C-H2(bm12) /KhEg mice and those that received syngeneic donor splenocytes yielded similar observations. CD74 deficiency reduced lupus-like autoimmunity and kidney pathology in chronic graft-versus-host mice. This investigation establishes the direct participation of CD74 in autoimmunity and highlights a potential role for CD74 in kidney TECs, together with professional APCs in systemic lupus erythematosus.

  6. [Hypertension in women].

    PubMed

    Tagle, Rodrigo; Tagle V, Rodrigo; Acevedo, Mónica; Valdés, Gloria

    2013-02-01

    The present review examines the types of hypertension that women may suffer throughout life, their physiopathological characteristics and management. In early life, the currently used low-dose oral contraceptives seldom cause hypertension. Pregnancy provokes preeclampsia, its main medical complication, secondary to inadequate transformation of the spiral arteries and the subsequent multisystem endothelial damage caused by deportation of placental factors and microparticles. Hypertension in preeclampsia is an epiphenomenon which needs to be controlled at levels that reduce maternal risk without impairing placental perfusion. The hemodynamic changes of pregnancy may unmask a hypertensive phenotype, may exacerbate a chronic hypertension, or may complicate hypertension secondary to lupus, renovascular lesions, and pheochromocytoma. On the other hand a primary aldosteronism may benefit from the effect of progesterone and present as a postpartum hypertension. A hypertensive pregnancy, especially preeclampsia, represents a risk for cardiac, vascular and renal disease in later life. Menopause may mimic a pheochromocytoma, and is associated to endothelial dysfunction and salt-sensitivity. Among women, non-pharmacological treatment should be forcefully advocated, except for sodium restriction during pregnancy. The blockade of the renin-angiotensin system should be avoided in women at risk of pregnancy; betablockers could be used with precautions during pregnancy; diuretics, ACE inhibitors and angiotensin receptor antagonists should not be used during breast feeding. Collateral effects of antihypertensives, such as hyponatremia, cough and edema are more common in women. Thus, hypertension in women should be managed according to the different life stages.

  7. Prevalence and outcome in systemic sclerosis associated pulmonary arterial hypertension: application of a registry approach

    PubMed Central

    Mukerjee, D; St, G; Coleiro, B; Knight, C; Denton, C; Davar, J; Black, C; Coghlan, J

    2003-01-01

    Objective: To determine the prevalence of systemic sclerosis associated pulmonary arterial hypertension (SScPAH), evaluate outcome, and identify predictors of mortality in a large patient cohort. Methods: A prospective four year follow up study of 794 patients (722 from our own unit and 72 referrals). All patients screened for PAH using a combination of echocardiography, lung function testing, and clinical assessment. Patients with suspected raised pulmonary artery systolic pressures of >35 mm Hg, carbon monoxide transfer factor (TLCO) <50% predicted, or a precipitous fall in TLCO >20% over a one year period with no pulmonary fibrosis, and patients with SSc with breathlessness with no pulmonary fibrosis found were investigated with right heart catheterisation. All patients with SScPAH were treated in accordance with current best practice. Results: The prevalence of PAH was 12% (89/722) by right heart catheter. The survival was 81%, 63%, and 56% at 1, 2, and 3 years from the diagnosis (in 89 patients from our own cohort and 59/72 referrals). Haemodynamic indices of right ventricular failure—raised mRAP (hazard ratio 21), raised mPAP (hazard ratio 20), and low CI (hazard ratio 11) predicted an adverse outcome There was no significant difference in survival between patients with SScPAH with (n=40) and without (n=108) pulmonary fibrosis (p=0.3). Conclusions: The prevalence of SScPAH in this cohort was similar to that of other catheter based studies and lower than that of previous echo based studies. The 148 patients with SScPAH actively treated had comparable outcomes to those of the cohorts with primary pulmonary hypertension. A high mRAP was the strongest haemodynamic predictor of mortality. To improve prognosis, future treatments need to be implemented at an earlier disease stage to prevent right ventricular decompensation. PMID:14583573

  8. Systemic sclerosis associated pulmonary hypertension: improved survival in the current era

    PubMed Central

    Williams, M H; Das, C; Handler, C E; Akram, M R; Davar, J; Denton, C P; Smith, C J; Black, C M; Coghlan, J G

    2006-01-01

    Objectives To measure survival, haemodynamic function and functional class in patients with systemic sclerosis associated pulmonary arterial hypertension (SSc‐PAH) in two treatment eras. Methods Six year longitudinal study of 92 consecutive patients with SSc‐PAH diagnosed by cardiac catheterisation. Data were collected both prospectively and retrospectively. Patients were given basic treatment (diuretics, digoxin, oxygen and warfarin). Where clinically indicated, a prostanoid was used as advanced treatment (historical control group). From 2002, the range of treatments available expanded to include bosentan, which was generally the preferred treatment (current treatment era group). Survival was measured from the date of diagnosis of pulmonary hypertension by cardiac catheterisation. Six minute walking distance and haemodynamic function were measured at the time of diagnosis and at least one month after treatment was started. Results The historical control group comprised 47 patients, all of whom received basic treatment; 27 of these were also treated with prostanoids. The current treatment era group comprised 45 patients, all of whom received bosentan as preferred treatment. Kaplan–Meier survival in the historical control group was 68% at one year and 47% at two years. Survival in the current treatment era group was 81% and 71% (p  =  0.016) at one and two years, respectively. Pulmonary vascular resistance increased in the historical control group (by 147 dyn·s·cm−5), whereas in the current treatment era group, it remained stable over an average of nine months (decrease of 16 dyn·s·cm−5, p < 0.006). Conclusion Survival of selected patients with SSc‐PAH has improved in the current treatment era. In contrast to patients treated historically with basic drugs and prostanoids, patients treated in the current treatment era had improved survival associated with a lack of deterioration in cardiac haemodynamic function. PMID:16339813

  9. Blockade of the renin-angiotensin system increases adiponectin concentrations in patients with essential hypertension.

    PubMed

    Furuhashi, Masato; Ura, Nobuyuki; Higashiura, Katsuhiro; Murakami, Hideyuki; Tanaka, Marenao; Moniwa, Norihito; Yoshida, Daisuke; Shimamoto, Kazuaki

    2003-07-01

    Adiponectin, an adipocyte-derived protein, has been suggested to play an important role in insulin sensitivity. We examined the association between insulin sensitivity (M value) evaluated by the euglycemic-hyperinsulinemic glucose clamp and adiponectin concentrations in 30 essential hypertensives (EHT) and 20 normotensives (NT) and investigated the effect of blockade of the renin-angiotensin system (RAS) on adiponectin concentrations. EHT were divided into 12 insulin-resistant EHT (EHT-R) and 18 non-insulin-resistant EHT (EHT-N) using mean-1 SD of the M value in NT. There were no intergroup differences in age, gender, and body mass index (BMI). EHT-R had significantly higher levels of insulin and triglyceride and lower levels of adiponectin than did NT and EHT-N. EHT-R had higher levels of free fatty acid and lower levels of high-density lipoprotein (HDL) cholesterol than did EHT-N. Adiponectin concentrations were positively correlated with M value and HDL cholesterol and negatively correlated with BMI, insulin, free fatty acid, and triglyceride but not with blood pressure. M value, BMI, and HDL cholesterol were independent determinants of adiponectin concentrations in multiple and stepwise regression analyses. Sixteen EHT were treated with an angiotensin-converting enzyme inhibitor (temocapril, 4 mg/d; n=9) or an angiotensin II receptor blocker (candesartan, 8 mg/d; n=7) for 2 weeks. Treatment with temocapril or candesartan significantly decreased blood pressure and increased M value and adiponectin concentrations but did not affect BMI and HDL cholesterol. These results suggest that hypoadiponectinemia is related to insulin resistance in essential hypertension and that RAS blockade increases adiponectin concentrations with improvement in insulin sensitivity.

  10. [Energy-dependent pathogenesis in chronic hypertension].

    PubMed

    Postnov, Iu V

    2009-01-01

    The review compiled mainly from the works of the author's laboratory continues to develop a new area in arterial hypertension studies. The author considers the major manifestation of the pathology, i. e. the stable increase in systemic blood pressure (BP), is in a direct causal relationship to cell and tissue energy deficiency. The energy deficiency is caused by impaired energy conversion in the cell mitochondria, uncoupling of oxidation and phosphorylation, and decreased ATP production. The cause of the latter in primary hypertension may be a mitochondrial calcium overload resulting from generalized abnormalities in membranous cytosol Ca2+ concentration regulation. In secondary forms of hypertension, uncoupling agents, such as thyroid hormones, angiotensin II, cyclosporine II, low temperatures, etc., may act as triggers of mitochondrial dysfunction. Hypertension begins with the activation of an efferent component of the sympathetic nervous system that supplies the vascular periphery. The sympathetic centers in the medulla oblongata seem to be involved in the activation process. Elevated systemic BP develops in order to compensate for ATF deficiency as a measure for correcting metabolic disturbances. Further systemic BP stabilization occurs with the involvement of the kidney that, exposed to elevated BP, begins functioning in a special switching (shifting) mode. Such a mode allows the kidney to avoid salt and water losses and at the same time to maintain the required (elevated) systemic BP, by affecting the mechanism of intrarenal regulation on the feedback principle. Resetting fixation takes place with the development of sclerotic changes in the kidney and hyalinosis in the renal medulla. Vascular system remodeling, including myocardial hypertrophic changes and capillary network rarefaction, is an essential element of BP stabilization. Hypertension becomes irreversible, by losing the features of compensatory and adaptive nature, and refractory to antihypertensive

  11. Effect of Ginger and Turmeric Rhizomes on Inflammatory Cytokines Levels and Enzyme Activities of Cholinergic and Purinergic Systems in Hypertensive Rats.

    PubMed

    Akinyemi, Ayodele Jacob; Thomé, Gustavo Roberto; Morsch, Vera Maria; Bottari, Nathieli B; Baldissarelli, Jucimara; de Oliveira, Lizielle Souza; Goularte, Jeferson Ferraz; Belló-Klein, Adriane; Duarte, Thiago; Duarte, Marta; Boligon, Aline Augusti; Athayde, Margareth Linde; Akindahunsi, Akintunde Afolabi; Oboh, Ganiyu; Schetinger, Maria Rosa Chitolina

    2016-05-01

    Inflammation exerts a crucial pathogenic role in the development of hypertension. Hence, the aim of the present study was to investigate the effects of ginger (Zingiber officinale) and turmeric (Curcuma longa) on enzyme activities of purinergic and cholinergic systems as well as inflammatory cytokine levels in Nω-nitro-L-arginine methyl ester hydrochloride-induced hypertensive rats. The rats were divided into seven groups (n = 10); groups 1-3 included normotensive control rats, hypertensive (Nω-nitro-L-arginine methyl ester hydrochloride) rats, and hypertensive control rats treated with atenolol (an antihypertensive drug), while groups 4 and 5 included normotensive and hypertensive (Nω-nitro-L-arginine methyl ester hydrochloride) rats treated with 4 % supplementation of turmeric, respectively, and groups 6 and 7 included normotensive and hypertensive rats treated with 4 % supplementation of ginger, respectively. The animals were induced with hypertension by oral administration of Nω-nitro-L-arginine methyl ester hydrochloride, 40 mg/kg body weight. The results revealed a significant increase in ATP and ADP hydrolysis, adenosine deaminase, and acetylcholinesterase activities in lymphocytes from Nω-nitro-L-arginine methyl ester hydrochloride hypertensive rats when compared with the control rats. In addition, an increase in serum butyrylcholinesterase activity and proinflammatory cytokines (interleukin-1 and - 6, interferon-γ, and tumor necrosis factor-α) with a concomitant decrease in anti-inflammatory cytokines (interleukin-10) was observed in Nω-nitro-L-arginine methyl ester hydrochloride hypertensive rats. However, dietary supplementation of both rhizomes was efficient in preventing these alterations in hypertensive rats by decreasing ATP hydrolysis, acetylcholinesterase, and butyrylcholinesterase activities and proinflammatory cytokines in hypertensive rats. Thus, these activities could suggest a possible insight about the protective

  12. Socioeconomic Disparities in the Prevalence, Diagnosis, and Control of Hypertension in the Context of a Universal Health Insurance System.

    PubMed

    Lee, Hoo Yeon

    2017-04-01

    A lower use of preventive intervention in low socioeconomic populations has been described in countries with universal coverage health care systems, but little is known about the possible socioeconomic inequalities in secondary prevention in a universal health insurance system. Data from the 2010-2013 Korea National Health and Nutrition Examination Survey, a nationwide survey, were analyzed. A total of 20,044 subjects older than 30 years of age were included after excluding subjects with missing data. Prevalence ratios were calculated using Poisson regression models with robust variance to explore factors associated with the prevalence, unawareness, and inappropriate control of hypertension. Hypertension prevalence decreased with increasing education and income level. We observed an inverse association between education level and undiagnosed hypertension among women, but not men. Socioeconomic level was not associated with inadequate control of hypertension among men or women. Future interventions should include primary prevention efforts targeted at lower socioeconomic populations to reduce disparities. There is substantial room for improvement in secondary prevention efforts. Monitoring strategies may highlight gaps in the preventive and care services offered to the most vulnerable individuals and encourage governments and practitioners to address these gaps.

  13. Renin–angiotensin–aldosterone system gene polymorphisms in gestational hypertension and preeclampsia: A case–control gene-association study

    PubMed Central

    Li, Xun; Tan, Hongzhuan; Zhou, Shujin; Hu, Shimin; Zhang, Tianyi; Li, Yangfen; Dou, Qianru; Lai, Zhiwei; Chen, Fenglei

    2016-01-01

    Pregnancy-induced hypertension (PIH, including preeclampsia [PE] and gestational hypertension [GH]) and cardiovascular diseases (CVDs) have some metabolic changes and risk factors in common. Many studies have reported associations between single nucleotide polymorphisms (SNPs) of renin–angiotensin–aldosterone system (RAAS) genes and CVDs (particularly hypertension), and their findings have provided candidate SNPs for research on genetic correlates of PIH. We explored the association between hypertension-related RAAS SNPs and PIH in a Chinese population. A total of 130 cases with PE, 67 cases with GH, and 316 controls were recruited. Six candidate SNPs of the RAAS system were selected. Multiple logistic regression analysis adjusting for maternal age, fetal sex, and gestational diabetes mellitus showed significant associations between angiotensinogen (AGT) rs3789678 T/C and GH (p = 0.0088) and between angiotensin II receptor type 1 (AGTR1) rs275645 G/A and PE (p = 0.0082). The study population was further stratified by maternal age (<30 and ≥30 years), and stratified and crossover analyses were conducted to determine genetic associations in different age groups. Our findings suggest that the impacts of different SNPs might be affected by maternal age; however, the effect of this potential gene–age interaction on PIH needs further exploration. PMID:27910864

  14. Socioeconomic Disparities in the Prevalence, Diagnosis, and Control of Hypertension in the Context of a Universal Health Insurance System

    PubMed Central

    2017-01-01

    A lower use of preventive intervention in low socioeconomic populations has been described in countries with universal coverage health care systems, but little is known about the possible socioeconomic inequalities in secondary prevention in a universal health insurance system. Data from the 2010-2013 Korea National Health and Nutrition Examination Survey, a nationwide survey, were analyzed. A total of 20,044 subjects older than 30 years of age were included after excluding subjects with missing data. Prevalence ratios were calculated using Poisson regression models with robust variance to explore factors associated with the prevalence, unawareness, and inappropriate control of hypertension. Hypertension prevalence decreased with increasing education and income level. We observed an inverse association between education level and undiagnosed hypertension among women, but not men. Socioeconomic level was not associated with inadequate control of hypertension among men or women. Future interventions should include primary prevention efforts targeted at lower socioeconomic populations to reduce disparities. There is substantial room for improvement in secondary prevention efforts. Monitoring strategies may highlight gaps in the preventive and care services offered to the most vulnerable individuals and encourage governments and practitioners to address these gaps. PMID:28244279

  15. Portal Hypertension

    MedlinePlus

    ... Obesity to Liver Cancer Additional Content Medical News Portal Hypertension By Steven K. Herrine, MD, Thomas Jefferson ... Liver Hepatic Encephalopathy Jaundice in Adults Liver Failure Portal Hypertension (See also Overview of Liver Disease .) Portal ...

  16. Hypertension - overview

    MedlinePlus Videos and Cool Tools

    If left untreated, hypertension can lead to the thickening of arterial walls causing its lumen, or blood passage way, to narrow in diameter. ... the narrowed arterial openings. In addition, people with hypertension may be more susceptible to stroke.

  17. [Regeneration of endocrine gastroenteropancreatic system in experimental and clinical pathology: concept development and current problems].

    PubMed

    Ivanova, V F

    2013-01-01

    Literature review contains the literature data and the results of author's own investigations describing the coming into being and the development of the concepts on the regeneration of endocrine gastroenteropancreatic (GEP) system under the conditions of norm, experimental and clinical pathology. Data analysis permitted to reveal the similarities and differences in the course of this process in various organs of the digestive system. Endocrine GEP system renewal occurs at different levels of its organization. At the tissue level, the endocrine cells renewal occurs via the transformation of exocrine cells into the endocrine ones and as a result of differentiation from stem cells via the "agranular" cell stage which are precursors of the endocrine cells. This pathway of regeneration is the major one after the damage. Regeneration at cellular level occurs through mitotic division of the differentiated endocrine cells (early stage of regeneration) and as a result of the formation granules with different hormonal profile in D-cells. At the intracellular level, the regeneration is realized through the intracellular structure restoration after their damage induced by the increase of cell functional activity accompanied by degranulation and dystrophic changes development

  18. A System Design for Studying Geriatric Patients with Dementia and Hypertension Based on Daily Living Information

    NASA Astrophysics Data System (ADS)

    Xu, Weifeng; Betz, Willian R.; Frezza, Stephen T.; Liu, Yunkai

    2011-08-01

    Geriatric patients with dementia and hypertension (DAH) suffer both physically and financially. The needs of these patients mainly include improving the quality of daily living and reducing the cost of long-term care. Traditional treatment approaches are strained to meet these needs. The goal of the paper is to design an innovative system to provide cost-effective quality treatments for geriatric patients with DAH by collecting and analyzing the multi-dimensional personal information, such as observations in daily living (ODL) from a non-clinical environment. The proposed ODLs in paper include activities, cleanliness, blood pressure, medication compliance and mood changes. To complete the system design, an incremental user-centered strategy is exploited to assemble needs of patients, caregivers, and clinicians. A service-oriented architecture (SOA) is employed to make full use of existing devices, software systems, and platforms. This health-related knowledge can be interpreted and utilized to help patients with DAH remain in their homes safely and improve their life quality while reducing medical expenditures.

  19. [Cardiovascular complications of hypertensive crisis].

    PubMed

    Rosas-Peralta, Martín; Borrayo-Sánchez, Gabriela; Madrid-Miller, Alejandra; Ramírez-Arias, Erick; Pérez-Rodríguez, Gilberto

    2016-01-01

    It is inexorable that a proportion of patients with systemic arterial hypertension will develop a hypertensive crisis at some point in their lives. The hypertensive crises can be divided in hypertensive patients with emergency or hypertensive emergency, according to the presence or absence of acute end-organ damage. In this review, we discuss the cardiovascular hypertensive emergencies, including acute coronary syndrome, congestive heart failure, aortic dissection and sympathomimetic hypertensive crises (those caused by cocaine use included). Each is presented in a unique way, although some patients with hypertensive emergency report non-specific symptoms. Treatment includes multiple medications for quick and effective action with security to reduce blood pressure, protect the function of organs remaining, relieve symptoms, minimize the risk of complications and improve patient outcomes.

  20. Polymorphisms of APLN-APLNR system are associated with essential hypertension in Mexican-Mestizo individuals.

    PubMed

    Esteban-Martínez, Rosa Lilia; Pérez-Razo, Juan Carlos; Vargas-Alarcón, Gilberto; Martínez-Rodríguez, Nancy; Cano-Martínez, Luis Javier; López-Hernández, Luz Berenice; Rojano-Mejía, David; Canto, Patricia; Coral-Vazquez, Ramón Mauricio

    2016-08-01

    The aim of this study was to evaluate if polymorphisms of APLN and APLNR genes may play a role as susceptibility markers for hypertension in a group of Mexican-Mestizo patients. A case-control study was carried out including normotensive and hypertensive individuals. For these, two polymorphisms of APLN (rs3761581 and rs56204867) and two of APLNR () genes were genotyped by 5' exonuclease TaqMan assay in 400 normotensive individuals and 383 patients. The results showed that, under an additive model adjusted by BMI, HDL, triglycerides, glucose and family history of essential hypertension, the rs7119375 and rs10501367 polymorphisms of APLNR gene were associated significantly with a decreased risk of essential hypertension (P=0.039 and P=0.029, respectively). Besides, the haplotypes analysis of these polymorphisms showed that H1 haplotype was associated with an increased risk of essential hypertension (P=0.026), while the H2 haplotype was associated with a decreased risk (P=0.032). Contrary, the rs3761581 and rs56204867 polymorphisms of APLN gene were not associated with essential hypertension (P=0.1707 and P=0.0769, respectively). The data suggest that APLNR rs7119375 and rs10501367 are associated with a decreased risk of essential hypertension in our Mexican-Mestizo studied group, but further studies are warranted.

  1. Lupus anticoagulant in systemic lupus erythematosus: a clinical and renal pathological study.

    PubMed

    Farrugia, E; Torres, V E; Gastineau, D; Michet, C J; Holley, K E

    1992-11-01

    Circulating lupus anticoagulant (LA) is associated with thrombosis in large and small vessels. To determine how often the presence of LA is associated with thrombosis within the renal microcirculation, 33 patients with systemic lupus erythematosus (SLE), renal dysfunction, and LA were identified over a 25-year period (LA group) and 32 patients with renal SLE but with normal gross coagulation screen were matched for age, sex, and biopsy timing (C group). Prevalences of serositis, neuropsychiatric illness, leukopenia, thrombocytopenia, hemolysis, anti-DS-DNA elevation, and complement reduction were similar. Arthritis was less and biologic false-positive (BFP) syphilis serology more common in LA. More LA patients had thrombotic events (LA 39% v C 13%; P = 0.014); bleeding episodes, including postbiopsy, were similar. At biopsy, hypertension (LA 55%, C 41%), serum creatinine (mean +/- SD: LA 186 +/- 168 mumol/L [2.1 +/- 1.9 mg/dL] v C 150 +/- 168 mumol/L [1.7 +/- 1.9 mg/dL]) and proteinuria (LA 2.6 +/- 3.1 g/24 h v C 3.1 +/- 2.7) were similar. Lesions by World Health Organization (WHO) class, activity, and chronicity indices, as well as immunofluorescence (IF) and electron microscopy (EM) findings, were not significantly different. Occlusive glomerular, arteriolar, and arterial fibrin thrombi, along with varying degrees of renal thrombotic microangiopathy, were seen in five of 33 patients with LA, but zero of 32 C patients (P = 0.053); three of these five patients died soon after biopsy. Overall, mortality was not different between LA and C. We conclude that the majority of patients with SLE, renal dysfunction, and LA exhibit renal morphologic findings indistinguishable from patients without LA. However, a significant minority of LA patients have thrombotic microangiopathy in their biopsy, which is accompanied by a worse prognosis.

  2. Baroreflex sensitivity and essential hypertension in adolescents.

    PubMed

    Honzíková, N; Fiser, B

    2009-01-01

    It has been known for many years that baroreflex sensitivity is lowered in hypertensive patients. There are several known factors implicating this association, e.g. high blood pressure leads to remodeling of the carotid arterial wall, to its stiffness and to a diminished activation of baroreceptors; leptin released from a fatty tissue activates the sympathetic nervous system etc. On the other hand, low baroreflex sensitivity (BRS, usually quantified in ms/mmHg) can be inborn. Studies on primary hypertension in children and adolescents have brought new information about the role of baroreflex in the development of an early stage of primary hypertension. BRS lower than 3.9 ms/mmHg was found in 5 % of healthy subjects. This value approaches the critical value for the risk of sudden cardiac death in patients after myocardial infarction and corresponds to the value present in hypertensive patients. A decreased BRS and BRSf (baroreflex sensitivity expressed in mHz/mmHg, index independent of the mean cardiac interval), was found not only in children with hypertension, but also in those with white-coat hypertension. This is in accordance with a single interpretation. The decrease of BRS/BRSf precedes a pathological blood pressure increase. The contribution of obesity and BRS/BRSf to the development of hypertension in adolescents was also compared. Both factors reach a sensitivity and a specificity between 60 % and 65 %, but there is no correlation between the values of the body mass index and BRS either in the group of hypertensive patients or in healthy controls. If a receiver operating curve (sensitivity versus specificity) is plotted for both values together using logistic regression analysis, a sensitivity higher than 70 % and a specificity over 80 % are reached. This means that low baroreflex sensitivity is an independent risk factor for the development of primary hypertension. Studies demonstrate that adolescents with increased blood pressure and with BRS under 7 ms

  3. Dysregulated renin-angiotensin-aldosterone system contributes to pulmonary arterial hypertension

    PubMed Central

    De Man, Frances; Tu, Ly; Handoko, Louis; Rain, Silvia; Ruiter, Gerrina; François, Charlène; Schalij, Ingrid; Dorfmüller, Peter; Simonneau, Gérald; Fadel, Elie; Perros, Frederic; Boonstra, Anco; Postmus, Piet; Van Der Velden, Jolanda; Vonk-Noordegraaf, Anton; Humbert, Marc; Eddahibi, Saadia; Guignabert, Christophe

    2012-01-01

    Rationale Patients with idiopathic pulmonary arterial hypertension (iPAH) often have a low cardiac output. To compensate, neurohormonal systems like renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system are upregulated but this may have long-term negative effects on the progression of iPAH. Objectives Assess systemic and pulmonary RAAS-activity in iPAH-patients and determine the efficacy of chronic RAAS-inhibition in experimental PAH. Measurements and Main Results We collected 79 blood samples from 58 iPAH-patients in the VU University Medical Center Amsterdam (between 2004–2010), to determine systemic RAAS-activity. We observed increased levels of renin, angiotensin (Ang) I and AngII, which was associated with disease progression (p<0.05) and mortality (p<0.05). To determine pulmonary RAAS-activity, lung specimens were obtained from iPAH-patients (during lung transplantation, n=13) and controls (during lobectomy or pneumonectomy for cancer, n=14). Local RAAS-activity in pulmonary arteries of iPAH-patients was increased, demonstrated by elevated ACE-activity in pulmonary endothelial cells and increased AngII type 1 (AT1) receptor expression and signaling. In addition, local RAAS- upregulation was associated with increased pulmonary artery smooth muscle cell proliferation via enhanced AT1-receptor signaling in iPAH-patients compared to controls. Finally, to determine the therapeutic potential of RAAS-activity, we assessed the chronic effects of an AT1-receptor antagonist (losartan) in the monocrotaline PAH-rat model (60 mg/kg). Losartan delayed disease progression, decreased RV afterload and pulmonary vascular remodeling and restored right ventricular-arterial coupling in PAH-rats. Conclusions Systemic and pulmonary RAAS-activities are increased in iPAH-patients and associated with increased pulmonary vascular remodeling. Chronic inhibition of RAAS by losartan is beneficial in experimental PAH. PMID:22859525

  4. Computational intelligent gait-phase detection system to identify pathological gait.

    PubMed

    Senanayake, Chathuri M; Senanayake, S M N Arosha

    2010-09-01

    An intelligent gait-phase detection algorithm based on kinematic and kinetic parameters is presented in this paper. The gait parameters do not vary distinctly for each gait phase; therefore, it is complex to differentiate gait phases with respect to a threshold value. To overcome this intricacy, the concept of fuzzy logic was applied to detect gait phases with respect to fuzzy membership values. A real-time data-acquisition system was developed consisting of four force-sensitive resistors and two inertial sensors to obtain foot-pressure patterns and knee flexion/extension angle, respectively. The detected gait phases could be further analyzed to identify abnormality occurrences, and hence, is applicable to determine accurate timing for feedback. The large amount of data required for quality gait analysis necessitates the utilization of information technology to store, manage, and extract required information. Therefore, a software application was developed for real-time acquisition of sensor data, data processing, database management, and a user-friendly graphical-user interface as a tool to simplify the task of clinicians. The experiments carried out to validate the proposed system are presented along with the results analysis for normal and pathological walking patterns.

  5. Survival of patients with pathologically proven multiple system atrophy: a meta-analysis.

    PubMed

    Ben-Shlomo, Y; Wenning, G K; Tison, F; Quinn, N P

    1997-02-01

    A systematic review of the neurologic literature identified 433 cases of pathologically proven multiple system atrophy over a 100-year period. Earlier case reports included patients younger in age with more frequent cerebellar involvement. Mean age of onset was 54.2 years (range 31 to 78) and survival was 6.2 years (range 0.5 to 24). Survival analysis showed a secular trend from a median duration of 4.9 years for publications between 1887 and 1970 to 6.8 years between 1991 and 1994. Older age of onset was associated with shorter survival; the hazard ratio for patients with onset after 60 years was 1.8 (95% CI 1.4 to 2.3) compared with patients between 31 and 49 years. Cerebellar features were associated with marginally increased survival (6.1 years versus 5.4 years; p = 0.04). There were no difference in survival according to gender, parkinsonian, or pyramidal features or whether the patient was classified as striatonigral degeneration or olivopontocerebellar atrophy type. These results demonstrate the poor prognosis for patients with multiple system atrophy but may be biased toward the worst cases. Future research needs to recruit more representative samples.

  6. Shack-Hartmann sensor based optical quality testing of whole slide imaging systems for digital pathology

    NASA Astrophysics Data System (ADS)

    Shakeri, S. M.; Hulsken, Bas; van Vliet, Lucas J.; Stallinga, Sjoerd

    2015-03-01

    Whole Slide Imaging (WSI) systems are used in the emerging field of digital pathology for capturing high-resolution images of tissue slides at high throughput. We present a technique to measure the optical aberrations of WSI systems using a Shack-Hartmann wavefront sensor as a function of field position. The resulting full-field aberration maps for the lowest order astigmatism and coma are analyzed using nodal aberration theory. According to this theory two coefficients describe the astigmatism and coma inherent to the optical design and another six coefficients are needed to describe the cumulative effects of all possible misalignments on astigmatism and coma. The nodal aberration theory appears to fit well to the experimental data. We have measured and analyzed the full-field aberration maps for two different objective lens-tube lens assemblies and found that only the optical design related astigmatism coefficient differed substantially between the two cases, but in agreement with expectations. We have also studied full-field aberration maps for intentional decenter and tilt and found that these affect the misalignment coefficient for constant coma (decenter) and the misalignment coefficient for linear astigmatism (tilt), while keeping all other nodal aberration theory coefficients constant.

  7. Systemic lupus erythematosus and pulmonary arterial hypertension: links, risks, and management strategies

    PubMed Central

    Tselios, Konstantinos; Gladman, Dafna D; Urowitz, Murray B

    2017-01-01

    Systemic lupus erythematosus (SLE) is characterized by the second highest prevalence of pulmonary arterial hypertension (PAH), after systemic sclerosis, among the connective tissue diseases. SLE-associated PAH is hemodynamically defined by increased mean pulmonary artery pressure at rest (≥25 mmHg) with normal pulmonary capillary wedge pressure (≤15 mmHg) and increased pulmonary vascular resistance. Estimated prevalence ranges from 0.5% to 17.5% depending on the diagnostic method used and the threshold of right ventricular systolic pressure in studies using transthoracic echocardiogram. Its pathogenesis is multifactorial with vasoconstriction, due to imbalance of vasoactive mediators, leading to hypoxia and impaired vascular remodeling, collagen deposition, and thrombosis of the pulmonary circulation. Multiple predictive factors have been recognized, such as Raynaud’s phenomenon, pleuritis, pericarditis, anti-ribonuclear protein, and antiphospholipid antibodies. Secure diagnosis is based on right heart catheterization, although transthoracic echocardiogram has been shown to be reliable for patient screening and follow-up. Data on treatment mostly come from uncontrolled observational studies and consist of immunosuppressive drugs, mainly corticosteroids and cyclophosphamide, as well as PAH-targeted approaches with endothelin receptor antagonists (bosentan), phosphodiesterase type 5 inhibitors (sildenafil), and vasodilators (epoprostenol). Prognosis is significantly affected, with 1- and 5-year survival estimated at 88% and 68%, respectively. PMID:28053559

  8. Pulmonary Arterial Hypertension in Systemic Lupus Erythematosus: Current Status and Future Direction

    PubMed Central

    Dhala, Atiya

    2012-01-01

    Pulmonary arterial hypertension (PAH) is commonly associated with connective tissue diseases (CTDs) including systemic sclerosis and systemic lupus erythematosus (SLE). The prevalence of PAH in SLE is estimated to be 0.5% to 17.5%. The pathophysiology of PAH involves multiple mechanisms from vasculitis and in-situ thrombosis to interstitial pulmonary fibrosis which increases pulmonary vascular resistance, potentially leading to right heart failure. Immune and inflammatory mechanisms may play a significant role in the pathogenesis or progression of PAH in patients with CTDs, establishing a role for anti-inflammatory and immunosuppressive therapies. The leading predictors of PAH in SLE are Raynaud phenomenon, anti-U1RNP antibody, and anticardiolipin antibody positivity. The first-line of diagnostic testing for patients with suspected SLE-associated PAH (SLE-aPAH) involves obtaining a Doppler echocardiogram. Once the diagnosis is confirmed by right heart catheterization, SLE-aPAH patients are generally treated with oxygen, anticoagulants, and vasodilators. Although the prognosis and therapeutic responsiveness of these patients have improved with the addition of intensive immunosuppressive therapies, these treatments are still largely unproven. Recent data put the one-year survival rate for SLE-aPAH patients at 94%. Pregnant women are most at risk of dying due to undiagnosed SLE-aPAH, and screening should be considered essential in this population. PMID:22489252

  9. Systemic lupus erythematosus and pulmonary arterial hypertension: links, risks, and management strategies.

    PubMed

    Tselios, Konstantinos; Gladman, Dafna D; Urowitz, Murray B

    2017-01-01

    Systemic lupus erythematosus (SLE) is characterized by the second highest prevalence of pulmonary arterial hypertension (PAH), after systemic sclerosis, among the connective tissue diseases. SLE-associated PAH is hemodynamically defined by increased mean pulmonary artery pressure at rest (≥25 mmHg) with normal pulmonary capillary wedge pressure (≤15 mmHg) and increased pulmonary vascular resistance. Estimated prevalence ranges from 0.5% to 17.5% depending on the diagnostic method used and the threshold of right ventricular systolic pressure in studies using transthoracic echocardiogram. Its pathogenesis is multifactorial with vasoconstriction, due to imbalance of vasoactive mediators, leading to hypoxia and impaired vascular remodeling, collagen deposition, and thrombosis of the pulmonary circulation. Multiple predictive factors have been recognized, such as Raynaud's phenomenon, pleuritis, pericarditis, anti-ribonuclear protein, and antiphospholipid antibodies. Secure diagnosis is based on right heart catheterization, although transthoracic echocardiogram has been shown to be reliable for patient screening and follow-up. Data on treatment mostly come from uncontrolled observational studies and consist of immunosuppressive drugs, mainly corticosteroids and cyclophosphamide, as well as PAH-targeted approaches with endothelin receptor antagonists (bosentan), phosphodiesterase type 5 inhibitors (sildenafil), and vasodilators (epoprostenol). Prognosis is significantly affected, with 1- and 5-year survival estimated at 88% and 68%, respectively.

  10. [Hypertension and arteriosclerosis].

    PubMed

    Sasamura, Hiroyuki; Itoh, Hiroshi

    2011-01-01

    Hypertension is a known risk factor for arteriosclerosis, and causes both atherosclero= sis of medium-large arteries and arteriolosclerosis of the arterioles. Elevated blood pressure causes damage to the endothelium and vascular wall through both mechanical and humoral factors. We and others have shown that inhibition of the renin-angiotensin system at a 'critical period' during the development of hypertension results in a permanent suppression of hypertension in animal models. We have also reported that high-dose renin-angiotensin inhibition results in regression of hypertension, possibly by regression of renal arteriolar hypertrophy. These results suggest that understanding the process of arterial remodeling may play a key role in the development of new strategies for prevention and regression of hypertension and arteriosclerosis.

  11. Hypertension in pregnancy.

    PubMed

    Vest, Amanda R; Cho, Leslie S

    2014-03-01

    Hypertensive disorders of pregnancy represent the second commonest cause of direct maternal death and complicate an estimated 5-10 % of pregnancies. Classification systems aim to separate hypertension similar to that seen outside pregnancy (chronic and gestational hypertension) from the potentially fatal pregnancy-specific conditions. Preeclampsia, HELLP syndrome, and eclampsia represent increasing severities of this disease spectrum. The American College of Obstetricians and Gynecologists' 2013 guidelines no longer require proteinuria as a diagnostic criterion, because of its variable appearance in the disease spectrum. The cause involves inadequate cytotrophoblastic invasion of the myometrium, resulting in placental hypoperfusion and diffuse maternal endothelial dysfunction. Changes in angiogenic and antiangiogentic peptide profiles precede the onset of clinical preeclampsia. Women with preeclampsia should be closely monitored and receive magnesium sulfate intravenously if severe features, HELLP syndrome, or eclampsia occur. Definitive therapy is delivery of the fetus. Hypertension in pregnancy increases future maternal risk of hypertension and cardiovascular disorders.

  12. Role of the central nervous system in the development of hypertension produced by chronic nitric oxide blockade in rats.

    PubMed

    Nakata, T; Takeda, K; Harada, S; Oguni, A; Hatta, T; Kawa, T; Itoh, H; Sasaki, S; Nakagawa, M

    2001-01-01

    We examined the role of the central nervous system, and particularly the renin-angiotensin (RA) system, in the development of hypertension produced by chronic inhibition of NO synthesis. In experiment 1, Wistar rats drank either nitro-L-arginine-methyl ester (L-NAME) or tap water. Before L-NAME treatment rats were divided into 6 groups. Four of them were administered either losartan or artificial cerebroventricular fluid (a-CSF) intracerebroventricularly (i.c.v.) for 1 week using an osmotic mini pump. The other two groups were administered the same amount of losartan intravenously (i.v.). In experiment 2, cardiovascular responses to acute i.c.v. losartan and muscimol, a GABA(A) agonist, were examined in conscious L-NAME-treated rats. Finally, in experiment 3, effects of ablation of the AV3V (anteroventral third ventricle) area, known to be one of the centers of cardiovascular control, were tested in the development of L-NAME hypertension. The development of hypertension by L-NAME treatment was attenuated with chronic i.c.v. losartan in a dose-dependent manner, while i.v. losartan had no effect. One week after cessation of i.c.v. losartan, blood pressure was elevated to the same level as in a-CSF-infused, L-NAME-treated rats. Acute i.c.v. losartan produced no cardiovascular changes in either L-NAME-treated or control rats. On the other hand, although i.c.v. muscimol elicited depressor effects in both groups, these responses were significantly larger in L-NAME-treated rats. Cardiovascular responses to i.v. hexamethonium were similar in both groups. The existence of prior lesions in the AV3V area significantly attenuated the development of L-NAME-induced hypertension. These results indicate that the central RA system plays an important role in the development of hypertension produced by chronic inhibition of NO synthase. Moreover, disorder of the central GABA system, rather than that of the RA system, might be important in the maintenance of hypertension in this model.

