Science.gov

Sample records for pathological systemic hypertension

  1. 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.

  2. 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…

  3. The evolving definition of systemic arterial hypertension.

    PubMed

    Ram, C Venkata S; Giles, Thomas D

    2010-05-01

    Systemic hypertension is an important risk factor for premature cardiovascular disease. Hypertension also contributes to excessive morbidity and mortality. Whereas excellent therapeutic options are available to treat hypertension, there is an unsettled issue about the very definition of hypertension. At what level of blood pressure should we treat hypertension? Does the definition of hypertension change in the presence of co-morbid conditions? This article covers in detail the evolving concepts in the diagnosis and management of hypertension.

  4. 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.

  5. [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

  6. [Heart pathology of extracardiac origin. IV. Pulmonary hypertension in chronic respiratory diseases].

    PubMed

    Barberà, J A

    1998-01-01

    Pulmonary hypertension is the major cardiovascular complication of chronic respiratory disorders and its development is a sign of poor prognosis. Pulmonary circulation is characterized by its low vascular tone and the response to hypoxia by vasoconstriction. Pulmonary endothelium plays an important role in modulating these characteristics. Structural abnormalities of pulmonary arteries in pulmonary hypertension affect preferentially the intimal layer and may damage the endothelial cells. Endothelial dysfunction of pulmonary arteries has been recognized in the different forms of pulmonary hypertension. Vasodilators are recommended for the treatment of primary pulmonary hypertension. However, in pulmonary hypertension associated with chronic respiratory disorders, both systemic and selective pulmonary vasodilators are not indicated since they may worsen gas exchange due to the inhibition of hypoxic vasoconstriction. The most effective treatment of pulmonary hypertension associated with chronic hypoxic lung diseases is long-term oxygen therapy. PMID:9522610

  7. Cardiovascular magnetic resonance in systemic hypertension

    PubMed Central

    2012-01-01

    Systemic hypertension is a highly prevalent potentially modifiable cardiovascular risk factor. Imaging plays an important role in the diagnosis of underlying causes for hypertension, in assessing cardiovascular complications of hypertension, and in understanding the pathophysiology of the disease process. Cardiovascular magnetic resonance (CMR) provides accurate and reproducible measures of ventricular volumes, mass, function and haemodynamics as well as uniquely allowing tissue characterization of diffuse and focal fibrosis. In addition, CMR is well suited for exclusion of common secondary causes for hypertension. We review the current and emerging clinical and research applications of CMR in hypertension. PMID:22559053

  8. 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.

  9. 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

  10. Pathology

    SciTech Connect

    Rubin, E.; Farber, J.L. )

    1988-01-01

    This book contains 29 chapters. Some of the titles are: Genetic and Systemic Diseases; Cell Injury; Inflammation; The Gastrointestinal o Tract; The Pancreas; Environmental and Nutritional Pathology; Infectious and Parasitic Diseases; and Blood Vessels.

  11. 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

  12. Hypertension

    PubMed Central

    LePine, Todd

    2012-01-01

    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. PMID:24278815

  13. 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.

  14. Glutathione system in young spontaneously hypertensive rats.

    PubMed

    Lee, S K; Arunkumar, Sundaram; Sirajudeen, K N S; Singh, H J

    2010-12-01

    Glutathione (GSH) forms a part of the antioxidant system that plays a vital role in preventing oxidative stress, and an imbalance in the oxidant/antioxidant system has been linked to the pathogenesis of hypertension. The aim of this study was to investigate the status of the GSH system in the kidney of spontaneously hypertensive rats (SHR). Components of the GSH system, including glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), and total GSH content, were measured in the kidneys of 4, 6, 8, 12, and 16 weeks old SHR and Wistar-Kyoto (WKY) rats. Systolic blood pressure of SHR was significantly higher from the age of 6 weeks onwards compared with age-matched WKY rats. GPx activity in the SHR was significantly lower from the age of 8 weeks onwards when compared to that in age-matched WKY rats. No significant differences were evident in the GPx-1 protein abundance, and its relative mRNA levels, GR, GST activity, and total GSH content between SHR and age-matched WKY rats. The lower GPx activity suggests of an impairment of the GSH system in the SHR, which might be due to an abnormality in its protein rather than non-availability of a cofactor. Its role in the development of hypertension in SHR however remains unclear.

  15. Hypertension, chronic kidney disease, and renal pathology in a child with hermansky-pudlak syndrome.

    PubMed

    Gordillo, Roberto; Del Rio, Marcela; Thomas, David B; Flynn, Joseph T; Woroniecki, Robert P

    2011-01-01

    We report a child with Hermansky-Pudlak Syndrome (HPS) and chronic kidney disease (stage II) with histological diagnosis of focal segmental glomerulosclerosis (FSGS). A 15-year-old male of Puerto Rico ancestry with history of HPS, hypertension (HTN), asthma, obesity, and chronic kidney disease (CKD) stage II presented with new-onset proteinuria without edema. His blood pressure had been controlled, serum creatinine had been 0.9-1.4 mg/dL, and first morning urine protein/creatinine ratio (UPC) ranged from 0.2 to 0.38. Due to persistent nonorthostatic proteinuria with CKD, renal biopsy was performed and FSGS (not otherwise specified) with chronic diffuse tubulopathy (tubular cytoplasmic droplets) and acute tubular injury was reported. Ceroid-like material is known to infiltrate tissues (i.e., lungs, colon, and kidney) in HPS, but the reason for the renal insufficiency is unknown. Nonspecific kidney disease and in one adult case IgA nephropathy with ANCA-positive glomerulonephritis have previously been reported in patients with Hermansky-Pudlak syndrome. To our knowledge, we report the first pediatric renal pathology case of HPS associated with CKD. This paper discusses presentation and management of renal disease in HPS.

  16. [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. PMID:27284843

  17. [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.

  18. Intratubular Renin-Angiotensin System in Hypertension

    PubMed Central

    Suzaki, Yuki; Prieto-Carrasquero, Minolfa C.; Kobori, Hiroyuki

    2009-01-01

    It is well recognized that the renin-angiotensin system plays an important role in the regulation of arterial pressure and sodium homeostasis. Recent years, many studies have shown that local tissue angiotensin II levels are differentially regulated and cannot be explained on the basis of circulating concentrations. All of the components needed for angiotensin II generation are present within the various compartments in the kidney including the renal interstitium and the tubular network. The cascade of the renin-angiotensin system demonstrates three major possible sites for the pharmacological interruption of the renin-angiotensin system: the interaction of renin with its substrate, angiotensinogen, the angiotensin converting enzyme, and angiotensin II type 1 receptors. This brief article will focus on the role of the intratubular renin-angiotensin system in the pathophysiology of hypertension and the responses to the renin-angiotensin system blockade by renin inhibitors, angiotensin converting enzyme inhibitors and angiotensin II type 1 receptor blockers. PMID:19789728

  19. An Anatomic Pathology System Using the File Manager

    PubMed Central

    Ginsburg, R. E.; Tatarczuk, J. R.; Roy, G. R.

    1981-01-01

    An Anatomic Pathology System incorporating patient data from surgical pathology, cytopathology and autopsy pathology is presented. The System includes four interconnected files created with the aid of the File Manager. One file, containing patient demographic data, can be used as a connecting node to other patient databases. Five MUMPS routines, using File Manager functions, allow System users unfamiliar with computers and computer programming to easily enter, edit and retrieve patient information. Retrieved information is in a format to reconstruct, when possible, a patient's medical history from the pathology database and to correlate surgical pathology, cytopathology and autopsy pathology data.

  20. Hypertension: renin-angiotensin-aldosterone system alterations.

    PubMed

    Te Riet, Luuk; van Esch, Joep H M; Roks, Anton J M; van den Meiracker, Anton H; Danser, A H Jan

    2015-03-13

    Blockers of the renin-angiotensin-aldosterone system (RAAS), that is, renin inhibitors, angiotensin (Ang)-converting enzyme (ACE) inhibitors, Ang II type 1 receptor antagonists, and mineralocorticoid receptor antagonists, are a cornerstone in the treatment of hypertension. How exactly they exert their effect, in particular in patients with low circulating RAAS activity, also taking into consideration the so-called Ang II/aldosterone escape that often occurs after initial blockade, is still incompletely understood. Multiple studies have tried to find parameters that predict the response to RAAS blockade, allowing a personalized treatment approach. Consequently, the question should now be answered on what basis (eg, sex, ethnicity, age, salt intake, baseline renin, ACE or aldosterone, and genetic variance) a RAAS blocker can be chosen to treat an individual patient. Are all blockers equal? Does optimal blockade imply maximum RAAS blockade, for example, by combining ≥2 RAAS blockers or by simply increasing the dose of 1 blocker? Exciting recent investigations reveal a range of unanticipated extrarenal effects of aldosterone, as well as a detailed insight in the genetic causes of primary aldosteronism, and mineralocorticoid receptor blockers have now become an important treatment option for resistant hypertension. Finally, apart from the deleterious ACE-Ang II-Ang II type 1 receptor arm, animal studies support the existence of protective aminopeptidase A-Ang III-Ang II type 2 receptor and ACE2-Ang-(1 to 7)-Mas receptor arms, paving the way for multiple new treatment options. This review provides an update about all these aspects, critically discussing the many controversies and allowing the reader to obtain a full understanding of what we currently know about RAAS alterations in hypertension. PMID:25767283

  1. Revelations about carotid body function through its pathological role in resistant hypertension.

    PubMed

    Paton, Julian F R; Ratcliffe, Laura; Hering, Dagmara; Wolf, Jacek; Sobotka, Paul A; Narkiewicz, Krzysztof

    2013-08-01

    Much recent attention has been given to the carotid body because of its potential role in cardiovascular disease states. One disease, neurogenic hypertension, characterised by excessive sympathetic activity, appears dependent on carotid body activity that may or may not be accompanied by sleep-disordered breathing. Herein, we review recent literature suggesting that the carotid body acquires tonicity in hypertension. We predict that carotid glomectomy will be a powerful way to temper excessive sympathetic discharge in diseases such as hypertension. We propose a model to explain that signalling from the 'hypertensive' carotid body is tonic, and hypothesise that there will be a sub-population of glomus cells that channel separately into reflex pathways controlling sympathetic motor outflows. PMID:23828147

  2. [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.

  3. [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. PMID:27172721

  4. Relationship between magnification and resolution in digital pathology systems.

    PubMed

    Sellaro, Tiffany L; Filkins, Robert; Hoffman, Chelsea; Fine, Jeffrey L; Ho, Jon; Parwani, Anil V; Pantanowitz, Liron; Montalto, Michael

    2013-08-22

    Many pathology laboratories are implementing digital pathology systems. The image resolution and scanning (digitization) magnification can vary greatly between these digital pathology systems. In addition, when digital images are compared with viewing images using a microscope, the cellular features can vary in size. This article highlights differences in magnification and resolution between the conventional microscopes and the digital pathology systems. As more pathologists adopt digital pathology, it is important that they understand these differences and how they ultimately translate into what the pathologist can see and how this may impact their overall viewing experience.

  5. 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.

  6. [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.

  7. 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

  8. Estrogen promotes microvascular pathology in female stroke-prone spontaneously hypertensive rats.

    PubMed

    Stier, Charles T; Chander, Praveen N; Rosenfeld, Louis; Powers, C Andrew

    2003-07-01

    Estrogen produces both beneficial and adverse effects on cardiovascular health via mechanisms that remain unclear. Stroke-prone spontaneously hypertensive rats (SHRSP) maintained on Stroke-Prone Rodent Diet and 1% NaCl drinking water (starting at 8 wk of age) rapidly develop stroke and malignant nephrosclerosis that can be prevented, despite continued hypertension, by drugs targeting angiotensin II and aldosterone actions. This study evaluated estrogen's effects in the SHRSP model. Female SHRSP that were sham operated (SHAM), ovariectomized (OVX) at 4 wk of age, or OVX and treated with estradiol benzoate (E2,30 microg x kg-1 x wk-1) were studied. In a survival protocol, OVX rats lived significantly longer (15.1 +/- 0.3 wk) compared with SHAM (13.6 +/- 0.2 wk) or OVX+E2 rats (12.4 +/- 0.2 wk). In a protocol in which animals were matched for age, at 11.5 wk, terminal systolic blood pressure and urine protein excretion were elevated in SHAM and OVX+E2 rats compared with OVX rats; blood urea nitrogen, renal microvascular and glomerular lesions, and plasma renin concentration were elevated in OVX+E2 relative to SHAM or OVX rats. In a survival protocol using intact female SHRSP, treatment with an antiestrogen (tamoxifen, 7 mg.kg-1.wk-1) prolonged survival by >2 wk compared with controls (P < 0.01). The data indicate that estrogen promotes microangiopathy in the kidney and stroke in saline-drinking SHRSP.

  9. Pathologic findings and laboratory data in a new strain of obese hypertensive rats.

    PubMed Central

    Koletsky, S.

    1975-01-01

    A new strain of rat characterized by genetic obesity, endogenous hyperlipidemia, and hypertension was obtained in this laboratory. The abnormal phenotype is inherited as a homozygous recessive trait. The animals exhibit marked hypertriglyceridemia, moderate hypercholesterolemia, and an electrophoretic pattern resembling that of human Type IV hyperlipoproteinemia. The average life-span is less than 1 year, due largely to the development of premature renal and vascular disease. The kidney lesion has both glomerulonephritic and nephrosclerotic components and is accompanied by marked proteinuria. About 12% of animals develop urinary tract calculi. The vascular disease consists of fibrous and fatty-fibrous intimal plaques, and polyarteritis. The obese animal offers a useful model for investigating abnormal lipid metabolism and the etiology and pathogenesis of atherosclerosis. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:1171627

  10. Treatment of systemic hypertension associated with kidney disease.

    PubMed

    Buoncompagni, Simona; Bowles, Mary H

    2013-05-01

    Systemic hypertension is an increasingly diagnosed disorder in dogs and cats and frequently occurs secondary to chronic kidney disease. Prevention of damage to organs such as the kidneys, brain, heart, and eyes is one of the primary concerns in the management of veterinary patients with hypertension. This article reviews the guidelines for antihypertensive therapy in patients with, or at risk for, kidney disease, including the initiation of treatment and currently recommended medications.

  11. Protocol care for hypertension supported by an expert system.

    PubMed

    Takahashi, E; Yoshida, K; Izuno, T; Miyakawa, M; Sugimori, H

    1995-01-01

    1. PURPOSE. Hypertension if one of the major prevalent diseases that influences the prognosis of chronic diseases. Primary care should attract much attention in the management of hypertension. The management of hypertension includes not only the use of antihypertensiove drugs, but also the modification of unhealthy lifestyles. Multi-dimensional approaches are required for the management of hypertensive patients. This system supports the standard protocol care for hypertensive patients and the database for clinical epidemiology. 2. DESIGN CONSIDERATIONS. This system has several functions that support the appropriate management of hypertensive patients. The first one is clinical database management. The second is the evaluation of the clinical conditions in hypertension. The third is the decision support system for the selection of treatments for hypertension. 3. SYSTEM DESCRIPTION. This system administers the clinical database, which includes symptoms and signs, laboratory data, and prescriptions. The database deals with the temporal course of the patient's status. The system that evaluates the patient's condition and the decision support system have some knowledge bases. The knowledge bases consist of the evaluation of the patient's condition, the appropriate selection of laboratory examinations, and suggestions for treatments, which involve a life-style modification and the proper prescription of medication. 4. STATUS REPORTS. The relational database was developed for handling the patient's records. These records were displayed on the terminal according to the temporal sequence. The graphical representations of the medical data were displayed in order to understand the patient's status. 5. LESSON LEARNED. This kind of protocol care system is expected to support the proper medical care of patients. Excess medications and laboratory examinations will be excluded under the protocol care, thus reducing unnecessary medical expense. The system will enhance the

  12. 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.

  13. 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

  14. 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

  15. Systemic hypertension and hypertensive retinopathy following PPA overdose in a dog.

    PubMed

    Ginn, Jennifer A; Bentley, Ellison; Stepien, Rebecca L

    2013-01-01

    A 4 yr old spayed female Labrador retriever was examined 4 hr after ingesting an overdose of phenylpropanolamine (PPA). Clinical signs included anxiety, piloerection, mucosal ulceration, cardiac arrhythmia, mydriasis, and hyphema. Clinicopathologic abnormalities included elevated creatine kinase (CK) and aspartate aminotransferase (AST), proteinuria, and pigmenturia. Ventricular tachycardia and severe systemic hypertension were documented. Hyphema and retinal detachment were documented oculus uterque (OU). Phenoxybenzamine, sotalol, and esmolol resolved the ventricular tachycardia, and blood pressure was controlled with nitroprusside. All clinicopathologic and cardiac abnormalities resolved within 7 days, and ocular changes resolved within 1 mo. Monitoring of blood pressure and rapid pharmacologic intervention were successful in controlling hypertension secondary to PPA overdose and minimizing retinal damage.

  16. Expert systems for clinical pathology reporting.

    PubMed

    Edwards, Glenn A

    2008-08-01

    * Conventional automated interpretative reporting systems use standard or "canned" comments for patient reports. These are result-specific and do not generally refer to the patient context. * Laboratory information systems (LIS) are limited in their application of patient-specific content of reporting. * Patient-specific interpretation requires extensive cross-referencing to other information contained in the LIS such as previous test results, other related tests, and clinical notes, both current and previous. * Expert systems have the potential to improve reporting quality by enabling patient-specific reporting in clinical laboratories.

  17. 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. PMID:11912866

  18. 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...

  19. The sympathetic nervous system in hypertension: back to the future?

    PubMed

    Esler, Murray

    2015-02-01

    The seventeenth century London neuroanatomical school headed by Thomas Willis published the first images of the sympathetic nervous system. Nineteenth century European physiologists characterised these as the "pressor nerves". Von Euler's demonstration that the sympathetic transmitter was norepinephrine brought the field into the modern era. Sympathetic nervous system responses are regionally differentiated; human regional sympathetic activity is best studied by recording from postganglionic sympathetic efferents directed to the skeletal muscle vasculature (clinical microneurography) and by measurement of organ-specific norepinephrine release to plasma from sympathetic nerves (regional "norepinephrine spillover"). With these techniques, the sympathetic nervous system became accessible to clinical scientists, allowing the demonstration that sympathetic nervous system activation is crucial in the development and outcomes of cardiovascular disorders, most notably heart failure and essential hypertension. Activation of the renal sympathetic outflow is pivotal in the pathogenesis of essential hypertension. An important goal for clinical scientists is translation of knowledge of pathophysiology, such as this, into better treatment for patients. Although disputed, the case is strong that in hypertension, we are now on the cusp of effective "mechanisms to management" transition, with the use of catheter-based renal sympathetic nerve ablation for treating drug-resistant hypertension.

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

    PubMed Central

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

    2015-01-01

    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

  1. 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.

  2. Hypertension

    MedlinePlus

    ... y Cuidadores Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ... Women's Health Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ...

  3. System for pathology categorization and retrieval in chest radiographs

    NASA Astrophysics Data System (ADS)

    Avni, Uri; Greenspan, Hayit; Konen, Eli; Sharon, Michal; Goldberger, Jacob

    2011-03-01

    In this paper we present an overview of a system we have been developing for the past several years for efficient image categorization and retrieval in large radiograph archives. The methodology is based on local patch representation of the image content, using a bag of visual words approach and similarity-based categorization with a kernel based SVM classifier. We show an application to pathology-level categorization of chest x-ray data, the most popular examination in radiology. Our study deals with pathology detection and identification of individual pathologies including right and left pleural effusion, enlarged heart and cases of enlarged mediastinum. The input from a radiologist provided a global label for the entire image (healthy/pathology), and the categorization was conducted on the entire image, with no need for segmentation algorithms or any geometrical rules. An automatic diagnostic-level categorization, even on such an elementary level as healthy vs pathological, provides a useful tool for radiologists on this popular and important examination. This is a first step towards similarity-based categorization, which has a major clinical implications for computer-assisted diagnostics.

  4. Computer-assisted pathology encoding and reporting system (CAPER).

    PubMed

    Aller, R D; Robboy, S J; Poitras, J W; Altshuler, B S; Cameron, M; Prior, M C; Miao, S; Barnett, G O

    1977-12-01

    An on-line computer-assisted pathology encoding and reportying system (CAPER) has been developed by the Department of Pathology and Laboratory of Computer Science of the Massachusetts General Hospital for a department of surgical pathology that processes more than 25,000 specimens yearly. CAPER performs clerical functions, including the accessioning of specimens, monitoring their state of completion, production of log books, billing, statistics, and transfer of diagnoses to other hospital departments. It also permits instantaneous display of all diagnoses rendered within two years, printout within 24 hours of all older diagnoses for any patient, and retrieval of all specimens with any given diagnosis, further defined by any data item (e.g., age) stored in the computer file.

  5. The sympathetic nervous system and baroreflexes in hypertension and hypotension.

    PubMed

    Izzo, J L; Taylor, A A

    1999-06-01

    Blood pressure and blood volume are closely regulated by the interrelated actions of the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS). Reflex vasoconstriction caused by parallel SNS and RAAS activation is modulated by two interactive negative feedback systems called baroreflex. The aortic-carotid baroreflex systems respond to momentary changes in systolic blood pressure, adjusting the degree of SNS-dependent peripheral vasoconstriction and cardiac output to allow maintenance of a relatively constant perfusion pressure. Cardiopulmonary baroreflexes respond to momentary changes in cardiac filling, adjusting the degree of peripheral venoconstriction and venous return to maintain cardiac preload and stroke volume. Under normal conditions, each baroreflex system exhibits a degree of tonic negative feedback so that it can alter SNS output immediately, providing counterregulatory increases or decreases in pressure or volume to maintain homeostasis. The SNS is inappropriately active in obesity and hypertension and plays a causal or permissive role in all forms of chronic hypertension. If the negative feedback control exerted by the baroreflexes over the SNS and renin-angiotensin-aldosterone system (RAAS) were perfect, chronic hypertension would not occur. Activity of the baroreflexes, however, is chronically altered by maladaptive changes such as cardiac and vascular fibrosis and hypertrophy. Long-term increases in SNS and RAAS activity also exert ongoing deleterious effects on the heart and vasculature by directly facilitating further cardiac hypertrophy and arterial stiffening. These effects appear to contribute to a vicious cycle of chronic hypertension and target organ damage. Other syndromes of abnormal blood pressure (BP) control, including orthostatic hypotension and baroreflex failure are examples of abnormal baroreflex activity and SNS control. PMID:10981075

  6. Calpain mediates pulmonary vascular remodeling in rodent models of pulmonary hypertension, and its inhibition attenuates pathologic features of disease.

    PubMed

    Ma, Wanli; Han, Weihong; Greer, Peter A; Tuder, Rubin M; Toque, Haroldo A; Wang, Kevin K W; Caldwell, R William; Su, Yunchao

    2011-11-01

    Pulmonary hypertension is a severe and progressive disease, a key feature of which is pulmonary vascular remodeling. Several growth factors, including EGF, PDGF, and TGF-β1, are involved in pulmonary vascular remodeling during pulmonary hypertension. However, increased knowledge of the downstream signaling cascades is needed if effective clinical interventions are to be developed. In this context, calpain provides an interesting candidate therapeutic target, since it is activated by EGF and PDGF and has been reported to activate TGF-β1. Thus, in this study, we examined the role of calpain in pulmonary vascular remodeling in two rodent models of pulmonary hypertension. These data showed that attenuated calpain activity in calpain-knockout mice or rats treated with a calpain inhibitor resulted in prevention of increased right ventricular systolic pressure, right ventricular hypertrophy, as well as collagen deposition and thickening of pulmonary arterioles in models of hypoxia- and monocrotaline-induced pulmonary hypertension. Additionally, inhibition of calpain in vitro blocked intracellular activation of TGF-β1, which led to attenuated Smad2/3 phosphorylation and collagen synthesis. Finally, smooth muscle cells of pulmonary arterioles from patients with pulmonary arterial hypertension showed higher levels of calpain activation and intracellular active TGF-β. Our data provide evidence that calpain mediates EGF- and PDGF-induced collagen synthesis and proliferation of pulmonary artery smooth muscle cells via an intracrine TGF-β1 pathway in pulmonary hypertension. PMID:22005303

  7. [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. PMID:27284844

  8. [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.

  9. Systemic hypertension in dogs with leishmaniasis: prevalence and clinical consequences.

    PubMed

    Cortadellas, Oscar; del Palacio, María Josefa Fernández; Bayón, Alejandro; Albert, Angel; Talavera, Jesús

    2006-01-01

    A prospective study was performed (November 1998 to December 2003) to determine the prevalence of systemic hypertension (SH) in dogs with glomerular disease secondary to leishmaniasis. One hundred and five dogs with leishmaniasis were screened and staged for the presence of renal disease (RD) and SH. For the purpose of the study, RD was defined as serum creatinine concentration > or = 1.4 mg/dL, a urine protein/creatinine ratio > or = 0.5, or both. SH was defined as a systolic blood pressure (SBP) > or =180 mm Hg or an SBP between 150 and 179 mm Hg in the presence of clinical manifestations of SH. Fifty-two (49.5%) of the dogs had some degree of RD, and 32 (61.5%) of these dogs were diagnosed with SH. Moreover, SH also was diagnosed in 3 dogs without RD. Left ventricular hypertrophy (LVH), estimated by echocardiography, was the most frequently observed systemic consequence of hypertension, being present in 32 (91.4%) of the hypertensive dogs. Echocardiographic abnormalities were not detected in any of the 33 dogs with leishmaniasis without RD, which were used as controls. Ocular consequences of SH were observed in only 2 (5.7%) of the dogs with hypertension. We conclude that SH is prevalent in dogs with RD secondary to leishmaniasis, not only in the more severe stages but also in the early course of the illness before azotemia becomes apparent. Canine leishmaniasis may be a useful natural model to study SH secondary to glomerular disease.

  10. Tissue plasminogen activator in central nervous system physiology and pathology

    PubMed Central

    Melchor, Jerry P.; Strickland, Sidney

    2005-01-01

    Summary Although conventionally associated with fibrin clot degradation, recent work has uncovered new functions for the tissue plasminogen activator (tPA)/plasminogen cascade in central nervous system physiology and pathology. This extracellular proteolytic cascade has been shown to have roles in learning and memory, stress, neuronal degeneration, addiction and Alzheimer’s disease. The current review considers the different ways tPA functions in the brain. PMID:15841309

  11. TRPV4 channels: physiological and pathological role in cardiovascular system.

    PubMed

    Randhawa, Puneet Kaur; Jaggi, Amteshwar Singh

    2015-11-01

    TRPV4 channels are non-selective cation channels permeable to Ca(2+), Na(+), and Mg(2+) ions. Recently, TRPV4 channels have received considerable attention as these channels are widely expressed in the cardiovascular system including endothelial cells, cardiac fibroblasts, vascular smooth muscles, and peri-vascular nerves. Therefore, these channels possibly play a pivotal role in the maintenance of cardiovascular homeostasis. TRPV4 channels critically regulate flow-induced arteriogenesis, TGF-β1-induced differentiation of cardiac fibroblasts into myofibroblasts, and heart failure-induced pulmonary edema. These channels also mediate hypoxia-induced increase in proliferation and migration of pulmonary artery smooth muscle cells and progression of pulmonary hypertension. These channels also maintain flow-induced vasodilation and preserve vascular function by directly activating Ca(2+)-dependent KCa channels. Furthermore, these may also induce vasodilation and maintain blood pressure indirectly by evoking the release of NO, CGRP, and substance P. The present review discusses the evidences and the potential mechanisms implicated in diverse responses including arteriogenesis, cardiac remodeling, congestive heart failure-induced pulmonary edema, pulmonary hypertension, flow-induced dilation, regulation of blood pressure, and hypoxic preconditioning.

  12. Systemic and renal-specific sympathoinhibition in obesity hypertension.

    PubMed

    Lohmeier, Thomas E; Iliescu, Radu; Liu, Boshen; Henegar, Jeffrey R; Maric-Bilkan, Christine; Irwin, Eric D

    2012-02-01

    Chronic pressure-mediated baroreflex activation suppresses renal sympathetic nerve activity. Recent observations indicate that chronic electric activation of the carotid baroreflex produces sustained reductions in global sympathetic activity and arterial pressure. Thus, we investigated the effects of global and renal specific suppression of sympathetic activity in dogs with sympathetically mediated, obesity-induced hypertension by comparing the cardiovascular, renal, and neurohormonal responses to chronic baroreflex activation and bilateral surgical renal denervation. After control measurements, the diet was supplemented with beef fat, whereas sodium intake was held constant. After 4 weeks on the high-fat diet, when body weight had increased ≈50%, fat intake was reduced to a level that maintained this body weight. This weight increase was associated with an increase in mean arterial pressure from 100±2 to 117±3 mm Hg and heart rate from 86±3 to 130±4 bpm. The hypertension was associated with a marked increase in cumulative sodium balance despite an approximately 35% increase in glomerular filtration rate. The importance of increased tubular reabsorption to sodium retention was further reflected by ≈35% decrease in fractional sodium excretion. Subsequently, both chronic baroreflex activation (7 days) and renal denervation decreased plasma renin activity and abolished the hypertension. However, baroreflex activation also suppressed systemic sympathetic activity and tachycardia and reduced glomerular hyperfiltration while increasing fractional sodium excretion. In contrast, glomerular filtration rate increased further after renal denervation. Thus, by improving autonomic control of cardiac function and diminishing glomerular hyperfiltration, suppression of global sympathetic activity by baroreflex activation may have beneficial effects in obesity beyond simply attenuating hypertension.

  13. 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

  14. 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

  15. TissueCypher™: A systems biology approach to anatomic pathology

    PubMed Central

    Prichard, Jeffrey W.; Davison, Jon M.; Campbell, Bruce B.; Repa, Kathleen A.; Reese, Lia M.; Nguyen, Xuan M.; Li, Jinhong; Foxwell, Tyler; Taylor, D. Lansing; Critchley-Thorne, Rebecca J.

    2015-01-01

    Background: Current histologic methods for diagnosis are limited by intra- and inter-observer variability. Immunohistochemistry (IHC) methods are frequently used to assess biomarkers to aid diagnoses, however, IHC staining is variable and nonlinear and the manual interpretation is subjective. Furthermore, the biomarkers assessed clinically are typically biomarkers of epithelial cell processes. Tumors and premalignant tissues are not composed only of epithelial cells but are interacting systems of multiple cell types, including various stromal cell types that are involved in cancer development. The complex network of the tissue system highlights the need for a systems biology approach to anatomic pathology, in which quantification of system processes is combined with informatics tools to produce actionable scores to aid clinical decision-making. Aims: Here, we describe a quantitative, multiplexed biomarker imaging approach termed TissueCypher™ that applies systems biology to anatomic pathology. Applications of TissueCypher™ in understanding the tissue system of Barrett's esophagus (BE) and the potential use as an adjunctive tool in the diagnosis of BE are described. Patients and Methods: The TissueCypher™ Image Analysis Platform was used to assess 14 epithelial and stromal biomarkers with known diagnostic significance in BE in a set of BE biopsies with nondysplastic BE with reactive atypia (RA, n = 22) and Barrett's with high-grade dysplasia (HGD, n = 17). Biomarker and morphology features were extracted and evaluated in the confirmed BE HGD cases versus the nondysplastic BE cases with RA. Results: Multiple image analysis features derived from epithelial and stromal biomarkers, including immune biomarkers and morphology, showed significant differences between HGD and RA. Conclusions: The assessment of epithelial cell abnormalities combined with an assessment of cellular changes in the lamina propria may serve as an adjunct to conventional pathology in the

  16. Alopecia in Systemic Amyloidosis: Trichoscopic-Pathologic Correlation

    PubMed Central

    Miteva, Mariya; Wei, Erin; Milikowski, Clara; Tosti, Antonella

    2015-01-01

    Alopecia in systemic amyloidosis is very rare and has been described as individual cases of diffuse nonscarring alopecia and a case of alopecia universalis. We report the trichoscopic findings in alopecia associated with systemic amyloidosis. The most prominent feature was a salmon colored halo (0.3-1 mm in diameter) surrounding the follicular ostia. Other features included broken hairs and black dots. The salmon colored halo correlated on pathology with the perifollicular deposition of amyloid. The horizontal sections showed that the sebaceous glands were preserved which supports the nonscarring pattern of the alopecia. PMID:26903748

  17. 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.

  18. The effect of exercise training on the pulmonary arterial system in patients with pulmonary hypertension.

    PubMed

    Arena, Ross; Cahalin, Lawrence P; Borghi-Silva, Audrey; Myers, Jonathan

    2015-01-01

    Given the unique and clinically ominous pathology associated with pulmonary arterial (PA) hypertension (PH) and its implications for the eventual deterioration of right ventricular function, exercise training (ET) was historically not recommended. More recently, a body of literature demonstrating the safety and efficacy of ET in PH has emerged. The primary focus of this review is to provide a synopsis of current evidence assessing the effects of ET on the PA system in patients with PH. The current body of evidence is relatively small and it is not clear if ET improves PA function or vessel characteristics. Nevertheless, studies have consistently found ET leads to numerous clinically relevant benefits including increased: 1) aerobic capacity, 2) muscle strength, 3) exercise tolerance, and 4) quality of life. Thus, ET, given its clinical benefits, is likely to enjoy increased utilization in patients with PH.

  19. Testosterone increases: sodium reabsorption, blood pressure, and renal pathology in female spontaneously hypertensive rats on a high sodium diet.

    PubMed

    Liu, Bei; Ely, Daniel

    2011-01-01

    Estrogen (E) and testosterone (T) are important in the sexually dimorphic pattern of blood pressure (BP) development. The goal was to examine the effects of endogenous E and exogenous T in the development of hypertension in female spontaneously hypertensive rats (SHR) on a high sodium diet. Female SHR (N = 27, 5-week) were divided into four groups: (1) control (n = 8), (2) ovariectomized (OVX, n = 26), (3) testosterone implants with intact ovaries (T, n = 6), and (4) ovariectomized + testosterone implants (OVX+T, n = 7). T was given immediately after OVX and replaced every two weeks and they were fed a 3% NaCl diet. BP was measured weekly and plasma norepinephrine (NE) analyzed by HPLC. OVX+T females exhibited the greatest elevation in BP (190 ± 4.0 mmHg) compared to controls at 15 weeks of age (140 ± 3.4 mmHg, P < .001) and a pattern of hypertension development similar to that of male SHR. Females with T treatment showed evidence of glomerulosclerosis. In conclusion, T accelerated the development of hypertension similar to the BP pattern observed in males; the presence of ovaries attenuated the T induced increase in BP; T increased renal sodium reabsorption, and T increased glomerulosclerosis.

  20. Exercise-Induced Systemic Venous Hypertension in the Fontan Circulation.

    PubMed

    Navaratnam, Devaraj; Fitzsimmons, Samantha; Grocott, Michael; Rossiter, Harry B; Emmanuel, Yaso; Diller, Gerard-Paul; Gordon-Walker, Timothy; Jack, Sandy; Sheron, Nick; Pappachan, John; Pratap, Jayant Nick; Vettukattil, Joseph J; Veldtman, Gruschen

    2016-05-15

    Increasingly end-organ injury is being demonstrated late after institution of the Fontan circulation, particularly liver fibrosis and cirrhosis. The exact mechanisms for these late phenomena remain largely elusive. Hypothesizing that exercise induces precipitous systemic venous hypertension and insufficient cardiac output for the exercise demand, that is, a possible mechanism for end-organ injury, we sought to demonstrate the dynamic exercise responses in systemic venous perfusion (SVP) and concurrent end-organ perfusion. Ten stable Fontan patients and 9 control subjects underwent incremental cycle ergometry-based cardiopulmonary exercise testing. SVP was monitored in the right upper limb, and regional tissue oxygen saturation was monitored in the brain and kidney using near-infrared spectroscopy. SVP rose profoundly in concert with workload in the Fontan group, described by the regression equation 15.97 + 0.073 watts per mm Hg. In contrast, SVP did not change in healthy controls. Regional renal (p <0.01) and cerebral tissue saturations (p <0.001) were significantly lower and decrease more rapidly in Fontan patients. We conclude that in a stable group of adult patients with Fontan circulation, high-intensity exercise was associated with systemic venous hypertension and reduced systemic oxygen delivery. This physiological substrate has the potential to contribute to end-organ injury.

  1. 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.

  2. Role of the sympathetic nervous system in hypertension and hypertension-related cardiovascular disease.

    PubMed

    Seravalle, Gino; Mancia, Giuseppe; Grassi, Guido

    2014-06-01

    A number of cardiovascular disease have been shown to be characterized by a marked increase in sympathetic drive to the heart and the peripheral circulation. This is the case for essential hypertension, congestive heart failure, cardiac arrhythmias, obesity, metabolic syndrome, obstructive sleep apnea, and chronic renal disease. This review focuses on the most recent findings documenting the role of sympathetic neural factors in the development and progression of the hypertensive state as well as in the pathogenesis of hypertension-related target organ damage. It also reviews the role of sympathetic neural factors in the development of cardiovascular diseases not necessarily strictly related to the hypertensive state, such as congestive heart failure, cardiac arrhythmias, obesity, metabolic syndrome and renal failure. The paper will finally review the pharmacological and non-pharmacological interventions acting on the sympathetic drive. Emphasis will be given to the new approaches, such as renal nerves ablation and carotid baroreceptor stimulation, which have been shown to exert sympathoinhibitory effects.

  3. Gender differences in development of hypertension in spontaneously hypertensive rats: role of the renin-angiotensin system.

    PubMed

    Reckelhoff, J F; Zhang, H; Srivastava, K

    2000-01-01

    Previous data strongly support a role for androgens in promoting the gender difference in hypertension in the spontaneously hypertensive rat(s) (SHR), but the mechanism is not clear. Because males develop higher blood pressures than do females, we hypothesize that androgens may affect the renin-angiotensin system to promote the development of hypertension in male SHR. The present study was performed to determine the effect of converting enzyme inhibition (CEI) on the development of hypertension in SHR. Male, female, castrated male, and ovariectomized (ovx) female SHR (n=10 per gender per treatment group) received enalapril (250 mg/L) in drinking water for 8 to 10 weeks. Some ovx females were also given testosterone chronically. At 17 to 19 weeks of age, 24-hour protein excretion and mean arterial pressure were measured. By 13 weeks of age, male rats had higher systolic blood pressures by tail plethysmography than did the other rats, and CEI reduced blood pressures to similar levels in all groups. At 17 to 19 weeks, the same trend was found by direct measurement of mean arterial pressure. The ovx females treated with testosterone had serum testosterone and blood pressure levels similar to those found in males. CEI reduced mean arterial pressure to similar levels in all gender groups. Untreated males and ovx females given testosterone had significantly higher levels of urinary protein excretion than did the other groups, and CEI had no effect on proteinuria in any of the rats. These data suggest that the development of hypertension in SHR regardless of sex steroids is mediated by the renin-angiotensin system. However, the data further suggest that androgens promote the exacerbation of hypertension in male SHR via a mechanism involving the renin-angiotensin system.

  4. Right Ventricular Dysfunction in Systemic Sclerosis Associated Pulmonary Arterial Hypertension

    PubMed Central

    Tedford, Ryan J.; Mudd, James O.; Girgis, Reda E.; Mathai, Stephen C.; Zaiman, Ari L.; Housten-Harris, Traci; Boyce, Danielle; Kelemen, Benjamin W.; Bacher, Anita C.; Shah, Ami A.; Hummers, Laura K.; Wigley, Fredrick M.; Russell, Stuart D.; Saggar, Rajeev; Saggar, Rajan; Maughan, W. Lowell; Hassoun, Paul M.; Kass, David A.

    2013-01-01

    Background Systemic sclerosis associated pulmonary artery hypertension (SScPAH) has a worse prognosis compared to idiopathic pulmonary arterial hypertension (IPAH), with a median survival of 3 years after diagnosis often due to right ventricular (RV) failure. We tested if SScPAH or systemic sclerosis related pulmonary hypertension with interstitial lung disease (SSc-ILD-PH) imposes a greater pulmonary vascular load than IPAH and/or leads to worse RV contractile function. Methods and Results We analyzed pulmonary artery pressures and mean flow in 282 patients with pulmonary hypertension (166 SScPAH, 49 SSc-ILD-PH, 67 IPAH). An inverse relation between pulmonary resistance (RPA) and compliance (CPA) was similar for all three groups, with a near constant resistance × compliance product. RV pressure-volume loops were measured in a subset, IPAH (n=5) and SScPAH (n=7) as well as SSc without PH (SSc-no-PH, n=7) to derive contractile indexes (end-systolic elastance [Ees] and preload recruitable stroke work [Msw]), measures of right ventricular load (arterial elastance [Ea]), and RV-pulmonary artery coupling (Ees/Ea). RV afterload was similar in SScPAH and IPAH (RPA=7.0±4.5 vs. 7.9±4.3 Wood units; Ea=0.9±0.4 vs. 1.2±0.5 mmHg/mL; CPA=2.4±1.5 vs. 1.7±1.1 mL/mmHg; p>0.3 for each). Though SScPAH did not have greater vascular stiffening compared to IPAH, RV contractility was more depressed (Ees=0.8±0.3 vs. 2.3±1.1, p<0.01; Msw=21±11 vs. 45±16, p=0.01), with differential RV-PA uncoupling (Ees/Ea=1.0±0.5 vs. 2.1±1.0, p=.03). This ratio was higher in SSc-no-PH (Ees/Ea = 2.3±1.2, p=0.02 vs. SScPAH). Conclusions RV dysfunction is worse in SScPAH compared to IPAH at similar afterload, and may be due to intrinsic systolic function rather than enhanced pulmonary vascular resistive and/or pulsatile loading. PMID:23797369

  5. Contribution of central amiloride-sensitive transport systems to the development of hypertension in spontaneously hypertensive rats.

    PubMed

    Seto, S; Kitamura, S; Nagao, S; Nonaka, M; Akahoshi, M; Yano, K

    2001-07-01

    This study was conducted to examine if central amiloride-sensitive transport systems are involved in the development and/or maintenance of hypertension in spontaneously hypertensive rats (SHR). Either amiloride (75 microg/60 microl/day) or artificial cerebrospinal fluid (aCSF, 60 microl/day) was infused centrally (i.c.v.) for 4 weeks to development (4-5-weeks-old) and maintenance (10-12-weeks-old) phases of hypertension in SHR. In development phase, amiloride i.c.v. (n=14) blunted the elevation of blood pressure (BP) compared to aCSF i.c.v. (n=9) (amiloride vs. aCSF; after 3 weeks of i.c.v., 146+/-3 vs. 166+/-5 mmHg, P<0.001). The difference of BP at 3 weeks of i.c.v. was canceled after ganglionic block with hexamethonium (115+/-4 vs. 117+/-5 mmHg). Further, pressor responsiveness to norepinephrine was augmented in amiloride i.c.v. rats (amiloride, n=11 vs. aCSF, n=6; %Delta BP at 800 ng/kg/min.: 16.9+/-1.3 vs. 10.8+/-1.4 mmHg, P<0.05) and this augmentation disappeared after ganglionic block. Pressor responsiveness to angiotensin II and cumulative sodium balance did not differ in the two groups. Intravenous administration of amiloride at the same dose did not attenuate the development of hypertension. On the other hand, in maintenance phase, amiloride i.c.v. by the same protocol as in development phase had no effect on BP in SHR. Also, amiloride i.c.v. did not affect BP in normotensive Wistar-Kyoto rats. These results suggest that central amiloride-sensitive transport systems are involved in the development, but not in the maintenance, of hypertension in SHR through the modulation of autonomic neural mechanisms.

  6. 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.

  7. [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.

  8. 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.

  9. The serotonin transporter promotes a pathological estrogen metabolic pathway in pulmonary hypertension via cytochrome P450 1B1

    PubMed Central

    2016-01-01

    Abstract Pulmonary arterial hypertension (PAH) is a devastating vasculopathy that predominates in women and has been associated with dysregulated estrogen and serotonin signaling. Overexpression of the serotonin transporter (SERT+) in mice results in an estrogen-dependent development of pulmonary hypertension (PH). Estrogen metabolism by cytochrome P450 1B1 (CYP1B1) contributes to the pathogenesis of PAH, and serotonin can increase CYP1B1 expression in human pulmonary arterial smooth muscle cells (hPASMCs). We hypothesized that an increase in intracellular serotonin via increased SERT expression may dysregulate estrogen metabolism via CYP1B1 to facilitate PAH. Consistent with this hypothesis, we found elevated lung CYP1B1 protein expression in female SERT+ mice accompanied by PH, which was attenuated by the CYP1B1 inhibitor 2,3′,4,5′-tetramethoxystilbene (TMS). Lungs from female SERT+ mice demonstrated an increase in oxidative stress that was marked by the expression of 8-hydroxyguanosine; however, this was unaffected by CYP1B1 inhibition. SERT expression was increased in monocrotaline-induced PH in female rats; however, TMS did not reverse PH in monocrotaline-treated rats but prolonged survival. Stimulation of hPASMCs with the CYP1B1 metabolite 16α-hydroxyestrone increased cellular proliferation, which was attenuated by an inhibitor (MPP) of estrogen receptor alpha (ERα) and a specific ERα antibody. Thus, increased intracellular serotonin caused by increased SERT expression may contribute to PAH pathobiology by dysregulation of estrogen metabolic pathways via increased CYP1B1 activity. This promotes PASMC proliferation by the formation of pathogenic metabolites of estrogen that mediate their effects via ERα. Our studies indicate that targeting this pathway in PAH may provide a promising antiproliferative therapeutic strategy. PMID:27162617

  10. 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. PMID:24786445

  11. 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.

  12. 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

  13. 3D-Pathology: a real-time system for quantitative diagnostic pathology and visualisation in 3D

    NASA Astrophysics Data System (ADS)

    Gottrup, Christian; Beckett, Mark G.; Hager, Henrik; Locht, Peter

    2005-02-01

    This paper presents the results of the 3D-Pathology project conducted under the European EC Framework 5. The aim of the project was, through the application of 3D image reconstruction and visualization techniques, to improve the diagnostic and prognostic capabilities of medical personnel when analyzing pathological specimens using transmitted light microscopy. A fully automated, computer-controlled microscope system has been developed to capture 3D images of specimen content. 3D image reconstruction algorithms have been implemented and applied to the acquired volume data in order to facilitate the subsequent 3D visualization of the specimen. Three potential application fields, immunohistology, cromogenic in situ hybridization (CISH) and cytology, have been tested using the prototype system. For both immunohistology and CISH, use of the system furnished significant additional information to the pathologist.

  14. 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

  15. 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.

