bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Fuzzy Expert System for the Identification of Severity of Carpal Tunnel Syndrome
Authors: Kunhimangalam Reeda , Ovallath Sujith , Joseph Paul K.
Published: September 2013

The diagnosis of carpal tunnel syndrome, a peripheral nerve disorder, at the earliest possible stage is very crucial because if left untreated it may cause permanent nerve damage reducing the chances of successful treatment. Here a novel Fuzzy Expert System designed using MATLAB is proposed for identification of severity of CTS. The data used were the nerve conduction study data obtained from Kannur Medical College, India. It consists of thirteen input fields, which include the clinical values of the diagnostic test and the clinical symptoms, and the output field gives the disease severity. The results obtained match with the expert’s opinion with 98.4% accuracy and high degrees of sensitivity and specificity. Since quantification of the intensity of CTS is a crucial step in the electrodiagnostic procedure and is important for defining prognosis and therapeutic measures, such an expert system can be of immense use in those regions where the service of such specialists may not be readily available. It may also prove useful in combination with other systems in providing diagnostic and predictive medical opinions and can add value if introduced into the routine clinical consultations to arrive at the most accurate medical diagnosis in a timely manner.
Interpolation of Transonic Flows Using a Proper Orthogonal Decomposition Method
Authors: Malouin Benoit , Trépanier Jean-Yves , Gariépy Martin
Published: September 2013

A proper orthogonal decomposition (POD) method is used to interpolate the flow around an airfoil for various Mach numbers and angles of attack in the transonic regime. POD uses a few numerical simulations, called snapshots, to create eigenfunctions. These eigenfunctions are combined using weighting coefficients to create a new solution for different values of the input parameters. Since POD methods are linear, their interpolation capabilities are quite limited when dealing with flow presenting nonlinearities, such as shocks. In order to improve their performance for cases involving shocks, a new method is proposed using variable fidelity. The main idea is to use POD to interpolate the difference between the CFD solution obtained on two different grids, a coarse one and a fine one. Then, for any new input parameter value, a coarse grid solution is computed using CFD and the POD interpolated difference is added to predict the fine grid solution. This allows some nonlinearities associated with the flow to be introduced. Results for various Mach numbers and angles of attack are compared to full CFD results. The variable fidelity-based POD method shows good improvement over the classical approach.
Depression Symptoms and Risk Factors in Adult Emergency Department Patients: A Multisite Cross-Sectional Prevalence Survey
Authors: Khav Nancy , Weiland Tracey J. , Jelinek George A. , Knott Jonathan C. , Salzberg Michael
Published: September 2013

Objectives. To identify the proportion of adult emergency department (ED) patients who screen positive for depression. Secondary aims were to identify factors associated with a positive depression screen and determine predictors of a positive depression screen. Methods. This cross-sectional, prevalence survey of ED patients was conducted at two inner-city hospitals. 350 ED patients were screened for depression using the Patient Health Questionnaire-9 (PHQ-9). Clinical and demographic risk factors were examined through medical records and additional questionnaires. Results. Of 350 participants screened, 50 (14.3%; 95% CI = 11.0–18.4%) screened positive. Independent predictors of depression risk included self-reported depression and/or a previous diagnosis of depression (OR = 8.345; 95% CI = 3.524–19.762), seeing a mental health service provider in the past 6 months (OR = 4.518; 95% CI = 2.107–9.690), and previous discussion about mental health with a local doctor (OR = 2.369; 95% CI = 1.025–5.475). Conclusion. ED patients were found to be at a higher risk of depression than the general population. ED-based depression screening, particularly of high-risk populations, has the potential to increase case detection rates and allow earlier management of these patients. Further research and validation of an ED-based depression screening tool are required.
Postfire Burnt-Wood Management Affects Plant Damage by Ungulate Herbivores
Authors: Castro Jorge
Published: September 2013