  13. The Influence of Health Systems on Hypertension Awareness, Treatment, and Control: A Systematic Literature Review

    PubMed Central

    Maimaris, Will; Paty, Jared; Perel, Pablo; Legido-Quigley, Helena; Balabanova, Dina; Nieuwlaat, Robby; Mckee, Martin

    2013-01-01

    Background Hypertension (HT) affects an estimated one billion people worldwide, nearly three-quarters of whom live in low- or middle-income countries (LMICs). In both developed and developing countries, only a minority of individuals with HT are adequately treated. The reasons are many but, as with other chronic diseases, they include weaknesses in health systems. We conducted a systematic review of the influence of national or regional health systems on HT awareness, treatment, and control. Methods and Findings Eligible studies were those that analyzed the impact of health systems arrangements at the regional or national level on HT awareness, treatment, control, or antihypertensive medication adherence. The following databases were searched on 13th May 2013: Medline, Embase, Global Health, LILACS, Africa-Wide Information, IMSEAR, IMEMR, and WPRIM. There were no date or language restrictions. Two authors independently assessed papers for inclusion, extracted data, and assessed risk of bias. A narrative synthesis of the findings was conducted. Meta-analysis was not conducted due to substantial methodological heterogeneity in included studies. 53 studies were included, 11 of which were carried out in LMICs. Most studies evaluated health system financing and only four evaluated the effect of either human, physical, social, or intellectual resources on HT outcomes. Reduced medication co-payments were associated with improved HT control and treatment adherence, mainly evaluated in US settings. On balance, health insurance coverage was associated with improved outcomes of HT care in US settings. Having a routine place of care or physician was associated with improved HT care. Conclusions This review supports the minimization of medication co-payments in health insurance plans, and although studies were largely conducted in the US, the principle is likely to apply more generally. Studies that identify and analyze complexities and links between health systems arrangements

  14. Prevalence of diabetes mellitus and hypertension among Indian glaucoma patients and evaluation of systemic therapy.

    PubMed

    Dave, Abhishek; Bali, Shveta Jindal; Sharma, Reetika; Khurana, Aruj K; Gupta, Raghav; Dada, Tanuj

    2013-10-01

    To study the prevalence and systemic control and evaluate the adequacy of therapy of diabetes mellitus (DM) and hypertension (HT) in glaucoma patients visiting a tertiary care eye facility at a university hospital. Consecutive cases with primary open-angle glaucoma (POAG) or primary angle-closure glaucoma (PACG) attending the outpatient services were evaluated for the presence of DM and HT and any systemic/ocular medications being taken were recorded. Of 615 glaucoma cases evaluated, 281 (45.7 %) were POAG and 334 (54.3 %) were PACG. The mean age was 58.19 ± 10.8 years with males comprising 60.5 % of the study group. Two hundred and ninety-two (47.5 %) glaucoma patients had HT and 181 (29.4 %) had DM, including 97 (15.8 %) patients who had both. One hundred and thirty-three (47.3 %) patients with POAG and 159 (47.6 %) patients with PACG had HT. Ninety-seven (34.5 %) POAG patients and 84 (25.1 %) PACG patients were diabetics. One hundred and sixty-one (55.1 %) HT patients had blood pressure above control levels and 88 (48.6 %) diabetics had uncontrolled blood sugars. Twenty-eight (9.6 %) patients with HT were found to be taking combined systemic and topical β-blocker therapy. A large majority of adult glaucoma patients had concurrent systemic disease, which was not adequately controlled. Patients were using systemic medications with known interactions with ocular hypotensive medications. This study highlights the unmet need for better coordination between ophthalmologists and physicians to improve the overall health of glaucoma patients.

  15. [One of the variants of larvate cyclothymic disorder simulating pathology of the locomotor system].

    PubMed

    Lisina, M A

    1990-01-01

    Based on the reported data and the authors' findings 40 cases of larvate cyclothymia are described. The pivotal symptomatology of the disease involved masked hypochondriac subdepressions that imitated pathology of the bones and joints. In view of this fact the mental disease could not be recognized by the physicians and was diagnosed erroneously as a pathology of the bones and joints. The author provides a 3-component structure of the given hypochondriac depressions and differential diagnostic criteria for their separation from genuine pathology of the bones and joints.

  16. The pathology of orthopedic implant failure is mediated by innate immune system cytokines.

    PubMed

    Landgraeber, Stefan; Jäger, Marcus; Jacobs, Joshua J; Hallab, Nadim James

    2014-01-01

    All of the over 1 million total joint replacements implanted in the US each year are expected to eventually fail after 15-25 years of use, due to slow progressive subtle inflammation at the bone implant interface. This inflammatory disease state is caused by implant debris acting, primarily, on innate immune cells, that is, macrophages. This slow progressive pathological bone loss or "aseptic loosening" is a potentially life-threatening condition due to the serious complications in older people (>75 yrs) of total joint replacement revision surgery. In some people implant debris (particles and ions from metals) can influence the adaptive immune system as well, giving rise to the concept of metal sensitivity. However, a consensus of studies agrees that the dominant form of this response is due to innate reactivity by macrophages to implant debris where both danger (DAMP) and pathogen (PAMP) signalling elicit cytokine-based inflammatory responses. This paper discusses implant debris induced release of the cytokines and chemokines due to activation of the innate (and the adaptive) immune system and the subsequent formation of osteolysis. Different mechanisms of implant-debris reactivity related to the innate immune system are detailed, for example, danger signalling (e.g., IL-1β, IL-18, IL-33, etc.), toll-like receptor activation (e.g., IL-6, TNF-α, etc.), apoptosis (e.g., caspases 3-9), bone catabolism (e.g., TRAP5b), and hypoxia responses (Hif1-α). Cytokine-based clinical and basic science studies are in progress to provide diagnosis and therapeutic intervention strategies.

  17. Concurrent central nervous system infective pathology in a severely immunocompromised patient

    PubMed Central

    Swe, Thein; Laurent, Bordes P.; Shah, Nickul N.

    2016-01-01

    To our knowledge and literature search, concurrent cryptococcal meningitis and neurosyphilis in a patient have rarely been reported. Here, we report a 37-year-old male with HIV infection presented with headache and dizziness for 5 days along with memory difficulty and personality changes for about 1 week. During the hospital stay, cryptococcal meningitis was confirmed with positive cerebral spinal fluid (CSF) cryptococcal antigen titer (1:320) and positive CSF culture. Diagnosis of neurosyphilis was made based upon CSF white blood cell count of 85 cells/μL, with CSF total protein of 87 mg/dL, reactive CSF treponemal antibody, and fluorescent treponemal antibody. The patient was treated with amphotericin B, flucytosine, fluconazole, and benzathine penicillin G, and the patient was recovered and discharged. HIV patients are at high risk of developing severe infections of the central nervous system. Awareness should be made not only to single infection but also for dual pathology for a better and life-saving management. PMID:28217607

  18. Magnetic resonance imaging of reconstructed ferritin as an iron-induced pathological model system

    NASA Astrophysics Data System (ADS)

    Balejcikova, Lucia; Strbak, Oliver; Baciak, Ladislav; Kovac, Jozef; Masarova, Marta; Krafcik, Andrej; Frollo, Ivan; Dobrota, Dusan; Kopcansky, Peter

    2017-04-01

    Iron, an essential element of the human body, is a significant risk factor, particularly in the case of its concentration increasing above the specific limit. Therefore, iron is stored in the non-toxic form of the globular protein, ferritin, consisting of an apoferritin shell and iron core. Numerous studies confirmed the disruption of homeostasis and accumulation of iron in patients with various diseases (e.g. cancer, cardiovascular or neurological conditions), which is closely related to ferritin metabolism. Such iron imbalance enables the use of magnetic resonance imaging (MRI) as a sensitive technique for the detection of iron-based aggregates through changes in the relaxation times, followed by the change in the inherent image contrast. For our in vitrostudy, modified ferritins with different iron loadings were prepared by chemical reconstruction of the iron core in an apoferritin shell as pathological model systems. The magnetic properties of samples were studied using SQUID magnetometry, while the size distribution was detected via dynamic light scattering. We have shown that MRI could represent the most advantageous method for distinguishing native ferritin from reconstructed ferritin which, after future standardisation, could then be suitable for the diagnostics of diseases associated with iron accumulation.

  19. Proposal of Gleason-like grading system of canine prostate carcinoma in veterinary pathology practice.

    PubMed

    Palmieri, Chiara; Grieco, Valeria

    2015-12-01

    Gleason grading - the most useful predictor of prognosis for prostate cancer in men - was updated at a 2005 consensus conference by the International Society of Urological Pathology. Since Gleason-like growth patterns have been recognised in dogs, this study aimed to apply the modified Gleason grading to 45 canine prostate carcinomas. A single primary growth pattern was observed in 28 cases, a secondary pattern in 11 cases and a tertiary pattern in 6 cases. Cribriform, solid and small acinar/ductal were the most common primary, secondary and tertiary morphological patterns, respectively. The highest Gleason score (GS10) was obtained in 46.7% of cases. Nine of 14 metastasizing cases were classified as GS10. Gleason pattern 5 was present in 33 of cases. This study suggests that the modified Gleason grading, based on specific histological growth patterns existing in canine prostate carcinomas, may be accepted as a grading system for histopathology in the practice settings in order to complete the clinical assessment for the best management of the patient.

  20. Local and Systemic RAGE Axis Changes in Pulmonary Hypertension: CTEPH and iPAH

    PubMed Central

    Moser, Bernhard; Megerle, Anna; Bekos, Christine; Janik, Stefan; Szerafin, Tamás; Birner, Peter; Schiefer, Ana-Iris; Mildner, Michael; Lang, Irene; Skoro-Sajer, Nika; Sadushi-Kolici, Roela; Taghavi, Shahrokh; Klepetko, Walter; Ankersmit, Hendrik Jan

    2014-01-01

    Objective The molecular determinants of chronic thromboembolic pulmonary hypertension (CTEPH) and idiopathic pulmonary arterial hypertension (iPAH) remain poorly understood. The receptor for advanced glycation endproducts (RAGE) and its ligands: HMGB1 and S100A9 are involved in inflammatory disorders. We sought to investigate the role of the RAGE axis in patients with CTEPH undergoing pulmonary endarterectomy (PEA), iPAH undergoing lung transplantation (LuTX). The high pulmonary vascular resistance in CTEPH/iPAH results in pressure overload of the right ventricle. We compared sRAGE measurements to that of patients with aortic valve stenosis (AVS) – pressure overload of the left ventricle. Methods We enrolled patients with CTEPH(26), iPAH(15), AVS(15) and volunteers(33). Immunohistochemistry with antibodies to RAGE and HMGB1 was performed on PEA specimens and lung tissues. We employed enzyme-linked immunosorbent assays to determine the concentrations of sRAGE, esRAGE, HMGB1 and S100A9 in serum of volunteers and patients with CTEPH, iPAH, AVS before and after PEA, LuTX and aortic valve replacement (AVR). Results In endarterectomised tissues from patients with CTEPH RAGE and HMGB1 were identified in myofibroblasts (α-SMA+vimentin+CD34−), recanalizing vessel-like structures of distal myofibrotic tissues and endothelium of neointima. RAGE was differentially expressed in prototypical Heath Edwards lesions in iPAH. We found significantly increased serum concentrations of sRAGE, esRAGE and HMGB1 in CTEPH. In iPAH, sRAGE and esRAGE were significantly higher than in controls. Serum concentrations of sRAGE were significantly elevated in iPAH(p<0.001) and CTEPH(p = 0.001) compared to AVS. Serum sRAGE was significantly higher in iPAH compared to CTEPH(p = 0.042) and significantly reduced in AVS compared to controls(p = 0.001). There were no significant differences in sRAGE serum concentrations before and after surgical therapy for CTEPH, iPAH or AVS

  1. [Portal hypertension in children. Follow-up after portal systemic shunts (author's transl)].

    PubMed

    Bernard, O; Alvarez, F; Alagille, D

    1982-01-01

    The retrospective study of 115 children in whom a successful portosystemic shunt was carried out for portal hypertension, provides the following conclusions: 1) Patency of the shunt must be checked by esophageal endoscopy, six months postoperatively. A patent shunt can be expected when the size of the spleen and/or thrombocytopenia improve in the early post-operative period. Early ultrasound examination is also very useful in that respect. 2) None of the children with extrahepatic portal vein obstruction or congenital hepatic fibrosis presented with clinical signs of portal systemic encephalopathy (PSE). 3) Eight of 30 children with cirrhosis presented with one or more clinical episodes of PSE. Some were transient allowing for a normal diet to be resumed later on. 4) It is thus advisable to give children with cirrhosis a low protein diet in the months after surgery. Protein content of the diet can usually be increased progressively over a period of one to two years. 5) Whenever splenectomy is necessary, it is mandatory to prevent pneumococcal infections with the pneumococcal vaccine and daily treatment with oral penicillin.

  2. Current Approaches to the Treatment of Systemic-Sclerosis-Associated Pulmonary Arterial Hypertension (SSc-PAH).

    PubMed

    Sobanski, Vincent; Launay, David; Hachulla, Eric; Humbert, Marc

    2016-02-01

    Pulmonary arterial hypertension (PAH) is a severe condition causing significant morbidity and mortality in patients with systemic sclerosis (SSc). Despite the use of specific treatments, SSc-PAH survival remains poorer than in idiopathic PAH (IPAH). Recent therapeutic advances in PAH show a lower magnitude of response in SSc-PAH and a higher risk of adverse events, as compared to IPAH. The multifaceted underlying mechanisms and the multisystem nature of SSc probably explain part of the worse outcomes in SSc-PAH compared to IPAH. This review describes the current management of SSc-PAH with an emphasis on the impact of the different organ involvements in the prognosis and treatment response. An earlier detection of PAH and a better characterization of the clinical phenotypes of SSc-PAH are warranted in clinical practice and future trials. Determinants of prognosis, surrogate markers of clinical improvement or worsening, and relevance of the common endpoints used in clinical trials should be evaluated in this specific population. A multidisciplinary approach in expert referral centers is mandatory for SSc-PAH management.

  3. Stress and hypertension.

    PubMed

    Zimmerman, R S; Frohlich, E D

    1990-09-01

    The relationships between stress and hypertension have been evaluated extensively. Acutely, stress has been shown to increase blood pressure by increasing cardiac output and the heart rate without affecting total peripheral resistance. Acute stress has been found to increase levels of catecholamines, cortisol, vasopressin, endorphins and aldosterone, which may in part explain the increase in blood pressure. However, a primary role for the activation of the sympathetic nervous system has recently been suggested in several studies. Studies in the rat are beginning to determine specific central nervous system pathways which transform stressful stimuli into signals triggering a cardiovascular response without direct cortical participation. Furthermore, acute stress reduces renal sodium excretion, which contributes to an increase in blood pressure. Several studies suggest that prolonged stress may predispose people and animals to prolonged hypertension and certain populations are at risk for the development of stress-induced hypertension. It is likely that prolonged stress-induced hypertension is the result of neurohormonal trophic factors which cause vascular hypertrophy or atherosclerosis. Because stress can affect measurement of blood pressure due to the phenomenon of 'white-coat hypertension', ambulatory blood pressure monitoring is emerging as an important feature in the evaluation of patients with hypertension. Finally, relaxation techniques are being used increasingly in the treatment of patients with hypertension.

  4. A multi-level system quality improvement intervention to reduce racial disparities in hypertension care and control: study protocol

    PubMed Central

    2013-01-01

    Background Racial disparities in blood pressure control have been well documented in the United States. Research suggests that many factors contribute to this disparity, including barriers to care at patient, clinician, healthcare system, and community levels. To date, few interventions aimed at reducing hypertension disparities have addressed factors at all of these levels. This paper describes the design of Project ReD CHiP (Reducing Disparities and Controlling Hypertension in Primary Care), a multi-level system quality improvement project. By intervening on multiple levels, this project aims to reduce disparities in blood pressure control and improve guideline concordant hypertension care. Methods Using a pragmatic trial design, we are implementing three complementary multi-level interventions designed to improve blood pressure measurement, provide patient care management services and offer expanded provider education resources in six primary care clinics in Baltimore, Maryland. We are staggering the introduction of the interventions and will use Statistical Process Control (SPC) charting to determine if there are changes in outcomes at each clinic after implementation of each intervention. The main hypothesis is that each intervention will have an additive effect on improvements in guideline concordant care and reductions in hypertension disparities, but the combination of all three interventions will result in the greatest impact, followed by blood pressure measurement with care management support, blood pressure measurement with provider education, and blood pressure measurement only. This study also examines how organizational functioning and cultural competence affect the success of the interventions. Discussion As a quality improvement project, Project ReD CHiP employs a novel study design that specifically targets multi-level factors known to contribute to hypertension disparities. To facilitate its implementation and improve its sustainability, we have

  5. Effect of magnetic bracelets on the coagulation and anticoagulation systems of the blood of patients with hypertension

    NASA Technical Reports Server (NTRS)

    Bublis, V. V.; Zabrodina, L. V.; Platonova, A. T.; Meyerova, Y. A.

    1974-01-01

    The data which have been obtained on the influence of magnetic bracelets on the coagulation and anticoagulation systems of the blood indicate that the wearing of magnetic bracelets results in a decrease in the coagulation activity of the blood and an increase in the activity of the anticoagulation system. These changes must be viewed as favorable for patients with cardiovascular pathology.

  6. Pulmonary hypertension in systemic lupus erythematosus: an independent predictor of patient survival

    PubMed Central

    Min, Hong Ki; Lee, Jae Ho; Jung, Seung Min; Lee, Jennifer; Kang, Kwi Young; Kwok, Seung-Ki; Ju, Ji Hyeon; Park, Kyung-Su

    2015-01-01

    Background/Aims We investigated whether transthoracic echocardiography-suspected pulmonary hypertension (PH) affects survival in systemic lupus erythematosus (SLE) patients and examined factors associated with PH occurrence and survival. Methods This retrospective single-center study included 154 Korean SLE patients fulfilling the American College of Rheumatology criteria (January 1995 to June 2013). Student t test, Mann-Whitney U test, Kaplan-Meier curves, and log-rank tests were used for comparisons. Results A total of 35 SLE patients with PH (SLE/PH+) and 119 without PH (SLE/PH-) were analyzed. Higher percentages of interstitial lung disease, Raynaud's phenomenon (RP), World Health Organization functional classification III/IV, and cardiomegaly were found in SLE/PH+ compared to SLE/PH-. Furthermore, the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index was significantly higher in SLE/PH+ (2.46 ± 1.245 vs. 1.00 ± 1.235), whereas survival rates were significantly higher in SLE/PH- in log-rank tests (p = 0.001). In multivariate analysis, the adjusted mortality hazard ratio (HR) for SLE/PH+ patients was 3.10. Subgroup analysis demonstrated a higher percentage of lupus nephritis in the SLE/PH+ patients who died (p = 0.039) and low complement-3 levels (p = 0.007). In univariate analysis, the mortality HR for SLE/PH+ patients with lupus nephritis was 4.62, whereas the presence of RP decreased the mortality risk in multivariate analysis; adjusted HR, 0.10. Conclusions PH is an independent factor predicting survival in SLE patients. The presence of lupus nephritis resulted in an increased trend for mortality, whereas coexistence of RP was associated with a better survival prognosis in SLE/PH+ patients. PMID:25750566

  7. Malignant hypertension

    MedlinePlus

    ... Lippincott Williams & Wilkins; 2009:chap 89. Read More Acute kidney failure Alertness - decreased Angina Heart attack Preeclampsia Pulmonary edema Renovascular hypertension Seizures Stroke Review ...

  8. The effect of an NO donor, pentaerythrityl tetranitrate, on biochemical, functional, and morphological attributes of cardiovascular system of spontaneously hypertensive rats.

    PubMed

    Dovinová, Ima; Cacányiová, Sona; Fáberová, Viera; Kristek, Frantisek

    2009-03-01

    The status of nitric oxide (NO) in spontaneously hypertensive rats (SHR) is unclear and its bioavailability may be affected by imbalance with reactive oxygen species. We studied cardiovascular effects of an NO donor, pentaerythrityl tetranitrate (PETN) in SHR. We used Wistar rats, SHR and SHR treated with PETN (200 mg/kg/day). After six weeks, myocardium and aorta from each group were taken for biochemical and iliac artery for functional and morphological study. Long-term administration of PETN to SHR increased cGMP level in platelets and did not affect blood pressure. In myocardium, the therapy resulted in a decrease in cardiac hypertrophy and MDA level, and the increased antioxidant enzyme activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx). In aorta, PETN decreased the NO-synthase activity and had no affect on the enzyme activities of SOD and GPx or on MDA level. In the iliac artery, the endothelium-dependent relaxation to acetylcholine was slightly improved and the maximum vasoconstriction to noradrenaline was decreased. Wall thickness, cross-sectional area, inner diameter, and wall thickness/ inner diameter measured after perfusion fixation (120 mmHg) were not affected. The small effect of PETN on cardiovascular system suggests that NO deficiency is probably not the main cause of pathological alterations in SHR.

  9. Left ventricular ejection fraction response during exercise in asymptomatic systemic hypertension

    SciTech Connect

    Miller, D.D.; Ruddy, T.D.; Zusman, R.M.; Okada, R.D.; Strauss, H.W.; Kanarek, D.J.; Christensen, D.; Federman, E.B.; Boucher, C.A.

    1987-02-15

    To study the effect of mild-to-moderate elevations in diastolic blood pressure (BP) on systolic left ventricular (LV) function, 28 hypertensive patients and 20 normal subjects underwent upright exercise first-pass radionuclide angiography. All were asymptomatic, had normal rest and exercise electrocardiographic findings and no evidence of LV hypertrophy or coronary artery disease. LV function at rest was similar in the 2 groups, but with exercise hypertensive patients had a greater end-systolic volume (69 +/- 19 vs 51 +/- 19 ml, p less than 0.002) and lower ejection fraction (EF) (0.59 +/- 0.09 vs 0.72 +/- 0.07, p less than 0.0001), stroke volume (101 +/- 28 vs 130 +/- 36 ml, p less than 0.005) and peak oxygen uptake (23 +/- 7 vs 33 +/- 9 ml/kl/min, p less than 0.05). Hypertensive patients were separated into 3 groups: group 1-12 patients with an increase in EF with exercise greater than or equal to 0.05; group 2-7 patients with a change in EF with exercise less than 0.05; and group 3-9 patients with a decrease in EF with exercise greater than or equal to 0.05. Group 3 hypertensive patients were older, had a higher heart rate at rest and lower peak oxygen uptake. Rest LV function was similar in the 3 hypertensive subgroups, but exercise end-systolic volumes were higher in groups 2 and 3. Exercise thallium-201 images was normal in all but 1 of 14 hypertensive group 2 or 3 patients.

  10. Pathological gambling.

    PubMed

    Hollander, E; Buchalter, A J; DeCaria, C M

    2000-09-01

    With increasing access to gambling facilities through casinos, the Internet, and other venues, PG is a rapidly emerging mental health concern. This impulse-control disorder tends to be comorbid with a wide range of other disorders and is reportedly associated with a high rate of suicide. For most gamblers, gambling is a form of entertainment, but for many individuals, the activity leads to far-reaching disruption of family and work. The personal and societal financial ramifications are severe, and many individuals with PG end up in the criminal justice system. An understanding of the neurobiology of PG is beginning to surface. 5-HT is linked to behavioral initiation and disinhibition, which are important in the onset of the gambling cycle and the difficulty in ceasing the behavior. Norepinephrine is associated with the arousal and risk taking in patients with PG. Dopamine is linked to positive and negative reward, the addictive component of this disorder. Effective treatment strategies for pathological gamblers are emerging. Potentially useful pharmacologic agents include SRIs (clomipramine and fluvoxamine), mood stabilizers for pathological gamblers with comorbid bipolar disorders (lithium), and naltrexone. Cognitive-behavioral psychotherapies offer promising results in the treatment of patients with this disorder. To devise prevention and early-intervention programs, research is needed to identify specific features of the individuals at risk for gambling problems. Education targeting vulnerable youth that show early signs of gambling behavior may be worthwhile and should be investigated further. Funding is necessary to support these endeavors, so perhaps a portion of tax revenues generated from the gambling industry should go toward specialized treatment facilities, educational efforts, and research into the neurobiology and treatment of PG.

  11. Effect of Forest Walking on Autonomic Nervous System Activity in Middle-Aged Hypertensive Individuals: A Pilot Study

    PubMed Central

    Song, Chorong; Ikei, Harumi; Kobayashi, Maiko; Miura, Takashi; Taue, Masao; Kagawa, Takahide; Li, Qing; Kumeda, Shigeyoshi; Imai, Michiko; Miyazaki, Yoshifumi

    2015-01-01

    There has been increasing attention on the therapeutic effects of the forest environment. However, evidence-based research that clarifies the physiological effects of the forest environment on hypertensive individuals is lacking. This study provides scientific evidence suggesting that a brief forest walk affects autonomic nervous system activity in middle-aged hypertensive individuals. Twenty participants (58.0 ± 10.6 years) were instructed to walk predetermined courses in forest and urban environments (as control). Course length (17-min walk), walking speed, and energy expenditure were equal between the forest and urban environments to clarify the effects of each environment. Heart rate variability (HRV) and heart rate were used to quantify physiological responses. The modified semantic differential method and Profile of Mood States were used to determine psychological responses. The natural logarithm of the high-frequency component of HRV was significantly higher and heart rate was significantly lower when participants walked in the forest than when they walked in the urban environment. The questionnaire results indicated that, compared with the urban environment, walking in the forest increased “comfortable”, “relaxed”, “natural” and “vigorous” feelings and decreased “tension-anxiety,” “depression,” “anxiety-hostility,” “fatigue” and “confusion”. A brief walk in the forest elicited physiological and psychological relaxation effects on middle-aged hypertensive individuals. PMID:25739004

  12. Comparative analysis of non-adherence to medication treatment for systemic arterial hypertension in urban and rural populations 1

    PubMed Central

    Magnabosco, Patricia; Teraoka, Eliana Cavalari; de Oliveira, Edward Meirelles; Felipe, Elisangela Aparecida; Freitas, Dayana; Marchi-Alves, Leila Maria

    2015-01-01

    OBJECTIVE: to evaluate the indexes and the main factors associated with non-adherence to medication treatment for systemic arterial hypertension between urban and rural areas. METHOD: analytical study based on an epidemiological survey with a sample of 247 hypertensive residents of rural and urban areas, with application of a socio-demographic and economic questionnaire, and treatment adherence assessment. The Pearson's Chi-square test was used and the odds ratio (OD) was calculated to analyze the factors related to non-adherence. RESULTS: the prevalence of non-adherence was 61.9% and it was higher in urban areas (63.4%). Factors significantly associated with non-adherence were: male gender (OR=1.95; 95% CI 1.08-3.50), age 20-59 years old (OR=2.51; 95% CI 1.44-4.39), low economic status (OR=1.95; 95% CI 1.09-3.47), alcohol consumption (OR=5.92, 95% CI 1.73-20.21), short time of hypertension diagnosis (OR=3.07; 95% CI 1.35-6.96) and not attending the health service for routine consultations (OR=2.45; 1.35-4.42). CONCLUSION: the socio-demographic/economic characteristics, lifestyle habits and how to relate to health services were the factors that presented association with non-adherence regardless of the place of residence. PMID:25806627

  13. 17β-Estradiol protects against the progression of hypertension during adulthood in a mouse model of systemic lupus erythematosus.

    PubMed

    Gilbert, Emily L; Mathis, Keisa W; Ryan, Michael J

    2014-03-01

    Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disorder with a high prevalence of hypertension and cardiovascular disease. Because SLE predominantly affects women, estrogen is commonly implicated as a contributor to SLE disease progression. Using an established mouse model of SLE (female NZBWF1), we tested whether estrogen has a causal role in the development of hypertension in adulthood. Thirty-week-old SLE and control mice (NZW/LacJ) underwent either a sham or ovariectomy (OVX) procedure. 17β-Estradiol (E2; 5 μg/mouse, twice/week, subcutaneously) was administered to a subset of OVX mice. Mean arterial pressure (in mm Hg) was increased in SLE mice (134±4 versus 119±3 in controls). Contrary to our hypothesis, OVX exacerbated the hypertension in female SLE mice (153±3; P<0.05 versus SLE sham), and repletion of E2 prevented the OVX-induced increase in blood pressure (132±2). The prevalence of albuminuria was increased in SLE mice compared with controls (37% versus 0%). OVX increased the prevalence in SLE mice (70% versus 37% in SLE shams). Repletion of E2 completely prevented albuminuria in OVX SLE mice. Renal cortical tumor necrosis factor α was increased in SLE mice compared with controls and was further increased in OVX SLE. The OVX-induced increase in renal tumor necrosis factor α expression was prevented by repletion of E2. Treatment of OVX SLE mice with the tumor necrosis factor α inhibitor, etanercept, blunted the OVX-induced increase in blood pressure (140±2) and prevalence of albuminuria (22%). These data suggest that 17β-estradiol protects against the progression of hypertension during adulthood in SLE, in part, by reducing tumor necrosis factor α.

  14. Central renin-angiotensin system activation and inflammation induced by high fat diet sensitize angiotensin II-elicited hypertension

    PubMed Central

    Xue, Baojian; Thunhorst, Robert L.; Yu, Yang; Guo, Fang; Beltz, Terry G.; Felder, Robert B.; Johnson, Alan Kim

    2016-01-01

    Obesity has been shown to promote renin-angiotensin system (RAS) activity and inflammation in the brain and to be accompanied by increased sympathetic activity and blood pressure (BP). Our previous studies demonstrated that administration of a subpressor dose of angiotensin (Ang) II sensitizes subsequent Ang II-elicited hypertension. The present study tested whether high fat diet (HFD) feeding also sensitizes the Ang II-elicited hypertensive response and whether HFD-induced sensitization is mediated by an increase in RAS activity and inflammatory mechanisms in the brain. HFD did not increase baseline BP, but enhanced the hypertensive response to Ang II compared to a normal fat diet. The sensitization produced by the HFD was abolished by concomitant central infusions of either a tumor necrosis factor α (TNF-α) synthesis inhibitor, pentoxifylline, an Ang II type 1 receptor (AT1-R) blocker, irbesartan or an inhibitor of microglial activation, minocycline. Furthermore, central pretreatment with TNF-α mimicked the sensitizing action of a central subpressor dose of Ang II, whereas central pentoxifylline or minocycline abolished this Ang II-induced sensitization. RT-PCR analysis of lamina terminalis tissue indicated that HFD feeding, central TNF-α or a central subpressor dose of Ang II upregulated mRNA expression of several components of the RAS and proinflammatory cytokines, whereas inhibition of AT1-R and of inflammation reversed these changes. The results suggest that HFD-induced sensitization of Ang II-elicited hypertension is mediated by upregulation of the brain RAS and of central proinflammatory cytokines. PMID:26573717

  15. Oxidative Stress Causes Imbalance of Renal Renin Angiotensin System (RAS) Components and Hypertension in Obese Zucker Rats

    PubMed Central

    Luo, Hao; Wang, Xinquan; Chen, Caiyu; Wang, Jialiang; Zou, Xue; Li, Chuanwei; Xu, Zaicheng; Yang, Xiaoli; Shi, Weibin; Zeng, Chunyu

    2015-01-01

    Background Oxidative stress plays an important role in the pathogenesis of hypertension, especially in obesity‐related hypertension. The natriuretic and antinatriuretic components of the renal renin angiotensin system (RAS) maintain sodium homeostasis and blood pressure. Here, we test the hypothesis that increased oxidative stress leads to the imbalance of RAS components and hypertension in obese Zucker rats. Methods and Results Lean and obese rats received vehicle or tempol, a superoxide dismutase mimetic in the drinking water for 4 weeks. Compared with vehicle‐treated lean rats, vehicle‐treated obese rats exhibited higher blood pressure and increased renal oxidative stress, accompanied by increased diuretic and natriuretic responses to AT1R antagonist (Candesartan) and AT2R agonist (CGP‐42112A) and reduced diuretic and natriuretic response to MasR agonist (Ang‐[1 to 7]). Moreover, obese rats had higher ACE, AT1R and AT2R, lower ACE2 and MasR expressions in the kidney. All of the above‐mentioned abnormalities were reversed to some degree by tempol treatment. In primary cultures of renal proximal tubular (RPT) cells from lean and obese rats, tempol treatment also increased AT2R, ACE2, and MasR expressions but decreased AT1R and ACE expressions in obese rats. Conclusions Taken together, our study indicated that the imbalance of renal RAS components was associated with increased oxidative stress in obese rats. Furthermore, antioxidant treatment with tempol reversed the imbalance of renal RAS components and led to diuresis and natriuresis, which, at least in part, explains the blood pressure‐lowering effect of antioxidant supplementation in obesity‐related hypertension. PMID:25687731

  16. Sequential activation of the intrarenal renin-angiotensin system in the progression of hypertensive nephropathy in Goldblatt rats.

    PubMed

    Kim, Yang Gyun; Lee, Sang Ho; Kim, Se-Yun; Lee, Arah; Moon, Ju Young; Jeong, Kyung-Hwan; Lee, Tae Won; Lim, Sung Jig; Sohn, Il Suk; Ihm, Chun-Gyoo

    2016-07-01

    The intrarenal renin-angiotensin system (RAS) has an important role in generating and maintaining hypertension in two-kidney, one-clip (2K1C) rats. This study evaluated how various intrarenal RAS components contributed to hypertension not only in the maintenance period (5w; 5 wk after operation) but also earlier (2w; 2 wk after operation). We inserted a 2.5-mm clip into the left renal artery of Sprague-Dawley rats and euthanized them at 2w and 5w following the operation. Systolic blood pressure increased within 1 wk after the operation, and left ventricular hypertrophy occurred in 2K1C rats. At 2w, juxtaglomerular apparatus (JGA) and collecting duct (CD) renin increased in clipped kidney (CK) of 2K1C rats. The tubular angiotensin I-converting enzyme (ACE) was not changed, but peritubular ACE2 decreased in nonclipped kidney (NCK) and CK of 2K1C rats. At 5w, ACE and CD renin were enhanced, and ACE2 was still lessened in both kidneys of 2K1C rats. However, plasma renin activity (PRA) was not different from that in sham rats. In proximal tubules of CK, the ANG II type 1 receptor (AT1R) was not suppressed, but the Mas receptor (MasR) was reduced; thus the AT1R/MasR ratio was elevated. Although hypoxic change in CK could not be excluded, the JGA renin of CK and CD renin in both kidneys was highly expressed independent of time. Peritubular ACE2 changed in the earlier period, and uninhibited AT1R in proximal tubules of CK was presented in the maintenance period. In 2K1C rats, attenuated ACE2 seems to contribute to initiating hypertension while upregulated ACE in combination with unsuppressed AT1R may have a key role in maintaining hypertension.

  17. Teaching General and Systemic Pathology in a New Veterinary School. II. Materials and Costs

    ERIC Educational Resources Information Center

    Crowell, W. A.; And Others

    1976-01-01

    The amounts, types and costs of materials used to initiate a Year II (sophomore) pathology course in the L.S.U. School of Veterinary Medicine were tabulated. Use of the autotutorial method resulted in slightly greater costs than the traditional method, but this was offset by general satisfaction with it. (Author/LBH)

  18. Teaching General and Systemic Pathology in a New Veterinary School. I. Method of Instruction

    ERIC Educational Resources Information Center

    Crowell, W. A.; And Others

    1976-01-01

    The Year II pathology course presented to the first two classes of veterinary students at L.S.U. was favorably evaluated. The method of instruction included learner objectives, the autotutorial approach with minicourses, modified mastery evaluation, and the Postlethwait means of presentation. (Author/LBH)

  19. Pulmonary Hypertension

    MedlinePlus

    ... on Twitter. What Is Pulmonary Hypertension? Pulmonary hypertension (PULL-mun-ary HI-per-TEN-shun), or PH, is increased pressure in the pulmonary arteries. These arteries carry blood from your heart to your lungs to pick up oxygen. PH causes symptoms such as shortness of ...

  20. Portal hypertension: Imaging of portosystemic collateral pathways and associated image-guided therapy.

    PubMed

    Bandali, Murad Feroz; Mirakhur, Anirudh; Lee, Edward Wolfgang; Ferris, Mollie Clarke; Sadler, David James; Gray, Robin Ritchie; Wong, Jason Kam

    2017-03-14

    Portal hypertension is a common clinical syndrome, defined by a pathologic increase in the portal venous pressure. Increased resistance to portal blood flow, the primary factor in the pathophysiology of portal hypertension, is in part due to morphological changes occurring in chronic liver diseases. This results in rerouting of blood flow away from the liver through collateral pathways to low-pressure systemic veins. Through a variety of computed tomographic, sonographic, magnetic resonance imaging and angiographic examples, this article discusses the appearances and prevalence of both common and less common portosystemic collateral channels in the thorax and abdomen. A brief overview of established interventional radiologic techniques for treatment of portal hypertension will also be provided. Awareness of the various imaging manifestations of portal hypertension can be helpful for assessing overall prognosis and planning proper management.

  1. Portal hypertension: Imaging of portosystemic collateral pathways and associated image-guided therapy

    PubMed Central

    Bandali, Murad Feroz; Mirakhur, Anirudh; Lee, Edward Wolfgang; Ferris, Mollie Clarke; Sadler, David James; Gray, Robin Ritchie; Wong, Jason Kam

    2017-01-01

    Portal hypertension is a common clinical syndrome, defined by a pathologic increase in the portal venous pressure. Increased resistance to portal blood flow, the primary factor in the pathophysiology of portal hypertension, is in part due to morphological changes occurring in chronic liver diseases. This results in rerouting of blood flow away from the liver through collateral pathways to low-pressure systemic veins. Through a variety of computed tomographic, sonographic, magnetic resonance imaging and angiographic examples, this article discusses the appearances and prevalence of both common and less common portosystemic collateral channels in the thorax and abdomen. A brief overview of established interventional radiologic techniques for treatment of portal hypertension will also be provided. Awareness of the various imaging manifestations of portal hypertension can be helpful for assessing overall prognosis and planning proper management. PMID:28348478

  2. Modelling of pathologies of the nervous system by the example of computational and electronic models of elementary nervous systems

    NASA Astrophysics Data System (ADS)

    Shumilov, V. N.; Syryamkin, V. I.; Syryamkin, M. V.

    2015-11-01

    formation of connections between neurons in simplest biological objects. Based on the correspondence of function of the created models to function of biological nervous systems we suggest the use of computational and electronic models of the brain for the study of its function under normal and pathological conditions, because operating principles of the models are built on principles imitating the function of biological nervous systems and the brain.

  3. Modelling of pathologies of the nervous system by the example of computational and electronic models of elementary nervous systems

    SciTech Connect

    Shumilov, V. N. Syryamkin, V. I. Syryamkin, M. V.

    2015-11-17

    formation of connections between neurons in simplest biological objects. Based on the correspondence of function of the created models to function of biological nervous systems we suggest the use of computational and electronic models of the brain for the study of its function under normal and pathological conditions, because operating principles of the models are built on principles imitating the function of biological nervous systems and the brain.

  4. Increased risk of systemic lupus erythematosus in pregnancy-induced hypertension

    PubMed Central

    Lin, Li-Te; Wang, Peng-Hui; Tsui, Kuan-Hao; Cheng, Jiin-Tsuey; Cheng, Jin-Shiung; Huang, Wei-Chun; Tang, Pei-Ling; Hu, Li-Yu

    2016-01-01

    Abstract Dysregulation of the immune system plays a role in the pathogenesis of both, pregnancy-induced hypertension (PIH) and systemic lupus erythematosus (SLE). It is well known that SLE predisposes to be complicated with PIH. However, few studies have attempted to investigate whether PIH increased subsequent SLE risk. The objectives of this study were to assess the association between PIH and subsequent SLE risk and identify predictive risk factors. Patients with newly diagnosed PIH were selected from the Taiwan National Health Insurance Research Database (NHIRD) and compared with a matched cohort without PIH based on age and the year of delivery. The incidence of new-onset SLE was evaluated in both cohorts. The overall observational period was from January 1, 2000 to December 31, 2013. Among the 23.3 million individuals registered in the NHIRD, 29,091 patients with PIH and 116,364 matched controls were identified. The incidence of SLE was higher among patients with PIH than in the matched controls (incidence rate ratio [IRR] = 4.02, 95% confidence interval [CI] 3.98–4.05, P < 0.0001). The IRR for subsequent SLE development remained significantly higher in all stratifications during the follow-up years. The multivariate Cox regression model was performed and the results showed that PIH may be an independent risk factors for the development of subsequent SLE (hazard ratio [HR] = 2.87, 95% CI 2.07–3.98, P < 0.0001). Moreover, multivariate Cox regression model was used again among the PIH cohort only in order to identify the possible risk factors for subsequent SLE in the population with PIH. Patients with PIH may have higher risk of developing newly diagnosed SLE than those without PIH. In addition, among individuals who have experienced PIH, those younger than 30 years, having experienced preeclampsia/eclampsia, single parity, preterm birth, or chronic kidney disease, may display an increased subsequent risk of SLE. PMID:27472738

  5. Onset and Regression of Pregnancy-Induced Cardiac Alterations in Gestationally Hypertensive Mice: The Role of the Natriuretic Peptide System.