  16. 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

  17. Study on User Interface of Pathology Picture Archiving and Communication System

    PubMed Central

    Kim, Dasueran; Kang, Peter; Yun, Jungmin; Park, Sung-Hye; Seo, Jeong-Wook

    2014-01-01

    Objectives It is necessary to improve the pathology workflow. A workflow task analysis was performed using a pathology picture archiving and communication system (pathology PACS) in order to propose a user interface for the Pathology PACS considering user experience. Methods An interface analysis of the Pathology PACS in Seoul National University Hospital and a task analysis of the pathology workflow were performed by observing recorded video. Based on obtained results, a user interface for the Pathology PACS was proposed. Results Hierarchical task analysis of Pathology PACS was classified into 17 tasks including 1) pre-operation, 2) text, 3) images, 4) medical record viewer, 5) screen transition, 6) pathology identification number input, 7) admission date input, 8) diagnosis doctor, 9) diagnosis code, 10) diagnosis, 11) pathology identification number check box, 12) presence or absence of images, 13) search, 14) clear, 15) Excel save, 16) search results, and 17) re-search. And frequently used menu items were identified and schematized. Conclusions A user interface for the Pathology PACS considering user experience could be proposed as a preliminary step, and this study may contribute to the development of medical information systems based on user experience and usability. PMID:24627818

  18. 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

  19. Classification Systems in Renal Pathology: Promises and Problems.

    PubMed

    Stokes, M Barry

    2014-09-01

    Kidney diseases are morphologically heterogeneous. Pathologic classifications of renal disease permit standardization of diagnosis and may identify clinical-pathologic subgroups with different outcomes and/or responses to treatment. To date, classifications have been proposed for lupus nephritis, allograft rejection, IgA nephropathy, focal segmental glomerulosclerosis, antineutrophil cytoplasmic antibody -related glomerulonephritis, and diabetic glomerulosclerosis. These classifications share several limitations related to lack of specificity, reproducibility, validation, and relevance to clinical practice. They offer a standardized approach to diagnosis, however, which should facilitate communication and clinical research.

  20. Ascending Aorta Elastography After Kawasaki Disease Compared to Systemic Hypertension.

    PubMed

    Nandlall, Ian; Maurice, Roch L; Fournier, Anne; Merouani, Aïcha; Dahdah, Nagib

    2015-10-01

    Kawasaki disease (KD) is a systemic vasculitis, classically affecting large- and medium-size arteries. The coronary arteries draw most of the clinical attention, whereas few studies have taken interest in the ascending aorta. Using a proprietary imaging-based mechanical biomarker (ImBioMark), we sought to determine aortic stiffness in KD compared to systemic hypertension (HTN) and healthy children. We evaluated parasternal long-axis views focused on the ascending aorta in 20 controls, 12 KD, and 8 HTN as a comparative clinical model of vascular stiffness. We calculated systolic and diastolic aortic wall strain with ImBioMark. Strain was tested for normality against height, systolic, and diastolic blood pressure in normal subjects. Strain from KD and HTN was normalized (Z score) accordingly. Z score comparisons were performed using nonparametric statistics. Age was similar between KD and HTN (9.1 ± 5.3 and 9.9 ± 5.3 years old; p = NS). Systolic and diastolic strain values were normally distributed against height, systolic blood pressure, and diastolic blood pressure in healthy subjects. HTN subjects had abnormal systolic and diastolic strain values (p < 0.0001). Whereas KD subjects had normal diastolic strain, systolic strain was significantly lower (p < 0.001), and systolic strain was intermediate between controls and HTN. There were no significant differences in aortic strain among KD, however, according to the presence of coronary artery aneurysms. Despite normal blood pressure, the ascending aorta in KD exhibits reduced strain during systole. This may reflect in situ rigidity of the aorta. The normal diastolic strain in KD may, in contrast, reflect normal peripheral vascular resistance. PMID:25921428

  1. Pathological heterogeneity of idiopathic central nervous system inflammatory demyelinating disorders.

    PubMed

    Lucchinetti, C

    2008-01-01

    The last decade has seen a resurgence of interest in MS neuropathology. This resurgence was partly fueled by the development of new molecular and histochemical tools to examine the MS lesion microscopically, as well as technological advances in neuroimaging, which permit a dynamic assessment of lesion formation and disease progression. The heterogeneous pathology of MS in relation to stage of lesion activity, phase of disease, and clinical course is discussed. Pathological studies reveal that the immune factors associated with multiple different effector mechanisms contribute to the inflammation, demyelination, and tissue injury observed in MS lesions. While many agree that pathological heterogeneity exists in white matter demyelinated lesions, it is uncertain whether these observations are patient-dependent and reflect pathogenic heterogeneity or, alternatively, are stage-dependent with multiple mechanisms occurring sequentially within a given patient. Evidence supporting both concepts is presented. Remyelination is present in MS lesions; however, the factors contributing to the extent of repair and oligodendrocyte survival differ depending on the disease phase. A variable and patient-dependent extent of remyelination is observed in chronic MS cases and will likely need to be considered when designing future clinical trials aimed to promote CNS repair. MS is one member of a spectrum of CNS idiopathic inflammatory demyelinating disorders that share the basic pathological hallmark of CNS inflammatory demyelination. Advances based on recent systematic clinicopathologic-serologic correlative approaches have led to novel insights with respect to the classification of these disorders, as well as a better understanding of the underlying pathogenic mechanisms.

  2. Musculoskeletal Pathology.

    PubMed

    Peat, Frances J; Kawcak, Christopher E

    2015-08-01

    The current understanding of pathology as it relates to common diseases of the equine musculoskeletal system is reviewed. Conditions are organized under the fundamental categories of developmental, exercise-induced, infectious, and miscellaneous pathology. The overview of developmental pathology incorporates the new classification system of juvenile osteochondral conditions. Discussion of exercise-induced pathology emphasizes increased understanding of the contribution of cumulative microdamage caused by repetitive cyclic loading. Miscellaneous musculoskeletal pathology focuses on laminitis, which current knowledge indicates should be regarded as a clinical syndrome with a variety of possible distinct mechanisms of structural failure that are outlined in this overview. PMID:26037607

  3. The heart and pulmonary arterial hypertension in systemic sclerosis.

    PubMed

    Vandecasteele, Els H; De Pauw, Michel; Brusselle, Guy; Decuman, Saskia; Piette, Yves; De Keyser, Filip; Smith, V

    2016-02-01

    Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by vasculopathy and progressive fibrosis of the skin and visceral organs (gastrointestinal tract, heart, kidneys and lungs). Although the prevalence is low, SSc is a disease with high morbidity and mortality. Since pulmonary arterial hypertension (PAH) associated with SSc (SSc-PAH) and clinically evident cardiac involvement is associated with increased mortality, the cardiac complications and PAH in SSc are reviewed. Both diffuse cutaneous (DcSSc) and limited cutaneous (LcSSc) subgroups are at risk for cardiac involvement and SSc-PAH. Cardiac involvement can be divided in pericardial involvement, myocardial involvement and rhythm disturbances and mostly occurs asymptomatically. However, when symptomatic, it is associated with a poor prognosis. Screening for asymptomatic cardiac involvement should be considered in SSc in order to initiate treatment in an early stage. However, there are no randomized controlled trials on treatment options for cardiac involvement in SSc. SSc-PAH is a devastating complication of SSc, which can develop early in DcSSc and LcSSc. Screening for PAH should be performed since screening leads to earlier diagnosis and earlier treatment is associated with a better prognosis. Today, screening is performed by clinical judgement and echocardiography. Recently the DETECT algorithm, a 2-step screening algorithm is proposed in a SSc-subgroup at increased risk for PAH, but further validation is needed. Despite current treatment options with prostacyclins, endothelin-1 receptor antagonists and phosphodiesterase type-5 inhibitors, mortality remains high. Several promising new treatment options for PAH are evaluated in phase II and III clinical trials. PMID:27075793

  4. Comparison of bevantolol and atenolol for systemic hypertension.

    PubMed

    Fairhurst, G J

    1986-11-26

    In an international, randomized, double-blind trial involving 229 patients, 400 mg of bevantolol was compared with 100 mg of atenolol (both in single daily doses) in the management of mild to moderate hypertension (diastolic blood pressure [BP] 95 to 115 mm Hg after a 4-week placebo washout period). Patients were then randomized to 12 weeks of treatment with either drug. Patients were evaluated at 2, 4, 8 and 12 weeks during the drug treatment period. Efficacy measurements were based on sitting and standing BP and heart rate. Adverse experiences were recorded on patient checklists, by spontaneous complaints and by 12-lead electrocardiography and funduscopy. A subgroup of 104 patients had heart rate and BP determinations every 24 to 26 hours after drug ingestion. Overall results showed both drugs to be comparably effective; no real difference was shown after 12 weeks of treatment. Bevantolol caused a more gradual BP decrease than atenolol. Both regimens were associated with decreased heart rate (less marked with bevantolol, p less than 0.001). Data from the 24-hour assessment subgroup showed similar results for both drugs, with a somewhat lower decrease in BP for bevantolol, which persisted throughout the study. Both drugs lowered sitting BP; the decrease was significantly less with bevantolol after the second week of therapy. The mean number of adverse experiences was similar for both drugs; cardiovascular side effects were less frequent with bevantolol. Patients taking bevantolol showed a higher incidence of digestive system side effects. Bevantolol maintained a 24-hour antihypertensive effect.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Resolution of pulmonary hypertension complication during venovenous perfusion-induced systemic hyperthermia application.

    PubMed

    Ballard-Croft, Cherry; Wang, Dongfang; Jones, Cameron; Wang, Jingkun; Pollock, Robert; Jubak, Bob; Topaz, Stephen; Zwischenberger, Joseph B

    2013-01-01

    We are developing a venovenous perfusion-induced systemic hyperthermia (vv-PISH) system for advanced cancer treatment. The vv-PISH system consistently delivered hyperthermia to adult healthy swine, but significant pulmonary hypertension developed during the heating phase. The goal of this study was to develop a method to prevent pulmonary hypertension. We hypothesized that pulmonary hypertension results from decreased priming solution air solubility, which causes pulmonary gas embolism. Healthy adult sheep (n = 3) were used to establish a standard vv-PISH sheep model without priming solution preheating. In subsequent sheep (n = 7), the priming solution was preheated (42-46°C) and the hyperthermia circuit flushed with CO2. All sheep survived the experiment and achieved 2 hours of 42°C hyperthermia. In the group lacking priming solution preheating, significant pulmonary hypertension (35-44 mm Hg) developed. In the sheep with priming solution preheating, pulmonary artery pressure was very stable without pulmonary hypertension. Blood electrolytes were in physiologic range, and complete blood counts were unaffected by hyperthermia. Blood chemistries revealed no significant liver or kidney damage. Our simple strategy of priming solution preheating completely resolved the problem of pulmonary hypertension as a milestone toward developing a safe and easy-to-use vv-PISH system for cancer treatment.

  6. Resolution of pulmonary hypertension complication during venovenous perfusion-induced systemic hyperthermia application.

    PubMed

    Ballard-Croft, Cherry; Wang, Dongfang; Jones, Cameron; Wang, Jingkun; Pollock, Robert; Jubak, Bob; Topaz, Stephen; Zwischenberger, Joseph B

    2013-01-01

    We are developing a venovenous perfusion-induced systemic hyperthermia (vv-PISH) system for advanced cancer treatment. The vv-PISH system consistently delivered hyperthermia to adult healthy swine, but significant pulmonary hypertension developed during the heating phase. The goal of this study was to develop a method to prevent pulmonary hypertension. We hypothesized that pulmonary hypertension results from decreased priming solution air solubility, which causes pulmonary gas embolism. Healthy adult sheep (n = 3) were used to establish a standard vv-PISH sheep model without priming solution preheating. In subsequent sheep (n = 7), the priming solution was preheated (42-46°C) and the hyperthermia circuit flushed with CO2. All sheep survived the experiment and achieved 2 hours of 42°C hyperthermia. In the group lacking priming solution preheating, significant pulmonary hypertension (35-44 mm Hg) developed. In the sheep with priming solution preheating, pulmonary artery pressure was very stable without pulmonary hypertension. Blood electrolytes were in physiologic range, and complete blood counts were unaffected by hyperthermia. Blood chemistries revealed no significant liver or kidney damage. Our simple strategy of priming solution preheating completely resolved the problem of pulmonary hypertension as a milestone toward developing a safe and easy-to-use vv-PISH system for cancer treatment. PMID:23820278

  7. [Treatment of systemic hypertension associated with kidney disease in the dog and cat].

    PubMed

    Buoncompagni, S; Bowles, M H

    2014-01-01

    Systemic hypertension is an increasingly diagnosed disorder in dogs and cats and frequently occurs secondary to chronic kidney disease. Prevention of damage to organs such as the kidneys, brain, heart, and eyes is one of the primary concerns in the management of veterinary patients with hypertension. This article reviews the guidelines for antihypertensive therapy in patients with, or at risk for, kidney disease, including the initiation of treatment and currently recommended medications.

  8. 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.

  9. Effect of melatonin supplementation and cross-fostering on renal glutathione system and development of hypertension in spontaneously hypertensive rats.

    PubMed

    Siew-Keah, Lee; Sundaram, Arunkumar; Sirajudeen, K N S; Zakaria, Rahimah; Singh, H J

    2014-03-01

    Antenatal and postnatal environments are hypothesised to influence the development of hypertension. This study investigates the synergistic effect of cross-fostering and melatonin supplementation on the development of hypertension and renal glutathione system in spontaneously hypertensive rats (SHR). In one experiment, 1-day-old male SHR pups were fostered to either SHR (shr-SHR) or Wistar-Kyoto rats, (shr-WKY). In a concurrent experiment, SHR dams were given melatonin in drinking water (10 mg/kg body weight) from day 1 of pregnancy. Immediately following delivery, 1-day-old male pups were fostered either to SHR (Mel-shr-SHR) or WKY (Mel-shr-WKY) dams receiving melatonin supplementation until weaning on day 21. Upon weaning, melatonin supplementation was continued to these pups until the age of 16 weeks. Systolic blood pressures (SBP) were recorded at the age of 4, 6, 8, 12 and 16 weeks. Renal antioxidant activities were measured. Mean SBP of shr-WKY, Mel-shr-SHR and Mel-shr-WKY was significantly lower than that in shr-SHR until the age of 8 weeks. At 12 and 16 weeks of age, mean SBP of Mel-shr-WKY was lower than those in non-treated shr-SHR and shr-WKY pups but was not significantly different from that in Mel-shr-SHR. Renal glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities were significantly higher in Mel-shr-SHR and Mel-shr-WKY at 16 weeks of age. It appears that combination of cross-fostering and melatonin supplementation exerts no synergistic effect on delaying the rise in blood pressure in SHR. The elevated GPx and GST activities are likely to be due to the effect of melatonin supplementation.

  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. [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. PMID:27661285

  12. Role of glutathione metabolism and glutathione-related antioxidant defense systems in hypertension.

    PubMed

    Robaczewska, J; Kedziora-Kornatowska, K; Kozakiewicz, M; Zary-Sikorska, E; Pawluk, H; Pawliszak, W; Kedziora, J

    2016-06-01

    The risk of developing chronic hypertension increases with age. Among others factors, increased oxidative stress is a well-recognized etiological factor for the development of hypertension. The co-occurrence of oxidative stress and hypertension may occur as a consequence of a decrease in antioxidant defense system activity or elevated reactive oxygen species generation. Glutathione is a major intracellular thiol-disulfide redox buffer that serves as a cofactor for many antioxidant enzymes. Glutathione-related parameters are altered in hypertension, suggesting that there is an association between the glutathione-related redox system and hypertension. In this review, we provide mechanistic explanations for how glutathione maintains blood pressure. More specifically, we discuss glutathione's role in combating oxidative stress and maintaining nitric oxide bioavailability via the formation of nitrosothiols and nitrosohemoglobin. Although impaired vasodilator responses are observed in S-nitrosothiol-deficient red blood cells, this potential hypertensive mechanism is currently overlooked in the literature. Here we fill in this gap by discussing the role of glutathione in nitric oxide metabolism and controlling blood pressure. We conclude that disturbances in glutathione metabolism might explain age-dependent increases in blood pressure. PMID:27511994

  13. 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

  14. Hypertensive emergencies.

    PubMed

    Feitosa-Filho, Gilson Soares; Lopes, Renato Delascio; Poppi, Nilson Tavares; Guimarães, Hélio Penna

    2008-09-01

    Emergencies and hypertensive crises are clinical situations which may represent more than 25% of all medical emergency care. Considering such high prevalence, physicians should be prepared to correctly identify these crises and differentiate between urgent and emergent hypertension. Approximately 3% of all visits to emergency rooms are due to significant elevation of blood pressure. Across the spectrum of blood systemic arterial pressure, hypertensive emergency is the most critical clinical situation, thus requiring special attention and care. Such patients present with high blood pressure and signs of acute specific target organ damage (such as acute myocardial infarction, unstable angina, acute pulmonary edema, eclampsia, and stroke). Key elements of diagnosis and specific treatment for the different presentations of hypertensive emergency will be reviewed in this article. The MedLine and PubMed databases were searched for pertinent abstracts, using the key words "hypertensive crises" and "hypertensive emergencies". Additional references were obtained from review articles. Available English language clinical trials, retrospective studies and review articles were identified, reviewed and summarized in a simple and practical way. The hypertensive crisis is a clinical situation characterized by acute elevation of blood pressure followed by clinical signs and symptoms. These signs and symptoms may be mild (headache, dizziness, tinnitus) or severe (dyspnea, chest pain, coma or death). If the patient presents with mild symptoms, but without acute specific target organ damage, diagnosis is hypertensive urgency. However, if severe signs and symptoms and acute specific target organ damage are present, then the patient is experiencing a hypertensive emergency. Some patients arrive at the emergency rooms with high blood pressure, but without any other sign or symptom. In these cases, they usually are not taking their medications correctly. Therefore, this is not a

  15. Equine laryngeal hemiplegia. Part V. Central nervous system pathology.

    PubMed

    Cahill, J I; Goulden, B E

    1986-11-01

    Evidence of long central nerve fibre degeneration (axonal spheroids) in the lateral cuneate nuclei was found in all eight Thoroughbreds affected clinically and subclinically with equine laryngeal hemiplegia, but in only one of six control animals. It was considered that these spheroids may signify a central nervous component of the disease process of laryngeal hemiplegia although until further investigations are performed no firm conclusions regarding the relationship of these findings with laryngeal hemiplegia could be made. Examination of the left and right nucleus ambiguus of clinical and subclinical laryngeal hemiplegic horses revealed no pathological alterations.

  16. Ocular Hypertension

    MedlinePlus

    ... Español Eye Health / Eye Health A-Z Ocular Hypertension Sections What Is Ocular Hypertension? Ocular Hypertension Causes ... Hypertension Diagnosis Ocular Hypertension Treatment What Is Ocular Hypertension? Written by: Kierstan Boyd Reviewed by: J Kevin ...

  17. Obstructive sleep apnea/hypopnea and systemic hypertension.

    PubMed

    Durán-Cantolla, Joaquín; Aizpuru, Felipe; Martínez-Null, Cristina; Barbé-Illa, Ferrán

    2009-10-01

    Obstructive sleep apnea/hypopnea (OSAH) syndrome is a highly prevalent condition. Severe OSAH affects 2-6% of the population, although only 10% of subjects are correctly diagnosed and treated. OSAH is an important and unresolved public health care problem because of its role in the development of cardiovascular events, negative impact on quality of life, and as a cause of traffic accidents. Longitudinal and cross-sectional studies have shown a strong association between OSAH and hypertension. Moreover, a number of open-label studies, the majority of 21 controlled studies included in the present review, a systematic review, and 4 recent meta-analyses have shown a reduction of blood pressure (BP) of about 2 mm Hg with continuous positive airway pressure (CPAP). This lowering of blood pressure is significant in terms of reduction of both cardiovascular and cerebrovascular risk and death. The effect is greater in hypertensive subjects and in those with more severe OSAH. Accordingly, treatment with CPAP could be considered in patients with severe OSAH and hypertension even in the absence of symptoms. The challenge to researchers is to find markers for discriminating subjects in whom blood pressure will decrease from non-responders. This will help to refine relevant clinical indicators for CPAP treatment in clinical practice.

  18. [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.

  19. The human sympathetic nervous system: its relevance in hypertension and heart failure.

    PubMed

    Parati, Gianfranco; Esler, Murray

    2012-05-01

    Evidence assembled in this review indicates that sympathetic nervous system dysfunction is crucial in the development of heart failure and essential hypertension. This takes the form of persistent and adverse activation of sympathetic outflows to the heart and kidneys in both conditions. An important goal for clinical scientists is translation of the knowledge of pathophysiology, such as this, into better treatment for patients. The achievement of this 'mechanisms to management' transition is at different stages of development with regard to the two disorders. Clinical translation is mature in cardiac failure, knowledge of cardiac neural pathophysiology having led to the introduction of beta-adrenergic blockers, an effective therapy. With essential hypertension perhaps we are on the cusp of effective translation, with recent successful testing of selective catheter-based renal sympathetic nerve ablation in patients with resistant hypertension, an intervention firmly based on the demonstration of activation of the renal sympathetic outflow. Additional evidence in this regard is provided by the results of pilot studies exploring the possibility to reduce blood pressure in resistant hypertensives through electrical stimulation of the area of carotid baroreceptors. Despite the general importance of the sympathetic nervous system in blood pressure regulation, and the specific demonstration that the blood pressure elevation in essential hypertension is commonly initiated and sustained by sympathetic nervous activation, drugs antagonizing this system are currently underutilized in the care of patients with hypertension. Use of beta-adrenergic blocking drugs is waning, given the propensity of this drug class to have adverse metabolic effects, including predisposition to diabetes development. The blood pressure lowering achieved with carotid baroreceptor stimulation and with the renal denervation device affirms the importance of the sympathetic nervous system in

  20. The human sympathetic nervous system: its relevance in hypertension and heart failure.

    PubMed

    Parati, Gianfranco; Esler, Murray

    2012-05-01

    Evidence assembled in this review indicates that sympathetic nervous system dysfunction is crucial in the development of heart failure and essential hypertension. This takes the form of persistent and adverse activation of sympathetic outflows to the heart and kidneys in both conditions. An important goal for clinical scientists is translation of the knowledge of pathophysiology, such as this, into better treatment for patients. The achievement of this 'mechanisms to management' transition is at different stages of development with regard to the two disorders. Clinical translation is mature in cardiac failure, knowledge of cardiac neural pathophysiology having led to the introduction of beta-adrenergic blockers, an effective therapy. With essential hypertension perhaps we are on the cusp of effective translation, with recent successful testing of selective catheter-based renal sympathetic nerve ablation in patients with resistant hypertension, an intervention firmly based on the demonstration of activation of the renal sympathetic outflow. Additional evidence in this regard is provided by the results of pilot studies exploring the possibility to reduce blood pressure in resistant hypertensives through electrical stimulation of the area of carotid baroreceptors. Despite the general importance of the sympathetic nervous system in blood pressure regulation, and the specific demonstration that the blood pressure elevation in essential hypertension is commonly initiated and sustained by sympathetic nervous activation, drugs antagonizing this system are currently underutilized in the care of patients with hypertension. Use of beta-adrenergic blocking drugs is waning, given the propensity of this drug class to have adverse metabolic effects, including predisposition to diabetes development. The blood pressure lowering achieved with carotid baroreceptor stimulation and with the renal denervation device affirms the importance of the sympathetic nervous system in

  1. 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

  2. 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.

  3. [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).

  4. [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.

  5. 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

  6. [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

  7. [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

  8. 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.

  9. Pathology tickler: an HL7 monitoring system to provide clinical feedback

    NASA Astrophysics Data System (ADS)

    Mongkolwat, Pattanasak; Davis, Elizabeth; Bhalodia, Pankit; Singh, Harinder; Channin, David S.

    2003-05-01

    The purpose of this project is to develop a software system to provide feedback to radiologists and other clinicians from interventional procedures in which they participate. Using Health Level Seven (HL7) traffic between the anatomy/pathology information system and other major information systems, we were able to develop a semi-automatic 'tickler' system that can notify clinicians of pathology results as well as the absence of pathology results after a specified time interval. By using this system, radiologists can get more rapid feedback concerning their interpretations and thereby learn to distinguish false positive from true positive cases. Potentially, fewer patients would fall through the follow-up cracks when using our system versus a paper-based method. The system demonstrates, among other things, how HL7 information can be a powerful tool at an institution when used for purposes for which it was not intentionally designed.

  10. [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.

  11. Renin-Angiotensin System Genes Polymorphisms and Essential Hypertension in Burkina Faso, West Africa

    PubMed Central

    Tchelougou, Daméhan; Kologo, Jonas K.; Karou, Simplice D.; Yaméogo, Valentin N.; Bisseye, Cyrille; Djigma, Florencia W.; Ouermi, Djeneba; Compaoré, Tegwindé R.; Assih, Maléki; Pietra, Virginio; Zabsonré, Patrice; Simpore, Jacques

    2015-01-01

    Objective. This study aimed to investigate the association between three polymorphisms of renin-angiotensin system and the essential hypertension in the population of Burkina Faso. Methodology. This was a case-control study including 202 cases and 204 matched controls subjects. The polymorphisms were identified by a classical and a real-time PCR. Results. The AGT 235M/T and AT1R 1166A/C polymorphisms were not associated with the hypertension while the genotype frequencies of the ACE I/D polymorphism between patients and controls (DD: 66.83% and 35.78%, ID: 28.22% and 50.98%, II: 4.95% and 13.24%, resp.) were significantly different (p < 10−4). The genotype DD of ACE gene (OR = 3.40, p < 0.0001), the increasing age (OR = 3.83, p < 0.0001), obesity (OR = 4.84, p < 0.0001), dyslipidemia (OR = 3.43, p = 0.021), and alcohol intake (OR = 2.76, p < 0.0001) were identified as the independent risk factors for hypertension by multinomial logistic regression. Conclusion. The DD genotype of the ACE gene is involved in susceptibility to hypertension. Further investigations are needed to better monitor and provide individualized care for hypertensive patients. PMID:26351579

  12. Renal Oxidative Stress Induced by Long-Term Hyperuricemia Alters Mitochondrial Function and Maintains Systemic Hypertension

    PubMed Central

    Cristóbal-García, Magdalena; García-Arroyo, Fernando E.; Arellano-Buendía, Abraham S.; Madero, Magdalena; Rodríguez-Iturbe, Bernardo; Pedraza-Chaverrí, José; Zazueta, Cecilia; Johnson, Richard J.; Sánchez Lozada, Laura-Gabriela

    2015-01-01

    We addressed if oxidative stress in the renal cortex plays a role in the induction of hypertension and mitochondrial alterations in hyperuricemia. A second objective was to evaluate whether the long-term treatment with the antioxidant Tempol prevents renal oxidative stress, mitochondrial alterations, and systemic hypertension in this model. Long-term (11-12 weeks) and short-term (3 weeks) effects of oxonic acid induced hyperuricemia were studied in rats (OA, 750 mg/kg BW), OA+Allopurinol (AP, 150 mg/L drinking water), OA+Tempol (T, 15 mg/kg BW), or vehicle. Systolic blood pressure, renal blood flow, and vascular resistance were measured. Tubular damage (urine N-acetyl-β-D-glucosaminidase) and oxidative stress markers (lipid and protein oxidation) along with ATP levels were determined in kidney tissue. Oxygen consumption, aconitase activity, and uric acid were evaluated in isolated mitochondria from renal cortex. Short-term hyperuricemia resulted in hypertension without demonstrable renal oxidative stress or mitochondrial dysfunction. Long-term hyperuricemia induced hypertension, renal vasoconstriction, tubular damage, renal cortex oxidative stress, and mitochondrial dysfunction and decreased ATP levels. Treatments with Tempol and allopurinol prevented these alterations. Renal oxidative stress induced by hyperuricemia promoted mitochondrial functional disturbances and decreased ATP content, which represent an additional pathogenic mechanism induced by chronic hyperuricemia. Hyperuricemia-related hypertension occurs before these changes are evident. PMID:25918583

  13. Renal oxidative stress induced by long-term hyperuricemia alters mitochondrial function and maintains systemic hypertension.

    PubMed

    Cristóbal-García, Magdalena; García-Arroyo, Fernando E; Tapia, Edilia; Osorio, Horacio; Arellano-Buendía, Abraham S; Madero, Magdalena; Rodríguez-Iturbe, Bernardo; Pedraza-Chaverrí, José; Correa, Francisco; Zazueta, Cecilia; Johnson, Richard J; Lozada, Laura-Gabriela Sánchez

    2015-01-01

    We addressed if oxidative stress in the renal cortex plays a role in the induction of hypertension and mitochondrial alterations in hyperuricemia. A second objective was to evaluate whether the long-term treatment with the antioxidant Tempol prevents renal oxidative stress, mitochondrial alterations, and systemic hypertension in this model. Long-term (11-12 weeks) and short-term (3 weeks) effects of oxonic acid induced hyperuricemia were studied in rats (OA, 750 mg/kg BW), OA+Allopurinol (AP, 150 mg/L drinking water), OA+Tempol (T, 15 mg/kg BW), or vehicle. Systolic blood pressure, renal blood flow, and vascular resistance were measured. Tubular damage (urine N-acetyl-β-D-glucosaminidase) and oxidative stress markers (lipid and protein oxidation) along with ATP levels were determined in kidney tissue. Oxygen consumption, aconitase activity, and uric acid were evaluated in isolated mitochondria from renal cortex. Short-term hyperuricemia resulted in hypertension without demonstrable renal oxidative stress or mitochondrial dysfunction. Long-term hyperuricemia induced hypertension, renal vasoconstriction, tubular damage, renal cortex oxidative stress, and mitochondrial dysfunction and decreased ATP levels. Treatments with Tempol and allopurinol prevented these alterations. Renal oxidative stress induced by hyperuricemia promoted mitochondrial functional disturbances and decreased ATP content, which represent an additional pathogenic mechanism induced by chronic hyperuricemia. Hyperuricemia-related hypertension occurs before these changes are evident.

  14. Gender and the systemic hypertension-snoring association: a questionnaire-based case-control study.

    PubMed

    Marrone, O; Bonsignore, M R; Fricano, L; Lo Coco, R; Cerasola, G; Bonsignore, G

    1998-01-01

    Since the role of gender in the association between hypertension and snoring is unknown, we studied it while accounting for age and body mass index (BMI) as confounding variables. A questionnaire on snoring was administered to 90 hypertensive (HT) subjects (45 men and 45 women) and to 90 normotensive (NT) subjects matched for gender, age and BMI. As expected, snoring was more commonly reported by men than by women, but no significant difference was found between HT and NT men, irrespective of age. Conversely, heavy snoring was more frequently reported by HT than NT women; habitual snoring was more common among young (age < 50 years) HT than NT women; and heavy snoring was more common among older (age > 50 years) HT than NT women. These data suggest an effect of gender on the hypertension-snoring association: in men, snoring may be accounted for by age and BMI whether or not hypertension is present, whereas in women the natural history of snoring appears different and more severe in HT than in NT. Although the mechanism(s) responsible for the differences between men and women are obscure at present, gender may be an important variable in the systemic hypertension-snoring association. PMID:9551872

  15. [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.

  16. The renin-angiotensin system and hypertension in autosomal recessive polycystic kidney disease.

    PubMed

    Goto, Miwa; Hoxha, Nita; Osman, Rania; Dell, Katherine Macrae

    2010-12-01

    Hypertension is a well-recognized complication of autosomal recessive polycystic kidney disease (ARPKD). The renin-angiotensin system (RAS) is a key regulator of blood pressure; however, data on the RAS in ARPKD are limited and conflicting, showing both up- and down-regulation. In the current study, we characterized intrarenal and systemic RAS activation in relationship to hypertension and progressive cystic kidney disease in the ARPKD orthologous polycystic kidney (PCK) rat. Clinical and histological measures of kidney disease, kidney RAS gene expression by quantitative real-time PCR, angiotensin II (Ang II) immunohistochemistry, and systemic Ang I and II levels were assessed in 2-, 4-, and 6-month-old cystic PCK and age-matched normal rats. PCK rats developed hypertension and progressive cystic kidney disease without significant worsening of renal function or relative kidney size. Intrarenal renin, ACE and Ang II expression was increased significantly in cystic kidneys; angiotensinogen and Ang II Type I receptor were unchanged. Systemic Ang I and II levels did not differ. This study demonstrates that intrarenal, but not systemic, RAS activation is a prominent feature of ARPKD. These findings help reconcile previous conflicting reports and suggest that intrarenal renin and ACE gene upregulation may represent a novel mechanism for hypertension development or exacerbation in ARPKD.

  17. 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. PMID:20422212

  18. Molecular adaptations in vasoactive systems during acute stroke in salt-induced hypertension.

    PubMed

    Ventura, Nicole M; Peterson, Nichole T; Tse, M Yat; Andrew, R David; Pang, Stephen C; Jin, Albert Y

    2015-01-01

    Investigations regarding hypertension and dietary sodium, both factors that influence stroke risk, have previously been limited to using genetically disparate treatment and control groups, namely the stroke-prone, spontaneously hypertensive rat and Wistar-Kyoto rat. In this investigation, we have characterized and compared cerebral vasoactive system adaptations following stroke in genetically identical, salt-induced hypertensive, and normotensive control mice. Briefly, ANP(+/-) (C57BJ/6 × SV129 background) mice were fed chow containing either 0.8% NaCl (NS) or 8.0% NaCl (HS) for 7 weeks. Transient cerebral ischemia was induced by middle cerebral artery occlusion (MCAO). Infarct volumes were measured 24-h post-reperfusion and the mRNA expression of five major vasoactive systems was characterized using qPCR. Along with previous publications, our data validate a salt-induced hypertensive state in ANP(+/-) mice fed HS chow as they displayed left ventricular hypertrophy, increased systolic blood pressure, and increased urinary sodium excretion. Following MCAO, mice fed HS exhibited larger infarct volumes than their dietary counterparts. In addition, significant up-regulation in Et-1 and Nos3 mRNA expression in response to salt and stroke suggests implications with increased cerebral damage in this group. In conclusion, our data demonstrate increased cerebral susceptibility to stroke in salt-induced hypertensive mice. More importantly, however, we have characterized a novel method of investigating hypertension and stroke with the use of genetically identical treatment and control groups. This is the first investigation in which genetic confounding variables have been eliminated. PMID:25391363

  19. Ocular Perfusion Pressure and Pulsatile Ocular Blood Flow in Normal and Systemic Hypertensive Patients

    PubMed Central

    Figueiredo, Carlos R; Miranda, Rafaela Morais; Cunha, Patricia LT; M Kanadani, Tereza Cristina; Dorairaj, Syril

    2015-01-01

    ABSTRACT Purpose: Glaucomatous neuropathy can be a consequence of insufficient blood supply, increase in intraocular pressure (IOP), or other risk factors that diminish the ocular blood flow. To determine the ocular perfusion pressure (OPP) in normal and systemic hypertensive patients. Materials and methods: One hundred and twenty-one patients were enrolled in this prospective and comparative study and underwent a complete ophthalmologic examination including slit lamp examination, Goldmann applanation tonometry, stereoscopic fundus examination, and pulsatile ocular blood flow (POBF) measurements. The OPP was calculated as being the medium systemic arterial pressure (MAP) less the IOP. Only right eye values were considered for calculations using Student’s t-test. Results: The mean age of the patients was 57.5 years (36-78), and 68.5% were women. There was a statistically significant difference in the OPP of the normal and systemic hypertensive patients (p < 0.05). The difference in the OPP between these groups varied between 8.84 and 17.9 mm Hg. Conclusion: The results of this study suggest that although the systemic hypertensive patients have a higher OPP in comparison to normal patients, this increase does not mean that they also have a higher OBF (as measured by POBF tonograph). This may be caused by chronic changes in the vascular network and in the blood hemodynamics in patients with systemic hypertension. How to cite this article: Kanadani FN, Figueiredo CR, Miranda RM, Cunha PLT, Kanadani TCM, Dorairaj S. Ocular Perfusion Pressure and Pulsatile Ocular Blood Flow in Normal and Systemic Hypertensive Patients. J Curr Glaucoma Pract 2015;9(1):16-19. PMID:26997827

  20. 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.

  1. Methanol intoxication: pathological changes of central nervous system (17 cases).

    PubMed

    Karayel, Ferah; Turan, Arzu A; Sav, Aydin; Pakis, Isil; Akyildiz, Elif U; Ersoy, Gokhan

    2010-03-01

    The nervous system has increased susceptibility for methanol intoxication. The aim of this study is to investigate various central nervous system lesions of methanol intoxication in 17 cases autopsied in the mortuary department of the Council of Forensic Medicine in Istanbul, Turkey. The reasons of methanol intoxication in the cases was likely the unwitting ingestion of methanol while drinking illegal alcohol. Survival times ranged from several hours to days. In 8 cases (47%), cerebral edema and in 9 cases (53%) at occipital, temporal and parietal cortex, basal ganglia and pons, petechial bleeding was observed. In addition to these findings, hemorrhagic necrosis were observed in thalamus, putamen, and globus pallidus in 5 cases (29.4%) and, in cerebral cortex in another 3 cases (17.6%). In 3 of the cases (17.6%) in which cerebral edema was found, herniation findings accompanied to the situation and in 2 cases (11.7%), pons bleeding was observed. Around the basal ganglia, in 2 of the cases with hemorrhagic necrosis, the situation ended with a ventricular compression. In 7 cases (41%), the associated findings of chronic ischemic changes in cortical neurons, lacunae formation, degeneration of granular cell layer of the cerebellum, and reactive gliosis were considered as the results of chronic alcoholism.

  2. [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. PMID:26973987

  3. The systemic pathology of cerebral malaria in African children

    PubMed Central

    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). PMID:25191643

  4. Curcumin aggravates CNS pathology in experimental systemic lupus erythematosus.

    PubMed

    Foxley, Sean; Zamora, Marta; Hack, Bradley; Alexander, Rebecca Rashmi; Roman, Brian; Quigg, Richard John; Alexander, Jessy John

    2013-04-01

    Complement activation and inflammation are key disease features of systemic lupus erythematosus. Curcumin is an anti-inflammatory agent that inhibits the complement cascade. Therefore, we hypothesized that curcumin will be protective in CNS lupus. To assess the effect of curcumin on CNS-lupus, MRL/lpr mice were used. Brain MRI showed that curcumin (30mg/kg body wt. i.p. from 12-20 weeks) worsened regional brain atrophy. The volumes of the lateral and third ventricles are significantly increased (150%-213% and 107%-140%, without and with treatment respectively compared to MRL+/+ controls). The hippocampus was reduced further (83%-81%) by curcumin treatment. In line with increased brain atrophy, there were edematous cells (41% increase in cell size in MRL/lpr compared to MRL+/+ mice. The cell size was further increased by 28% when treated with curcumin; p<0.02) in the cortex. In line with increased atrophy and edema, there was a significant increase (p<0.02) in the mRNA and protein expression of the water channel protein, aquaporin 4 in these mice. The increase in the matrix proteins, glial fibrillary acidic protein and vimentin in lupus mice in the hippocampus was prevented by curcumin. Curcumin increased IgG deposits and decreased C3 deposits in brain with a corresponding increase in immune complexes and decrease in C3 concentration (by 60% in MRL/lpr mice Vs. MRL+/+ mice and a further 26% decrease when treated with curcumin) in circulation. Decrease in C3 could alter the transport of immune complexes leading to an increase in IgG deposits which could induce inflammatory pathways thereby leading to worsening of the disease. The neurological outcome as measured by maze performance indicates that the curcumin treated mice performed poorly compared to the untreated counterparts. Our results for the first time provide evidence that at the dose used in this study, curcumin aggravates some CNS disease manifestations in experimental lupus brain. Therefore, until a safe

  5. 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

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

    PubMed Central

    Kalil, Graziela Z; Haynes, William G

    2013-01-01

    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. PMID:22048570

  7. Effect of a renin-system inhibitor on blood-vessel adaptation in spontaneously hypertensive rats.

    PubMed

    Gould, A B; Goodman, S A

    1987-07-01

    We tested the hypothesis that a metabolic error may be the triggering mechanism which leads to blood-vessel hypertrophy and hypertension. Young spontaneously hypertensive rats (SHR) were fed a moderately high salt diet to exacerbate the purported metabolic error. Haematocrit values and rubidium transport were measured as evidence of renal ATP deficiency and blood-vessel adaptation. The renin system was inhibited in two groups of SHR by giving them enalapril to determine whether angiotensin II was involved in blood-vessel adaptation. Spontaneously hypertensive rats fed the moderately high salt diet had higher haematocrit values than normotensive rats fed the same diet or SHR fed Purina rat food, suggesting a renal ATP deficiency. Spontaneously hypertensive rats had higher Na+,K+-ATPase activity in thoracic aorta after 60 min incubation than a similar group given enalapril (P less than 0.001), suggesting blood-vessel adaptation. Possibly, angiotensin II within the vasa vasorum stimulates hypertrophy which, according to the Folkow hypothesis, leads to higher blood pressure, but may concomitantly increase the respiratory chain units which provide ATP for renal function and ion transport.

  8. 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

  9. [Principles in the organization of voluntary certifying system for studies and services in pathologic anatomy].

    PubMed

    Pal'tsev, M A; Kakturskiĭ, L V

    2006-01-01

    The aim of voluntary certification is to improve the quality of pathology service and to implement it under the Russian Federation's laws and existing standards. The noncommercial organization "Voluntary Certifying System for Postmortem Studies" has been set up, which includes expert groups comprising highly skilled specialists.

  10. Blast injury of the auditory system: a review of the mechanisms and pathology.

    PubMed

    Garth, R J

    1994-11-01

    Blast injury of the auditory system is uncommon and our knowledge incomplete. This article reviews the literature to date giving an account of the interactions of blast waves with the ear, the mechanisms of injury, the pathology, the clinical features, and an outline of management principles. PMID:7829942

  11. Activation of the Endothelin System Mediates Pathological Angiogenesis during Ischemic Retinopathy

    PubMed Central

    Patel, Chintan; Narayanan, S. Priya; Zhang, Wenbo; Xu, Zhimin; Sukumari-Ramesh, Sangeetha; Dhandapani, Krishnan M.; Caldwell, R. William; Caldwell, Ruth B.

    2015-01-01

    Retinopathy of prematurity adversely affects premature infants because of oxygen-induced damage of the immature retinal vasculature, resulting in pathological neovascularization (NV). Our pilot studies using the mouse model of oxygen-induced retinopathy (OIR) showed marked increases in angiogenic mediators, including endothelins and endothelin receptor (EDNR) A. We hypothesized that activation of the endothelin system via EDNRA plays a causal role in pathological angiogenesis and up-regulation of angiogenic mediators, including vascular endothelial growth factor A (VEGFA) in OIR. Mice were exposed to 75% oxygen from post-natal day P7 to P12, treated with either vehicle or EDNRA antagonist BQ-123 or EDNRB antagonist BQ-788 on P12, and kept at room air from P12 to P17 (ischemic phase). RT-PCR analysis revealed increased levels of EDN2 and EDNRA mRNA, and Western blot analysis revealed increased EDN2 expression during the ischemic phase. EDNRA inhibition significantly increased vessel sprouting, resulting in enhanced physiological angiogenesis and decreased pathological NV, whereas EDNRB inhibition modestly improved vascular repair. OIR triggered significant increases in VEGFA protein and mRNA for delta-like ligand 4, apelin, angiopoietin-2, and monocyte chemoattractant protein-1. BQ-123 treatment significantly reduced these alterations. EDN2 expression was localized to retinal glia and pathological NV tufts of the OIR retinas. EDN2 also induced VEGFA protein expression in cultured astrocytes. In conclusion, inhibition of the EDNRA during OIR suppresses pathological NV and promotes physiological angiogenesis. PMID:25203536

  12. 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.

  13. 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.

  14. High incidence of pulmonary arterial hypertension in systemic sclerosis patients with anti-centriole autoantibodies.

    PubMed

    Hamaguchi, Yasuhito; Matsushita, Takashi; Hasegawa, Minoru; Ueda-Hayakawa, Ikuko; Sato, Sinichi; Takehara, Kazuhiko; Fujimoto, Manabu

    2015-09-01

    Systemic sclerosis (SSc)-related autoantibodies are useful tools in identifying clinically homogenous subsets of patients and predicting their prognosis. In this report, we described five SSc patients with anti-centriole antibodies. All five patients were females and had digital ulcers/gangrene. Four of five (80%) patients had pulmonary arterial hypertension (PAH). None of the five patients had active pulmonary fibrosis or developed renal crisis. Anti-centriole antibodies may be a marker for PAH and digital ulcers/gangrene.

  15. [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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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

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

    PubMed

    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

    2016-07-28

    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

  2. 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.

  3. Recent Update of Renin-angiotensin-aldosterone System in the Pathogenesis of Hypertension.

    PubMed

    Moon, Ju-Young

    2013-12-01

    The activation of renin-angiotensin-aldosterine system(RAAS) is one of the main pathogenesis of hypertension. All the components of RAAS are present in the kidneys at higher concentrations compared to plasma levels, and intrarenal formation of angiotensin II (Ang II) is independent of the systemic RAAS. There are some unique features in intrarenal RAAS compared to systemic RAAS. Unlike JG cells where Ang II inhibits renin release via the AngII type 1 (AT1) receptor by negative feedback, in the collecting duct Ang II stimulates renin expression via the AT1 receptor. Upregulated renin produced in the distal nephron may be able to support continued intrarenal Ang II formation leading to amplification or maintenance of the hypertensive state.The recently discovered angiotensin-converting enzyme-related carboxypeptidase 2 (ACE2)-Angiotensin-(1-7) Ang-(1-7)-Mas receptor axis has an opposing function to that of the ACE-Ang II-AT1 receptor axis.The ACE2 deficiency was associated with an increase in blood pressure, and ACE2 knockout mice have highlighted hypertensive response to Ang II infusion associated with exaggerated accumulation of Ang II in the kidney. Recently, several numbers of patients have been evaluated as the activators of ACE2-Ang-(1-7)-Mas receptor axis, which can be divided into two main classes: aimed to increase the activity of ACE2, and directed to stimulate the Ang-(1-7) receptor Mas. In order to investigate new targets for hypertension and kidney disease, further research on the function of the ACE-Ang-(1-7)-Mas receptor axis is required.

  4. 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

  5. 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

  6. Trientine and renin-angiotensin system blockade ameliorate progression of glomerular morphology in hypertensive experimental diabetic nephropathy.