I analyze the effect of post-fire burnt wood management on herbivore attack on a woody plant species (Ulex parviflorus). Two experimental plots of ca. 20 hectares were established at two elevations in a burnt area in a Mediterranean mountain (Sierra Nevada, Spain). Three replicates of three treatments differing in post-fire burnt wood management were established per plot: “no intervention” (NI, all trees remained standing), “partial cut plus lopping” (PCL, felling the trees, cutting the main branches, and leaving all the biomassin situ), and “salvage logging” (SL; removal of logs and elimination of woody debris). Risk of herbivory and damage intensity were monitored for two years. The pattern of attack by ungulate herbivores varied among treatments and years. In any case, there was an overall reduction in the risk of herbivory in the PCL treatment, presumably because the highest habitat complexity in this treatment hampered ungulate movement and foraging. As a result, the burnt logs and branches spread over the ground acted as a physical barrier that protected seedlings from herbivores. This protection may be used for the regeneration of shrubs and trees, and it is of interest for the regeneration of burnt sites either naturally or by reforestation.
Production of Hesperetin Using a Covalently Multipoint Immobilized Diglycosidase from Acremonium sp. DSM24697
Authors: Piñuel Lucrecia , Breccia Javier D. , Guisán Jose M. , López-Gallego Fernando
Published: September 2013

The diglycosidase α-rhamnosyl-β-glucosidase (EC 3.2.1.168) from the fungus Acremonium sp. DSM24697 was immobilized on several agarose-based supports. Covalent multipoint immobilization onto glyoxyl-activated agarose was selected as the more stable preparation at high concentration of dimethyl sulfoxide (DMSO) and high temperature. The optimal conditions for the immobilization process involved an incubation of the enzyme with agarose beads containing 220 μmol of glyoxyl groups per gram at pH 10 and 25°C for 24 h. The hydrolysis of hesperidin carried out in 10% v/v DMSO at 60°C for 2 h reached 64.6% substrate conversion and a specific productivity of 2.40 mmol h-1 g-1. Under these conditions, the process was performed reutilizing the catalyst for up to 18 cycles, maintaining >80% of the initial activity and a constant productivity 2.96 ± 0.42 µmol-1 h-1 g-1. To the best of our knowledge, such productivity is the highest achieved for hesperetin production through an enzymatic approach.
Long-Term Treatment with Mammalian Target of Rapamycin Inhibitor Does Not Benefit Patients with Autosomal Dominant Polycystic Kidney Disease: A Meta-Analysis
Authors: Xue Cheng , Dai Bing , Mei Changlin
Published: September 2013

Background: The role of the mammalian target of rapamycin (mTOR) inhibition in the treatment of autosomal dominant polycystic kidney disease (ADPKD) remains unclear. This meta-analysis included all randomized controlled trials (RCTs) that used mTOR inhibitors (TORIs) to halt the progression of ADPKD. Methods: Databases including MEDLINE, EMBASE, and the Cochrane Library were searched to find relevant trials. RCTs of TORI treatment in patients with ADPKD were included. Effects on the primary outcome [total kidney volume (TKV)] and secondary outcomes [changes in cyst volume (CV) and parenchymal volume (PV), glomerular filtration rate (GFR), proteinuria, and adverse events] were analyzed. Results: The results of 5 RCTs, which included 619 patients, were analyzed. TORIs did not significantly reduce TKV [mean difference (WMD) -90.01 ml, 95% CI -235.49 to 55.47, p = 0.23; I2 = 0%; p for heterogeneity = 0.67]. CV decreased after TORI treatment (WMD -15.08 ml, 95% CI -17.82 to -12.34, p < 0.00001), and PV did not change (WMD -0.55 ml, 95% CI -64.55 to 63.45, p = 0.99). There was no significant difference in GFR between the TORI-treated and control groups (WMD 4.94 ml/min, 95% CI -0.81 to 10.68, p = 0.09). Proteinuria was significantly higher in the TORI-treated group than in the control group (standard mean difference 0.27, 95% CI 0.09-0.44, p = 0.002). Conclusion: Long-term treatment with TORIs does not benefit patients with ADPKD.
FLAIR-Only Progression in Bevacizumab-Treated Relapsing Glioblastoma Does Not Predict Short Survival
Authors: Schaub Christina , Greschus Susanne , Seifert Mirko , Waha Andreas , Blasius Elias , Rasch Katja , Landwehr Christiane , Mack Frederic , Schäfer Niklas , Stuplich Moritz , Kebir Sied , Vilz Belinda , Scheffler Björn , Boström Jan , Simon Matthias , Urbach Horst , Glas Martin , Herrlinger Ulrich
Published: September 2013