    PubMed

    Ventura, Nicole M; Li, Terry Y; Tse, M Yat; Andrew, R David; Tayade, Chandrakant; Jin, Albert Y; Pang, Stephen C

    2015-12-01

    Pregnancy induces cardiovascular adaptations in response to increased volume overload. Aside from the hemodynamic changes that occur during pregnancy, the maternal heart also undergoes structural changes. However, cardiac modulation in pregnancies complicated by gestational hypertension is incompletely understood. The objectives of the current investigation were to determine the role of the natriuretic peptide (NP) system in pregnancy and to assess alterations in pregnancy-induced cardiac hypertrophy between gestationally hypertensive and normotensive dams. Previously we have shown that mice lacking the expression of atrial NP (ANP; ANP(-/-)) exhibit a gestational hypertensive phenotype. In the current study, female ANP(+/+) and ANP(-/-) mice were mated with ANP(+/+) males. Changes in cardiac size and weight were evaluated across pregnancy at Gestational Days 15.5 and 17.5 and Postnatal Days 7, 14, and 28. Nonpregnant mice were used as controls. Physical measurement recordings and histological analyses demonstrated peak cardiac hypertrophy occurring at 14 days postpartum in both ANP(+/+) and ANP(-/-) dams with little to no change during pregnancy. Additionally, left ventricular expression of the renin-angiotensin system (RAS) and NP system was quantified by real-time quantitative polymerase chain reaction. Up-regulation of Agt and AT(1a) genes was observed late in pregnancy, while Nppa and Nppb genes were significantly up-regulated postpartum. Our data suggest that pregnancy-induced cardiac hypertrophy may be influenced by the RAS throughout gestation and by the NP system postpartum. Further investigations are required to gain a complete understanding of the mechanistic aspects of pregnancy-induced cardiac hypertrophy.

  6. Pressure-volume regulation in hypertension.

    PubMed

    Hall, J E; Guyton, A C; Brands, M W

    1996-06-01

    In all forms of hypertension, including human essential hypertension, pressure natriuresis is abnormal because sodium excretion is the same as in normotension despite increased arterial pressure. Considerable evidence indicates that this resetting of pressure natriuresis plays a key role in causing hypertension, rather than merely occurring as an adaptation to increased blood pressure. Because human essential hypertension is a heterogeneous disease, it is likely that multiple neurohumoral and intrarenal defects contribute to abnormal pressure natriuresis and increased blood pressure. Physiological studies have shown that renal abnormalities that cause increased distal and collecting tubule reabsorption, decreased glomerular filtration coefficient or loss of nephrons also cause decreased slope of pressure natriuresis (salt-sensitive hypertension), whereas increased preglomerular resistance causes a parallel shift of pressure natriuresis (salt-insensitive hypertension). Comparison of the characteristics of pressure natriuresis (such as salt-sensitivity of blood pressure) in hypertensive subjects with those forms of experimental hypertension of known origin can provide insight into the etiology of human hypertension. With long-standing hypertension, pathological changes in the glomeruli and renal arterioles may further shift pressure natriuresis and exacerbate hypertension.

  7. A Pathological Brain Detection System based on Extreme Learning Machine Optimized by Bat Algorithm.

    PubMed

    Lu, Siyuan; Qiu, Xin; Shi, Jianpin; Li, Na; Lu, Zhi-Hai; Chen, Peng; Yang, Meng-Meng; Liu, Fang-Yuan; Jia, Wen-Juan; Zhang, Yudong

    2016-10-19

    (Aim) It is beneficial to classify brain images as healthy or pathological automatically, because 3D brain images can generate so much information that it is time consuming and tedious for manual analysis. Among various 3D brain imaging techniques, magnetic resonance (MR) imaging is the most suitable for brain, and it is now widely applied in hospitals, because it is helpful in the four ways of diagnosis, prognosis, pre-surgical, and postsurgical procedures. Although there are automatic detection methods, they suffer from low accuracy. (Method) Therefore, we proposed a novel approach which employed 2D discrete wavelet transform (DWT), and calculated the entropies of the subbands as features. Then, a bat algorithm optimized extreme learning machine (BA-ELM) was trained to identify pathological brains from healthy controls. A 10x10-fold cross validation was performed to evaluate the out-of-sample performance. (Result) The method achieved a sensitivity of 99.04%, a specificity of 93.89%, and an overall accuracy of 98.33% over 132 MR brain images. (Conclusion) The experimental results suggest the proposed approach is accurate and robust in pathological brain detection.

  8. Impaired Nrf2 regulation of mitochondrial biogenesis in rostral ventrolateral medulla on hypertension induced by systemic inflammation.

    PubMed

    Wu, Kay L H; Wu, Chih-Wei; Chao, Yung-Mei; Hung, Chun-Ying; Chan, Julie Y H

    2016-08-01

    Oxidative stress in rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons reside, is involved in the development of hypertension under systemic inflammation. Mitochondrial dysfunction contributes to tissue oxidative stress. In this study, we sought to investigate whether hypertension developed under systemic inflammation is attributable to impaired mitochondrial biogenesis in RVLM. In normotensive Sprague-Dawley rats, intraperitoneal infusion of a low dose Escherichia coli lipopolysaccharide (LPS) for 7 days promoted a pressor response, alongside a decrease in mitochondrial DNA (mtDNA) copy number, reductions in protein expression of nuclear DNA-encoded transcription factors for mitochondrial biogenesis, including mitochondrial transcription factor A (TFAM) and nuclear factor erythroid-derived 2-like 2 (Nrf2), and suppression of nuclear translocation of the phosphorylated Nrf2 (p-Nrf2) in RVLM neurons; all of which were abrogated by treatment with intracisternal infusion of an interleukin-1β (IL-1β) blocker, IL-1Ra, or a mobile mitochondrial electron carrier, coenzyme Q10 (CoQ10). Microinjection into RVLM of IL-1β suppressed the expressions of p-Nrf2 and TFAM, and evoked a pressor response; conversely, the Nrf2 inducer, tert-butylhydroquinone, lessened the LPS-induced suppression of TFAM expression and pressor response. At cellular level, exposure of neuronal N2a cells to IL-1β decreased mtDNA copy number, increased protein interaction of Nrf2 to its negative regulator, kelch-like ECH-associated protein 1 (Keap1), and reduced DNA binding activity of p-Nrf2 to Tfam gene. Together these results indicate that defect mitochondrial biogenesis in RVLM neurons entailing redox-sensitive and IL-1β-dependent suppression of TFAM because of the increase in the formation of Keap1/Nrf2 complex, reductions in nuclear translocation of the activated Nrf2 and its binding to the Tfam gene promoter may underlie hypertension developed under the LPS

  9. Evaluation of choroidal thickness via enhanced depth-imaging optical coherence tomography in patients with systemic hypertension

    PubMed Central

    Gök, Mustafa; Karabaş, V Levent; Emre, Ender; Akşar, Arzu Toruk; Aslan, Mehmet Ş; Ural, Dilek

    2015-01-01

    Purpose: The purpose was to evaluate choroidal thickness via spectral domain optical coherence tomography (SD-OCT) and to compare the data with those of 24-h blood pressure monitoring, elastic features of the aorta, and left ventricle systolic functions, in patients with systemic hypertension. Materials and Methods: This was a case-control, cross-sectional prospective study. A total of 116 patients with systemic hypertension, and 116 healthy controls over 45 years of age, were included. Subfoveal choroidal thickness (SFCT) was measured using a Heidelberg SD-OCT platform operating in the enhanced depth imaging mode. Patients were also subjected to 24-h ambulatory blood pressure monitoring (ABPM) and standard transthoracic echocardiography (STTE). Patients were divided into dippers and nondippers using ABPM data and those with or without left ventricular hypertrophy (LVH+ and LVH-) based on STTE data. The elastic parameters of the aorta, thus aortic strain (AoS), the beta index (BI), aortic distensibility (AoD), and the left ventricular mass index (LVMI), were calculated from STTE data. Results: No significant difference in SFCT was evident between patients and controls (P ≤ 0.611). However, a significant negative correlation was evident between age and SFCT in both groups (r = −0.66/−0.56, P ≤ 0.00). No significant SFCT difference was evident between the dipper and nondipper groups (P ≤ 0.67), or the LVH (+) and LVH (-) groups (P ≤ 0.84). No significant correlation was evident between SFCT and any of AoS, BI, AoD, or LVMI. Discussion: The choroid is affected by atrophic changes associated with aging. Even in the presence of comorbid risk factors including LVH and arterial stiffness, systemic hypertension did not affect SFCT. PMID:25971169

  10. Exhaled nitric oxide in pulmonary arterial hypertension associated with systemic sclerosis

    PubMed Central

    Mathai, Stephen C.; Hummers, Laura K.; Shah, Ami A.; Wigley, Fredrick M.; Lechtzin, Noah; Hassoun, Paul M.; Girgis, Reda E.

    2016-01-01

    Abstract The fractional exhaled concentration of nitric oxide (FENO) has been shown to be reduced in idiopathic pulmonary arterial hypertension (PAH) but has not been adequately studied in PAH associated with systemic sclerosis (SSc). We measured FENO at an expiratory flow rate of 50 mL/s in 21 treatment-naive patients with SSc-associated PAH (SSc-PAH), 94 subjects with SSc without pulmonary involvement, and 84 healthy volunteers. Measurements of FENO at additional flow rates of 100, 150, and 250 mL/s were obtained to derive the flow-independent nitric oxide exchange parameters of maximal airway flux (J′awNO) and steady-state alveolar concentration (CANO). FENO at 50 mL/s was similar (P = 0.22) in the SSc-PAH group (19 ± 12 parts per billion [ppb]) compared with the SSc group (17 ± 12 ppb) and healthy control group (21 ± 11 ppb). No change was observed after 4 months of targeted PAH therapy in 14 SSc-PAH group patients (P = 0.9). J′awNO was modestly reduced in SSc group subjects without lung disease (1.2 ± 0.5 nl/s) compared with healthy controls (1.64 ± 0.9; P < 0.05) but was similar to that in the SSc-PAH group. CANO was elevated in individuals with SSc-PAH (4.8 ± 2.6 ppb) compared with controls with SSc (3.3 ± 1.4 ppb) and healthy subjects (2.6 ± 1.5 ppb; P < 0.001 for both). However, after adjustment for the diffusing capacity of CO, there was no significant difference in CANO between individuals with SSc-PAH and controls with SSc. We conclude that FENO is not useful for the diagnosis of PAH in SSc. Increased alveolar nitric oxide in SSc-PAH likely represents impaired diffusion into pulmonary capillary blood. PMID:28090297

  11. Dual-Enzyme-Loaded Multifunctional Hybrid Nanogel System for Pathological Responsive Ultrasound Imaging and T2-Weighted Magnetic Resonance Imaging.

    PubMed

    Wang, Xia; Niu, Dechao; Li, Pei; Wu, Qing; Bo, Xiaowan; Liu, Boji; Bao, Song; Su, Teng; Xu, Huixiong; Wang, Qigang

    2015-06-23

    A dual-enzyme-loaded multifunctional hybrid nanogel probe (SPIO@GCS/acryl/biotin-CAT/SOD-gel, or SGC) has been developed for dual-modality pathological responsive ultrasound (US) imaging and enhanced T2-weighted magnetic resonance (MR) imaging. This probe is composed of functionalized superparamagnetic iron oxide particles, a dual enzyme species (catalase and superoxide dismutase), and a polysaccharide cationic polymer glycol chitosan gel. The dual-modality US/MR imaging capabilities of the hybrid nanogel for responsive US imaging and enhanced T2-weighted MR imaging have been evaluated both in vitro and in vivo. These results show that the hybrid nanogel SGC can exhibit efficient dual-enzyme biocatalysis with pathological species for responsive US imaging. SGC also demonstrates increased accumulation in acidic environments for enhanced T2-weighted MR imaging. Further research on these nanogel systems may lead to the development of more efficient US/MR contrast agents.

  12. The blockade of renin-angiotensin-aldosterone system in hemodialysis patients to control hypertension and prevent cardiovascular disease: optimal pharmacotherapy.

    PubMed

    Morishita, Yoshiyuki; Kusano, Eiji

    2011-10-01

    Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in hemodialysis (HD) patients. Hypertension (HT) is a major risk factor for CVD. The renin-angiotensin-aldosterone system (RAAS) plays pivotal roles in the pathogenesis of HT in HD patients. Previous studies suggested that the blockade of RAAS may be effective to control blood pressure (BP) and to prevent CVD in HD patients. A certain level of preventive effects against CVD by RAAS blockade in HD patients has been reported independently from a BP lowering effect. This review focuses on the effect of blocking RAAS in HD patients for the control of HT and the prevention of CVD.

  13. Mechanisms of remodelling of small arteries, antihypertensive therapy and the immune system in hypertension.

    PubMed

    Schiffrin, Ernesto L

    2015-12-04

    This review summarizes my lecture for the 2015 Distinguished Scientist Award from the Canadian Society of Clinical Investigation, and is based mainly on studies in my laboratory on the mechanisms of remodelling of small arteries in experimental animal and human hypertension and on treatments that lower blood pressure and improve structure and function of resistance vessels. Small resistance arteries undergo either inward eutrophic or hypertrophic remodelling, which raises blood pressure and impairs tissue perfusion. These vascular changes are corrected by some antihypertensive drugs, which may lead to improved outcomes. Vasoconstriction, growth, oxidative stress and inflammation are some of the mechanisms, within the vascular wall, that can be beneficially affected by antihypertensive agents. These antihypertensive-sensitive mechanisms are reviewed in this review, together with the inflammatory and immune mechanisms that may participate in hypertension and associated cardiovascular injury. Molecular studies, based on this research, will hopefully identify novel diagnostic and therapeutic targets, which will improve our ability to prevent and treat hypertension and cardiovascular disease.

  14. Key role of the RhoA/Rho kinase system in pulmonary hypertension.

    PubMed

    Connolly, Michelle J; Aaronson, Philip I

    2011-02-01

    Pulmonary hypertension (PH) is a general term comprising a spectrum of pulmonary hypertensive disorders which have in common an elevation of mean pulmonary arterial pressure (mPAP). The prototypical form of the disease, termed pulmonary arterial hypertension (PAH), is a rare but lethal syndrome with a complex aetiology characterised by increased pulmonary vascular resistance (PVR) and progressive elevation of mPAP; patients generally die from heart failure. Current therapies are inadequate and median survival is less than three years. PH due to chronic hypoxia (CH) is a condition separate from PAH and is strongly associated with chronic obstructive pulmonary disease (COPD). An early event in the pathogenesis of this form of PH is hypoxic pulmonary vasoconstriction (HPV), an acute homeostatic process that maintains the ventilation-perfusion ratio during alveolar hypoxia. The mechanisms underlying HPV remain controversial, but RhoA/Rho kinase (ROK)-mediated Ca²+-sensitisation is considered important. Increasing evidence also implicates RhoA/ROK in PASMC proliferation, inflammatory cell recruitment and the regulation of cell motility, all of which are involved in the pulmonary vascular remodelling occurring in all forms of PH. ROK is therefore a potential therapeutic target in treating PH of various aetiologies. Here, we examine current concepts regarding the aetiology of PAH and also PH due to CH, focusing on the contribution that RhoA/ROK-mediated processes may make to their development and on ROK inhibitors as potential therapies.

  15. Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension

    PubMed Central

    Muñoz-Durango, Natalia; Fuentes, Cristóbal A.; Castillo, Andrés E.; González-Gómez, Luis Martín; Vecchiola, Andrea; Fardella, Carlos E.; Kalergis, Alexis M.

    2016-01-01

    Arterial hypertension is a common condition worldwide and an important predictor of several complicated diseases. Arterial hypertension can be triggered by many factors, including physiological, genetic, and lifestyle causes. Specifically, molecules of the renin-angiotensin-aldosterone system not only play important roles in the control of blood pressure, but they are also associated with the genesis of arterial hypertension, thus constituting a need for pharmacological interventions. Chronic high pressure generates mechanical damage along the vascular system, heart, and kidneys, which are the principal organs affected in this condition. In addition to mechanical stress, hypertension-induced oxidative stress, chronic inflammation, and the activation of reparative mechanisms lead to end-organ damage, mainly due to fibrosis. Clinical trials have demonstrated that renin-angiotensin-aldosterone system intervention in hypertensive patients lowers morbidity/mortality and inflammatory marker levels as compared to placebo patients, evidencing that this system controls more than blood pressure. This review emphasizes the detrimental effects that a renin-angiotensin-aldosterone system (RAAS) imbalance has on health considerations above and beyond high blood pressure, such as fibrotic end-organ damage. PMID:27347925

  16. Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension.

    PubMed

    Muñoz-Durango, Natalia; Fuentes, Cristóbal A; Castillo, Andrés E; González-Gómez, Luis Martín; Vecchiola, Andrea; Fardella, Carlos E; Kalergis, Alexis M

    2016-06-23

    Arterial hypertension is a common condition worldwide and an important predictor of several complicated diseases. Arterial hypertension can be triggered by many factors, including physiological, genetic, and lifestyle causes. Specifically, molecules of the renin-angiotensin-aldosterone system not only play important roles in the control of blood pressure, but they are also associated with the genesis of arterial hypertension, thus constituting a need for pharmacological interventions. Chronic high pressure generates mechanical damage along the vascular system, heart, and kidneys, which are the principal organs affected in this condition. In addition to mechanical stress, hypertension-induced oxidative stress, chronic inflammation, and the activation of reparative mechanisms lead to end-organ damage, mainly due to fibrosis. Clinical trials have demonstrated that renin-angiotensin-aldosterone system intervention in hypertensive patients lowers morbidity/mortality and inflammatory marker levels as compared to placebo patients, evidencing that this system controls more than blood pressure. This review emphasizes the detrimental effects that a renin-angiotensin-aldosterone system (RAAS) imbalance has on health considerations above and beyond high blood pressure, such as fibrotic end-organ damage.

  17. Hypertension screening

    NASA Technical Reports Server (NTRS)

    Foulke, J. M.

    1975-01-01

    An attempt was made to measure the response to an announcement of hypertension screening at the Goddard Space Center, to compare the results to those of previous statistics. Education and patient awareness of the problem were stressed.

  18. Pulmonary Hypertension

    MedlinePlus

    Pulmonary hypertension (PH) is high blood pressure in the arteries to your lungs. It is a serious condition. If you have ... and you can develop heart failure. Symptoms of PH include Shortness of breath during routine activity, such ...

  19. Obesity: A Perspective from Hypertension.

    PubMed

    Susic, Dinko; Varagic, Jasmina

    2017-01-01

    The prevalence of obesity-related hypertension is high worldwide and has become a major health issue. The mechanisms by which obesity relates to hypertensive disease are still under intense research scrutiny, and include altered hemodynamics, impaired sodium homeostasis, renal dysfunction, autonomic nervous system imbalance, endocrine alterations, oxidative stress and inflammation, and vascular injury. Most of these contributing factors interact with each other at multiple levels. Thus, as a multifactorial and complex disease, obesity-related hypertension should be recognized as a distinctive form of hypertension, and specific considerations should apply in planning therapeutic approaches to treat obese individuals with high blood pressure.

  20. Renal denervation for resistant hypertension.

    PubMed

    Almeida, Manuel de Sousa; Gonçalves, Pedro de Araújo; Oliveira, Eduardo Infante de; Carvalho, Henrique Cyrne de

    2015-02-01

    There is a marked contrast between the high prevalence of hypertension and the low rates of adequate control. A subset of patients with suboptimal blood pressure control have drug-resistant hypertension, in the pathophysiology of which chronic sympathetic hyperactivation is significantly involved. Sympathetic renal denervation has recently emerged as a device-based treatment for resistant hypertension. In this review, the pathophysiological mechanisms linking the sympathetic nervous system and cardiovascular disease are reviewed, focusing on resistant hypertension and the role of sympathetic renal denervation. An update on experimental and clinical results is provided, along with potential future indications for this device-based technique in other cardiovascular diseases.

  1. Effects of captopril on the renin angiotensin system, oxidative stress, and endothelin in normal and hypertensive rats.

    PubMed

    Bolterman, Rodney J; Manriquez, Melissa C; Ortiz Ruiz, M Clara; Juncos, Luis A; Romero, J Carlos

    2005-10-01

    There is substantial evidence suggesting that angiotensin II plays an important role in elevating blood pressure of spontaneously hypertensive rats, despite normal plasma renin activity, and that converting enzyme inhibitors (captopril) can effectively normalize blood pressure in the spontaneously hypertensive rats. One mechanism by which angiotensin II induces hypertension is via oxidative stress and endothelin, as seen in subpressor angiotensin II-induced hypertension. In fact, it has been shown that antioxidants lower mean arterial pressure in spontaneously hypertensive rats. However, the relationship between angiotensin II, oxidative stress, and endothelin in the spontaneously hypertensive rats is still relatively undefined. This study examines the relationship between mean arterial pressure, plasma renin activity, angiotensin II, oxidative stress, and endothelin in spontaneously hypertensive rats compared with normotensive Wistar Kyoto rats, and the effects of captopril on this association. Untreated spontaneously hypertensive rats had increased plasma angiotensin II levels despite normal plasma renin activity, oxidative stress, and endothelin. Captopril treatment in spontaneously hypertensive rats lowered mean arterial pressure, angiotensin II, oxidative stress, and endothelin, and increased plasma renin activity. In contrast, captopril increased plasma renin activity (suggesting effective captopril treatment) but did not significantly alter mean arterial pressure, angiotensin II, oxidative stress, or endothelin of Wistar Kyoto rats. These results suggest that in spontaneously hypertensive rats, angiotensin II is a primary instigator of hypertension, and that captopril selectively lowers angiotensin II, oxidant stress, and endothelin, which in turn may contribute to the blood pressure-lowering efficacy of captopril in spontaneously hypertensive rats.

  2. Snakes and Hypertension.

    PubMed

    Miller, Edward D

    2017-02-01

    Inhibition of Angiotensin Conversion in Experimental Renovascular Hypertension. By Miller ED Jr, Samuels A, Haber E, and Barger AC. Science 1972; 177:1108-9. Reprinted with permission from AAAS.Constriction of the renal artery and controlled reduction of renal perfusion pressure is followed by a prompt increase in systemic renin activity and a concomitant rise in blood pressure in trained, unanesthetized dogs. The elevated blood pressure induced by the renal artery stenosis can be prevented by prior treatment with the nonapeptide Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro, which blocks conversion of angiotensin I to angiotensin II. Further, the nonapeptide can restore systemic pressure to normal in the early phase of renovascular hypertension. These results offer strong evidence that the renin- angiotensin system is responsible for the initiation of hypertension in the unilaterally nephrectomized dog with renal artery constriction.

  3. Development of a new real-time PCR system for simultaneous detection of bacteria and fungi in pathological samples.

    PubMed

    Fukumoto, Hitomi; Sato, Yuko; Hasegawa, Hideki; Saeki, Hidehisa; Katano, Harutaka

    2015-01-01

    A novel system for simultaneous detection of pathogenic bacteria and fungi in pathological samples was developed using a real-time polymerase chain reaction (PCR) system. This system, designated the "multi-microbial real-time PCR", has the potential to simultaneously detect 68 bacterial and 9 fungal species in a 96-well plate format. All probe-primer sets were designed to produce amplicons smaller than 210 bp using formalin-fixed paraffin-embedded samples as input. The specificity and sensitivity of each probe-primer set were tested against DNA extracted from pure cultures of specific pathogens. The multi-microbial real-time PCR system revealed profiles of microorganism infection in lung samples collected at autopsy from 10 patients with acquired immunodeficiency syndrome. Staphylococcus aureus was the most common microbe detected (n=8), but with low copy numbers. High copy numbers of Pseudomonas aeruginosa were detected in the lung samples with abscess (n=6). Enterococcus faecium (n=6), Elizabethkingia meningoseptica (n=4), and Candida albicans (n=4) were also frequently detected. In addition, a latent infection of Mycobacterium tuberculosis was detected in one case of pneumonia. In conclusion, this multi-microbial real-time PCR system can be useful for detecting bacteria and fungi in pathological specimens from patients with uncertain diagnoses.

  4. The prognostic significance of the 2014 International Society of Urological Pathology (ISUP) grading system for prostate cancer.

    PubMed

    Samaratunga, Hemamali; Delahunt, Brett; Gianduzzo, Troy; Coughlin, Geoff; Duffy, David; LeFevre, Ian; Johannsen, Shulammite; Egevad, Lars; Yaxley, John

    2015-10-01

    The 2005 International Society of Urological Pathology (ISUP) modified Gleason grading system was further amended in 2014 with the establishment of grade groupings (ISUP grading). This study examined the predictive value of ISUP grading, comparing results with recognised prognostic parameters.Of 3700 men undergoing radical prostatectomy (RP) reported at Aquesta Pathology between 2008 and 2013, 2079 also had a positive needle biopsy available for review. We examined the association between needle biopsy 2014 ISUP grade and 2005 modified Gleason score, tumour volume, pathological stage of the subsequent RP tumour, as well as biochemical recurrence-free survival (BRFS). The median age was 62 (range 32-79 years). Median serum prostate specific antigen was 5.9 (range 0.4-69 ng/mL). For needle biopsies, 280 (13.5%), 1031 (49.6%), 366 (17.6%), 77 (3.7%) and 325 (15.6%) were 2014 ISUP grades 1-5, respectively. Needle biopsy 2014 ISUP grade showed a significant association with RP tumour volume (p < 0.001), TNM pT and N stage (p < 0.001) and BRFS (p < 0.001). Multivariate analysis using Cox proportional hazards regression model showed serum prostate specific antigen (PSA) at the time of diagnosis and ISUP grade >2 to be significantly associated with BRFS.This study provides evidence of the prognostic significance of ISUP grading for thin core needle biopsy of prostate.

  5. Multiple system atrophy of the cerebellar type (MSA-C) with concomitant beta-amyloid and tau pathology.

    PubMed

    Bujan, Bartosz; Hofer, Markus J; Oertel, Wolfgang H; Pagenstecher, Axel; Bürk, Katrin

    2013-01-01

    Multiple system atrophy (MSA) is a rapidly progressive sporadic α-synucleinopathy with adult onset characterized by progressive cerebellar ataxia, basal ganglia symptoms, autonomic dysfunction and pyramidal tract signs. While full-blown dementia is considered an exclusion criterion according to Consensus Guidelines, mild cognitive deficits such as fronto-executive dysfunction have been reported in some MSA individuals. However, the underlying anatomic correlate still has to be elucidated. We here report a 74-year-old patient with a clinical diagnosis of "probable MSA of the cerebellar type (MSA-C)" who developed pronounced clinical symptoms of fronto-executive dysfunction. Neuropathologic investigations revealed (1) numerous glial cytoplasmic inclusions (GCI) in the putamen, mesencephalon and cerebellum, (2) pronounced betaamyloid pathology in the frontal lobe and (3) mild hippocampal τ-pathology. In this patient, fronto-executive dysfunction can easily be explained by frontal degeneration typical for AD. These findings challenge the concept of cognitive dysfunction as a core feature of MSA as long as concomitant pathology other than MSA has not been reliably excluded by post mortem analysis.

  6. Fetal Programming and Cardiovascular Pathology

    PubMed Central

    Alexander, Barbara T.; Dasinger, John Henry; Intapad, Suttira

    2016-01-01

    Low birth weight serves as a crude proxy for impaired growth during fetal life and indicates a failure for the fetus to achieve its full growth potential. Low birth weight can occur in response to numerous etiologies that include complications during pregnancy, poor prenatal care, parental smoking, maternal alcohol consumption or stress. Numerous epidemiological and experimental studies demonstrate that birth weight is inversely associated with blood pressure and coronary heart disease. Sex and age impact the developmental programming of hypertension. In addition, impaired growth during fetal life also programs enhanced vulnerability to a secondary insult. Macrosomia, which occurs in response to maternal obesity, diabetes and excessive weight gain during gestation, is also associated with increased cardiovascular risk. Yet, the exact mechanisms that permanently change the structure, physiology and endocrine health of an individual across their lifespan following altered growth during fetal life are not entirely clear. Transmission of increased risk from one generation to the next in the absence of an additional prenatal insult indicates an important role for epigenetic processes. Experimental studies also indicate that the sympathetic nervous system, the renin angiotensin system, increased production of oxidative stress and increased endothelin play an important role in the developmental programming of blood pressure in later life. Thus, this review will highlight how adverse influences during fetal life and early development program an increased risk for cardiovascular disease including high blood pressure and provide an overview of the underlying mechanisms that contribute to the fetal origins of cardiovascular pathology. PMID:25880521

  7. The shift in the "paradigm" of the pharmacology of hypertension.

    PubMed

    Flordellis, Christodoulos S; Goumenos, Dimitrios; Kourounis, George; Tsementzis, Sotirios A; Paris, Hervé; Vlachojiannis, Jaannis

    2004-01-01

    Until recently elevated blood pressure was considered as a hemodynamic entity representing an increase in workload for the heart and the arterial tree. Control of hypertension meant hemodynamic unloading, through inhibition of vasoconstrictor pathways, principally renin-angiotensin system and sympathetic system. In recent years however a new pharmacological approach has evolved as a result of (i) the dissociation of endothelial dysfunction and vascular pathology from increased blood pressure; (ii) the recognition that endothelial dysfunction regards not only the vascular reactivity, but also promotes atherosclerosis and thrombosis; and (iii) an improved understanding of the complexity of local-tissue renin angiotensin system and of the vasodilatory and cytoprotective role of natriuretic peptides. This has led to a reconsideration of existing medicines in terms of specification on endothelial function, more rationalized application of drugs and search for new compounds targeting both vasodilatory and anti-proliferative pathways. Examples include beta1-adrenergic antagonists, such as Nebivolol and Carvedilol, and vasopeptidase inhibitors, such as Omapatrilat, that inhibit simultaneously the angiotensin converting enzyme and neutral endopeptidase. Furthermore the identification of genetic polymorphisms in the effectors involved in the pathophysiology of hypertension or in the response to anti-hypertensive drugs, such as the p22phox subunit of NADPH oxidase, alpha-adducin or adrenergic receptors, has promoted the prospective of both better understanding of hypertension and individualized strategies for its treatment.

  8. Estrogen regulation of the brain renin-angiotensin system in protection against angiotensin II-induced sensitization of hypertension.

    PubMed

    Xue, Baojian; Zhang, Zhongming; Beltz, Terry G; Guo, Fang; Hay, Meredith; Johnson, Alan Kim

    2014-07-15

    This study investigated sex differences in the sensitization of angiotensin (ANG) II-induced hypertension and the role of central estrogen and ANG-(1-7) in this process. Male and female rats were implanted for telemetered blood pressure (BP) recording. A subcutaneous subpressor dose of ANG II was given alone or concurrently with intracerebroventricular estrogen, ANG-(1-7), an ANG-(1-7) receptor antagonist A-779 or vehicle for 1 wk (induction). After a 1-wk rest (delay), a pressor dose of ANG II was given for 2 wk (expression). In males and ovariectomized females, subpressor ANG II had no sustained effect on BP during induction, but produced an enhanced hypertensive response to the subsequent pressor dose of ANG II during expression. Central administration of estrogen or ANG-(1-7) during induction blocked ANG II-induced sensitization. In intact females, subpressor ANG II treatment produced a decrease in BP during induction and delay, and subsequent pressor ANG II treatment given during expression produced only a slight but significant increase in BP. However, central blockade of ANG-(1-7) by intracerebroventricular infusion of A-779 during induction restored the decreased BP observed in females during induction and enhanced the pressor response to the ANG II treatment during expression. RT-PCR analyses indicated that estrogen given during induction upregulated mRNA expression of the renin-angiotensin system (RAS) antihypertensive components, whereas both central estrogen and ANG-(1-7) downregulated mRNA expression of RAS hypertensive components in the lamina terminalis. The results indicate that females are protected from ANG II-induced sensitization through central estrogen and its regulation of brain RAS.

  9. Estrogen regulation of the brain renin-angiotensin system in protection against angiotensin II-induced sensitization of hypertension

    PubMed Central

    Zhang, Zhongming; Beltz, Terry G.; Guo, Fang; Hay, Meredith; Johnson, Alan Kim

    2014-01-01

    This study investigated sex differences in the sensitization of angiotensin (ANG) II-induced hypertension and the role of central estrogen and ANG-(1–7) in this process. Male and female rats were implanted for telemetered blood pressure (BP) recording. A subcutaneous subpressor dose of ANG II was given alone or concurrently with intracerebroventricular estrogen, ANG-(1–7), an ANG-(1–7) receptor antagonist A-779 or vehicle for 1 wk (induction). After a 1-wk rest (delay), a pressor dose of ANG II was given for 2 wk (expression). In males and ovariectomized females, subpressor ANG II had no sustained effect on BP during induction, but produced an enhanced hypertensive response to the subsequent pressor dose of ANG II during expression. Central administration of estrogen or ANG-(1–7) during induction blocked ANG II-induced sensitization. In intact females, subpressor ANG II treatment produced a decrease in BP during induction and delay, and subsequent pressor ANG II treatment given during expression produced only a slight but significant increase in BP. However, central blockade of ANG-(1–7) by intracerebroventricular infusion of A-779 during induction restored the decreased BP observed in females during induction and enhanced the pressor response to the ANG II treatment during expression. RT-PCR analyses indicated that estrogen given during induction upregulated mRNA expression of the renin-angiotensin system (RAS) antihypertensive components, whereas both central estrogen and ANG-(1–7) downregulated mRNA expression of RAS hypertensive components in the lamina terminalis. The results indicate that females are protected from ANG II-induced sensitization through central estrogen and its regulation of brain RAS. PMID:24858844

  10. Alterations in myocardial thallium-201 distribution in patients with chronic systemic hypertension undergoing single-photon emission computed tomography

    SciTech Connect

    DePuey, E.G.; Guertler-Krawczynska, E.; Perkins, J.V.; Robbins, W.L.; Whelchel, J.D.; Clements, S.D.

    1988-08-01

    To characterize thallium-201 distribution in single-photon emission computed tomography (SPECT) cardiac images and polar bullseye maps, 100 patients with chronic systemic hypertension due to end-stage renal disease were studied and the results compared with those in 35 normotensive control subjects. Thallium-201 SPECT was performed after exercise in all control subjects and 70 hypertensive patients, and after intravenous dipyridamole in 30 patients. A frequent finding in hypertensive patients was a fixed decrease in the normal lateral-to-septal count density ratio in immediate thallium-201 SPECT images (1.02 +/- 0.10 vs 1.17 +/- 0.08 in control subjects, p less than 0.00001) and in 3-hour delayed images (1.02 +/- 0.11 vs 1.11 +/- 0.08 in control subjects, p less than 0.00001). No significant difference in count density ratio was present in patients undergoing treadmill versus diypridamole intervention. In 35 patients the count density ratio was greater than 2.0 standard deviations below the normal mean, creating the false impression of a fixed lateral defect (i.e., myocardial infarction). In 12 patients, myocardial wall thickness was measured at end-diastole by 2-dimensional echocardiography. Wall thickness was increased (greater than 11 mm) in all patients. The mean lateral-to-septal wall thickness ratio was 1.08 +/- 1.11; in no patient was the ratio less than 0.76 to indicate selective septal hypertrophy. The lateral-to-septal wall thickness and lateral-to-septal thallium-201 count density ratios correlated poorly (r = 0.43).

  11. Systemic hyperosmolality improves beta-glucuronidase distribution and pathology in murine MPS VII brain following intraventricular gene transfer.

    PubMed

    Ghodsi, A; Stein, C; Derksen, T; Martins, I; Anderson, R D; Davidson, B L

    1999-11-01

    Mucopolysaccharidosis VII, a classical lysosomal storage disease, is caused by deficiency of the enzyme beta-glucuronidase. Central nervous system (CNS) manifestations are severe with accumulations of storage vacuoles in all cell types. Intraventricular gene transfer can lead to transduction of the ependyma, with production and secretion of beta-glucuronidase into the cerebral spinal fluid and underlying cortex resulting in reversal of disease pathology restricted to the periventricular areas. We tested if systemic hyperosmolality would increase the distribution of beta-glucuronidase in brain parenchyma after intraventricular virus injection. Mice were administered mannitol, intraperitoneally, 20 days after gene transfer and 1 day prior to sacrifice. Mannitol-induced systemic hyperosmolality caused a marked penetration of beta-glucuronidase into the brain parenchyma. If mannitol was administered at the time of the intraventricular injection of virus, there was penetration of vector across the ependymal cell layer, with infection of cells in the subependymal region. This also resulted in increased beta-glucuronidase activity throughout the brain. Sections of brains from beta-glucuronidase-deficient mice showed correction of cellular pathology in the subependymal region plus cortical structures away from the ventricular wall. These data indicate that virus-mediated gene transfer to the brain via the ventricles, coupled with systemic mannitol administration, can lead to extensive CNS distribution of beta-glucuronidase with concomitant correction of the storage defect. Our findings have positive therapeutic implications for the treatment of CNS disorders with gene transfer vectors and recombinant proteins.

  12. Hypertensive retinopathy in a cat

    PubMed Central

    Van Boxtel, Sherry A.

    2003-01-01

    A 12-year-old cat presented for sudden blindness was diagnosed with hypertensive retinopathy on the basis of ophthalmologic and ultrasonic examination. Renal failure due to a large intranephric cyst obstructing the right ureter and renal artery was the suggested cause of the systemic hypertension. The cat died 8 hours after unilateral nephrectomy. PMID:12650046

  13. Developing an interactive mobile phone self-report system for self-management of hypertension. Part 1: patient and professional perspectives.

    PubMed

    Bengtsson, Ulrika; Kasperowski, Dick; Ring, Lena; Kjellgren, Karin

    2014-10-01

    Low adherence remains a struggle in hypertension management, despite improvement efforts. Presuming that increased patient participation is a possible approach, we collaborated with patients and healthcare professionals to design a self-report system to support self-management. The study aimed to explore and describe relevant aspects of hypertension and hypertension treatment, for use in the development of an interactive mobile phone self-report system. It further aimed to suggest which clinical measures, lifestyle measures, symptoms and side-effects of treatment would be meaningful to include in such a system. Five focus group interviews were performed with 15 patients and 12 healthcare professionals, and data was analysed using thematic analysis. Patients suggested trust, a good relationship with caregivers, and well-being as important aspects of hypertension self-management. Furthermore, they regarded blood pressure, dizziness, stress, headache and tiredness as important outcomes to include. Patients sought to understand interconnections between symptoms and variations in blood pressure, whilst healthcare professionals doubted patients' ability to do so. Healthcare professionals emphasized accessibility, clear and consistent counselling, complication prevention and educational efforts. The study presents aspects of importance for follow-up to understand the interplay between blood pressure and daily life experiences for patients with hypertension.

  14. Crossover comparison of atenolol, enalapril, hydrochlorothiazide and isradipine for isolated systolic systemic hypertension.