    PubMed

    Moya-Olano, Leire; Milne, Helen Marie; Robinson, Jillian Margaret; Hill, Jonathan Vernon; Frampton, Christopher Miles; Abbott, Helen Frances; Turner, Rufus; Kettle, Anthony James; Endre, Zoltán Huba

    2011-11-01

    A comparison of the efficacy of the copper chelator, trientine, with combined renin angiotensin system (RAS) blockade on the progression of glomerular pathology in the diabetic (mREN-2)27 rat is reported. Animals were treated for 2 months with trientine, combined RAS blockers, combined trientine plus RAS blockers or none. Treatments began after inducing diabetes with streptozotocin. Physiological data were recorded monthly and light microscopic glomerular features were scored. Plasma allantoin and both plasma and renal protein carbonyls were measured as markers of oxidative stress. Trientine and RAS blockade decreased proteinuria and albuminuria and prevented an increase in creatinine clearance and kidney weight. Both reduced the diabetes-related glomerular features of mesangiolysis and glomerular segmental hypocellularity and trientine prevented severe tuft-to-capsule adhesion and reduced tubularization. Hypertension-related severe mesangial matrix expansion and global hypercellularity were increased by both treatments, which may reflect repair of mesangiolysis. Trientine reduced plasma but not renal protein carbonyls or plasma allantoin. In this model, trientine prevented the development of many diabetes-specific features similarly to RAS blockade. Amelioration of oxidative stress and features commonly observed in human diabetic nephropathy (DN), support a diabetes-related defect in copper (Cu) metabolism. The addition of Cu(II) chelation may improve current DN therapy.

  7. Low Response of Renin–Angiotensin System to Sodium Intake Intervention in Chinese Hypertensive Patients

    PubMed Central

    Feng, Weijing; Cai, Qingqing; Yuan, Woliang; Liu, Yu; Bardeesi, Adham Sameer A.; Wang, Jingfeng; Chen, Jie; Huang, Hui

    2016-01-01

    Abstract The interactions of sodium balance and response of renin–angiotensin–aldosterone system are important for maintaining the hemodynamic stability in physiological conditions. However, the influence of short-term sodium intake intervention in the response of renin–angiotensin system (RAS) on hypertensive patients is still unclear. Thus, we conducted a clinical trial to investigate the effects of short-term sodium intake intervention on the response of RAS in hypertensive patients. One hundred twenty-five primary Chinese hypertensive patients were divided into high, moderate, and low sodium groups by 24-hour urinary sodium excretion (UNa+). All the patients received a 10-day dietary sodium intake intervention with standardized sodium (173.91mmol/day) and potassium (61.53mmol/day). Blood pressure, urinary sodium, urinary potassium, plasma sodium, potassium, creatinine, the levels of plasma renin activity, plasma angiotensin II concentrations (AT-II), and plasma aldosterone concentrations were detected before and after the intervention. Before the intervention, no differences were found in blood pressure and RAS among 3 groups. After standardized dietary sodium intake intervention, both UNa+ excretion and systolic pressure decreased in high-sodium group, while they increased in moderate and low-sodium groups. Intriguingly, there were no changes in the levels of plasma renin activity, AT-II, and plasma aldosterone concentrations among 3 groups during the intervention. The present study demonstrated that the influenced sodium excretion and blood pressure by short-term sodium intake intervention were independent of RAS quick response in Chinese hypertensive patients. PMID:26871780

  8. Wallerian Degeneration in Central Nervous System: Dynamic Associations between Diffusion Indices and Their Underlying Pathology

    PubMed Central

    Piao, Yueshan; Guo, Deyu; Zhu, Zixin; Tian, Xin; Li, Kuncheng; Yu, Chunshui

    2012-01-01

    Background Although diffusion tensor imaging has been used to monitor Wallerian degeneration, the exact relationship between the evolution of diffusion indices and its underlying pathology, especially in central nervous system, remains largely unknown. Here we aimed to address this question using a cat Wallerian degeneration model of corticospinal tract. Methodology/Principal Findings Twenty-five domestic mature Felis catus were included in the present study. The evolution of diffusion indices, including mean diffusivity (MD), fractional anisotropy (FA), primary (λ1) and transverse eigenvalues (λ23) of the degenerated corticospinal tract, were observed at baseline (before modeling) and at 2, 4, 6, 8, 10, 15, 20, 25, 30, 45 and 60 days after modeling in 4 cats. Pathological examinations were performed at eight time points mentioned above. Wallerian degeneration can be detected as early as the 2nd day after modeling by both diffusion tensor imaging and pathology. According to the evolution of diffusion indices, Wallerian degeneration can be classified into 2 stages. During the early stage (within 8 days after modeling), progressive disintegration of axons and myelin sheaths underlies the decreases in FA and λ1 and the increase in λ23. However, during the late stage (after 8 days), the gradual increases in FA, MD and λ1 and the unchanged λ23 seem to be a comprehensive reflection of the pathological processes including microglia activation, myelin clearance, and astrocytosis. Conclusions/Significance Our findings help the understanding of the altered diffusion indices in the context of pathology and suggest that diffusion tensor imaging has the potential to monitor the processes of Wallerian degeneration in the central nervous system in vivo after acute damage. PMID:22829950

  9. [Alterations of calcium, magnesium, and zinc in essential hypertension:their relation to the renin-angiotensin-aldosterone system].

    PubMed

    García Zozaya, J L; Padilla Viloria, M

    1997-11-01

    Based on our studies at the Hypertension research unit, we have found that the renin-angiotensin aldosterone. System (RAAS) undergoes several changes being the following the most relevant: Low plasma renin concentration (LPRC), while the plasma Aldosterone concentration is high (HPAC). At the same time we found calcium metabolism alterations: High urine calcium excretion, low serum ionic calcium and high PTH level. This alterations are more evident if the elder patient become hypertensive. We have found this changes in several groups in our community: black, ancient, obese and diabetic patients; who more often suffer hypertension and they must be followed up closely. In this group there are the sodium dependent hypertensive and they are the one who can get beneficial effects from the low salt diet and high calcium intake. When we studied the low plasma renin hypertensive we found the calcium changes mentioned before in ancient patient, as well as, high urine Zinc excretion. When we gave and oral calcium supplement to these patients, we saw that the calcium and Zinc alterations mentioned before were corrected. The high plasma renin concentration hypertensive patients showed low serum magnesium concentration and high urine magnesium excretion. A brief comment on the possible role of oxidative stress on essential hypertension is made. PMID:9471228

  10. Serum VEGF levels are related to the presence of pulmonary arterial hypertension in systemic sclerosis

    PubMed Central

    Papaioannou, Andriana I; Zakynthinos, Epaminondas; Kostikas, Konstantinos; Kiropoulos, Theodoros; Koutsokera, Angela; Ziogas, Athanasios; Koutroumpas, Athanasios; Sakkas, Lazaros; Gourgoulianis, Konstantinos I; Daniil, Zoe D

    2009-01-01

    Background The association between systemic sclerosis and pulmonary arterial hypertension (PAH) is well recognized. Vascular endothelial growth factor (VEGF) has been reported to play an important role in pulmonary hypertension. The aim of the present study was to examine the relationship between systolic pulmonary artery pressure, clinical and functional manifestations of the disease and serum VEGF levels in systemic sclerosis. Methods Serum VEGF levels were measured in 40 patients with systemic sclerosis and 13 control subjects. All patients underwent clinical examination, pulmonary function tests and echocardiography. Results Serum VEGF levels were higher in systemic sclerosis patients with sPAP ≥ 35 mmHg than in those with sPAP < 35 mmHg (352 (266, 462 pg/ml)) vs (240 (201, 275 pg/ml)) (p < 0.01), while they did not differ between systemic sclerosis patients with sPAP < 35 mmHg and controls. Serum VEGF levels correlated to systolic pulmonary artery pressure, to diffusing capacity for carbon monoxide and to MRC dyspnea score. In multiple linear regression analysis, serum VEGF levels, MRC dyspnea score, and DLCO were independent predictors of systolic pulmonary artery pressure. Conclusion Serum VEGF levels are increased in systemic sclerosis patients with sPAP ≥ 35 mmHg. The correlation between VEGF levels and systolic pulmonary artery pressure may suggest a possible role of VEGF in the pathogenesis of PAH in systemic sclerosis. PMID:19426547

  11. 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.

  12. Exercise stress echocardiography for detection of pulmonary arterial hypertension in a patient with systemic sclerosis.

    PubMed

    Cotrim, Carlos; Cordeiro, Ana; Loureiro, Maria José; Santos, Maria José; Simões, Otília; Cordeiro, Pedro; da Silva, J Canas; Carrageta, Manuel

    2006-02-01

    The authors report the case of a 57-year-old patient, diagnosed with systemic sclerosis 16 years ago. She had been followed in the rheumatology outpatient clinic since 2003 and complained of marked fatigue and dyspnea on exertion. In addition to full medical evaluation, she also underwent standard Doppler echocardiography at rest, which was unremarkable, and exercise stress echocardiography. In the latter examination, she was diagnosed with pulmonary arterial hypertension, later confirmed during right heart catheterization. The authors discuss the potential value of this methodology for the study of patients with systemic sclerosis.

  13. 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%.

  14. Harnessing the Immune System for Treatment and Detection of Tau Pathology

    PubMed Central

    Congdon, Erin E.; Krishnaswamy, Senthilkumar; Sigurdsson, Einar M.

    2014-01-01

    The tau protein is an attractive target for therapy and diagnosis. We started a tau immunotherapy program about 13 years ago and have since demonstrated that active and passive immunotherapies diminish tau pathology and improve function, including cognition, in different mouse models. These findings have been confirmed and extended by several groups. We routinely detect neuronal, and to a lesser extent microglial, antibody uptake correlating with tau pathology. Antibodies bind tau aggregates in the endosomal/lysosomal system, enhancing clearance presumably by promoting their disassembly. Extracellular clearance has recently been shown by others, using antibodies that apparently are not internalized. As most pathological tau is neuronal, intracellular targeting may be more efficacious. However, extracellular tau may be more accessible to antibodies, with tau-antibody complexes a target for microglial phagocytosis. The extent of involvement of each pathway may depend on numerous factors including antibody properties, degree of pathology, and experimental model. On the imaging front, multiple tau ligands derived from β-sheet dyes have been developed by several groups, some with promising results in clinical PET tests. Postmortem analysis should clarify their tau specificity, as in theory and based on histological staining, those are likely to have some affinity for various amyloids. We are developing antibody-derived tau probes that should be more specific, and have in mouse models shown in vivo detection and binding to pathological tau after peripheral injection. These are exciting times for research on tau therapies and diagnostic agents that hopefully can be applied to humans in the near future. PMID:24603943

  15. Harnessing the immune system for treatment and detection of tau pathology.

    PubMed

    Congdon, Erin E; Krishnaswamy, Senthilkumar; Sigurdsson, Einar M

    2014-01-01

    The tau protein is an attractive target for therapy and diagnosis. We started a tau immunotherapy program about 13 years ago and have since demonstrated that active and passive immunotherapies diminish tau pathology and improve function, including cognition, in different mouse models. These findings have been confirmed and extended by several groups. We routinely detect neuronal, and to a lesser extent microglial, antibody uptake correlating with tau pathology. Antibodies bind tau aggregates in the endosomal/lysosomal system, enhancing clearance presumably by promoting their disassembly. Extracellular clearance has recently been shown by others, using antibodies that apparently are not internalized. As most pathological tau is neuronal, intracellular targeting may be more efficacious. However, extracellular tau may be more accessible to antibodies, with tau-antibody complexes a target for microglial phagocytosis. The extent of involvement of each pathway may depend on numerous factors including antibody properties, degree of pathology, and experimental model. On the imaging front, multiple tau ligands derived from β-sheet dyes have been developed by several groups, some with promising results in clinical PET tests. Postmortem analysis should clarify their tau specificity, as in theory and based on histological staining, those are likely to have some affinity for various amyloids. We are developing antibody-derived tau probes that should be more specific, and have in mouse models shown in vivo detection and binding to pathological tau after peripheral injection. These are exciting times for research on tau therapies and diagnostic agents that hopefully can be applied to humans in the near future.

  16. The sympathetic nervous system through the ages: from Thomas Willis to resistant hypertension.

    PubMed

    Esler, Murray

    2011-07-01

    The 17th century London neuroanatomical school headed by Thomas Willis provided us with the first identifiable images of the sympathetic nervous system. Nineteenth century giants of European physiology (Bernard, Waller and Brown-Sequard) identified these as the 'pressor nerves'. Von Euler's demonstration that the sympathetic transmitter was noradrenaline brought the field into the modern era. The development of ganglion-blocking drugs by Paton, whose name this review commemorates, allowed comprehensive pharmacological antagonism of this system in patients. With the development of contemporary techniques for recording from human sympathetic nerves and quantifying rates of noradrenaline release, the sympathetic nervous system became accessible to clinical scientists investigating possible contributions to cardiovascular and other diseases. Sympathetic nervous system responses typically are regionally differentiated, with activation in one outflow sometimes accompanying no change or sympathetic inhibition in another. Regional sympathetic activity is best studied in humans by recording from postganglionic sympathetic efferents (multi-unit or single-fibre recording) and by isotope dilution-derived measurement of organ-specific noradrenaline release to plasma from sympathetic nerves (regional 'noradrenaline spillover'). With the application of these techniques, evidence has been assembled in the past three decades which indicates that sympathetic nervous system activation is crucial in the development of cardiovascular disorders, most notably heart failure and essential hypertension. An important goal for clinical scientists is translation of knowledge of pathophysiology, such as this, into better treatment for patients. The achievement of this 'mechanisms to management' transition is mature in cardiac failure, with knowledge of cardiac neural pathophysiology having led to introduction of β-adrenergic blockers, an effective therapy. Perhaps we are now on the cusp of

  17. [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.

  18. Retrieval in a Computer-assisted Pathology Encoding and Reporting System (CAPER).

    PubMed

    Robboy, S J; Altshuler, B S; Chen, H Y

    1981-05-01

    A previous report described an online computer-assisted pathology encoding and reporting system (CAPER) developed at the Massachusetts General Hospital that accessions specimens, monitors their state of completion, produces all log books, and permits instantaneous display of all diagnoses rendered within a three-year period. The present report updates the functions currently available and describes a new function that enables the pathologist, independent of computer programmer support, to request complex, in-depth searches of the entire accumulated pathology data base, which at present contains in excess of 150,000 cases and 5,000,000 pieces of information. The pathologist can instruct the system to compare more than 30 types of data items through the development of Boolean expressions. The report also describes the test codes that were developed to reflect the work product of the surgical pathology division, form the basis for automated billing and compilation of monthly and yearly statistics, and are an integral part of the long-term data base for in-depth searches.

  19. Design and analysis of a content-based pathology image retrieval system.

    PubMed

    Zheng, Lei; Wetzel, Arthur W; Gilbertson, John; Becich, Michael J

    2003-12-01

    A prototype, content-based image retrieval system has been built employing a client/server architecture to access supercomputing power from the physician's desktop. The system retrieves images and their associated annotations from a networked microscopic pathology image database based on content similarity to user supplied query images. Similarity is evaluated based on four image feature types: color histogram, image texture, Fourier coefficients, and wavelet coefficients, using the vector dot product as a distance metric. Current retrieval accuracy varies across pathological categories depending on the number of available training samples and the effectiveness of the feature set. The distance measure of the search algorithm was validated by agglomerative cluster analysis in light of the medical domain knowledge. Results show a correlation between pathological significance and the image document distance value generated by the computer algorithm. This correlation agrees with observed visual similarity. This validation method has an advantage over traditional statistical evaluation methods when sample size is small and where domain knowledge is important. A multi-dimensional scaling analysis shows a low dimensionality nature of the embedded space for the current test set.

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

    PubMed

    Wehner, A; Hartmann, K; Hirschberger, J

    2008-02-01

    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.

  1. 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. PMID:27250502

  2. 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.

  3. 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.

  4. 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. PMID:26214351

  5. Pattern-recognition system, designed on GPU, for discriminating between injured normal and pathological knee cartilage.

    PubMed

    Kostopoulos, Spiros; Sidiropoulos, Konstantinos; Glotsos, Dimitris; Athanasiadis, Emmanouil; Boutsikou, Konstantina; Lavdas, Eleftherios; Oikonomou, Georgia; Fezoulidis, Ioannis V; Vlychou, Marianna; Hantes, Michael; Cavouras, Dionisis

    2013-06-01

    The aim was to design a pattern-recognition (PR) system for discriminating between normal and pathological knee articular cartilage of the medial femoral (MFC) and tibial condyles (MTC). The data set comprised segmented regions of interest (ROIs) from coronal and sagittal 3-T magnetic resonance images of the MFC and MTC cartilage of young patients, 28 with abnormality-free knee and 16 with pathological findings. The PR system was designed employing the probabilistic neural network classifier, textural features from the segmented ROIs and the leave-one-out evaluation method, while the PR system's precision to "unseen" data was assessed by employing the external cross-validation method. Optimal system design was accomplished on a consumer graphics processing unit (GPU) using Compute Unified Device Architecture parallel programming. PR system design on the GPU required about 3.5 min against 15 h on a CPU-based system. Highest classification accuracies for the MFC and MTC cartilages were 93.2% and 95.5%, and accuracies to "unseen" data were 89% and 86%, respectively. The proposed PR system is housed in a PC, equipped with a consumer GPU, and it may be easily retrained when new verified data are incorporated in its repository and may be of value as a second-opinion tool in a clinical environment.

  6. 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.

  7. 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

  8. Portal Hypertension

    MedlinePlus

    ... Chronic Hepatitis C Additional Content Medical News Portal Hypertension By Steven K. Herrine, MD NOTE: This is ... Hepatic Encephalopathy Jaundice in Adults Liver Failure Portal Hypertension Portal hypertension is abnormally high blood pressure in ...

  9. [Secondary hypertension].

    PubMed

    Yoshida, Yuichi; Shibata, Hirotaka

    2015-11-01

    Hypertension is a common disease and a crucial predisposing factor of cardiovascular diseases. Approximately 10% of hypertensive patients are secondary hypertension, a pathogenetic factor of which can be identified. Secondary hypertension consists of endocrine, renal, and other diseases. Primary aldosteronism, Cushing's syndrome, pheochromocytoma, hyperthyroidism, and hypothyroidism result in endocrine hypertension. Renal parenchymal hypertension and renovascular hypertension result in renal hypertension. Other diseases such as obstructive sleep apnea syndrome are also very prevalent in secondary hypertension. It is very crucial to find and treat secondary hypertension at earlier stages since most secondary hypertension is curable or can be dramatically improved by specific treatment. One should keep in mind that screening of secondary hypertension should be done at least once in a daily clinical practice. PMID:26619670

  10. Systemic sclerosis-associated pulmonary hypertension: why disease-specific composite endpoints are needed

    PubMed Central

    2011-01-01

    Pulmonary arterial hypertension (PAH) is a serious complication of systemic sclerosis (SSc). In clinical trials PAH-SSc has been grouped with other forms, including idiopathic PAH. The primary endpoint for most pivotal studies was improvement in exercise capacity. However, composite clinical endpoints that better reflect long-term outcome may be more meaningful. We discuss potential endpoints and consider why the same measures may not be appropriate for both idiopathic PAH and PAH-SSc due to inherent differences in clinical outcome and management strategies of these two forms of PAH. Failure to take this into account may compromise progress in managing PAH in SSc. PMID:21699746

  11. Monitoring and Diagnostic Approaches for Pulmonary Arterial Hypertension in Patients with Systemic Sclerosis.

    PubMed

    Valenzuela, Antonia; Nandagopal, Saranya; Steen, Virginia D; Chung, Lorinda

    2015-08-01

    Pulmonary arterial hypertension (PAH) is one of the leading causes of death in patients with systemic sclerosis (SSc). Given the high prevalence and poor survival of SSc-PAH, and that aggressive management of mild disease may be associated with better outcomes, screening is critical. Right heart catheterization (RHC) is the gold standard for the definitive diagnosis of PAH, and should be performed in those patients in whom this diagnosis is suspected. Once a diagnosis of PAH is confirmed by RHC, treatment with PAH-specific therapies should be initiated as soon as possible.

  12. Role of Renin-Angiotensin-Aldosterone System in Metabolic Syndrome and Obesity-related Hypertension.

    PubMed

    Kamide, K

    2014-08-12

    Several recent clinical trials show that blocking agents of the renin-angiotensin-aldosterone system (RAAS) reduce cardiovascular events in patients with metabolic syndrome based on insulin resistance and obesity, especially accumulated visceral fat. Our laboratory has focused on the relationship between the vascular RAAS and the action of insulin on the vasculature. We first revealed that the addition of insulin to cultured vascular smooth muscle cells (VSMC) markedly increases angiotensinogen and angiotensin II (Ang II) expression and production. Insulin addition also induces VSMC growth that is inhibited by the blockade of the RAAS by either ACEI or ARB which suggests a role for the RAAS in insulin-mediated growth. Insulin has a quite different effect on cultured vascular endothelial cells (EC) as it reduces angiotensinogen and renin expression. However, insulin added to EC induces a marked activation of ACE and the activated ACE promotes the conversion of Ang I to Ang II and cell growth under conditions of high insulin concentration. Ang II induces the progression of atherosclerosis through the production of oxidative stress that blocks insulin signaling and accelerates atherosclerosis. In this paper, we attempt to clarify the relationship between insulin resistance, the RAAS, and oxidative stress in vascular tissues to mimic in vivo conditions found in patients with metabolic syndrome and obesity-related hypertension as previously I reviewed in "Current Hypertension Reviews" in 2010 [1]. In addition, I update the relationships between vascular RAAS and insulin resistance for the last 4 years. JSH-2014 [2] states that the target goals of blood pressure (BP) for diabetes patients is lower than 130/80 mmHg, whereas updated JNC 8 [3] and ESH-ESC 2013 [4] recommends the target BP was changed to <140/90 mmHg for hypertensive patients with diabetes. Patients with diabetes and hypertension have reduced mortality as well as improved cardiovascular and cerebrovascular

  13. Regulation of dopamine system responsivity and its adaptive and pathological response to stress

    PubMed Central

    Belujon, Pauline; Grace, Anthony A.

    2015-01-01

    Although, historically, the norepinephrine system has attracted the majority of attention in the study of the stress response, the dopamine system has also been consistently implicated. It has long been established that stress plays a crucial role in the pathogenesis of psychiatric disorders. However, the neurobiological mechanisms that mediate the stress response and its effect in psychiatric diseases are not well understood. The dopamine system can play distinct roles in stress and psychiatric disorders. It is hypothesized that, even though the dopamine (DA) system forms the basis for a number of psychiatric disorders, the pathology is likely to originate in the afferent structures that are inducing dysregulation of the DA system. This review explores the current knowledge of afferent modulation of the stress/DA circuitry, and presents recent data focusing on the effect of stress on the DA system and its relevance to psychiatric disorders. PMID:25788601

  14. 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

  15. [The role of endocannabinoid system in physiological and pathological processes in the eye].

    PubMed

    Nadolska, Krystyna; Goś, Roman

    2008-01-01

    Plant of Cannabis sativa/ marihuana except for its psychotropic effects possesses a range of pharmacological properties, that has been utilized for medical purposes over a period of millenia. Investigations concerning biochemical mechanism of action of the main and most active pharmacological compound of Cannabis sativa, cannabinoid 9-THC, contributed to the discovery of cannabinoid receptors both in the central nervous system (CNS) and peripheral tissues, that mediated actions of this substance. The discovery made possible identification of a new, endogenous signaling system reffered to as the endocannabinoid system. Besides cannabinoid receptors CB1 and CB2, the system includes it's endogenic ligands (endocannabinoids) and compounds that participate in their biosynthesis and inactivation. Structure and functioning of the endocannabinoid system is conservative in all vertebrates. It's activation with plant, synthetic and endogenous cannabinoids has an influence on multiple physiological and pathological processes within the eye.

  16. Swine model of chronic postcapillary pulmonary hypertension with right ventricular remodeling: long-term characterization by cardiac catheterization, magnetic resonance, and pathology.

    PubMed

    Pereda, Daniel; García-Alvarez, Ana; Sánchez-Quintana, Damián; Nuño, Mario; Fernández-Friera, Leticia; Fernández-Jiménez, Rodrigo; García-Ruíz, José Manuel; Sandoval, Elena; Aguero, Jaume; Castellá, Manuel; Hajjar, Roger J; Fuster, Valentín; Ibáñez, Borja

    2014-07-01

    Pulmonary hypertension (PH) is prevalent and carries high morbidity and mortality, mostly due to right ventricular (RV) dysfunction. Postcapillary PH is the most frequent form but there are no large-animal models available. We developed and characterized a porcine model of postcapillary PH by non-restrictive banding of the confluent of both inferior pulmonary veins (n = 10; sham controls n = 3). Right heart catheterization and magnetic resonance were performed before the procedure and monthly during 4 months. All banded animals developed PH. Compared to controls, banded animals presented higher mean pulmonary artery pressure [median (first to third quartile) 30 mmHg (25-37) vs. 20 mmHg (18-23); p = 0.018] and higher pulmonary vascular resistance [5.2 WU (3.8-7.1) vs. 2.3 WU (2.1-3.5); p = 0.028] after 2 months. Differences in indexed RV end-systolic volume [42 mL/m(2) (36-53) vs. 24 mL/m(2) (24-33); p = 0.028] and RV ejection fraction [59 % (54-63) vs. 66 % (64-68); p = 0.028] were also significant after 2 months. Differences remained significant throughout the study. Histopathology revealed increased lung weight and fibrosis but no increase in average water content. Also, remodeling on pulmonary arteries including increased medial and intimal thickness and fibrosis and RV myocardial disarray and fibrosis was demonstrated. Lung remodeling findings were similar in all pulmonary lobes.

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

    PubMed

    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

  18. 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

  19. Diminished L-arginine bioavailability in hypertension.

    PubMed

    Moss, Monique B; Brunini, Tatiana M C; Soares De Moura, Roberto; Novaes Malagris, Lúcia E; Roberts, Norman B; Ellory, J Clive; Mann, Giovanni E; Mendes Ribeiro, Antônio C

    2004-10-01

    L-Arginine is the precursor of NO (nitric oxide), a key endogenous mediator involved in endothelium-dependent vascular relaxation and platelet function. Although the concentration of intracellular L-arginine is well above the Km for NO synthesis, in many cells and pathological conditions the transport of L-arginine is essential for NO production (L-arginine paradox). The present study was designed to investigate the modulation of L-arginine/NO pathway in systemic arterial hypertension. Transport of L-arginine into RBCs (red blood cells) and platelets, NOS (NO synthase) activity and amino acid profiles in plasma were analysed in hypertensive patients and in an animal model of hypertension. Influx of L-arginine into RBCs was mediated by the cationic amino acid transport systems y+ and y+L, whereas, in platelets, influx was mediated only via system y+L. Chromatographic analyses revealed higher plasma levels of L-arginine in hypertensive patients (175+/-19 micromol/l) compared with control subjects (137+/-8 micromol/l). L-Arginine transport via system y+L, but not y+, was significantly reduced in RBCs from hypertensive patients (60+/-7 micromol.l(-1).cells(-1).h(-1); n=16) compared with controls (90+/-17 micromol.l(-1).cells(-1).h(-1); n=18). In human platelets, the Vmax for L-arginine transport via system y+L was 86+/-17 pmol.10(9) cells(-1).min(-1) in controls compared with 36+/-9 pmol.10(9) cells(-1).min(-1) in hypertensive patients (n=10; P<0.05). Basal NOS activity was decreased in platelets from hypertensive patients (0.12+/-0.02 pmol/10(8) cells; n=8) compared with controls (0.22+/-0.01 pmol/10(8) cells; n=8; P<0.05). Studies with spontaneously hypertensive rats demonstrated that transport of L-arginine via system y+L was also inhibited in RBCs. Our findings provide the first evidence that hypertension is associated with an inhibition of L-arginine transport via system y+L in both humans and animals, with reduced availability of L-arginine limiting NO synthesis

  20. Diminished L-arginine bioavailability in hypertension.

    PubMed

    Moss, Monique B; Brunini, Tatiana M C; Soares De Moura, Roberto; Novaes Malagris, Lúcia E; Roberts, Norman B; Ellory, J Clive; Mann, Giovanni E; Mendes Ribeiro, Antônio C

    2004-10-01

    L-Arginine is the precursor of NO (nitric oxide), a key endogenous mediator involved in endothelium-dependent vascular relaxation and platelet function. Although the concentration of intracellular L-arginine is well above the Km for NO synthesis, in many cells and pathological conditions the transport of L-arginine is essential for NO production (L-arginine paradox). The present study was designed to investigate the modulation of L-arginine/NO pathway in systemic arterial hypertension. Transport of L-arginine into RBCs (red blood cells) and platelets, NOS (NO synthase) activity and amino acid profiles in plasma were analysed in hypertensive patients and in an animal model of hypertension. Influx of L-arginine into RBCs was mediated by the cationic amino acid transport systems y+ and y+L, whereas, in platelets, influx was mediated only via system y+L. Chromatographic analyses revealed higher plasma levels of L-arginine in hypertensive patients (175+/-19 micromol/l) compared with control subjects (137+/-8 micromol/l). L-Arginine transport via system y+L, but not y+, was significantly reduced in RBCs from hypertensive patients (60+/-7 micromol.l(-1).cells(-1).h(-1); n=16) compared with controls (90+/-17 micromol.l(-1).cells(-1).h(-1); n=18). In human platelets, the Vmax for L-arginine transport via system y+L was 86+/-17 pmol.10(9) cells(-1).min(-1) in controls compared with 36+/-9 pmol.10(9) cells(-1).min(-1) in hypertensive patients (n=10; P<0.05). Basal NOS activity was decreased in platelets from hypertensive patients (0.12+/-0.02 pmol/10(8) cells; n=8) compared with controls (0.22+/-0.01 pmol/10(8) cells; n=8; P<0.05). Studies with spontaneously hypertensive rats demonstrated that transport of L-arginine via system y+L was also inhibited in RBCs. Our findings provide the first evidence that hypertension is associated with an inhibition of L-arginine transport via system y+L in both humans and animals, with reduced availability of L-arginine limiting NO synthesis

  1. 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.

  2. Screening for Hypertension Using Diagnostic Triaging: An Interactive Policy Analysis System

    PubMed Central

    Heidenberger, Kurt

    1982-01-01

    The paper describes the development of a system for screening and group-specific diagnostic management of patients with hypertension. Based on a single-period long-term model, the system is of potential value for administrative health care planning focusing on an effective allocation of a limited budget. Since the overall goal is insight not numbers the system is to be used in a “what...if” mode. The user specifies the problem he wants to consider choosing the decision criterion, the evaluation parameters and the algorithms. Input data can be modified interactively as well. Design criteria include flexibility, expandability, adaptability to various populations, and also portability and low-cost operation.

  3. Tinnitus: pathology of synaptic plasticity at the cellular and system levels

    PubMed Central

    Guitton, Matthieu J.

    2012-01-01

    Despite being more and more common, and having a high impact on the quality of life of sufferers, tinnitus does not yet have a cure. This has been mostly the result of limited knowledge of the biological mechanisms underlying this adverse pathology. However, the last decade has witnessed tremendous progress in our understanding on the pathophysiology of tinnitus. Animal models have demonstrated that tinnitus is a pathology of neural plasticity, and has two main components: a molecular, peripheral component related to the initiation phase of tinnitus; and a system-level, central component-related to the long-term maintenance of tinnitus. Using the most recent experimental data and the molecular/system dichotomy as a framework, we describe here the biological basis of tinnitus. We then discuss these mechanisms from an evolutionary perspective, highlighting similarities with memory. Finally, we consider how these discoveries can translate into therapies, and we suggest operative strategies to design new and effective combined therapeutic solutions using both pharmacological (local and systemic) and behavioral tools (e.g., using tele-medicine and virtual reality settings). PMID:22408611

  4. 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.

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

    PubMed Central

    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. PMID:26884889

  6. 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

  7. [Support by telecommunication of decisions in diagnostic pathology. Experience with the first telepathology system in Hungary].

    PubMed

    Gombás, P; Szende, B; Stotz, G

    1996-10-20

    The term of telepathology can be determined as diagnostic work of the pathologist at distance via an interactive telecommunication connection in which the image of the specimen appears on a monitor instead of viewing it directly through a microscope. Being a part of the telemedicine, the fast development of the telepathology is based on the revolution of the new digital technology. Technical advances of telecommunication and of image procession in the latest 80s have provided the means to transfer huge amount of visual information in narrow communication bandwidth in two direction link. In 1995 multiple live image transmission with simultaneous voice transfer has been performed between the Department of Pathology of MI Central Hospital and 1.st Institute of Pathology and Experimental Cancer Research of Semmelweis Medical University, Budapest. Transfer rate via ISDN channel was 128 kbit/sec. The first live image telemedicine system in CCE/NIS countries has achieved transmission of cytological smears, frozen sections and paraffin embedded slides supplemented with immunohistochemical preparations. Quality of visual information using video-conference software of standard H.320 was suitable for diagnosis. Development of global telepathology services depends on compatibility of different systems and on comprehensive examinations of cost, accessibility and quality for the clients and providers of telemedicine. Recent paper surveys shortly the historical development of the telepathology, analyses the essence of the new consultation technology, summaries the first experiences in Hungary and raises some questions have to be answered in the near future.

  8. 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

  9. Epigenetic Modifications in Essential Hypertension

    PubMed Central

    Wise, Ingrid A.; Charchar, Fadi J.

    2016-01-01

    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. PMID:27023534

  10. Hyperuricemia and hypertension.

    PubMed

    Feig, Daniel I

    2012-11-01

    Over the past century, uric acid has been considered a possible risk factor for hypertension and cardiovascular disease. However, only in the past decade, animal models and clinical trials have supported a more mechanistic link. Results from animal models suggest a 2-phase mechanism for the development of hyperuricemic hypertension in which uric acid induces acute vasoconstriction by activation of renin-angiotensin system, followed by uric acid uptake into vascular smooth muscle cells leading to cellular proliferation and secondary arteriolosclerosis that impairs pressure natriuresis. This acute hypertension remains uric acid dependent and sodium independent, whereas the chronic hypertension becomes uric acid independent and sodium dependent. Small clinical trials, performed in adolescents with newly diagnosed essential hypertension, demonstrate that reduction of serum uric acid can reduce blood pressure. Although more research is clearly necessary, the available data suggest that uric acid is likely causative in some cases of early onset hypertension.

  11. Hypertensive crisis in children.

    PubMed

    Chandar, Jayanthi; Zilleruelo, Gastón

    2012-05-01

    Hypertensive crisis is rare in children and is usually secondary to an underlying disease. There is strong evidence that the renin-angiotensin system plays an important role in the genesis of hypertensive crisis. An important principle in the management of children with hypertensive crisis is to determine if severe hypertension is chronic, acute, or acute-on-chronic. When it is associated with signs of end-organ damage such as encephalopathy, congestive cardiac failure or renal failure, there is an emergent need to lower blood pressures to 25-30% of the original value and then accomplish a gradual reduction in blood pressure. Precipitous drops in blood pressure can result in impairment of perfusion of vital organs. Medications commonly used to treat hypertensive crisis in children are nicardipine, labetalol and sodium nitroprusside. In this review, we discuss the pathophysiology, differential diagnosis and recent developments in management of hypertensive crisis in children.

  12. Accelerating Pathology Image Data Cross-Comparison on CPU-GPU Hybrid Systems

    PubMed Central

    Wang, Kaibo; Huai, Yin; Lee, Rubao; Wang, Fusheng; Zhang, Xiaodong; Saltz, Joel H.

    2012-01-01

    As an important application of spatial databases in pathology imaging analysis, cross-comparing the spatial boundaries of a huge amount of segmented micro-anatomic objects demands extremely data- and compute-intensive operations, requiring high throughput at an affordable cost. However, the performance of spatial database systems has not been satisfactory since their implementations of spatial operations cannot fully utilize the power of modern parallel hardware. In this paper, we provide a customized software solution that exploits GPUs and multi-core CPUs to accelerate spatial cross-comparison in a cost-effective way. Our solution consists of an efficient GPU algorithm and a pipelined system framework with task migration support. Extensive experiments with real-world data sets demonstrate the effectiveness of our solution, which improves the performance of spatial cross-comparison by over 18 times compared with a parallelized spatial database approach. PMID:23355955

  13. Accelerating Pathology Image Data Cross-Comparison on CPU-GPU Hybrid Systems.

    PubMed

    Wang, Kaibo; Huai, Yin; Lee, Rubao; Wang, Fusheng; Zhang, Xiaodong; Saltz, Joel H

    2012-07-01

    As an important application of spatial databases in pathology imaging analysis, cross-comparing the spatial boundaries of a huge amount of segmented micro-anatomic objects demands extremely data- and compute-intensive operations, requiring high throughput at an affordable cost. However, the performance of spatial database systems has not been satisfactory since their implementations of spatial operations cannot fully utilize the power of modern parallel hardware. In this paper, we provide a customized software solution that exploits GPUs and multi-core CPUs to accelerate spatial cross-comparison in a cost-effective way. Our solution consists of an efficient GPU algorithm and a pipelined system framework with task migration support. Extensive experiments with real-world data sets demonstrate the effectiveness of our solution, which improves the performance of spatial cross-comparison by over 18 times compared with a parallelized spatial database approach.

  14. Wnt and lithium: a common destiny in the therapy of nervous system pathologies?

    PubMed

    Meffre, Delphine; Grenier, Julien; Bernard, Sophie; Courtin, Françoise; Dudev, Todor; Shackleford, Ghjuvan'Ghjacumu; Jafarian-Tehrani, Mehrnaz; Massaad, Charbel

    2014-04-01

    Wnt signaling is required for neurogenesis, the fate of neural progenitors, the formation of neuronal circuits during development, neuron positioning and polarization, axon and dendrite development and finally for synaptogenesis. This signaling pathway is also implicated in the generation and differentiation of glial cells. In this review, we describe the mechanisms of action of Wnt signaling pathways and their implication in the development and correct functioning of the nervous system. We also illustrate how a dysregulated Wnt pathway could lead to psychiatric, neurodegenerative and demyelinating pathologies. Lithium, used for the treatment of bipolar disease, inhibits GSK3β, a central enzyme of the Wnt/β-catenin pathway. Thus, lithium could, to some extent, mimic Wnt pathway. We highlight the possible dialogue between lithium therapy and modulation of Wnt pathway in the treatment of the diseases of the nervous system.

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

    PubMed Central

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

    2011-01-01

    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 AT2 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. PMID:21951628

  16. 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.

  17. Systemic Inflammation: Methodological Approaches to Identification of the Common Pathological Process

    PubMed Central

    Zotova, N. V.; Chereshnev, V. A.; Gusev, E. Yu.

    2016-01-01

    We defined Systemic inflammation (SI) as a “typical, multi-syndrome, phase-specific pathological process, developing from systemic damage and characterized by the total inflammatory reactivity of endotheliocytes, plasma and blood cell factors, connective tissue and, at the final stage, by microcirculatory disorders in vital organs and tissues.” The goal of the work: to determine methodological approaches and particular methodical solutions for the problem of identification of SI as a common pathological process. SI can be defined by the presence in plasma of systemic proinflammatory cell stress products—cytokines and other inflammatory mediators, and also by the complexity of other processes signs. We have developed 2 scales: 1) The Reactivity Level scale (RL)–from 0 to 5 points: 0-normal level; RL-5 confirms systemic nature of inflammatory mediator release, and RL- 2–4 defines different degrees of event probability. 2) The SI scale, considering additional criteria along with RL, addresses more integral criteria of SI: the presence of ≥ 5 points according to the SI scale proves the high probability of SI developing. To calculate the RL scale, concentrations of 4 cytokines (IL-6, IL-8, IL-10, TNF-α) and C-reactive protein in plasma were examined. Additional criteria of the SI scale were the following: D-dimers>500ng/ml, cortisol>1380 or <100nmol/l, troponin I≥0.2ng/ml and/or myoglobin≥800ng/ml. 422 patients were included in the study with different septic (n-207) and aseptic (n-215) pathologies. In 190 cases (of 422) there were signs of SI (lethality 38.4%, n-73). In only 5 of 78 cases, lethality was not confirmed by the presence of SI. SI was registered in 100% of cases with septic shock (n-31). There were not significant differences between AU-ROC of CR, SI scale and SOFA to predict death in patients with sepsis and trauma. PMID:27153324

  18. 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

  19. Idiopathic systemic granulomatous pathology causing sudden death due to myocarditis: a rare case report.

    PubMed

    Singh, Harpal; Kundal, Ramesh

    2015-01-01

    Idiopathic granulomatous myocarditis is extremely rare, particularly since the introduction of drugs effective against tuberculosis (TB), viruses, fungi and the effective treatment of sarcoidosis. Here is a case of a 65-year-old female prisoner having history of sudden collapse and ultimately death. Autopsy findings of various viscera on histopathological examination show granulomatous pathology, that is, in spleen, liver and in the left ventricular wall of heart. Ziehl-Neelsen staining of the sections show the absence of acid fast bacilli, negative for fungal staining as most of the granulomas are noncaseating type with presence of giant cells having no asteroid body and Schuamann body, real-time polymerase chain reaction for TB is negative. Idiopathic giant cell myocarditis is a disease of relatively young adults, that is, between 3 rd and 4 th decade of life. So, this case is strongly considered to be a case of sudden death due to myocarditis as a result of idiopathic systemic granulomatous pathology, a rare case in in literature. PMID:25673606

  20. Development of fetal brain renin–angiotensin system and hypertension programmed in fetal origins

    PubMed Central

    Mao, Caiping; Shi, Lijun; Xu, Feichao; Zhang, Lubo; Xu, Zhice

    2010-01-01

    Since the concept of fetal origins of adult diseases was introduced in 1980s, the development of the renin–angiotensin system (RAS) in normal and abnormal patterns has attracted attention. Recent studies have shown the importance of the fetal RAS in both prenatal and postnatal development. This review focuses on the functional development of the fetal brain RAS, and ontogeny of local brain RAS components in utero. The central RAS plays an important role in the control of fetal cardiovascular responses, body fluid balance, and neuroendocrine regulation. Recent progress has been made in demonstrating that altered fetal RAS development as a consequence of environmental insults may impact on “programming” of hypertension later in life. Given that the central RAS is of equal importance to the peripheral RAS in cardiovascular regulation, studies on the fetal brain RAS development in normal and abnormal patterns could shed light on “programming” mechanisms of adult cardiovascular diseases in fetal origins. PMID:19428956

  1. 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.

  2. 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.

  3. 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.

  4. 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. PMID:24320073

  5. Effect of angiotensin II receptor blockade on autonomic nervous system function in patients with essential hypertension.

    PubMed

    Krum, Henry; Lambert, Elisabeth; Windebank, Emma; Campbell, Duncan J; Esler, Murray

    2006-04-01

    It has long been proposed that the renin-angiotensin system exerts a stimulatory influence on the sympathetic nervous system, including augmentation of central sympathetic outflow and presynaptic facilitation of norepinephrine release from sympathetic nerves. We tested this proposition in 19 patients with essential hypertension, evaluating whether the angiotensin receptor blockers (ARBs) eprosartan and losartan had identifiable antiadrenergic properties. This was done in a prospective, randomized, three-way placebo-controlled study of crossover design. Patients were randomized to 600 mg of eprosartan daily, 50 mg of losartan daily, or placebo. The treatment period was 4 wk, with 2-wk washout periods. Multiunit firing rates in efferent sympathetic nerves distributed to skeletal muscle vasculature (muscle sympathetic nerve activity, MSNA) were measured with microneurography, testing whether ARBs inhibit central sympathetic outflow. In parallel, isotope dilution methodology was used to measure whole body norepinephrine spillover to plasma. Mean blood pressure on placebo was 151/98 mmHg, with both ARBs causing reductions of approximately 11 mmHg systolic and 6 mmHg diastolic pressure, placebo corrected. Both MSNA [35 +/- 12 bursts/min (mean +/- SD) on placebo] and whole body norepinephrine spillover [366 +/- 247 ng/min] were unchanged by ARB administration, indicating that the ARBs did not materially inhibit central sympathetic outflow or act presynaptically to reduce norepinephrine release at existing rates of nerve firing. These findings contrast with the easily demonstrable reduction in sympathetic nervous activity produced by antihypertensive drugs of the imidazoline-binding class, which are known to act within the brain to inhibit sympathetic nervous outflow. We conclude that sympathetic nervous inhibition is not a major component of the blood pressure-lowering action of ARBs in essential hypertension.

  6. 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

  7. 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…

  8. 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.

  9. An interactive telemedicine system for remote speech-language pathology treatment.

    PubMed

    Brennan, D M; Barker, L M

    2004-01-01

    There is significant potential for delivering speech-language pathology services using telemedicine methods. However, current telemedicine and videoconferencing equipment has limitations that constrain the speech-language therapeutic interventions that can be delivered remotely. This work aimed to develop a telemedicine system that would extend the capabilities of existing videoconferencing equipment and integrate an array of clinically relevant and validated therapeutic tools and techniques. Through a user-centered iterative design framework, an earlier prototype system was expanded and enhanced to enable greater interaction between a speech-language clinician and client during a telemedicine session. The final system utilizes H.323 Internet-based videoconferencing with integrated T.120 data sharing features and allows for a wide range of treatment material and therapeutic interventions to be delivered to a remote client. The protocol for a case-study evaluation designed to evaluate the system as a means for providing comprehensive speech-language treatment has been developed and testing is underway. Preliminary results indicate that the system is a viable alternative to face-to-face treatment for adult clients with neurological impairments. PMID:17271377

  10. A systematic review on randomized control trials on rennin angiotensin aldosterone system inhibitors role in managing hypertension among hemodialysis patients.

    PubMed

    Aftab, Raja Ahsan; Khan, Amer Hayat; Adnan, Azreen Syazril; Jannah, Nurul

    2016-01-01

    Randomized control trials (RCTs) are considered as most rigors way of determining the cause-effect relationship of a treatment and outcome. Activation of rennin angiotensin aldosterone system (RAAS) is an important contributor to hypertension in hemodialysis patients. The prevalence of hypertension in hemodialysis patients varies from 60% to 80% and hypertension management alone with conventional hemodialysis is insufficient. Hence, the current review was aimed to investigate the effect of RAAS inhibitors in managing hypertension among hemodialysis patients in a randomized control trial. Using PUBMED and EMBASE databases, randomized control trial with primary or secondary outcomes related to the effect of RAAS inhibitors on blood pressure among hemodialysis patients were included for analysis. The current review also assessed the quality of reporting of RCT. A total of eight RCT met inclusion criteria for current review. According to modified jaded scale, one (12.5%) study scored four points for quality reporting, whereas two (25%) studies scored one point that was the least score. The mean score for all included studies was 2.25. Six (75%) of the eight RCT included, involved ARB in hypertension management among hemodialysis patients, whereas two (25%) studies involved angiotensin-converting enzyme (ACE) inhibitors. Of the siz RCT involving ARB, two (33.3%) RCT also included ACE inhibitors comparison group. Altogether six (75%) studies report a reduction in blood pressure with the use of RAAS inhibitors compared to control group; however, of the six studies, two (33.3%) reported that the reduction in blood pressure was not significant. Whereas, two (25%) studies reported no reduction in blood pressure compared to the control group. The findings from current review do not indicate a clear pattern for a role of RAAS inhibitors for hypertension control among hemodialysis patients. PMID:26853680

  11. Prospects for improving outcomes in systemic sclerosis-related pulmonary hypertension.

    PubMed

    Thakkar, V; Nikpour, M; Stevens, W M; Proudman, S M

    2015-03-01

    Pulmonary arterial hypertension (PAH) is a leading cause of morbidity and mortality in patients with systemic sclerosis (SSc). Approximately one in 10 will develop PAH during their lifetime. These patients have a worse prognosis than those with PAH due to other causes. The most common clinical feature of SSc-PAH in the early stages is non-specific exercise intolerance that can be erroneously attributed to other manifestations of SSc. Screening provides an opportunity for early identification of SSc-PAH and prompt initiation of therapies with the potential to improve quality of life and survival. International guidelines recommend annual transthoracic Doppler echocardiography (TTE), but TTE has limitations. The tricuspid regurgitant jet required for estimating the systolic pulmonary artery pressure is absent in up to 39% of patients, including a proportion with PAH. This has prompted a move to new screening algorithms that are less dependent on TTE. Not all pulmonary hypertension (PH) in patients with SSc is PAH. Other causes include PH secondary to left heart disease, interstitial lung disease-related PH, chronic thromboembolic PH and pulmonary veno-occlusive disease. With the advent of evidence-based therapies, including newer agents such as macitentan, riociguat and selexipag, the establishment of centres with expertise in PAH and the focus on early detection, there has been considerable improvement in survival. The role of anti-coagulation for SSc-PAH has been the subject of a recent meta-analysis of nine observational studies that suggests it may confer a survival benefit, but to date, there have been no randomised controlled trials to confirm this.