Objectives: In this study, we analyzed the prognostic value of different MRI progression patterns for survival in patients with recurrent malignant glioma treated with the vascular endothelial growth factor antibody bevacizumab. Patients and Methods: Twenty-six adult patients with recurrent malignant glioma treated with bevacizumab or bevacizumab/irinotecan were retrospectively analyzed for the development of contrast-enhanced (T1-weighted MRI) and T2/FLAIR lesions. According to the progression pattern, patients were divided into 3 subgroups: (1) patients with primarily progressive contrast-enhanced lesions in the first MRI after initiation of therapy (‘primary PD group'); (2) patients with stable or regressive enhanced lesions but progressive FLAIR lesions (‘FLAIR-only PD group'), and (3) patients with stable or regressive contrast-enhanced T1 and FLAIR lesions (‘no PD group'). Results: Overall survival (OS) in the 6 patients in the FLAIR-only PD group was not significantly different from the 11 patients in the no PD group (median 311 vs. 254 days, respectively). In contrast, survival in the FLAIR-only PD group was significantly better (p = 0.025) than in the primary PD group. Conclusion: FLAIR-only progression is not an independent prognostic factor negatively influencing OS in recurrent glioblastoma treated with bevacizumab and should not lead to discontinuation of bevacizumab therapy.
Cyr61 is a target for heparin in reducing MV3 melanoma cell adhesion and migration via the integrin VLA-4
Authors: Schütze Norbert , Jüngel Eva , Blaheta Roman , Naggi Annamaria , Torri Giangiacomo , Schmitz Patrick , Gerber Ursula , Bendas Gerd
Published: September 2013

The integrin VLA-4 is important for the metastatic dissemination of melanoma cells. We could recently show that heparin can block VLA-4 binding, which contributes, next to blocking P-and L-selectin, to the understanding of antimetastatic activities of heparin. The matricellular ligand Cyr61, secreted by numerous tumours, is responsible for increased tumourigenicity and metastasis. This has been attributed to Cyr61 binding to, and thus activating integrins. However, a VLA-4/Cyr61 axis has not yet been reported. Since Cyr61 possesses heparin binding capabilities, Cyr61 can be supposed as potential target for heparin to indirectly interfere with integrin functions. The present in vitro studies address (i) the existence of a Cyr61/VLA-4 axis and (ii) the functional relevance of heparin interference via Cyr61. The C-terminal module III of Cyr61 could be exposed as nanomolar affine binding site for VLA-4. A shRNA-based knockdown of Cyr61 in MV3 human melanoma cells reduced VLA-4-mediated cell binding to VCAM-1, migration on fibronectin, and integrin signalling functions significantly. Using a biosensor approach we provide insight into heparin interference with this process. The low-molecular-weight heparin tinzaparin, but not the pentasaccharide fondaparinux, binds module IV of Cyr61 with micromolar affinity. But tinzaparin cannot interfere with Cyr61 accumulation onto syndecan-4, indicating different Cyr61 binding sites for heparin and other GAGs. Nonetheless, tinzaparin affects the VLA-4 binding and signalling functions selectively via Cyr61 already at very low concentration most likely by blocking the cellular secreted free Cyr61. This study emphasises Cyr61 as promising, and hitherto not considered target for heparin to selectively influence integrin functions.
Enhanced active metabolite generation and platelet inhibition with prasugrel compared to clopidogrel regardless of genotype in thienopyridine metabolic pathways
Authors: Angiolillo Dominick J. , Ferreiro Jose L. , Jakubowski Joseph A. , Winters Kenneth J. , Effron Mark B. , Duvvuru Suman , Costigan Timothy M. , Sundseth Scott S. , Walker Joseph R. , Saucedo Jorge F. , Kleiman Neal S. , Varenhorst Christoph , Braun Oscar Ö.
Published: September 2013