    PubMed

    Silagy, C A; McNeil, J J; McGrath, B P

    1992-11-15

    The benefit of antihypertensive therapy in reducing cardiovascular morbidity and mortality associated with isolated systolic hypertension has now been established by the Systolic Hypertension in the Elderly Program. However, there is little information about the relative effectiveness of different drug regimens in this condition. This study compared the efficacy and tolerability of 50 mg of atenolol, 10 mg of enalapril, 25 mg of hydrochlorothiazide and 2.5 mg of isradipine in the treatment of isolated systolic hypertension. After a 3-week placebo run-in phase, 24 subjects were randomized into a 4-period double-blind crossover study by use of an orthogonal latin square design. Treatment periods were of 6 weeks' duration with titration to a higher dose after 4 weeks in those not reaching goal blood pressure (BP). Each active treatment was followed by a 3-week placebo washout. Casual clinic and 24-hour ambulatory BP (Accutracker II) were measured at the end of each treatment phase. Routine biochemistry was also performed after the placebo run-in, at the end of each active treatment phase, and after the placebo run-out. Of the 24 subjects entered (mean age 72.3 years, 38% men) 20 completed the whole study. Mean +/- standard deviation of supine clinic and daytime ambulatory BP on entry were 181/79 +/- 21/9 mm Hg and 165/82 +/- 23/15 mm Hg, respectively. All drugs reduced mean casual and ambulatory BP significantly relative to placebo but only hydrochlorothiazide and enalapril produced a consistent hypotensive effect throughout the entire 24-hour period. Isradipine and enalapril exhibited a relatively greater effect on reducing systolic BP than either hydrochlorothiazide or atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Common Functional Genetic Variants in Catecholamine Storage Vesicle Protein Promoter Motifs Interact to Trigger Systemic Hypertension

    PubMed Central

    Zhang, Kuixing; Rao, Fangwen; Wang, Lei; Rana, Brinda K.; Ghosh, Sajalendu; Mahata, Manjula; Salem, Rany M.; Rodriguez-Flores, Juan L.; Fung, Maple M.; Waalen, Jill; Tayo, Bamidele; Taupenot, Laurent; Mahata, Sushil K.; O'Connor, Daniel T.

    2010-01-01

    Objectives The purpose of this study was to explore transcriptional mechanisms whereby genetic variation in the CHGB promoter influence BP and hypertension. Background Hypertension is a complex trait in which deranged autonomic control of the circulation may be an etiological culprit. Chromogranin B (CHGB) is a major soluble protein in the core of catecholamine storage vesicles, playing a necessary (catalytic) role in the biogenesis of secretory vesicles. Previously we found that genetic variation at CHGB influenced plasma CHGB expression as well as autonomic function, and that BP association was maximal towards the 5′ end of the gene. Methods After polymorphism discovery, we functionally characterized the 2 common variants in the proximal CHGB promoter, A-296C and A-261T, which lay within the same haplotype block in black and white populations. CHGB promoter activity was studied by haplotype/luciferase reporter transfection. Transcriptional mechanisms were probed by EMSA and ChIP. Results The A-296C variant disrupted a c-FOS motif, and exhibited differential mobility shifting to chromaffin cell nuclear proteins during EMSA, differential binding of endogenous c-FOS on ChIP, and differential transcriptional response to exogenous c-FOS. A-261T disrupted motifs for SRY and YY1, with similar consequences for gel mobility during EMSA, endogenous factor binding during ChIP, and transcriptional responses to the exogenous factors. 2-SNP haplotype analyses demonstrated a profound (p∼3×10-20) effect of CHGB promoter variation on BP in the European ancestry population, with a rank order of CT

  16. Development and Validation of a Clinical and Computerised Decision Support System for Management of Hypertension (DSS-HTN) at a Primary Health Care (PHC) Setting

    PubMed Central

    Anchala, Raghupathy; Di Angelantonio, Emanuele; Prabhakaran, Dorairaj; Franco, Oscar H.

    2013-01-01

    Background Hypertension remains the top global cause of disease burden. Decision support systems (DSS) could provide an adequate and cost-effective means to improve the management of hypertension at a primary health care (PHC) level in a developing country, nevertheless evidence on this regard is rather limited. Methods Development of DSS software was based on an algorithmic approach for (a) evaluation of a hypertensive patient, (b) risk stratification (c) drug management and (d) lifestyle interventions, based on Indian guidelines for hypertension II (2007). The beta testing of DSS software involved a feedback from the end users of the system on the contents of the user interface. Software validation and piloting was done in field, wherein the virtual recommendations and advice given by the DSS were compared with two independent experts (government doctors from the non-participating PHC centers). Results The overall percent agreement between the DSS and independent experts among 60 hypertensives on drug management was 85% (95% CI: 83.61 - 85.25). The kappa statistic for overall agreement for drug management was 0.659 (95% CI: 0.457 - 0.862) indicating a substantial degree of agreement beyond chance at an alpha fixed at 0.05 with 80% power. Receiver operator curve (ROC) showed a good accuracy for the DSS, wherein, the area under curve (AUC) was 0.848 (95% CI: 0.741 - 0.948). Sensitivity and specificity of the DSS were 83.33 and 85.71% respectively when compared with independent experts. Conclusion A point of care, pilot tested and validated DSS for management of hypertension has been developed in a resource constrained low and middle income setting and could contribute to improved management of hypertension at a primary health care level. PMID:24223984

  17. Paradoxical hypertension with cardiac tamponade.

    PubMed

    Argulian, Edgar; Herzog, Eyal; Halpern, Dan G; Messerli, Franz H

    2012-10-01

    Subacute (medical) tamponade develops over a period of days or even weeks. Previous studies have shown that subacute tamponade is uncommonly associated with hypotension. On the contrary, many of those patients are indeed hypertensive at initial presentation. We sought to determine the prevalence and predictors of hypertensive cardiac tamponade and hemodynamic response to pericardial effusion drainage. We conducted a retrospective study of patients who underwent pericardial effusion drainage for subacute pericardial tamponade. Diagnosis of pericardial tamponade was established by the treating physician based on clinical data and supportive echocardiographic findings. Patients were defined as hypertensive if initial systolic blood pressure (BP) was ≥140 mm Hg. Thirty patients with subacute tamponade who underwent pericardial effusion drainage were included in the analysis. Eight patients (27%) were hypertensive with a mean systolic BP of 167 compared to 116 mm Hg in 22 nonhypertensive patients. Hypertensive patients with tamponade were more likely to have advanced renal disease (63% vs 14%, p <0.05) and pre-existing hypertension (88% vs 46, p <0.05) and less likely to have systemic malignancy (0 vs 41%, p <0.05). Systolic BP decreased significantly in patients with hypertensive tamponade after pericardial effusion drainage. Those results are consistent with previous studies with an estimated prevalence of hypertensive tamponade from 27% to 43%. In conclusion, a hypertensive response was observed in approximately 1/3 of patients with subacute pericardial tamponade. Relief of cardiac tamponade commonly resulted in a decrease in BP.

  18. [Hypertension and osteoporosis].

    PubMed

    Nakagami, Hironori; Morishita, Ryuichi

    2013-04-01

    The number of patients with high blood pressure and osteoporosis are increased year by year in our society. In hypertension patients, excess urinary calcium secretion induces secondary parathyroidism to increase serum calcium level by calcium release from bone, which may accelerate osteoporosis. In this aspect, there are several reports that anti-hypertensive drugs, especially thiazides, increase bone mineral density and decrease the incidence of bone fracture. In addition, we demonstrated that renin-angiotensin system can be involved in the process of osteoporosis. Angiotensin II significantly induced the expression of RANKL (receptor activator of NF-κB ligand) in osteoblasts, leading to the activation of osteoclasts, while these effects were completely blocked by an Ang II type 1 receptor blockade. Recently, it has been reported that angiotensin receptor blockade clinically decreased the incidence of bone fracture. Renin-angiotensin system might be common molecule to regulate both hypertension and osteoporosis.

  19. [Obesity and hypertension].

    PubMed

    Simonyi, Gábor; Kollár, Réka

    2013-11-03

    The frequency of hypertension and obesity is gradually growing in Hungary. At present 68.5% of men and 78% of women are obese. Hypertension and obesity are the most important risk factors of morbidity and mortality from cardiovascular disease. The relationship between increased sympathetic activity and hypertension is well known. Waist circumference and body fat mass correlate significantly with sympathetic activity, in which hyperlipidemia plays also a role. The increased activity of renin-angiotensin-aldosterone system via its vascular and renal effects also contributes to an increase of blood pressure. Increased sympathetic activity with decreasing vagal tone accompanying the imbalance of the autonomous nervous system is independent and significant risk factor of cardiovascular events including sudden cardiac death.

  20. [Functional, involutional and pathological oral changes with age. 6. Systemic disease].

    PubMed

    Castellanos, J L; Díaz Guzman, L

    1990-01-01

    The present study was realized to determine the frequency variety and concentration of old and new health disease in patients attending a school of Dentistry, classification to an age variable. This paper ends a series of articles about estomatological changes associated to an aging process. The main findings indicate that when patients grow older an increment in variety and number of pathological personal background. The results suggest a very well defined difference in the prevalence and concentration among subjects over and under 50 years. The risk factor was 1:1 in patients older than that. The importance of considering the Clinical history in patients as a determining factor in the global dental evaluation, for the decision. making in treatment planning.

  1. Storage and retrieval of SNOP-coded pathologic diagnoses using offsite computing and optical character recognizing systems.

    PubMed

    Cechner, R L; Carter, J R

    1976-05-01

    A computerized cross-reference system for retrieving autopsy and surgical pathology cases on the basis of case number or diagnosis has been implemented. The system achieves economy and flexibility by using offsite computer service bureaus for job production, eliminating the need for expensive onsite equipment. Coded diagnoses may be typed using the OCR (Optical Character Recognition) font simultaneously with or separately from the clinical documentation. The flexibility of new OCR equipment permits production of machine-readable code sheets with an ordinary pencil and completely eliminates the need for typing. The system produces year-to-date books that list all diagnoses, on an accumulating basis, in alphabetic order by SNOP* topology, morphology, etiology and function, and will be compatible with SNOMed. Because all data are stored on magnetic tape, they may be manipulated and retrieved as desired through user programming. The initial setup cost was dollar 1,000 for programming and testing, and production runs and all report printing cost about dollar 1,000 per year (autopsies and surgical pathology cases), which is about 1.1 cents per diagnosis.

  2. A new wide field-of-view confocal imaging system and its applications in drug discovery and pathology

    NASA Astrophysics Data System (ADS)

    Li, Gang; Damaskinos, Savvas; Dixon, Arthur E.; Lee, Lucy E. J.

    2005-11-01

    Conventional widefield light microscopy and confocal scanning microscopy have been indispensable for pathology and drug discovery research. Clinical specimens from diseased tissues are examined, new drug candidates are tested on drug targets, and the morphological and molecular biological changes of cells and tissues are observed. High throughput screening of drug candidates requires highly efficient screening instruments. A standard biomedical slide is 1 by 3 inches (25.4 by 76.2 mm) in size. A typical tissue specimen is 10 mm in diameter. To form a high resolution image of the entire specimen, a conventional widefield light microscope must acquire a large number of small images of the specimen, and then tile them together, which is tedious, inefficient and error-prone. A patented new wide field-of-view confocal scanning laser imaging system has been developed for tissue imaging, which is capable of imaging an entire microscope slide without tiling. It is capable of operating in brightfield, reflection and epi-fluorescence imaging modes. Three (red, green and blue (RGB)) lasers are used to produce brightfield and reflection images, and to excite various fluorophores. This new confocal system makes examination of large biomedical specimens more efficient, and makes fluorescence examination of large specimens possible for the first time without tiling. Description of the new confocal technology and applications of the imaging system in pathology and drug discovery research, for example, imaging large tissue specimens, tissue microarrays, and zebrafish sections, are reported in this paper.

  3. The renin-angiotensin system. Normal physiology and changes in older hypertensives.

    PubMed

    Hall, J E; Coleman, T G; Guyton, A C

    1989-08-01

    The long-term effects of angiotensin (ANGII) on arterial pressure regulation appear to be closely linked to volume homeostasis, via the renal-pressure natriuresis mechanism, both in normal humans and in older hypertensives. In response to disturbances such as increased sodium intake, suppression of ANGII and aldosterone formation greatly amplifies the effectiveness of the pressure natriuresis mechanism, thereby preventing large increases in body fluid volumes and minimizing the rise in blood pressure needed to maintain sodium balance. When ANGII levels are inappropriately elevated, the antinatriuretic effects of ANGII cause increased arterial pressure, which then serves to maintain sodium and water balance via the pressure natriuresis mechanism. The primary intrarenal and extrarenal mechanisms by which ANGII controls renal excretion and arterial pressure include: (1) a direct effect of ANGII on tubular sodium transport; (2) a preferential constrictor action of ANGII on efferent arterioles, which increases sodium reabsorption by altering peritubular capillary physical forces (efferent arteriolar constriction also prevents excessive decreases in glomerular filtration rate when renal perfusion is compromised, such as in renal artery stenosis); and (3) extrarenal effects of ANGII, including stimulation of aldosterone secretion. Current evidence suggests that the direct effects of ANGII on the kidney are quantitatively more important than indirect effects mediated by aldosterone. In older hypertensives, plasma renin activity and aldosterone concentration are often suppressed, perhaps due to loss of functional nephrons and increased sodium chloride delivery to the macula densa of the remaining nephrons.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Effects of Emotional Stimuli on Cardiovascular Responses in Patients with Essential Hypertension Based on Brain/Behavioral Systems

    PubMed Central

    Taban Sadeghi, Mohammadreza; Namdar, Hossein; Vahedi, Shahram; Aslanabadi, Naser; Ezzati, Davoud; Sadeghi, Babak

    2013-01-01

    Introduction: Effects of emotional stimuli on hemodynamics in patients with essential hypertension based on brain/behavioral systems have not been studied broadly. Methods: Eighty five essential hypertensive male patients who had completed Carver-White BIS/BAS scale were enrolled to the study. Later, 25 BIS and 25 BAS patients were selected and their blood pressure and heart rate were recorded prior to stimuli induction. Participants were then exposed to stressor pictures. After that, 15 minutes of relaxation and cognitive tasks were performed. Finally, the participants were exposed to pleasant pictures. The blood pressure and heart rate were recorded after presenting of 2 stimuli. Results: Our study showed that BIS patients achieved higher scores in diastolic blood pressure and heart rate in comparison with BAS patients after presenting stressful stimuli. Also, BAS patients achieved lower scores in systolic blood pressure and heart rate in comparison with BIS patients after presenting pleasant stimuli. Conclusion: In summary, BIS patients experience negative emotions more than BAS patients. Therefore, the role of induced mood states is important in relation to physical health. PMID:24404349

  5. Comparative Analysis of Renin-Angiotensin System (RAS)-Related Gene Expression Between Hypertensive and Normotensive Rats

    PubMed Central

    Williamson, Chad R.; Khurana, Sandhya; Nguyen, Phong; Byrne, Collin J.; Tai, T.C.

    2017-01-01

    Background The renal renin-angiotensin system (RAS) is physiologically important for blood pressure regulation. Altered regulation of RAS-related genes has been observed in an animal model of hypertension (spontaneously hypertensive rats – SHRs). The current understanding of certain RAS-related gene expression differences between Wistar-Kyoto rats (WKYs) and SHRs is either limited or has not been compared. The purpose of this study was to compare the regulation of key RAS-related genes in the kidneys of adult WKYs and SHRs. Material/Methods Coronal sections were dissected through the hilus of kidneys from 16-week-old male WKYs and SHRs. RT-PCR analysis was performed for Ace, Ace2, Agt, Agtr1a, Agtr1b, Agtr2, Atp6ap2 (PRR), Mas1, Ren, Rnls, and Slc12a3 (NCC). Results Increased mRNA expression was observed for Ace, Ace2, Agt, Agtr1a, Agtr1b, and Atp6ap2 in SHRs compared to WKYs. Mas1, Ren, Slc12a3, and Rnls showed no difference in expression between animal types. Conclusions This study shows that the upregulation of several key RAS-related genes in the kidney may account for the increased blood pressure of adult SHRs. PMID:28138124

  6. Development of a mobile device optimized cross platform-compatible oral pathology and radiology spaced repetition system for dental education.

    PubMed

    Al-Rawi, Wisam; Easterling, Lauren; Edwards, Paul C

    2015-04-01

    Combining active recall testing with spaced repetition increases memory retention. The aim of this study was to evaluate and compare students' perception and utilization of an electronic spaced repetition oral pathology-radiology system in dental hygiene education and predoctoral dental education. The study employed an open-source suite of applications to create electronic "flashcards" that can be individually adjusted for frequency of repetition, depending on a user's assessment of difficulty. Accessible across multiple platforms (iOS, Android, Linux, OSX, Windows) as well as via any web-based browser, this framework was used to develop an oral radiology-oral pathology database of case-based questions. This system was introduced in two courses: sophomore oral pathology for dental students and sophomore radiology for dental hygiene students. Students were provided free software and/or mobile tablet devices as well as a database of 300 electronic question cards. Study participants were surveyed on frequency and extent of use. Perception-based surveys were used to evaluate their attitudes towards this technology. Of the eligible students, 12 of 22 (54.5%) dental hygiene and 49 of 107 (45.8%) dental students responded to the surveys. Adoption rates and student feedback were compared between the two groups. Among the respondents, acceptance of this technology with respect to educational usefulness was similar for the dental and dental hygiene students (median=5 on a five-point scale; dental hygiene interquartile range (IQR)=0; dental IQR=1). Only a minority of the survey respondents (25% dental, 33% dental hygiene) took advantage of one of the main benefits of this technology: automated spaced repetition.

  7. Cloud-Based Smart Health Monitoring System for Automatic Cardiovascular and Fall Risk Assessment in Hypertensive Patients.

    PubMed

    Melillo, P; Orrico, A; Scala, P; Crispino, F; Pecchia, L

    2015-10-01

    The aim of this paper is to describe the design and the preliminary validation of a platform developed to collect and automatically analyze biomedical signals for risk assessment of vascular events and falls in hypertensive patients. This m-health platform, based on cloud computing, was designed to be flexible, extensible, and transparent, and to provide proactive remote monitoring via data-mining functionalities. A retrospective study was conducted to train and test the platform. The developed system was able to predict a future vascular event within the next 12 months with an accuracy rate of 84 % and to identify fallers with an accuracy rate of 72 %. In an ongoing prospective trial, almost all the recruited patients accepted favorably the system with a limited rate of inadherences causing data losses (<20 %). The developed platform supported clinical decision by processing tele-monitored data and providing quick and accurate risk assessment of vascular events and falls.

  8. Inguinoscrotal pathology

    PubMed Central

    Guerra, Luis; Leonard, Michael

    2017-01-01

    Infants, children, and adolescents with inguinoscrotal pathology comprise a significant proportion of emergency department and outpatient visits. Visits to the emergency department primarily comprise individuals presenting with scrotal pain due to testicular torsion or torsion of the testicular appendages. At such time, immediate urological consultation is sought. Outpatient visits comprise those individuals with undescended testes, hydroceles, and varicoceles. Rare, but important problems, such as pediatric testicular tumours, may also present in the office setting. Many of these outpatient visits are to primary care physicians, who should have an appreciation of the timing and need for referral. The purpose of this review is to familiarize the general urologist and primary care physician with these varied pathologies and give insight into their assessment and management. Some of these same conditions are seen in adult patients, but there are some significant differences in their management in the pediatric group. In addition, the utility of imaging studies, such as ultrasound, are discussed within each pathological entity. It is hoped that this overview will assist our general urology and primary care colleagues in patient management for diverse inguinoscrotal pathologies. PMID:28265317

  9. Renal pathology in reptiles.

    PubMed

    Zwart, Peernel

    2006-01-01

    The class of Reptilia varies widely. Both the gross morphology and microscopic anatomy of the kidneys are specific for each species. In each species of reptile, the physiology of the renal system has adapted to the specific conditions of life, including, among other factors, the type of food, environmental temperature, and the availability of water. The pathology of the kidneys in reptiles has been poorly studied, but in recent years a number of investigators have specifically studied reptilian renal pathology.

  10. Gαi2-protein-mediated signal transduction: central nervous system molecular mechanism countering the development of sodium-dependent hypertension.

    PubMed

    Wainford, Richard D; Carmichael, Casey Y; Pascale, Crissey L; Kuwabara, Jill T

    2015-01-01

    Excess dietary salt intake is an established cause of hypertension. At present, our understanding of the neuropathophysiology of salt-sensitive hypertension is limited by a lack of identification of the central nervous system mechanisms that modulate sympathetic outflow and blood pressure in response to dietary salt intake. We hypothesized that impairment of brain Gαi2-protein-gated signal transduction pathways would result in increased sympathetically mediated renal sodium retention, thus promoting the development of salt-sensitive hypertension. To test this hypothesis, naive or renal denervated Dahl salt-resistant and Dahl salt-sensitive (DSS) rats were assigned to receive a continuous intracerebroventricular control scrambled or a targeted Gαi2-oligodeoxynucleotide infusion, and naive Brown Norway and 8-congenic DSS rats were fed a 21-day normal or high-salt diet. High salt intake did not alter blood pressure, suppressed plasma norepinephrine, and evoked a site-specific increase in hypothalamic paraventricular nucleus Gαi2-protein levels in naive Brown Norway, Dahl salt-resistant, and scrambled oligodeoxynucleotide-infused Dahl salt-resistant but not DSS rats. In Dahl salt-resistant rats, Gαi2 downregulation evoked rapid renal nerve-dependent hypertension, sodium retention, and sympathoexcitation. In DSS rats, Gαi2 downregulation exacerbated salt-sensitive hypertension via a renal nerve-dependent mechanism. Congenic-8 DSS rats exhibited sodium-evoked paraventricular nucleus-specific Gαi2-protein upregulation and attenuated hypertension, sodium retention, and global sympathoexcitation compared with DSS rats. These data demonstrate that paraventricular nucleus Gαi2-protein-gated pathways represent a conserved central molecular pathway mediating sympathoinhibitory renal nerve-dependent responses evoked to maintain sodium homeostasis and a salt-resistant phenotype. Impairment of this mechanism contributes to the development of salt-sensitive hypertension.

  11. Pathological involvement of the motor neuron system and hippocampal formation in motor neuron disease-inclusion dementia.

    PubMed

    Toyoshima, Yasuko; Piao, Yue-Shan; Tan, Chun-Feng; Morita, Masahiro; Tanaka, Masaharu; Oyanagi, Kiyomitsu; Okamoto, Koichi; Takahashi, Hitoshi

    2003-07-01

    We report two patients with motor neuron disease-inclusion dementia, with special reference to the pathology of the motor neuron system and hippocampal formation. The ages of the patients at death were 55 and 62 years, and the disease durations were 8 and 3 years, respectively. The two patients exhibited progressive frontotemporal dementia in the absence of motor neuron signs. At autopsy, both cases exhibited frontotemporal lobar atrophy with ubiquitin-positive, and tau- and alpha-synuclein-negative neuronal inclusions. As expected from the clinical signs, in both cases, the upper and lower motor neuron systems were well preserved: no Bunina bodies or ubiquitinated inclusions were detected in the motor neurons. However, of great importance was that when visualized immunohistochemically, the Golgi apparatus and trans-Golgi network often exhibited fragmentation in the lower motor neurons (the spinal anterior horn cells). In one of the cases, a decrease in the amount of Golgi apparatus was also a frequent feature in the upper motor neurons (Betz cells in the motor cortex). Moreover, in both cases, circumscribed degeneration affecting the CA1-subiculum border zone was evident in the hippocampal formation. These findings further strengthen the idea that, pathologically, motor neuron disease-inclusion dementia is a rare phenotype of amyotrophic lateral sclerosis.

  12. No Hypertensive Disorder of Pregnancy; No Preeclampsia-eclampsia; No Gestational Hypertension; No Hellp Syndrome. Vascular Disorder of Pregnancy Speaks for All.

    PubMed

    Berhan, Yifru

    2016-03-01

    Hypertensive disorders complicate 5%-10% of pregnancies with increasing incidence mainly due to upward trends in obesity globally. In the last century, several terminologies have been introduced to describe the spectrum of this disease. The current and widely used classification of hypertensive pregnancy disorders was introduced in 1972 and in 1982, but has not been free of controversy and confusion. Unlike other diseases, the existing terminology combines signs and symptoms, but does not describe the underlying pathology of the disease itself. In this commentary, a detailed account is given to vascular disorder of pregnancy (VDP) as an inclusive terminology taking into account the underlying pathology of the disease on affected organs and systems. A simple and uniform classification scheme for VDP is proposed.

  13. New drugs in hypertension.

    PubMed Central

    Myers, M. G.

    1977-01-01

    Clonidine, propranolol, bethanidine and debrisoquine effectively decrease blood pressure by suppressing renin secretion or interfering with function of the sympathetic nervous system. In man these compounds exert an antihypertensive effect within several hours or days and their duration of action is sufficient to permit administration twice or thrice daily. Clonidine and propranolol are especially useful if sexual dysfunction or postural hypotension is undesirable. Although bethanidine and debrisoquine may produce these adverse effects, they are beneficial in severe hypertension and produce fewer side effects than guanethidine. Clonidine frequently causes sedation, and rebound hypertension may occur with sudden cessation of therapy. Injudicious use of propranolol may provoke heart failure or asthma in susceptible individuals. The combination of a thiazide diuretic with propranolol and one of hydralazine, bethanidine and debrisoquine may be used to treat severe or complicated hypertension. PMID:343894

  14. An efficient and reproducible method for quantifying macrophages in different experimental models of central nervous system pathology

    PubMed Central

    Donnelly, Dustin J.; Gensel, John C.; Ankeny, Daniel P.; van Rooijen, Nico; Popovich, Phillip G.

    2009-01-01

    Historically, microglia/macrophages are quantified in the pathological central nervous system (CNS) by counting cell profiles then expressing the data as cells/mm2. However, because it is difficult to visualize individual cells in dense clusters and in most cases it is unimportant to know the absolute number of macrophages within lesioned tissue, alternative methods may be more efficient for quantifying the magnitude of the macrophage response in the context of different experimental variables (e.g., therapeutic intervention or time post-injury/infection). The present study provides the first in-depth comparison of different techniques commonly used to quantify microglial/macrophage reactions in the pathological spinal cord. Individuals from the same and different laboratories applied techniques of digital image analysis (DIA), standard cell profile counting and a computer-assisted cell counting method with unbiased sampling to quantify macrophages in focal inflammatory lesions, disseminated lesions caused by autoimmune inflammation or at sites of spinal trauma. Our goal was to find a simple, rapid and sensitive method with minimal variability between trials and users. DIA was consistently the least variable and most time-efficient method for assessing the magnitude of macrophage responses across lesions and between users. When used to evaluate the efficacy of an anti-inflammatory treatment, DIA was 5–35x faster than cell counting and was sensitive enough to detect group differences while eliminating inter-user variability. Since lesions are clearly defined and single profiles of microglia/macrophages are difficult to discern in most pathological specimens of brain or spinal cord, DIA offers significant advantages over other techniques for quantifying activated macrophages. PMID:19393692

  15. Association of Renal Resistive Index, Renal Pulsatility Index, Systemic Hypertension, and Albuminuria with Survival in Dogs with Pituitary-Dependent Hyperadrenocorticism

    PubMed Central

    Chen, Hung-Yin; Lien, Yu-Hsin

    2016-01-01

    An increased renal resistive index (RI) and albuminuria are markers of target organ damage secondary to systemic hypertension. This study evaluated associations between systemic blood pressure (SBP), renal RI, pulsatility index (PI), and albuminuria in dogs with pituitary-dependent hyperadrenocorticism (PDH). Predictors of overall mortality were investigated. Twenty client-owned dogs with PDH and 20 clinically healthy client-owned dogs as matched controls were included. Incidence rates of systemic hypertension (SBP ≥ 160 mmHg), albuminuria, and increased renal RI (≥ 0.70) and PI (≥ 1.45) in the control group were 5%, 0%, 5%, and 0%, respectively, compared to 35%, 40%, 50%, and 35%, respectively, in the PDH group (P = 0.001, P < 0.001, P < 0.001, and P = 0.001, resp.). No association between systemic hypertension, renal RI, renal PI, and albuminuria was observed. PDH was the only predictor of albuminuria and increased renal RI. Survival was not affected by increased renal PI, systemic hypertension, or albuminuria. Increased renal RI (≥ 0.70) was the only predictor of overall mortality in dogs with PDH. PMID:27340403

  16. Coagulation and Fibrinolytic System Protein Profiles in Women with Normal Pregnancies and Pregnancies Complicated by Hypertension

    PubMed Central

    Hale, Sarah A.; Sobel, Burton; Benvenuto, Anna; Schonberg, Adrienne; Badger, Gary J.; Bernstein, Ira M.

    2012-01-01

    Objective The current study longitudinally evaluated concentrations of fibrinogen (Fib), D-Dimer, plasminogen activator type-1 (PAI-1) and tissue type plasminogen activator (T-Pa) before pregnancy and in the first and third trimesters of pregnancy with a focus on the pregnancy transition. Study design Twenty healthy, nonsmoking, nulliparous women, aged 29.8 ± 3.0 years, BMI 23.3 ± 3.2 kg/m2 were studied during menstrual cycle day 8 ± 4 and again in early (11 – 15 wks) and late (31 – 34 wks) pregnancy. Seventeen women had singleton conceptions and delivered at term with uncomplicated pregnancies (CTL) and three women developed complicated hypertension (CH) during pregnancy after the third trimester (late pregnancy) evaluation. Data are means ± SEM, Significance was based on p < 0.05. Results Fib was the only protein evaluated that increased in early pregnancy relative to the prepregnancy assessment. D-dimer, PAI-1 and T-Pa increased in the third trimester compared with prepregnant and early pregnant values (p < .001). T-PA was significantly higher during late pregnancy in CH subjects compared with CTL (8.1 ± 0.7 ng/ml vs. 5.0 ± 0.2 ng/ml, p = .02). There were no other differences between groups. Conclusions Increases in fibrinogen are evident in early pregnancy whereas fibrinolysis, perhaps in response to the procoagulant environment of pregnancy, is increased during late pregnancy. Before development of clinically overt hypertension, T-Pa is increased without concomitant changes in other proteins assessed. This is consistent with altered endothelial function with preeclampsia that may contribute to, or reflect, the vasculopathy accompanying this disorder. PMID:22712057

  17. Coagulation and Fibrinolytic System Protein Profiles in Women with Normal Pregnancies and Pregnancies Complicated by Hypertension.

    PubMed

    Hale, Sarah A; Sobel, Burton; Benvenuto, Anna; Schonberg, Adrienne; Badger, Gary J; Bernstein, Ira M

    2012-04-01

    OBJECTIVE: The current study longitudinally evaluated concentrations of fibrinogen (Fib), D-Dimer, plasminogen activator type-1 (PAI-1) and tissue type plasminogen activator (T-Pa) before pregnancy and in the first and third trimesters of pregnancy with a focus on the pregnancy transition. STUDY DESIGN: Twenty healthy, nonsmoking, nulliparous women, aged 29.8 ± 3.0 years, BMI 23.3 ± 3.2 kg/m(2) were studied during menstrual cycle day 8 ± 4 and again in early (11 - 15 wks) and late (31 - 34 wks) pregnancy. Seventeen women had singleton conceptions and delivered at term with uncomplicated pregnancies (CTL) and three women developed complicated hypertension (CH) during pregnancy after the third trimester (late pregnancy) evaluation. Data are means ± SEM, Significance was based on p < 0.05. RESULTS: Fib was the only protein evaluated that increased in early pregnancy relative to the prepregnancy assessment. D-dimer, PAI-1 and T-Pa increased in the third trimester compared with prepregnant and early pregnant values (p < .001). T-PA was significantly higher during late pregnancy in CH subjects compared with CTL (8.1 ± 0.7 ng/ml vs. 5.0 ± 0.2 ng/ml, p = .02). There were no other differences between groups. CONCLUSIONS: Increases in fibrinogen are evident in early pregnancy whereas fibrinolysis, perhaps in response to the procoagulant environment of pregnancy, is increased during late pregnancy. Before development of clinically overt hypertension, T-Pa is increased without concomitant changes in other proteins assessed. This is consistent with altered endothelial function with preeclampsia that may contribute to, or reflect, the vasculopathy accompanying this disorder.

  18. Indapamide is superior to thiazide in the preservation of renal function in patients with renal insufficiency and systemic hypertension.

    PubMed

    Madkour, H; Gadallah, M; Riveline, B; Plante, G E; Massry, S G

    1996-02-22

    The long-term effects of indapamide or hydrochlorothiazide on blood presssure and renal function were examined in patents with impaired renal function and moderate hypertension. Both drugs controlled hypertension and blood pressure remained normal during the 2 years of the study. Despite this comparable control of hypertension, indapamide therapy was associated with a 28.5 +/- 4.4% increase in creatinine clearance, whereas treatment with hydrochlorothiazide was associated with a 17.4 +/- 3.0% decrease in creatinine clearance. The results of the study indicate that indapamide is superior to hydrochlorothiazide in the treatment of patients with impaired renal function and moderate hypertension.

  19. The cellular and molecular pathology of the motor system in hereditary spastic paraparesis due to mutation of the spastin gene.

    PubMed

    Wharton, Stephen B; McDermott, Christopher J; Grierson, Andrew J; Wood, Jonathan D; Gelsthorpe, Catherine; Ince, Paul G; Shaw, Pamela J

    2003-11-01

    Hereditary spastic paraparesis (HSP) is a genetically heterogeneous disorder, the most common cause of which is mutation of the spastin gene. Recent evidence suggests a role for spastin in microtubule dynamics, but the distribution of the protein within the CNS is unknown. The core neuropathology of HSP is distal degeneration of the lateral corticospinal tract and of fasciculus gracilis, but there are few neuropathological studies of cases with a defined mutation. We aimed to determine the distribution of spastin expression in the human CNS and to investigate the cellular pathology of the motor system in HSP due to mutation of the spastin gene. Using an antibody to spastin, we have carried out immunohistochemistry on postmortem brain. We have demonstrated that spastin is a neuronal protein. It is widely expressed in the CNS so that the selectivity of the degeneration in HSP is not due to the normal cellular distribution of the protein. We have identified mutation of the spastin gene in 3 autopsy cases of HSP. Distal degeneration of long tracts in the spinal cord, consistent with a dying back axonopathy, was accompanied by a microglial reaction. The presence of novel hyaline inclusions in anterior horn cells and an alteration in immunostaining for cytoskeletal proteins and mitochondria indicates that long tract degeneration is accompanied by cytopathology in the motor system and may support a role for derangement of cytoskeletal function. All 3 cases also demonstrated evidence of tau pathology outside the motor system, suggesting that the neuropathology is not confined to the motor system in spastin-related HSP.

  20. The systemic vascular resistance response: a cardiovascular response modulating blood viscosity with implications for primary hypertension and certain anemias.

    PubMed

    Sloop, Gregory D; Weidman, Joseph J; St Cyr, John A

    2015-12-01

    Without an active regulatory feedback loop, increased blood viscosity could lead to a vicious cycle of ischemia, increased erythropoiesis, further increases of blood viscosity, decreased tissue perfusion with worsened ischemia, further increases in red cell mass, etc. We suggest that an increase in blood viscosity is detected by mechanoreceptors in the left ventricle which upregulate expression of cardiac natriuretic peptides and soluble erythropoietin receptor. This response normalizes systemic vascular resistance and blood viscosity at the cost of producing 'anemia of chronic disease or inflammation' or 'hemolytic anemia' both of which are better described as states of compensated hyperviscosity. Besides its role in disease, this response is also active in the physiologic adaptation to chronic exercise. Malfunction of this response may cause primary hypertension.

  1. Natural Regulatory T Cells Control Coronary Arteriolar Endothelial Dysfunction in Hypertensive Mice

    PubMed Central

    Matrougui, Khalid; Zakaria, Abd Elmageed; Kassan, Modar; Choi, Sookyoung; Nair, Devika; Gonzalez-Villalobos, Romer A.; Chentoufi, Aziz A.; Kadowitz, Philip; Belmadani, Souad; Partyka, Megan

    2011-01-01

    Coronary artery disease in patients with hypertension is increasing worldwide and leads to severe cardiovascular complications. The cellular and molecular mechanisms that underlie this pathologic condition are not well understood. Experimental and clinical research indicates that immune cells and inflammation play a central role in the pathogenesis of cardiovascular diseases. Recently, it has been reported that CD4+CD25+ regulatory T cells (Tregs) regulate heart fibrosis in hypertension. In this study, we determined the role of Tregs in coronary arteriolar endothelial dysfunction in angiotensin II–dependent hypertensive mice. Mice infused with angiotensin II had significantly increased blood pressure, as determined using telemetry, and apoptotic Treg numbers, as measured using flow cytometry. The mice displayed inflammation, assessed by macrophage activation/infiltration into coronary arterioles and the heart, and increased local tumor necrosis factor-α release, which participates in reduced coronary arteriolar endothelial-dependent relaxation in response to acetylcholine using an arteriograph. Hypertensive mice injected with Tregs isolated from control mice had significantly reduced macrophage activation and infiltration, reduced tumor necrosis factor-α release, and improved coronary arteriolar endothelium-dependent relaxation. Our novel data indicate that Tregs are important in the development of coronary arteriolar endothelial dysfunction in hypertension. These results suggest a new direction in the investigation of vascular disease in hypertension and could lead to a therapeutic strategy that involves immune system modulation using Tregs. PMID:21224080

  2. Developing an interactive mobile phone self-report system for self-management of hypertension. Part 2: content validity and usability.

    PubMed

    Bengtsson, Ulrika; Kjellgren, Karin; Höfer, Stefan; Taft, Charles; Ring, Lena

    2014-10-01

    Self-management support tools using technology may improve adherence to hypertension treatment. There is a need for user-friendly tools facilitating patients' understanding of the interconnections between blood pressure, wellbeing and lifestyle. This study aimed to examine comprehension, comprehensiveness and relevance of items, and further to evaluate the usability and reliability of an interactive hypertension-specific mobile phone self-report system. Areas important in supporting self-management and candidate items were derived from five focus group interviews with patients and healthcare professionals (n = 27), supplemented by a literature review. Items and response formats were drafted to meet specifications for mobile phone administration and were integrated into a mobile phone data-capture system. Content validity and usability were assessed iteratively in four rounds of cognitive interviews with patients (n = 21) and healthcare professionals (n = 4). Reliability was examined using a test-retest. Focus group analyses yielded six areas covered by 16 items. The cognitive interviews showed satisfactory item comprehension, relevance and coverage; however, one item was added. The mobile phone self-report system was reliable and perceived easy to use. The mobile phone self-report system appears efficiently to capture information relevant in patients' self-management of hypertension. Future studies need to evaluate the effectiveness of this tool in improving self-management of hypertension in clinical practice.

  3. Hypertensive emergencies. Etiology and management.

    PubMed

    Tuncel, Meryem; Ram, Venkata C S

    2003-01-01

    Although systemic hypertension is a common clinical disorder, hypertensive emergencies are unusual in clinical practice. Situations that qualify as hypertensive emergencies include accelerated or malignant hypertension, hypertensive encephalopathy, acute left ventricular failure, acute aortic dissection, pheochromocytoma crisis, interaction between tyramine-containing foods or drugs and monoamine oxidase inhibitors, eclampsia, drug-induced hypertension and possibly intracranial hemorrhage. It is important to recognize these conditions since immediate lowering of systemic blood pressure is indicated. The diagnosis of hypertensive emergencies depends on the clinical manifestations rather than on the absolute level of the blood pressure. Depending on the target organ that is affected, the manifestations of hypertensive emergencies can be quite expressive, yet variable. Thus, the physician has to make the clinical diagnosis urgently in order to render appropriate therapy. Several parenteral drugs can quickly and effectively lower the blood pressure in hypertensive emergencies. Intravenous fenoldopam, a selective dopamine (DA1) receptor agonist, offers the advantage of improving renal blood flow and causing natriuresis. Intravenous nicardipine may be beneficial in reserving tissue perfusion in patients with ischemic disorders. Whereas trimethaphan camsilate is the drug of choice for managing acute aortic dissection, hydralazine remains the drug of choice for the treatment of eclampsia. The alpha-adrenoceptor, phentolamine, is useful in patients with pheochromocytoma crisis. Enalaprilat is the only ACE inhibitor available for parenteral use and may be particularly useful in treating hypertensive emergencies in patients with heart failure. However, ACE inhibitors may cause a precipitous fall in blood pressure in patients who are hypovolemic. Although useful as adjunctive therapy in hypertensive crises, diuretics should be used with caution in these patients because prior

  4. Developmental Origins of Hypoxic Pulmonary Hypertension and Systemic Vascular Dysfunction: Evidence from Humans.

    PubMed

    Sartori, Claudio; Rimoldi, Stefano F; Duplain, Hervé; Stuber, Thomas; Garcin, Sophie; Rexhaj, Emrush; Allemann, Yves; Scherrer, Urs

    2016-01-01

    Epidemiological studies have shown an association between pathologic events occurring during fetal/perinatal life and the development of cardiovascular and metabolic disease in adulthood. These observations have led to the so-called developmental origin of adult disease hypothesis. More recently, evidence has been provided that the pulmonary circulation is also an important target for the developmental programming of adult disease in both experimental animal models and in humans. Here we will review this evidence and provide insight into mechanisms that may play a pathogenic role.