  12. 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

  13. 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.

  14. Malignant hypertension

    MedlinePlus

    ... NY: McGraw Hill; 2008:chap 280. Linas SL. Hypertensive crisis: emergency and urgency. In: Vincent J-L, Abraham ... Saunders; 2011:chap 88. Shayne P, Lynch CA. Hypertensive crisis. In: Adams JG, ed. Emergency Medicine: Clinical Essentials . ...

  15. [Pathology of the heart conducting system in the thanatogenesis of sudden death from alcoholic cardiomyopathy and coronary heart disease].

    PubMed

    Kul'bitskiĭ, B N; Larev, Z V; Fedulova, M V; Denisova, O P; Bogomolov, D V

    2012-01-01

    The present literature review is focused on the contribution of various pathological changes in the heart conducting system to the tanatogenesis of sudden death from alcoholic cardiomyopathy and coronary heart disease viewed from the perspective of a forensic medical expert. The currently available data on the disorders in the heart conducting system in the subjects with these diseases are presented. Various aspects of pathology of the heart conducting system are considered in the modern and historical contexts. The prospects for the further investigations into the tanatogenic mechanisms of sudden death by reason of alcoholic cardiomyopathy and coronary heart disease are outlined. PMID:22686063

  16. [Pathology of the heart conducting system in the thanatogenesis of sudden death from alcoholic cardiomyopathy and coronary heart disease].

    PubMed

    Kul'bitskiĭ, B N; Larev, Z V; Fedulova, M V; Denisova, O P; Bogomolov, D V

    2012-01-01

    The present literature review is focused on the contribution of various pathological changes in the heart conducting system to the tanatogenesis of sudden death from alcoholic cardiomyopathy and coronary heart disease viewed from the perspective of a forensic medical expert. The currently available data on the disorders in the heart conducting system in the subjects with these diseases are presented. Various aspects of pathology of the heart conducting system are considered in the modern and historical contexts. The prospects for the further investigations into the tanatogenic mechanisms of sudden death by reason of alcoholic cardiomyopathy and coronary heart disease are outlined.

  17. [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.

  18. Synoptic reporting in tumor pathology: advantages of a web-based system.

    PubMed

    Qu, Zhenhong; Ninan, Shibu; Almosa, Ahmed; Chang, K G; Kuruvilla, Supriya; Nguyen, Nghia

    2007-06-01

    The American College of Surgeons Commission on Cancer (ACS-CoC) mandates that pathology reports at ACS-CoC-approved cancer programs include all scientifically validated data elements for each site and tumor specimen. The College of American Pathologists (CAP) has produced cancer checklists in static text formats to assist reporting. To be inclusive, the CAP checklists are pages long, requiring extensive text editing and multiple intermediate steps. We created a set of dynamic tumor-reporting templates, using Microsoft Active Server Page (ASP.NET), with drop-down list and data-compile features, and added a reminder function to indicate missing information. Users can access this system on the Internet, prepare the tumor report by selecting relevant data from drop-down lists with an embedded tumor staging scheme, and directly transfer the final report into a laboratory information system by using the copy-and-paste function. By minimizing extensive text editing and eliminating intermediate steps, this system can reduce reporting errors, improve work efficiency, and increase compliance.

  19. [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

  20. Increased Functional Connectivity between Prefrontal Cortex and Reward System in Pathological Gambling

    PubMed Central

    Koehler, Saskia; Ovadia-Caro, Smadar; van der Meer, Elke; Villringer, Arno; Heinz, Andreas

    2013-01-01

    Pathological gambling (PG) shares clinical characteristics with substance-use disorders and is thus discussed as a behavioral addiction. Recent neuroimaging studies on PG report functional changes in prefrontal structures and the mesolimbic reward system. While an imbalance between these structures has been related to addictive behavior, whether their dysfunction in PG is reflected in the interaction between them remains unclear. We addressed this question using functional connectivity resting-state fMRI in male subjects with PG and controls. Seed-based functional connectivity was computed using two regions-of-interest, based on the results of a previous voxel-based morphometry study, located in the prefrontal cortex and the mesolimbic reward system (right middle frontal gyrus and right ventral striatum). PG patients demonstrated increased connectivity from the right middle frontal gyrus to the right striatum as compared to controls, which was also positively correlated with nonplanning aspect of impulsiveness, smoking and craving scores in the PG group. Moreover, PG patients demonstrated decreased connectivity from the right middle frontal gyrus to other prefrontal areas as compared to controls. The right ventral striatum demonstrated increased connectivity to the right superior and middle frontal gyrus and left cerebellum in PG patients as compared to controls. The increased connectivity to the cerebellum was positively correlated with smoking in the PG group. Our results provide further evidence for alterations in functional connectivity in PG with increased connectivity between prefrontal regions and the reward system, similar to connectivity changes reported in substance use disorder. PMID:24367675

  1. Stress and hypertension.

    PubMed

    Kulkarni, S; O'Farrell, I; Erasi, M; Kochar, M S

    1998-12-01

    Stress can cause hypertension through repeated blood pressure elevations as well as by stimulation of the nervous system to produce large amounts of vasoconstricting hormones that increase blood pressure. Factors affecting blood pressure through stress include white coat hypertension, job strain, race, social environment, and emotional distress. Furthermore, when one risk factor is coupled with other stress producing factors, the effect on blood pressure is multiplied. Overall, studies show that stress does not directly cause hypertension, but can have an effect on its development. A variety of non-pharmacologic treatments to manage stress have been found effective in reducing blood pressure and development of hypertension, examples of which are meditation, acupressure, biofeedback and music therapy. Recent results from the National Health and Nutrition Examination Survey indicate that 50 million American adults have hypertension (defined to be a systolic blood pressure of greater than 139 mm Hg or a diastolic blood pressure of greater than 89 mm Hg). In 95% of these cases, the cause of hypertension is unknown and they are categorized as "essential" hypertension. Although a single cause may not be identified, the general consensus is that various factors contribute to blood pressure elevation in essential hypertension. In these days of 70 hour work weeks, pagers, fax machines, and endless committee meetings, stress has become a prevalent part of people's lives; therefore the effect of stress on blood pressure is of increasing relevance and importance. Although stress may not directly cause hypertension, it can lead to repeated blood pressure elevations, which eventually may lead to hypertension. In this article we explore how stress can cause hypertension and what can be done about it.

  2. 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. PMID:27450650

  3. 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.

  4. 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.

  5. 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.

  6. [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.

  7. Renin angiotensinogen system gene polymorphisms and essential hypertension among people of West African descent: a systematic review.

    PubMed

    Reiter, L M; Christensen, D L; Gjesing, A P

    2016-08-01

    This systematic review investigates the high level of hypertension found among urban dwellers in West Africa and in the West African Diaspora in the Americas in relation to variants within the genes encoding the renin angiotensinogen system. For comparison, the results from the Caucasian populations are reviewed as well. Through a PubMed search, 1252 articles were identified and 28 eligible articles assessed in detail of which 13 included a Caucasian population. The results suggest that among the people of West African descent and among the people of Caucasian descent, hypertension is partly related to a number of single nucleotide polymorphisms (SNPs) and haplotypes in the renin gene, the angiotensinogen gene, the angiotensinogen I-converting enzyme gene and the angiotensinogen II type 1 receptor gene. Concordance between these two populations was found for some SNPs. However, for others, it was found that the SNPs associating with hypertension and the disease allele frequencies differed between these populations. Understanding the importance of these variants in a modern life setting may assist our understanding of the increased risk of developing hypertension among West Africans. Because of inconsistency in the results, low statistical power and methodological differences between studies, these results can only be taken as indicative of an association.

  8. [Childhood hypertension].

    PubMed

    Takemura, Tsukasa

    2015-11-01

    For accurate diagnosis of childhood hypertension, selection of appropriate manchette size according to the child age and the circumstantial size of upper limb is essentially important. In addition, except for the emergency case of hypertension, repeated measurement of blood pressure would be desirable in several weeks interval. Recently, childhood hypertension might be closely related to the abnormality of maternal gestational period caused by the strict diet and the maternal smoking. Developmental Origins of Health and Disease(DOHaD) theory is now highlighted in the pathogenesis of adulthood hypertension. To prevent hypertension of small-for-date baby in later phase of life, maternal education for child nursing should be conducted. In children, secondary hypertension caused by renal, endocrinologic, or malignant disease is predominant rather than idiopathic hypertension. PMID:26619664

  9. 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.

  10. The underestimated potential of the immune system in prevention of Alzheimer's disease pathology.

    PubMed

    Mohajeri, M Hasan

    2007-09-01

    Genetic and environmental factors leading to Alzheimer's disease (AD) converge in a pathogenic pathway that leads to the accumulation of mis-folded amyloid peptide (Abeta) in the brain. Removal of Abeta from the brain has thus been the focus of academic and industrial research in the last decade. The concept of immunization therapy could be proven in animal models mimicking amyloid pathology but a multicenter clinical trial in which AD patients were vaccinated with aggregated Abeta has resulted in somewhat unanticipated and partially conflicting results. The occurrence of meningoencephalitis in 6% of vaccinated individuals forced the discontinuation of the clinical study, preventing the generation of sufficient data for an unequivocal statement about the effectiveness of such a therapy approach. This study, however, clearly showed that vaccination induced the production of antibodies against Abeta in some immunized patients. Moreover, circulating anti-Abeta antibodies are found in healthy humans suggesting a protective role of such physiological antibodies. Nonetheless, the physiological role of the immune system in preventing AD is not fully understood. This article summarizes crucial animal and clinical data underscoring the potential of the immune system for AD treatment.

  11. Connectivity of Pathology: The Olfactory System as a Model for Network-Driven Mechanisms of Alzheimer’s Disease Pathogenesis

    PubMed Central

    Franks, Katherine H.; Chuah, Meng Inn; King, Anna E.; Vickers, James C.

    2015-01-01

    The pathogenesis of Alzheimer’s disease (AD) has been postulated to preferentially impact specific neural networks in the brain. The olfactory system is a well-defined network that has been implicated in early stages of the disease, marked by impairment in olfaction and the presence of pathological hallmarks of the disease, even before clinical presentation. Discovering the cellular mechanisms involved in the connectivity of pathology will provide insight into potential targets for treatment. We review evidence from animal studies on sensory alteration through denervation or enrichment, which supports the notion of using the olfactory system to investigate the implications of connectivity and activity in the spread of pathology in AD. PMID:26696886

  12. Persistent Aortic Arch Hypoplasia After Coarctation Treatment Is Associated With Late Systemic Hypertension

    PubMed Central

    Quennelle, Sophie; Powell, Andrew J; Geva, Tal; Prakash, Ashwin

    2015-01-01

    Background Mild transverse aortic arch (TAA) hypoplasia is common after coarctation treatment, but is considered benign in the absence of an arm-leg systolic blood pressure (SBP) difference. Hypertension (HTN) is a common long-term morbidity after successful coarctation treatment. We examined whether mild TAA hypoplasia after coarctation treatment is associated with late systemic HTN. Methods and Results We retrospectively reviewed 92 patients (median age, 19.9 years; range, 4.9 to 57.8; 60% male) 14.1±10.3 years after successful coarctation treatment (surgery in 63, stent in 16, and balloon dilation in 13), excluding those with resting right arm-leg blood pressure gradient >20 mm Hg, atypical coarctation, and major associated heart defects. Minimum body-surface area (BSA)-adjusted TAA cross-sectional area (CSA) was calculated from cardiac magnetic resonance (CMR) images. On follow-up, 38 of 92 (41%) patients had systemic HTN using standard criteria. Systemic HTN was independently associated with smaller TAA CSA/BSA (P=0.006; odds ratio [OR], 6.41 per 0.5 cm2/m2 decrease), higher age at CMR (P=0.03; OR, 1.57 per 5-year increase), and in a subset (n=61), higher arm-leg SBP difference during exercise (P=0.05; OR, 1.03 per 1-mm-Hg increase). Lower ratio of TAA diameter/descending aorta diameter was associated with a larger increase in right arm SBP during peak exercise (P=0.006; r2=0.11). Conclusions Persistent mild aortic arch hypoplasia, even in the absence of an arm-leg SBP difference at rest, is associated with late systemic HTN. Further studies should be undertaken to determine whether more-aggressive arch reconstruction at initial repair can reduce the incidence of systemic HTN. PMID:26112642

  13. Mitochondrial energy conversion disturbance with decrease in ATP production as a source of systemic arterial hypertension.

    PubMed

    Postnov, Yuvenalii V; Orlov, Sergei N; Budnikov, Yegor Y; Doroschuk, Alexander D; Postnov, Anton Y

    2007-12-01

    Despite numerous efforts, including recent genetic and molecular biology studies, the immediate cause of stationary elevated blood pressure (BP) in any kind of hypertension has not been satisfactorily explained. This review deals with the cellular mechanisms underlying decreased energy status documented in different tissues from experimental rat models of primary and secondary hypertension as well as the involvement of these abnormalities in the pathogenesis of the disease. Such analyses allow us to hypothesize that dysfunction of mitochondrial energy conversion, caused by distinct stimuli, including generalized disturbances of intracellular Ca(2+) handling and mitochondria calcium overload found in primary hypertension, leads to uncoupling of oxidation and phosphorylation and attenuated ATP synthesis. Examples of arterial hypertension accompanied by mitochondrial uncoupling and cell ATP depletion (hyperthyroidism, cold hypertension, cyclosporine A intake, etc.) may be considered as an additional argument supporting this opinion. It means also that despite of differences in triggering mechanisms of mitochondrial dysfunction in all these models, the final outcome, i.e. decreased mitochondrial ATP production, is similar. Attenuated intracellular ATP content, in turn, results in the long-term maintenance of elevated BP by increased sympathetic outflow, whereas augmented ROS production following mitochondrial dysfunction lowers the capacity of the NO-dependent vascular relaxation. In the light of these data the cause of stationary elevated BP in chronic arterial hypertension should be regarded as a compensatory response to decreased mitochondrial ATP synthesis.

  14. HW 03-2 EFFECT OF CPAP ON THE TREATMENT OF RESISTANT HYPERTENSION.

    PubMed

    Kim, Seong Hwan

    2016-09-01

    Resistant hypertension is defined as blood pressure that remains above 140/90 mmHg in spite of the concurrent use of three antihypertensive agents of different classes at optimal dosing, of which one should be a diuretic. Accordingly, it is not synonymous with uncontrolled hypertension. Among a variety of risk factors, obstructive sleep apnea (OSA), which is a common type of sleep-disordered breathing, has been recognized a well-established risk factor for resistant hypertension. Indeed, both European and American guidelines for the management of arterial hypertension stated that OSA is a modifiable cause of resistant hypertension. Although the true incidence of resistance hypertension remains unknown, a significant portion of patients with resistant hypertension are thought to have OSA because of an increasing trend in the incidence of OSA worldwide. OSA is very common in hypertensive patients (up to 50%), and also difficult to reach the target blood pressure. According to The Sleep Heart Health Study, the patients with moderate to severe OSA had three times higher odds of having hypertension. In addition, because other large population-based studies have confirmed that OSA is a risk factor for resistant hypertension, a polysomnography examination (a sleep study) should be tested in patients with resistant hypertension. Even in some OSA patients, resistant hypertension could be the first sign without typical symptoms without a history of snoring, witnessed apnea, or excessive daytime sleepiness. The main pathologic mechanisms on how OSA contributes to the development of resistant hypertension include the downstream physiologic effects of recurrent hypoxia, endothelial dysfunction, autonomic nervous dysfunction, increased SNS activity, nocturnal fluid shifts, and overactivation of the renin-angiotensin system. These processes are directly and indirectly interrelated to the development of resistant hypertension. Although various treatment modalities for OSA in

  15. Renal (tissue) kallikrein-kinin system in the kidney and novel potential drugs for salt-sensitive hypertension.

    PubMed

    Katori, Makoto; Majima, Masataka

    2014-01-01

    A large variety of antihypertensive drugs, such as angiotensin converting enzyme inhibitors, diuretics, and others, are prescribed to hypertensive patients, with good control of the condition. In addition, all individuals are generally believed to be salt sensitive and, thus, severe restriction of salt intake is recommended to all. Nevertheless, the physiological defense mechanisms in the kidney against excess salt intake have not been well clarified. The present review article demonstrated that the renal (tissue) kallikrein-kinin system (KKS) is ideally situated within the nephrons of the kidney, where it functions to inhibit the reabsorption of NaCl through the activation of bradykinin (BK)-B2 receptors localized along the epithelial cells of the collecting ducts (CD). Kinins generated in the CD are immediately inactivated by two kidney-specific kinin-inactivating enzymes (kininases), carboxypeptidase Y-like exopeptidase (CPY), and neutral endopeptidase (NEP). Our work demonstrated that ebelactone B and poststatin are selective inhibitors of these kininases. The reduced secretion of the urinary kallikrein is linked to the development of salt-sensitive hypertension, whereas potassium ions and ATP-sensitive potassium channel blockers ameliorate salt-sensitive hypertension by accelerating the release of renal kallikrein. On the other hand, ebelactone B and poststatin prolong the life of kinins in the CD after excess salt intake, thereby leading to the augmentation of natriuresis and diuresis, and the ensuing suppression of salt-sensitive hypertension. In conclusion, accelerators of the renal kallikrein release and selective renal kininase inhibitors are both novel types of antihypertensive agents that may be useful for treatment of salt-sensitive hypertension. PMID:25130040

  16. Portal hypertensive polyps, a new entity?

    PubMed

    Martín Domínguez, Verónica; Díaz Méndez, Ariel; Santander, Cecilio; García-Buey, Luisa

    2016-05-01

    We present a case of a 62 year old woman with history of liver cirrhosis secondary to autoimmune hepatitis, with portal hypertension and coagulopathy. Gastroscopy findings were a polypoid and polylobed lesions in the gastric antrum. These were removed and the pathological study described hyperplastic polyps with edema, vascular congestion and hyperplasia of smooth muscle, corresponding to "portal hypertensive polyps" (PHP). PMID:27188590

  17. Resistant Hypertension.

    PubMed

    Doroszko, Adrian; Janus, Agnieszka; Szahidewicz-Krupska, Ewa; Mazur, Grzegorz; Derkacz, Arkadiusz

    2016-01-01

    Resistant hypertension is a severe medical condition which is estimated to appear in 9-18% of hypertensive patients. Due to higher cardiovascular risk, this disorder requires special diagnosis and treatment. The heterogeneous etiology, risk factors and comorbidities of resistant hypertension stand in need of sophisticated evaluation to confirm the diagnosis and select the best therapeutic options, which should consider lifestyle modifications as well as pharmacological and interventional treatment. After having excluded pseudohypertension, inappropriate blood pressure measurement and control as well as the white coat effect, suspicion of resistant hypertension requires an analysis of drugs which the hypertensive patient is treated with. According to one definition - ineffective treatment with 3 or more antihypertensive drugs including diuretics makes it possible to diagnose resistant hypertension. A multidrug therapy including angiotensin - converting enzyme inhibitors, angiotensin II receptor blockers, beta blockers, diuretics, long-acting calcium channel blockers and mineralocorticoid receptor antagonists has been demonstrated to be effective in resistant hypertension treatment. Nevertheless, optional, innovative therapies, e.g. a renal denervation or baroreflex activation, may create a novel pathway of blood pressure lowering procedures. The right diagnosis of this disease needs to eliminate the secondary causes of resistant hypertension e.g. obstructive sleep apnea, atherosclerosis and renal or hormonal disorders. This paper briefly summarizes the identification of the causes of resistant hypertension and therapeutic strategies, which may contribute to the proper diagnosis and an improvement of the long term management of resistant hypertension.

  18. Intrarenal mouse renin-angiotensin system during ANG II-induced hypertension and ACE inhibition.

    PubMed

    Gonzalez-Villalobos, Romer A; Satou, Ryousuke; Ohashi, Naro; Semprun-Prieto, Laura C; Katsurada, Akemi; Kim, Catherine; Upchurch, G M; Prieto, Minolfa C; Kobori, Hiroyuki; Navar, L Gabriel

    2010-01-01

    Angiotensin-converting enzyme (ACE) inhibition (ACEi) ameliorates the development of hypertension and the intrarenal ANG II augmentation in ANG II-infused mice. To determine if these effects are associated with changes in the mouse intrarenal renin-angiotensin system, the expression of angiotensinogen (AGT), renin, ACE, angiotensin type 1 receptor (AT(1)R) mRNA (by quanitative RT-PCR) and protein [by Western blot (WB) and/or immunohistochemistry (IHC)] were analyzed. C57BL/6J male mice (9-12 wk old) were distributed as controls (n = 10), ANG II infused (ANG II = 8, 400 ng x kg(-1) x min(-1) for 12 days), ACEi only (ACEi = 10, lisinopril, 100 mg/l), and ANG II infused + ACEi (ANG II + ACEi = 11). When compared with controls (1.00), AGT protein (by WB) was increased by ANG II (1.29 +/- 0.13, P < 0.05), and this was not prevented by ACEi (ACEi + ANG II, 1.31 +/- 0.14, P < 0.05). ACE protein (by WB) was increased by ANG II (1.21 +/- 0.08, P < 0.05), and it was reduced by ACEi alone (0.88 +/- 0.07, P < 0.05) or in combination with ANG II (0.80 +/- 0.07, P < 0.05). AT(1)R protein (by WB) was increased by ANG II (1.27 +/- 0.06, P < 0.05) and ACEi (1.17 +/- 0.06, P < 0.05) but not ANG II + ACEi [1.15 +/- 0.06, not significant (NS)]. Tubular renin protein (semiquantified by IHC) was increased by ANG II (1.49 +/- 0.23, P < 0.05) and ACEi (1.57 +/- 0.15, P < 0.05), but not ANG II + ACEi (1.10 +/- 0.15, NS). No significant changes were observed in AGT, ACE, or AT(1)R mRNA. In summary, reduced responses of intrarenal tubular renin, ACE, and the AT(1)R protein to the stimulatory effects of chronic ANG II infusions, in the presence of ACEi, are associated with the effects of this treatment to ameliorate augmentations in blood pressure and intrarenal ANG II content during ANG II-induced hypertension. PMID:19846570

  19. Intrarenal mouse renin-angiotensin system during ANG II-induced hypertension and ACE inhibition

    PubMed Central

    Satou, Ryousuke; Ohashi, Naro; Semprun-Prieto, Laura C.; Katsurada, Akemi; Kim, Catherine; Upchurch, G. M.; Prieto, Minolfa C.; Kobori, Hiroyuki; Navar, L. Gabriel

    2010-01-01

    Angiotensin-converting enzyme (ACE) inhibition (ACEi) ameliorates the development of hypertension and the intrarenal ANG II augmentation in ANG II-infused mice. To determine if these effects are associated with changes in the mouse intrarenal renin-angiotensin system, the expression of angiotensinogen (AGT), renin, ACE, angiotensin type 1 receptor (AT1R) mRNA (by quanitative RT-PCR) and protein [by Western blot (WB) and/or immunohistochemistry (IHC)] were analyzed. C57BL/6J male mice (9–12 wk old) were distributed as controls (n = 10), ANG II infused (ANG II = 8, 400 ng·kg−1·min−1 for 12 days), ACEi only (ACEi = 10, lisinopril, 100 mg/l), and ANG II infused + ACEi (ANG II + ACEi = 11). When compared with controls (1.00), AGT protein (by WB) was increased by ANG II (1.29 ± 0.13, P < 0.05), and this was not prevented by ACEi (ACEi + ANG II, 1.31 ± 0.14, P < 0.05). ACE protein (by WB) was increased by ANG II (1.21 ± 0.08, P < 0.05), and it was reduced by ACEi alone (0.88 ± 0.07, P < 0.05) or in combination with ANG II (0.80 ± 0.07, P < 0.05). AT1R protein (by WB) was increased by ANG II (1.27 ± 0.06, P < 0.05) and ACEi (1.17 ± 0.06, P < 0.05) but not ANG II + ACEi [1.15 ± 0.06, not significant (NS)]. Tubular renin protein (semiquantified by IHC) was increased by ANG II (1.49 ± 0.23, P < 0.05) and ACEi (1.57 ± 0.15, P < 0.05), but not ANG II + ACEi (1.10 ± 0.15, NS). No significant changes were observed in AGT, ACE, or AT1R mRNA. In summary, reduced responses of intrarenal tubular renin, ACE, and the AT1R protein to the stimulatory effects of chronic ANG II infusions, in the presence of ACEi, are associated with the effects of this treatment to ameliorate augmentations in blood pressure and intrarenal ANG II content during ANG II-induced hypertension. PMID:19846570

  20. The Association between ESR and CRP and Systemic Hypertension in Sarcoidosis

    PubMed Central

    Mirsaeidi, Mehdi; Omar, Hesham R.; Ebrahimi, Golnaz; Campos, Micheal

    2016-01-01

    Introduction. The association between the level of systemic inflammation and systemic hypertension (sHTN) among subjects with sarcoidosis has not been previously explored. Methods. A retrospective study was conducted to investigate the relation between the level of systemic inflammation in sarcoidosis, measured by various serum inflammatory markers, and sHTN. Results. Among a total of 108 cases with sarcoidosis (mean age: 53.4 years, 76.9% females), 55 (50.9%) had sHTN and 53 (49.1%) were normotensive. ESR was highly associated with sHTN. The patients with sHTN had higher mean ESR levels compared with normotensives (48.8 ± 35 versus 23.2 ± 27 mm/hr, resp.; P = 0.001). ROC curve analysis for ESR revealed an AUC value of 0.795 (95% CI: 0.692–0.897; P = 0.0001). With regard to CRP, there was a trend towards higher mean values in sHTN group (3.4 versus 1.7 mg/L; P = 0.067) and significantly higher prevalence of sHTN in the highest CRP quartile compared to the lowest one (69.6% versus 30%; OR 4.95; P = 0.017). ROC curve analysis for CRP revealed an AUC value of 0.644 (95% CI: 0.518–0.769; P = 0.03). On multivariate analysis, ESR and the CRP remained independent predictors for sHTN among subjects with sarcoidosis. Conclusion. Systemic inflammation is associated with the presence of sHTN in sarcoidosis. PMID:27433355

  1. Pathologic Correlates of Primary Central Nervous System Lymphoma Defined in an Orthotopic Xenograft Model

    PubMed Central

    Kadoch, Cigall; Dinca, Eduard B.; Voicu, Ramona; Chen, Lingjing; Nguyen, Diana; Parikh, Seema; Karrim, Juliana; Shuman, Marc A.; Lowell, Clifford A.; Treseler, Patrick A.; James, C. David; Rubenstein, James L.

    2014-01-01

    Purpose The prospect for advances in the treatment of patients with primary central nervous system lymphoma (PCNSL) is likely dependent on the systematic evaluation of its pathobiology. Animal models of PCNSL are needed to facilitate the analysis of its molecular pathogenesis and for the efficient evaluation of novel therapeutics. Experimental Design We characterized the molecular pathology of CNS lymphoma tumors generated by the intracerebral implantation of Raji B lymphoma cells in athymic mice. Lymphoma cells were modified for bioluminescence imaging to facilitate monitoring of tumor growth and response to therapy. In parallel, we identified molecular features of lymphoma xenograft histopathology that are evident in human PCNSL specimens. Results Intracerebral Raji tumors were determined to faithfully reflect the molecular pathogenesis of PCNSL, including the predominant immunophenotypic state of differentiation of lymphoma cells and their reactive microenvironment. We show the expression of interleukin-4 by Raji and other B lymphoma cell lines in vitro and by Raji tumors in vivo and provide evidence for a role of this cytokine in the M2 polarization of lymphoma macrophages both in the murine model and in diagnostic specimens of human PCNSL. Conclusion Intracerebral implantation of Raji cells results in a reproducible and invasive xenograft model, which recapitulates the histopathology and molecular features of PCNSL, and is suitable for preclinical testing of novel agents. We also show for the first time the feasibility and accuracy of tumor bioluminescence in the monitoring of a highly infiltrative brain tumor. PMID:19276270

  2. Characterizing psychological dimensions in non-pathological subjects through autonomic nervous system dynamics

    PubMed Central

    Nardelli, Mimma; Valenza, Gaetano; Cristea, Ioana A.; Gentili, Claudio; Cotet, Carmen; David, Daniel; Lanata, Antonio; Scilingo, Enzo P.

    2015-01-01

    The objective assessment of psychological traits of healthy subjects and psychiatric patients has been growing interest in clinical and bioengineering research fields during the last decade. Several experimental evidences strongly suggest that a link between Autonomic Nervous System (ANS) dynamics and specific dimensions such as anxiety, social phobia, stress, and emotional regulation might exist. Nevertheless, an extensive investigation on a wide range of psycho-cognitive scales and ANS non-invasive markers gathered from standard and non-linear analysis still needs to be addressed. In this study, we analyzed the discerning and correlation capabilities of a comprehensive set of ANS features and psycho-cognitive scales in 29 non-pathological subjects monitored during resting conditions. In particular, the state of the art of standard and non-linear analysis was performed on Heart Rate Variability, InterBreath Interval series, and InterBeat Respiration series, which were considered as monovariate and multivariate measurements. Experimental results show that each ANS feature is linked to specific psychological traits. Moreover, non-linear analysis outperforms the psychological assessment with respect to standard analysis. Considering that the current clinical practice relies only on subjective scores from interviews and questionnaires, this study provides objective tools for the assessment of psychological dimensions. PMID:25859212

  3. Novel potential treatment modalities for ocular hypertension: focus on angiotensin and bradykinin system axes.

    PubMed

    Sharif, Najam A

    2015-04-01

    Despite the availability of modern surgical procedures, new drug delivery techniques, health authority-approved single topical ocular drugs, and combination products thereof, there continues to be an unmet medical need for novel treatment modalities for preserving vision. This is especially true for the treatment of glaucoma and the high risk factor often associated with this ocular disease, elevated intraocular pressure (IOP). Undesirable local or systemic side effects, frequency of dosing, lack of sustained IOP lowering, and lack of prevention of diurnal IOP spikes are among the greatest challenges. The very recent discovery, characterization, and publication of 2 novel IOP-lowering agents that pertain to the renin-angiotensin and kallikrein-kinin axes potentially offer novel means to treat and control ocular hypertension (OHT). Here, some contextual introductory information is provided first, followed by more detailed discussion of the properties and actions of diminazene aceturate (DIZE; a novel angiotensin-converting enzyme-2 activator) and FR-190997 (a nonpeptide bradykinin receptor-2 agonist) in relation to their anti-OHT activities in rodent and cynomolgus monkey eyes, respectively. It is anticipated that these compounds will pave the way for future discovery, development, and marketing of novel drugs to treat glaucoma and thus help save sight for millions of people afflicted with this slow progressive optic neuropathy. PMID:25599263

  4. 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.

  5. Central Renin-Angiotensin System Activation and Inflammation Induced by High-Fat Diet Sensitize Angiotensin II-Elicited Hypertension.

    PubMed

    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 activity and inflammation in the brain and to be accompanied by increased sympathetic activity and blood pressure. 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 renin-angiotensin system activity and inflammatory mechanisms in the brain. HFD did not increase baseline blood pressure, but enhanced the hypertensive response to Ang II compared with a normal-fat diet. The sensitization produced by the HFD was abolished by concomitant central infusions of either a tumor necrosis factor-α synthesis inhibitor, pentoxifylline, an Ang II type 1 receptor blocker, irbesartan, or an inhibitor of microglial activation, minocycline. Furthermore, central pretreatment with tumor necrosis factor-α mimicked the sensitizing action of a central subpressor dose of Ang II, whereas central pentoxifylline or minocycline abolished this Ang II-induced sensitization. Real-time quantitative reverse transcription-polymerase chain reaction analysis of lamina terminalis tissue indicated that HFD feeding, central tumor necrosis factor-α, or a central subpressor dose of Ang II upregulated mRNA expression of several components of the renin-angiotensin system and proinflammatory cytokines, whereas inhibition of Ang II type 1 receptor 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 renin-angiotensin system and of central proinflammatory cytokines.

  6. Role of the Immune System in Hypertension: Modulation by Dietary Antioxidants

    PubMed Central

    Vasdev, Sudesh; Stuckless, Jennifer; Richardson, Vernon

    2011-01-01

    Hypertension is a major health problem worldwide. Individuals with hypertension are at an increased risk for stroke, heart disease, and kidney failure. Although the etiology of essential hypertension has a genetic component, lifestyle factors such as diet play an important role. Insulin resistance is a common feature of hypertension in both humans and animal models affecting glucose and lipid metabolism producing excess aldehydes including methylglyoxal. These aldehydes react with proteins to form conjugates called advanced glycation end products (AGEs). This alters protein structure and function and can affect vascular and immune cells leading to their activation and secretion of inflammatory cytokines. AGEs also act via receptors for advanced glycation end products on these cells altering the function of antioxidant and metabolic enzymes, and ion channels. This results in an increase in cytosolic free calcium, decrease in nitric oxide, endothelial dysfunction, oxidative stress, peripheral vascular resistance, and infiltration of vascular and kidney tissue with inflammatory cells leading to hypertension. Supplementation with dietary antioxidants including vitamins C, E, or B6, thiols such as cysteine and lipoic acid, have been shown to lower blood pressure and plasma inflammatory cytokines in animal models and humans with essential hypertension. A well-balanced diet rich in antioxidants that includes vegetables, fruits, low fat dairy products, low salt, and includes whole grains, poultry, fish and nuts, lowers blood pressure and vascular inflammation. These antioxidants may achieve their antihypertensive and anti-inflammatory/immunomodulatory effects by reducing AGEs and improving insulin resistance and associated alterations. Dietary supplementation with antioxidants may be a beneficial, inexpensive, front-line alterative treatment modality for hypertension. PMID:23204821

  7. Cardiac involvement in acromegaly: specific myocardiopathy or consequence of systemic hypertension?

    PubMed

    López-Velasco, R; Escobar-Morreale, H F; Vega, B; Villa, E; Sancho, J M; Moya-Mur, J L; García-Robles, R

    1997-04-01

    To evaluate the relative contributions of past or present GH hypersecretion and of hypertension to the cardiac abnormalities present in acromegaly, we have studied the serum GH and insulin-like growth factor I concentrations, systolic and diastolic blood pressures, and morphological and functional cardiac indexes as measured by echocardiography-Doppler, in 39 patients with active or cured acromegaly, 16 hypertensive controls, and 17 normotensive controls. Hypertension was present in 42.8% of patients with active acromegaly and in 28.0% of patients in which acromegaly was cured. Hypertension was independently related to an increase in indexes of cardiac morphology (left ventricular mass, left ventricular posterior wall thickness, interventricular septum thickness, relative wall thickness with respect to the diastolic diameter of the left ventricle, and left atrial end-systolic diameter), systolic function (stroke volume, fractional shortening, and end-systolic stress), and diastolic function (isovolumic relaxation time and maximal late diastolic flow velocity) and to a reduction in the early to late maximal diastolic flow velocity ratio. Acromegaly was related to an increase in left ventricular mass, stroke volume, cardiac output, and isovolumic relaxation time, which were independent from the presence of hypertension. End-systolic stress was reduced by acromegaly. In the five patients in which active acromegaly was successfully treated, left ventricular mass and left ventricular posterior wall thickness were reduced 1 yr later. In conclusion, the asymptomatic morphological and functional cardiac abnormalities present in acromegalic patients are independently related to acromegaly and hypertension, pointing to the existence to a specific acromegalic myocardiopathy that might be aggravated by the coexistence of hypertension.

  8. [Endocrine hypertension].

    PubMed

    Takeda, R

    1993-03-01

    Endocrine Hypertension, is, in a narrow sense, defined as adrenal hypertension, including mainly pheochromocytoma, Cushing's syndrome, a syndrome of primary aldosteronism and it's related mineralocorticoid excess disorders. In memory of a great contribution to hypertensiology by the late Prof. Murakami, who was the first author to write on pheochromocytoma in Japan, this paper is dedicated to reviewing the current status of adrenal hypertension in Japan from the epidemiological viewpoint, putting emphasis upon the clinical characteristics of aged patients with adrenal hypertension. Secondly, some topics in the research field of each adrenal hypertension are briefly introduced. Thirdly, our recent data are presented, showing 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) mRNA expression in resistance vessels and decreased 11 beta-HSD activities in vessels in SHR which supports the hypothesis that there might exist a subtype identified as partial impairment of 11 beta-HSD in patients with essential hypertension. PMID:8331819

  9. Pulmonary Hypertension and Other Potentially Fatal Pulmonary Complications in Systemic Juvenile Idiopathic Arthritis

    PubMed Central

    Kimura, Yukiko; Weiss, Jennifer E.; Haroldson, Kathryn L.; Lee, Tzielan; Punaro, Marilynn; Oliveira, Sheila; Rabinovich, Egla; Riebschleger, Meredith; Antón, Jordi; Blier, Peter R.; Gerloni, Valeria; Hazen, Melissa M; Kessler, Elizabeth; Onel, Karen; Passo, Murray H; Rennebohm, Robert M; Wallace, Carol A; Woo, Patricia; Wulffraat, Nico

    2015-01-01

    Objectives Systemic Juvenile Idiopathic Arthritis (sJIA) is characterized by fevers, rash and arthritis, for which IL1 and IL6 inhibitors appear effective. Pulmonary artery hypertension (PAH), interstitial lung disease (ILD) and alveolar proteinosis (AP) have been recently reported in sJIA patients with increased frequency. Our aim was to characterize and compare these cases to a larger cohort of sJIA patients. Methods sJIA patients who developed PAH, ILD and/or AP were identified through an electronic listserv, and their demographic, sJIA and pulmonary disease characteristics, and medication exposure information were collected. These features were compared to a cohort of sJIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Results Patients (N=25) were significantly (p<0.05) more likely than the CARRA registry cohort (N=389) to be female, have more systemic features, and to have been exposed to an IL-1 inhibitor, tocilizumab, infliximab, corticosteroids, intravenous immunoglobulin, cyclosporine and cyclophosphamide. Eighty% were diagnosed after 2004. Twenty (80%) patients had MAS during their disease course and 15 (60%) had MAS at pulmonary diagnosis. Sixteen patients had PAH, 5 AP and 7 ILD. Seventeen (68%) patients were taking or recently (≤1 month) discontinued a biologic agent at pulmonary symptom onset; 12 (48%) were taking anti-IL1 therapy (primarily anakinra). Seventeen (68%) patients died at a mean of 8.8 months from pulmonary diagnosis. Conclusions PAH, AP and ILD are under-recognized complications of sJIA which are frequently fatal. These may be the result of severe uncontrolled systemic disease activity, and may be influenced by medication exposure. PMID:23139240

  10. Heme oxygenase and the immune system in normal and pathological pregnancies

    PubMed Central

    Ozen, Maide; Zhao, Hui; Lewis, David B.; Wong, Ronald J.; Stevenson, David K.

    2015-01-01

    Normal pregnancy is an immunotolerant state. Many factors, including environmental, socioeconomic, genetic, and immunologic changes by infection and/or other causes of inflammation, may contribute to inter-individual differences resulting in a normal or pathologic pregnancy. In particular, imbalances in the immune system can cause many pregnancy-related diseases, such as infertility, abortions, pre-eclampsia, and preterm labor, which result in maternal/fetal death, prematurity, or small-for-gestational age newborns. New findings imply that myeloid regulatory cells and regulatory T cells (Tregs) may mediate immunotolerance during normal pregnancy. Effector T cells (Teffs) have, in contrast, been implicated to cause adverse pregnancy outcomes. Furthermore, feto-maternal tolerance affects the developing fetus. It has been shown that the Treg/Teff balance affects litter size and adoptive transfer of pregnancy-induced Tregs can prevent fetal rejection in the mouse. Heme oxygenase-1 (HO-1) has a protective role in many conditions through its anti-inflammatory, anti-apoptotic, antioxidative, and anti-proliferative actions. HO-1 is highly expressed in the placenta and plays a role in angiogenesis and placental vascular development and in regulating vascular tone in pregnancy. In addition, HO-1 is a major regulator of immune homeostasis by mediating crosstalk between innate and adaptive immune systems. Moreover, HO-1 can inhibit inflammation-induced phenotypic maturation of immune effector cells and pro-inflammatory cytokine secretion and promote anti-inflammatory cytokine production. HO-1 may also be associated with T-cell activation and can limit immune-based tissue injury by promoting Treg suppression of effector responses. Thus, HO-1 and its byproducts may protect against pregnancy complications by its immunomodulatory effects, and the regulation of HO-1 or its downstream effects has the potential to prevent or treat pregnancy complications and prematurity. PMID

  11. Heme oxygenase and the immune system in normal and pathological pregnancies.

    PubMed

    Ozen, Maide; Zhao, Hui; Lewis, David B; Wong, Ronald J; Stevenson, David K

    2015-01-01

    Normal pregnancy is an immunotolerant state. Many factors, including environmental, socioeconomic, genetic, and immunologic changes by infection and/or other causes of inflammation, may contribute to inter-individual differences resulting in a normal or pathologic pregnancy. In particular, imbalances in the immune system can cause many pregnancy-related diseases, such as infertility, abortions, pre-eclampsia, and preterm labor, which result in maternal/fetal death, prematurity, or small-for-gestational age newborns. New findings imply that myeloid regulatory cells and regulatory T cells (Tregs) may mediate immunotolerance during normal pregnancy. Effector T cells (Teffs) have, in contrast, been implicated to cause adverse pregnancy outcomes. Furthermore, feto-maternal tolerance affects the developing fetus. It has been shown that the Treg/Teff balance affects litter size and adoptive transfer of pregnancy-induced Tregs can prevent fetal rejection in the mouse. Heme oxygenase-1 (HO-1) has a protective role in many conditions through its anti-inflammatory, anti-apoptotic, antioxidative, and anti-proliferative actions. HO-1 is highly expressed in the placenta and plays a role in angiogenesis and placental vascular development and in regulating vascular tone in pregnancy. In addition, HO-1 is a major regulator of immune homeostasis by mediating crosstalk between innate and adaptive immune systems. Moreover, HO-1 can inhibit inflammation-induced phenotypic maturation of immune effector cells and pro-inflammatory cytokine secretion and promote anti-inflammatory cytokine production. HO-1 may also be associated with T-cell activation and can limit immune-based tissue injury by promoting Treg suppression of effector responses. Thus, HO-1 and its byproducts may protect against pregnancy complications by its immunomodulatory effects, and the regulation of HO-1 or its downstream effects has the potential to prevent or treat pregnancy complications and prematurity. PMID

  12. 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

  13. [Mitochondrial energy conversion disturbance with decrease in ATP production as a source of systemic arterial hypertension].

    PubMed

    Postnov, Iu V; Orlov, S N; Budnikov, E Iu; Doroshchuk, A D; Postnov, A Iu

    2008-01-01

    This review deals with the cellular mechanisms underlying decreased energy status documented in different tissues from experimental rat models of primary and secondary hypertension as well as the involvement of these abnormalities in the pathogenesis of the disease. Such analyses allow us to hypothesize that dysfunction of mitochondrial energy conversion, caused by distinct stimuli, including generalized disturbances of intracellular Ca2+ handling and mitochondria calcium overload found in primary hypertension, leads to uncoupling of oxidation and phosphorylation and attenuated ATP synthesis. Examples of arterial hypertension accompanied by mitochondrial uncoupling and cell ATP depletion (hyperthyroidism, cold hypertension, cyclosporine A intake, etc.) may be considered as an additional argument supporting this opinion. It means also that despite of differences in triggering mechanisms of mitochondrial dysfunction in all these models, the final outcome, i.e. decreased mitochondrial ATP production, is similar. Attenuated intracellular ATP content, in turn, results in the long-term maintenance of elevated BP by increased sympathetic outflow, whereas augmented ROS production following mitochondrial dysfunction lowers the capacity of the NO-dependent vascular relaxation. In the light of these data the cause of stationary elevated BP in chronic arterial hypertension should be regarded as a compensatory response to decreased mitochondrial ATP synthesis.

  14. 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.

  15. Regulatory networks and complex interactions between the insulin and angiotensin II signalling systems: models and implications for hypertension and diabetes.

    PubMed

    Cizmeci, Deniz; Arkun, Yaman

    2013-01-01

    The cross-talk between insulin and angiotensin II signalling pathways plays a significant role in the co-occurrence of diabetes and hypertension. We developed a mathematical model of the system of interactions among the biomolecules that are involved in the cross-talk between the insulin and angiotensin II signalling pathways. We have identified several feedback structures that regulate the dynamic behavior of the individual signalling pathways and their interactions. Different scenarios are simulated and dominant steady-state, dynamic and stability characteristics are revealed. The proposed mechanistic model describes how angiotensin II inhibits the actions of insulin and impairs the insulin-mediated vasodilation. The model also predicts that poor glycaemic control induced by diabetes contributes to hypertension by activating the renin angiotensin aystem.

  16. Osler's pathology.

    PubMed

    Pai, S A

    2000-12-01

    Sir William Osler, one of the giants of clinical medicine, had his initial training as a pathologist. He was one of the physicians responsible for the impact that autopsies have had on medicine. He also contributed to the development of laboratory medicine. Osler made significant discoveries in anatomic pathology and hematology. His expertise was restricted not just to human pathology, but also to veterinary pathology. His mentors played a fundamental role in his achievements in academics.