Clopidogrel response varies according to the presence of genetic polymorphisms. The CYP2C19*2 allele has been associated with impaired response; conflicting results have been reported for CYP2C19*17, ABCB1, and PON1 genotypes. We assessed the impact of CYP2C19, PON1, and ABCB1 polymorphisms on clopidogrel and prasugrel pharmacodynamic (PD) and pharmacokinetic (PK) parameters. Aspirin-treated patients (N=194) with coronary artery disease from two independent, prospective, randomised, multi-centre studies comparing clopidogrel (75 mg) and prasugrel (10 mg) were genotyped and classified by predicted CYP2C19 metaboliser phenotype (ultra metabolisers [UM] = *17 carriers; extensive metabolisers [EM] = *1/1 homozygotes; reduced metabolisers [RM] = *2 carriers). ABCB1 T/T and C/T polymorphisms and PON1 A/A, A/G and G/G polymorphisms were also genotyped. PD parameters were assessed using VerifyNow® P2Y12 and vasodilator stimulated phosphoprotein (VASP) expressed as platelet reactivity index (PRI) after 14 days of maintenance dosing. Clopidogrel and prasugrel active metabolite (AM) exposure was calculated in a cohort of 96 patients. For clopidogrel, genetic variants in CYP2C19, but not ABCB1 or PON1, affected PK and PD. For prasugrel, none of the measured genetic variants affected PK or PD. Compared with clopidogrel, platelet inhibition with prasugrel was greater even in the CYP2C19 UM phenotype. Prasugrel generated more AM and achieved greater platelet inhibition than clopidogrel irrespective of CYP2C19, ABCB1, and PON1 polymorphisms. The lack of effect from genetic variants on prasugrel AM generation or antiplatelet activity is consistent with previous studies in healthy volunteers and is consistent with improved efficacy in acute coronary syndrome patients managed with percutaneous coronary intervention.
Identification of Na+,K+-ATPase inhibitors of volume-expanded hog plasma.
Authors: Inagami T , Tamura M
Published: September 2013

Na+,K+-adenosine triphosphatase (ATPase) inhibitors possessing inhibitory activities against the specific binding of ouabain to Na+,K+-ATPase and 86Rb uptake into hog erythrocytes have been purified from the plasma of hog acutely infused with saline. The purifications were performed by a combination of Amberlite XAD-2 adsorption chromatography and several steps of high performance liquid chromatography using four different types of columns. Inhibitors purified to homogeneity were identified as linoleic and oleic acids, gamma-stearoyllysophosphatidylcholine, gamma-arachidoyllysophosphatidylcholine, gamma-linoleoyllysophosphatidylcholine, and gamma-oleoyllysophosphatidylcholine. Small amounts of beta-arachidoyllysophosphatidylcholine, gamma-docosapentaenoyllysophosphatidylcholine, gamma-eicosatrienoyllysophosphatidylcholine, and gamma-palmitoyllysophosphatidylcholine were also detected by both fast atom bombardment mass and proton nuclear magnetic resonance spectrometric studies. Only gamma-acyllysophosphatidylcholines showed inhibitory activities on Na+,K+-ATPase and ouabain-binding activities. These lysophosphatidylcholines and unsaturated free fatty acids were effective at 100 microM levels in attaining 50% inhibition of the enzyme activity. The ouabain-displacing activity in plasma caused by these compounds increased with time during saline infusion. The maximal plasma levels of these components were approximately 10 times higher than that in the preinfusion plasma sample.
Calcium in the regulation of aldosterone secretion and vascular smooth muscle contraction.
Authors: Rasmussen H , Barrett P , Takuwa Y , Apfeldorf W
Published: September 2013