  5. Comparison of the AJCC, MSTS, and Modified Spanier Systems for Clinical and Pathologic Staging of Osteosarcoma.

    PubMed

    Cates, Justin M M

    2017-03-01

    The prognostic performance of the 2 most commonly used staging systems for skeletal sarcoma (the American Joint Committee on Cancer [AJCC] and Musculoskeletal Tumor Society [MSTS] systems) have never been compared analytically. Another staging system originally proposed by Spanier has not yet been validated. Given the recent release of the 8th edition of the AJCC Cancer Staging Manual, this study was designed to directly compare these anatomic staging systems in a series of 153 high-grade, intramedullary osteosarcomas. Kaplan-Meier curves were plotted and pairwise comparisons between each stage category were performed. Predictive accuracy of each staging system for determining 5-year disease-free survival was evaluated by comparing areas under receiver-operating characteristic curves generated from logistic regression analysis. Multiple concordance indices were calculated using bootstrapping methods (200 replications). ρk and R were estimated as measures of the variation in survival outcomes explained by the regression models. The AJCC, MSTS, and a modified version of the Spanier staging systems showed similar discriminatory abilities and no significant differences in the levels of contrast between different tumor stages across staging systems. Addition of T-category information from each staging system contributed significant prognostic information compared with a Cox proportional hazard regression model consisting only of the presence or absence of metastatic disease as a measure of disease extent. Concordance indices and predictive accuracy for 5-year disease-free survival were not significantly different among the different staging systems either. Similar findings were observed after accounting for other important prognostic variables. Additional studies are necessary to determine performance parameters of each staging system for other types of skeletal sarcoma. Prognostic performance of osteosarcoma staging systems would also be improved by incorporating

  6. Central nervous system tumors and related intracranial pathologies in radium dial workers

    SciTech Connect

    Stebbings, J.H.; Semkiw, W.

    1988-01-01

    Among the female radiation workers in the radium dial industry there is no overall excess of brain or central nervous system tumors. A significant excess did appear, however, in one of three major cohorts; the excess was not due to an excess of gliomas and cannot be ascribed with certainty to radium or external radiation. A significant proportional excess of tumors outside the brain was observed, and is consistent with irradiation of nervous system tissue from adjacent bone. Early deaths from brain abscess or mastoiditis, which are coded as diseases of the nervous system and sense organs, were observed. 12 refs., 11 tabs.

  7. Paroxysmal Hypertension Induced by an Insulinoma

    PubMed Central

    Harada, Ko; Hanayama, Yoshihisa; Hasegawa, Kou; Iwamuro, Masaya; Hagiya, Hideharu; Yoshida, Ryuichi; Otsuka, Fumio

    2017-01-01

    Insulinoma is a rare, usually benign, pancreatic neuroendocrine tumor. The clinical features of an insulinoma are fasting hypoglycemia with neuroglycopenic symptoms including confusion and unusual behavior, while hypertension is usually not associated with the disease. We herein report a patient with insulinoma who manifested paroxysmal hypertension and neuroglycopenic symptoms. The possible etiology of hypertension induced by an insulinoma is catecholamine release in response to hypoglycemia, which may cause acute hypertension through activation of the sympatho-adrenal system. This case implies that sustained hyperinsulinemia due to insulinoma can be functionally linked to the induction of paroxysmal hypertension. PMID:28202863

  8. Integrating Omics Technologies to Study Pulmonary Physiology and Pathology at the Systems Level

    PubMed Central

    Pathak, Ravi Ramesh; Davé, Vrushank

    2014-01-01

    Assimilation and integration of “omics” technologies, including genomics, epigenomics, proteomics, and metabolomics has readily altered the landscape of medical research in the last decade. The vast and complex nature of omics data can only be interpreted by linking molecular information at the organismic level, forming the foundation of systems biology. Research in pulmonary biology/medicine has necessitated integration of omics, network, systems and computational biology data to differentially diagnose, interpret, and prognosticate pulmonary diseases, facilitating improvement in therapy and treatment modalities. This review describes how to leverage this emerging technology in understanding pulmonary diseases at the systems level –called a “systomic” approach. Considering the operational wholeness of cellular and organ systems, diseased genome, proteome, and the metabolome needs to be conceptualized at the systems level to understand disease pathogenesis and progression. Currently available omics technology and resources require a certain degree of training and proficiency in addition to dedicated hardware and applications, making them relatively less user friendly for the pulmonary biologist and clinicians. Herein, we discuss the various strategies, computational tools and approaches required to study pulmonary diseases at the systems level for biomedical scientists and clinical researchers. PMID:24802001

  9. Effects of Antihypertensive Agents on Intestinal Contractility in the Spontaneously Hypertensive Rat: Angiotensin Receptor System Downregulation by Losartan.

    PubMed

    Patten, Glen Stephen; Abeywardena, Mahinda Yapa

    2017-02-01

    Hypertension is an inflammatory condition controlled by the renin angiotensin system and is linked to kidney disease, diabetes mellitus, and recently to dysfunction of the gut. The aim of this study was to determine what effect antihypertensive drug treatments may have on intestinal function of the spontaneously hypertensive rat (SHR). In the first experiment, SHRs were treated with enalapril, hydralazine, or with no treatment as a control. In the second experiment, SHRs were treated with losartan or with no treatment as a control. All drug treatments led to significant lowering of blood pressure after 16 weeks. At termination, intact tissue sections of the ileum and colon were induced to contract ex vivo by KCl; electrical stimulation; and agonists carbachol, angiotensin II, and prostaglandin E2 (PGE2). There were no differences in ileal or colonic contractility due to hydralazine or enalapril compared with no-treatment SHR control. However, for the ileum, the losartan group responded significantly more to KCl and carbachol while responding less to angiotensin II, with no difference for PGE2 compared with the no-treatment SHR control. In contrast, the colon responded similarly to KCl, electrical stimulation, and PGE2 but responded significantly less to angiotensin II. These results demonstrate that the ileum responds differently (with KCl and carbachol as agonists) to the colon after losartan treatment, whereas there is a reduced contractile response in both the ileum and colon following losartan treatment. Although there are few well documented major contraindications for angiotensin receptor blockers, the modulation of gut contractility by losartan may have wider implications for bowel health.

  10. Effects of Antihypertensive Agents on Intestinal Contractility in the Spontaneously Hypertensive Rat: Angiotensin Receptor System Downregulation by Losartan

    PubMed Central

    Abeywardena, Mahinda Yapa

    2017-01-01

    Hypertension is an inflammatory condition controlled by the renin angiotensin system and is linked to kidney disease, diabetes mellitus, and recently to dysfunction of the gut. The aim of this study was to determine what effect antihypertensive drug treatments may have on intestinal function of the spontaneously hypertensive rat (SHR). In the first experiment, SHRs were treated with enalapril, hydralazine, or with no treatment as a control. In the second experiment, SHRs were treated with losartan or with no treatment as a control. All drug treatments led to significant lowering of blood pressure after 16 weeks. At termination, intact tissue sections of the ileum and colon were induced to contract ex vivo by KCl; electrical stimulation; and agonists carbachol, angiotensin II, and prostaglandin E2 (PGE2). There were no differences in ileal or colonic contractility due to hydralazine or enalapril compared with no-treatment SHR control. However, for the ileum, the losartan group responded significantly more to KCl and carbachol while responding less to angiotensin II, with no difference for PGE2 compared with the no-treatment SHR control. In contrast, the colon responded similarly to KCl, electrical stimulation, and PGE2 but responded significantly less to angiotensin II. These results demonstrate that the ileum responds differently (with KCl and carbachol as agonists) to the colon after losartan treatment, whereas there is a reduced contractile response in both the ileum and colon following losartan treatment. Although there are few well documented major contraindications for angiotensin receptor blockers, the modulation of gut contractility by losartan may have wider implications for bowel health. PMID:27903643

  11. Systemic Arterial Hypertension in the Emergency Service: medication adherence and understanding of this disease

    PubMed Central

    Vancini-Campanharo, Cássia Regina; Oliveira, Gabriella Novelli; Andrade, Thaisa Fernanda Landim; Okuno, Meiry Fernanda Pinto; Lopes, Maria Carolina Barbosa Teixeira; Batista, Ruth Ester Assayag

    2015-01-01

    Objective: to identify the epidemiological profile of hypertension patients, how much they understand about the disease and the rate of adherence to treatment by these patients who had been hospitalized in the Brazilian emergency service. Methods: this cross-sectional study was performed with 116 patients, both male and female and aged over 18 years, who had been hospitalized in the Emergency Service of a University Hospital between March and June, 2013. The studied variables were data referring to socio-demographics, comorbidities, physical activity and knowledge regarding the disease. Patient adherence to treatment and the identification of the barriers were respectively evaluated using the Morisky test and the Brief Medication Questionnaire. Results: most of the patients involved in this study were women (55%), with white skin color (55%), married (51%), retirees or pensioners (64%) and with a low educational level (58%). Adherence to treatment, in most cases (55%), was moderate and the most prevalent adherence barrier was recall (67%). When medication was acquired at no cost to the patient, there was greater adherence to treatment. Conclusion: this study's patients had a moderate understanding about the disease. The high correlation between the number of drugs used and the recall barrier suggests that monotherapy is an option that can facilitate treatment adherence and reduce how often the patients forget to take their medication. PMID:26626007

  12. The adrenergic system in pulmonary arterial hypertension: bench to bedside (2013 Grover Conference series).

    PubMed

    Bristow, Michael R; Quaife, Robert A

    2015-09-01

    In heart failure with reduced left ventricular ejection fraction (HFrEF), adrenergic activation is a key compensatory mechanism that is a major contributor to progressive ventricular remodeling and worsening of heart failure. Targeting the increased adrenergic activation with β-adrenergic receptor blocking agents has led to the development of arguably the single most effective drug therapy for HFrEF. The pressure-overloaded and ultimately remodeled/failing right ventricle (RV) in pulmonary arterial hypertension (PAH) is also adrenergically activated, which raises the issue of whether an antiadrenergic strategy could be effectively employed in this setting. Anecdotal experience suggests that it will be challenging to administer an antiadrenergic treatment such as a β-blocking agent to patients with established moderate-severe PAH. However, the same types of data and commentary were prevalent early in the development of β-blockade for HFrEF treatment. In addition, in HFrEF approaches have been developed for delivering β-blocker therapy to patients who have extremely advanced heart failure, and these general principles could be applied to RV failure in PAH. This review examines the role played by adrenergic activation in the RV faced with PAH, contrasts PAH-RV remodeling with left ventricle remodeling in settings of sustained increases in afterload, and suggests a possible approach for safely delivering an antiadrenergic treatment to patients with RV dysfunction due to moderate-severe PAH.

  13. Comparison of four lung scoring systems for the assessment of the pathological outcomes derived from Actinobacillus pleuropneumoniae experimental infections

    PubMed Central

    2014-01-01

    Background In this study, four lung lesion scoring methods (Slaughterhouse Pleurisy Evaluation System [SPES], Consolidation Lung Lesion Score [LLS], Image analyses [IA] and Ratio of lung weight/body weight [LW/BW]) were compared for the assessment of the different pathological outcomes derived from an Actinobacillus pleuropneumoniae (App) experimental infection model. Moreover, pathological data was coupled with clinical (fever, inappetence and clinical score), production (average daily weigh gain [ADWG]) and diagnostic (PCR, ELISA and bacterial isolation) parameters within the four infection outcomes (peracute, acute, subclinically infected and non-infected). Results From the 61 inoculated animals, 9 were classified as peracute (presence of severe App-like clinical signs and lesions and sudden death or euthanasia shortly after inoculation), 31 as acutely affected (presence of App-like clinical signs and lesions and survival until the end of the experiment), 12 as subclinically infected (very mild or no clinical signs but App infection confirmed) and 9 as non-infected animals (lack of App-like clinical signs and lack of evidence of App infection). A significant correlation between all lung lesion scoring systems was found with the exception of SPES score versus LW/BW. SPES showed a statistically significant association with all clinical, production and diagnostic (with the exception of PCR detection of App in the tonsil) variables assessed. LLS and IA showed similar statistically significant associations as SPES, with the exception of seroconversion against App at necropsy. In contrast, LW/BW was statistically associated only with App isolation in lungs, presence of App-like lesions and ELISA OD values at necropsy. Conclusions In conclusion, SPES, LLS and IA are economic, fast and easy-to-perform lung scoring methods that, in combination with different clinical and diagnostic parameters, allow the characterization of different outcomes after App infection. PMID

  14. Complexity and forensic pathology.

    PubMed

    Jones, Richard Martin

    2015-12-01

    It has become increasingly apparent that nonlinearity and complexity are the norm in human physiological systems, the relevance of which is informing an enhanced understanding of basic pathological processes such as inflammation, the host response to severe trauma, and critical illness. This article will explore how an understanding of nonlinear systems and complexity might inform the study of the pathophysiology of deaths of medicolegal interest, and how 'complexity thinking' might usefully be incorporated into modern forensic medicine and forensic pathology research, education and practice.

  15. Wireless system for monitoring Intra-abdominal pressure in patient with severe abdominal pathology

    NASA Astrophysics Data System (ADS)

    Sokolovskiy, S. S.; Shtotskiy, Y. V.; Leljanov, A. D.

    2017-01-01

    The paper discusses an experimental design of the wireless system for monitoring intra-abdominal pressure (IAP) using Bluetooth Low Energy technology. The possibility of measuring IAP via the bladder using a wireless pressure sensor with a hydrophobic bacteria filter between the liquid transmitting medium and the sensor element is grounded.

  16. The National Outcomes Measurement System for Pediatric Speech-Language Pathology

    ERIC Educational Resources Information Center

    Mullen, Robert; Schooling, Tracy

    2010-01-01

    Purpose: The American Speech-Language-Hearing Association's (ASHA's) National Outcomes Measurement System (NOMS) was developed in the late 1990s. The primary purpose was to serve as a source of data for speech-language pathologists (SLPs) who found themselves called on to provide empirical evidence of the functional outcomes associated with their…

  17. [The issues of assessment of medical support of patients with pathology of blood circulation system].

    PubMed

    Maksimova, T M; Lushkina, N P; Ogryzko, Ye V

    2012-01-01

    The analysis of report forms No 12 "The information about number of diseases registered in patients residing in the area of medical institution supports" and No14 "The information about functioning of hospital" demonstrated that in conditions of ambulatory policlinic institutions there is no active monitoring of patients with diseases of blood circulation system. These diseases are the major causes of population mortality.

  18. Validation of a whole slide imaging system for primary diagnosis in surgical pathology: A community hospital experience

    PubMed Central

    Buck, Thomas P.; Dilorio, Rebecca; Havrilla, Lauren; O’Neill, Dennis G.

    2014-01-01

    Guidelines for validating whole slide imaging (WSI) for primary diagnosis in surgical pathology have been recommended by an expert panel commissioned by the College of American Pathologists. The implementation of such a system using these validation guidelines has not been reported from the community hospital setting. The objective was to implement a WSI system, validate each pathologist using the system and run the system in parallel with routine glass slide interpretation. Six pathologists re-reviewed approximately 300 previously diagnosed specimens each, divided equally between glass slides and digital images (scanned at ×20). Baseline intraobserver discordance rates (glass to glass) were calculated and compared to discordance rates between the original glass slide interpretation and the reviewed digital slide interpretation. A minimum of 3 months was used as the washout period. After validation, a subset of daily cases was diagnosed in parallel using traditional microscopy (TM) and WSI over an 8-month period. The TM and WSI discordance rates ranged from 3.3% to 13.3% and 2.1% to 10.1%, respectively. There was no statistically significant difference among the pathologists. The parallel study yielded similar rates of discordances. In our laboratory, after appropriate implementation and training, there was no difference between the WSI and TM methods. PMID:25535591

  19. Validation of a whole slide imaging system for primary diagnosis in surgical pathology: A community hospital experience.

    PubMed

    Buck, Thomas P; Dilorio, Rebecca; Havrilla, Lauren; O'Neill, Dennis G

    2014-01-01

    Guidelines for validating whole slide imaging (WSI) for primary diagnosis in surgical pathology have been recommended by an expert panel commissioned by the College of American Pathologists. The implementation of such a system using these validation guidelines has not been reported from the community hospital setting. The objective was to implement a WSI system, validate each pathologist using the system and run the system in parallel with routine glass slide interpretation. Six pathologists re-reviewed approximately 300 previously diagnosed specimens each, divided equally between glass slides and digital images (scanned at ×20). Baseline intraobserver discordance rates (glass to glass) were calculated and compared to discordance rates between the original glass slide interpretation and the reviewed digital slide interpretation. A minimum of 3 months was used as the washout period. After validation, a subset of daily cases was diagnosed in parallel using traditional microscopy (TM) and WSI over an 8-month period. The TM and WSI discordance rates ranged from 3.3% to 13.3% and 2.1% to 10.1%, respectively. There was no statistically significant difference among the pathologists. The parallel study yielded similar rates of discordances. In our laboratory, after appropriate implementation and training, there was no difference between the WSI and TM methods.

  20. Influence of renovascular hypertension on the distribution of vasoactive intestinal peptide in the stomach and heart of rats.

    PubMed

    Kasacka, Irena; Piotrowska, Żaneta; Janiuk, Izabela

    2015-11-01

    Arterial hypertension is associated with serious dysfunction of the cardiovascular system and digestive system. Given the relevant role of vasoactive intestinal peptide (VIP) in the regulation of digestion process, control of blood pressure and heart rate as well as cardio- and gastro-protective character of the peptide, it appeared worthwhile to undertake the research aimed at immunohistochemical identification and evaluation of VIP-positive structures in the pylorus and heart of hypertensive rats. Up to now, this issue has not been investigated. The experimental model of hypertension in rats according to Goldblatt (two-kidney one clip model of hypertension) was used in the study. The experimental material (pylorus and heart) was collected in the sixth week of the study. VIP-containing structures were evaluated using immunohistochemical and morphometric methods. The analysis of the results showed a significant increase in the number of immunoreactive VIP structures and in the intensity of immunohistochemical staining in the stomach and in the heart of hypertensive rats. Our findings indicate that VIP is an important regulator of cardiovascular and digestive system in physiological and pathological conditions. However, to better understand the exact role of VIP in hypertension further studies need to be carried out.

  1. Neurohistochemical and electron microscopic investigations of pathological and age-related changes in the cardiovascular system.

    PubMed

    Shvalev, V N; Guski, H; Fernández-Britto, J E; Sosunov, A A; Pavlovich, E R; Anikin AYu; Zhuchkova, N I; Kargina-Terentyeva, R A

    1992-01-01

    Neurohistochemical and electron microscopic investigations of the autonomic nervous system (ANS) of man and animals suggest that its ontogenesis can be divided into the premediatory, mediatory and postmediatory periods of development. The postmediatory period begins heterochronically in various ganglia of the ANS. A normal process of early cardiac desympathization usually occurs at the age of 35 to 60 years. Specific changes of preceding sudden cardiac death are elicited in different parts of the ANS and adrenal glands. This is accompanied by focal myocardial desympathization. Coronary vessels and conducting system which may influence myocardial hypersensitivity zones to catecholamines are involved in the process of destabilization of the cardiac function. Moreover, relationships are demonstrated which exist between the atherosclerotic lesions of the aortic wall and the status of its nerve plexuses.

  2. Novel Indications for Benzodiazepine Antagonist Flumazenil in GABA Mediated Pathological Conditions of the Central Nervous System.

    PubMed

    Hulse, Gary; Kelty, Erin; Hood, Sean; Norman, Amanda; Basso, Maria Rita; Reece, Albert Stuart

    2015-01-01

    This review paper discusses the central role of gamma-aminobutyric acid (GABA) in diverse physiological systems and functions and the therapeutic potential of the benzodiazepine antagonist flumazenil (Ro 15- 1788) for a wide range of disorders of the central nervous system (CNS). Our group and others have studied the potential of flumazenil as a treatment for benzodiazepine dependence. A small but growing body of research has indicated that flumazenil may also have clinical application in CNS disorders such as Parkinson's disease, idiopathic hypersomnia and amyotrophic lateral sclerosis. Despite this body of research the therapeutic potential of flumazenil remains poorly understood and largely unrealized. The purpose of this paper is not to provide an exhaustive review of all possible therapeutic applications for flumazenil but rather to stimulate research interest, and discussion of the exciting therapeutic potential of this drug for a range of chronic debilitating conditions.

  3. Pathologic, immunohistochemical, and electron microscopic findings in naturally occurring virulent systemic feline calicivirus infection in cats.

    PubMed

    Pesavento, P A; MacLachlan, N J; Dillard-Telm, L; Grant, C K; Hurley, K F

    2004-05-01

    Infection with feline calicivirus (FCV) is a common cause of upper respiratory and oral disease in cats. FCV infection is rarely fatal, however, virulent, systemic strains of FCV (VS-FCV) that cause alopecia, cutaneous ulcers, subcutaneous edema, and high mortality in affected cats have recently been described. Seven cats with natural VS-FCV infection all had subcutaneous edema and ulceration of the oral cavity, with variable ulceration of the pinnae, pawpads, nares, and skin. Other lesions that were present in some affected cats included bronchointerstitial pneumonia, and pancreatic, hepatic, and splenic necrosis. Viral antigen was present within endothelial and epithelial cells in affected tissues as determined by immunohistochemical staining with a monoclonal antibody to FCV. Mature intranuclear and intracytoplasmic virions in necrotic epithelial cells were identified by transmission electron microscopy. VS-FCV infection causes epithelial cell cytolysis and systemic vascular compromise in susceptible cats, leading to cutaneous ulceration, severe edema, and high mortality.

  4. Strengths and Limitations of Model Systems for the Study of Urinary Tract Infections and Related Pathologies

    PubMed Central

    Barber, Amelia E.; Norton, J. Paul; Wiles, Travis J.

    2016-01-01

    SUMMARY Urinary tract infections (UTIs) are some of the most common bacterial infections worldwide and are a source of substantial morbidity among otherwise healthy women. UTIs can be caused by a variety of microbes, but the predominant etiologic agent of these infections is uropathogenic Escherichia coli (UPEC). An especially troubling feature of UPEC-associated UTIs is their high rate of recurrence. This problem is compounded by the drastic increase in the global incidence of antibiotic-resistant UPEC strains over the past 15 years. The need for more-effective treatments for UTIs is driving research aimed at bettering our understanding of the virulence mechanisms and host-pathogen interactions that occur during the course of these infections. Surrogate models of human infection, including cell culture systems and the use of murine, porcine, avian, teleost (zebrafish), and nematode hosts, are being employed to define host and bacterial factors that modulate the pathogenesis of UTIs. These model systems are revealing how UPEC strains can avoid or overcome host defenses and acquire scarce nutrients while also providing insight into the virulence mechanisms used by UPEC within compromised individuals, such as catheterized patients. Here, we summarize our current understanding of UTI pathogenesis while also giving an overview of the model systems used to study the initiation, persistence, and recurrence of UTIs and life-threatening sequelae like urosepsis. Although we focus on UPEC, the experimental systems described here can also provide valuable insight into the disease processes associated with other bacterial pathogens both within the urinary tract and elsewhere within the host. PMID:26935136

  5. Requests for VIP Treatment in Pathology: Implications for Social Justice and Systems-Based Practice.

    PubMed

    Sheffield, Virginia; Smith, Lauren B

    2016-08-01

    Preferential treatment of patients whom we deem "very important" is a practice that is common in our health care system. The impact of this designation and the care that results is rarely studied or scrutinized. Although we assume that this type of treatment results in superior outcomes, this assumption can be wrong for a variety of reasons, which we discuss here. In addition to expressing unjust preferential treatment for some patients and not others, VIP medicine could compromise patient safety.

  6. Mechanism of hypertension in diabetic nephropathy

    PubMed Central

    Nazar, Chaudhary Muhammad Junaid

    2014-01-01

    High prevalence of hypertension is observed in diabetic patients of both the types. Diabetic nephropathy is one of the major reason for high morbidity, mortality and financial burden in such hypertensive diabetic patients. For this review, electronic databases including PubMed/Medline, Embase, Cochrane and Google scholar were searched from 1990-2013. Multiple inter-related factors are responsible for the development of hypertension and therefore nephropathy in the chronic diabetic patients. Majority of such factors are identified to lead to extensive sodium reabsorption and peripheral vasoconstriction and thus leading to microvascular complications like nephropathy. Management of hypertension by targeting such mediators is the highly recommended therapy for controlling and treating diabetic nephropathy. Clinical trials suggests that drugs inhibiting the renin-angiotensin-aldosterone pathway should be used as the first-line agents for the management of hypertensive diabetic nephropathy patients. These agents are effective in slowing the progression of the end-stage kidney disease as well as lowering albuminuria. Researchers are also investigating the effectiveness of drug combination for better management of hypertension and diabetic nephropathy. The present article is a review of the evidences which explains the underlying pathological changes which leads to the development of nephropathy in a hypertensive diabetic patients. The review also observes the clinical trials for different anti-hypertensive drugs which are recommended for the treatment of such patients. PMID:28197463

  7. Hemodynamic effects of dilevalol in patients with systemic hypertension and left ventricular dysfunction.

    PubMed

    Kinhal, V; Kulkarni, A; Pozderac, R; Cubbon, J

    1989-06-05

    Hemodynamic and left ventricular function parameters were measured in patients with mild to moderate hypertension and compromised left ventricular function who were given dilevalol, an antihypertensive agent with selective beta 2-agonism and nonselective beta-antagonist activity. After a 2- to 3-week placebo washout period, 9 patients were given dilevalol titrated upward from 100 to 600 mg twice daily over a 7-week period to achieve a supine diastolic blood pressure of less than 90 mm Hg with a decrease of greater than or equal to 10 mm Hg from baseline. Multigated radionuclide ventriculography and systolic and diastolic time intervals were performed after the pretreatment placebo washout, at the end of 2 weeks' maintenance dosing, and after a 7- to 10-day post-treatment discontinuation and placebo washout period. At an average daily dose of dilevalol, 444 mg, heart rate at rest decreased significantly (p less than 0.01) during treatment and increased during post-treatment placebo. Systolic and diastolic blood pressures at rest decreased significantly (p less than 0.01) during treatment and increased during post-treatment placebo. At maximal exercise, changes in blood pressure and heart rate were significantly blunted (p less than 0.05) during treatment. Ejection fraction at rest increased significantly (p less than 0.01) during treatment, with no significant change occurring during exercise, and decreased during post-treatment placebo. Preejection period decreased significantly during treatment (p less than 0.005) and increased during post-treatment placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Effect of docosahexaenoic acid monoacylglyceride on systemic hypertension and cardiovascular dysfunction.

    PubMed

    Morin, Caroline; Rousseau, Eric; Blier, Pierre U; Fortin, Samuel

    2015-07-01

    ω-3 Fatty acid supplementation has been associated with lower blood pressure. Cardiovascular diseases are also known to be linked directly to an increase in ω-6 and a reduction in ω-3 fatty acid levels in blood circulation and tissues. To determine the effect of docosahexaenoic acid monoglycerides (MAG-DHA) on blood pressure, lipid profiles, and vascular remodeling in rats fed a high-fat/high-carbohydrate (HFHC) diet. Studies were performed in male rats subjected to 8 wk of HFHC diet supplemented or not with 3 g/day MAG-DHA. After 8 wk of daily MAG-DHA treatment, rats in the HFHC + MAG-DHA group had lower arterial blood pressure and heart rate compared with the HFHC group. Moreover, MAG-DHA prevented the increase aortic wall thickness, whereas lipid analysis of aortic tissues revealed an increase in DHA/AA ratio correlated with the production of resolvin D2 and D3 metabolites. Histological analysis revealed that MAG-DHA prevented the development of LVH in the HFHC group. Serum lipid profile analysis further showed a decrease in total cholesterol (TC) and LDL, including very low-density lipoprotein (VLDL) and triglyceride (TG) levels, together with an increase in HDL levels after 8 wk of MAG-DHA treatment compared with the HFHC group. Furthermore, daily MAG-DHA treatment resulted in reduced proinflammatory marker levels such as CRP, IL-6, TNFα, and IL-1β. Altogether, these findings revealed that per os administration of MAG-DHA prevents HFHC-diet induced hypertension and LVH in rats.

  9. Pulmonary Hypertension

    PubMed Central

    Kim, John S.; McSweeney, Julia; Lee, Joanne; Ivy, Dunbar

    2015-01-01

    Objective Review the pharmacologic treatment options for pulmonary arterial hypertension (PAH) in the cardiac intensive care setting and summarize the most-recent literature supporting these therapies. Data Sources and Study Selection Literature search for prospective studies, retrospective analyses, and case reports evaluating the safety and efficacy of PAH therapies. Data Extraction Mechanisms of action and pharmacokinetics, treatment recommendations, safety considerations, and outcomes for specific medical therapies. Data Synthesis Specific targeted therapies developed for the treatment of adult patients with PAH have been applied for the benefit of children with PAH. With the exception of inhaled nitric oxide, there are no PAH medications approved for children in the US by the FDA. Unfortunately, data on treatment strategies in children with PAH are limited by the small number of randomized controlled clinical trials evaluating the safety and efficacy of specific treatments. The treatment options for PAH in children focus on endothelial-based pathways. Calcium channel blockers are recommended for use in a very small, select group of children who are responsive to vasoreactivity testing at cardiac catheterization. Phosphodiesterase type 5 inhibitor therapy is the most-commonly recommended oral treatment option in children with PAH. Prostacyclins provide adjunctive therapy for the treatment of PAH as infusions (intravenous and subcutaneous) and inhalation agents. Inhaled nitric oxide is the first line vasodilator therapy in persistent pulmonary hypertension of the newborn, and is commonly used in the treatment of PAH in the Intensive Care Unit (ICU). Endothelin receptor antagonists have been shown to improve exercise tolerance and survival in adult patients with PAH. Soluble Guanylate Cyclase Stimulators are the first drug class to be FDA approved for the treatment of chronic thromboembolic pulmonary hypertension. Conclusions Literature and data supporting the

  10. Pulmonary hypertension is not a risk factor for RVAD use and death after left ventricular assist system support.

    PubMed

    Smedira, N G; Massad, M G; Navia, J; Vargo, R L; Patel, A N; Cook, D J; McCarthy, P M

    1996-01-01

    Unlike transplantation candidates, patients with pulmonary hypertension (PHTN) and a high transpulmonary gradient do not appear to be at increased risk for right ventricular dysfunction after left ventricular assist system implant. To verify this observation, we reviewed 63 patients supported with the HeartMate (Thermo Cardiosystems, Inc, Woburn, MA) left ventricular assist system. Patients were divided into two groups: patients with PHTN (47 patients) had mean pulmonary artery pressure > 30 mm Hg and/or pulmonary vascular resistance > 4 Wood units, and the remainder of patients did not have PHTN (16 patients). Both groups were similar in age (mean, 51 years), gender distribution (% men, 83% vs 94%, not significant), and number of patients with ischemic cardiomyopathy (72% vs 69%, not significant). More patients in the group without PHTN required extracorporeal membrane oxygenation support (38% vs 12%, p = .06). Right ventricular assist device support was instituted in five (11%) patients with PHTN and four (25%) patients without PHTN. A significantly larger number of patients without PHTN died while on support (14% vs 44%, p = .01). Survival after transplantation in both groups was > 90%. Patients with PHTN have higher transpulmonary gradient, show a significant decrease in pulmonary pressure after left ventricular assist system implantation, and have a higher transplantation rate compared to patients without PHTN. A larger patient cohort is needed to determine if the absence of PHTN is a risk factor for RVAD need and poor outcome after LVAS support.

  11. [Hypertensive emergency and urgence].

    PubMed

    Gegenhuber, Alfons; Lenz, Kurt

    2003-12-01

    gradual reduction on an out-patient basis, depending on the patient's medical history and on any underlying chronic disease. Organ manifestations in the course of a hypertensive emergency concern the cardiovascular system and are associated with the symptoms of acute left-ventricular heart failure, the acute coronary syndrome or acute aortic dissection. In the brain the patient may have symptoms of hypertensive encephalopathy, hemorrhage, ischemia; in the kidney he/she may develop acute failure. The patient's blood pressure should be reduced rapidly during the treatment. It should not be reduced to the normal value, but by approximately 20-30% of the baseline value. The reason for a stepwise reduction in blood pressure is the fact that patients with chronic hypertension have an altered autoregulation curve. Acute normotension would lead to hypoperfusion in these patients. Those with aortic dissection or pulmonary edema are excepted from the rule of gradual blood pressure reduction. In the presence of these diseases, blood pressure must be reduced rapidly to normal values. Patients with a hypertensive emergency should always be admitted to the hospital. Parenteral treatment is given preference, since the effect of the treatment is rapid and occurs within a calculable period of time. Thus, parenteral treatment can also be better regulated than medication administered orally or by the sublingual route. Several antihypertensives are available for this purpose. The selection of the substance greatly depends on the existing organ failure as well as the reliable effectiveness and the regulability of the applied antihypertensive.

  12. Optimization of a 3D Dynamic Culturing System for In Vitro Modeling of Frontotemporal Neurodegeneration-Relevant Pathologic Features.

    PubMed

    Tunesi, Marta; Fusco, Federica; Fiordaliso, Fabio; Corbelli, Alessandro; Biella, Gloria; Raimondi, Manuela T

    2016-01-01

    Frontotemporal lobar degeneration (FTLD) is a severe neurodegenerative disorder that is diagnosed with increasing frequency in clinical setting. Currently, no therapy is available and in addition the molecular basis of the disease are far from being elucidated. Consequently, it is of pivotal importance to develop reliable and cost-effective in vitro models for basic research purposes and drug screening. To this respect, recent results in the field of Alzheimer's disease have suggested that a tridimensional (3D) environment is an added value to better model key pathologic features of the disease. Here, we have tried to add complexity to the 3D cell culturing concept by using a microfluidic bioreactor, where cells are cultured under a continuous flow of medium, thus mimicking the interstitial fluid movement that actually perfuses the body tissues, including the brain. We have implemented this model using a neuronal-like cell line (SH-SY5Y), a widely exploited cell model for neurodegenerative disorders that shows some basic features relevant for FTLD modeling, such as the release of the FTLD-related protein progranulin (PRGN) in specific vesicles (exosomes). We have efficiently seeded the cells on 3D scaffolds, optimized a disease-relevant oxidative stress experiment (by targeting mitochondrial function that is one of the possible FTLD-involved pathological mechanisms) and evaluated cell metabolic activity in dynamic culture in comparison to static conditions, finding that SH-SY5Y cells cultured in 3D scaffold are susceptible to the oxidative damage triggered by a mitochondrial-targeting toxin (6-OHDA) and that the same cells cultured in dynamic conditions kept their basic capacity to secrete PRGN in exosomes once recovered from the bioreactor and plated in standard 2D conditions. We think that a further improvement of our microfluidic system may help in providing a full device where assessing basic FTLD-related features (including PRGN dynamic secretion) that may be

  13. Development and fluidic simulation of microneedles for painless pathological interfacing with living systems

    NASA Astrophysics Data System (ADS)

    Chakraborty, Suman; Tsuchiya, Kazuyoshi

    2008-06-01

    In this paper, we investigate the development and fluidic analysis of microneedles integrated with painless blood extraction systems that aim to mimic the female mosquito's blood sampling techniques in certain respects. The microneedles are fabricated by employing the sputtering deposition method. A fluid mechanical analysis is presented toward predicting the transport mechanisms inside the microneedle as dynamically evolving consequences of the resistive forces and the aiding surface tension influences. The theoretical predictions are comprehensively compared to experimental data, and excellent agreements are found for all cases.

  14. The Role of Gap Junction Channels During Physiologic and Pathologic Conditions of the Human Central Nervous System

    PubMed Central

    Basilio, Daniel; Sáez, Juan C.; Orellana, Juan A.; Raine, Cedric S.; Bukauskas, Feliksas; Bennett, Michael V. L.; Berman, Joan W.

    2013-01-01

    Gap junctions (GJs) are expressed in most cell types of the nervous system, including neuronal stem cells, neurons, astrocytes, oligodendrocytes, cells of the blood brain barrier (endothelial cells and astrocytes) and under inflammatory conditions in microglia/macrophages. GJs connect cells by the docking of two hemichannels, one from each cell with each hemichannel being formed by 6 proteins named connexins (Cx). Unapposed hemichannels (uHC) also can be open on the surface of the cells allowing the release of different intracellular factors to the extracellular space. GJs provide a mechanism of cell-to-cell communication between adjacent cells that enables the direct exchange of intracellular messengers, such as calcium, nucleotides, IP3, and diverse metabolites, as well as electrical signals that ultimately coordinate tissue homeostasis, proliferation, differentiation, metabolism, cell survival and death. Despite their essential functions in physiological conditions, relatively little is known about the role of GJs and uHC in human diseases, especially within the nervous system. The focus of this review is to summarize recent findings related to the role of GJs and uHC in physiologic and pathologic conditions of the central nervous system. PMID:22438035

  15. Oxidative stress in the pathology and treatment of systemic lupus erythematosus

    PubMed Central

    Perl, Andras

    2014-01-01

    Oxidative stress is increased in systemic lupus erythematosus (SLE), and it contributes to immune system dysregulation, abnormal activation and processing of cell-death signals, autoantibody production and fatal comorbidities. Mitochondrial dysfunction in T cells promotes the release of highly diffusible inflammatory lipid hydroperoxides, which spread oxidative stress to other intracellular organelles and through the bloodstream. Oxidative modification of self antigens triggers autoimmunity, and the degree of such modification of serum proteins shows striking correlation with disease activity and organ damage in SLE. In T cells from patients with SLE and animal models of the disease, glutathione, the main intracellular antioxidant, is depleted and serine/threonine-protein kinase mTOR undergoes redox-dependent activation. In turn, reversal of glutathione depletion by application of its amino acid precursor, N-acetylcysteine, improves disease activity in lupus-prone mice; pilot studies in patients with SLE have yielded positive results that warrant further research. Blocking mTOR activation in T cells could conceivably provide a well-tolerated and inexpensive alternative approach to B-cell blockade and traditional immunosuppressive treatments. Nevertheless, compartmentalized oxidative stress in self-reactive T cells, B cells and phagocytic cells might serve to limit autoimmunity and its inhibition could be detrimental. Antioxidant therapy might also be useful in ameliorating damage caused by other treatments. This Review thus seeks to critically evaluate the complexity of oxidative stress and its relevance to the pathogenesis and treatment of SLE. PMID:24100461

  16. Saliva between normal and pathological. Important factors in determining systemic and oral health

    PubMed Central

    Iorgulescu, Gabriela

    2009-01-01

    There is a tendency in current medical research to explore the importance and symptomatology of saliva. The question to which increasingly more researchers from the medico-legal, systemic and dental fields tried to answer and bring together arguments for a greater emphasis is referring to the role of saliva in the health of the patient. Up until our time, people have looked at the importance of saliva from another perspective: saliva helped in pasting envelopes or stamps, or mostly in reported cases of public speakers faced with the impossibility of having a coherent speech due to sensations of dry mouth. This ‘dry mouth’ condition, named xerostomia in medical terms, has been used since antiquity as a test in detecting lies, knowing since then that the inhibition of emotional salivary glands, the feeling of ‘dry mouth’ is caused by anxiety, thus being a potential incrimination. Although hundreds of publications have insisted on the etiology and complications of the salivary gland hypofunction, only a few health professionals used to harvest saliva tests. As in the case of urine and blood, saliva quality and quantity are affected by a multitude of medical conditions and treatments, as well as the patient's psychological state. A review of the formation, function and dysfunction of salivary glands may convey the significant role played by saliva in health and disease, especially in detection and recognition of salivary gland hypofunction, systemic disease, and the psychological states, and thus prevent complications caused by these conditions. PMID:20112475

  17. Perturbations of the endocannabinoid system in mantle cell lymphoma: correlations to clinical and pathological features

    PubMed Central

    Wasik, Agata M.; Nygren, Lina; Almestrand, Stefan; Zong, Fang; Flygare, Jenny; Wennerholm, Stefanie Baumgartner; Saft, Leonie; Andersson, Patrik; Kimby, Eva; Wahlin, Björn E.; Christensson, Birger; Sander, Birgitta

    2014-01-01

    The cannabinoid receptors are upregulated in many types of cancers, including mantle cell lymphoma (MCL) and have been suggested to constitute novel therapeutic targets. The expression pattern of the key members of the endocannabinoid system was analyzed in a well-characterized MCL patient cohort and correlated to biological features. 107 tumor tissues were analyzed for the mRNA levels of cannabinoid receptors 1 and 2 (CNR1 and CNR2) and the two main enzymes regulating the endocannabinoid anandamide levels in tissue: NAPEPLD and FAAH (participating in synthesis and degradation, respectively). NAPEPLD, CNR1 and CNR2 were overexpressed while FAAH expression was reduced in MCL compared to non-malignant B-cells. Both low CNR1 and high FAAH levels correlated with lymphocytosis (p=0.016 and p=0.022, respectively) and with leukocytosis (p=0.0018 and p=0.047). Weak to moderate CNR1 levels were a feature of SOX11 negative MCL (p=0.006). Both high CNR2 and high FAAH levels correlated to anemia (p=0.0006 and p=0.038, respectively). In conclusion, the relative expression of the anandamide synthesizing and metabolizing enzymes in MCL is heavily perturbed. This finding, together with high expression of cannabinoid receptors, could favor enhanced anandamide signaling and suggest that targeting the endocannabinoid system might be considered as part of lymphoma therapy. PMID:25594062

  18. Pathologic Roles of Receptor-Associated Prorenin System in Idiopathic Epiretinal Membrane

    PubMed Central

    Dong, Yoko; Kanda, Atsuhiro; Noda, Kousuke; Saito, Wataru; Ishida, Susumu

    2017-01-01

    Receptor-associated prorenin system (RAPS) refers to the pathogenic mechanism whereby prorenin binding to (pro)renin receptor [(P)RR] dually activates tissue renin-angiotensin system (RAS) and RAS-independent signaling via (P)RR. The aim of this study is to determine the association of RAPS with idiopathic epiretinal membrane (iERM). Reverse transcription-PCR indicated the expression of RAPS components, including (P)RR and Ang II type 1 receptor (AT1R), in iERM tissues and human Müller glial cell line. Double-labeling analyses demonstrated that (P)RR and AT1R were detected in cells positive for glial fibrillary acidic protein, a marker for glial cells, and co-localized with prorenin and angiotensinogen, respectively. Administration of prorenin to Müller glial cells enhanced mRNA expression of fibroblast growth factor 2, while Ang II application stimulated the expression of glial cell line-derived neurotrophic factor, nerve growth factor, and transforming growth factor-β1. These expression levels induced by prorenin or Ang II were reversed by (P)RR or AT1R blockade, respectively. Immunofluorescence revealed tissue co-localization of (P)RR and AT1R with the products of the upregulated genes in vitro. The present findings suggest the involvement of RAPS in the pathogenesis of iERM. PMID:28276504

  19. Pulmonary Arterial Hypertension

    MedlinePlus

    ... What Is Pulmonary Hypertension? To understand pulmonary hypertension (PH) it helps to understand how blood ows throughout ... is too high, it is called pulmonary hypertension (PH). How the pressure in the right side of ...