  17. Hypertension as a low-grade systemic inflammatory condition that has its origins in the perinatal period.

    PubMed

    Das, U N

    2006-02-01

    Genetics, oxidative stress: superoxide anion (O2*-) and hydrogen peroxide (H2O2), endothelial nitric oxide (eNO), lipid peroxides, anti-oxidants, endothelin, angiotensin converting enzyme (ACE) activity, angiotensinII, transforming growth factor-beta (TGF-beta), insulin, homocysteine, asymmetrical dimethyl arginine, proinflammatory cytokines: interleukin-6 (IL-6), tumor necrosis factor-a (TNF-alpha), C-reactive protein (hs-CRP), and long-chain polyunsaturated fatty acids (LCPUFAs), and activity of NAD(P)H oxidase have a role in human essential hypertension. There is a close interaction between endogenous molecules: eNO, endothelin, cytokines, and nutrients: folic acid, L-arginine, tetrahydrobiopterin (H4B), vitamin B6, vitamin B12, vitamin C, and LCPUFAs. Statins mediate some, if not all, of their actions through LCPUFAs, whereas these fatty acids (especially omega-3 fatty acids) suppress cyclo-oxygenase activity and the synthesis of pro-inflammatory cytokines, and activate parasympathetic nervous system, actions that reduce the risk of major vascular events. Some LCPUFAs form precursors to lipoxins and resolvins that have anti-inflammatory actions. Low-grade systemic inflammation seen in hypertension seems to have its origins in the perinatal period and availability of adequate amounts of LCPUFAs during the critical periods of brain growth prevents the development of hypertension. This indicates that preventive strategies aimed at decreasing the incidence of hypertension and its associated conditions such as atherosclerosis, type 2 diabetes, coronary heart disease (CHD), and cardiac failure in adulthood need to be instituted during the perinatal period if they are to be effective. PMID:16715619

  18. Renal implications of arterial hypertension.

    PubMed

    Ruilope, L M

    1997-03-01

    Renal vascular damage caused by arterial hypertension participates in alterations of the systemic vascular function and structure. Nephrosclerosis seems to run in parallel with the systemic atherosclerosis that accounts for the increased cardiovascular morbidity and mortality seen in hypertensive patients. Parameters indicating the existence of an alteration in renal function (increased serum creatinine, proteinuria and microalbuminuria) are independent predictors for an increased cardiovascular morbidity and mortality. Hence, parameters of renal function must be considered in any stratification of cardiovascular risk in hypertensive patients.

  19. 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.

  20. SNOMED CT in pathology.

    PubMed

    García-Rojo, Marcial; Daniel, Christel; Laurinavicius, Arvydas

    2012-01-01

    Pathology information systems have been using SNOMED II for many years, and in most cases, they are in a migration process to SNOMED CT. COST Action IC0604 (EURO-TELEPATH) has considered terminology normalization one of its strategic objectives. This paper reviews the use of SNOMED CT in healthcare, with a special focus in pathology. Nowadays, SNOMED CT is mainly used for concept search and coding of clinical data. Some ontological errors found in SNOMED CT are described. The Integrating the Healthcare Enterprise (IHE) initiative has fostered the use of SNOMED CT, also in Pathology, as recommended in the Supplement Anatomic Pathology Structured Reports of the IHE Anatomic Pathology Technical Framework. Rule governing concept post-coordination is also described. Some recent initiatives are trying to define a SNOMED CT subset for Pathology. The Spanish Society of Pathology has defined a subset for specimens and procedures in Pathology. Regarding diagnosis coding, the morphological abnormality sub-hierarchy of SNOMED CT need to be significantly extended and improved to become useful for pathologists. A consensus is needed to encode pathology reports with the adequate hierarchies and concepts. This will make the implementation of pathology structured reports more feasible.

  1. Thiazide treatment of systemic hypertension: effects on serum magnesium and ventricular ectopic activity.

    PubMed

    Hollifield, J W

    1989-04-18

    Clinical and investigational evidence has proved an association between thiazide-induced electrolyte imbalances and ventricular arrhythmias. It is hypothesized that this increases the potential for sudden unexplained death. Elderly hypertensive patients are at particular risk because of their tendency to have significantly depressed serum magnesium levels, which decrease even further when treated with thiazide diuretics. Potassium supplementation does not effectively restore electrolyte balance unless accompanied by magnesium. Therefore, concomitant administration of potassium and magnesium supplementation appears to be an approach to reducing the risk of arrhythmias and death in thiazide-treated hypertensive patients.

  2. Hypertensive Vasculopathy

    PubMed Central

    Park, Jeong Bae

    2014-01-01

    An exclusive interview by Prof. Jeong Bae Park conducted with Dr. Rhian M. Touyz in Seoul while she was visiting for the Korean Society of Hypertension, May 10, 2014. In this interview, Dr. Touyz explains and describes hypertensive vasculopathy. PMID:26587442

  3. Relevance of Partitioning DLCO to Detect Pulmonary Hypertension in Systemic Sclerosis

    PubMed Central

    Wémeau-Stervinou, Lidwine; De Groote, Pascal; Remy-Jardin, Martine; Denis, Guillaume; Lambert, Marc; Lamblin, Nicolas; Morell-Dubois, Sandrine; Fertin, Marie; Lefevre, Guillaume; Sobanski, Vincent; Le Rouzic, Olivier; Hatron, Pierre-Yves; Wallaert, Benoit; Hachulla, Eric; Perez, Thierry

    2013-01-01

    We investigated whether partitioning DLCO into membrane conductance for CO (DmCO) and pulmonary capillary blood volume (Vcap) was helpful in suspecting precapillary pulmonary (arterial) hypertension (P(A)H) in systemic sclerosis (SSc) patients with or without interstitial lung disease (ILD). We included 63 SSc patients with isolated PAH (n=6), isolated ILD (n=19), association of both (n=12) or without PAH and ILD (n=26). Partitioning of DLCO was performed by the combined DLNO/DLCO method. DLCO, DmCO and Vcap were equally reduced in patients with isolated PAH and patients with isolated ILD but Vcap/alveolar volume (VA) ratio was significantly lower in the isolated PAH group. In patients without ILD, DLCO, DmCO, Vcap and Vcap/VA ratio were reduced in patients with isolated PAH when compared to patients without PAH and both Vcap/VA and DLCO had the highest AUC to detect PAH. In patients with ILD, Vcap had the highest AUC and performed better than DLCO to detect PH in this subgroup. In conclusion, Vcap/VA was lower in PAH than in ILD in SSC whereas DLCO was not different. Vcap/VA ratio and DLCO had similar high performance to detect PAH in patients without ILD. Vcap had better AUC than DLCO, DmCO and FVC/DLCO ratio to detect PH in SSC patients with ILD. These results suggest that partitioning of DLCO might be of interest to detect P(A)H in SSC patients with or without ILD. PMID:24205063

  4. Survival in systemic sclerosis-associated pulmonary arterial hypertension in the modern management era

    PubMed Central

    Launay, David; Sitbon, Olivier; Hachulla, Eric; Mouthon, Luc; Gressin, Virginie; Rottat, Laurence; Clerson, Pierre; Cordier, Jean-François; Simonneau, Gerald; Humbert, Marc

    2013-01-01

    Objective To assess the survival and prognostic factors in patients with newly diagnosed incident systemic sclerosis (SSc)–associated pulmonary arterial hypertension (PAH) in the modern management era. Methods Prospectively enrolled SSc patients in the French PAH Network between January 2006 and November 2009, with newly diagnosed PAH and no interstitial lung disease, were analysed (85 patients, mean age 64.9±12.2 years). Median follow-up after PAH diagnosis was 2.32 years. Results A majority of patients were in NYHA functional class III–IV (79%). Overall survival was 90% (95% CI 81% to 95%), 78% (95% CI 67% to 86%) and 56% (95% CI 42% to 68%) at 1, 2 and 3 years from PAH diagnosis, respectively. Age (HR: 1.05, 95% CI 1.01 to 1.09, p=0.012) and cardiac index (HR: 0.49, 95% CI 0.27 to 0.89, p=0.019) were significant predictors in the univariate analysis. We also observed strong trends for gender, SSc subtypes, New York Heart Association functional class, pulmonary vascular resistance and capacitance to be significant predictors in the univariate analysis. Conversely, six-min walk distance, mean pulmonary arterial and right atrial pressures were not significant predictors. In the multivariate model, gender was the only independent factor associated with survival (HR: 4.76, 95% CI 1.35 to 16.66, p=0.015 for male gender). Conclusions Incident SSc-associated PAH remains a devastating disease even in the modern management era. Age, male gender and cardiac index were the main prognosis factors in this cohort of patients. Early detection of less severe patients should be a priority. PMID:23178295

  5. Severity of systemic sclerosis-associated pulmonary arterial hypertension in African Americans.

    PubMed

    Blanco, Isabel; Mathai, Stephen; Shafiq, Majid; Boyce, Danielle; Kolb, Todd M; Chami, Hala; Hummers, Laura K; Housten, Traci; Chaisson, Neal; Zaiman, Ari L; Wigley, Fredrick M; Tedford, Ryan J; Kass, David A; Damico, Rachel; Girgis, Reda E; Hassoun, Paul M

    2014-07-01

    African Americans (AA) with systemic sclerosis (SSc) have a worse prognosis compared to Americans of European descent (EA). We conducted the current study to test the hypothesis that AA patients with SSc have more severe disease and poorer outcomes compared to EA patients when afflicted with pulmonary arterial hypertension (PAH). We studied 160 consecutive SSc patients with PAH diagnosed by right heart catheterization, comparing demographics, hemodynamics, and outcomes between AA and EA patients. The cohort included 29 AA and 131 EA patients with similar baseline characteristics except for increased prevalence of diffuse SSc in AA. AA patients had worse functional class (FC) (80% FC III-IV vs 53%; p = 0.02), higher brain natriuretic peptide (NT-pro-BNP) (5729 ± 9730 pg/mL vs 1892 ± 2417 pg/mL; p = 0.02), more depressed right ventricular function, a trend toward lower 6-minute walk distance (263 ± 111  m vs 333 ± 110  m; p = 0.07), and worse hemodynamics (cardiac index 1.95 ± 0.58 L/min/m vs 2.62 ± 0.80 L/min/m; pulmonary vascular resistance 10.3 ± 6.2 WU vs 7.6 ± 5.0 WU; p  < 0.05) compared with EA patients. Kaplan-Meier survival estimates for AA and EA patients, respectively, were 62% vs 73% at 2 years and 26% vs 44% at 5 years (p  > 0.05). In conclusion, AA patients with SSc-PAH are more likely to have diffuse SSc and to present with significantly more severe PAH compared with EA patients. AA patients also appear to have poorer survival, though larger studies are needed to investigate this association definitively.

  6. Effects of Ocular Hypertension in the Visual System of Pigmented Mice

    PubMed Central

    Valiente-Soriano, Francisco J.; Salinas-Navarro, Manuel; Jiménez-López, Manuel; Alarcón-Martínez, Luis; Ortín-Martínez, Arturo; Bernal-Garro, José M.; Avilés-Trigueros, Marcelino; Agudo-Barriuso, Marta; Villegas-Pérez, María P.; Vidal-Sanz, Manuel

    2015-01-01

    To study the effects of ocular hypertension (OHT) on the visual system of C57BL/6 pigmented mice, the limbal and episcleral veins of the left eye were laser photocoagulated (LP). LP increased the intraocular pressure during the first five days (d), reaching basal values at 7d. To investigate the effect of OHT on the retinal ganglion cell (RGC) retrograde axonal transport, hydroxistilbamidine methanesulfonate (OHSt) was applied to both superior colliculi (SCi) and the retinas were dissected 2 or 4 weeks after LP. To determine RGC survival, these same retinas were immunoreacted against Brn3a (general RGC population) and melanopsin (intrinsically photosensitive RGCs, m+RGCs). To study whether OHT affected non-RGC neurons in the ganglion cell layer (GCL), RGCs were immunodetected with Brn3a and all GCL nuclei counterstained with DAPI in a group of animals examined 4 weeks post-LP. Innervation of the SCi was examined at 10 days, 8 or 14 weeks after LP with the orthogradely transported cholera toxin subunit-B. OHT resulted in diffuse and sectorial loss of OHSt+RGCs (50% at 2 weeks and 62% at 4 weeks) and in a comparable loss of Brn3a+RGCs at the same time intervals. m+RGCs decreased to 59% at 2 weeks and to 46% at 4 weeks, such loss was diffuse, did not parallel the sectorial loss of the general RGC population and was more severe in the superior-temporal retina. In the GCL, cell loss is selective for RGCs and does not affect other non-RGC neurons. The retinotectal innervation appeared significantly reduced at 10 days (55.7%) and did not progress further up to 14 weeks (46.6%). Thus, LP-induced OHT results in retrograde degeneration of RGCs and m+RGCs, as well as in the loss of CTB-labelled retinotectal terminals. PMID:25811653

  7. Mechanisms responsible for postmenopausal hypertension in a rat model: Roles of the renal sympathetic nervous system and the renin-angiotensin system.

    PubMed

    Maranon, Rodrigo O; Reckelhoff, Jane F

    2016-02-01

    Hypertension in postmenopausal women is less well controlled than in age-matched men. The aging female SHR is a model of postmenopausal hypertension that is mediated in part by activation of the renin-angiotensin system (RAS) and by the renal sympathetic nervous system. In this study, the hypothesis was tested that renal denervation would lower the blood pressure in old female SHR and would attenuate the antihypertensive effects of AT1 receptor antagonism. Retired breeder female SHR were subjected to right uninephrectomy (UNX) and left renal denervation (RD) or UNX and sham, and 2 weeks later, baseline mean arterial pressure (MAP; radiotelemetry) was measured for 4 days, and then rats were treated with angiotensin (AT1) receptor antagonist, losartan (40 mg/kg/day po) for 6 days. Renal denervation reduced MAP in old females compared to sham (172 ± 6 vs. 193 ± 6 mm Hg; P < 0.05). Losartan reduced MAP in both sham and RD rats similarly (numerically and by percentage) (142 ± 10 vs. 161 ± 6 mm Hg; P < 0.05 vs. RD, P < 0.05 vs. baseline). However, female SHR rats remained significantly hypertensive despite both pharmacological intervention and RD. The data suggest that both the renal sympathetic nervous system and the RAS have independent effects to control the blood pressure in old female SHR. Since the denervated rats treated with losartan remained hypertensive, the data also suggest that other mechanisms than the RAS and renal sympathetic nervous system contribute to the hypertension in old female SHR. The data also suggest that multiple mechanisms may mediate the elevated blood pressure in postmenopausal women.

  8. Upregulation of the Renin-Angiotensin-Aldosterone-Ouabain System in the Brain Is the Core Mechanism in the Genesis of All Types of Hypertension

    PubMed Central

    Takahashi, Hakuo

    2012-01-01

    Basic research using animal models points to a causal role of the central nervous system in essential hypertension; however, since clinical research is technically difficult to perform, this connection has not been confirmed in humans. Recently, renal nerve ablation in humans proved to continuously decrease blood pressure in resistant hypertension. Furthermore, when electrical stimulation was continuously applied to the carotid baroreceptor nerve of human adults, their blood pressure lowered. These findings promoted the concept that the central nervous system may actually be involved in the pathogenesis of essential hypertension, which is closely associated with excess sodium intake. We have demonstrated that endogenous digitalis plays a key role in hypertension associated with excess sodium intake via sympathetic activation in rats. Increased sodium concentration inside the brain activates epithelial sodium channels and the renin-angiotensin-aldosterone system in the brain. Aldosterone releases ouabain from neurons in the paraventricular nucleus in the hypothalamus. Angiotensin II and aldosterone of peripheral origin reach the brain to augment sympathetic outflow. Collectively essential hypertension associated with excess sodium intake and obesity, renovascular hypertension, and primary aldosteronism and pseudoaldosteronism all seem to have a common cause originating from the central nervous system. PMID:23316343

  9. [Resistant hypertension].

    PubMed

    Feldstein, Carlos A

    2008-04-01

    Resistant hypertension, defined as a persistent blood pressure over 140/90 mmHg despite the use of three antihypertensive drugs including a diuretic, is unusual. The diagnosis requires ruling out initially pseudoresistance and a lack of compliance with treatment. Ambulatory blood pressure recording allow the recognition of white coat hypertension. When there is a clinical or laboratory suspicion, secondary causes of hypertension should be discarded. Excessive salt intake, the presence of concomitant diseases such as diabetes mellitus, chronic renal disease, obesity, and psychiatric conditions such as panic attacks, anxiety and depression, should also be sought. The presence of target organ damage requires a more aggressive treatment of hypertension. Recent clinical studies indicate that the administration of aldosterone antagonists as a fourth therapeutic line provides significant additional blood pressure reduction, when added to previous antihypertensive regimens in subjects with resistant hypertension. The possible blood pressure lowering effects of prolonged electrical activation of carotid baroreceptors is under investigation. PMID:18769797

  10. [Resistant hypertension].

    PubMed

    Feldstein, Carlos A

    2008-04-01

    Resistant hypertension, defined as a persistent blood pressure over 140/90 mmHg despite the use of three antihypertensive drugs including a diuretic, is unusual. The diagnosis requires ruling out initially pseudoresistance and a lack of compliance with treatment. Ambulatory blood pressure recording allow the recognition of white coat hypertension. When there is a clinical or laboratory suspicion, secondary causes of hypertension should be discarded. Excessive salt intake, the presence of concomitant diseases such as diabetes mellitus, chronic renal disease, obesity, and psychiatric conditions such as panic attacks, anxiety and depression, should also be sought. The presence of target organ damage requires a more aggressive treatment of hypertension. Recent clinical studies indicate that the administration of aldosterone antagonists as a fourth therapeutic line provides significant additional blood pressure reduction, when added to previous antihypertensive regimens in subjects with resistant hypertension. The possible blood pressure lowering effects of prolonged electrical activation of carotid baroreceptors is under investigation.

  11. 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

  12. Effect of forest walking on autonomic nervous system activity in middle-aged hypertensive individuals: a pilot study.

    PubMed

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

    2015-03-01

    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.

  13. Effect of forest walking on autonomic nervous system activity in middle-aged hypertensive individuals: a pilot study.

    PubMed

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

    2015-03-01

    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

  14. 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.

  15. [SIGNIFICANCE OF MAGNESIUM IN PHISIOLOGY AND PATHOLOGY OF THE DIGESTIVE SYSTEM].

    PubMed

    Grigus, Ya I; Mikhaylova, O D; Gorbunov A Yu; Vakhrushev, Ya M

    2015-01-01

    The article describes the physiological role of magnesium in the human body and its importance for metabolic processes. The reasons for the development of magnesium deficiency and hypermagnesaemia and its clinical symptoms are shown. The specialties of magnesium metabolism disturbances in gastroenterological pathology are described. Particular attention paid to the correction of magnesium levels with deviations of its content in the organism.

  16. 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)

  17. An analysis of pathology knowledge and decision making for the development of artificial intelligence-based consulting systems.

    PubMed

    Smeulders, A W; van Ginneken, A M

    1989-06-01

    This paper partly addresses the question "What artificial intelligence (AI) tools are appropriate for which parts of pathology?" by analyzing the structure and components of knowledge in pathology (e.g., observations plus archival and reference data) and which aspects of that knowledge should be expressible in an AI consulting system. The different aspects of uncertainty (observational, prevalence and validity) play an important role in both human and computer-based decision-making processes, as do relationships between the components of knowledge. The design of an AI consultant system is discussed in terms of the way uncertainty is expressed and in how many parameters, the way uncertainty is propagated (Bayes, certainty factors, Dempster-Schafer, logic or Pathfinder heuristic methods), whether the system reasons from data to a conclusion or vice versa and what the aim of the system is. The suitability of an AI tool is determined by the knowable facts of the pathology subfield, by the match with its knowledge structure and by its requirements. While the success of an AI tool will partly depend on an appropriate definition of its scope, the appropriate combinatoric also depends on the expertise of the user.

  18. Is neuroradiological imaging sufficient for exclusion of intracranial hypertension in children? Intracranial hypertension syndrome without evident radiological symptoms.

    PubMed

    Larysz, Dawid; Larysz, Patrycja; Klimczak, Andrzej; Mandera, Marek

    2010-01-01

    There are still many important questions about algorithms and clinical scenarios in the context of children with clinical intracranial hypertension symptoms (IHS) without radiological findings. Such conditions could appear in different clinical situations, including slit ventricle syndrome, overdrainage syndrome, normal volume hydrocephalus, or idiopathic intracranial hypertension. Many articles have defined specific treatment strategies for various forms of IHS, including ventriculoperitoneal shunting, medication for shunt-related migraine, steroids, and valve upgrades with antisiphoning devices or programmable systems. This study is an attempt to define the proper diagnostic procedures and treatment options for patients with various forms of IHS without evident neuroradiological findings. The authors discuss possible pathological mechanisms leading to IHS in the pediatric population. The authors present six children treated in their center. All of the children presented clinical manifestation of intracranial hypertension without evident neuroradiological findings in CT and/or MRI examinations. In three cases, the final diagnosis was slit ventricle syndrome; in two cases, normal volume hydrocephalus; in another case, idiopathic intracranial hypertension. The treatment options included short-term steroid (dexamethasone) administration and ventriculoperitoneal shunting using programmable systems. In one case of idiopathic intracranial hypertension, ICP monitoring was also performed. The authors discuss possible diagnostic and treatment strategies for the aforementioned cases. There are still many controversies about management of children with clinical symptoms of intracranial hypertension that are not confirmed in neuroimaging. It seems that our understanding of intracranial hypertension in the pediatric population is not nearly as sophisticated or complete as we might have imagined. Ventriculoperitoneal shunting with antisiphoning devices and/or short

  19. The hypertension-diabetes continuum.

    PubMed

    Cheung, Bernard M Y

    2010-04-01

    Hypertension and type 2 diabetes are both common chronic conditions that affect a major proportion of the general population. They tend to occur in the same individual, suggesting common predisposing factors, which can be genetic or environmental. Although the genes causing hypertension or diabetes await elucidation, the environmental causes of these diseases are well known. Obesity and physical activity are the 2 leading factors that predispose to both diseases. Individuals with abdominal obesity are likely to develop lipid abnormalities and elevation of blood pressure and glucose. In time, hypertension and diabetes ensue. Because of the shared etiology, there is substantial overlap between hypertension and diabetes. In the Hong Kong Cardiovascular Risk Factor Prevalence Study, 40% of the subjects in the community had either raised blood pressure or raised blood glucose. Only 42% of people with diabetes had normal blood pressure and only 56% of people with hypertension had normal glucose tolerance. The presence of hypertension or diabetes should alert the clinician to the possibility of the other condition. Obesity, lipid abnormalities, raised blood pressure, and glucose are all components of the metabolic syndrome. The syndrome therefore implies a pathologic process, which is potentially reversible in the early stages. Previous efforts targeting smoking, hypertension, and hypercholesterolemia have started to bear fruit. However, obesity is on the increase in developed and developing countries. It is now time to focus on obesity and the metabolic syndrome, which require more a public health than a pharmacologic approach. PMID:20422737

  20. 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.

  1. 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.

  2. 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.

  3. The Krüppel-Like Factors in Female Reproductive System Pathologies

    PubMed Central

    Simmen, Rosalia C.M.; Heard, Melissa E.; Simmen, Angela M.; Montales, Maria Theresa M.; Marji, Meera; Scanlon, Samantha; Pabona, John Mark P.

    2015-01-01

    Female reproductive tract pathologies arise largely from dysregulation of estrogen and progesterone receptor signaling leading to aberrant cell proliferation, survival and differentiation. The signaling pathways orchestrated by these nuclear receptors are complex, require the participation of many nuclear proteins serving as key binding partners or targets and involve a range of paracrine and autocrine regulatory circuits. Members of the Krüppel-like family of transcription factors are ubiquitously expressed in reproductive tissues and have been increasingly implicated as critical co-regulators and integrators of steroid hormone actions. Here we explore the involvement of KLF family members in uterine pathology, describe their currently known molecular mechanisms and discuss their potential as targets for therapeutic intervention. PMID:25654975

  4. Clinical pathological characteristics of breast cancer patients with secondary diabetes after systemic therapy: a retrospective multicenter study.

    PubMed

    Juanjuan, Li; Wen, Wei; Zhongfen, Liu; Chuang, Chen; Jing, Cheng; Yiping, Gong; Changhua, Wang; Dehua, Yu; Shengrong, Sun

    2015-09-01

    The objective of this study was to investigate the clinical pathological characteristics of breast cancer (BC) patients with secondary diabetes after systemic therapy without preexisting diabetes. A total of 1434 BC patients received systemic therapy and were analyzed retrospectively. Fasting plasma glucose (FPG) levels were monitored prior to the treatments, during the course of systemic therapy, and at the follow-up visits. Cox regression models were used to estimate the associations between the clinical pathological characteristics of BC and the cause-specific hazard of developing secondary diabetes. Among the 1434 BC patients, 151 had preexisting type 2 diabetes. Of the remaining 1283 patients with normal FPG levels prior to the systemic therapy, 59 developed secondary diabetes and 72 displayed secondary impaired fasting glucose (IFG) over a mean follow-up of 41 months. The prevalence of secondary type 2 diabetes in BC patients was 4.6 % (59/1283), which was obviously higher than that of the normal control group (1.4 %, P < 0.001). The percentage of older patients (P < 0.05), menopausal patients (P < 0.001), and obese patients (P < 0.01) tended to be lower in the secondary diabetic group. In addition, these patients with secondary diabetes had later pathological stages (P < 0.01), more lymph node metastasis (P < 0.05), negative estrogen receptor (ER) expression (P < 0.05), and smaller size of tumors (P < 0.05). After adjusting for age and BMI, the risk of developing secondary diabetes and IFG in subjects with later pathological stage BC (hazard ratio (HR) = 1.623; 95 % confidence interval (CI) 1.128-2.335 (P < 0.01)), negative progesterone receptor (PR) expression (HR = 0.530; 95 % CI 0.372-0.755 (P < 0.001)), positive human epidermal growth factor receptor 2 (HER2) expression (HR = 1.822; 95 % CI 1.230-2.700 (P < 0.01)), and more lymph node metastasis (HR = 1.595; 95 % CI 1.128-2.258 (P < 0

  5. Whole slide images for primary diagnostics of urinary system pathology: a feasibility study

    PubMed Central

    Al-Janabi, Shaimaa; Huisman, André; Jonges, Geertruida N.; ten Kate, Fiebo J.W.; Goldschmeding, Roel; van Diest, Paul J.

    2014-01-01

    Introduction: During the last decade, whole slide images (WSI) have been used in many areas of pathology such as teaching, research, digital archiving, teleconsultation and quality assurance testing. However, WSI have as yet not much been used for upfront diagnostics because of the lack of validation studies. Objectives: The aim of this study was to test the feasibility of WSI for primary diagnosis of urinary tract pathology. Materials and Methods: 100 consecutive urinary tract biopsies and resections which had been diagnosed conventionally between the years 2008-2009 were scanned at 20× magnification, and rediagnosed by two pathologists on WSI, having the original clinical information available, but blinded to the original diagnoses. Original and WSI diagnoses were compared and classified as concordant, slightly discordant (without clinical consequences) and discordant. Results: Original and WSI based rediagnosis were concordant in 87% of the cases. Original and WSI diagnosis were slightly discordant in 8% of cases. Major discrepancies with clinical or prognostic implications were founded in only 5 cases. However, for 6 out of the 13 discrepancies, WSI based diagnoses were considered to be better than the original diagnoses. Conclusion: Primary diagnostics of urinary tract specimens can be reliably done on WSI. Further improvements of image resolution may help to increase diagnostic accuracy and WSI acceptance in routine pathology. PMID:25610886

  6. 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

  7. Application of Molecular Pathology in Endocrine Pathology.

    PubMed

    Linke, Ebru Serinsoz; Tezel, Gaye Güler

    2015-01-01

    Rapid growth in knowledge of cell and molecular biology led to the increased usage of molecular techniques in anatomical pathology. This is also due to the advances achieved in the techniques introduced in the last few years which are less laborious as compared to the techniques used at the beginning of the "molecular era". The initial assays were also very expensive and were not performed except for selected centers. Moreover, the clinicians were not sure how to make use of the accumulating molecular information. That situation has also changed and molecular techniques are being performed in a wide variety of medical settings which also has a reflection on the endocrine system pathology among other organ systems. This review will provide an update of genetic changes observed in different endocrine system pathologies and their diagnostic, therapeutic and prognostic values.

  8. Assessment of intravenous fenoldopam mesylate in the management of severe systemic hypertension.

    PubMed

    Munger, M A; Rutherford, W F; Anderson, L; Hakki, A I; Gonzalez, F M; Bednarczyk, E M; Emmanuel, G; Weed, S G; Panacek, E A; Green, J A

    1990-05-01

    To evaluate the acute BP response to iv fenoldopam mesylate (FNP), 14 patients with severe hypertension (diastolic BP 120 to 170 mm Hg) were studied in an open-label trial. Initial infusion rate of FNP was 0.1 microgram/kg.min. Titration to diastolic BP goal (95 to 110 mm Hg) was followed by a constant infusion phase (greater than or equal to 6 h), a detitration phase (2 h), and a postinfusion phase. FNP reduced BP by 27/29 mm Hg (p less than .001) with no significant effect on heart rate. Maintenance of the BP effect was noted through the 6 h of constant rate infusion. Mild, transient vasodilating-associated adverse effects were noted with FNP. We conclude that FNP is an effective, well-tolerated iv antihypertensive agent for acute BP reduction in a severely hypertensive population. PMID:1970283

  9. 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.

  10. 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 ...

  11. Spontaneously hypertensive rat as a model of vascular brain disorder: microanatomy, neurochemistry and behavior.

    PubMed

    Tayebati, Seyed Khosrow; Tomassoni, Daniele; Amenta, Francesco

    2012-11-15

    Arterial hypertension is the main risk factor for stroke and plays a role in the development of vascular cognitive impairment (VCI) and vascular dementia (VaD). An association between hypertension and reduced cerebral blood flow and VCI is documented and arterial hypertension in midlife is associated with a higher probability of cognitive impairment. These findings suggest that arterial hypertension is a main cause of vascular brain disorder (VBD). Spontaneously hypertensive rat (SHR) is the rat strain most extensively investigated and used for assessing hypertensive brain damage and treatment of it. They are normotensive at birth and at 6months they have a sustained hypertension. Time-dependent rise of arterial blood pressure, the occurrence of brain atrophy, loss of nerve cells and glial reaction are phenomena shared to some extent with hypertensive brain damage in humans. SHR present changes of some neurotransmitter systems that may have functional and behavioral relevance. An impaired cholinergic neurotransmission characterizes SHR, similarly as reported in patients affected by VaD. SHR are also characterized by a dopaminergic hypofunction and noradrenergic hyperactivity similarly as occurs in attention-deficit with hyperactivity disorder (ADHD). Microanatomical, neurochemical and behavioral data on SHR are in favor of the hypothesis that this strain is a suitable model of VBD. Changes in catecholaminergic transmission put forward SHR as a possible model of ADHD as well. Hence SHR could represent a multi-faced model of two important groups of pathologies, VBD and ADHD. As for most models, researchers should always consider that SHR offer some similarities with corresponding human pathologies, but they do not suffer from the same disease. This paper reviews the main microanatomical, neurochemical and behavioral characteristics of SHR with particular reference as an animal model of brain vascular injury.

  12. 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.

  13. [Hypertensive retinopathy].

    PubMed

    Genevois, Olivier; Paques, Michel

    2010-01-20

    Acute hypertensive retinopathy should be distinguished from retinal arteriolosclerosis. The presence of microvascular abnormalities in the ocular fundus increases the risk of heart and/or brain attack. At the clinical level, the current classification of chronic hypertensive retinopathy is based on the long-term risk of stroke. In research, a great number of studies are focused on the predictive value of retinal vascular diameters related to the general micro- and macrovascular disease. PMID:20222306

  14. [Hypertensive retinopathy].

    PubMed

    Genevois, Olivier; Paques, Michel

    2010-01-20

    Acute hypertensive retinopathy should be distinguished from retinal arteriolosclerosis. The presence of microvascular abnormalities in the ocular fundus increases the risk of heart and/or brain attack. At the clinical level, the current classification of chronic hypertensive retinopathy is based on the long-term risk of stroke. In research, a great number of studies are focused on the predictive value of retinal vascular diameters related to the general micro- and macrovascular disease.

  15. 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.

  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 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

  17. 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.

  18. 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

    2016-01-01

    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

  19. Pulmonary Hypertension

    PubMed Central

    Newman, John H.

    2005-01-01

    The modern era in cardiopulmonary medicine began in the 1940s, when Cournand and Richards pioneered right-heart catheterization. Until that time, no direct measurement of central vascular pressure had been performed in humans. Right-heart catheterization ignited an explosion of insights into function and dysfunction of the pulmonary circulation, cardiac performance, ventilation–perfusion relationships, lung–heart interactions, valvular function, and congenital heart disease. It marked the beginnings of angiocardiography with its diagnostic implications for diseases of the left heart and peripheral circulation. Pulmonary hypertension was discovered to be the consequence of a large variety of diseases that either raised pressure downstream of the pulmonary capillaries, induced vasoconstriction, increased blood flow to the lung, or obstructed the pulmonary vessels, either by embolism or in situ fibrosis. Hypoxic vasoconstriction was found to be a major cause of acute and chronic pulmonary hypertension, and surprising vasoreactivity of the pulmonary vascular bed was discovered to be present in many cases of severe pulmonary hypertension, initially in mitral stenosis. Diseases as disparate as scleroderma, cystic fibrosis, kyphoscoliosis, sleep apnea, and sickle cell disease were found to have shared consequences in the pulmonary circulation. Some of the achievements of Cournand and Richards and their scientific descendents are discussed in this article, including success in the diagnosis and treatment of idiopathic pulmonary arterial hypertension, chronic thromboembolic pulmonary hypertension, and management of hypoxic pulmonary hypertension. PMID:15994464

  20. Vascular Inflammatory Cells in Hypertension

    PubMed Central

    Harrison, David G.; Marvar, Paul J.; Titze, Jens M.

    2012-01-01

    Hypertension is a common disorder with uncertain etiology. In the last several years, it has become evident that components of both the innate and adaptive immune system play an essential role in hypertension. Macrophages and T cells accumulate in the perivascular fat, the heart and the kidney of hypertensive patients, and in animals with experimental hypertension. Various immunosuppressive agents lower blood pressure and prevent end-organ damage. Mice lacking lymphocytes are protected against hypertension, and adoptive transfer of T cells, but not B cells in the animals restores their blood pressure response to stimuli such as angiotensin II or high salt. Recent studies have shown that mice lacking macrophages have blunted hypertension in response to angiotensin II and that genetic deletion of macrophages markedly reduces experimental hypertension. Dendritic cells have also been implicated in this disease. Many hypertensive stimuli have triggering effects on the central nervous system and signals arising from the circumventricular organ seem to promote inflammation. Studies have suggested that central signals activate macrophages and T cells, which home to the kidney and vasculature and release cytokines, including IL-6 and IL-17, which in turn cause renal and vascular dysfunction and lead to blood pressure elevation. These recent discoveries provide a new understanding of hypertension and provide novel therapeutic opportunities for treatment of this serious disease. PMID:22586409

  1. 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. PMID:26325670

  2. 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.

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

    PubMed Central

    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. PMID:26823918

  5. Comparative trial of doxazosin and atenolol on cardiovascular risk reduction in systemic hypertension. The Alpha Beta Canada Trial Group.

    PubMed

    Carruthers, G; Dessain, P; Fodor, G; Newman, C; Palmer, W; Sim, D

    1993-03-01

    The impact of treating hypertension on coronary artery disease has been less than anticipated from epidemiologic studies of cardiovascular risk factors. It has been suggested that adverse effects on lipids of traditional diuretic or beta-blocker regimens may diminish the potential benefits of antihypertensive therapy. Patients with mild to moderate systemic hypertension and normal serum lipids (n = 191) were randomly assigned to doxazosin or atenolol. After dose titration to goal diastolic blood pressure of < or = 90 mm Hg, patients continued treatment for a further 24 weeks. The principal outcome measurement was overall coronary artery disease risk using the Framingham formula. Relative risk of coronary artery disease was reduced to 92.4% of baseline (p = 0.144) for evaluable patients taking atenolol (n = 71), and to 74.6% (p = 0.0001) for patients taking doxazosin (n = 51): atenolol versus doxazosin, p = 0.0074. In patients who met the strict Framingham criteria for age, total cholesterol and high density lipoprotein cholesterol, the relative risk of coronary artery disease for patients taking atenolol (n = 23) was reduced to 86.2% of baseline (p = 0.082), and to 67.4% (p = 0.0004) for patients taking doxazosin (n = 18): atenolol versus doxazosin, p = 0.049. Alpha blockade with doxazosin was more effective than beta blockade with atenolol in reducing the risk of coronary artery disease in hypertensive patients because of the beneficial effects of doxazosin on high-density lipoprotein cholesterol. Overall withdrawal rate was greater in the alpha-blocker group because of a lower response rate and more adverse events.

  6. Types of Pulmonary Hypertension

    MedlinePlus

    ... from the NHLBI on Twitter. Types of Pulmonary Hypertension The World Health Organization divides pulmonary hypertension (PH) ... are called pulmonary hypertension.) Group 1 Pulmonary Arterial Hypertension Group 1 PAH includes: PAH that has no ...

  7. Uric acid and hypertension.

    PubMed

    Feig, Daniel I

    2011-09-01

    A link between serum uric acid and the development of hypertension was first hypothesized in the 1870s. Although numerous epidemiologic studies in the 1980s and 1990s suggested an association, relatively little attention was paid to it until recently. Animal models have suggested a two-step pathogenesis by which uric acid initially activates the renin angiotensin system and suppresses nitric oxide, leading to uric acid-dependent increase in systemic vascular resistance, followed by a uric acid-mediated vasculopathy, involving renal afferent arterioles, resulting in a late sodium-sensitive hypertension. Initial clinical trials in young patients have supported these mechanisms in young patients but do not yet support pharmacologic reduction of serum uric acid as first-line therapy for hypertension.

  8. [Obesity and hypertension].

    PubMed

    Simonyi, Gábor; Kollár, Réka

    2013-11-01

    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.

  9. Recent Strategies in Treatment of Pulmonary Arterial Hypertension, A Review

    PubMed Central

    Fallah, Flora

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a disease characterized by an elevation in pulmonary artery pressure that can lead to right ventricular failure and death. The pulmonary circulation has to accommodate the entire cardiac output in each cardiac cycle and evolution has adapted to this by making it a low-pressure high-flow system. However, pathology can affect both the arterial and venous components of this system. Pulmonary venous hypertension mainly refers to diseases that result in elevated venous pressure and occurs mainly from mitral valve and left-sided heart disease. Standard treatment options include oral anticoagulation, diuretics, oxygen supplementation, and for a small percentage of patients, calcium channel blockers. Newer treatments include prostacyclin analogues, endothelin receptor antago¬nists, and phosphodiesterase type 5 inhibitors. This article reviews the current treatments strategies for PAH and provides guidelines for its management. PMID:25946920

  10. 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

  11. [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. PMID:2144118

  12. [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.

  13. [An expert system of aiding decision making in breast pathology connected to a clinical data base].

    PubMed

    Brunet, M; Durrleman, S; Ferber, J; Ganascia, J G; Hacene, K; Hirt, F; Jouniaux, F; Meeus, L

    1987-01-01

    The René Huguenin Cancer Center holds a medical file for each patient which is intended to store and process medical data. Since 1970, we introduced computerization: a development plan was elaborated and simultaneously a statistical software (Clotilde--GSI/CFRO) was selected. Thus, we now have access to a large database, structured according to medical rationale, and utilizable with methods of artificial intelligence towards three objectives: improved data acquisition, decision making and exploitation. The first application was to breast pathology, which represents one of the Center's primary activities. The structure of the data concerning patients is by all criteria part of the medical knowledge. This information needs to be presented as well as processed with a suitable language. To this end, we chose a language-oriented object, Mering II, usable with Apple and IBM 4 micro-computers. This project has already allowed to work out an operational model. PMID:3620732

  14. A consensus approach to maintain a knowledge based system in pathology.

    PubMed Central

    LeBozec, C.; Zapletal, E.; Degoulet, P.; Jaulent, M. C.

    2001-01-01

    The IDEM (Images and Diagnosis from Example in Medicine) software is a computerized environment able to store unambiguous descriptions of histopathologic images from pathologists. Medical imaging could benefit from such environments if they can easily and continuously be maintained. Within the IDEM environment, we developed a knowledge management module coupled with a consensus module to support knowledge acquisition and maintenance by the experts of the domain. Two pathologists, a senior and junior pathologist, reviewed fifty-three cases of breast pathology. Our findings indicate 1) that the IDEM knowledge management module allows experts to describe images by selecting terms and defining new ones if necessary, allowing the construction of a glossary for the domain and 2) that the consensus module, developed to store valid multi-experts cases, contributes also to validate new terms of the glossary and to refine semantic distance between terms. Such methodology could be applied to others highly evolving medical domains. PMID:11825210

  15. Pathology informatics fellowship training: Focus on molecular pathology

    PubMed Central

    Mandelker, Diana; Lee, Roy E.; Platt, Mia Y.; Riedlinger, Gregory; Quinn, Andrew; Rao, Luigi K. F.; Klepeis, Veronica E.; Mahowald, Michael; Lane, William J.; Beckwith, Bruce A.; Baron, Jason M.; McClintock, David S.; Kuo, Frank C.; Lebo, Matthew S.; Gilbertson, John R.

    2014-01-01

    Background: Pathology informatics is both emerging as a distinct subspecialty and simultaneously becoming deeply integrated within the breadth of pathology practice. As specialists, pathology informaticians need a broad skill set, including aptitude with information fundamentals, information systems, workflow and process, and governance and management. Currently, many of those seeking training in pathology informatics additionally choose training in a second subspecialty. Combining pathology informatics training with molecular pathology is a natural extension, as molecular pathology is a subspecialty with high potential for application of modern biomedical informatics techniques. Methods and Results: Pathology informatics and molecular pathology fellows and faculty evaluated the current fellowship program's core curriculum topics and subtopics for relevance to molecular pathology. By focusing on the overlap between the two disciplines, a structured curriculum consisting of didactics, operational rotations, and research projects was developed for those fellows interested in both pathology informatics and molecular pathology. Conclusions: The scope of molecular diagnostics is expanding dramatically as technology advances and our understanding of disease extends to the genetic level. Here, we highlight many of the informatics challenges facing molecular pathology today, and outline specific informatics principles necessary for the training of future molecular pathologists. PMID:24843823

  16. Microparticles in physiological and in pathological conditions.

    PubMed

    Roos, Maria Augusta; Gennero, Luisa; Denysenko, Tetyana; Reguzzi, Stefano; Cavallo, Giovanni; Pescarmona, Gian Piero; Ponzetto, Antonio

    2010-10-01

    Chronic diseases pose a severe burden to modern National Health Systems. Individuals nowadays have a far more extended lifespan than in the past, but healthy living was only scantily extended. As much as longer life is desirable, it is saddened by chronic diseases and organ malfunctions. One contributor to these problems was recognized to be represented by microparticles (MPs). Our purpose is to better understand MPs, to contrast their ominous threat and possible clinical importance. For this intent we correlated MPs with thrombotic pathologies, hemophilia, malaria, diabetes, cardiovascular diseases, endothelial dysfunctions, pulmonary hypertension, ischemic stroke, pre-eclampsia, rheumatologic diseases-rheumatoid arthritis, polymyositis-dermatomyositis, angiogenesis and tumor progression-cancer; we listed the possibilities of using them to improve transfusion methods, as a marker for acute allograft rejection, in stem cell transplantation, as neuronal biomarkers, to understand gender-specific susceptibility for diseases and to improve vaccination methods and we presented some methods for the detection of MPs. PMID:20941744

  17. [Function of hypothalamic-pituitary-adrenocortical system in hypertensive rats of ISIAH strain].

    PubMed

    Khvorostova, Iu V; Goriakin, S V; Pertrova, G V; Filipenko, M L; Shikhevich, S G; Redina, O E; Dymshits, G M; Markel', A L

    2002-11-01

    Functional activity of hypothalamic-pituitary-adrenocortical axis has been studied under control and restraint stress conditions in rats with inherited stress-sensitive arterial hypertension (ISIAH strain) and in normotensive WAG (Wistar Albino Glaxo) strain. The levels of hypothalamic CRH-mRNA (in control and 2 hrs stress), pituitary and plasma ACTH and plasma corticosterone (in control and after 5, 15 or 30 min of restraint stress), were evaluated. Hypothalamic CRH-mRNA level was found to be approximately the same in the control rats of both strains. In control conditions, the pituitary and plasma ACTH content in ISIAH rats was significantly lower whereas the corticosterone level in the plasma differed from each other in both strain. The restraint stress resulted in a statistically significant increase of the CRH-mRNA in ISIAH rats and not in the WAG rats. Moreover, in spite of the lower ACTH level in stressed ISIAH rats, the corticosterone blood plasma concentration in hypetensive rats was significantly higher. The data obtained confirm the idea that the stress-dependent hypertension might be related to an enhanced sensitivity of the main endocrine links involved in the stress response organization. PMID:12587270

  18. Effects of dietary calcium on erythrocyte sodium ion transport systems in spontaneously hypertensive rats.

    PubMed

    Fujito, K; Yokomatsu, M; Ishiguro, N; Numahata, H; Tomino, Y; Koide, H

    1991-01-01

    The alteration of sodium ion transport in red blood cells was observed in SHR and patients with essential hypertension. The purpose of the present study was to determine the effects of dietary calcium intake on blood pressure and sodium ion transport of red blood cells in SHR. The SHR were fed a diet with three different levels of calcium contents as follows: 0.1% (low), 0.6% (normal) and 4.0% (high) of calcium between 6 and 20 weeks of age. At 20 weeks of age, the levels of erythrocyte sodium efflux, sodium or potassium contents in the red blood cells were measured. On the high Ca diet, SHR showed an attenuation of the increase in blood pressure. On the low Ca diet, SHR showed an enhancement of hypertension. In proportion of increasing of dietary calcium contents, SHR had a lower level of sodium content in the RBC and a higher activity of the sodium pump. However, the passive sodium permeability and sodium-potassium cotransport in SHR were similar among the three different Ca diets. It is concluded that the amounts of dietary Ca might be related to the regulation of blood pressure by changing the sodium pump of the cell membrane in SHR.

  19. 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. PMID:25838016

  20. 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.

  1. 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.

  2. 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. PMID:26276015

  3. Ventricular and vascular stiffening in aging and hypertension.

    PubMed

    Faconti, L; Bruno, R M; Ghiadoni, L; Taddei, S; Virdis, A

    2015-01-01

    The assessment of arterial stiffness, a common feature of aging, exacerbated by pathological conditions like hypertension, has become an attractive tool for identifying structural and functional changes of the arteries even in an early stage of the atherosclerotic disease. Arterial stiffness has been recognized as an important physio-pathological determinant for the age-related rise in systolic blood pressure, demonstrating also an independent predictive value for cardiovascular events. In the recent decades, many techniques and indices to evaluate vascular stiffness have been developed and extensive data concerning their prognostic value have been collected. Moreover, it has become clear that vessel and heart must be considered as a unique system, in which combined stiffness of vessel and heart interacts to limit cardiovascular performance. In this review, main methods and indices used to estimate arterial and ventricular stiffness are presented, focusing on their alteration in physiological aging and arterial hypertension. Furthermore, the concept of ventricular-arterial coupling is explained in order to give an insight to the interplay between arterial and ventricular stiffness in aging and hypertension.