A model of angiotensin II action has been developed in which the flow of information from cell surface to cell interior proceeds by two temporally distinct branches: a calmodulin branch largely responsible for initiating the response; and a C-kinase branch for sustaining it. There are at least two initial events: a prompt and sustained increase in calcium influx rate, and prompt hydrolysis of phosphatidylinositol 4,5-bisphosphate. The latter leads to the generation of water-soluble inositol 1,4,5-trisphosphate and lipid soluble diacylglycerol. The rise in inositol 1,4,5-trisphosphate concentration causes the redistribution of intracellular calcium, a transient rise in the calcium concentration in the cytosol, and the activation of calmodulin-dependent enzymes, including protein kinase(s). As a result, several cellular proteins are rapidly phosphorylated and initiate the cellular response. The rise in calcium and these initial phosphorylation events are transient, however, so that an additional mechanism is necessary to sustain the response. The rise in diacylglycerol content, along with the transient rise in cytosolic calcium, leads to a shift of the C-kinase from a calcium-insensitive to a calcium-sensitive, plasma membrane-associated form. In this location, the activity of C-kinase is regulated by the rate of calcium flux across the plasma membrane. As a result of the activity of the C-kinase, a second set of cellular proteins becomes phosphorylated, and these control the sustained phase of the response.
Control of ion fluxes by mitogenic polypeptides.
Authors: Glaser L , Whiteley B
Published: September 2013

Several ion fluxes are stimulated when mitogenic polypeptides are added to cells. The precise mechanism by which this activation takes place is not understood, but compelling evidence exists in the case of the activation of sodium-hydrogen exchange that it requires the tyrosine kinase activity associated with the mitogen receptor. The activation of sodium-hydrogen exchange by mitogens is associated with changes in intracellular pH that appear to be permissive but not causal in allowing cells to proceed through the cell cycle. When added to cells, mitogens also activate protein kinase C, which acts as part of a feedback loop to control the activity of the mitogen receptor. Possible mechanisms for this control are discussed.
The Milan hypertensive rat as a model for studying cation transport abnormality in genetic hypertension.
Authors: Ferrari P , Barber B R , Torielli L , Ferrandi M , Salardi S , Bianchi G
Published: September 2013

Environmental factors, genetic polymorphisms, and different experimental designs have been the main impediments to evaluating a genetic association between cell membrane cation transport abnormalities and human essential or genetic hypertension. We review the results obtained in the Milan hypertensive strain of rats (MHS) and in its appropriate control normotensive strain (MNS) to illustrate our approach to defining the role of cation transport abnormality in a type of genetic hypertension. Before the development of a difference in blood pressure between the two strains, the comparison of kidney and erythrocyte functions showed that MHS had an increased glomerular filtration rate and urinary output, and lower plasma renin and urine osmolality. Kidney cross-transplantation between the strains showed that hypertension is transplanted with the kidney. Proximal tubular cell volume and sodium content were lower in MHS while sodium transport across the brush border membrane vesicles of MHS was faster. Erythrocytes in MHS were smaller and had lower sodium concentration, and Na+-K+ cotransport and passive permeability were faster. The differences in volume, sodium content, and Na+-K+ cotransport between erythrocytes of the two strains persisted after transplantation of bone marrow to irradiated F1 (MHS X MNS) hybrids. Moreover, in normal segregating F2 hybrid populations there was a positive correlation between blood pressure and Na+-K+ cotransport. These results suggest a genetic and functional link in MHS between cell membrane cation transport abnormalities and hypertension. Thus erythrocyte cell membrane may be used for approaching the problem of defining the genetically determined molecular mechanism underlying the development of a type of essential hypertension.
Genetic studies of cation tests and hypertension.
Authors: Williams R R , Hasstedt S J , Hunt S C , Wu L L , Ash K O
Published: September 2013