  20. Pulmonary Hypertension in Scleroderma

    MedlinePlus

    PULMONARY HYPERTENSION IN SCLERODERMA PULMONARY HYPERTENSION Pulmonary hypertension (PH) is high blood pressure in the blood vessels ... with scleroderma are at increased risk for developing PH from several mechanisms. Frequently patients with scleroderma have ...

  1. Types of Pulmonary Hypertension

    MedlinePlus

    ... Hypertension The World Health Organization divides pulmonary hypertension (PH) into five groups. These groups are organized based ... lungs. Group 2 Pulmonary Hypertension Group 2 includes PH with left heart disease. Conditions that affect the ...

  2. Glutamate system, amyloid ß peptides and tau protein: functional interrelationships and relevance to Alzheimer disease pathology.

    PubMed

    Revett, Timothy J; Baker, Glen B; Jhamandas, Jack; Kar, Satyabrata

    2013-01-01

    Alzheimer disease is the most prevalent form of dementia globally and is characterized premortem by a gradual memory loss and deterioration of higher cognitive functions and postmortem by neuritic plaques containing amyloid ß peptide and neurofibrillary tangles containing phospho-tau protein. Glutamate is the most abundant neurotransmitter in the brain and is essential to memory formation through processes such as long-term potentiation and so might be pivotal to Alzheimer disease progression. This review discusses how the glutamatergic system is impaired in Alzheimer disease and how interactions of amyloid ß and glutamate influence synaptic function, tau phosphorylation and neurodegeneration. Interestingly, glutamate not only influences amyloid ß production, but also amyloid ß can alter the levels of glutamate at the synapse, indicating that small changes in the concentrations of both molecules could influence Alzheimer disease progression. Finally, we describe how the glutamate receptor antagonist, memantine, has been used in the treatment of individuals with Alzheimer disease and discuss its effectiveness.

  3. Base Excision Repair in Physiology and Pathology of the Central Nervous System

    PubMed Central

    Bosshard, Matthias; Markkanen, Enni; van Loon, Barbara

    2012-01-01

    Relatively low levels of antioxidant enzymes and high oxygen metabolism result in formation of numerous oxidized DNA lesions in the tissues of the central nervous system. Accumulation of damage in the DNA, due to continuous genotoxic stress, has been linked to both aging and the development of various neurodegenerative disorders. Different DNA repair pathways have evolved to successfully act on damaged DNA and prevent genomic instability. The predominant and essential DNA repair pathway for the removal of small DNA base lesions is base excision repair (BER). In this review we will discuss the current knowledge on the involvement of BER proteins in the maintenance of genetic stability in different brain regions and how changes in the levels of these proteins contribute to aging and the onset of neurodegenerative disorders. PMID:23203191

  4. Ebola epidemic exposes the pathology of the global economic and political system.

    PubMed

    Sanders, David; Sengupta, Amit; Scott, Vera

    2015-01-01

    While the current Ebola epidemic spiraled out of control to become the biggest in history, the global public health response has been criticized as "too little, too late." Many, like the World Health Organization, are asking what lessons have been learned from this epidemic. We present an analysis of the political economy of this Ebola outbreak that reveals the importance of addressing the social determinants that facilitated the exposure of populations, previously unaffected by Ebola Virus Disease, to infection and restricted the capacity for an effective medical response. To prevent further such crises, the global public health community has a responsibility to advocate for health system investment and development and for fundamental pro-poor changes to economic and power relations in the region.

  5. [Effect of 5-month guanfacine treatment on the renin-angiotensin-aldosterone system and some metabolic factors in patients with diabetes mellitus type II and hypertension].

    PubMed

    Jaromczyk-Slisz, J; Kubasik, A; Jasiel-Wojculewicz, H; Badzio, T; Krupa-Wojciechowska, B

    The group of the investigated included 25 individuals (11 F, 14 M), aged 55 +/- 1.5 years, with diabetes type II and hypertension. Known diabetes duration was 4.9 +/- 0.8 years and known hypertension duration--7.4 +/- 1.4 years. Two weeks after administering placebo in place of hypertension drugs applied so far, guanfacine was included as the only hypertensive drug. The dosage was increased from 0.5 mg up to 3 mg daily until a good control of blood pressure was achieved. The diabetic treatment, diet and the smoking habit were unchanged. The resting activity of the renin-angiotension-aldosterone system (RAA), cholesterol, triglycerides, HDL and LDL, serum glucose levels and HbA1c were assayed after a 5-month guanfacine period. After treatment a significant decrease in blood pressure both systolic and diastolic (p < 0.001), heart rate (p < 0.005) and plasma renin activity (p < 0.02) were observed. Preliminary measurements of RAA activity and its changes during treatment were not helpful in predicting guanfacine hypotensive effect. The level of lipids, lipoproteins, atherogenic factors, glucose and HbA1c did not change significantly during the study.

  6. Radiation-Induced Central Nervous System Death - A study of the Pathologic Findings in Monkeys Irradiated with Massive Doses of Cobalt-60 (Gamma) Radiation

    DTIC Science & Technology

    1959-04-01

    U.S. DEPARTMENT OF COMMERCE National Technical Information Service AD-AO36 168 RADIATION-INDUCED CENTRAL NERVOUS SYSTEM DEATH - A STUDY OF THE...ý." - ý " . :..’ýý.ý-. .. , . ý 4 ý .. -- ’ý.- -!:;:ý’,. 1,ý,-: WJiAUOK4KOUED CENTRAL NERVOUS SYSTEM NT A Study of the Pathologic Findings in...University SCHOOL OF AVIATION MEDICINE, USAF Randolph AFB, Texas April 1959 7757-. AdIAIONH-INDUCED CENTRAL NEVOUS $Y$194 DUTH A Study of the Pathologic

  7. Treating Hypertension in Pregnancy.

    PubMed

    Schlembach, Dietmar; Homuth, Volker; Dechend, Ralf

    2015-08-01

    Hypertension is present in about 10 % of all pregnancies. The frequency of chronic hypertension and that of gestational hypertension is increasing. The management of pregnant women with hypertension remains a significant, but controversial, public health problem. Although treatment of hypertension in pregnancy has shown to reduce maternal target organ damage, considerable debate remains concerning treatment. We review current evidence regarding treatment goals, the ideal treatment starting time, and which drugs are available for the treatment of hypertension in pregnancy.

  8. Pathology of Extranodal Lymphoma.

    PubMed

    Heckendorn, Emily; Auerbach, Aaron

    2016-07-01

    An overview of the pathology of extranodal lymphoma is presented. The emphasis of this presentation is on the classification system of extranodal lymphomas, including both B-cell and T-cell lymphomas, based on their morphology, phenotype, and molecular alterations.

  9. Development and evaluation of an automated histology classification system for veterinary pathology.

    PubMed

    Hattel, Arthur; Monga, Vishal; Srinivas, Umamahesh; Gillespie, Jim; Brooks, Jason; Fisher, Jenny; Jayarao, Bhushan

    2013-11-01

    A 2-stage algorithmic framework was developed to automatically classify digitized photomicrographs of tissues obtained from bovine liver, lung, spleen, and kidney into different histologic categories. The categories included normal tissue, acute necrosis, and inflammation (acute suppurative; chronic). In the current study, a total of 60 images per category (normal; acute necrosis; acute suppurative inflammation) were obtained from liver samples, 60 images per category (normal; acute suppurative inflammation) were obtained from spleen and lung samples, and 60 images per category (normal; chronic inflammation) were obtained from kidney samples. An automated support vector machine (SVM) classifier was trained to assign each test image to a specific category. Using 10 training images/category/organ, 40 test images/category/organ were examined. Employing confusion matrices to represent category-specific classification accuracy, the classifier-attained accuracies were found to be in the 74-90% range. The same set of test images was evaluated using a SVM classifier trained on 20 images/category/organ. The average classification accuracies were noted to be in the 84-95% range. The accuracy in correctly identifying normal tissue and specific tissue lesions was markedly improved by a small increase in the number of training images. The preliminary results from the study indicate the importance and potential use of automated image classification systems in the histologic identification of normal tissues and specific tissue lesions.

  10. Experimental pneumococcal meningitis causes central nervous system pathology without inducing the 72-kd heat shock protein.

    PubMed Central

    Täuber, M. G.; Kennedy, S. L.; Tureen, J. H.; Lowenstein, D. H.

    1992-01-01

    We examined whether experimental pneumococcal meningitis induced the 72-kd heat shock protein (HSP72), a sensitive marker of neuronal stress in other models of central nervous system (CNS) injury. Brain injury was characterized by vasculitis, cerebritis, and abscess formation in the cortex of infected animals. The extent of these changes correlated with the size of the inoculum (P less than 0.003) and with pathophysiologic parameters of disease severity, i.e., cerebrospinal fluid (CSF) lactate (r = 0.61, P less than 0.0001) and CSF glucose concentrations (r = -0.55, P less than 0.0001). Despite the presence of numerous cortical regions having morphologic evidence of injury, HSP72 was not detected in most animals. When present, only rare neurons were HSP72 positive. Western blot analysis of brain samples confirmed the paucity of HSP72 induction. The lack of neuronal HSP72 expression in this model suggests that at least some of the events leading to neuronal injury in meningitis are unique, when compared with CNS diseases associated with HSP72 induction. Images Figure 1 Figure 2 Figure 3 PMID:1632471

  11. Neural stem cells and their role in the pathology and classification of central nervous system tumors.

    PubMed

    Tihan, Tarik; Pekmezci, Melike; Karnezis, Anthony

    2011-01-01

    Today, one of the most popular and controversial topics in medicine is undoubtedly the rapidly developing field of stem cell research. Some of the controversy in this field arises from lack of uniform terminology and different interpretation of concepts such as brain tumor stem cells. In addition, lack of reliable and universal markers that can identify stem cells and define precursor cells in a particular differentiation pathway further confounds the interpretation of results in many studies. Stem cells are undoubtedly critical in normal cellular development as well as tumor biology and better characterization of these cells is likely to have profound influence on the classification schemes of tumors. In this manuscript, we present the generally accepted definitions of key concepts in stem cell biology and review some of the related molecular pathways. In addition, we put forth our position on how progress in this field should be affecting the future classification schemes of central nervous system neoplasia. We strongly believe that the ever increasing knowledge in the field of neural and brain tumor stem cells should be influential in the subsequent attempts to classify brain tumors.

  12. A hybrid mock circulatory system: testing a prototype under physiologic and pathological conditions.

    PubMed

    Ferrari, Gianfranco; De Lazzari, Claudio; Kozarski, Maciej; Clemente, Fabrizio; Górczyńska, Krystyna; Mimmo, Rita; Monnanni, Eliana; Tosti, Giancarlo; Guaragno, Marco

    2002-01-01

    Hydraulic models of circulation are used to test mechanical heart assist devices and for research and training purposes. However, when compared with numerical models, they are rather expensive and often not sufficiently flexible or accurate. Flexibility and accuracy can be improved by merging numerical models with physical models, thus obtaining a hybrid model where numerical and physical sections are connected by an electrohydraulic interface. This concept is applied here to represent left ventricular function. The resulting hybrid model is inserted into the existing closed loop model of circulation. The hybrid model reproduces ventricular function by a variable elastance numerical model. Its interaction with the hydraulic sections is governed by measuring left atrial and systemic arterial pressures and computing the left ventricular output flow by the resolution of the corresponding equations. This signal is used to control a flow generator reproduced by a gear pump driven by a DC motor. Results obtained under different circulatory conditions demonstrate the behavior of the ventricular model on the pressure-volume plane and report the trend of the main hemodynamic variables.

  13. The role of the renin-angiotensin-aldosterone system in the pathobiology of pulmonary arterial hypertension (2013 Grover Conference series).

    PubMed

    Maron, Bradley A; Leopold, Jane A

    2014-06-01

    Pulmonary arterial hypertension (PAH) is associated with aberrant pulmonary vascular remodeling that leads to increased pulmonary artery pressure, pulmonary vascular resistance, and right ventricular dysfunction. There is now accumulating evidence that the renin-angiotensin-aldosterone system is activated and contributes to cardiopulmonary remodeling that occurs in PAH. Increased plasma and lung tissue levels of angiotensin and aldosterone have been detected in experimental models of PAH and shown to correlate with cardiopulmonary hemodynamics and pulmonary vascular remodeling. These processes are abrogated by treatment with angiotensin receptor or mineralocorticoid receptor antagonists. At a cellular level, angiotensin and aldosterone activate oxidant stress signaling pathways that decrease levels of bioavailable nitric oxide, increase inflammation, and promote cell proliferation, migration, extracellular matrix remodeling, and fibrosis. Clinically, enhanced renin-angiotensin activity and elevated levels of aldosterone have been detected in patients with PAH, which suggests a role for angiotensin and mineralocorticoid receptor antagonists in the treatment of PAH. This review will examine the current evidence linking renin-angiotensin-aldosterone system activation to PAH with an emphasis on the cellular and molecular mechanisms that are modulated by aldosterone and may be of importance for the pathobiology of PAH.

  14. Polymorphism of the Fractalkine Receptor CX3CR1 and Systemic Sclerosis-associated Pulmonary Arterial Hypertension

    PubMed Central

    Marasini, Bianca; Cossutta, Roberta; Selmi, Carlo; Pozzi, Maria Rosa; Gardinali, Marco; Massarotti, Marco; Erario, Maddalena; Battaglioli, Lodovica; Biondi, Maria Luisa

    2005-01-01

    Fractalkine (FKN) and its receptor CX3CR1 are critical mediators in the vascular and tissue damage of several chronic diseases, including systemic sclerosis (SSc) and pulmonary arterial hypertension (PAH). Interestingly, the V249I and T280M genetic polymorphisms influence CX3CR1 expression and function. We investigated whether these polymorphisms are associated with PAH secondary to SSc. CX3CR1 genotypes were analyzed by PCR and sequencing in 76 patients with limited SSc and 204 healthy controls. PAH was defined by colorDoppler echocardiography. Homozygosity for 249II as well as the combined presence of 249II and 280MM were significantly more frequent in patients with SSc compared to controls (17 vs 6%, p = 0.0034 and 5 vs 1%, p = 0.0027, respectively). The 249I and 280M alleles were associated with PAH (odd ratio [OR] 2.2, 95% confidence interval [CI] 1.01-4.75, p = 0.028 and OR 7.37, 95%CI: 2.45-24.60, p = 0.0001, respectively). In conclusion, the increased frequencies of 249I and 280M CX3CR1 alleles in a subgroup of patients with SSc-associated PAH suggest a role for the fractalkine system in the pathogenesis of this condition. Further, the 249I allele might be associated with susceptibility to SSc. PMID:16584113

  15. Polymorphism of the fractalkine receptor CX3CR1 and systemic sclerosis-associated pulmonary arterial hypertension.

    PubMed

    Marasini, Bianca; Cossutta, Roberta; Selmi, Carlo; Pozzi, Maria Rosa; Gardinali, Marco; Massarotti, Marco; Erario, Maddalena; Battaglioli, Lodovica; Biondi, Maria Luisa

    2005-12-01

    Fractalkine (FKN) and its receptor CX3CR1 are critical mediators in the vascular and tissue damage of several chronic diseases, including systemic sclerosis (SSc) and pulmonary arterial hypertension (PAH). Interestingly, the V249I and T280M genetic polymorphisms influence CX3CR1 expression and function. We investigated whether these polymorphisms are associated with PAH secondary to SSc. CX3CR1 genotypes were analyzed by PCR and sequencing in 76 patients with limited SSc and 204 healthy controls. PAH was defined by colorDoppler echocardiography. Homozygosity for 249II as well as the combined presence of 249II and 280MM were significantly more frequent in patients with SSc compared to controls (17 vs 6%, p = 0.0034 and 5 vs 1%, p = 0.0027, respectively). The 249I and 280M alleles were associated with PAH (odd ratio [OR] 2.2, 95% confidence interval [CI] 1.01-4.75, p = 0.028 and OR 7.37, 95%CI: 2.45-24.60, p = 0.0001, respectively). In conclusion, the increased frequencies of 249I and 280M CX3CR1 alleles in a subgroup of patients with SSc-associated PAH suggest a role for the fractalkine system in the pathogenesis of this condition. Further, the 249I allele might be associated with susceptibility to SSc.

  16. Pathology of extramedullary mastocytosis.

    PubMed

    Doyle, Leona A; Hornick, Jason L

    2014-05-01

    Mastocytosis encompasses a group of clinically and pathologically heterogeneous disorders most commonly involving the skin, which typically takes the form of urticaria pigmentosa. Mastocytosis may also involve other organs, most often bone marrow, followed by gastrointestinal tract, liver, spleen, and lymph nodes. The presence of extracutaneous involvement by mastocytosis is a major diagnostic criterion for systemic disease. However, mast cell infiltrates are often subtle in skin and extracutaneous organs, and the histologic features of mastocytosis at different anatomic sites may be variable. This article reviews the pathologic features and clinical correlates of mastocytosis involving skin and other extramedullary sites.

  17. Palmitoylethanolamide treatment reduces blood pressure in spontaneously hypertensive rats: involvement of cytochrome p450-derived eicosanoids and renin angiotensin system.

    PubMed

    Mattace Raso, Giuseppina; Pirozzi, Claudio; d'Emmanuele di Villa Bianca, Roberta; Simeoli, Raffaele; Santoro, Anna; Lama, Adriano; Di Guida, Francesca; Russo, Roberto; De Caro, Carmen; Sorrentino, Raffaella; Calignano, Antonio; Meli, Rosaria

    2015-01-01

    Palmitoylethanolamide (PEA), a peroxisome proliferator-activated receptor-α agonist, has been demonstrated to reduce blood pressure and kidney damage secondary to hypertension in spontaneously hypertensive rat (SHR). Currently, no information is available concerning the putative effect of PEA on modulating vascular tone. Here, we investigate the mechanisms underpinning PEA blood pressure lowering effect, exploring the contribution of epoxyeicosatrienoic acids, CYP-dependent arachidonic acid metabolites, as endothelium-derived hyperpolarizing factors (EDHF), and renin angiotensin system (RAS) modulation. To achieve this aim SHR and Wistar-Kyoto rats were treated with PEA (30 mg/kg/day) for five weeks. Functional evaluations on mesenteric bed were performed to analyze EDHF-mediated vasodilation. Moreover, mesenteric bed and carotid were harvested to measure CYP2C23 and CYP2J2, the key isoenzymes in the formation of epoxyeicosatrienoic acids, and the soluble epoxide hydrolase, which is responsible for their degradation in the corresponding diols. Effect of PEA on RAS modulation was investigated by analyzing angiotensin converting enzyme and angiotensin receptor 1 expression. Here, we showed that EDHF-mediated dilation in response to acetylcholine was increased in mesenteric beds of PEA-treated SHR. Western blot analysis revealed that the increase in CYP2C23 and CYP2J2 observed in SHR was significantly attenuated in mesenteric beds of PEA-treated SHR, but unchanged in the carotids. Interestingly, in both vascular tissues, PEA significantly decreased the soluble epoxide hydrolase protein level, accompanied by a reduced serum concentration of its metabolite 14-15 dihydroxyeicosatrienoic acid, implying a reduction in epoxyeicosatrienoic acid hydrolisis. Moreover, PEA treatment down-regulated angiotensin receptor 1 and angiotensin converting enzyme expression, indicating a reduction in angiotensin II-mediated effects. Consistently, a damping of the activation of

  18. Palmitoylethanolamide Treatment Reduces Blood Pressure in Spontaneously Hypertensive Rats: Involvement of Cytochrome P450-Derived Eicosanoids and Renin Angiotensin System

    PubMed Central

    Mattace Raso, Giuseppina; Pirozzi, Claudio; d'Emmanuele di Villa Bianca, Roberta; Simeoli, Raffaele; Santoro, Anna; Lama, Adriano; Di Guida, Francesca; Russo, Roberto; De Caro, Carmen; Sorrentino, Raffaella; Calignano, Antonio; Meli, Rosaria

    2015-01-01

    Palmitoylethanolamide (PEA), a peroxisome proliferator-activated receptor-α agonist, has been demonstrated to reduce blood pressure and kidney damage secondary to hypertension in spontaneously hypertensive rat (SHR). Currently, no information is available concerning the putative effect of PEA on modulating vascular tone. Here, we investigate the mechanisms underpinning PEA blood pressure lowering effect, exploring the contribution of epoxyeicosatrienoic acids, CYP-dependent arachidonic acid metabolites, as endothelium-derived hyperpolarizing factors (EDHF), and renin angiotensin system (RAS) modulation. To achieve this aim SHR and Wistar-Kyoto rats were treated with PEA (30 mg/kg/day) for five weeks. Functional evaluations on mesenteric bed were performed to analyze EDHF-mediated vasodilation. Moreover, mesenteric bed and carotid were harvested to measure CYP2C23 and CYP2J2, the key isoenzymes in the formation of epoxyeicosatrienoic acids, and the soluble epoxide hydrolase, which is responsible for their degradation in the corresponding diols. Effect of PEA on RAS modulation was investigated by analyzing angiotensin converting enzyme and angiotensin receptor 1 expression. Here, we showed that EDHF-mediated dilation in response to acetylcholine was increased in mesenteric beds of PEA-treated SHR. Western blot analysis revealed that the increase in CYP2C23 and CYP2J2 observed in SHR was significantly attenuated in mesenteric beds of PEA-treated SHR, but unchanged in the carotids. Interestingly, in both vascular tissues, PEA significantly decreased the soluble epoxide hydrolase protein level, accompanied by a reduced serum concentration of its metabolite 14-15 dihydroxyeicosatrienoic acid, implying a reduction in epoxyeicosatrienoic acid hydrolisis. Moreover, PEA treatment down-regulated angiotensin receptor 1 and angiotensin converting enzyme expression, indicating a reduction in angiotensin II-mediated effects. Consistently, a damping of the activation of

  19. Malignant involvement of the peripheral nervous system in patients with cancer: multimodality imaging and pathologic correlation.

    PubMed

    Crush, Andrew Bryce; Howe, Benjamin Matthew; Spinner, Robert J; Amrami, Kimberly K; Hunt, Christopher Harker; Johnson, Geoffrey B; Murphy, Robert C; Morreale, Robert F; Peller, Patrick J

    2014-01-01

    The clinical and imaging evaluation of peripheral neuropathies in patients with cancer is challenging. It is critically important to differentiate malignant invasion of the peripheral nervous system from nonmalignant causes, such as radiation-induced neuritis, neuropathy associated with chemotherapy, and inflammatory neuropathies. Contrast material-enhanced magnetic resonance (MR) imaging is the initial noninvasive test of choice; however, interpretation can be challenging when the anatomic features are distorted by prior surgery, radiation, or both. Fluorine 18 ((18)F)-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is an imaging adjunct to MR imaging that is particularly helpful for evaluating peripheral nerves because the metabolic activity depicted with (18)F-FDG PET/CT helps differentiate malignant from benign disease and assists in making certain management decisions. For example, sites of high (18)F-FDG activity in a peripheral nerve can be targeted to increase the diagnostic yield of a biopsy because malignant involvement of peripheral nerves can be patchy. Of note, (18)F-FDG PET/CT can show clinically unsuspected metastases elsewhere in the body. If cancer is found, (18)F-FDG PET/CT allows excellent assessment of treatment response. (18)F-FDG PET/CT is also useful in evaluating primary nerve sheath tumors in that such tumors with low metabolic activity on FDG PET/CT images are unlikely to be malignant, although the specificity is limited. It is essential to have a good understanding of the imaging characteristics of benign and malignant causes of peripheral neuropathy if (18)F-FDG PET/CT is to be used effectively for accurate diagnosis.

  20. Inhibition of pathological brain angiogenesis through systemic delivery of AAV vector expressing soluble FLT1.

    PubMed

    Shen, F; Mao, L; Zhu, W; Lawton, M T; Pechan, P; Colosi, P; Wu, Z; Scaria, A; Su, H

    2015-11-01

    The soluble vascular endothelial growth factor (VEGF) receptor 1 (sFLT1) has been tested in both animals and humans for anti-angiogenic therapies, for example, age-related macular degeneration. We hypothesized that adeno-associated viral vector (AAV)-mediated sFLT1 expression could be used to inhibit abnormal brain angiogenesis. We tested the anti-angiogenic effect of sFLT1 and the feasibility of using AAV serotype 9 to deliver sFLT1 through intravenous injection (IV) to the brain angiogenic region. AAVs were packaged in AAV serotypes 1 and 2 (stereotactic injection) and 9 (IV injection). Brain angiogenesis was induced in adult mice through stereotactic injection of AAV1-VEGF. AAV2-sFLT02 containing sFLT1 VEGF-binding domain (domain 2) was injected into the brain angiogenic region, and AAV9-sFLT1 was injected into the jugular vein at the time of or 4 weeks after AAV1-VEGF injection. We showed that AAV2-sFLT02 inhibited brain angiogenesis at both time points. IV injection of AAV9-sFLT1 inhibited angiogenesis only when the vector was injected 4 weeks after angiogenic induction. Neither lymphocyte infiltration nor neuron loss was observed in AAV9-sFLT1-treated mice. Our data show that systemically delivered AAV9-sFLT1 inhibits angiogenesis in the mouse brain, which could be utilized to treat brain angiogenic diseases such as brain arteriovenous malformation.

  1. Clinical and Pathological Findings of a Fatal Systemic Capillary Leak Syndrome (Clarkson Disease)

    PubMed Central

    Zancanaro, Andrea; Serafini, Francesco; Fantin, Giuseppe; Murer, Bruno; Cicardi, Marco; Bonanni, Luca; Dalla Vestra, Michele; Scanferlato, Mauro; Mazzanti, Giovanni; Presotto, Fabio

    2015-01-01

    Abstract Systemic capillary leak syndrome (SCLS) is a rare disorder with episodes of hypotension, hypoalbuminemia, and hemoconcentration. During attacks endothelial hyperpermeability results in leakage of plasma proteins into the interstitial space. Attacks vary in severity and may be lethal. A 49-year-old previously healthy man was admitted to hospital for hypovolemic shock, anasarca with pleuropericardial effusion, muscle fatigue, and oliguria occurring after a flu-like syndrome. Laboratory data showed an increase in hematocrit (65%), leucocytes (24.590 μ/L), creatinine (2.5 mg/dL), creatine phosphokinase (10.000 U/L), and a decrease in serum albumin (17 g/L) without proteinuria. Immunoglobulins of class G/λ monoclonal gammopathy were detected (1.3 g/L). The initial suspicions addressed to a protein-loosing syndrome or to an effort-related rhabdomyolysis. Initial therapy was based on steroids, albumin, and high molecular weight plasma expanders (hydroxyethyl starch). Because of high hematocrit, phlebotomy was also performed. The patient had complete clinical remission and a diagnosis of SCLS was finally made. He received prophylactic therapy with verapamil and theophylline that was self-stopped for intolerance (hypotension and tachycardia). He had a new crisis 2 days after a physical effort, and was admitted in intensive care unit. The patient died for severe hypovolemic shock with multiorgan failure and sudden cardiac arrest 15 hours after hospital admission. Postmortem investigation revealed massive interstitial edema of main organs with myocardial hyperacute ischemia. Studies on SCLS are limited for the rarity of the disease and its unpredictable course. Both prophylactic and acute crisis treatments are empirical and optimal management of severe attacks is still lacking. PMID:25738482

  2. Inhibition of pathological brain angiogenesis through systemic delivery of AAV vector expressing soluble FLT1

    PubMed Central

    Shen, Fanxia; Mao, Lei; Zhu, Wan; Lawton, Michael T.; Pechan, Peter; Colosi, Peter; Wu, Zhijian; Scaria, Abraham; Su, Hua

    2015-01-01

    The soluble vascular endothelial growth factor (VEGF) receptor 1 (sFLT1) has been tested in both animals and humans for anti-angiogenic therapies, e.g., age-related macular degeneration. We hypothesized that adeno-associated viral vector (AAV)-mediated sFLT1 expression could be used to inhibit abnormal brain angiogenesis. We tested the anti-angiogenic effect of sFLT1 and the feasibility of using AAV serotype 9 to deliver sFLT1 through intravenous injection (IV) to the brain angiogenic region. AAV vectors were packaged in AAV serotypes 1 and 2 (stereotactic injection) and 9 (IV-injection). Brain angiogenesis was induced in adult mice through stereotactic injection of AAV1-VEGF. AAV2-sFLT02 containing sFLT1 VEGF-binding domain (domain 2) was injected into the brain angiogenic region, and AAV9-sFLT1 was injected into the jugular vein at the time of or 4 weeks after AAV1-VEGF injection. We showed that AAV2-sFLT02 inhibited brain angiogenesis at both time points. Intravenous injection of AAV9-sFLT1 inhibited angiogenesis only when the vector was injected 4 weeks after angiogenic induction. Neither lymphocyte infiltration nor neuron loss was observed in AAV9-sFLT1-treated mice. Our data show that systemically delivered AAV9-sFLT1 inhibits angiogenesis in the mouse brain, which could be utilized to treat brain angiogenic diseases such as brain arteriovenous malformation. PMID:26090874

  3. Clinical and pathological findings of a fatal systemic capillary leak syndrome (Clarkson disease): a case report.

    PubMed

    Zancanaro, Andrea; Serafini, Francesco; Fantin, Giuseppe; Murer, Bruno; Cicardi, Marco; Bonanni, Luca; Dalla Vestra, Michele; Scanferlato, Mauro; Mazzanti, Giovanni; Presotto, Fabio

    2015-03-01

    Systemic capillary leak syndrome (SCLS) is a rare disorder with episodes of hypotension, hypoalbuminemia, and hemoconcentration. During attacks endothelial hyperpermeability results in leakage of plasma proteins into the interstitial space. Attacks vary in severity and may be lethal.A 49-year-old previously healthy man was admitted to hospital for hypovolemic shock, anasarca with pleuropericardial effusion, muscle fatigue, and oliguria occurring after a flu-like syndrome. Laboratory data showed an increase in hematocrit (65%), leucocytes (24.590 μ/L), creatinine (2.5 mg/dL), creatine phosphokinase (10.000 U/L), and a decrease in serum albumin (17 g/L) without proteinuria. Immunoglobulins of class G/λ monoclonal gammopathy were detected (1.3 g/L). The initial suspicions addressed to a protein-loosing syndrome or to an effort-related rhabdomyolysis. Initial therapy was based on steroids, albumin, and high molecular weight plasma expanders (hydroxyethyl starch). Because of high hematocrit, phlebotomy was also performed. The patient had complete clinical remission and a diagnosis of SCLS was finally made. He received prophylactic therapy with verapamil and theophylline that was self-stopped for intolerance (hypotension and tachycardia). He had a new crisis 2 days after a physical effort, and was admitted in intensive care unit. The patient died for severe hypovolemic shock with multiorgan failure and sudden cardiac arrest 15 hours after hospital admission. Postmortem investigation revealed massive interstitial edema of main organs with myocardial hyperacute ischemia.Studies on SCLS are limited for the rarity of the disease and its unpredictable course. Both prophylactic and acute crisis treatments are empirical and optimal management of severe attacks is still lacking.

  4. Health Systems Readiness to Manage the Hypertension Epidemic in Primary Health Care Facilities in the Western Cape, South Africa: A Study Protocol

    PubMed Central

    Yaya, Sanni; Labonté, Ronald

    2016-01-01

    Background Developing countries are undergoing a process of epidemiological transition from infectious to noncommunicable diseases, described by the United Nations Secretary General Ban Ki-Moon as ‘‘a public health emergency in slow motion.” One of the most prevalent in sub-Saharan Africa is hypertension, which is a complex chronic condition often referred to as a “silent killer” and key contributor to the development of cardiovascular and cerebrovascular diseases. Hypertensive patients in this setting are estimated to increase from 74.7 million in 2008 to 125.5 million in 2025, a 68% increase. However, there is an important gap between emerging high-level policies and recommendations, and the near-absence of practical guidance and experience delivering long-term medical care for noncommunicable diseases within resource-limited health systems. Objective To address this gap, our study will consist of field investigations to determine the minimum health systems requirements to ensure successful delivery of antihypertensive medications when scaling-up interventions to control the hypertension epidemic. Methods A cross-sectional analytic study will be conducted in the Western Cape using a mixed-method approach with two semistructured interview guides. The first will be for health professionals involved in the care of hypertensive patients within at least 6 community health centers (3 urban and 3 rural) to understand the challenges associated with their care. The second will be to map and assess the current supply chain management system of antihypertensive medications by interviewing key informants at different levels of the processes. Finally, modeling and simulation tools will be used to understand how to estimate minimum numbers of health workers required at each supply chain interval to ensure successful delivery of medications when scaling-up interventions. Results Funding for the study was secured through a Doctoral Research Award in October 2014 from

  5. First report of fatal systemic Halicephalobus gingivalis infection in two Lipizzaner horses from Romania: clinical, pathological, and molecular characterization.

    PubMed

    Taulescu, Marian A; Ionicã, Angela M; Diugan, Eva; Pavaloiu, Alexandra; Cora, Roxana; Amorim, Irina; Catoi, Cornel; Roccabianca, Paola

    2016-03-01

    Halicephalobus gingivalis (H. gingivalis) causes a rare and fatal infection in horses and humans. Despite the zoonotic potential and severity of the disease, the epidemiology and pathogenesis of halicephalobiasis are still poorly understood. Several European cases of equine halicephalobiasis have been documented; however, in South-Eastern European countries, including Romania, equine neurohelminthiasis caused by H. gingivalis has not been previously described. Two Lipizzaner horses with a clinical history of progressive neurological signs were referred to the Pathology Department of the Cluj-Napoca (Romania) for necropsy. Both horses died with severe neurological signs. Gross examination and cytological, histological, and molecular analyses were performed. The stallions came from two different breeding farms. No history of traveling outside Romania was recorded. At necropsy, granulomatous and necrotizing lesions were observed in the kidneys, lymph nodes, brain, retroperitoneal adipose tissue, and lungs, indicating a systemic infection. Parasitological and histopathological analyses evidenced larval and adult forms of rhabditiform nematodes consistent with Halicephalobus species. Parasites were observed in both lymph and blood vessels of different organs and were also identified in urine samples. A subunit of the large-subunit ribosomal RNA gene (LSU rDNA) of H. gingivalis (673 bp) was amplified from lesions in both horses.To the authors' knowledge, this is the first report of equine systemic H. gingivalis infection in Romania and in South-Eastern Europe. Our findings provide new insights into the geographic distribution of specific genetic lineages of H. gingivalis, while also raising public health awareness, as the parasite is zoonotic.

  6. Next-Generation Pathology.

    PubMed

    Caie, Peter D; Harrison, David J

    2016-01-01

    The field of pathology is rapidly transforming from a semiquantitative and empirical science toward a big data discipline. Large data sets from across multiple omics fields may now be extracted from a patient's tissue sample. Tissue is, however, complex, heterogeneous, and prone to artifact. A reductionist view of tissue and disease progression, which does not take this complexity into account, may lead to single biomarkers failing in clinical trials. The integration of standardized multi-omics big data and the retention of valuable information on spatial heterogeneity are imperative to model complex disease mechanisms. Mathematical modeling through systems pathology approaches is the ideal medium to distill the significant information from these large, multi-parametric, and hierarchical data sets. Systems pathology may also predict the dynamical response of disease progression or response to therapy regimens from a static tissue sample. Next-generation pathology will incorporate big data with systems medicine in order to personalize clinical practice for both prognostic and predictive patient care.