  4. Hypercortisolism in obesity-associated hypertension.

    PubMed

    Varughese, Amy G; Nimkevych, Oksana; Uwaifo, Gabriel I

    2014-07-01

    Obesity is prevalent worldwide and associated with co-morbidities that result in increased cardiovascular risk. Hypertension is the most prevalent obesity comorbidity associated with increased cardiovascular risk. Obesity hypertension is a distinct subtype of essential hypertension. While endogenous Cushing's syndrome is an uncommon cause of both obesity and hypertension, the recent recognition of other hypercortisolemic states has raised the profile of hypercortisolism as an important contributor in obesity hypertension. The high prevalence of exogenous, iatrogenic, pseudo, and subclinical Cushing's syndromes makes hypercortisolism an important diagnostic consideration in the evaluation and management of patients with obesity hypertension who are resistant to conventional management. Available data suggest that the renin-angiotensin-aldosterone system modulating antihypertensives have the best efficacy in hypercortisolism-mediated obesity hypertension. Strategies aimed at reducing cortisol production and action also have utility. This review provides a comprehensive overview of the epidemiology, etiopathogenesis and management options available for glucocorticoid-mediated obesity hypertension.

  5. Neurological theory of hypertension.

    PubMed

    Eggers, A E

    2003-06-01

    Review of the older literature on the relationship between migraine and hypertension, written in the era before either condition could be treated, discloses a high rate of co-morbidity. A neurological theory of essential hypertension is proposed in which the two diseases are brought together into one entity. It is hypothesized that abnormally functioning serotonergic pacemaker cells in the dorsal raphe nucleus, as part of a chronic stress response, inappropriately activate and inhibit parts of the central and autonomic nervous systems, so as to cause the two conditions. This theory builds on a previously published neural theory of migraine.

  6. Endothelial and Non-Endothelial Coronary Blood Flow Reserve and Left Ventricular Dysfunction in Systemic Hypertension

    PubMed Central

    Rocha, Aloísio Marchi; Salemi, Vera Maria Cury; Neto, Pedro Alves Lemos; Matsumoto, Afonso Yoshikiro; Pereira, Valéria Fontenelle Angelim; Fernandes, Fábio; Nastari, Luciano; Mady, Charles

    2009-01-01

    OBJECTIVES: We evaluated the impairment of endothelium-dependent and endothelium-independent coronary blood flow reserve after administration of intracoronary acetylcholine and adenosine, and its association with hypertensive cardiac disease. INTRODUCTION: Coronary blood flow reserve reduction has been proposed as a mechanism for the progression of compensated left ventricular hypertrophy to ventricular dysfunction. METHODS: Eighteen hypertensive patients with normal epicardial coronary arteries on angiography were divided into two groups according to left ventricular fractional shortening (FS). Group 1 (FS ≥0.25): n=8, FS=0.29 ± 0.03; Group 2 (FS <0.25): n=10, FS= 0.17 ± 0.03. RESULTS: Baseline coronary blood flow was similar in both groups (Group 1: 80.15 ± 26.41 mL/min, Group 2: 100.09 ± 21.51 mL/min, p=NS). In response to adenosine, coronary blood flow increased to 265.1 ± 100.2 mL/min in Group 1 and to 300.8 ± 113.6 mL/min (p <0.05) in Group 2. Endothelium-independent coronary blood flow reserve was similar in both groups (Group 1: 3.31 ± 0.68 and Group 2: 2.97 ± 0.80, p=NS). In response to acetylcholine, coronary blood flow increased to 156.08 ± 36.79 mL/min in Group 1 and to 177.8 ± 83.6 mL/min in Group 2 (p <0.05). Endothelium-dependent coronary blood flow reserve was similar in the two groups (Group 1: 2.08 ± 0.74 and group Group 2: 1.76 ± 0.61, p=NS). Peak acetylcholine/peak adenosine coronary blood flow response (Group 1: 0.65 ± 0.27 and Group 2: 0.60 ± 0.17) and minimal coronary vascular resistance (Group 1: 0.48 ± 0.21 mmHg/mL/min and Group 2: 0.34 ± 0.12 mmHg/mL/min) were similar in both groups (p= NS). Casual diastolic blood pressure and end-systolic left ventricular stress were independently associated with FS. CONCLUSIONS: In our hypertensive patients, endothelium-dependent and endothelium-independent coronary blood flow reserve vasodilator administrations had similar effects in patients with either normal or decreased left

  7. Obesity-induced hypertension develops in young rats independently of the renin-angiotensin-aldosterone system.

    PubMed

    Smith, Anita D; Brands, Michael W; Wang, Mong-Heng; Dorrance, Anne M

    2006-03-01

    A correlation exists between obesity and hypertension. In the currently available models of diet-induced obesity, the treatment of rats with a high fat (HF) diet does not begin until adulthood. Our aim was to develop and characterize a model of pre-pubescent obesity-induced hypertension. Male Sprague-Dawley rats were fed a HF diet (35% fat) for 10 weeks, beginning at age 3 weeks. Blood pressure was measured by tail-cuff, and a terminal blood sample was obtained to measure fasting blood glucose, insulin, plasma renin, aldosterone, thiobarbitutic acid reactive substances (TBARS), and free 8-isoprostanes levels. The vascular reactivity in the aorta was assessed using a myograph. Blood pressure was increased in rats fed the HF diet (HF, 161 +/- 2 mm Hg vs. control, 137 +/- 2 mm Hg, P < 0.05). Blood glucose (HF, 155 +/- 4 mg/dL vs. control, 123 +/- 5 mg/dL, P < 0.05), insulin (HF, 232 +/- 63 pM vs. control, 60 +/- 11 pM, P < 0.05), TBARS (expressed as nM of malondialdehyde [MDA]/ml [HF, 1.8 +/- 0.37 nM MDA/ml vs. control 1.05 +/- 0.09 nM MDA/ml, P < 0.05]), and free 8-isoprostanes (HF, 229 +/- 68 pg/ml vs. control, 112 +/- 9 pg/ml, P < 0.05) levels were elevated in the HF diet group. Interestingly, plasma renin and aldosterone levels were not different between the groups. The maximum vasoconstriction to phenylephrine (10(-4) M) was increased in the HF diet group (HF, 26.1 +/- 1.5 mN vs. control 22.3 +/- 1.2 mN, P < 0.05). In conclusion, pre-pubescent rats become hypertensive and have increased oxidative stress and enhanced vasoconstriction when fed a HF diet. Surprisingly, this occurs without the increase in renin or aldosterone levels seen in the adult models of diet-induced obesity.

  8. [Clinical pathology].

    PubMed

    Dimitrijević, Jovan

    2006-05-01

    This work describes the basic elements of pathology used in clinical practice. Pathology plays an important role in clinical and scientific work, but only a few areas of pathology will be covered. Although the contribution of oncological and surgical pathology to therapy is the most well known, the cases chosen here will involve infectious pathology, diseases of the kidney and the liver, autoimmune diseases, as well as organ transplantation. Especially important is the description of methods that enable more accurate morphological diagnoses, such as histochemistry, immunohistochemistry, immunofluorescence, and electronic microscopy. Previous experience and joint work with clinical doctors have enabled the definition of significant morphological elements as well as of essential methods of pathohistological diagnosis. Besides, as is often the case, although disease symptoms are difficult to discern and biochemical results do not show significant changes compared to normal values, the results of biopsy come as a surprise to clinical doctors. For example, in virus hepatitis B involving so-called asymptomatic HBsAg carriers, we discovered every morphological form of hepatitis, from minimal lesions to chronic, persistent, and active hepatitis. With hepatitis C, certain morphological lesions point to the etiopathogenesis of this disease and thus help to confirm the diagnosis and to instigate therapy on time. Another significant experience involves kidney biopsies in cases when clinical findings are asymptomatic. Often, in such cases, morphological findings point to glomerulonephritis and glomerulopathy at different stages. Timely and subtle morphological diagnostics offer a more precise explanation for the pathological injury of tissues than other diagnostic methods. In this way, by adopting new methods, the work of pathologists is included more and more in everyday clinical practice. The inclusion of pathologists in a transplantation team makes sure a proper selection of

  9. Osteoarthritis: Pathology, Mouse Models, and Nanoparticle Injectable Systems for Targeted Treatment.

    PubMed

    Holyoak, Derek T; Tian, Ye F; van der Meulen, Marjolein C H; Singh, Ankur

    2016-06-01

    Osteoarthritis (OA) is a progressive, degenerative disease of articulating joints that not only affects the elderly, but also involves younger, more active individuals with prolonged participation in high physical-demand activities. Thus, effective therapies that are easy to adopt clinically are critical in limiting the societal burden associated with OA. This review is focused on intra-articular injectable regimens and provides a comprehensive look at existing in vivo models of OA that might be suitable for developing, testing, and finding a cure for OA by intra-articular injections. We first discuss the pathology, molecular mechanisms responsible for the initiation and progression of OA, and challenges associated with disease-specific targeting of OA. We proceed to discuss available animal models of OA and provide a detailed perspective on the use of mouse models in studies of experimental OA. We finally provide a closer look at intra-articular injectable treatments for OA, focusing on biomaterials-based nanoparticles, and provide a comprehensive overview of the various nanometer-size ranges studied. PMID:27044450

  10. Portopulmonary hypertension.

    PubMed

    Lv, Yong; Han, Guohong; Fan, Daiming

    2016-07-01

    Portopulmonary hypertension (PoPH) refers to the condition that pulmonary arterial hypertension (PAH) occur in the stetting of portal hypertension. The development of PoPH is thought to be independent of the severity of portal hypertension or the etiology or severity of liver disease. PoPH results from excessive vasoconstriction, vascular remodeling, and proliferative and thrombotic events within the pulmonary circulation that lead to progressive right ventricular failure and ultimately to death. Untreated PoPH is associated with a poor prognosis. As PoPH is frequently asymptomatic or symptoms are generally non-specific, patients should be actively screened for the presence of PoPH. Two-dimensional transthoracic echocardiography is a useful non-invasive screening tool, but a definitive diagnosis requires invasive hemodynamic confirmation by right heart catheterization. Despite a dearth of randomized, prospective data, an ever-expanding clinical experience shows that patients with PoPH benefit from therapy with PAH-specific medications including with endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and/or prostanoids. Due to high perioperative mortality, transplantation should be avoided in those patients who have severe PoPH that is refractory to medical therapy. PMID:27002212

  11. Systemic and renal effects of chronic angiotensin converting enzyme inhibition with captopril in hypertensive diabetic patients.

    PubMed

    Stornello, M; Valvo, E V; Vasques, E; Leone, S; Scapellato, L

    1989-09-01

    Nine outpatients with mild to moderate arterial hypertension, type 2 diabetes mellitus and persistent macroalbuminuria were studied. After 1 month of placebo, the patients were treated with 50 mg captopril twice a day for the following 6 months. Blood pressure and urinary albumin excretion were significantly reduced but no relationship was found between these two variables. No changes were detected in the renal plasma flow, glomerular filtration rate, filtration fraction, renal vascular resistance or metabolic pattern. Captopril significantly reduced blood pressure and albuminuria without any change in the renal function. The decrease in albuminuria may be related to the reduction in blood pressure as well as to a direct effect of captopril on glomerular haemodynamics.

  12. The renin-angiotensin system: a target of and contributor to dyslipidemias, altered glucose homeostasis, and hypertension of the metabolic syndrome.

    PubMed

    Putnam, Kelly; Shoemaker, Robin; Yiannikouris, Frederique; Cassis, Lisa A

    2012-03-15

    The renin-angiotensin system (RAS) is an important therapeutic target in the treatment of hypertension. Obesity has emerged as a primary contributor to essential hypertension in the United States and clusters with other metabolic disorders (hyperglycemia, hypertension, high triglycerides, low HDL cholesterol) defined within the metabolic syndrome. In addition to hypertension, RAS blockade may also serve as an effective treatment strategy to control impaired glucose and insulin tolerance and dyslipidemias in patients with the metabolic syndrome. Hyperglycemia, insulin resistance, and/or specific cholesterol metabolites have been demonstrated to activate components required for the synthesis [angiotensinogen, renin, angiotensin-converting enzyme (ACE)], degradation (ACE2), or responsiveness (angiotensin II type 1 receptors, Mas receptors) to angiotensin peptides in cell types (e.g., pancreatic islet cells, adipocytes, macrophages) that mediate specific disorders of the metabolic syndrome. An activated local RAS in these cell types may contribute to dysregulated function by promoting oxidative stress, apoptosis, and inflammation. This review will discuss data demonstrating the regulation of components of the RAS by cholesterol and its metabolites, glucose, and/or insulin in cell types implicated in disorders of the metabolic syndrome. In addition, we discuss data supporting a role for an activated local RAS in dyslipidemias and glucose intolerance/insulin resistance and the development of hypertension in the metabolic syndrome. Identification of an activated RAS as a common thread contributing to several disorders of the metabolic syndrome makes the use of angiotensin receptor blockers and ACE inhibitors an intriguing and novel option for multisymptom treatment.

  13. Assessment of left ventricular filling in patients with systemic hypertension. A Doppler echocardiographic study.

    PubMed

    Faggiano, P; Rusconi, C; Orlando, G; Pavia, L; Ghizzoni, G; Maestri, M; Gardini, A; Simoncelli, U; Sorgato, A

    1989-06-01

    To assess left ventricular (LV) diastolic function in patients with hypertension, a Doppler echocardiographic study of transmitral blood flow (TBF) was performed in 46 hypertensive patients (H), 18 without (H1) and 28 with (H2) left ventricular hypertrophy and in 25 age-matched normal subjects (N). All patients showed normal systolic function. The following indices of Doppler TBF were measured: peak flow velocity during early filling (Evel), atrial systole (Avel) and their ratio (E/Avel); area under early filling phase (Earea), area under atrial systole (Aarea), expressed as a percentage of total diastolic area and their ratio (E/Aarea); deceleration half-time (DHT) of early filling phase. When compared with N, H1 and H2 showed significant reductions in early filling indices and an increase in atrial contribution parameters. (Evel = 0.62 +/- 0.1(N), 0.52 +/- 0.1(H1) P less than 0.01, 0.44 +/- 0.1(H2) P less than 0.001; Earea = 56 +/- 5(N), 48 +/- 5(H1) P less than 0.001, 43 +/- 6(H2) P less than 0.001; Avel = 0.49 +/- 0.1(N), 0.59 +/- 0.1(H1) P less than 0.01, 0.69 +/- 0.14(H2) P less than 0.001; Aarea = 26 +/- 5(N), 41 +/- 4(H1) P less than 0.001, 47 +/- 7(H2) P less than 0.001). Also DHT was significantly prolonged, compared with N (80 +/- 12 msec), in H1 (90 +/- 12 msec, P less than 0.01) and H2 (105 +/- 20 msec, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2769673

  14. Unprovoked atrial tachyarrhythmias in aging spontaneously hypertensive rats: the role of the autonomic nervous system.

    PubMed

    Scridon, Alina; Gallet, Clément; Arisha, Moussa M; Oréa, Valérie; Chapuis, Bruno; Li, Na; Tabib, Alain; Christé, Georges; Barrès, Christian; Julien, Claude; Chevalier, Philippe

    2012-08-01

    Experimental models of unprovoked atrial tachyarrhythmias (AT) in conscious, ambulatory animals are lacking. We hypothesized that the aging, spontaneously hypertensive rat (SHR) may provide such a model. Baseline ECG recordings were acquired with radiotelemetry in eight young (14-wk-old) and eight aging (55-wk-old) SHRs and in two groups of four age-matched Wistar-Kyoto (WKY) rats. Quantification of AT and heart rate variability (HRV) analysis were performed based on 24-h ECG recordings in unrestrained rats. All animals were submitted to an emotional stress protocol (air-jet). In SHRs, carbamylcholine injections were also performed. Spontaneous AT episodes were observed in all eight aging SHRs (median, 91.5; range, 4-444 episodes/24 h), but not in young SHRs or WKY rats. HRV analysis demonstrated significantly decreased low frequency components in aging SHRs compared with age-matched WKY rats (P < 0.01) and decreased low/high frequency ratios in both young (P < 0.01) and aging (P = 0.01) SHRs compared with normotensive controls. In aging SHRs, emotional stress significantly reduced the number of arrhythmic events, whereas carbamylcholine triggered AT and significantly increased atrial electrical instability. This study reports the occurrence of unprovoked episodes of atrial arrhythmia in hypertensive rats, and their increased incidence with aging. Our results suggest that autonomic imbalance with relative vagal hyperactivity may be responsible for the increased atrial arrhythmogenicity observed in this model. We also provide evidence that, in this model, the sympatho-vagal imbalance preceded the occurrence of arrhythmia. These results indicate that aging SHRs may provide valuable insight into the understanding of atrial arrhythmias.

  15. Prediction of the left ventricular mass from the electrocardiogram in systemic hypertension.

    PubMed

    de Vries, S O; Heesen, W F; Beltman, F W; Kroese, A H; May, J F; Smit, A J; Lie, K I

    1996-05-01

    Although echocardiography provides a reliable method to determine left ventricular (LV) mass, it may not be available in all settings. Numerous electrocardiographic (ECG) criteria for the detection of LV hypertrophy have been developed, but few attempts have been made to predict the LV mass itself from the ECG. In a community-based survey program in the general population, 277 subjects were identified with untreated diastolic hypertension (diastolic blood pressure 95 to 115 mm Hg, 3 occasions) or isolated systolic hypertension (diastolic blood pressure <95 mm Hg and systolic blood pressure 160 to 220 mm Hg, 3 occasions). All subjects underwent ECG and echocardiography on the same day. A multiple linear regression analysis was performed using a random training sample of the data set (n = 185). The independent variables included both ECG and non-ECG variables. The resulting model was used to predict the LV mass in the remainder of the data set, the validation sample (n = 92). Using sex, age, body surface area, the S-voltage in V1 and V4, and the duration of the terminal P in V1 as independent variables, the model explained 45% of the variance (r = 0.67) in the training sample and 42% (r = 0.65) in the validation sample. This result exceeded that of 2 existing ECG models for LV mass (r = 0.40 and 0.41). The correlations between LV mass and combinations of ECG variables used for the detection of LV hypertrophy, such as the Sokolow-Lyon Voltage (r = 0.03) and the Cornell Voltage (r = 0.31), were comparatively low. In settings where echocardiography is not available or is too expensive and time-consuming, prediction of the LV mass from the ECG may offer a valuable alternative. PMID:8644648

  16. 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

  17. Hypertensive leucocytosis.

    PubMed

    Rajkumari, Rolinda; Laishram, Deben; Thiyam, Joshna; Javan, Ng

    2013-04-01

    There are studies showing association of high WBC count with the higher incidence of hypertension though a few are done in the Indian population. The present study was conducted with the view to find any significant increase in total leucocyte count and differential leucocyte count in hypertensive patient Twenty-seven hypertensives with 12 males and 15 females and 27 age and sex matched control subjects (normotensive) were studied. Hypertension was defined when the systolic BP > or = 140 mmHg or diastolic BP > or = 90 mmHg or history of taking antihypertensive medicine. Three blood pressure recordings at an interval of 2 minutes were taken after the patient was made to sit for 30 minutes with a standard mercury sphygmomanometer in the left arm. The disappearance of sound was used for diastolic blood pressure. Blood was drawn into EDTA containing vials. Two separate counts were performed: First for total leucocyte count (TLC) and second for determination of percentage of polymorphonuclear cells. For the TLC, 0.5 part of blood mixed with 10 part of Turk's fluid followed by counting of leucocyte in a counting chamber under light microscope. The percentage of polymorphonuclear leucocyte was performed on a slide after making the slide and staining it with Leishman's stain. The erythrocyte sedimentation rate (ESR) was performed using Wintrobe's methods. The first 1 hour reading on the Wintrobe's tube was taken for analysis. The total leucocyte count (TLC) for the study group as compared to the controls were 7413.70 +/- 735.45 cells/cmm and 5236.30 +/- 528.77 cells/ cmm which was statistically significant. The mean percentage neutrophils were 62.04 +/- 4.99 for study group and 53.00 +/- 3.44 for the controls; the mean percentage lymphocytes for the study group and the controls were 34.37 +/- 4.55 and 39.11 +/- 4.40 respectively. Both the mean percentage neutrophils and lymphocytes showed significant differences. The mean erythrocyte sedimentation rate (ESR) also showed

  18. Tissue kallikrein-kinin therapy in hypertension and organ damage.

    PubMed

    Chao, Julie; Bledsoe, Grant; Chao, Lee

    2014-01-01

    Tissue kallikrein is a serine proteinase that cleaves low molecular weight kininogen to produce kinin peptides, which in turn activate kinin receptors to trigger multiple biological functions. In addition to its kinin-releasing activity, tissue kallikrein directly interacts with the kinin B2 receptor, protease-activated receptor-1, and gamma-epithelial Na channel. The tissue kallikrein-kinin system (KKS) elicits a wide spectrum of biological activities, including reducing hypertension, cardiac and renal damage, restenosis, ischemic stroke, and skin wound injury. Both loss-of-function and gain-of-function studies have shown that the KKS plays an important endogenous role in the protection against health pathologies. Tissue kallikrein/kinin treatment attenuates cardiovascular, renal, and brain injury by inhibiting oxidative stress, apoptosis, inflammation, hypertrophy, and fibrosis and promoting angiogenesis and neurogenesis. Approaches that augment tissue kallikrein-kinin activity might provide an effective strategy for the treatment of hypertension and associated organ damage. PMID:25130039

  19. Animal models in obesity and hypertension.

    PubMed

    Segal-Lieberman, Gabriella; Rosenthal, Talma

    2013-06-01

    Although obesity is a well-known risk factor for hypertension, the mechanisms by which hypertension develops in obese patients are not entirely clear. Animal models of obesity and their different susceptibilities to develop hypertension have revealed some of the mechanisms linking obesity and hypertension. Adipose tissue is an endocrine organ secreting hormones that impact blood pressure, such as elements of the renin-angiotensin system whose role in hypertension have been established. In addition, the appetite-suppressing adipokine leptin activates the sympathetic nervous system via the melanocortin system, and this activation, especially in the kidney, increases blood pressure. Leptin secretion from adipocytes is increased in most models of obesity due to leptin resistance, although the resistance is often selective to the anorexigenic effect, while the susceptibility to the hypertensive effect remains intact. Understanding the pathways by which obesity contributes to increased blood pressure will hopefully pave the way to and better define the appropriate treatment for obesity-induced hypertension.

  20. Effect of Chronic Administration of Estradiol on Responsiveness of Isolated Systemic and Pulmonary Blood Vessels from Ovariectomized Wistar Rats with Hypoxic Pulmonary Hypertension.

    PubMed

    Artem'eva, M M; Kovaleva, Yu O; Medvedev, O S; Medvedeva, N A

    2015-08-01

    The long-term (4 weeks) administration of estradiol (15 μg/kg/day) to ovariectomized female Wistar rats induced hypoxic pulmonary hypertension and significantly (p<0.05) diminished relaxation of perfused serotonin-preconstricted isolated vascular segments of the pulmonary artery in response to estradiol (10(-6) M). At the same time, the isolated segments of systemic popliteal artery demonstrated a diminished response to serotonin and increased relaxation induced by acetylcholine (10(-5) M) or estradiol (10(-5) M) in comparison with preconstricted control vessels. Moderation of responsiveness to estradiol in pulmonary circulation can be one of the factors underlying the pro-hypertensive action of estradiol in female rats with hypoxic pulmonary hypertension.

  1. Long Noncoding RNA H19 in Digestive System Cancers: A Meta-Analysis of Its Association with Pathological Features

    PubMed Central

    Lin, Yang; Zhang, Xiaohui; Ying, Rongchao

    2016-01-01

    Long noncoding RNA (lncRNA) H19 has been reported to be upregulated in malignant digestive tumors, but its clinical relevance is not yet established. The meta-analysis was to investigate the association between H19 expression and pathological features of digestive system cancers. The databases of PubMed, EMBase, Web of Science, CNKI, and WanFang were searched for the related studies. A total of 478 patients from 6 studies were finally included. The meta-analysis showed that the patient group of high H19 expression had a higher risk of poorly differentiated grade, deep tumor invasion (T2 stage or more), lymph node metastasis, and advanced TNM stage than the group of low H19 expression, although there was no difference between them in terms of distant metastasis. Therefore, the high expression of lncRNA H19 might predict poor oncological outcomes of patients with digestive system cancers. PMID:27738631

  2. Severe pulmonary hypertension as the initial manifestation of systemic lupus erythematosus: a case report and review of the literature.

    PubMed

    Prete, M; Fatone, M C; Vacca, A; Racanelli, V; Perosa, F

    2014-01-01

    Severe pulmonary arterial hypertension (PAH) is rarely observed as the initial manifestation of systemic lupus erythematosus (SLE), and the diagnosis is often delayed. Here we present the case of a 32-year-old woman with severe PAH as the initial manifestation of SLE, who was successfully treated with mycophenolate mofetil and cyclosporine. This case offered the opportunity to critically review the epidemiology data, predictive markers, and pathogenic pathways of SLE-associated PAH (SLE-PAH) in relation to the currently available therapeutic options and to the main clinical trials of the last 10 years focused on the treatment of SLE-PAH. Mycophenolate mofetil and cyclosporine - currently used in the maintenance phase of the disease in certain clinical settings - should be considered, as an alternative to cyclophosphamide, in future clinical trials aimed at evaluating the most effective treatment of SLE-PAH at presentation.

  3. 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.

  4. Central nervous system tumors: a single center pathology review of 34,140 cases over 60 years

    PubMed Central

    2013-01-01

    Background Tumor epidemiology is a significant part of CNS (central nervous system) tumor studies. Reassessment of original sections can update our knowledge of tumor spectrum. Here, we discuss the features of CNS tumor pathology in a single center. Methods A total of 34140 cases from 1950 to 2009 were collected; sections from 1990 to 2009 were reassessed according to WHO 2007 classification, and cases from 1950 to 1989 were classified according to the previous pathological diagnosis. Results Seven CNS tumor categories during 1990 to 2009 were as follow: neuroepithelial tissue (38.0%), tumors of the meninges (36.5%), tumors of the sellar region (4.1%), germ cell tumors (1.3%), tumors of cranial and paraspinal nerves (13.3%), lymphomas and hematopoietic neoplasm (1.7%), metastatic tumors (5.1%), where histological types by age and sex were diverse. Overall, males exceeded females in distributions of most CNS tumor subtypes, while tumors of the meninges occurred more frequently in females. The case number of lymphomas and hematopoietic neoplasms grew the fastest during the past five years, and the distribution of neuroepithelial tumors remained stable over the past twenty years. Conclusions Despite the possibilities of cross sample biases, the data in this series could suggest a similar CNS tumor spectrum as might occur in other developing countries. PMID:23639346

  5. Hypertension in obesity: is leptin the culprit?

    PubMed

    Simonds, Stephanie E; Cowley, Michael A

    2013-02-01

    The number of obese or overweight humans continues to increase worldwide. Hypertension is a serious disease that often develops in obesity, but it is not clear how obesity increases the risk of hypertension. However, both obesity and hypertension increase the risk of cardiovascular diseases (CVD). In this review, we examine how obesity may increase the risk of developing hypertension. Specifically, we discuss how the adipose-derived hormone leptin influences the sympathetic nervous system (SNS), through actions in the brain to elevate energy expenditure (EE) while also contributing to hypertension in obesity.

  6. [The normal ultrastructure of the erythrocytes and in experimental portal hypertension].

    PubMed

    Gaĭvoronskiĭ, I V; Chepur, S V; Nichiporuk, G I; Tikhonova, L P

    1997-01-01

    Erythrocyte types were studied in portal and femoral veins blood in intact dog and in the experimental portal hypertension under scanning electron microscope. Three basic types (discoid, polygonal and spherocyte) were distinguished. Analysis of the material obtained confirmed the suggestion on the existence of stable erythrocyte types both in normal conditions and pathology. Content of these types in blood of vessels named is different. Inferior caval vein system is inaccessible for erythrocytes with significantly altered shape because they are unable to penetrate liver sinusoids. In portal hypertension essential increase of these erythrocytes number occurs and they are encountered in femoral vein blood. These forms obviously pass into the general blood flow through multiple collaterals. One of the criteria for portal hypertension diagnostics is suggested so as the method of evaluating portal vein shunts in conditions of the formed collateral blood stream.

  7. Hypertension in blacks: clinical overview.

    PubMed

    Hildreth, C; Saunders, E

    1991-01-01

    Although the decline in stroke and other cardiovascular morbid and mortal events has been occurring since the 1940s, the steeper decline since 1968 has been attributed to improved hypertension awareness, treatment, and control. However, in spite of this encouraging trend from the population in general, surveys from the 1970s and our more recent survey from the Maryland Hypertension Program indicate that hypertension control among blacks remains unacceptably poor, particularly in view of the high prevalence. Of special concern are black men, who have the highest prevalence of any group and the poorest control rate (see Tables 6-1 through 6-4). According to Gillum and Gillum, "High rates of non-compliance with follow-up and drug therapy seriously compromised the efforts of community-wide programs. Indeed, non-compliance with therapeutic or preventive health advice is now the major barrier to effective hypertension control in the United States." Impediments to ideal hypertension control in black communities can be divided into three categories 1. Severity of hypertension in blacks. 2. Barriers related to the medical care system, including inadequate financial resources (see also Chapter 5), inconveniently located health care facilities, long waiting times, and inaccessibility to health education, specifically as it relates to hypertension. 3. Barriers related to the social, psychosocial, and sociopolitical environment, which include problems of underemployment, unemployment, racism, and strained racial relationships. In summary, one could say that, in spite of generally improved hypertension control in the United States, the group that has the worse problems (blacks, especially males) is not benefiting as much as the general population. The strategy for treating black patients with hypertension is little different from that applied to all other patients. However, consideration must be given to the patients' lifestyle. The cultural differences in diet especially must

  8. Polymorphisms in genes of the renin-angiotensin-aldosterone system and renal cell cancer risk: interplay with hypertension and intakes of sodium, potassium and fluid.

    PubMed

    Deckers, Ivette A; van den Brandt, Piet A; van Engeland, Manon; van Schooten, Frederik-Jan; Godschalk, Roger W; Keszei, András P; Schouten, Leo J

    2015-03-01

    Hypertension is an established risk factor for renal cell cancer (RCC). The renin-angiotensin-aldosterone system (RAAS) regulates blood pressure and is closely linked to hypertension. RAAS additionally influences homeostasis of electrolytes (e.g. sodium and potassium) and fluid. We investigated single nucleotide polymorphisms (SNPs) in RAAS and their interactions with hypertension and intakes of sodium, potassium and fluid regarding RCC risk in the Netherlands Cohort Study (NLCS), which was initiated in 1986 and included 120,852 participants aged 55 to 69 years. Diet and lifestyle were assessed by questionnaires and toenail clippings were collected. Genotyping of toenail DNA was performed using the SEQUENOM® MassARRAY® platform for a literature-based selection of 13 candidate SNPs in seven key RAAS genes. After 20.3 years of follow-up, Cox regression analyses were conducted using a case-cohort approach including 3,583 subcohort members and 503 RCC cases. Two SNPs in AGTR1 were associated with RCC risk. AGTR1_rs1492078 (AA vs. GG) decreased RCC risk [hazard ratio (HR) (95% confidence interval (CI)): 0.70(0.49-1.00)], whereas AGTR1_rs5186 (CC vs. AA) increased RCC risk [HR(95%CI): 1.49(1.08-2.05)]. Associations were stronger in participants with hypertension. The RCC risk for AGT_rs3889728 (AG + AA vs. GG) was modified by hypertension (p interaction = 0.039). SNP-diet interactions were not significant, although HRs suggested interaction between SNPs in ACE and sodium intake. SNPs in AGTR1 and AGT influenced RCC susceptibility, and their effects were modified by hypertension. Sodium intake was differentially associated with RCC risk across genotypes of several SNPs, yet some analyses had probably inadequate power to show significant interaction. Results suggest that RAAS may be a candidate pathway in RCC etiology.

  9. Hematopoietic tumors of the female genital system: imaging features with pathologic correlation.

    PubMed

    Salem, Usama; Menias, Christine O; Shaaban, Akram; Bhosale, Priya R; Youssef, Ayda; Elsayes, Khaled M

    2014-08-01

    Various hematopoietic neoplasms can involve the female genital system. The most common hematological malignancy that involves the female genital system is lymphoma and secondary involvement is more common than primary genital lymphoma. Rarely, leukemic infiltration and extramedullary plasmacytomas of the female genital tract may also occur. Being infrequent, these lesions are commonly misdiagnosed radiologically. Therefore, understanding these malignancies of the female genital system and recognizing their imaging features are of utmost clinical importance. Although definitive diagnosis can be made only by histological analysis, imaging of these tumors plays an important role in detecting lesion extensions, guiding biopsies, staging disease, planning therapy, and detecting recurrence.

  10. 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.

  11. Long-term effects of stress reduction on mortality in persons > or = 55 years of age with systemic hypertension.

    PubMed

    Schneider, Robert H; Alexander, Charles N; Staggers, Frank; Rainforth, Maxwell; Salerno, John W; Hartz, Arthur; Arndt, Stephen; Barnes, Vernon A; Nidich, Sanford I

    2005-05-01

    Psychosocial stress contributes to high blood pressure and subsequent cardiovascular morbidity and mortality. Previous controlled studies have associated decreasing stress with the Transcendental Meditation (TM) program with lower blood pressure. The objective of the present study was to evaluate, over the long term, all-cause and cause-specific mortality in older subjects who had high blood pressure and who participated in randomized controlled trials that included the TM program and other behavioral stress-decreasing interventions. Patient data were pooled from 2 published randomized controlled trials that compared TM, other behavioral interventions, and usual therapy for high blood pressure. There were 202 subjects, including 77 whites (mean age 81 years) and 125 African-American (mean age 66 years) men and women. In these studies, average baseline blood pressure was in the prehypertensive or stage I hypertension range. Follow-up of vital status and cause of death over a maximum of 18.8 years was determined from the National Death Index. Survival analysis was used to compare intervention groups on mortality rates after adjusting for study location. Mean follow-up was 7.6 +/- 3.5 years. Compared with combined controls, the TM group showed a 23% decrease in the primary outcome of all-cause mortality after maximum follow-up (relative risk 0.77, p = 0.039). Secondary analyses showed a 30% decrease in the rate of cardiovascular mortality (relative risk 0.70, p = 0.045) and a 49% decrease in the rate of mortality due to cancer (relative risk 0.49, p = 0.16) in the TM group compared with combined controls. These results suggest that a specific stress-decreasing approach used in the prevention and control of high blood pressure, such as the TM program, may contribute to decreased mortality from all causes and cardiovascular disease in older subjects who have systemic hypertension.

  12. Prenatal exposure to interleukin-6 results in hypertension and alterations in the renin–angiotensin system of the rat

    PubMed Central

    Samuelsson, Anne-Maj; Alexanderson, Camilla; Mölne, Johan; Haraldsson, Börje; Hansell, Peter; Holmäng, Agneta

    2006-01-01

    Cytokines are emerging as important in developmental processes. They may induce alterations in normal gene expression patterns, activate angiotensinogen transcription, or alter expression of the renin–angiotensin system (RAS). To determine whether prenatal exposure to interleukin-6 (IL-6) influences gene expression of the intrarenal RAS and contributes to renal dysfunction and hypertension in adulthood, we exposed female rats to IL-6 early (EIL-6 females) and late (LIL-6 females) in pregnancy and analysed blood pressure in the offspring at 5–20 weeks of age. Renal fluid and electrolyte excretion was assessed in clearance experiments, mRNA expression by real-time PCR, and protein levels by Western blot. Systolic pressure was increased at 5 weeks in IL-6 females and at 11 weeks in males. Circulatory RAS levels were increased in all IL-6 females, but angiotensin-1-converting enzyme (ACE) activity was increased only in LIL-6 females. LIL-6 males and IL-6 females showed decreased urinary flow rate and urinary sodium and potassium excretion. Dopamine excretion was decreased IL-6 females. In adult renal cortex, renin expression was increased in all IL-6 females, but angiotensinogen mRNA was increased only in LIL-6 females; AT1 receptor (AT1-R) mRNA and protein levels were increased in LIL-6 females, whereas AT2 receptor (AT2-R) levels were decreased in LIL-6 females and EIL-6 males. In adult renal medulla, AT1-R protein levels were increased in LIL-6 females, and AT2-R mRNA and protein levels were decreased in EIL-6 males and LIL-6 females. Prenatal IL-6 exposure may cause hypertension by altering the renal and circulatory RAS and renal fluid and electrolyte excretion, especially in females. PMID:16825309

  13. 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

  14. [Indexes of integrative activity of motor system in norm and at neuromotor pathology].

    PubMed

    Aleksanian, Z A; Romanov, S P

    2012-11-01

    Characteristics of integrative activity of motor control system are received by the methods of the time series analysis. The methods allow to give an objective estimation of human brain pyramidal and extrapyramidal systems functional state. Authors consider the voluntary regulation of isometric effort as a model of movement and investigate this effort as the integrative motor output of a motor control system. Using of peculiar methodology of non-invasive research of parameters of isometric effort as indexes of CNS integrative activity, and application of modern methods of the time-series analysis has allowed to receive a new data concerning an estimation of activity of structures of motor control system in norm and in some neurodegenerative diseases of CNS (Parkinson's diseases, multiple sclerosis). These results represent the new knowledge in the field of movement physiology, and also expand opportunity of hardware diagnostics of neuromotor dysfunctions.

  15. 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.

  16. Levels and actions of neuroactive steroids in the nervous system under physiological and pathological conditions: Sex-specific features.

    PubMed

    Melcangi, Roberto C; Giatti, Silvia; Garcia-Segura, Luis M

    2016-08-01

    Neuroactive steroids regulate the physiology of the central and peripheral nervous system, exert neuroprotective actions and represent interesting tools for therapeutic strategies against neurodegenerative and psychiatric disorders. Sex differences in their levels are detected not only under physiological conditions but are also modified in a sex-dependent way in different pathological alterations such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, traumatic brain injury, spinal cord injury, stroke, diabetic encephalopathy, psychiatric disorders and peripheral neuropathy. Interestingly, many of these disorders show sex differences in their incidence, symptomatology and/or neurodegenerative outcome. The neuroprotective actions of neuroactive steroids, together with the sex specific regulation of its levels might provide the basis to design sex-specific neuroprotective therapies. Indeed, some experiments here discussed suggest the viability of this approach. PMID:26657814

  17. Postsurgical Pathologies Associated with Intradural Electrical Stimulation in the Central Nervous System: Design Implications for a New Clinical Device

    PubMed Central

    Gibson-Corley, Katherine N.; Flouty, Oliver; Oya, Hiroyuki; Gillies, George T.; Howard, Matthew A.

    2014-01-01

    Spinal cord stimulation has been utilized for decades in the treatment of numerous conditions such as failed back surgery and phantom limb syndromes, arachnoiditis, cancer pain, and others. The placement of the stimulating electrode array was originally subdural but, to minimize surgical complexity and reduce the risk of certain postsurgical complications, it became exclusively epidural eventually. Here we review the relevant clinical and experimental pathologic findings, including spinal cord compression, infection, hematoma formation, cerebrospinal fluid leakage, chronic fibrosis, and stimulation-induced neurotoxicity, associated with the early approaches to subdural electrical stimulation of the central nervous system, and the spinal cord in particular. These findings may help optimize the safety and efficacy of a new approach to subdural spinal cord stimulation now under development. PMID:24800260

  18. 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

  19. Identification of a retinal aldosterone system and the protective effects of mineralocorticoid receptor antagonism on retinal vascular pathology.

    PubMed

    Wilkinson-Berka, Jennifer L; Tan, Genevieve; Jaworski, Kassie; Miller, Antonia G

    2009-01-01

    Blockade of the renin-angiotensin-aldosterone system (RAAS) is being evaluated as a treatment for diabetic retinopathy; however, whether the mineralocorticoid receptor (MR) and aldosterone influence retinal vascular pathology is unknown. We examined the effect of MR antagonism on pathological angiogenesis in rats with oxygen-induced retinopathy (OIR). To determine the mechanisms by which the MR and aldosterone may influence retinal angiogenesis; inflammation and glucose-6-phosphate dehydrogenase (G6PD) were evaluated in OIR and cultured bovine retinal endothelial cells (BRECs) and bovine retinal pericytes (BRPs). In OIR, MR antagonism (spironolactone) was antiangiogenic. Aldosterone may mediate the pathogenic actions of MR in the retina, with 11beta-hydroxysteroid dehydrogenase type 2 mRNA being detected and with aldosterone stimulating proliferation and tubulogenesis in BRECs and exacerbating angiogenesis in OIR, which was attenuated with spironolactone. The MR and aldosterone modulated retinal inflammation, with leukostasis and monocyte chemoattractant protein-1 mRNA and protein in OIR being reduced by spironolactone and increased by aldosterone. A reduction in G6PD may be an early response to aldosterone. In BRECs, BRPs, and early OIR, aldosterone reduced G6PD mRNA, and in late OIR, aldosterone increased mRNA for the NAD(P)H oxidase subunit Nox4. A functional retinal MR-aldosterone system was evident with MR expression, translocation of nuclear MR, and aldosterone synthase expression, which was modulated by RAAS blockade. We make the first report that MR and aldosterone influence retinal vasculopathy, which may involve inflammatory and G6PD mechanisms. MR antagonism may be relevant when developing treatments for retinopathies that target the RAAS.

  20. 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

  1. Influence of renovascular hypertension on the distribution of vasoactive intestinal peptide in the stomach and heart of rats

    PubMed Central

    Piotrowska, Żaneta; Janiuk, Izabela

    2015-01-01

    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. PMID:25990439

  2. 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.

  3. [Use of computerized tomography in the study of the etiology of various forms of symptomatic arterial hypertension].

    PubMed

    Shapkina, L S; Pogrebnaia, G N; Tolua, F I

    1988-01-01

    In 181 patients with arterial hypertension of various genesis clinical-laboratory data were compared with those obtained by computed tomography of kidneys and adrenal glands for etiology verification. Computer tomography is proved to be a valuable noninvasive method for elucidation of retroperitoneal space organs pathology which can cause arterial hypertension. Hormonal-active tumors are better identified when patients are purposely selected according to the catecholamine and VMA levels as well as the state of renin-angiotensin-aldosterone system. Computer tomography allowed determination of alterations in kidneys including those not identifiable by other methods (small cysts in kidneys, tumors, concrements).

  4. NGF in Early Embryogenesis, Differentiation, and Pathology in the Nervous and Immune Systems.

    PubMed

    Bracci-Laudiero, Luisa; De Stefano, Maria Egle

    2016-01-01

    The physiology of NGF is extremely complex, and although the study of this neurotrophin began more than 60 years ago, it is far from being concluded. NGF, its precursor molecule pro-NGF, and their different receptor systems (i.e., TrkA, p75NTR, and sortilin) have key roles in the development and adult physiology of both the nervous and immune systems. Although the NGF receptor system and the pathways activated are similar for all types of cells sensitive to NGF, the effects exerted during embryonic differentiation and in committed mature cells are strikingly different and sometimes opposite. Bearing in mind the pleiotropic effects of NGF, alterations in its expression and synthesis, as well as variations in the types of receptor available and in their respective levels of expression, may have profound effects and play multiple roles in the development and progression of several diseases. In recent years, the use of NGF or of inhibitors of its receptors has been prospected as a therapeutic tool in a variety of neurological diseases and injuries. In this review, we outline the different roles played by the NGF system in various moments of nervous and immune system differentiation and physiology, from embryonic development to aging. The data collected over the past decades indicate that NGF activities are highly integrated among systems and are necessary for the maintenance of homeostasis. Further, more integrated and multidisciplinary studies should take into consideration these multiple and interactive aspects of NGF physiology in order to design new therapeutic strategies based on the manipulation of NGF and its intracellular pathways.

  5. Plasma Molecular Signatures in Hypertensive Patients With Renin-Angiotensin System Suppression: New Predictors of Renal Damage and De Novo Albuminuria Indicators.

    PubMed

    Baldan-Martin, Montserrat; Mourino-Alvarez, Laura; Gonzalez-Calero, Laura; Moreno-Luna, Rafael; Sastre-Oliva, Tamara; Ruiz-Hurtado, Gema; Segura, Julian; Lopez, Juan Antonio; Vazquez, Jesus; Vivanco, Fernando; Alvarez-Llamas, Gloria; Ruilope, Luis M; de la Cuesta, Fernando; Barderas, Maria G

    2016-07-01

    Albuminuria is a risk factor strongly associated with cardiovascular disease, the first cause of death in the general population. It is well established that renin-angiotensin system suppressors prevent the development of new-onset albuminuria in naïf hypertensive patients and diminish its excretion, but we cannot forget the percentage of hypertensive patients who develop de novo albuminuria. Here, we applied multiple proteomic strategy with the purpose to elucidate specific molecular pathways involved in the pathogenesis and provide predictors and chronic organ damage indicators. Briefly, 1143 patients were followed up for a minimum period of 3 years. One hundred and twenty-nine hypertensive patients chronically renin-angiotensin system suppressed were recruited, classified in 3 different groups depending on their albuminuria levels (normoalbuminuria, de novo albuminuria, and sustained albuminuria), and investigated by multiple proteomic strategies. Our strategy allowed us to perform one of the deepest plasma proteomic analysis to date, which has shown 2 proteomic signatures: (1) with predictive value of de novo albuminuria and (2) sustained albuminuria indicator proteins. These proteins are involved in inflammation, immune as well as in the proteasome activation occurring in situations of endoplasmic reticulum stress. Furthermore, these results open the possibility of a future strategy based on anti-immune therapy to treat hypertension which could help to prevent the development of albuminuria and, hence, the progression of kidney damage. PMID:27217411

  6. Plasma Molecular Signatures in Hypertensive Patients With Renin-Angiotensin System Suppression: New Predictors of Renal Damage and De Novo Albuminuria Indicators.