  7. Essential Hypertension vs. Secondary Hypertension Among Children

    PubMed Central

    Banker, Ashish; Shete, Sanjay; Hashmi, Syed Sharukh; Tyson, John E.; Barratt, Michelle S.; Hecht, Jacqueline T.; Milewicz, Diane M.; Boerwinkle, Eric

    2015-01-01

    BACKGROUND The aim was to determine the proportions and correlates of essential hypertension among children in a tertiary pediatric hypertension clinic. METHODS We evaluated 423 consecutive children and collected demographic and clinical history by retrospective chart review. RESULTS We identified 275 (65%) hypertensive children (blood pressure >95th percentile per the “Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents”) from 423 children referred to the clinic for history of elevated blood pressure. The remainder of the patients had normotension (11%), white coat hypertension (11%), prehypertension (10%), and pending diagnosis (3%). Among the 275 hypertensive children, 43% (n = 119; boys = 56%; median age = 12 years; range = 3–17 years) had essential hypertension and 57% (n = 156; boys = 66%; median age = 9 years; range = 0.08–19 years) had secondary hypertension. When compared with those with secondary hypertension, those with essential hypertension had a significantly older age at diagnosis (P = 0.0002), stronger family history of hypertension (94% vs. 68%; P < 0.0001), and lower prevalence of preterm birth (20% vs. 46%; P < 0.001). There was a bimodal distribution of age of diagnosis in those with secondary hypertension. CONCLUSIONS The phenotype of essential hypertension can present as early as 3 years of age and is the predominant form of hypertension in children after age of 6 years. Among children with hypertension, those with essential hypertension present at an older age, have a stronger family history of hypertension, and have lower prevalence of preterm birth. PMID:24842390

  8. Hypertension in Chronic Glomerulonephritis

    PubMed Central

    2015-01-01

    Chronic glomerulonephritis (GN), which includes focal segmental glomerulosclerosis and proliferative forms of GN such as IgA nephropathy, increases the risk of hypertension. Hypertension in chronic GN is primarily volume dependent, and this increase in blood volume is not related to the deterioration of renal function. Patients with chronic GN become salt sensitive as renal damage including arteriolosclerosis progresses and the consequent renal ischemia causes the stimulation of the intrarenal renin-angiotensin-aldosterone system(RAAS). Overactivity of the sympathetic nervous system also contributes to hypertension in chronic GN. According to the KDIGO guideline, the available evidence indicates that the target BP should be ≤140mmHg systolic and ≤90mmHg diastolic in chronic kidney disease patients without albuminuria. In most patients with an albumin excretion rate of ≥30mg/24 h (i.e., those with both micro-and macroalbuminuria), a lower target of ≤130mmHg systolic and ≤80mmHg diastolic is suggested. The use of agents that block the RAAS system is recommended or suggested in all patients with an albumin excretion rate of ≥30mg/ 24 h. The combination of a RAAS blockade with a calcium channel blocker and a diuretic may be effective in attaining the target BP, and in reducing the amount of urinary protein excretion in patients with chronic GN. PMID:26848302

  9. Progression of Prehypertension to Hypertension in Adolescents

    PubMed Central

    Redwine, Karen M.; Falkner, Bonita

    2013-01-01

    In the 2004 report from the National High Blood Pressure (BP) Education Program Working Group on BP in Children and Adolescents, the term “high normal BP” was replaced with the designation “prehypertension”. It was proposed that BP levels that were higher than normal but did not reach the level of hypertension posed an increased risk for progression to hypertension. The overall intent of this description was to help identify children who were at the greatest risk for the development of hypertension. These are children and adolescents for whom targeted prevention programs are expected to be most beneficial. Following the 2004 report, the prehypertension condition has been examined and described in adolescents as well as adults. This review summarizes the knowledge that has been gained on prehypertension including clinical characteristics, rates of progression to hypertension, and evidence of cardiovascular pathology. PMID:22878957

  10. KCNA5 gene is not confirmed as a systemic sclerosis-related pulmonary arterial hypertension genetic susceptibility factor

    PubMed Central

    2012-01-01

    Introduction Potassium voltage-gated channel shaker-related subfamily member 5 (KCNA5) is implicated in vascular tone regulation, and its inhibition during hypoxia produces pulmonary vasoconstriction. Recently, a protective association of the KCNA5 locus with systemic sclerosis (SSc) patients with pulmonary arterial hypertension (PAH) was reported. Hence, the aim of this study was to replicate these findings in an independent multicenter Caucasian SSc cohort. Methods The 2,343 SSc cases (179 PAH positive, confirmed by right-heart catheterization) and 2,690 matched healthy controls from five European countries were included in this study. Rs10744676 single-nucleotide polymorphism (SNP) was genotyped by using a TaqMan SNP genotyping assay. Results Individual population analyses of the selected KCNA5 genetic variant did not show significant association with SSc or any of the defined subsets (for example, limited cutaneous SSc, diffuse cutaneous SSc, anti-centromere autoantibody positive and anti-topoisomerase autoantibody positive). Furthermore, pooled analyses revealed no significant evidence of association with the disease or any of the subsets, not even the PAH-positive group. The comparison of PAH-positive patients with PAH-negative patients showed no significant differences among patients. Conclusions Our data do not support an important role of KCNA5 as an SSc-susceptibility factor or as a PAH-development genetic marker for SSc patients. PMID:23270786

  11. Prevalence of Pulmonary Arterial Hypertension in Korean Adult Patients with Systemic Sclerosis: Result of a Pilot Echocardiographic Screening Study

    PubMed Central

    Yoo, Su-Jin; Park, Yunseon; Lee, Jae-Hwan; Sun, Byung-Joo; Kim, Jinhyun; Yoo, In Seol; Shim, Seung Cheol

    2016-01-01

    Background Pulmonary arterial hypertension (PAH) is a major cause of morbidity and mortality among patients with systemic sclerosis (SSc). Early detection and prompt treatment of PAH associated with SSc (SSc-PAH) result in better prognosis. We conducted echocardiographic study to presume the prevalence of PAH in Korean adult SSc patients and to diagnose SSc-PAH in their early stages with right heart catheterization (RHC). Methods We performed free of charge echocardiographic study including 37 adult SSc patients at the Chungnam National University Hospital. The possibility of PAH is determined by the estimation of pulmonary arterial pressure by peak tricuspid regurgitation velocity of > 3.0 m/s. Patients with possible PAH were recommended to undergo RHC to confirm the diagnosis. Results In 37 patients, 8 patients were suspected with PAH. Among them, 6 patients agreed to be examined with RHC, and 4 were confirmed with PAH. The prevalence of possible PAH was 21.6% (8 of 37 patients), and that of confirmed PAH was 10.8% (4 of 37 patients). Four patients who were confirmed with SSc-PAH through RHC have been treated with specific pulmonary vasodilators and maintained stable. Conclusion Eight patients (21.6%) were possible PAH and 4 (10.8%) were diagnosed as SSc-PAH by RHC after the echocardiographic screening study of 37 adult SSc patients. PMID:28090259

  12. Neuropathy optic glaucomatosa induced by systemic hypertension through activation endothelin-1 signaling pathway in central retinal artery in rats

    PubMed Central

    Prayitnaningsih, Seskoati; Sujuti, Hidayat; Effendi, Maksum; Abdullah, Aulia; Anandita, Nanda Wahyu; Yohana, Febriani; Permatasari, Nur; Widodo, Mohamad Aris

    2016-01-01

    AIM To evaluate effect of hypertension on retinal ganglion cell (RGC) apoptosis, intraocular pressure (IOP), and the activation of endothelin-1 (ET-1) signaling pathway in central retinal artery (CRA) in rats. METHODS The experimental study was performed on 20 male Sprague Dawley rats that were divided into control group, and hypertension groups. The hypertension was induced by subcutaneous deoxycorticoacetate (DOCA) 10 mg/kg twice a week and administered 0.9% NaCl solution daily for 2, 6, and 10wk. Blood pressure (BP) was measured using animal BP analyzer. IOP was measured by handheld tonometry. Retinal tissue preparations by paraffin blocks were made after enucleation. The expression of ET-1, eNOS, ET-1 receptor A (ETRA), ET-1 receptor B (ETRB), and phosphorylated myosin light chain kinase (MLCK), and caldesmon (CaD) in CRA and RGC apoptosis were evaluated through immunofluorescent staining method then observed using laser scanning confocal microscopy. RESULTS BP significantly increased in all of the hypertension groups compared to control (P=0.001). Peak IOP elevation (7.78±4.14 mm Hg) and RGC apoptosis (576.15±33.28 Au) occurred on 2wk of hypertension. ET-1 expression (1238.6±55.1 Au) and eNOS expression (2814.2±70.7 Au) were found highest in 2wk of hypertension, although the ratio of ET-1/eNOS decreased since 2wk. ETRA reached peak expression in 10wk of hypertension (1219.4±6.3 Au), while ETRB significantly increased only in 2 weeks group (1069.2±9.6 Au). The highest MLCK expression (1190.09±58.32 Au), CaD (1670.28±18.36 Au) were also found in 2wk of hypertension. CONCLUSION Hypertension effects to activation of ET-1 signaling pathway significantly in CRA, elevation of IOP, and RGC apoptosis. The highest value was achieved at 2wk, which is the development phase of hypertension. PMID:27990358

  13. Relation of C-reactive protein, fibrinogen, and cardiorespiratory fitness to risk of systemic hypertension in men.

    PubMed

    Jae, Sae Young; Kurl, Sudhir; Laukkanen, Jari A; Lee, Chong-Do; Choi, Yoon-Ho; Fernhall, Bo; Franklin, Barry A

    2015-06-15

    We investigated the relation between inflammation and incident hypertension, independent of obesity, and tested the associations of cardiorespiratory fitness (fitness) and indexes of inflammation for the development of hypertension in 2,475 normotensive men. Inflammatory markers were C-reactive protein (CRP) and fibrinogen. Fitness was directly measured by peak oxygen uptake during sign/symptom-limited treadmill exercise testing to volitional fatigue; 266 men (10.7%) developed hypertension during an average of 4 years follow-up. After adjusting for potential confounding variables, the relative risk (RR) and 95% confidence interval (CI) for incident hypertension in those in the upper tertile versus lower tertile were 1.55 (95% CI 1.15 to 2.09) for CRP and 1.51 (95% CI 1.10 to 2.06) for fibrinogen. Although the association between fibrinogen and incident hypertension persisted after adjusting for body mass index (p = 0.049), the relation between CRP and incident hypertension was no longer statistically significant (p = 0.08). Fit men had a 27% decreased (RR 0.73, 95% CI 0.56 to 0.94) risk of incident hypertension compared with unfit men in a multivariable adjusted model. In the joint analysis, unfit men with upper CRP had 1.81 times (95% CI 1.21 to 2.70) and unfit men with upper fibrinogen had 2.03 times (95% CI 1.33 to 3.12) greater risks of incident hypertension compared with fit men with low CRP and fibrinogen, respectively. However, these risks did not significantly increase in fit men with upper CRP (RR 1.12, 95% CI 0.76 to 1.63) and fibrinogen (RR 1.26, 95% CI 0.86 to 1.85) groups. In conclusion, these results suggest that heightened levels of fibrinogen, but not CRP, are associated with incident hypertension, independent of body weight, and that high fitness attenuates the risk of incident hypertension across upper levels of inflammatory markers in men.

  14. Leptin Mediates High-Fat Diet Sensitization of Angiotensin II-Elicited Hypertension by Upregulating the Brain Renin-Angiotensin System and Inflammation.

    PubMed

    Xue, Baojian; Yu, Yang; Zhang, Zhongming; Guo, Fang; Beltz, Terry G; Thunhorst, Robert L; Felder, Robert B; Johnson, Alan Kim

    2016-05-01

    Obesity is characterized by increased circulating levels of the adipocyte-derived hormone leptin, which can increase sympathetic nerve activity and raise blood pressure. A previous study revealed that rats fed a high-fat diet (HFD) have an enhanced hypertensive response to subsequent angiotensin II administration that is mediated at least, in part, by increased activity of brain renin-angiotensin system and proinflammatory cytokines. This study tested whether leptin mediates this HFD-induced sensitization of angiotensin II-elicited hypertension by interacting with brain renin-angiotensin system and proinflammatory cytokine mechanisms. Rats fed an HFD for 3 weeks had significant increases in white adipose tissue mass, plasma leptin levels, and mRNA expression of leptin and its receptors in the lamina terminalis and hypothalamic paraventricular nucleus. Central infusion of a leptin receptor antagonist during HFD feeding abolished HFD sensitization of angiotensin II-elicited hypertension. Furthermore, central infusion of leptin mimicked the sensitizing action of HFD. Concomitant central infusions of the angiotensin II type 1 receptor antagonist irbesartan, the tumor necrosis factor-α synthesis inhibitor pentoxifylline, or the inhibitor of microglial activation minocycline prevented the sensitization produced by central infusion of leptin. RT-PCR analysis indicated that either HFD or leptin administration upregulated mRNA expression of several components of the renin-angiotensin system and proinflammatory cytokines in the lamina terminalis and paraventricular nucleus. The leptin antagonist and the inhibitors of angiotensin II type 1 receptor, tumor necrosis factor-α synthesis, and microglial activation all reversed the expression of these genes. The results suggest that HFD-induced sensitization of angiotensin II-elicited hypertension is mediated by leptin through upregulation of central renin-angiotensin system and proinflammatory cytokines.

  15. Acute and chronic systemic CB1 cannabinoid receptor blockade improves blood pressure regulation and metabolic profile in hypertensive (mRen2)27 rats.

    PubMed

    Schaich, Chris L; Shaltout, Hossam A; Brosnihan, K Bridget; Howlett, Allyn C; Diz, Debra I

    2014-08-01

    We investigated acute and chronic effects of CB1 cannabinoid receptor blockade in renin-angiotensin system-dependent hypertension using rimonabant (SR141716A), an orally active antagonist with central and peripheral actions. In transgenic (mRen2)27 rats, a model of angiotensin II-dependent hypertension with increased body mass and insulin resistance, acute systemic blockade of CB1 receptors significantly reduced blood pressure within 90 min but had no effect in Sprague-Dawley rats. No changes in metabolic hormones occurred with the acute treatment. During chronic CB1 receptor blockade, (mRen2)27 rats received daily oral administration of SR141716A (10 mg/kg/day) for 28 days. Systolic blood pressure was significantly reduced within 24 h, and at Day 21 of treatment values were 173 mmHg in vehicle versus 149 mmHg in drug-treated rats (P < 0.01). This accompanied lower cumulative weight gain (22 vs. 42 g vehicle; P < 0.001), fat mass (2.0 vs. 2.9% of body weight; P < 0.05), and serum leptin (2.8 vs. 6.0 ng/mL; P < 0.05) and insulin (1.0 vs. 1.9 ng/mL; P < 0.01), following an initial transient decrease in food consumption. Conscious hemodynamic recordings indicate twofold increases occurred in spontaneous baroreflex sensitivity (P < 0.05) and heart rate variability (P < 0.01), measures of cardiac vagal tone. The beneficial actions of CB1 receptor blockade in (mRen2)27 rats support the interpretation that an upregulated endocannabinoid system contributes to hypertension and impaired autonomic function in this angiotensin II-dependent model. We conclude that systemic CB1 receptor blockade may be an effective therapy for angiotensin II-dependent hypertension and associated metabolic syndrome.

  16. Pathological and Clinical Features and Management of Central Nervous System Hemangioblastomas in von Hippel-Lindau Disease

    PubMed Central

    Kobayashi, Natsuki; Nakanowatari, Satoshi

    2014-01-01

    Central nervous system (CNS) hemangioblastoma is the most common manifestation of von Hippel-Lindau (VHL) disease. It is found in 70–80% of VHL patients. Hemangioblastoma is a rare form of benign vascular tumor of the CNS, accounting for 2.0% of CNS tumors. It can occur sporadically or as a familial syndrome. CNS hemangioblastomas are typically located in the posterior fossa and the spinal cord. VHL patients usually develop a CNS hemangioblastoma at an early age. Therefore, they require a special routine for diagnosis, treatment and follow-up. The surgical management of symptomatic tumors depend on many factors such as symptom, location, multiplicity, and progression of the tumor. The management of asymptomatic tumors in VHL patients are controversial since CNS hemangioblastomas grow with intermittent quiescent and rapid-growth phases. Preoperative embolization of large solid hemangioblastomas prevents perioperative hemorrhage but is not necessary in every case. Radiotherapy should be reserved for inoperable tumors. Because of complexities of VHL, a better understanding of the pathological and clinical features of hemangioblastoma in VHL is essential for its proper management. PMID:28326249

  17. Optimization of a 3D Dynamic Culturing System for In Vitro Modeling of Frontotemporal Neurodegeneration-Relevant Pathologic Features

    PubMed Central

    Tunesi, Marta; Fusco, Federica; Fiordaliso, Fabio; Corbelli, Alessandro; Biella, Gloria; Raimondi, Manuela T.

    2016-01-01

    Frontotemporal lobar degeneration (FTLD) is a severe neurodegenerative disorder that is diagnosed with increasing frequency in clinical setting. Currently, no therapy is available and in addition the molecular basis of the disease are far from being elucidated. Consequently, it is of pivotal importance to develop reliable and cost-effective in vitro models for basic research purposes and drug screening. To this respect, recent results in the field of Alzheimer’s disease have suggested that a tridimensional (3D) environment is an added value to better model key pathologic features of the disease. Here, we have tried to add complexity to the 3D cell culturing concept by using a microfluidic bioreactor, where cells are cultured under a continuous flow of medium, thus mimicking the interstitial fluid movement that actually perfuses the body tissues, including the brain. We have implemented this model using a neuronal-like cell line (SH-SY5Y), a widely exploited cell model for neurodegenerative disorders that shows some basic features relevant for FTLD modeling, such as the release of the FTLD-related protein progranulin (PRGN) in specific vesicles (exosomes). We have efficiently seeded the cells on 3D scaffolds, optimized a disease-relevant oxidative stress experiment (by targeting mitochondrial function that is one of the possible FTLD-involved pathological mechanisms) and evaluated cell metabolic activity in dynamic culture in comparison to static conditions, finding that SH-SY5Y cells cultured in 3D scaffold are susceptible to the oxidative damage triggered by a mitochondrial-targeting toxin (6-OHDA) and that the same cells cultured in dynamic conditions kept their basic capacity to secrete PRGN in exosomes once recovered from the bioreactor and plated in standard 2D conditions. We think that a further improvement of our microfluidic system may help in providing a full device where assessing basic FTLD-related features (including PRGN dynamic secretion) that may

  18. Pulmonary arterial hypertension (ascites syndrome) in broilers: a review.

    PubMed

    Wideman, R F; Rhoads, D D; Erf, G F; Anthony, N B

    2013-01-01

    Pulmonary arterial hypertension (PAH) syndrome in broilers (also known as ascites syndrome and pulmonary hypertension syndrome) can be attributed to imbalances between cardiac output and the anatomical capacity of the pulmonary vasculature to accommodate ever-increasing rates of blood flow, as well as to an inappropriately elevated tone (degree of constriction) maintained by the pulmonary arterioles. Comparisons of PAH-susceptible and PAH-resistant broilers do not consistently reveal differences in cardiac output, but PAH-susceptible broilers consistently have higher pulmonary arterial pressures and pulmonary vascular resistances compared with PAH-resistant broilers. Efforts clarify the causes of excessive pulmonary vascular resistance have focused on evaluating the roles of chemical mediators of vasoconstriction and vasodilation, as well as on pathological (structural) changes occurring within the pulmonary arterioles (e.g., vascular remodeling and pathology) during the pathogenesis of PAH. The objectives of this review are to (1) summarize the pathophysiological progression initiated by the onset of pulmonary hypertension and culminating in terminal ascites; (2) review recent information regarding the factors contributing to excessively elevated resistance to blood flow through the lungs; (3) assess the role of the immune system during the pathogenesis of PAH; and (4) present new insights into the genetic basis of PAH. The cumulative evidence attributes the elevated pulmonary vascular resistance in PAH-susceptible broilers to an anatomically inadequate pulmonary vascular capacity, to excessive vascular tone reflecting the dominance of pulmonary vasoconstrictors over vasodilators, and to vascular pathology elicited by excessive hemodynamic stress. Emerging evidence also demonstrates that the pathogenesis of PAH includes characteristics of an inflammatory/autoimmune disease involving multifactorial genetic, environmental, and immune system components. Pulmonary

  19. Treatment of pediatric pulmonary hypertension

    PubMed Central

    Hawkins, Amy; Tulloh, Robert

    2009-01-01

    Pulmonary hypertension was once thought to be a rare condition and only managed in specialized centers. Now however, with the advent of echocardiography, it is found in many clinical scenarios, in the neonate with chronic lung disease, in the acute setting in the intensive care unit, in connective tissue disease and in cardiology pre- and postoperatively. We have a better understanding of the pathological process and have a range of medication which is starting to be able to palliate this previously fatal condition. This review describes the areas that are known in this condition and those that are less familiar. The basic physiology behind pulmonary hypertension and pulmonary vascular disease is explained. The histopathologic process and the various diagnostic tools are described and are followed by the current and future therapy at our disposal. PMID:19554091

  20. PULMONARY AND SYSTEMIC EFFECTS OF FOUR-WEEK DIESEL INHALATION IN HEALTHY AHD HYPERTENSIVE RATS

    EPA Science Inventory

    Diesel exhaust (DE) comprises a significant fraction of near road ambient particulate matter (PM). Exacerbated cardiac and pulmonary complications are noted in individuals residing near roadways. We examined pulmonary and systemic effects of diesel exhaust (DE) in healthy and hyp...

  1. Effects of Direct Renin Blockade on Renal & Systemic Hemodynamics and on RAAS Activity, in Weight Excess and Hypertension: A Randomized Clinical Trial

    PubMed Central

    Kwakernaak, A. J.; Roksnoer, L. C.; Lambers Heerspink, H. J.; van den Berg-Garrelds, I.; Lochorn, G. A.; van Embden Andres, J. H.; Klijn, M. A.; Kobori, H.; Danser, A. H. J.; Laverman, G. D.; Navis, G. J.

    2017-01-01

    Aim The combination of weight excess and hypertension significantly contributes to cardiovascular risk and progressive kidney damage. An unfavorable renal hemodynamic profile is thought to contribute to this increased risk and may be ameliorated by direct renin inhibition (DRI). The aim of this trial was to assess the effect of DRI on renal and systemic hemodynamics and on RAAS activity, in men with weight excess and hypertension. Methods A randomized, double-blind, cross-over clinical trial to determine the effect of DRI (aliskiren 300 mg/day), with angiotensin converting enzyme inhibition (ACEi; ramipril 10 mg/day) as a positive control, on renal and systemic hemodynamics, and on RAAS activity (n = 15). Results Mean (SEM) Glomerular filtration rate (101 (5) mL/min/1.73m2) remained unaffected by DRI or ACEi. Effective renal plasma flow (ERPF; 301 (14) mL/min/1.73m2) was increased in response to DRI (320 (14) mL/min/1.73m2, P = 0.012) and ACEi (317 (15) mL/min/1.73m2, P = 0.045). Filtration fraction (FF; 34 (0.8)%) was reduced by DRI only (32 (0.7)%, P = 0.044). Mean arterial pressure (109 (2) mmHg) was reduced by DRI (101 (2) mmHg, P = 0.008) and ACEi (103 (3) mmHg, P = 0.037). RAAS activity was reduced by DRI and ACEi. Albuminuria (20 [9–42] mg/d) was reduced by DRI only (12 [5–28] mg/d, P = 0.030). Conclusions In men with weight excess and hypertension, DRI and ACEi improved renal and systemic hemodynamics. Both DRI and ACEi reduced RAAS activity. Thus, DRI provides effective treatment in weight excess and hypertension. Trial Registration Dutch trial register, registration number: 2532 www.trialregister.nl PMID:28118402

  2. Mutation of SH2B3 (LNK), a genome-wide association study candidate for hypertension, attenuates Dahl salt-sensitive hypertension via inflammatory modulation.

    PubMed

    Rudemiller, Nathan P; Lund, Hayley; Priestley, Jessica R C; Endres, Bradley T; Prokop, Jeremy W; Jacob, Howard J; Geurts, Aron M; Cohen, Eric P; Mattson, David L

    2015-05-01

    Human genome-wide association studies have linked SH2B adaptor protein 3 (SH2B3, LNK) to hypertension and renal disease, although little experimental investigation has been performed to verify a role for SH2B3 in these pathologies. SH2B3, a member of the SH2B adaptor protein family, is an intracellular adaptor protein that functions as a negative regulator in many signaling pathways, including inflammatory signaling processes. To explore a mechanistic link between SH2B3 and hypertension, we targeted the SH2B3 gene for mutation on the Dahl salt-sensitive (SS) rat genetic background with zinc-finger nucleases. The resulting mutation was a 6-bp, in-frame deletion within a highly conserved region of the Src homology 2 (SH2) domain of SH2B3. This mutation significantly attenuated Dahl SS hypertension and renal disease. Also, infiltration of leukocytes into the kidneys, a key mediator of Dahl SS pathology, was significantly blunted in the Sh2b3(em1Mcwi) mutant rats. To determine whether this was because of differences in immune signaling, bone marrow transplant studies were performed in which Dahl SS and Sh2b3(em1Mcwi) mutants underwent total body irradiation and were then transplanted with Dahl SS or Sh2b3(em1Mcwi) mutant bone marrow. Rats that received Sh2b3(em1Mcwi) mutant bone marrow had a significant reduction in mean arterial pressure and kidney injury when placed on a high salt diet (4% NaCl). These data further support a role for the immune system as a modulator of disease severity in the pathogenesis of hypertension and provide insight into inflammatory mechanisms at play in human hypertension and renal disease.

  3. Progression of hypertension and kidney disease in aging fawn-hooded rats is mediated by enhanced influence of renin-angiotensin system and suppression of nitric oxide system and epoxyeicosanoids.

    PubMed

    Doleželová, Šárka; Jíchová, Šárka; Husková, Zuzana; Vojtíšková, Alžběta; Kujal, Petr; Hošková, Lenka; Kautzner, Josef; Sadowski, Janusz; Červenka, Luděk; Kopkan, Libor

    The fawn-hooded hypertensive (FHH) rat serves as a genetic model of spontaneous hypertension associated with glomerular hyperfiltration and proteinuria. However, the knowledge of the natural course of hypertension and kidney disease in FHH rats remains fragmentary and the underlying pathophysiological mechanisms are unclear. In this study, over the animals' lifetime, we followed the survival rate, blood pressure (telemetry), indices of kidney damage, the activity of renin-angiotensin (RAS) and nitric oxide (NO) systems, and CYP450-epoxygenase products (EETs). Compared to normotensive controls, no elevation of plasma and renal RAS was observed in prehypertensive and hypertensive FHH rats; however, RAS inhibition significantly reduced systolic blood pressure (137 ± 9 to 116 ± 8, and 159 ± 8 to 126 ± 4 mmHg, respectively) and proteinuria (62 ± 2 to 37 ± 3, and 132 ± 8 to 87 ± 5 mg/day, respectively). Moreover, pharmacological RAS inhibition reduced angiotensin (ANG) II and increased ANG 1-7 in the kidney and thereby may have delayed the progression of kidney disease. Furthermore, renal NO and EETs declined in the aging FHH rats but not in the control strain. The present results, especially the demonstration of exaggerated vascular responsiveness to ANG II, indicate that RAS may contribute to the development of hypertension and kidney disease in FHH rats. The activity of factors opposing the development of hypertension and protecting the kidney declined with age in this model. Therefore, therapeutic enhancement of this activity besides RAS inhibition could be attempted in the therapy of human hypertension associated with kidney disease.

  4. Racial Differences in Hypertension and Coronary Heart Disease in the U.S. Navy

    DTIC Science & Technology

    1983-12-01

    pressure are numerous and include changes in the kidneys, brain, heart and other major organs. At least three major types of vascular pathology are known...et al (29) which suggested that hypertension and coronary heart disease were different in their etiology and pathology . It was hypothesized that...blacks may be victimized more by infections and other pathologic processes in the genitourinary tract, processes which may lead to hypertensive disease

  5. Hypertensive Emergencies in Pregnancy.

    PubMed

    Olson-Chen, Courtney; Seligman, Neil S

    2016-01-01

    The prevalence of hypertensive disorders in pregnancy is increasing. The etiology and pathophysiology of hypertensive disorders in pregnancy remain poorly understood. Hypertensive disorders are a major cause of maternal and perinatal morbidity and mortality. Treatment of hypertension decreases the incidence of severe hypertension, but it does not impact rates of preeclampsia or other pregnancy complications. Several antihypertensive medications are commonly used in pregnancy, although there is a lack of randomized controlled trials. Severe hypertension should be treated immediately to prevent maternal end-organ damage. Appropriate antepartum, intrapartum, and postpartum management is important in caring for patients with hypertensive disorders.

  6. Regulation of the sympathetic nervous system by nitric oxide and oxidative stress in the rostral ventrolateral medulla: 2012 Academic Conference Award from the Japanese Society of Hypertension.

    PubMed

    Kishi, Takuya

    2013-10-01

    Sympathoexcitation has an important role in the pathogenesis of hypertension. Previous studies have demonstrated that nitric oxide (NO) and/or oxidative stress in the brain are important for the regulation of the sympathetic nervous system. We have investigated the role of NO derived from an overexpression of endothelial NO synthase (eNOS) or oxidative stress in the rostral ventrolateral medulla (RVLM), which is known as a vasomotor center in the brainstem, on the regulation of the sympathetic nervous system. Our results indicated that NO derived from an overexpression of eNOS in the RVLM caused sympathoinhibition via an increase in γ-amino butyric acid and that angiotensin II type 1 receptor (AT1R)-induced oxidative stress in the RVLM caused sympathoexcitation. We also demonstrated that oxidative stress in the RVLM caused sympathoexcitation via interactions with NO, effects on the signal transduction or apoptosis of the astrocytes. Furthermore, several orally administered AT1R blockers have been found to cause sympathoinhibition via a reduction in oxidative stress through the blockade of AT1R in the RVLM of hypertensive rats. In conclusion, our studies suggest that the increase in AT1R-induced oxidative stress and/or the decrease in NO in the RVLM mainly cause sympathoexcitation in hypertension.

  7. Systemic and Pulmonary Hypertension After Resuscitation with Cell-Free Hemoglobin

    DTIC Science & Technology

    1992-07-01

    according to published standards (24). Inorganic phosphate was measured on a blood chemistry analyzer (Cobas-Fara; Roche Diagnostic Systems, Nutley, NJ...alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) on the blood chemistry analyzer . The final 4 ml of blood was heparinized, centrifuged...milliliter of blood was placed in 2 ml of ice-cold perchioric acid (70% wt/vol), which was used to determine whole blood lactate in the blood chemistry

  8. The rise of governmentality in the Italian National Health System: physiology or pathology of a decentralized and (ongoing) federalist system?

    PubMed

    Lega, Federico; Sargiacomo, Massimo; Ianni, Luca

    2010-11-01

    In this paper, we aim to discuss the implications and lessons that can be learnt from the ongoing process of federalism affecting the Italian National Health System (INHS). Many countries are currently taking decisions concerning the decentralization or re-centralization of their health-care systems, with several key issues that are illustrated in the recent history of the INHS. The decentralization process of INHS has produced mixed results, as some regions took advantage of it to strengthen their systems, whereas others were not capable of developing an effective steering role. We argue that the mutual reinforcement of the decentralization and recentralization processes is not paradoxical, but is actually an effective way for the State to maintain control over the equity and efficiency of its health-care system while decentralizing at a regional level. In this perspective, we provide evidence backing up some of the assumptions made in previous works as well as new food-for thought - specifically on how governmentality and federalism should meet - to reshape the debate on decentralization in health care.

  9. Current Perspectives on Systemic Hypertension in Heart Failure with Preserved Ejection Fraction.

    PubMed

    Tam, Marty C; Lee, Ran; Cascino, Thomas M; Konerman, Matthew C; Hummel, Scott L

    2017-02-01

    Heart failure with preserved ejection fraction (HFpEF) is a prevalent but incompletely understood syndrome. Traditional models of HFpEF pathophysiology revolve around systemic HTN and other causes of increased left ventricular afterload leading to left ventricular hypertrophy (LVH) and diastolic dysfunction. However, emerging models attribute the development of HFpEF to systemic proinflammatory changes secondary to common comorbidities which include HTN. Alterations in passive ventricular stiffness, ventricular-arterial coupling, peripheral microvascular function, systolic reserve, and chronotropic response occur. As a result, HFpEF is heterogeneous in nature, making it difficult to prescribe uniform therapies to all patients. Nonetheless, treating systemic HTN remains a cornerstone of HFpEF management. Antihypertensive therapies have been linked to LVH regression and improvement in diastolic dysfunction. However, to date, no therapies have definitive mortality benefit in HFpEF. Non-pharmacologic management for HTN, including dietary modification, exercise, and treating sleep disordered breathing, may provide some morbidity benefit in the HFpEF population. Future research is need to identify effective treatments, perhaps in more specific subgroups, and focus may need to shift from reducing mortality to improving exercise capacity and symptoms. Tailoring antihypertensive therapies to specific phenotypes of HFpEF may be an important component of this strategy.

  10. Severe paroxysmal hypertension (pseudopheochromocytoma).

    PubMed

    Mann, Samuel J

    2008-02-01

    Paroxysmal hypertension always engenders a search for a catecholamine-secreting pheochromocytoma. Yet 98% of people with paroxysmal hypertension do not have this tumor. The cause and management of paroxysmal hypertension remain a mystery, and the subject of remarkably few papers. This review presents an approach to understanding and successfully treating this disorder. Patients experience symptomatic blood pressure surges likely linked to sympathetic nervous system stimulation. A specific personality profile associated with this disorder suggests a psychological basis, attributable to repressed emotion related to prior emotional trauma or a repressive (nonemotional) coping style. Based on this understanding, three forms of intervention, alone or in combination, appear successful: antihypertensive therapy with agents directed at the sympathetically mediated blood pressure elevation (eg, combined alpha- and beta-blockade or central alpha-agonists such as clonidine); psychopharmacologic interventions including anxiolytic and/or antidepressant agents; and psychological intervention, particularly reassurance and increased psychological awareness. An appropriately selected intervention can reduce or eliminate attacks in most patients.

  11. Beta blockers in hypertension.

    PubMed

    Thadani, U

    1983-11-10

    Beta-adrenoceptor antagonists are effective in the management of patients with mild-to-moderate hypertension. Noncardioselective agents, cardioselective agents and beta blockers with intrinsic sympathomimetic activity (ISA) are equally effective, provided they are used in equipotent doses. Beta blockers can be used as first-line therapy in the management of hypertension and can be safely combined with diuretics, vasodilators, or both, for a better control of blood pressure. The exact mechanism by which beta blockers decrease blood pressure remains speculative, but they all reduce cardiac output during long-term therapy; drugs with ISA lower cardiac output and heart rate less than do drugs without ISA. Pharmacokinetic properties of beta blockers differ widely; drugs metabolized by the liver have shorter plasma half-lives than drugs primarily excreted by the kidneys. Although many of the side effects of various beta blockers are similar, differences in water and lipid solubility account for a higher incidence of central nervous system side effects with lipid-soluble drugs (such as propranolol and metoprolol) than with hydrophilic drugs (such as atenolol and timolol). The incidence of cold extremities has been reported to be less with drugs with ISA, and the incidence of bronchospasm less with cardioselective drugs. In the management of uncomplicated mild-to-moderate hypertension, all beta blockers are equally effective and produce less troublesome side effects than alternative antihypertensive agents. For effective therapy beta blockers can be used in 2 divided daily doses or even once daily.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Treprostinil for pulmonary hypertension

    PubMed Central

    Skoro-Sajer, Nika; Lang, Irene; Naeije, Robert

    2008-01-01

    Treprostinil is a stable, long-acting prostacyclin analogue which can be administered as a continuous subcutaneous infusion using a portable miniature delivery system. Subcutaneous treprostinil has been shown in a large multicenter randomized controlled trial to improve exercise capacity, clinical state, functional class, pulmonary hemodynamics, and quality of life in patients with pulmonary arterial hypertension, an uncommon disease of poor prognosis. Side effects include facial flush, headache, jaw pain, abdominal cramping, and diarrhea, all typical of prostacyclin, and manageable by symptom-directed dose adjustments, and infusion site pain which may make further treatment impossible in 7%–10% of the patients. Long-term survival in pulmonary arterial hypertension patients treated with subcutaneous treprostinil is similar to that reported with intravenous epoprostenol. There are uncontrolled data suggesting efficacy of subcutaneous treprostinil in chronic thromboembolic pulmonary hypertension. Treprostinil can also be administered intravenously, although increased doses, up to 2–3 times those given subcutaneously, appear to be needed to obtain the same efficacy. Preliminary results of a randomized controlled trial of inhaled treprostinil on top of bosentan and sildenafil therapies have shown significance on the primary endpoint, which was exercise capacity as assessed by the distance walked in 6 minutes. Trials of oral formulations of treprostinil have been initiated. PMID:18827901

  13. Obesity and hypertension

    PubMed Central

    Jiang, Shu-Zhong; Lu, Wen; Zong, Xue-Feng; Ruan, Hong-Yun; Liu, Yi

    2016-01-01

    The imbalance between energy intake and expenditure is the main cause of excessive overweight and obesity. Technically, obesity is defined as the abnormal accumulation of ≥20% of body fat, over the individual's ideal body weight. The latter constitutes the maximal healthful value for an individual that is calculated based chiefly on the height, age, build and degree of muscular development. However, obesity is diagnosed by measuring the weight in relation to the height of an individual, thereby determining or calculating the body mass index. The National Institutes of Health have defined 30 kg/m2 as the limit over which an individual is qualified as obese. Accordingly, the prevalence of obesity in on the increase in children and adults worldwide, despite World Health Organization warnings. The growth of obesity and the scale of associated health issues induce serious consequences for individuals and governmental health systems. Excessive overweight remains among the most neglected public health issues worldwide, while obesity is associated with increasing risks of disability, illness and death. Cardiovascular diseases, the leading cause of mortality worldwide, particularly hypertension and diabetes, are the main illnesses associated with obesity. Nevertheless, the mechanisms underlying obesity-associated hypertension or other associated metabolic diseases remains to be adequately investigated. In the present review, we addressed the association between obesity and cardiovascular disease, particularly the biological mechanisms linking obesity and hypertension. PMID:27703502

  14. Bacterial, Fungal, and Parasitic Infections of the Central Nervous System: Radiologic-Pathologic Correlation and Historical Perspectives.

    PubMed

    Shih, Robert Y; Koeller, Kelly K

    2015-01-01

    Despite remarkable progress in prevention and treatment, infectious diseases affecting the central nervous system remain an important source of morbidity and mortality, particularly in less-developed countries and in immunocompromised persons. Bacterial, fungal, and parasitic pathogens are derived from living organisms and affect the brain, spinal cord, or meninges. Infections due to these pathogens are associated with a variety of neuroimaging patterns that can be appreciated at magnetic resonance imaging in most cases. Bacterial infections, most often due to Streptococcus, Haemophilus, and Neisseria species, cause significant meningitis, whereas the less common cerebritis and subsequent abscess formation have well-documented progression, with increasingly prominent altered signal intensity and corresponding contrast enhancement. Atypical bacterial infections are characterized by the development of a granulomatous response, classically seen in tuberculosis, in which the tuberculoma is the most common parenchymal form of the disease; spirochetal and rickettsial diseases are less common. Fungal infections predominate in immunocompromised hosts and are caused by yeasts, molds, and dimorphic fungi. Cryptococcal meningitis is the most common fungal infection, whereas candidiasis is the most common nosocomial infection. Mucormycosis and aspergillosis are characterized by angioinvasiveness and are associated with high morbidity and mortality among immunocompromised patients. In terms of potential exposure in the worldwide population, parasitic infections, including neurocysticercosis, toxoplasmosis, echinococcosis, malaria, and schistosomiasis, are the greatest threat. Rare amebic infections are noteworthy for their extreme virulence and high mortality. The objective of this article is to highlight the characteristic neuroimaging manifestations of bacterial, fungal, and parasitic diseases, with emphasis on radiologic-pathologic correlation and historical perspectives.

  15. [Hypertensive crisis: urgency and hypertensive emergency].

    PubMed

    Sobrino Martínez, Javier; Doménech Feria-Carot, Mónica; Morales Salinas, Alberto; Coca Payeras, Antonia

    2016-11-18

    Hypertensive crises lumped several clinical situations with different seriousness and prognosis. The differences between hypertensive urgency and hypertensive emergency depends on if this situation involves a vital risk for the patient. This risk is defined more by the severity of the organ damage than for the higher values of blood pressure. The hypertensive urgency not involves an immediately risk for the patient, for these reason, the treatment can be completed after discharged. Otherwise, the hypertensive emergency is a critical clinical condition that requires hospital assistance. Faced with a patient, with severe hypertension, asymptomatic or with unspecific symptoms we must be careful. First, we need to confirm the values of blood pressure, with several measures of blood pressure and investigate and treat factors, which triggered this situation. The objective of medical treatment for hypertensive urgency is to reduce blood pressure values (at least 20% of baseline values) but to avoid sudden reduction of these values. In hypertensive urgencies rapid acting drug should not be used because of the risk of ischemic stroke and use drugs with longer half-life. The cardiovascular risk of these patients is higher than that do not suffer hypertensive crisis. The treatment must be personalized in each hypertensive emergency and intravenous it’s the best route to treat these patients.