    PubMed

    Baldan-Martin, Montserrat; Mourino-Alvarez, Laura; Gonzalez-Calero, Laura; Moreno-Luna, Rafael; Sastre-Oliva, Tamara; Ruiz-Hurtado, Gema; Segura, Julian; Lopez, Juan Antonio; Vazquez, Jesus; Vivanco, Fernando; Alvarez-Llamas, Gloria; Ruilope, Luis M; de la Cuesta, Fernando; Barderas, Maria G

    2016-07-01

    Albuminuria is a risk factor strongly associated with cardiovascular disease, the first cause of death in the general population. It is well established that renin-angiotensin system suppressors prevent the development of new-onset albuminuria in naïf hypertensive patients and diminish its excretion, but we cannot forget the percentage of hypertensive patients who develop de novo albuminuria. Here, we applied multiple proteomic strategy with the purpose to elucidate specific molecular pathways involved in the pathogenesis and provide predictors and chronic organ damage indicators. Briefly, 1143 patients were followed up for a minimum period of 3 years. One hundred and twenty-nine hypertensive patients chronically renin-angiotensin system suppressed were recruited, classified in 3 different groups depending on their albuminuria levels (normoalbuminuria, de novo albuminuria, and sustained albuminuria), and investigated by multiple proteomic strategies. Our strategy allowed us to perform one of the deepest plasma proteomic analysis to date, which has shown 2 proteomic signatures: (1) with predictive value of de novo albuminuria and (2) sustained albuminuria indicator proteins. These proteins are involved in inflammation, immune as well as in the proteasome activation occurring in situations of endoplasmic reticulum stress. Furthermore, these results open the possibility of a future strategy based on anti-immune therapy to treat hypertension which could help to prevent the development of albuminuria and, hence, the progression of kidney damage.

  7. Animal models of portal hypertension

    PubMed Central

    Abraldes, Juan G; Pasarín, Marcos; García-Pagán, Juan Carlos

    2006-01-01

    Animal models have allowed detailed study of hemodynamic alterations typical of portal hypertension and the molecular mechanisms involved in abnormalities in splanchnic and systemic circulation associated with this syndrome. Models of prehepatic portal hypertension can be used to study alterations in the splanchnic circulation and the pathophysiology of the hyperdynamic circulation. Models of cirrhosis allow study of the alterations in intrahepatic microcirculation that lead to increased resistance to portal flow. This review summarizes the currently available literature on animal models of portal hypertension and analyzes their relative utility. The criteria for choosing a particular model, depending on the specific objectives of the study, are also discussed. PMID:17075968

  8. 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…

  9. [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.

  10. [Pathology of the internal organs and central nervous system in acquired immunodeficiency syndrome (with special reference to opportunistic infections)].

    PubMed

    Masini, T; Chinaglia, D; Riviera, L; Capricci, E; Gullotta, F; Spigolon, G; Bauer, A L

    1990-01-01

    Extracerebral and cerebral pathology in AIDS (with particular emphasis on the opportunistic infections). The Authors present the extracerebral pathology of 27 cases of AIDS observed at the Department of Pathology of Milan and the cerebral pathology of 80 cases of AIDS collected by three Institutes (Department of Pathology of Milan, Department of Pathology of Rimini and Department of Neuropathology of Münster) with particular emphasis on the pathology of the opportunistic infections. In the adults' group, the most frequent infections are the protozoan ones (T. gondii) followed with equal incidence by the viral and fungal diseases. In the pediatric group the viral diseases are the most frequently seen. Almost all of the adults show multiple infections in the same organ or in different organs. Diffuse lesions with heavy pathologic fields were observed also without tissue reaction. As to cerebral pathology AIDS' patients with opportunistic infections show focal symptoms, whereas the so called "subacute microglial encephalitis" generally appears as a demential syndrome. In cases with progressive multifocal leukoencephalopathy JC virus was always found and in one case also SV 40 - and BK virus. The diffuse demyelinization in some cases of HIV-Encephalopathy is aspecific. In HIV-positive newborns with cerebral signs, the lesions are characterized by oedema, spongiosis and microcalcifications of the basal ganglia; these are aspecific lesions which can be found in toxic and infectious encephalopathies.

  11. Modelling staphylococcal pneumonia in a human 3D lung tissue model system delineates toxin-mediated pathology.

    PubMed

    Mairpady Shambat, Srikanth; Chen, Puran; Nguyen Hoang, Anh Thu; Bergsten, Helena; Vandenesch, Francois; Siemens, Nikolai; Lina, Gerard; Monk, Ian R; Foster, Timothy J; Arakere, Gayathri; Svensson, Mattias; Norrby-Teglund, Anna

    2015-11-01

    Staphylococcus aureus necrotizing pneumonia is recognized as a toxin-mediated disease, yet the tissue-destructive events remain elusive, partly as a result of lack of mechanistic studies in human lung tissue. In this study, a three-dimensional (3D) tissue model composed of human lung epithelial cells and fibroblasts was used to delineate the role of specific staphylococcal exotoxins in tissue pathology associated with severe pneumonia. To this end, the models were exposed to the mixture of exotoxins produced by S. aureus strains isolated from patients with varying severity of lung infection, namely necrotizing pneumonia or lung empyema, or to purified toxins. The necrotizing pneumonia strains secreted high levels of α-toxin and Panton-Valentine leukocidin (PVL), and triggered high cytotoxicity, inflammation, necrosis and loss of E-cadherin from the lung epithelium. In contrast, the lung empyema strain produced moderate levels of PVL, but negligible amounts of α-toxin, and triggered limited tissue damage. α-toxin had a direct damaging effect on the epithelium, as verified using toxin-deficient mutants and pure α-toxin. Moreover, PVL contributed to pathology through the lysis of neutrophils. A combination of α-toxin and PVL resulted in the most severe epithelial injury. In addition, toxin-induced release of pro-inflammatory mediators from lung tissue models resulted in enhanced neutrophil migration. Using a collection of 31 strains from patients with staphylococcal pneumonia revealed that strains producing high levels of α-toxin and PVL were cytotoxic and associated with fatal outcome. Also, the strains that produced the highest toxin levels induced significantly greater epithelial disruption. Of importance, toxin-mediated lung epithelium destruction could be inhibited by polyspecific intravenous immunoglobulin containing antibodies against α-toxin and PVL. This study introduces a novel model system for study of staphylococcal pneumonia in a human setting. The

  12. Modelling staphylococcal pneumonia in a human 3D lung tissue model system delineates toxin-mediated pathology.

    PubMed

    Mairpady Shambat, Srikanth; Chen, Puran; Nguyen Hoang, Anh Thu; Bergsten, Helena; Vandenesch, Francois; Siemens, Nikolai; Lina, Gerard; Monk, Ian R; Foster, Timothy J; Arakere, Gayathri; Svensson, Mattias; Norrby-Teglund, Anna

    2015-11-01

    Staphylococcus aureus necrotizing pneumonia is recognized as a toxin-mediated disease, yet the tissue-destructive events remain elusive, partly as a result of lack of mechanistic studies in human lung tissue. In this study, a three-dimensional (3D) tissue model composed of human lung epithelial cells and fibroblasts was used to delineate the role of specific staphylococcal exotoxins in tissue pathology associated with severe pneumonia. To this end, the models were exposed to the mixture of exotoxins produced by S. aureus strains isolated from patients with varying severity of lung infection, namely necrotizing pneumonia or lung empyema, or to purified toxins. The necrotizing pneumonia strains secreted high levels of α-toxin and Panton-Valentine leukocidin (PVL), and triggered high cytotoxicity, inflammation, necrosis and loss of E-cadherin from the lung epithelium. In contrast, the lung empyema strain produced moderate levels of PVL, but negligible amounts of α-toxin, and triggered limited tissue damage. α-toxin had a direct damaging effect on the epithelium, as verified using toxin-deficient mutants and pure α-toxin. Moreover, PVL contributed to pathology through the lysis of neutrophils. A combination of α-toxin and PVL resulted in the most severe epithelial injury. In addition, toxin-induced release of pro-inflammatory mediators from lung tissue models resulted in enhanced neutrophil migration. Using a collection of 31 strains from patients with staphylococcal pneumonia revealed that strains producing high levels of α-toxin and PVL were cytotoxic and associated with fatal outcome. Also, the strains that produced the highest toxin levels induced significantly greater epithelial disruption. Of importance, toxin-mediated lung epithelium destruction could be inhibited by polyspecific intravenous immunoglobulin containing antibodies against α-toxin and PVL. This study introduces a novel model system for study of staphylococcal pneumonia in a human setting. The

  13. Modelling staphylococcal pneumonia in a human 3D lung tissue model system delineates toxin-mediated pathology

    PubMed Central

    Mairpady Shambat, Srikanth; Chen, Puran; Nguyen Hoang, Anh Thu; Bergsten, Helena; Vandenesch, Francois; Siemens, Nikolai; Lina, Gerard; Monk, Ian R.; Foster, Timothy J.; Arakere, Gayathri; Svensson, Mattias; Norrby-Teglund, Anna

    2015-01-01

    ABSTRACT Staphylococcus aureus necrotizing pneumonia is recognized as a toxin-mediated disease, yet the tissue-destructive events remain elusive, partly as a result of lack of mechanistic studies in human lung tissue. In this study, a three-dimensional (3D) tissue model composed of human lung epithelial cells and fibroblasts was used to delineate the role of specific staphylococcal exotoxins in tissue pathology associated with severe pneumonia. To this end, the models were exposed to the mixture of exotoxins produced by S. aureus strains isolated from patients with varying severity of lung infection, namely necrotizing pneumonia or lung empyema, or to purified toxins. The necrotizing pneumonia strains secreted high levels of α-toxin and Panton-Valentine leukocidin (PVL), and triggered high cytotoxicity, inflammation, necrosis and loss of E-cadherin from the lung epithelium. In contrast, the lung empyema strain produced moderate levels of PVL, but negligible amounts of α-toxin, and triggered limited tissue damage. α-toxin had a direct damaging effect on the epithelium, as verified using toxin-deficient mutants and pure α-toxin. Moreover, PVL contributed to pathology through the lysis of neutrophils. A combination of α-toxin and PVL resulted in the most severe epithelial injury. In addition, toxin-induced release of pro-inflammatory mediators from lung tissue models resulted in enhanced neutrophil migration. Using a collection of 31 strains from patients with staphylococcal pneumonia revealed that strains producing high levels of α-toxin and PVL were cytotoxic and associated with fatal outcome. Also, the strains that produced the highest toxin levels induced significantly greater epithelial disruption. Of importance, toxin-mediated lung epithelium destruction could be inhibited by polyspecific intravenous immunoglobulin containing antibodies against α-toxin and PVL. This study introduces a novel model system for study of staphylococcal pneumonia in a human

  14. 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. PMID:25910811

  15. Cardiac angiotensin-(1-12) expression and systemic hypertension in rats expressing the human angiotensinogen gene.

    PubMed

    Ferrario, Carlos M; VonCannon, Jessica; Jiao, Yan; Ahmad, Sarfaraz; Bader, Michael; Dell'Italia, Louis J; Groban, Leanne; Varagic, Jasmina

    2016-04-15

    Angiotensin-(1-12) [ANG-(1-12)] is processed into ANG II by chymase in rodent and human heart tissue. Differences in the amino acid sequence of rat and human ANG-(1-12) render the human angiotensinogen (hAGT) protein refractory to cleavage by renin. We used transgenic rats harboring the hAGT gene [TGR(hAGT)L1623] to assess the non-renin-dependent effects of increased hAGT expression on heart function and arterial pressure. Compared with Sprague-Dawley (SD) control rats (n= 11), male homozygous TGR(hAGT)L1623 (n= 9) demonstrated sustained daytime and nighttime hypertension associated with no changes in heart rate but increased heart rate lability. Increased heart weight/tibial length ratio and echocardiographic indexes of cardiac hypertrophy were associated with modest reduction of systolic function in hAGT rats. Robust human ANG-(1-12) immunofluorescence within myocytes of TGR(hAGT)L1623 rats was associated with a fourfold increase in cardiac ANG II content. Chymase enzymatic activity, using the rat or human ANG-(1-12) as a substrate, was not different in the cardiac tissue of SD and hAGT rats. Since both cardiac angiotensin-converting enzyme (ACE) and ACE2 activities were not different among the two strains, the changes in cardiac structure and function, blood pressure, and left ventricular ANG II content might be a product of an increased cardiac expression of ANG II generated through a non-renin-dependent mechanism. The data also underscore the existence in the rat of alternate enzymes capable of acting on hAGT protein. Homozygous transgenic rats expressing the hAGT gene represent a novel tool to investigate the contribution of human relevant renin-independent cardiac ANG II formation and function. PMID:26873967

  16. 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.

  17. Physiological, pathological, and engineered cell identity reprogramming in the central nervous system.

    PubMed

    Smith, Derek K; Wang, Lei-Lei; Zhang, Chun-Li

    2016-07-01

    Multipotent neural stem cells persist in restricted regions of the adult mammalian central nervous system. These proliferative cells differentiate into diverse neuron subtypes to maintain neural homeostasis. This endogenous process can be reprogrammed as a compensatory response to physiological cues, traumatic injury, and neurodegeneration. In addition to innate neurogenesis, recent research has demonstrated that new neurons can be engineered via cell identity reprogramming in non-neurogenic regions of the adult central nervous system. A comprehensive understanding of these reprogramming mechanisms will be essential to the development of therapeutic neural regeneration strategies that aim to improve functional recovery after injury and neurodegeneration. WIREs Dev Biol 2016, 5:499-517. doi: 10.1002/wdev.234 For further resources related to this article, please visit the WIREs website. PMID:27258392

  18. Requests for VIP Treatment in Pathology: Implications for Social Justice and Systems-Based Practice.

    PubMed

    Sheffield, Virginia; Smith, Lauren B

    2016-01-01

    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.

  19. Strengths and Limitations of Model Systems for the Study of Urinary Tract Infections and Related Pathologies.

    PubMed

    Barber, Amelia E; Norton, J Paul; Wiles, Travis J; Mulvey, Matthew A

    2016-06-01

    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.

  20. Pathologies in Living Kidney Donors Diagnosed in the Long-Term Care System.

    PubMed

    Kwapisz, M; Kieszek, R; Jędrzejko, K; Domagała, P; Bieniasz, M; Gozdowska, J; Zygier, D; Drozdowski, J; Zatorski, M; Nowaczyk, M; Palczewski, P; Pączek, L; Durlik, M; Chmura, A; Kwiatkowski, A

    2016-06-01

    Kidney donation should not lead to deterioration of the donor's health condition, both during the perisurgical period and in the long term. Safety of a living kidney donor becomes a prerequisite for his/her qualification. Detailed diagnostic procedures are performed to exclude any abnormalities of his/her health condition. Additionally, a long-term post-donation follow-up system for kidney donors has been set up in Poland besides the restrictive qualification system. Transplantation centers are obligated to provide a diagnostic procedures for living organ donors as a part of the monitoring of their health condition and to ensure them a medical follow-up for 10 years after the donation. A total of 141 cases of unilateral nephroureterectomy performed in 2003-2014 to obtain a kidney for transplantation were considered. Medical files of post-donation diagnostic or therapeutic methods and their outcomes were retrospectively analyzed. The aim of the study was to assess the efficacy of monitoring of donors' health condition within the framework of the long-term follow-up system for kidney donors in the aspect of detection of the donation-independent abnormalities. PMID:27496424

  1. 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 ...

  2. What Causes Pulmonary Hypertension?

    MedlinePlus

    ... from the NHLBI on Twitter. What Causes Pulmonary Hypertension? Pulmonary hypertension (PH) begins with inflammation and changes in the ... different types of PH. Group 1 pulmonary arterial hypertension (PAH) may have no known cause, or the ...

  3. Hormones and Hypertension

    MedlinePlus

    Fact Sheet Hormones and Hypertension What is hypertension? Hypertension, or chronic (long-term) high blood pressure, is a main cause of ... tobacco, alcohol, and certain medications play a part. Hormones made in the kidneys and in blood vessels ...

  4. 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

  5. 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

  6. 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.

  7. HW 01-3 CARDIAC AND VASCULAR MRI IN HYPERTENSION EVALUATION.

    PubMed

    Lee, Sang-Chol

    2016-09-01

    Chronic hypertension can result in deleterious effects on various vascular organs including the heart and vessels. Cardiovascular magnetic resonance (CMR) has the unique advantage of the ability to assess ventricular volumes and function, valvular abnormalities, vascular pathology, myocardial perfusion and tissue characterization with high accuracy and reproducibility and also avoid the risk of radiation. As this is the case, CMR seems to be an ideal method for comprehensive assessment of patients with systemic hypertension.In the heart itself, left ventricular hypertrophy with myocardial fibrosis and diastolic or systolic dysfunction of the left ventricle are all important consequences of systemic hypertension that can lead to increased morbidity and mortality. In addition, increased risk of coronary artery disease is another critical end-result of chronic hypertension. CMR can be utilized to assess all of these consequences using cine-MRI, late Gadolinium enhancement, tagging, and myocardial perfusion imaging.In the arteries, atheromatous plaque and aneurysm formation with the possibility of wall dissection or formation of intramural hematomas are important end-results of longstanding uncontrolled hypertension. With vascular MRI, all of these findings are assessable readily and accurately. Currently, newer techniques such as 4-D flow imaging of the aortic blood flow is being studied for use in understanding the mechanics of blood flow damaging the vessels. Another aspect of vascular MRI that is highly anticipated is the evaluation of pulsed wave velocity. With accurate measurement of vascular flow within any part of the body, and also precise measurement of the distance between various points of the aorta, the propagation velocities of the blood can be assessed with CMR and can be utilized to evaluate the effects of increased central blood pressure, instead of various assumptions using peripheral blood pressure for evaluation of PWV. In addition, evaluation of

  8. Pathological phenotypes and in vivo DNA cleavage by unrestrained activity of a phosphorothioate-based restriction system in Salmonella.

    PubMed

    Cao, Bo; Cheng, Qiuxiang; Gu, Chen; Yao, Fen; DeMott, Michael S; Zheng, Xiaoqing; Deng, Zixin; Dedon, Peter C; You, Delin

    2014-08-01

    Prokaryotes protect their genomes from foreign DNA with a diversity of defence mechanisms, including a widespread restriction-modification (R-M) system involving phosphorothioate (PT) modification of the DNA backbone. Unlike classical R-M systems, highly partial PT modification of consensus motifs in bacterial genomes suggests an unusual mechanism of PT-dependent restriction. In Salmonella enterica, PT modification is mediated by four genes dptB-E, while restriction involves additional three genes dptF-H. Here, we performed a series of studies to characterize the PT-dependent restriction, and found that it presented several features distinct with traditional R-M systems. The presence of restriction genes in a PT-deficient mutant was not lethal, but instead resulted in several pathological phenotypes. Subsequent transcriptional profiling revealed the expression of > 600 genes was affected by restriction enzymes in cells lacking PT, including induction of bacteriophage, SOS response and DNA repair-related genes. These transcriptional responses are consistent with the observation that restriction enzymes caused extensive DNA cleavage in the absence of PT modifications in vivo. However, overexpression of restriction genes was lethal to the host in spite of the presence PT modifications. These results point to an unusual mechanism of PT-dependent DNA cleavage by restriction enzymes in the face of partial PT modification.

  9. 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

  10. Interactions between thyroid and kidney function in pathological conditions of these organ systems: a review.

    PubMed

    van Hoek, Ingrid; Daminet, Sylvie

    2009-02-01

    Thyroidal status affects kidney function already in the embryonic stage. Thyroid hormones influence general tissue growth as well as tubular functions, electrolyte handling and neural input. Hyper- and hypo-functioning of the thyroid influences mature kidney function indirectly by affecting the cardiovascular system and the renal blood flow, and directly by affecting glomerular filtration, electrolyte pumps, the secretory and absorptive capacity of the tubuli, and the structure of the kidney. Hyperthyroidism accelerates several physiologic processes, a fact which is reflected in the decreased systemic vascular resistance, increased cardiac output (CO), increased renal blood flow (RBF), hypertrophic and hyperplastic tubuli, and increased glomerular filtration rate (GFR). Renal failure can progress due to glomerulosclerosis, proteinuria and oxidative stress. Hypothyroidism has a more negative influence on kidney function. Peripheral vascular resistance is increased with intrarenal vasoconstriction, and CO is decreased, causing decreased RBF. The influence on the different tubular functions is modest, although the transport capacity is below normal. The GFR is decreased up to 40% in hypothyroid humans. Despite the negative influences on glomerular and tubular kidney function, a hypothyroid state has been described as beneficial in kidney disease. Kidney disease is associated with decreased thyroid hormone concentrations caused by central effects and by changes in peripheral hormone metabolism and thyroid hormone binding proteins. Geriatric cats form an animal model of disease because both hyperthyroidism and chronic kidney disease (CKD) have high prevalence among them, and the link between thyroid and kidney affects the evaluation of clinical wellbeing and the possible treatment options. PMID:19133263

  11. Cytoplasmic dynein and its regulatory proteins in Golgi pathology in nervous system disorders.

    PubMed

    Jaarsma, Dick; Hoogenraad, Casper C

    2015-01-01

    The Golgi apparatus is a dynamic organelle involved in processing and sorting of lipids and proteins. In neurons, the Golgi apparatus is important for the development of axons and dendrites and maintenance of their highly complex polarized morphology. The motor protein complex cytoplasmic dynein has an important role in Golgi apparatus positioning and function. Together, with dynactin and other regulatory factors it drives microtubule minus-end directed motility of Golgi membranes. Inhibition of dynein results in fragmentation and dispersion of the Golgi ribbon in the neuronal cell body, resembling the Golgi abnormalities observed in some neurodegenerative disorders, in particular motor neuron diseases. Mutations in dynein and its regulatory factors, including the dynactin subunit p150Glued, BICD2 and Lis-1, are associated with several human nervous system disorders, including cortical malformation and motor neuropathy. Here we review the role of dynein and its regulatory factors in Golgi function and positioning, and the potential role of dynein malfunction in causing Golgi apparatus abnormalities in nervous system disorders. PMID:26578860

  12. Saliva between normal and pathological. Important factors in determining systemic and oral health.

    PubMed

    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

  13. 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

  14. Cardiovascular hypertensive emergencies.

    PubMed

    Papadopoulos, D P; Sanidas, E A; Viniou, N A; Gennimata, V; Chantziara, V; Barbetseas, I; Makris, T K

    2015-02-01

    Inevitably, a small proportion of patients with systematic hypertension will develop hypertensive crisis at some point. Hypertensive crises can be divided into hypertensive emergency or hypertensive urgency according to the presence or lack of acute target organ damage. In this review, we discuss cardiovascular hypertensive emergencies, including acute coronary syndrome, aortic dissection, congestive heart failure, and sympathomimetic hypertensive crises, including those caused by cocaine use. Each presents in a unique fashion, although some hypertensive emergency patients report nonspecific symptoms. Treatment includes several effective and rapid-acting medications to safely reduce the blood pressure, protect remaining end-organ function, relieve symptoms, minimize the risk of complications, and thereby improve patient outcomes.

  15. 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. PMID:26391140

  16. 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.

  17. 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.

  18. [Role of gasotransmitters in the pathogenesis of pulmonary hypertension].

    PubMed

    Wang, Yan-fei; Jin, Hong-fang; Tang, Chao-shu; Du, Jun-bao

    2006-06-18

    Pulmonary hypertension is a complicated and important pathological process in the development of a variety of cardiovascular and pulmonary diseases, and directly affects the development of the diseases and their prognosis. but its mechanisms are still not fully understood. Therefore, to clarify the mechanisms is an important task in this field. Nitric oxide (NO) and carbon monoxide (CO) have special significance in pulmonary circulation as compared with other organs for their special biological properties including continuous production, fast transmission and extensive action, etc, which attracts great attention in the life science research and initiates the new research field of gasotransmitters. Hydrogen sulfide (H2S), which has been recognized as a toxic gas, can be endogenously produced in the body. We considered it to be a new cardiovascular regulatory gasotransmitter based on the studies of its synthesis and distribution in cardiovascular system and cardiovascular effects under physiologic and pathophysiologic conditions. We found it exerted a general regulatory significance in cardiovascular diseases. Based on the research of the three gasotransmitters in hypoxic and high pulmonary blood flow-induced pulmonary hypertension, it was found that the dysfunction of the gasotransmitter pathways was involved in the pathogenesis of pulmonary hypertension and the supplement of gasotransmitters could alleviate pulmonary hypertension and pulmonary vascular remodeling. The mechanisms included that they could regulate vessel dilation, correct the imbalance between smooth muscle cell proliferation and apoptosis, inhibit the excess synthesis and stimulate the degradation of collagen, therefore inhibiting abnormal accumulation of collagen, etc. All these results indicated the significant regulatory effects of gasotransmitters in the pathogenesis of pulmonary hypertension.

  19. Role of microRNAs in central nervous system development and pathology.

    PubMed

    Meza-Sosa, Karla F; Valle-García, David; Pedraza-Alva, Gustavo; Pérez-Martínez, Leonor

    2012-01-01

    Gene expression regulation is essential for correct functioning of the cell. Complex processes such as development, apoptosis, cell differentiation, and cell cycling require a fine tuning of gene expression. MicroRNAs (miRNAs) are small RNAs that have been recognized as key components of the gene expression regulatory machinery. By sequence complementarity, miRNAs recognize target mRNAs and inhibit their function through degradation or by repressing their translation. The development of the central nervous system (CNS) requires precise and exquisitely regulated gene expression patterns. It is now widely recognized that miRNAs have the capacity to provide such fine regulation both in time and in space. High-throughput analyses as well as classical molecular biology approaches have allowed the identification of essential miRNAs for CNS development and function. Moreover, recent studies in several model organisms are beginning to show intricate regulatory networks involving miRNAs, transcription factors, and epigenetic regulators during CNS development. Here we review recent findings on the role that miRNAs play in the development of the CNS as well as in neuropathologies such as schizophrenia, Parkinson disease, and Alzheimer's disease, among others.

  20. Review on intermediate filaments of the nervous system and their pathological alterations.

    PubMed

    Lépinoux-Chambaud, Claire; Eyer, Joël

    2013-07-01

    Intermediate filaments (IFs) of the nervous system, including neurofilaments, α-internexin, glial fibrillary acidic protein, synemin, nestin, peripherin and vimentin, are finely expressed following elaborated cell, tissue and developmental specific patterns. A common characteristic of several neurodegenerative diseases is the abnormal accumulation of neuronal IFs in cell bodies or along the axon, often associated with impairment of the axonal transport and degeneration of neurons. In this review, we also present several perturbations of IF metabolism and organization associated with neurodegenerative disorders. Such modifications could represent strong markers of neuronal damages. Moreover, recent data suggest that IFs represent potential biomarkers to determine the disease progression or the differential stages of a neuronal disorder. Finally, recent investigations on IF expression and function in cancer provide evidence that they may be useful as markers, or targets of brain tumours, especially high-grade glioma. A better knowledge of the molecular mechanisms of IF alterations, combined to neuroimaging, is essential to improve diagnosis and therapeutic strategies of such neurodegenerative diseases and glioma.

  1. 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

  2. Primary hypertension in childhood.

    PubMed

    Bucher, Barbara S; Ferrarini, Alessandra; Weber, Nico; Bullo, Marina; Bianchetti, Mario G; Simonetti, Giacomo D

    2013-10-01

    There is growing concern about elevated blood pressure in children and adolescents, because of its association with the obesity epidemic. Moreover, cardiovascular function and blood pressure level are determined in childhood and track into adulthood. Primary hypertension in childhood is defined by persistent blood pressure values ≥ the 95th percentile and without a secondary cause. Preventable risk factors for elevated blood pressure in childhood are overweight, dietary habits, salt intake, sedentary lifestyle, poor sleep quality and passive smoking, whereas non-preventable risk factors include race, gender, genetic background, low birth weight, prematurity, and socioeconomic inequalities. Several different pathways are implicated in the development of primary hypertension, including obesity, insulin resistance, activation of the sympathetic nervous system, alterations in sodium homeostasis, renin-angiotensin system and altered vascular function. Prevention of adult cardiovascular disease should begin in childhood by regularly screening for high blood pressure, counseling for healthy lifestyle and avoiding preventable risk factors.

  3. 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

  4. 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

  5. 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

  6. Insights on the pathophysiology of Alzheimer's disease: The crosstalk between amyloid pathology, neuroinflammation and the peripheral immune system.

    PubMed

    Dá Mesquita, Sandro; Ferreira, Ana Catarina; Sousa, João Carlos; Correia-Neves, Margarida; Sousa, Nuno; Marques, Fernanda

    2016-09-01

    Alzheimer's disease (AD) is the most common form of dementia, whose prevalence is growing along with the increased life expectancy. Although the accumulation and deposition of amyloid beta (Aβ) peptides in the brain is viewed as one of the pathological hallmarks of AD and underlies, at least in part, brain cell dysfunction and behavior alterations, the etiology of this neurodegenerative disease is still poorly understood. Noticeably, increased amyloid load is accompanied by marked inflammatory alterations, both at the level of the brain parenchyma and at the barriers of the brain. However, it is debatable whether the neuroinflammation observed in aging and in AD, together with alterations in the peripheral immune system, are responsible for increased amyloidogenesis, decreased clearance of Aβ out of the brain and/or the marked deficits in memory and cognition manifested by AD patients. Herein, we scrutinize some important traits of the pathophysiology of aging and AD, focusing on the interplay between the amyloidogenic pathway, neuroinflammation and the peripheral immune system.

  7. Property of lysosomal storage disease associated with midbrain pathology in the central nervous system of Lamp-2-deficient mice.

    PubMed

    Furuta, Akiko; Kikuchi, Hisae; Fujita, Hiromi; Yamada, Daisuke; Fujiwara, Yuuki; Kabuta, Tomohiro; Nishino, Ichizo; Wada, Keiji; Uchiyama, Yasuo

    2015-06-01

    Lysosome-associated membrane protein-2 (LAMP-2) is the gene responsible for Danon disease, which is characterized by cardiomyopathy, autophagic vacuolar myopathy, and variable mental retardation. To elucidate the function of LAMP-2 in the central nervous system, we investigated the neuropathological changes in Lamp-2-deficient mice. Immunohistochemical observations revealed that Lamp-1 and cathepsin D-positive lysosomal structures increased in the large neurons of the mouse brain. Ubiquitin-immunoreactive aggregates and concanavalin A-positive materials were detected in these neurons. By means of ultrastructural studies, we found various-shaped accumulations, including lipofuscin, glycolipid-like materials, and membranous structures, in the neurons and glial cells of Lamp-2-deficient brains. In deficient mice, glycogen granules accumulated in hepatocyte lysosomes but were not observed in neurons. These pathological features indicate lysosomal storage disease; however, the findings are unlikely a consequence of deficiency of a single lysosomal enzyme. Although previous study results have shown a large amount of autophagic vacuoles in parenchymal cells of the visceral organs, these findings were rarely detected in the brain tissue except for some axons in the substantia nigra, in which abundant activated microglial cells with increased lipid peroxidation were observed. Thus, LAMP-2 in the central nervous system has a possible role in the degradation of the various macromolecules in lysosomes and an additional function concerning protection from oxidative stress, especially in the substantia nigra.

  8. 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.

  9. 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.

  10. Managing hypertension in type 2 diabetes mellitus.

    PubMed

    Horr, Samuel; Nissen, Steven

    2016-06-01

    Hypertension is a common problem in the diabetic population with estimates suggesting a prevalence exceeding 60%. Comorbid hypertension and diabetes mellitus are associated with high rates of macrovascular and microvascular complications. These two pathologies share overlapping risk factors, importantly central obesity. Treatment of hypertension is unequivocally beneficial and improves all-cause mortality, cardiovascular mortality, major cardiovascular events, and microvascular outcomes including nephropathy and retinopathy. Although controversial, current guidelines recommend a target blood pressure in the diabetic population of <140/90 mmHg, which is a similar target to that proposed for individuals without diabetes. Management of blood pressure in patients with diabetes includes both lifestyle modifications and pharmacological therapies. This article reviews the evidence for management of hypertension in patients with type 2 diabetes mellitus, and provides a recommended treatment strategy based on the available data.

  11. [Hypertensive crisis in children and adolescents].

    PubMed

    Skrzypczyk, Piotr; Roszkowska-Blaim, Maria; Daniel, Maria

    2013-12-01

    Hypertensive crisis is a sudden rise in blood pressure above 99 c. for sex, age and height +5 mm Hg. Depending on patient's symptoms, hypertensive crisis can be divided into hypertensive emergency severe arterial hypertension with target organ insufficiency and/r damage (central nervous system, heart, kidney, eye), and hypertensive urgency - severe arterial hypertension without target organ insufficiency and damage with non-specific symptoms like: headaches, vertigo, nasal bleeding, nausea, and vomiting. The most common causes of hypertensive crisis in neonates and infants are renal artery thrombosis, broncho-pulmonary dysplasia, and coarctation of aorta; in older children - kidney diseases and renal artery stenosis. In neonates and infants symptoms of cardiac failure predominate, whereas in older children symptoms from central nervous system (headaches, nausea, vomiting, changes in level of consciousness, seizures, focal deficits). Hypertensive crisis is treated with fast- and short-acting medications; 25% reduction of blood pressure within first 8 hours is recommended, with complete normalization within 24-48 hours. Hypertensive emergency should be treated with intravenous agents (labetalol, hydralazine, nicardipine, and sodium nitroprusside), hypertensive urgency with intravenous or oral agents like nifedipine, isradipine, clonidine and minoxidil. Nicardipine is a first-choice medication in neonates. PMID:24490470

  12. [Hypertensive crisis in children and adolescents].

    PubMed

    Skrzypczyk, Piotr; Roszkowska-Blaim, Maria; Daniel, Maria

    2013-12-01

    Hypertensive crisis is a sudden rise in blood pressure above 99 c. for sex, age and height +5 mm Hg. Depending on patient's symptoms, hypertensive crisis can be divided into hypertensive emergency severe arterial hypertension with target organ insufficiency and/r damage (central nervous system, heart, kidney, eye), and hypertensive urgency - severe arterial hypertension without target organ insufficiency and damage with non-specific symptoms like: headaches, vertigo, nasal bleeding, nausea, and vomiting. The most common causes of hypertensive crisis in neonates and infants are renal artery thrombosis, broncho-pulmonary dysplasia, and coarctation of aorta; in older children - kidney diseases and renal artery stenosis. In neonates and infants symptoms of cardiac failure predominate, whereas in older children symptoms from central nervous system (headaches, nausea, vomiting, changes in level of consciousness, seizures, focal deficits). Hypertensive crisis is treated with fast- and short-acting medications; 25% reduction of blood pressure within first 8 hours is recommended, with complete normalization within 24-48 hours. Hypertensive emergency should be treated with intravenous agents (labetalol, hydralazine, nicardipine, and sodium nitroprusside), hypertensive urgency with intravenous or oral agents like nifedipine, isradipine, clonidine and minoxidil. Nicardipine is a first-choice medication in neonates.

  13. Longitudinal left ventricular myocardial dysfunction assessed by 2D colour tissue Doppler imaging in a dog with systemic hypertension and severe arteriosclerosis.

    PubMed

    Nicolle, A P; Carlos Sampedrano, C; Fontaine, J J; Tessier-Vetzel, D; Goumi, V; Pelligand, L; Pouchelon, J-L; Chetboul, V

    2005-03-01

    A 12-year-old sexually intact male Vendee Griffon Basset was presented for acute pulmonary oedema. Severe systemic systolic arterial hypertension (SAH) was diagnosed (290 mmHg). Despite blood and abdominal ultrasound tests, the underlying cause of the systemic hypertension could not be determined, and primary SAH was therefore suspected. Conventional echocardiography showed eccentric left ventricular hypertrophy with normal fractional shortening. Despite this apparent normal systolic function, 2D colour tissue Doppler imaging (TDI) identified a marked longitudinal systolic left ventricular myocardial alteration, whereas radial function was still preserved. Three months later, the dog underwent euthanasia because of an acute episode of distal aortic thromboembolism. Necropsy revealed severe aortic and iliac arteriosclerosis. SAH related to arteriosclerosis is a common finding in humans, but has not been previously described in dogs. Moreover, its consequence on longitudinal myocardial function using TDI has never been documented before in this species.

  14. Immune Mechanisms in Arterial Hypertension.

    PubMed

    Wenzel, Ulrich; Turner, Jan Eric; Krebs, Christian; Kurts, Christian; Harrison, David G; Ehmke, Heimo

    2016-03-01

    Traditionally, arterial hypertension and subsequent end-organ damage have been attributed to hemodynamic factors, but increasing evidence indicates that inflammation also contributes to the deleterious consequences of this disease. The immune system has evolved to prevent invasion of foreign organisms and to promote tissue healing after injury. However, this beneficial activity comes at a cost of collateral damage when the immune system overreacts to internal injury, such as prehypertension. Renal inflammation results in injury and impaired urinary sodium excretion, and vascular inflammation leads to endothelial dysfunction, increased vascular resistance, and arterial remodeling and stiffening. Notably, modulation of the immune response can reduce the severity of BP elevation and hypertensive end-organ damage in several animal models. Indeed, recent studies have improved our understanding of how the immune response affects the pathogenesis of arterial hypertension, but the remarkable advances in basic immunology made during the last few years still await translation to the field of hypertension. This review briefly summarizes recent advances in immunity and hypertension as well as hypertensive end-organ damage.

  15. Renin and aldosterone measurements in the management of arterial hypertension.

    PubMed

    Viola, A; Monticone, S; Burrello, J; Buffolo, F; Lucchiari, M; Rabbia, F; Williams, T A; Veglio, F; Mengozzi, G; Mulatero, P

    2015-06-01

    Renin-angiotensin-aldosterone system (RAAS) is recognized as the main regulatory system of hemodynamics in man, and its derangements have a key role in the development and maintenance of arterial hypertension. Classification of the hypertensive states according to different patterns of renin and aldosterone levels ("RAAS profiling") allows the diagnosis of specific forms of secondary hypertension and may identify distinct hemodynamic subsets in essential hypertension. In this review, we summarize the application of RAAS profiling for the diagnostic assessment of hypertensive patients and discuss how the pathophysiological framework provided by RAAS profiling may guide therapeutic decision-making, especially in the context of uncontrolled hypertension not responding to multi-therapy.

  16. Determination of the effects of pulmonary arterial hypertension and therapy on the cardiovascular system of rats by impedance cardiography

    PubMed Central

    Buyukakilli, Belgin; Gurgul, Serkan; Cıtırık, Derya; Hallioglu, Olgu; Ozeren, Murat; Tasdelen, Bahar

    2014-01-01

    Aim To evaluate the effects of bosentan, sildenafil, and combined therapy on the cardiovascular system using impedance cardiography (ICG) in rats with monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Methods Seventy male Wistar-albino rats were randomized into five groups. A single dose of MCT was given to all rats, except to the control group. After 4 weeks, bosentan, sildenafil, and combined treatment was started and lasted for 3 weeks. The last group that developed PAH did not receive any medication. Echocardiographic evaluation was performed to determine the PAH development. Thoracic fluid content index (TFCI), stroke volume index (SI), heart rate (HR), cardiac index (CI), and myocardial contractility index (IC) were determined. All procedures were performed at the baseline and after 4 and 7 weeks. Results Echocardiographic parameters showed that the all MCT-injected rats developed PAH. There were no significant inter- and intra-group differences in TFCI, SI, and IC (P > 0.05), but at the 7th week, CI value in the sildenafil-treated PAH rats was significantly higher than in other groups and HR of PAH rats with combined therapy was significantly lower than in other groups. Conclusion PAH did not have an effect on LV function of rats, or if it did, the effect was compensated by physiological processes. Also, sildenafil treatment deteriorated the LV cardiac index. PMID:25358882

  17. 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

  18. [The evaluation of medicinal therapy under treatment of arterial hypertension in hospital].

    PubMed

    Maksimova, T M; Lushkina, N P; Alekseeva, N Yu; Lomakina, E A; Saurina, O S; Telnova, E A

    2015-01-01

    The article presents the analysis of data of "Study on Global AGEing and Adult Health, 2007-2010" (SAGE) concerning subjective judging of health, prevalence of ischemic heart disease under different levels of arterial pressure in similar age groups. An attempt is made to evaluate spectrum of pharmaceuticals applied in treatment of patients with arterial pressure in hospital at the level of oblast hospital. According official statistics of Minzdrav of Russia, in 20102 prevalence of diseases characterized by higher arterial pressure amounted to 10.5% in adult population and to 22.3% in population older than able-bodied age. At the same time, according SAGE data, prevalence of various forms of hypertension disease in population older than 50 years amounted to 52.8%. That is, this pathology is often missed in conditions of mass medical network. Thereafter, patients receive no necessary medicinal therapy. The one or another treatment was provided to almost 94% of patients with hypertension disease diagnosed by physician. At that, among patients received treatment the normal levels of both systolic and diastolic pressure were established in less than 20% of patients with hypertension. Therefore, the issue of effectiveness of applied methods of correction of arterial hypertension become a matter of interest. The appropriate treatment of hypertension is a mean to decrease complications and as a result to diminish mortality of diseases of circulatory system.

  19. 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.

  20. A microfluidic platform for systems pathology: multiparameter single-cell signaling measurements of clinical brain tumor specimens.

    PubMed

    Sun, Jing; Masterman-Smith, Michael D; Graham, Nicholas A; Jiao, Jing; Mottahedeh, Jack; Laks, Dan R; Ohashi, Minori; DeJesus, Jason; Kamei, Ken-ichiro; Lee, Ki-Bum; Wang, Hao; Yu, Zeta T F; Lu, Yi-Tsung; Hou, Shuang; Li, Keyu; Liu, Max; Zhang, Nangang; Wang, Shutao; Angenieux, Brigitte; Panosyan, Eduard; Samuels, Eric R; Park, Jun; Williams, Dirk; Konkankit, Vera; Nathanson, David; van Dam, R Michael; Phelps, Michael E; Wu, Hong; Liau, Linda M; Mischel, Paul S; Lazareff, Jorge A; Kornblum, Harley I; Yong, William H; Graeber, Thomas G; Tseng, Hsian-Rong

    2010-08-01

    The clinical practice of oncology is being transformed by molecular diagnostics that will enable predictive and personalized medicine. Current technologies for quantitation of the cancer proteome are either qualitative (e.g., immunohistochemistry) or require large sample sizes (e.g., flow cytometry). Here, we report a microfluidic platform-microfluidic image cytometry (MIC)-capable of quantitative, single-cell proteomic analysis of multiple signaling molecules using only 1,000 to 2,800 cells. Using cultured cell lines, we show simultaneous measurement of four critical signaling proteins (EGFR, PTEN, phospho-Akt, and phospho-S6) within the oncogenic phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway. To show the clinical application of the MIC platform to solid tumors, we analyzed a panel of 19 human brain tumor biopsies, including glioblastomas. Our MIC measurements were validated by clinical immunohistochemistry and confirmed the striking intertumoral and intratumoral heterogeneity characteristic of glioblastoma. To interpret the multiparameter, single-cell MIC measurements, we adapted bioinformatic methods including self-organizing maps that stratify patients into clusters that predict tumor progression and patient survival. Together with bioinformatic analysis, the MIC platform represents a robust, enabling in vitro molecular diagnostic technology for systems pathology analysis and personalized medicine. PMID:20631065

  1. A microfluidic platform for systems pathology: multiparameter single-cell signaling measurements of clinical brain tumor specimens

    PubMed Central

    Sun, Jing; Masterman-Smith, Michael; Graham, Nicholas A.; Jiao, Jing; Mottahedeh, Jack; Laks, Dan R.; Ohashi, Minori; DeJesus, Jason; Kamei, Ken-ichiro; Lee, Ki-Bum; Wang, Hao; Yu, Zeta T.F.; Lu, Yi-Tsung; Hou, Shuang; Li, Keyu; Liu, Max; Zhang, Nangang; Wang, Shutao; Angenieux, Brigitte; Panosyan, Eduard; Samuels, Eric R.; Park, Jun; Williams, Dirk; Konkankit, Vera; Nathanson, David; van Dam, R. Michael; Phelps, Michael E.; Wu, Hong; Liau, Linda M.; Mischel, Paul S.; Lazareff, Jorge A.; Kornblum, Harley I.; Yong, William H.; Graeber, Thomas G.; Tseng, Hsian-Rong

    2011-01-01

    The clinical practice of oncology is being transformed by molecular diagnostics that will enable predictive and personalized medicine. Current technologies for quantitation of the cancer proteome are either qualitative (e.g., immunohistochemistry) or require large sample sizes (e.g., flow cytometry). Here, we report a microfluidic platform, Microfluidic Image Cytometry (MIC), capable of quantitative, single-cell proteomic analysis of multiple signaling molecules using only 1,000-2,800 cells. Using cultured cell lines, we demonstrate simultaneous measurement of four critical signaling proteins (EGFR, PTEN, phospho-Akt and phospho-S6) within the oncogenic PI3K/Akt/mTOR signaling pathway. To demonstrate the clinical application of the MIC platform to solid tumors, we analyzed a panel of 19 human brain tumor biopsies, including glioblastomas. Our MIC measurements were validated by clinical immunohistochemistry and confirmed the striking inter- and intra-tumoral heterogeneity characteristic of glioblastoma. To interpret the multiparameter, single-cell MIC measurements, we adapted bioinformatic methods including self-organizing maps that stratify patients into clusters which predict tumor progression and patient survival. Together with bioinformatic analysis, the MIC platform represents a robust, enabling in vitro molecular diagnostic technology for systems pathology analysis and personalized medicine. PMID:20631065

  2. A microfluidic platform for systems pathology: multiparameter single-cell signaling measurements of clinical brain tumor specimens.

    PubMed

    Sun, Jing; Masterman-Smith, Michael D; Graham, Nicholas A; Jiao, Jing; Mottahedeh, Jack; Laks, Dan R; Ohashi, Minori; DeJesus, Jason; Kamei, Ken-ichiro; Lee, Ki-Bum; Wang, Hao; Yu, Zeta T F; Lu, Yi-Tsung; Hou, Shuang; Li, Keyu; Liu, Max; Zhang, Nangang; Wang, Shutao; Angenieux, Brigitte; Panosyan, Eduard; Samuels, Eric R; Park, Jun; Williams, Dirk; Konkankit, Vera; Nathanson, David; van Dam, R Michael; Phelps, Michael E; Wu, Hong; Liau, Linda M; Mischel, Paul S; Lazareff, Jorge A; Kornblum, Harley I; Yong, William H; Graeber, Thomas G; Tseng, Hsian-Rong

    2010-08-01

    The clinical practice of oncology is being transformed by molecular diagnostics that will enable predictive and personalized medicine. Current technologies for quantitation of the cancer proteome are either qualitative (e.g., immunohistochemistry) or require large sample sizes (e.g., flow cytometry). Here, we report a microfluidic platform-microfluidic image cytometry (MIC)-capable of quantitative, single-cell proteomic analysis of multiple signaling molecules using only 1,000 to 2,800 cells. Using cultured cell lines, we show simultaneous measurement of four critical signaling proteins (EGFR, PTEN, phospho-Akt, and phospho-S6) within the oncogenic phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway. To show the clinical application of the MIC platform to solid tumors, we analyzed a panel of 19 human brain tumor biopsies, including glioblastomas. Our MIC measurements were validated by clinical immunohistochemistry and confirmed the striking intertumoral and intratumoral heterogeneity characteristic of glioblastoma. To interpret the multiparameter, single-cell MIC measurements, we adapted bioinformatic methods including self-organizing maps that stratify patients into clusters that predict tumor progression and patient survival. Together with bioinformatic analysis, the MIC platform represents a robust, enabling in vitro molecular diagnostic technology for systems pathology analysis and personalized medicine.