  16. Evaluating factors influencing screening for pulmonary hypertension in systemic sclerosis: does disparity between available guidelines influence clinical practice?

    PubMed

    Pauling, John D; McHugh, Neil J

    2012-02-01

    Pulmonary arterial hypertension (PAH) is one of the leading causes of mortality in systemic sclerosis (SSc). We audited adherence with available recommendations regarding cardiopulmonary screening for PAH in SSc and explored potential factors influencing clinical practice. A retrospective case note review of 108 patients with SSc who had attended outpatient clinic over the previous year was undertaken. Records were scrutinised for evidence of previous assessment with trans-thoracic echocardiography (TTE) and pulmonary function tests (PFT), along with information regarding clinical phenotype and serological subset. The proportion of patients for whom screening had been undertaken within the previous 12 months was low, with significantly fewer having TTE compared with PFT assessment (34.7% vs. 53.1%, p = 0.014). The majority of patients had undergone TTE and PFT assessment within the previous 2 years, but a lower proportion had undergone TTE compared with PFT (69.4% vs. 82.7%, p = 0.044). There were strong trends for more frequent PFT assessment in younger patients, limited cutaneous SSc and worse previous PFT results. In contrast, the frequency of TTE assessment was not associated with previous investigation results or disease subtype. Serological profile did not influence the frequency of either TTE or PFT assessments. Disparity between available published guidelines may influence both the frequency and preference of PAH screening in SSc in clinical practice. The higher frequency of PFT assessment might reflect a perceived superiority amongst clinicians of PFT over TTE in the early identification of SSc-PAH. SSc-specific guidelines, possibly incorporating additional independent risk factors, may improve the cost-effectiveness and clinical efficacy of screening recommendations designed to ensure the early identification of PAH in patients with SSc.

  17. Interstitial lung disease increases mortality in systemic sclerosis patients with pulmonary arterial hypertension without affecting hemodynamics and exercise capacity.

    PubMed

    Michelfelder, M; Becker, M; Riedlinger, A; Siegert, E; Drömann, D; Yu, X; Petersen, F; Riemekasten, G

    2017-02-01

    Published data suggest that coexisting interstitial lung disease (ILD) has an impact on mortality in patients with systemic sclerosis (SSc) and pulmonary arterial hypertension (PAH), but there is scarce knowledge if this is reflected by hemodynamics, exercise capacity, autoantibody profile, or pulmonary function. In this partially retrospective study, 27 SSc-PAH patients were compared to 24 SSc-PAH patients with coexisting ILD respecting to survival, pulmonary function, hemodynamics, exercise capacity, and laboratory parameters. Survival was significantly worse in SSc-PAH-ILD patients than in SSc patients with isolated PAH (1, 5, and 10-year survival rates 86, 54, and 54% versus 96, 92, and 82%, p = 0.013). Compared to isolated SSc-PAH patients, patients with SSc-PAH-ILD revealed lower forced expiratory volume after 1 s (FEV1) values at the time of PAH diagnosis as well as 1 and 2 years later (p = 0.002) without significant decrease in the PAH course in both groups. At PAH diagnosis, diffusion capacity for carbon monoxide (DLCO) values were lower in the ILD-PAH group. Coexisting ILD was not associated with lower exercise capacity, different FEV1/forced vital capacity (FVC) ratio, higher WHO functional class, or reduced hemodynamics. Higher levels of antibodies against angiotensin and endothelin receptors predict mortality in all SSc-PAH patients but could not differentiate between PAH patients with and without ILD. Our study confirmed an impact of ILD on mortality in SSc-PAH patients. Pulmonary function parameters can be used to distinguish PAH from PAH-ILD. The higher mortality rate cannot be explained by differences in hemodynamics, exercise capacity, or autoantibody levels. Mechanisms of mortality remain to be studied.

  18. Automated Cancer Registry Notifications: Validation of a Medical Text Analytics System for Identifying Patients with Cancer from a State-Wide Pathology Repository

    PubMed Central

    Nguyen, Anthony N; Moore, Julie; O'Dwyer, John; Philpot, Shoni

    2016-01-01

    The paper assesses the utility of Medtex on automating Cancer Registry notifications from narrative histology and cytology reports from the Queensland state-wide pathology information system. A corpus of 45.3 million pathology HL7 messages (including 119,581 histology and cytology reports) from a Queensland pathology repository for the year of 2009 was analysed by Medtex for cancer notification. Reports analysed by Medtex were consolidated at a patient level and compared against patients with notifiable cancers from the Queensland Oncology Repository (QOR). A stratified random sample of 1,000 patients was manually reviewed by a cancer clinical coder to analyse agreements and discrepancies. Sensitivity of 96.5% (95% confidence interval: 94.5-97.8%), specificity of 96.5% (95.3-97.4%) and positive predictive value of 83.7% (79.6-86.8%) were achieved for identifying cancer notifiable patients. Medtex achieved high sensitivity and specificity across the breadth of cancers, report types, pathology laboratories and pathologists throughout the State of Queensland. The high sensitivity also resulted in the identification of cancer patients that were not found in the QOR. High sensitivity was at the expense of positive predictive value; however, these cases may be considered as lower priority to Cancer Registries as they can be quickly reviewed. Error analysis revealed that system errors tended to be tumour stream dependent. Medtex is proving to be a promising medical text analytic system. High value cancer information can be generated through intelligent data classification and extraction on large volumes of unstructured pathology reports. PMID:28269893

  19. Automated Cancer Registry Notifications: Validation of a Medical Text Analytics System for Identifying Patients with Cancer from a State-Wide Pathology Repository.

    PubMed

    Nguyen, Anthony N; Moore, Julie; O'Dwyer, John; Philpot, Shoni

    2016-01-01

    The paper assesses the utility of Medtex on automating Cancer Registry notifications from narrative histology and cytology reports from the Queensland state-wide pathology information system. A corpus of 45.3 million pathology HL7 messages (including 119,581 histology and cytology reports) from a Queensland pathology repository for the year of 2009 was analysed by Medtex for cancer notification. Reports analysed by Medtex were consolidated at a patient level and compared against patients with notifiable cancers from the Queensland Oncology Repository (QOR). A stratified random sample of 1,000 patients was manually reviewed by a cancer clinical coder to analyse agreements and discrepancies. Sensitivity of 96.5% (95% confidence interval: 94.5-97.8%), specificity of 96.5% (95.3-97.4%) and positive predictive value of 83.7% (79.6-86.8%) were achieved for identifying cancer notifiable patients. Medtex achieved high sensitivity and specificity across the breadth of cancers, report types, pathology laboratories and pathologists throughout the State of Queensland. The high sensitivity also resulted in the identification of cancer patients that were not found in the QOR. High sensitivity was at the expense of positive predictive value; however, these cases may be considered as lower priority to Cancer Registries as they can be quickly reviewed. Error analysis revealed that system errors tended to be tumour stream dependent. Medtex is proving to be a promising medical text analytic system. High value cancer information can be generated through intelligent data classification and extraction on large volumes of unstructured pathology reports.

  20. Influence of Physical Activity on Hypertension and Cardiac Structure and Function.

    PubMed

    Hegde, Sheila M; Solomon, Scott D

    2015-10-01

    The global burden of hypertension is rising and accounts for substantial morbidity and mortality. Lifestyle factors such as diet and physical inactivity contribute to this burden, further highlighting the need for prevention efforts to curb this public health epidemic. Regular physical activity is associated with lower blood pressure, reduced cardiovascular risk, and cardiac remodeling. While exercise and hypertension can both be associated with the development of left ventricular hypertrophy (LVH), the cardiac remodeling from hypertension is pathologic with an associated increase in myocyte hypertrophy, fibrosis, and risk of heart failure and mortality, whereas LVH in athletes is generally non-pathologic and lacks the fibrosis seen in hypertension. In hypertensive patients, physical activity has been associated with paradoxical regression or prevention of LVH, suggesting a mechanism by which exercise can benefit hypertensive patients. Further studies are needed to better understand the mechanisms underlying the benefits of physical activity in the hypertensive heart.

  1. Influence of Physical Activity on Hypertension and Cardiac Structure and Function

    PubMed Central

    Hegde, Sheila M.; Solomon, Scott D.

    2015-01-01

    The global burden of hypertension is rising and accounts for substantial morbidity and mortality. Lifestyle factors such as diet and physical inactivity contribute to this burden, further highlighting the need for prevention efforts to curb this public health epidemic. Regular physical activity is associated with lower blood pressure, reduced cardiovascular risk, and cardiac remodeling. While exercise and hypertension can both be associated with the development of left ventricular hypertrophy (LVH), the cardiac remodeling from hypertension is pathologic with an associated increase in myocyte hypertrophy, fibrosis, and risk of heart failure and mortality, whereas LVH in athletes is generally non-pathologic and lacks the fibrosis seen in hypertension. In hypertensive patients, physical activity has been associated with paradoxical regression or prevention of LVH, suggesting a mechanism by which exercise can benefit hypertensive patients. Further studies are needed to better understand the mechanisms underlying the benefits of physical activity in the hypertensive heart. PMID:26277725

  2. Effects of aqueous extract of Hibiscus sabdariffa on the renin-angiotensin-aldosterone system of Nigerians with mild to moderate essential hypertension: A comparative study with lisinopril

    PubMed Central

    Nwachukwu, Daniel Chukwu; Aneke, Eddy Ikemefuna; Obika, Leonard Fidelis; Nwachukwu, Nkiru Zuada

    2015-01-01

    Objectives: The present study investigated the effects of aqueous extract of Hibiscus sabdariffa (HS) on the three basic components of renin-angiotensin-aldosterone system: Plasma renin, serum angiotensin-converting enzyme (ACE), and plasma aldosterone (PA) in mild to moderate essential hypertensive Nigerians and compared with that of lisinopril, an ACE inhibitor. Materials and Methods: A double-blind controlled randomized clinical study was used. Seventy-eight newly diagnosed but untreated mild to moderate hypertensive subjects attending Medical Outpatients Clinic of Enugu State University Teaching Hospital, Enugu were recruited for the study. Those in Group A received placebo (150 mg/kg/day), Group B were given lisinopril (10 mg once daily) while those in Group C received aqueous extract of HS (150 mg/kg/day). After 4 weeks of treatment, the levels of plasma renin, serum ACE, and PA were determined. Results: HS and lisinopril significantly (P < 0.001) reduced PA compared to placebo by 32.06% and 30.01%, respectively. Their effects on serum ACE and plasma renin activity (PRA) were not significant compared to placebo; they reduced ACE by 6.63% and 5.67% but increased plasma PRA by 2.77% and 5.36%, respectively. Conclusion: HS reduced serum ACE and PA in mild to moderate hypertensive Nigerians with equal efficacy as lisinopril. These actions are possibly due to the presence of anthocyanins in the extract. PMID:26600645

  3. Prenatal inflammation-induced NF-κB dyshomeostasis contributes to renin-angiotensin system over-activity resulting in prenatally programmed hypertension in offspring

    PubMed Central

    Deng, Youcai; Deng, Yafei; He, Xiaoyan; Chu, Jianhong; Zhou, Jianzhi; Zhang, Qi; Guo, Wei; Huang, Pei; Guan, Xiao; Tang, Yuan; Wei, Yanling; Zhao, Shanyu; Zhang, Xingxing; Wei, Chiming; Namaka, Michael; Yi, Ping; Yu, Jianhua; Li, Xiaohui

    2016-01-01

    Studies involving the use of prenatally programmed hypertension have been shown to potentially contribute to prevention of essential hypertension (EH). Our previous research has demonstrated that prenatal inflammatory stimulation leads to offspring’s aortic dysfunction and hypertension in pregnant Sprague-Dawley rats challenged with lipopolysaccharide (LPS). The present study found that prenatal LPS exposure led to NF-κB dyshomeostasis from fetus to adult, which was characterized by PI3K-Akt activation mediated degradation of IκBα protein and impaired NF-κB self-negative feedback loop mediated less newly synthesis of IκBα mRNA in thoracic aortas (gestational day 20, postnatal week 7 and 16). Prenatal or postnatal exposure of the IκBα degradation inhibitor, pyrollidine dithiocarbamate, effectively blocked NF-κB activation, endothelium dysfunction, and renin-angiotensin system (RAS) over-activity in thoracic aortas, resulting in reduced blood pressure in offspring that received prenatal exposure to LPS. Surprisingly, NF-κB dyshomeostasis and RAS over-activity were only found in thoracic aortas but not in superior mesenteric arteries. Collectively, our data demonstrate that the early life NF-κB dyshomeostasis induced by prenatal inflammatory exposure plays an essential role in the development of EH through triggering RAS over-activity. We conclude that early life NF-κB dyshomeostasis is a key predictor of EH, and thus, NF-κB inhibition represents an effective interventional strategy for EH prevention. PMID:26877256

  4. Application of global positioning system methods for the study of obesity and hypertension risk among low-income housing residents in New York City: a spatial feasibility study.

    PubMed

    Duncan, Dustin T; Regan, Seann D; Shelley, Donna; Day, Kristen; Ruff, Ryan R; Al-Bayan, Maliyhah; Elbel, Brian

    2014-11-01

    The purpose of this study was to evaluate the feasibility of using global positioning system (GPS) methods to understand the spatial context of obesity and hypertension risk among a sample of low-income housing residents in New York City (n = 120). GPS feasibility among participants was measured with a pre- and post-survey as well as adherence to a protocol which included returning the GPS device as well as objective data analysed from the GPS devices. We also conducted qualitative interviews with 21 of the participants. Most of the sample was overweight (26.7%) or obese (40.0%). Almost one-third (30.8%) was pre-hypertensive and 39.2% was hypertensive. Participants reported high ratings of GPS acceptability, ease of use and low levels of wear-related concerns in addition to few concerns related to safety, loss or appearance, which were maintained after the baseline GPS feasibility data collection. Results show that GPS feasibility increased over time. The overall GPS return rate was 95.6%. Out of the total of 114 participants with GPS, 112 (98.2%) delivered at least one hour of GPS data for one day and 84 (73.7%) delivered at least one hour on 7 or more days. The qualitative interviews indicated that overall, participants enjoyed wearing the GPS devices, that they were easy to use and charge and that they generally forgot about the GPS device when wearing it daily. Findings demonstrate that GPS devices may be used in spatial epidemiology research in low-income and potentially other key vulnerable populations to understand geospatial determinants of obesity, hypertension and other diseases that these populations disproportionately experience.

  5. Application of global positioning system methods for the study of obesity and hypertension risk among low-income housing residents in New York City: a spatial feasibility study

    PubMed Central

    Duncan, Dustin T.; Regan, Seann D.; Shelley, Donna; Day, Kristen; Ruff, Ryan R.; Al-Bayan, Maliyhah; Elbel, Brian

    2016-01-01

    The purpose of this study was to evaluate the feasibility of using global positioning system (GPS) methods to understand the spatial context of obesity and hypertension risk among a sample of low-income housing residents in New York City (n = 120). GPS feasibility among participants was measured with a pre- and post-survey as well as adherence to a protocol which included returning the GPS device as well as objective data analysed from the GPS devices. We also conducted qualitative interviews with 21 of the participants. Most of the sample was overweight (26.7%) or obese (40.0%). Almost one-third (30.8%) was pre-hypertensive and 39.2% was hypertensive. Participants reported high ratings of GPS acceptability, ease of use and low levels of wear-related concerns in addition to few concerns related to safety, loss or appearance, which were maintained after the baseline GPS feasibility data collection. Results show that GPS feasibility increased over time. The overall GPS return rate was 95.6%. Out of the total of 114 participants with GPS, 112 (98.2%) delivered at least one hour of GPS data for one day and 84 (73.7%) delivered at least one hour on 7 or more days. The qualitative interviews indicated that overall, participants enjoyed wearing the GPS devices, that they were easy to use and charge and that they generally forgot about the GPS device when wearing it daily. Findings demonstrate that GPS devices may be used in spatial epidemiology research in low-income and potentially other key vulnerable populations to understand geospatial determinants of obesity, hypertension and other diseases that these populations disproportionately experience. PMID:25545926

  6. [CLINICAL AND BIOCHEMICAL CHARACTERISTICS OF DISORDERS OF THE NERVOUS SYSTEM AND THE RISKS OF COMMON PATHOLOGICAL SYNDROMES IN MERCURY PRODUCTION WORKERS].

    PubMed

    Kudaeva, I V; Dyakovich, O A; Katamanova, E V; Popkova, O V; Masnavieva, L B

    2015-01-01

    The occupational factors are assigned one out of main parts to the development of occupational and comorbid pathology. At the same time the social aspects of labor relations act as the most important factors influencing on the workers' self-assessment of health status. Quantitative risk assessment of the common pathological syndromes has identified the excess of share of persons with a minimum level of risk over the medium and high. In the structure of risks of common pathological syndromes there are prevailed risks for disorders of the cardiovascular and nervous systems and borderline mental disorders, which is a response to the impact of not only industrial, but also psychosocial factors. The results of self-assessment of health status and clinical examination of employees in conditions of mercury exposure show the similarity of the structure of diseases in these cases. In either event there are dominated diseases of the nervous and mental sphere, and from the comorbid pathology disorders of the cardiovascular system are prove to be important. Clinical manifestations of the mercury exposure, ranging from pre-clinical manifestations to marked changes from the side of the nervous system in toxic encephalopathy, are characterized by the presence of hyperkinetic syndrome. For pre-clinical and early forms of mercury poisoning there is also typical the presence of asthenic (emotional lability) disorders with autonomic dysfunction. Comorbidities in an internship working was manifested primarily by diseases of visual organs, cardiovascular system and diseases of the musculoskeletal system. Observed disorders of the nervous system and psycho-emotional sphere are caused, inter alia disturbances of the balance of catecholamines (the rise of norepinephrine in dynamics with a concomitant increase in the coefficient reflecting the degree of its metabolism: norepinephrine/epinephrine and norepinephrine/(adrenaline + Normetanephrine)) in the body.

  7. Systemic Hypertension and Transient Ischemic Attack in a 6-Year-Old Girl with Fibromuscular Dysplasia Treated with Percutaneous Angioplasty

    SciTech Connect

    Foa-Torres, Gustavo; Ganame, Javier; Juaneda, Ernesto; Peirone, Alejandro; Barcudi, Maria Silvina; Achaval, Alberto

    2010-02-15

    We describe a 6-year-old girl with arterial hypertension secondary to fibromuscular dysplasia with stenoses of both renal arteries and transient ischemic attack due to extracranial right internal carotid artery subtotal occlusion as well as left internal carotid artery stenosis. She was treated with percutaneous angioplasty of both renal and both carotid arteries.

  8. Influence of Diastolic Blood Pressure on Glaucoma Progression in Glaucoma Patients with Systemic Hypertension.

    PubMed

    Suić, Smiljka Popović; Skegro, Ivan; Jandroković, Sonja; Kordić, Rajko; Kutija, Maria Barisić

    2015-09-01

    The aim of this study is to determine relationship between glaucoma progression and diastolic blood pressure. It was conducted on 64 glaucoma patients at the Department of Ophthalmology of Clinical Hospital Centre Zagreb in three years period. The patients were on anti glaucoma therapy and had mean intraocular pressure values under 20 mmHg. At the same time they were on antihypertensive drug therapy. Patients were classified according Glaucoma Staging System based on the perimetric indices mean deviation (MD) and Pattern Standard Deviation into stage 2-4 (moderate glaucoma) at baseline. Rate of visual field progression was calculated in db/year for MD in the last three visits. Patients were divided in 3 groups according to progression--stabile, moderate and progressive. There was no statistically significant difference between 3 groups in terms of intraocular pressure values at baseline and in follow up period. After reviewing their blood pressure, the progressive group showed a significantly lower diastolic blood pressure compared to both stable group and the group with moderate progression. There was no statistical difference between the group with moderate progression and the stable group in terms of diastolic blood pressure. Results suggest that greater risk of glaucoma progression is connected with lower diastolic blood pressure. Diastolic pressure values could be important as one of the risk factors for progression in glaucoma patients with controlled intraocular pressure values.

  9. Pharmacokinetics and anti-hypertensive effect of metoprolol tartrate rectal delivery system.

    PubMed

    Abou el Ela, Amal El Sayeh F; Allam, Ayat A; Ibrahim, Ehsan H

    2016-01-01

    The main aim of this work was to develop rectal suppositories for better delivery of metoprolol tartrate (MT). The various bases used were fatty, water soluble and emulsion bases. The physical properties of the prepared suppositories were characterized such as weight variation, hardness, disintegration time, melting range and the drug content uniformity. The in vitro release of MT from the prepared suppositories was carried out. The evaluation of the pharmacological effects of MT on the blood pressure and heart rate of the healthy rabbits after the rectal administration compared to the oral tablets was studied. Moreover, the formulation with the highest in vitro release and the highest pharmacological effects would be selected for a further pharmacokinetics study compared to the oral tablets. The results revealed that the emulsion bases gave the highest rate of the drug release than the other bases used. The reduction effect of the emulsion MT suppository base on the blood pressure and heart rate was found to be faster and greater than that administered orally. The selected emulsion suppository base (F11) showed a significant increase in the AUC (1.88-fold) in rabbits as compared to the oral tablets. From the above results we can conclude that rectal route can serve as an efficient alternative route to the oral one for systemic delivery of MT which may be due to the avoidance of first-pass effect in the liver.

  10. Resistant hypertension and the Birmingham Hypertension Square.

    PubMed

    Felmeden, D C; Lip, G Y

    2001-06-01

    Recent guidelines for the treatment of hypertension place great emphasis on tighter blood pressure control, especially in the presence of hypertensive target organ damage and diabetes. In order to achieve these treatment targets, more patients will require a combination of antihypertensive medications. However, resistant hypertension may have many possible underlying causes, and clinicians should appreciate how to detect and tackle these potential problems. Effective and synergistic combinations are therefore of vital importance, especially in patients with resistant hypertension. The choice of rational first- and second-line drugs that act in synergy could lead to better blood pressure management as well as significant financial savings for health care resources. The use of the Birmingham Hypertension Square for the optimum choice of add-in drugs for the treatment of resistant hypertension may aid management.

  11. Hypertension in the liver clinic - polyarteritis nodosa in a patient with hepatitis B

    PubMed Central

    Laroia, Shalini Thapar; Lata, Suman

    2016-01-01

    Chronic hepatitis caused by hepatitis B virus (HBV) is an endemic disease in India. It is associated with extrahepatic manifestations like polyarteritis nodosa (PAN) which is a vasculitis like disorder, presenting in subacute or chronic phase; involving visceral and systemic vessels. It should always be considered as a possible etiology of hypertension in an underlying setting of hepatitis B. We describe a 56-year-male patient with a history of chronic HBV who presented to the outpatient clinic with history of recent onset hypertension and suspected liver disease. Further work up for the cause of recent hypertension included a contrast computerized tomography of abdomen, which revealed concomitant pathologies of chronic liver disease and multiple aneurysms in bilateral kidneys. This case illustrates the unusual presentation of extrahepatic manifestation of viral hepatitis in the form of PAN of kidneys. PAN as an independent entity may be missed in specialized clinics evaluating liver pathologies, due to its insidious onset, atypical clinical symptoms and multi-systemic manifestations. The knowledge of extrahepatic, renal and vascular manifestations of hepatitis B unrelated to liver disease should be considered by physicians at the time of diagnosis and management of patients with HBV. PMID:26989675

  12. [The pneumoperitoneum course forecasting and surgery tactic in the group of patients with acute and chronic cholecystitis and concomitant pathology of cardiovascular system].

    PubMed

    Korotkyĭ, V M; Soliaryk, S O; Tsyganok, A M; Sysak, O M

    2012-01-01

    The share of elderly and senile patients with acute cholecystitis concomitant cardiovascular pathology whom the laparoscopic cholecystectomy has been provided is increased. The heightened intraabdominal pressure has negative influence at the cardiovascular system, so the alternative ways for treatment of this group of patients are used in clinic. We propose the pneumoperitoneum model using the pneumatic belt which is fixed at the abdomen in preoperative period in patients with an acute and chronic cholecystitis. This model is useful to forecast cardiovascular disorders during future laparoscopic cholecystectomy. The arterial pressure level, pulse score and ECG are monitored during the test (90 min). Myocardial ischemia appearance seems that the risk of laparoscopic cholecystectomy with pneumoperitoneum is high. The alternative method of surgery in such group of patients (no pneumoperitoneum is applied) is laparoscopic assisted cholecystectomya from miniaccess. This method allows to reducing frequency of intra- and postoperative complications connected with pneumoperitoneum negative influence at the patients with concomitant pathology of cardiovascular system.

  13. Role of Endogenous Sulfur Dioxide in Regulating Vascular Structural Remodeling in Hypertension

    PubMed Central

    Chen, Selena; Tang, Chaoshu

    2016-01-01

    Sulfur dioxide (SO2), an emerging gasotransmitter, was discovered to be endogenously generated in the cardiovascular system. Recently, the physiological effects of endogenous SO2 were confirmed. Vascular structural remodeling (VSR), an important pathological change in many cardiovascular diseases, plays a crucial role in the pathogenesis of the diseases. Here, the authors reviewed the research progress of endogenous SO2 in regulating VSR by searching the relevant data from PubMed and Medline. In spontaneously hypertensive rats (SHRs) and pulmonary hypertensive rats, SO2/aspartate aminotransferase (AAT) pathway was significantly altered. SO2 inhibited vascular smooth muscle cell (VSMC) proliferation, promoted apoptosis, inhibited the synthesis of extracellular collagen but promoted its degradation, and enhanced antioxidative capacity, thereby playing a significant role in attenuating VSR. However, the detailed mechanisms needed to be further explored. Further studies in this field would be important for the better understanding of the pathogenesis of systemic hypertension and pulmonary hypertension. Also, clinical trials are needed to demonstrate if SO2 would be a potential therapeutic target in cardiovascular diseases. PMID:27721913

  14. Cortical and white matter mapping in the visual system-more than meets the eye: on the importance of functional imaging to understand visual system pathologies

    PubMed Central

    Raz, Noa; Levin, Netta

    2014-01-01

    Information transmission within the visual system is highly organized with the ultimate goal of accomplishing higher-order, complex visuo-spatial and object identity processing. Perception is dependent on the intactness of the entire system and damage at each stage—in the eye itself, the visual pathways, or within cortical processing—might result in perception disturbance. Herein we will review several examples of lesions along the visual system, from the retina, via the optic nerve and chiasm and through the occipital cortex. We will address their clinical manifestation and their cortical substrate. The latter will be studied via functional magnetic resonance imaging (fMRI) and Diffusion Tensor Imaging (DTI), enabling cortical, and white matter mapping of the human brain. In contrast to traditional signal recording, these procedures enable simultaneous evaluation of the entire brain network engaged when subjects undertake a particular task or evaluate the entirety of associated white matter pathways. These examples provided will highlight the importance of using advanced imaging methods to better understand visual pathologies. We will argue that clinical manifestation cannot always be explained solely by structural damage and a functional view is required to understand the clinical symptom. In such cases we recommend using advanced imaging methods to better understand the neurological basis of visual phenomena. PMID:25221482

  15. Cortical and white matter mapping in the visual system-more than meets the eye: on the importance of functional imaging to understand visual system pathologies.

    PubMed

    Raz, Noa; Levin, Netta

    2014-01-01

    Information transmission within the visual system is highly organized with the ultimate goal of accomplishing higher-order, complex visuo-spatial and object identity processing. Perception is dependent on the intactness of the entire system and damage at each stage-in the eye itself, the visual pathways, or within cortical processing-might result in perception disturbance. Herein we will review several examples of lesions along the visual system, from the retina, via the optic nerve and chiasm and through the occipital cortex. We will address their clinical manifestation and their cortical substrate. The latter will be studied via functional magnetic resonance imaging (fMRI) and Diffusion Tensor Imaging (DTI), enabling cortical, and white matter mapping of the human brain. In contrast to traditional signal recording, these procedures enable simultaneous evaluation of the entire brain network engaged when subjects undertake a particular task or evaluate the entirety of associated white matter pathways. These examples provided will highlight the importance of using advanced imaging methods to better understand visual pathologies. We will argue that clinical manifestation cannot always be explained solely by structural damage and a functional view is required to understand the clinical symptom. In such cases we recommend using advanced imaging methods to better understand the neurological basis of visual phenomena.

  16. Hotel Housekeeping Work Influences on Hypertension Management

    PubMed Central

    Sanon, Marie-Anne

    2013-01-01

    Background Characteristics of hotel housekeeping work increase the risk for hypertension development. Little is known about the influences of such work on hypertension management. Methods For this qualitative study, 27 Haitian immigrant hotel housekeepers from Miami-Dade County, FL were interviewed. Interview transcripts were analyzed with the assistance of the Atlas. ti software for code and theme identification. Results Influences of hotel housekeeping work on hypertension management arose both at the individual and system levels. Factors at the individual level included co-worker dynamics and maintenance of transmigrant life. Factors at the system level included supervisory support, workload, work pace, and work hiring practices. No positive influences were reported for workload and hiring practices. Conclusions Workplace interventions may be beneficial for effective hypertension management among hotel housekeepers. These work influences must be considered when determining effective methods for hypertension management among hotel housekeepers. PMID:23775918

  17. Pulmonary hypertension - at home

    MedlinePlus

    Pulmonary hypertension (PAH) is abnormally high blood pressure in the arteries of the lungs. With PAH, the right side ... Chin K, Channick RN. Pulmonary hypertension. In: Broaddus VC, Mason ... Textbook of Respiratory Medicine . 6th ed. Philadelphia, PA: ...

  18. Impact of Hypertension on Cognitive Function

    PubMed Central

    Iadecola, Costantino; Yaffe, Kristine; Biller, José; Bratzke, Lisa C.; Faraci, Frank M.; Gorelick, Philip B.; Gulati, Martha; Kamel, Hooman; Knopman, David S.; Launer, Lenore J.; Saczynski, Jane S.; Seshadri, Sudha; Zeki Al Hazzouri, Adina

    2017-01-01

    Background Age-related dementia, most commonly caused by Alzheimer disease or cerebrovascular factors (vascular dementia), is a major public health threat. Chronic arterial hypertension is a well-established risk factor for both types of dementia, but the link between hypertension and its treatment and cognition remains poorly understood. In this scientific statement, a multidisciplinary team of experts examines the impact of hypertension on cognition to assess the state of the knowledge, to identify gaps, and to provide future directions. Methods Authors with relevant expertise were selected to contribute to this statement in accordance with the American Heart Association conflict-of-interest management policy. Panel members were assigned topics relevant to their areas of expertise, reviewed the literature, and summarized the available data. Results Hypertension disrupts the structure and function of cerebral blood vessels, leads to ischemic damage of white matter regions critical for cognitive function, and may promote Alzheimer pathology. There is strong evidence of a deleterious influence of midlife hypertension on late-life cognitive function, but the cognitive impact of late-life hypertension is less clear. Observational studies demonstrated a cumulative effect of hypertension on cerebrovascular damage, but evidence from clinical trials that antihypertensive treatment improves cognition is not conclusive. Conclusions After carefully reviewing the literature, the group concluded that there were insufficient data to make evidence-based recommendations. However, judicious treatment of hypertension, taking into account goals of care and individual characteristics (eg, age and comorbidities), seems justified to safeguard vascular health and, as a consequence, brain health. PMID:27977393

  19. Correlation between propranolol in plasma and urine, renin-aldosterone system and blood pressure in essential hypertension.

    PubMed

    Pedersen, E B; Kornerup, H J; Pedersen, O L; Andreasen, F; Bjerregaard, P

    1981-01-01

    Thirty patients with mild or moderate essential hypertension, and a fixed elevation of diastolic blood pressure, were randomly allocated to three groups and treated with propranolol 40 mg x 4 (Group 1), 80 mg x 4 (group 2) and 160 mg x 4 (Group 3). Blood pressure (BP), pulse rate (PR), plasma renin activity (PRA), plasma aldosterone concentration (PAC), total plasma propranolol (tPP), free plasma propranolol (fPP), and 24 h urinary propranolol excretion (UP) were determined at the end of four consecutive periods: (A) after four weeks without any treatment; (B) after two to three weeks during which the propranolol dose was gradually increased to the intended level; (C) after four weeks, and (D) after eight weeks of unchanged treatment. The maximum reduction in diastolic BP occurred after period B, and in systolic BP after Period C, for Groups 2 and 3, and for all groups together; for Group 1, however, the maximum diastolic BP reduction was first seen after period C. PR was reduced to the same level in all groups after period B. After period B, PRA an PAC fell in all groups, and remained reduced during C and D Group 1. After periods C and D, PRA and PAC in Groups 2 and 3 did not differ significantly from the levels after period A; tPP, fPP and UP were significantly correlated with the propranolol dose, and were lowest in Group 1 and highest in Group 3; UP was negatively correlated with systolic but not diastolic BP in Periods B, C and D. In contrast neither fPP nor tPP were correlated with systolic or diastolic BP. There was no significant correlation between PRA, PAC and changes in PRA or PAC on the one hand and tPP, fPP, UP, BP or changes in BP on the other. It was concluded that propranolol effectively reduced BP, but diastolic BP reduction was most rapidly obtained at 320 and 640 mg daily, that the activity of the renin -aldosterone system was initially suppressed in all group, but for unknown reasons it increased towards the control level after seven to eleven

  20. System-based identification of toxicity pathways associated with multi-walled carbon nanotube-induced pathological responses

    SciTech Connect

    Snyder-Talkington, Brandi N.; Dymacek, Julian; Porter, Dale W.; Wolfarth, Michael G.; Mercer, Robert R.; Pacurari, Maricica; Denvir, James; Castranova, Vincent; Qian, Yong; Guo, Nancy L.

    2013-10-15

    The fibrous shape and biopersistence of multi-walled carbon nanotubes (MWCNT) have raised concern over their potential toxicity after pulmonary exposure. As in vivo exposure to MWCNT produced a transient inflammatory and progressive fibrotic response, this study sought to identify significant biological processes associated with lung inflammation and fibrosis pathology data, based upon whole genome mRNA expression, bronchoaveolar lavage scores, and morphometric analysis from C57BL/6J mice exposed by pharyngeal aspiration to 0, 10, 20, 40, or 80 μg MWCNT at 1, 7, 28, or 56 days post-exposure. Using a novel computational model employing non-negative matrix factorization and Monte Carlo Markov Chain simulation, significant biological processes with expression similar to MWCNT-induced lung inflammation and fibrosis pathology data in mice were identified. A subset of genes in these processes was determined to be functionally related to either fibrosis or inflammation by Ingenuity Pathway Analysis and was used to determine potential significant signaling cascades. Two genes determined to be functionally related to inflammation and fibrosis, vascular endothelial growth factor A (vegfa) and C-C motif chemokine 2 (ccl2), were confirmed by in vitro studies of mRNA and protein expression in small airway epithelial cells exposed to MWCNT as concordant with in vivo expression. This study identified that the novel computational model was sufficient to determine biological processes strongly associated with the pathology of lung inflammation and fibrosis and could identify potential toxicity signaling pathways and mechanisms of MWCNT exposure which could be used for future animal studies to support human risk assessment and intervention efforts. - Highlights: • A novel computational model identified toxicity pathways matching in vivo pathology. • Systematic identification of MWCNT-induced biological processes in mouse lungs • MWCNT-induced functional networks of lung

  1. Serum nitric oxide metabolite (NO(x)) levels in hypertensive patients at rest: a comparison of age, gender, blood pressure and complications using normotensive controls.

    PubMed

    Higashino, Hideaki; Miya, Hirohisa; Mukai, Hidenori; Miya, Yoshihisa

    2007-08-01

    1. Hypertensive patients have pathophysiological changes such as atherosclerosis, endothelial dysfunction and inflammations. The patients' serum nitric oxide metabolite (nitrate/nitrite; NO(x)) levels were measured in peripheral blood using normotensive controls for comparison. 2. The NO(x) levels in 175 hypertensive patients with or without comorbid diseases (aged 37-95 years; average 50.6 +/- 0.8 years) were compared with those in 80 normotensive controls (aged 25-73 years; average 37.1 +/- 1.8 years). 3. The NO(x) levels increased with age in both the normotensive and hypertensive women, but not in men. No difference was noted in the NO(x) levels between the normotensive and hypertensive patients without comorbid diseases. The mean value of NO(x) in male hypertensive patients aged under 50 years was close to that of female patients aged 51-60 years. Hypertensive males aged 61-70 years showed almost the same NO(x) levels as those of female patients aged over 81 years. A male group of hypertensive patients with diabetes, hyperlipaemia and renal disorder had a significantly higher NO(x) level compared with a normotensive control group. However, in female groups, only hypertensive patients with hyperlipaemia showed higher serum NO(x) values compared with the normotensive group. 4. These findings suggest that: (i) the occurrence of NO(x) in the serum is not solely the outcome of high blood pressure; (ii) higher serum NO(x) levels in older women are because of an oestrogen deficiency-induced cardiovascular disease; (iii) ageing effects on the circulation system are more apparent in men than in women; and (iv) measurement of NO(x) levels in the serum is helpful for understanding the pathological progress in male hypertensive patients with diseases such as diabetes mellitus, hyperlipaemia and renal disorder.

  2. Renoprotective effects of renin–angiotensin system inhibitor combined with calcium channel blocker or diuretic in hypertensive patients

    PubMed Central

    Cheng, Yiming; Huang, Rongshuang; Kim, Sehee; Zhao, Yuliang; Li, Yi; Fu, Ping

    2016-01-01

    Abstract Objectives: To conduct a meta-analysis of studies comparing the renoprotective effects of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) combined with either calcium channel blocker (CCB) or diuretic, but not both, in hypertensive patients. Data sources: Pubmed, Embase, Medline, and Cochrane databases were searched to identify randomized controlled trials (RCTs) of blood pressure lowering treatments in patients with hypertension. Study selection: RCTs comparing the renoprotective effects of ACEI/ARB plus CCB with ACEI/ARB plus diuretic in hypertensive patients, with at least one of the following reported outcomes: urinary protein, estimated glomerular filtration rate/creatinine clearance (eGFR/CrCl), or serum creatinine. Results: Based on 14 RCTs with 18,125 patients, statistically significant benefits were found in ACEI/ARB plus CCB for maintaining eGFR/CrCl (standardized mean difference [SMD] = 0.36; 95% confidence interval [CI]: 0.20–0.53; P < 0.001), serum creatinine reduction (mean difference [MD] = −0.05 mg/dL; 95% CI: −0.07 to −0.03; P < 0.001). However, no statistical differences were found between the 2 therapeutic strategies in terms of urinary protein (MD = 7.48%; 95% CI: –6.13% to 21.08%; P = 0.28; I2 = 92%). Conclusions: This meta-analysis concluded that ACEI/ARB plus CCB have a stronger effect on the maintenance of renal function in patients with hypertension than ACEI/ARB plus diuretic. PMID:27428210

  3. Hypertension in developing countries.

    PubMed

    Tibazarwa, Kemi B; Damasceno, Albertino A

    2014-05-01

    The past 2 decades have seen a considerable global increase in cardiovascular disease, with hypertension remaining by far the most common. More than one-third of adults in Africa are hypertensive; as in the urban populations of most developing countries. Being a condition that occurs with relatively few symptoms, hypertension remains underdetected in many countries; especially in developing countries where routine screening at any point of health care is grossly underutilized. Because hypertension is directly related to cardiovascular disease, this has led to hypertension being the leading cause of adverse cardiovascular outcomes, as a result of patients living, often unknowingly, with uncontrolled hypertension for prolonged periods of time. In Africa, hypertension is the leading cause of heart failure; whereas at global levels, hypertension is responsible for more than half of deaths from stroke, just less than half of deaths from coronary artery disease, and for more than one-tenth of all global deaths. In this review, we discuss the escalating occurrence of hypertension in developing countries, before exploring the strengths and weaknesses of different measures to control hypertension, and the challenges of adopting these measures in developing countries. On a broad level, these include steps to curb the ripple effect of urbanization on the health and disease profile of developing societies, and suggestions to improve loopholes in various aspects of health care delivery that affect surveillance and management of hypertension. Furthermore, we consider how the industrial sectors' contributions toward the burden of hypertension can also be the source of the solution.

  4. Evaluation of the Retinal Vasculature in