  3. [Hyperuricemia, diabetes and hypertension].

    PubMed

    Viazzi, Francesca; Bonino, Barbara; Ratto, Elena; Desideri, Giovambattista; Pontremoli, Roberto

    2015-01-01

    Hyperuricemia is frequently found in association with several condition predisposing to cardiovascular events such as arterial hypertension and diabetes mellitus. This has led researchers to investigate possible pathogenetic mechanisms underlying this association. Several experimental studies and some indirect clinical evidence support a causal link between mild hyperuricemia and the developement of hypertension as well as new onset diabetes. At the tissue level, chronic exposure to increased uric acid has been shown to promote vascular changes leading to renal ischemia as well as stimulation of the renin angiotensin system. Furthermore, uric acid has been shown to promote the development of insulin resistance, hypertrglyceridemia and haepatic steatosis through pro-oxidative mechanisms. These experimental pathophysiological changes may be partly preventable by hypouricemic treatments. Whether clinical implications of these findings are confirmed by solid clinical intervention trials, mild hyperuricemia may soon change its status from risk predictor to treatment target for patients at high cardiovascular and renal risk.

  4. 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

  5. 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.

  6. 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. PMID:25776069

  7. Emergency Management of Hypertension in Children

    PubMed Central

    Singh, Dinesh; Akingbola, Olugbenga; Yosypiv, Ihor; El-Dahr, Samir

    2012-01-01

    Systemic arterial hypertension in children has traditionally been thought to be secondary in origin. Increased incidence of risk factors like obesity, sedentary life-styles, and faulty dietary habits has led to increased prevalence of the primary arterial hypertension (PAH), particularly in adolescent age children. PAH has become a global epidemic worldwide imposing huge economic constraint on health care. Sudden acute increase in systolic and diastolic blood pressure can lead to hypertensive crisis. While it generally pertains to secondary hypertension, occurrence of hypertensive crisis in PAH is however rare in children. Hypertensive crisis has been further subclassified depending on presence or absence of end-organ damage into hypertensive emergency or urgency. Both hypertensive emergencies and urgencies are known to cause significant morbidity and mortality. Increasing awareness among the physicians, targeted at investigation of the pathophysiology of hypertension and its complications, better screening methods, generation, and implementation of novel treatment modalities will impact overall outcomes. In this paper, we discuss the etiology, pathogenesis, and management of hypertensive crisis in children. An extensive database search using keywords was done to obtain the information. PMID:22577545

  8. 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. PMID:26600442

  9. 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.

  10. Identification of the ghrelin-GHSR 1 system and its influence in the modulation of induced ocular hypertension in rabbit and rat eyes.

    PubMed

    Rocha-Sousa, A; Pereira-Silva, P; Tavares-Silva, M; Azevedo-Pinto, S; Rodrigues-Araújo, J; Pinho, S; Avelino, A; Falcão-Reis, F; Leite-Moreira, A

    2014-07-01

    Recent studies evidenced a decrease in ghrelin's aqueous humor levels in patients with glaucoma. The goal of our investigation was to study the effect of the ghrelin-GHSR-1a system in the modulation of intraocular pressure in acute ocular hypertension models and its expression and distribution in ocular tissues. Two animal models of acute ocular hypertension were used to study the effect of the ghrelin-GHSR-1a system in the modulation of intraocular pressure: the rabbit and the rat. Ocular hypertension was induced by an intravitreal injection of 20% NaCl. Ghrelin or des-acyl ghrelin were delivered subconjunctivally and the intraocular pressure was assessed by a rebound tonometer that was calibrated for each species. In addition, we have studied the influence of nitric oxide and prostaglandins on ghrelin's effect in the rabbit animal model. Finally, we determined by immunofluorescence the expression of ghrelin and GHSR-1 in the rat's ocular tissue. Ghrelin decreased the intraocular pressure in both animal models (maximum decrease: 43.8±12.0% in the rabbit and 29.0±7.46% in the rat). In the rabbit, this effect was blunted in the presence of l-NAME and ketorolac. Des-acyl ghrelin only decreased the intraocular pressure in the rat (maximum decrease: 34.9±8.15%). Ghrelin expression was detected in the ciliary processes and GHSR-1 expression was detected in the trabecular meshwork and ciliary body. The ghrelin-GHSR-1 system is expressed in the anterior segment of the eye. Ghrelin and des-acyl ghrelin are responsible for a hypotensive effect in acute ocular hypertension animal models.

  11. 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...

  12. Site-specific tumor grading system in colorectal cancer: multicenter pathologic review of the value of quantifying poorly differentiated clusters.

    PubMed

    Ueno, Hideki; Hase, Kazuo; Hashiguchi, Yojiro; Shimazaki, Hideyuki; Tanaka, Masafumi; Miyake, Ohki; Masaki, Tadahiko; Shimada, Yoshifumi; Kinugasa, Yusuke; Mori, Yoshiyuki; Kishimoto, Mitsuo; Kameoka, Shingo; Sato, Yu; Matsuda, Keiji; Nakadoi, Koichi; Shinto, Eiji; Nakamura, Takahiro; Sugihara, Kenichi

    2014-02-01

    The study aimed to determine the value of a novel site-specific grading system based on quantifying poorly differentiated clusters (PDC; Grade(PDC)) in colorectal cancer (CRC). A multicenter pathologic review involving 12 institutions was performed on 3243 CRC cases (stage I, 583; II, 1331; III, 1329). Cancer clusters of ≥5 cancer cells and lacking a gland-like structure (PDCs) were counted under a ×20 objective lens in a field containing the maximum clusters. Tumors with <5, 5 to 9, and ≥10 PDCs were classified as grades G1, G2, and G3, respectively. According to Grade(PDC), 1594, 1005, and 644 tumors were classified as G1, G2, and G3 and had 5-year recurrence-free survival rates of 91.6%, 75.4%, and 59.6%, respectively (P<0.0001). Multivariate analysis showed that Grade exerted an influence on prognostic outcome independently of TNM staging; approximately 20% and 46% of stage I and II patients, respectively, were selected by Grade(PDC) as a population whose survival estimate was comparable to or even worse than that of stage III patients. Grade(PDC) surpassed TNM staging in the ability to stratify patients by recurrence-free survival (Akaike information criterion, 2915.6 vs. 2994.0) and had a higher prognostic value than American Joint Committee on Cancer (AJCC) grading (Grade(AJCC)) at all stages. Regarding judgment reproducibility of grading tumors, weighted κ among the 12 institutions was 0.40 for Grade(AJCC) and 0.52 for Grade(PDC). Grade(PDC) has a robust prognostic power and promises to be of sufficient clinical value to merit implementation as a site-specific grading system in CRC.

  13. Local and systemic renin-angiotensin system participates in cardiopulmonary-renal interactions in monocrotaline-induced pulmonary hypertension in the rat.

    PubMed

    Malikova, Eva; Galkova, Kristina; Vavrinec, Peter; Vavrincova-Yaghi, Diana; Kmecova, Zuzana; Krenek, Peter; Klimas, Jan

    2016-07-01

    Renin-angiotensin system (RAS) is one of the pathophysiological mechanisms in heart failure. Recently, involvement of the kidney in the disease progression has been proposed in patients with pulmonary arterial hypertension (PAH). We hypothesized that local and systemic RAS could be the central regulators of cardiopulmonary-renal interactions in experimental monocrotaline-induced pulmonary hypertension (PH) in rats. Male 12-week-old Wistar rats were injected subcutaneously with monocrotaline (60 mg/kg). The experiment was terminated 4 weeks after monocrotaline administration. Using RT-PCR, we measured the expression of RAS-related genes in right and left ventricles, lungs and kidneys, together with indicators of renal dysfunction and damage. We observed a significantly elevated expression of angiotensin-converting enzyme (ACE) in both left and right ventricles and kidneys (P < 0.05), but a significantly decreased ACE in the lungs (P < 0.05). Kidneys showed a significant 2.5-fold increase in renin mRNA (P < 0.05) along with erythropoietin, TGFβ1, COX-2, NOS-1 and nephrin. Expression of erythropoietin correlated inversely with hemoglobin oxygen saturation and positively with renin expression. In conclusion, monocrotaline-induced PH exhibited similar alterations of ACE expression in the left and right ventricles, and in the kidney, in contrast to the lungs. Increased renal renin was likely a consequence of renal hypoxia/hypoperfusion, as was increased renal erythropoietin expression. Alterations in RAS in the monocrotaline model are probably a result of hypoxic state, and while they could serve as a compensatory mechanism at a late stage of the disease, they could be viewed also as an indicator of multiorgan failure in PAH. PMID:27344167

  14. Local and systemic renin-angiotensin system participates in cardiopulmonary-renal interactions in monocrotaline-induced pulmonary hypertension in the rat.

    PubMed

    Malikova, Eva; Galkova, Kristina; Vavrinec, Peter; Vavrincova-Yaghi, Diana; Kmecova, Zuzana; Krenek, Peter; Klimas, Jan

    2016-07-01

    Renin-angiotensin system (RAS) is one of the pathophysiological mechanisms in heart failure. Recently, involvement of the kidney in the disease progression has been proposed in patients with pulmonary arterial hypertension (PAH). We hypothesized that local and systemic RAS could be the central regulators of cardiopulmonary-renal interactions in experimental monocrotaline-induced pulmonary hypertension (PH) in rats. Male 12-week-old Wistar rats were injected subcutaneously with monocrotaline (60 mg/kg). The experiment was terminated 4 weeks after monocrotaline administration. Using RT-PCR, we measured the expression of RAS-related genes in right and left ventricles, lungs and kidneys, together with indicators of renal dysfunction and damage. We observed a significantly elevated expression of angiotensin-converting enzyme (ACE) in both left and right ventricles and kidneys (P < 0.05), but a significantly decreased ACE in the lungs (P < 0.05). Kidneys showed a significant 2.5-fold increase in renin mRNA (P < 0.05) along with erythropoietin, TGFβ1, COX-2, NOS-1 and nephrin. Expression of erythropoietin correlated inversely with hemoglobin oxygen saturation and positively with renin expression. In conclusion, monocrotaline-induced PH exhibited similar alterations of ACE expression in the left and right ventricles, and in the kidney, in contrast to the lungs. Increased renal renin was likely a consequence of renal hypoxia/hypoperfusion, as was increased renal erythropoietin expression. Alterations in RAS in the monocrotaline model are probably a result of hypoxic state, and while they could serve as a compensatory mechanism at a late stage of the disease, they could be viewed also as an indicator of multiorgan failure in PAH.

  15. In silico Therapeutics for Neurogenic Hypertension and Vasovagal Syncope

    PubMed Central

    Bojić, Tijana; Perović, Vladimir R.; Glišić, Sanja

    2016-01-01

    Neurocardiovascular diseases (NCVD) are the leading cause of death in the developed world and will remain so till 2020. In these diseases the pathologically changed nervous control of cardiovascular system has the central role. The actual NCV syndromes are neurogenic hypertension, representing the sympathetically mediated disorder, and vasovagal syncope, which is the vagally mediated disorders. Vasovagal syncope, the disease far from its etiological treatment, could benefit from recruiting and application of antimuscarinic drugs used in other parasympathetic disorders. The informational spectrum method (ISM), a method widely applied for the characterization of protein-protein interactions in the field of immunology, endocrinology and anti HIV drug discovery, was applied for the first time in the analysis of neurogenic hypertension and vasovagal syncope therapeutic targets. In silico analysis revealed the potential involvement of apelin in neurogenic hypertension. Applying the EIIP/ISM bioinformatics concept in investigation of drugs for treatment of vasovagal syncope suggests that 78% of tested antimuscarinic drugs could have anti vasovagal syncope effect. The presented results confirm that ISM is a promissing method for investigation of molecular mechanisms underlying pathophysiological proceses of NCV syndromes and discovery of therapeutics targets for their treatment. PMID:26834545

  16. 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.

  17. Congruence Couple Therapy for Pathological Gambling

    ERIC Educational Resources Information Center

    Lee, Bonnie K.

    2009-01-01

    Couple therapy models for pathological gambling are limited. Congruence Couple Therapy is an integrative, humanistic, systems model that addresses intrapsychic, interpersonal, intergenerational, and universal-spiritual disconnections of pathological gamblers and their spouses to shift towards congruence. Specifically, CCT's theoretical…

  18. 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

  19. Hypertension in developing countries.

    PubMed

    Ibrahim, M Mohsen; Damasceno, Albertino

    2012-08-11

    Data from different national and regional surveys show that hypertension is common in developing countries, particularly in urban areas, and that rates of awareness, treatment, and control are low. Several hypertension risk factors seem to be more common in developing countries than in developed regions. Findings from serial surveys show an increasing prevalence of hypertension in developing countries, possibly caused by urbanisation, ageing of population, changes to dietary habits, and social stress. High illiteracy rates, poor access to health facilities, bad dietary habits, poverty, and high costs of drugs contribute to poor blood pressure control. The health system in many developing countries is inadequate because of low funds, poor infrastructure, and inexperience. Priority is given to acute disorders, child and maternal health care, and control of communicable diseases. Governments, together with medical societies and non-governmental organisations, should support and promote preventive programmes aiming to increase public awareness, educate physicians, and reduce salt intake. Regulations for the food industry and the production and availability of generic drugs should be reinforced. PMID:22883510

  20. [Hypertension in patients after heart transplantation].

    PubMed

    Matysek, J; Piwowarska, W

    1995-01-01

    Arterial hypertension is a serious and common complication of cyclosporine administration in humans. The prevalence of arterial hypertension in patients following orthotopic heart transplantation ranges from 38% to 92%. There are several characteristic features of this form of hypertension, including very early onset--usually within 4 to 6 weeks after transplantation and persistence with little alteration overtime. Diurnal profile shows the lack of normal nocturnal decline in blood pressure (BP) and appearance of the highest values of BP early in the morning. This phenomenon is caused by altered regulation of BP due to cardiac denervation. There was shown no correlation between the dose of cyclosporine and development of posttransplant arterial hypertension. It develops also independently of many investigated pretransplant and posttransplant cardiovascular risk factors. A great deal of attention has been focused on explantation of cyclosporine influence leading to hypertension occurrence. suggested mechanisms of this action are: elevation of systemic vascular resistance, prostaglandines and tromboxance production imbalance, hypomagnesemia, increased intravascular volume, modulation of sympathetic activity, nephrotoxicity. Reninangiotensin system seems to be not significantly associated with posttransplant hypertension, whereas the role of corticosteroides is still controversal. Hypertension remains the most common complication associated with cyclosporine administration in heart transplant recipients. Mechanisms of cyclosporine action leading to development of hypertension are still unknown. Further investigation is also needed into clinical significance of posttransplant hypertension and its influence on long-term survival after heart transplantation as they remain undefined.

  1. [Retroperitoneal pathology].

    PubMed

    Zuluaga Gómez, A; Jiménez Verdejo, A

    2002-01-01

    The retroperitoneum is one of the most complex regions of human anatomy as it contains a variety organs and structures from different systems, in particular those belonging to the urinary and digestive tracts and the vascular systems. The emergence of different diagnostic imaging techniques has made easier to study the retroperitoneum. Thanks to ultrasonography, computerised tomography and magnetic resonance the assessment of retroperitoneal conditions has taken a great leap forwards permitting the anatomical connections and characteristics of the structures in this region to be reliably established. Owing to the location in the retroperitoneal space of the different organs of the digestive tract and the vascular system, a multidisciplinary approach is required involving the different surgical specialties. The urologist performs a large proportion of his surgical activity in this region and must, therefore, have a good knowledge of the different retroperitoneal organs belonging to the urinary tract and also the connections between these and other organs and structures of the retroperitoneal region.

  2. 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. PMID:26277725

  3. [Pathology of lung cancer].

    PubMed

    Theegarten, D; Hager, T

    2016-09-01

    Lung cancer is the leading cause of cancer death in men and the second most frequent cause in women. The pathology of lung tumors is of special relevance concerning therapy and prognosis and current classification systems have to be taken into consideration. The results of molecular tissue subtyping allow further classification and therapeutic options. The histological entities are mainly associated with typical X‑ray morphological features. PMID:27495784

  4. 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.

  5. 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

  6. [Hypertensive emergencies and urgencies].

    PubMed

    Phan, David Giang; Dreyfuss-Tubiana, Céline; Blacher, Jacques

    2015-01-01

    Hypertension is a common disease, the most common chronic disease. Hypertensive emergency is much less frequent and only affects 1 to 2 % of all hypertensive patients. The true hypertensive emergency is characterized by the serious damage of one hypertensive target organ and requires an urgent intravenous treatment. Isolated blood pressure elevation should not be regarded as a hypertensive emergency if there is no target organ damage, even if the blood pressure is very high. These situations of "false hypertensive emergency", or hypertensive urgencies, often requires an immediate treatment, but oral. Signs of visceral pain of true hypertensive emergency often are a poor general condition, severe headache, decreased visual acuity, neurological deficit of ischemic or hemorrhagic cause, confusion, dyspnea with orthopnoea revealing heart failure, angina, chest pain revealing an aortic dissection, proteinuria, acute renal failure or eclampsia. True hypertensive emergencies include several entities, namely: severe hypertension, malignant hypertension and accelerated hypertension. If malignant hypertension is not treated, the prognosis is poor with 50 % death risk in the following year.

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. Systemic hypertension and transient ischemic attack in a 6-year-old girl with fibromuscular dysplasia treated with percutaneous angioplasty.

    PubMed

    Foa-Torres, Gustavo; Ganame, Javier; Juaneda, Ernesto; Peirone, Alejandro; Barcudi, Maria Silvina; Achaval, Alberto

    2010-02-01

    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.

  12. [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. PMID:26856145

  13. [Target organ effects in untreated hypertension].

    PubMed

    Babici, D; M'Pio, I; Hadj-Aïssa, A; Ducher, M; Laville, M; Fauvel, J P

    2003-01-01

    The parallel investigation of the renal and cardiac complications of recent and never treated systemic hypertension has only rarely been undertaken. The aim of this study was to define the renal function of never treated hypertensive subjects, separated into white coat hypertensives (HTbb: n = 19, BP at consultation 153/97 mmHg) or permanent hypertensives (HT: n = 49, BP at consultation 169/104 mmHg) as a function of their 24 hour BP. Their renal functions were then compared with those of normotensive subjects (NT: n = 10). The 68 hypertensive subjects seen consecutively underwent renal function investigation (DFG: glomerular filtration rate, DPR: renal plasmatic debit, and muAlb: microalbuminuria over 24 hours), and myocardial echography (measurement of the left ventricular mass index, IMVG). The white coat hypertensives had a normal renal function, while the permanent hypertensives had a significant decrease in DPR and a significantly higher muAlb compared to the normotensives. Compared to the white coat hypertensives, the permanent hypertensives had a significantly lower DFG and DPR, as well as a higher muAlb and IMVG. In all the hypertensives (white coat and permanent) the 24 hour systolic BP was significantly correlated with muAlb (r = 0.51, p < 0.001), filtration fraction (r = 0.30, p < 0.05), and IMVG (r = 0.52, p < 0.001). The renal and myocardial parameters were not significantly correlated. In conclusion, there seems to be a continuum between the level of ambulatory BP and the effect on target organs without a parallel progression of the renal and myocardial effects. From a practical point of view, only ambulatory BP measurement allows differentiation of permanent hypertensives who have a very early renal and/or myocardial effect, while white coat hypertensives are spared.

  14. Arsenic causes aortic dysfunction and systemic hypertension in rats: Augmentation of angiotensin II signaling.

    PubMed

    Waghe, Prashantkumar; Sarath, Thengumpallil Sasindran; Gupta, Priyanka; Kandasamy, Kannan; Choudhury, Soumen; Kutty, Harikumar Sankaran; Mishra, Santosh Kumar; Sarkar, Souvendra Nath

    2015-07-25

    The groundwater pollutant arsenic can cause various cardiovascular disorders. Angiotensin II, a potent vasoconstrictor, plays an important role in vascular dysfunction by promoting changes in endothelial function, vascular reactivity, tissue remodeling and oxidative stress. We investigated whether modulation of angiotensin II signaling and redox homeostasis could be a mechanism contributing to arsenic-induced vascular disorder. Rats were exposed to arsenic at 25, 50 and 100ppm of sodium arsenite through drinking water consecutively for 90 days. Blood pressure was recorded weekly. On the 91st day, the rats were sacrificed for blood collection and isolation of thoracic aorta. Angiotensin converting enzyme and angiotensin II levels were assessed in plasma. Aortic reactivity to angiotensin II was assessed in organ-bath system. Western blot of AT1 receptors and G protein (Gαq/11), ELISA of signal transducers of MAP kinase pathway and reactive oxygen species (ROS) generation were assessed in aorta. Arsenic caused concentration-dependent increase in systolic, diastolic and mean arterial blood pressure from the 10th, 8th and 7th week onwards, respectively. Arsenic caused concentration-dependent enhancement of the angiotensin II-induced aortic contractile response. Arsenic also caused concentration-dependent increase in the plasma levels of angiotensin II and angiotensin converting enzyme and the expression of aortic AT1 receptor and Gαq/11 proteins. Arsenic increased aortic protein kinase C activity and the concentrations of protein tyrosine kinase, extracellular signal-regulated kinase-1/2 and vascular endothelial growth factor. Further, arsenic increased aortic mRNA expression of Nox2, Nox4 and p22phox, NADPH oxidase activity and ROS generation. The results suggest that arsenic-mediated enhancement of angiotensin II signaling could be an important mechanism in the arsenic-induced vascular disorder, where ROS could augment the angiotensin II signaling through activation

  15. Revealing the role of the autonomic nervous system in the development and maintenance of Goldblatt hypertension in rats.

    PubMed

    Oliveira-Sales, Elizabeth B; Toward, Marie Ann; Campos, Ruy R; Paton, Julian F R

    2014-07-01

    Despite extensive use of the renovascular/Goldblatt model of hypertension-2K-1C, and the use of renal denervation to treat drug resistant hypertensive patients, autonomic mechanisms that underpin the maintenance of this hypertension are important yet remain unclear. Our aim was to analyse cardiovascular autonomic function by power spectral density analysis of both arterial pressure and pulse interval measured continuously by radio telemetry for 6weeks after renal artery clipping. Mean arterial pressure increased from 106±5 to 185±2mmHg during 5weeks post clipping when it stabilized. A tachycardia developed during the 4th week, which plateaued between weeks 5 and 6. The gain of the cardiac vagal baroreflex decreased immediately after clipping and continued to do so until the 5th week when it plateaued (from -2.4±0.09 to -0.8±0.04bpm/mmHg; P<0.05). A similar time course of changes in the high frequency power spectral density of the pulse interval was observed (decrease from 13.4±0.6 to 8.3±0.01ms(2); P<0.05). There was an increase in both the very low frequency and low frequency components of systolic blood pressure that occurred 3 and 4weeks after clipping, respectively. Thus, we show for the first time the temporal profile of autonomic mechanisms underpinning the initiation, development and maintenance of renovascular hypertension including: an immediate depression of cardiac baroreflex gain followed by a delayed cardiac sympathetic predominance; elevated sympathetic vasomotor drive occurring after the initiation of the hypertension but coinciding during its mid-development and maintenance. PMID:24560525

  16. [Effect of mouth breathing on the severity of morphological and functional changes of dental system in patients with otolaryngologic pathology].

    PubMed

    Arsenina, O I; Piksaikina, K G; Popova, A V; Popova, N V

    2014-01-01

    The study included 282 patients aged 5 to 14 years with pathology of the pharyngeal tonsil. Diagnostic algorithm is presented. The study results allowed elaboration of complex rehabilitation of nasal breathing and miodynamic equilibrium in the maxillofacial region by means of elastopositioner.

  17. 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

  18. Evidence of low dimensional chaos in renal blood flow control in genetic and experimental hypertension

    NASA Astrophysics Data System (ADS)

    Yip, K.-P.; Marsh, D. J.; Holstein-Rathlou, N.-H.

    1995-01-01

    We applied a surrogate data technique to test for nonlinear structure in spontaneous fluctuations of hydrostatic pressure in renal tubules of hypertensive rats. Tubular pressure oscillates at 0.03-0.05 Hz in animals with normal blood pressure, but the fluctuations become irregular with chronic hypertension. Using time series from rats with hypertension we produced surrogate data sets to test whether they represent linearly correlated noise or ‘static’ nonlinear transforms of a linear stochastic process. The correlation dimension and the forecasting error were used as discriminating statistics to compare surrogate with experimental data. The results show that the original experimental time series can be distinguished from both linearly and static nonlinearly correlated noise, indicating that the nonlinear behavior is due to the intrinsic dynamics of the system. Together with other evidence this strongly suggests that a low dimensional chaotic attractor governs renal hemodynamics in hypertension. This appears to be the first demonstration of a transition to chaotic dynamics in an integrated physiological control system occurring in association with a pathological condition.

  19. [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.

  20. [Hypertension in the elderly].

    PubMed

    Handschin, Anja; Henny-Fullin, Katja; Buess, Daniel; Leuppi, Jörg; Dieterle, Thomas

    2015-06-01

    Arterial hypertension remains the most important risk factor for cardiovascular and renal diseases. In view of an increasing prevalence with older age and an increasingly aging population, the treatment of elderly patients with arterial hypertension will become increasingly important in daily practice. Arterial hypertension in the elderly differs in many aspects from arterial hypertension in younger patients. For example, isolated systolic hypertension is the predominant form of arterial hypertension in the elderly. In comparison to younger patients, treatment of hypertension in the elderly is less well investigated. However, available data suggest that lowering of blood pressure in the elderly and very elderly reduces the risk of heart failure, stroke, and even mortality. The best evidence for the treatment of hypertension in the elderly exists for diuretics and calcium antagonists. However, the primary choice of antihypertensive therapy should be guided by the presence of existing cardiovascular and/or renal comorbidities.

  1. Cirrhosis and Portal Hypertension

    MedlinePlus

    MENU Return to Web version Cirrhosis and Portal Hypertension Overview What is cirrhosis? In people who have ... lead to coma and death. What is portal hypertension? Normally, blood is carried to the liver by ...

  2. [Hypertensive urgency and emergency].

    PubMed

    Henny-Fullin, Katja; Buess, Daniel; Handschin, Anja; Leuppi, Jörg; Dieterle, Thomas

    2015-06-01

    European and North-American guidelines for the diagnosis and therapy of arterial hypertension refer to hypertensive crisis as an acute and critical increase of blood pressure>180/120 mmHg. Presence of acute hypertensive target organ damage, such as stroke, myocardial infarction or heart failure, in this situation defines a “hypertensive emergency”. In these patients, immediate lowering of blood pressure (about 25% within one to two hours) in an intensive care setting is mandatory to prevent further progression of target organ damage. In contrast to hypertensive emergencies, hypertensive urgencies are characterized by an acute and critical increase in blood pressure without signs or symptoms of acute hypertensive target organ damage. In these patients, blood pressure should be lowered within 24 to 48 hours in order to avoid hypertensive target organ damage. In general, hospitalization is not required, and oral antihypertensive therapy usually is sufficient. However, further and continuing outpatient care has to be ensured.

  3. 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

  4. An update on the role of adipokines in arterial stiffness and hypertension.

    PubMed

    Sabbatini, Andréa R; Fontana, Vanessa; Laurent, Stephane; Moreno, Heitor

    2015-03-01

    Adipokines are hormones produced by adipocytes and have been involved in multiple pathologic pathways, including inflammatory and cardiovascular complications in essential hypertension. Arterial stiffness is a frequent vascular complication that represents increased cardiovascular risk in hypertensive patients. Adipokines, such as adiponectin, leptin and resistin, might be implicated in hypertension, as well as in vascular alterations associated with this condition. Arterial stiffness has proven to be a predictor of cardiovascular events. Obesity and target-organ damage such as arterial stiffness are features associated with hypertension. This review aims to update the association between adipokines and arterial stiffness in essential and resistant hypertension (RHTN).

  5. Molecular genetics of essential hypertension.

    PubMed

    Singh, M; Singh, A K; Pandey, P; Chandra, S; Singh, K A; Gambhir, I S

    2016-01-01

    Hypertension is a major public health problem in the developing as well as in developed countries due to its high prevalence and its association with coronary heart disease, renal disease, stroke, peripheral vascular disease, and related disorders. Essential hypertension (EH) is the most common diagnosis in this disease, suggesting that a monocausal etiology has not been identified. However, a number of risk factors associated with EH have also been identified such as age, sex, demographic, environmental, genetic, and vascular factors. Recent advances in molecular biological research had achieved clarifying the molecular basis of Mendelian hypertensive disorders. Molecular genetic studies have now identified mutations in several genes that cause Mendelian forms of hypertension in humans. However, none of the single genetic variants has emerged from linkage or association analyses as consistently related to the blood pressure level in every sample and in all populations. Besides, a number of polymorphisms in candidate genes have been associated with differences in blood pressure. The most prominent candidate has been the polymorphisms in the renin-angiotensin-aldosterone system. In total, EH is likely to be a polygenic disorder that results from inheritance of a number of susceptibility genes and involves multiple environmental determinants. These determinants complicate the study of blood pressure variations in the general population. The complex nature of the hypertension phenotype makes large-scale studies indispensable, when screening of familial and genetic factors was intended. In this review, recent genetic studies exploring the molecular basis of EH, including different molecular pathways, are highlighted. PMID:27028574

  6. Depression in hypertensive subjects.

    PubMed

    Ramachandran, V; Parikh, G J; Srinivasan, V

    1983-10-01

    168 patients attending hypertension clinic were randomly selected for the study. They were thoroughly investigated using E.C.G., X-ray chest, Urine analysis, Blood sugar, Blood urea, Serum cholesterol, Serum K, Serum Na, Scrum creatinine and Uric acid level. Detailed psychiatric case history and mental examination was carried out. Beck Rating Scale was used to measure the depression. 25% of hypertensive subjects exhibited depressive features and their mean score in Beck Rating scale is 21.76. The mean score of non-depressives is 4.46. All patients were receiving methyl dopa.25 mg. twice or thrice daily with thiazide diuretic. No significant difference in the incidence of depression with the duration of medication was observed.The hypertension was classified into mild, moderate and severe depending on the diastolic pressure. Depression was more frequent in severe hypertensives but not to the statistically significant level.Further hypertensives were classified into:1. Hypertension without organ involvement2. Hypertension with LVH only3. Hypertension with additional organ involvement4. Malignant hypertensionDepression was significantly more frequent in hypertensives with complications and also hypertensives in whom the B.P. remained uncontrolled. As all the patients were on the same drug, the drug effect is common to all; hence, the higher incidence of depression in hypertensives with complications is due to the limitation and distress caused by the illness. PMID:21847301

  7. Evaluation of the Retinal Vasculature in Hypertension and Chronic Kidney Disease in an Elderly Population of Irish Nuns

    PubMed Central

    McGowan, Amy; Silvestri, Giuliana; Moore, Evelyn; Silvestri, Vittorio; Patterson, Christopher C.; Maxwell, Alexander P.; McKay, Gareth J.

    2015-01-01

    Background Chronic kidney disease (CKD) and hypertension are global public health problems associated with considerable morbidity, premature mortality and attendant healthcare costs. Previous studies have highlighted that non-invasive examination of the retinal microcirculation can detect microvascular pathology that is associated with systemic disorders of the circulatory system such as hypertension. We examined the associations between retinal vessel caliber (RVC) and fractal dimension (DF), with both hypertension and CKD in elderly Irish nuns. Methods Data from 1233 participants in the cross-sectional observational Irish Nun Eye Study (INES) were assessed from digital photographs with a standardized protocol using computer-assisted software. Multivariate regression analyses were used to assess associations with hypertension and CKD, with adjustment for age, body mass index (BMI), refraction, fellow eye RVC, smoking, alcohol consumption, ischemic heart disease (IHD), cerebrovascular accident (CVA), diabetes and medication use. Results In total, 1122 (91%) participants (mean age: 76.3 [range: 56–100] years) had gradable retinal images of sufficient quality for blood vessel assessment. Hypertension was significantly associated with a narrower central retinal arteriolar equivalent (CRAE) in a fully adjusted analysis (P = 0.002; effect size = -2.16 μm; 95% confidence intervals [CI]: -3.51, -0.81 μm). No significant associations between other retinal vascular parameters and hypertension or between any retinal vascular parameters and CKD were found. Conclusions Individuals with hypertension have significantly narrower retinal arterioles which may afford an earlier opportunity for tailored prevention and treatment options to optimize the structure and function of the microvasculature, providing additional clinical utility. No significant associations between retinal vascular parameters and CKD were detected. PMID:26327531

  8. 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

  9. Development of a New Classification Method for Penile Squamous Cell Carcinoma Based on Lymph Node Density and Standard Pathological Risk Factors: The ND Staging System

    PubMed Central

    Li, Zai-Shang; Yao, Kai; Chen, Peng; Wang, Bin; Mi, Qi-Wu; Chen, Jie-Ping; Li, Yong-Hong; Deng, Chuang-Zhong; Liu, Zhuo-Wei; Qin, Zi-Ke; Zhou, Fang-Jian; Han, Hui

    2016-01-01

    Object: In this study, we evaluated the role of lymph node density (LND) and validated whether LND increases the accuracy of survival prediction when combined with the American Joint Committee on Cancer (AJCC) pathological node (N) staging system for penile cancer (7th edition). Methods: A total of 270 Chinese penile cancer patients treated between March 1999 and October 2014 were retrospectively analyzed. LND was analyzed as a trichotomous variable for the prediction of DSS in this cohort. We developed a new prediction model, which we refer to as the ND staging system, that is based on LND and pathological N staging. The predictive accuracy of this model was further assessed using the concordance index. Results: LND was correlated with the laterality of lymph node metastasis, extranodal extension, pelvic lymph node metastases, and pathologic tumor (T) and N stages (P<0.05). In separate multivariate Cox regression models, the LND (hazard ratio [HR], 1.966, 95% confidence interval [CI], (1.112-3.473, P=0.020) yielded independent effects on the outcome. According to the LND classification, the 3-year disease-specific survival (DSS) rates for patients with LNDs <7.0%, 7.0 to 16.9%, and ≥17.0% were 90.9%, 66.5%, and 22.2%, respectively (P<7.0%; 7.0%-16.9%=0.006; P7.0-16.9%; ≥17.0%=0.001). The corresponding rates were 95.7%, 76.7%, and 28.1% for the ND1, ND2, and ND3 patients, respectively (PND1-ND2=0.047; PND2-ND3<0.001). The indexes indicated that the accuracy of the pathological ND category that incorporated LND was significantly increased. Conclusion: LND was associated with some prognosticators and is thus a prognostic factor. The ND staging system that incorporates the LND better reflects the prognoses of penile cancer patients. PMID:26918038

  10. Classification of hypertension in pregnancy.

    PubMed

    Brown, M A; de Swiet, M

    1999-03-01

    In many ways there should be no need to classify hypertensive disorders in clinical practice. The very presence of rising blood pressure should alert the clinician to seek evidence for the development of pre-eclampsia and whether there are any emerging abnormalities of fetal growth and/or maternal renal, cerebral, hepatic or coagulation functions which may necessitate specific treatment, including delivery. While such a view may be appropriate for experienced clinicians with an understanding of the pathophysiology of the hypertensive disorders of pregnancy, it is of little help to junior or less experienced medical staff. Moreover, without an agreed international classification system it is impossible to compare truly clinical outcome, intervention or basic research studies from different units as entry criteria to these studies may differ considerably across individual units and certainly across countries. In this chapter we highlight the limitations of the existing classification systems and propose a system that is based on our present understanding of the pathophysiology of pre-eclampsia. The proposed system is not a radical departure from previous classifications, with grouping of hypertensive subjects into gestational hypertension, pre-eclampsia and chronic (usually essential) hypertension. Proteinuria, while remaining a hallmark of pre-eclampsia, is no longer considered a 'sine qua non' for this disorder to be diagnosed, reflecting our greater understanding of the maternal and fetal abnormalities in pre-eclampsia since previous classification systems were developed. This classification system has been compared with the traditional system of diagnosing proteinuric pre-eclampsia in a study of 1183 women with hypertension in pregnancy: diagnosing pre-eclampsia in this new manner still stratifies a high-risk group of pregnant women and the proposed diagnosis of gestational hypertension in this system stratifies a group of women at low maternal and fetal risk

  11. A case report of pathologically complete response of a huge rectal cancer after systemic chemotherapy with mFOLFOX6.

    PubMed

    Okoshi, Kae; Nagayama, Satoshi; Furu, Moritoshi; Mori, Yukiko; Yoshizawa, Akihiko; Toguchida, Junya; Sakai, Yoshiharu

    2009-08-01

    A 54-year-old man was referred to our hospital because of a huge, unresectable rectal cancer occupying his entire pelvic space with a solitary liver metastasis. He had undergone a laparotomy for surgical resection, but ended up with a sigmoid colostomy due to possible invasion into the urinary bladder and pelvic wall. At the completion of seven cycles of FOLFOX regimen, radiographic examination revealed remarkable reduction of the primary rectal tumor and regional lymph nodes, and also a complete response (CR) of the liver metastasis. The tumor was extirpated without any macroscopic residues by a low anterior resection of the rectum, along with a partial resection of the urinary bladder and seminal vesicles. Since pathological and immunohistochemical examinations showed no viable cancer cells in any parts of the resected specimens, the lesion was regarded as a pathologically CR. Analysis for single-nucleotide polymorphisms in the genes involved in nucleotide excision repair, excision repair cross-complementing group 1 and xeroderma pigmentosum group D, showed a genotypic pattern sensitive to oxaliplatin. To our knowledge, this is a rare case of an initially unresectable primary rectal cancer, which was down-staged to a pathologically CR by FOLFOX chemotherapy instead of chemoradiotherapy.

  12. QT dispersion in adult hypertensives.

    PubMed Central

    Sani, Isa Muhammad; Solomon, Danbauchi Sulei; Imhogene, Oyati Albert; Ahmad, Alhassan Muhammad; Bala, Garko Sani

    2006-01-01

    Increased QT dispersion is associated with sudden cardiac death in congestive cardiac failure, hypertrophic cardiomyopathy and following myocardial infarction. Patients with hypertension--in particular, those with left ventricular hypertrophy (LVH)--are also at greater risk of sudden cardiac death. We examined whether QT dispersion, which is easily obtained from a routine ECG, correlates with LVH. One-hundred untreated patients with systemic hypertension and 78 normotensives had QT dispersion measured manually from a surface 12-lead electrocardiogram and two-dimensional echocardiography performed to measure interventricular septal thickness, posterior wall thickness and left ventricular internal diameter. Office blood pressure was also recorded. Multivariate analysis demonstrated significant relationships between QT dispersion and office systolic blood pressure, and left ventricular mass index. Manual measurement of QT dispersion might be a simple, noninvasive screening procedure to identify those hypertensives at greatest risk of sudden cardiac death in a third-world country. PMID:16623077

  13. Microarray analysis in pulmonary hypertension.

    PubMed

    Hoffmann, Julia; Wilhelm, Jochen; Olschewski, Andrea; Kwapiszewska, Grazyna

    2016-07-01

    Microarrays are a powerful and effective tool that allows the detection of genome-wide gene expression differences between controls and disease conditions. They have been broadly applied to investigate the pathobiology of diverse forms of pulmonary hypertension, namely group 1, including patients with idiopathic pulmonary arterial hypertension, and group 3, including pulmonary hypertension associated with chronic lung diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. To date, numerous human microarray studies have been conducted to analyse global (lung homogenate samples), compartment-specific (laser capture microdissection), cell type-specific (isolated primary cells) and circulating cell (peripheral blood) expression profiles. Combined, they provide important information on development, progression and the end-stage disease. In the future, system biology approaches, expression of noncoding RNAs that regulate coding RNAs, and direct comparison between animal models and human disease might be of importance. PMID:27076594

  14. Microarray analysis in pulmonary hypertension

    PubMed Central

    Hoffmann, Julia; Wilhelm, Jochen; Olschewski, Andrea

    2016-01-01

    Microarrays are a powerful and effective tool that allows the detection of genome-wide gene expression differences between controls and disease conditions. They have been broadly applied to investigate the pathobiology of diverse forms of pulmonary hypertension, namely group 1, including patients with idiopathic pulmonary arterial hypertension, and group 3, including pulmonary hypertension associated with chronic lung diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. To date, numerous human microarray studies have been conducted to analyse global (lung homogenate samples), compartment-specific (laser capture microdissection), cell type-specific (isolated primary cells) and circulating cell (peripheral blood) expression profiles. Combined, they provide important information on development, progression and the end-stage disease. In the future, system biology approaches, expression of noncoding RNAs that regulate coding RNAs, and direct comparison between animal models and human disease might be of importance. PMID:27076594

  15. Fixed-Dose Combinations of Renin–Angiotensin System Inhibitors and Calcium Channel Blockers in the Treatment of Hypertension

    PubMed Central

    Hsiao, Fu-Chih; Tung, Ying-Chang; Chou, Shing-Hsien; Wu, Lung-Sheng; Lin, Chia-Pin; Wang, Chun-Li; Lin, Yu-Sheng; Chang, Chee-Jen; Chu, Pao-Hsien

    2015-01-01

    Abstract Fixed-dose combinations (FDCs) of different regimens are recommended in guidelines for the treatment of hypertension. However, clinical studies comparing FDCs of angiotensin receptor blocker (ARB)/calcium channel blocker (CCB) and angiotensin-converting enzyme inhibitor (ACE inhibitor)/CCB in hypertensive patients are lacking. Using a propensity score matching of 4:1 ratio, this retrospective claims database study compared 2 FDC regimens, ARB/CCB and ACE inhibitor/CCB, in treating hypertensive patients with no known atherosclerotic cardiovascular disease. All patients were followed for at least 3 years or until the development of major adverse cardiovascular events (MACEs) during the study period. In addition, the effect of medication adherence on clinical outcomes was evaluated in subgroup analysis based on different portions of days covered. There was no significant difference in MACE-free survival (hazard ratio [HR]: 1.21; 95% confidence interval [CI]: 0.98–1.50; P = 0.08) and survival free from hospitalization for heart failure (HR: 1.15; 95% CI: 082–1.61; P = 0.431), new diagnosis of chronic kidney disease (HR: 0.98; 95% CI: 071–1.36; P = 0.906), and initiation of dialysis (HR: 0.99; 95% CI: 050–1.92; P = 0.965) between the 2 study groups. The results remained the same within each subgroup of patients with different adherence statuses. ARBs in FDC regimens with CCBs in the present study were shown to be as effective as ACE inhibitors at reducing the risks of MACEs, hospitalization for heart failure, new diagnosis of chronic kidney disease, and new initiation of dialysis in hypertensive patients, regardless of the medication adherence status. PMID:26705234

  16. 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

  17. Catheter-based renal denervation for resistant hypertension: 12-month results of the EnligHTN I first-in-human study using a multielectrode ablation system.

    PubMed

    Papademetriou, Vasilios; Tsioufis, Costas P; Sinhal, Ajay; Chew, Derek P; Meredith, Ian T; Malaiapan, Yuvi; Worthley, Matthew I; Worthley, Stephen G

    2014-09-01

    Renal denervation has emerged as a novel approach for the treatment of patients with drug-resistant hypertension. To date, only limited data have been published using multielectrode radiofrequency ablation systems. In this article, we present the 12-month data of EnligHTN I, a first-in-human study using a multielectrode ablation catheter. EnligHTN I enrolled 46 patients (average age, 60±10 years; on average 4.7±1.0 medications) with drug-resistant hypertension. Eligible patients were on ≥3 antihypertensive medications and had a systolic blood pressure (BP) ≥160 mm Hg (≥150 mm Hg for diabetics). Bilateral renal artery ablation was performed using a percutaneous femoral approach and standardized techniques. The average baseline office BP was 176/96 mm Hg, average 24-hour ambulatory BP was 150/83 mm Hg, and average home BP was 158/90 mm Hg. The average reductions (mm Hg) at 1, 3, 6, and 12 months were as follows: office: -28/-10, -27/-10, -26/-10, and -27/-11 mm Hg (P<0.001 for all); 24-hour ambulatory: -10/-5, -10/-5, -10/-6 (P<0.001 for all), and -7/-4 for 12 months (P<0.0094). Reductions in home measurements (based on 2-week average) were -9/-4, -8/-5,-10/-7, and -11/-6 mm Hg (P<0.001 at 12 months). At 12 months, there were no signals of worsening renal function and no new serious or life-threatening adverse events. One patient with baseline nonocclusive renal artery stenosis progressed to 75% diameter stenosis, requiring renal artery stenting. The 12-month data continue to demonstrate safety and efficacy of the EnligHTN ablation system in patients with drug-resistant hypertension. Home BP measurements parallel measurements obtained with 24-hour ambulatory monitoring.

  18. Improvement of hypertension, endothelial function and systemic inflammation following short-term supplementation with red beet (Beta vulgaris L.) juice: a randomized crossover pilot study.

    PubMed

    Asgary, S; Afshani, M R; Sahebkar, A; Keshvari, M; Taheri, M; Jahanian, E; Rafieian-Kopaei, M; Malekian, F; Sarrafzadegan, N

    2016-10-01

    Hypertension is a major risk factor for cardiovascular disease and has a prevalence of about one billion people worldwide. It has been shown that adherence to a diet rich in fruits and vegetables helps in decreasing blood pressure (BP). This study aimed to investigate the effect of raw beet juice (RBJ) and cooked beet (CB) on BP of hypertensive subjects. In this randomized crossover study, 24 hypertensive subjects aged 25-68 years old were divided into two groups. One group took RBJ for 2 weeks and the other group took CB. After 2 weeks of treatment, both groups had a washout for 2 weeks then switched to the alternate treatment. Each participant consumed 250 ml day(-1) of RBJ or 250 g day(-1) of CB each for a period of 2 weeks. Body weight, BP, flow-mediated dilation (FMD), lipid profile and inflammatory parameters were measured at baseline and after each period. According to the results, high-sensitivity C-reactive protein (hs-CRP) and tumour necrosis factor alpha (TNF-α) were significantly lower and FMD was significantly higher after treatment with RBJ compared with CB (P<0.05). FMD was significantly (P<0.05) increased, but systolic and diastolic BP, intracellular adhesion molecule-1 (ICAM-1), vascular endothelial adhesion molecule-1 (VCAM-1), hs-CRP, interleukin-6, E-selectin and TNF-α were significantly (P<0.05) decreased with RBJ or CB. Total antioxidant capacity was increased and non-high-density lipoprotein (HDL), low-density lipoprotein (LDL) and total cholesterol (TC) were decreased with RBJ but not with CB. Although both forms of beetroot were effective in improving BP, endothelial function and systemic inflammation, the raw beetroot juice had greater antihypertensive effects. Also more improvement was observed in endothelial function and systemic inflammation with RBJ compared with CB. PMID:27278926

  19. Improvement of hypertension, endothelial function and systemic inflammation following short-term supplementation with red beet (Beta vulgaris L.) juice: a r