Several tests of cation concentration and transport are being studied among members of large Utah pedigrees as part of a study of the genetic and environmental determinants of essential hypertension. Corrected urinary sodium excretion and plasma sodium concentration correlated well in spouses and siblings (r = 0.21-0.54, p less than 0.001), suggesting the effects of shared family environment (e.g., sodium intake). Intraerythrocytic sodium concentration and sodium-lithium countertransport showed no significant correlation in spouses and very significant correlations between siblings and between parents and offspring (r = 0.34-0.58, p less than 0.001), suggesting mostly genetic determination. Using maximum likelihood tests of different genetic models, both sodium-lithium countertransport and intraerythrocytic sodium showed predominantly polygenic determination (H2 = 70%) and some possible major gene determinants (H2 = 18-25%) for a total heritability of 89 to 95% for these characteristics. These data suggest both genes and shared family environment contribute to the familiality of cation tests. They also illustrate the need and utility of quantitative methods for objective analysis of pedigree data.
Epidemiological studies of sodium transport and hypertension.
Authors: McDonald A , Trevisan M , Cooper R , Stamler R , Gosch F , Ostrow D , Stamler J
Published: September 2013

Red blood cell membrane cation transport was measured in five population-based surveys and two randomized, controlled, dietary intervention studies to examine its associations with demographic, biological, and dietary variables in free-living individuals. A total of 508 individuals, 255 with high blood pressure, were studied. Both sexes, blacks and whites, and several age groups were represented. The intervention studies included short-term dietary sodium restriction in normotensive adolescents, and a 4-year multifactorial trial on weight, sodium, and alcohol in hypertensive adults. The findings from these surveys and intervention studies are summarized in this report. Sodium-stimulated lithium countertransport was significantly related to diastolic blood pressure in white adults (r = 0.28, p less than 0.001), and to systolic blood pressure in black children (r = 0.50, p less than 0.005) and white adolescents (r = 0.31, p less than 0.05). Lithium countertransport was related to sex and race, but not age. Body mass index had an independent relationship with lithium countertransport in some age groups. Lithium countertransport was lower in normotensive adults than in both younger and older hypertensive adults. Lithium countertransport did not differ significantly between subjects with hypertension treated with antihypertensive medications and those with untreated hypertension. Short-term dietary sodium restriction did not influence lithium countertransport in normotensive adolescents. Long-term dietary intervention was associated with low lithium countertransport in hypertensive adults able to maintain blood pressure control without medication. These findings indicate that lithium countertransport is related to blood pressure and hypertension among free-living individuals.
The natriuretic response to hydromineral imbalance.
Authors: Gruber K A
Published: September 2013

Many recent investigations of the mechanism of volume-expansion natriuresis fail to appreciate that the observed renal sodium excretion may not be dependent on an increase in intravascular volume, but rather on the infused sodium load or extracellular fluid volume expansion. With this in mind, the natriuresis of isotonic volume expansion, hypertonic saline infusion, and dehydration have a common basis: they present a relative or absolute sodium load. Lesions of forebrain periventricular tissue prevent the natriuretic response to these three states of body fluid imbalance. In this review we discuss the evidence for a common central nervous system-mediated natriuretic mechanism in response to disturbances of fluid and electrolyte balance. We also propose a role for pars intermedia-derived, proopiomelanocortin-derived peptides as humoral mediators of renal sodium excretion. Evidence from our laboratory, as well as others, provides data for a testable hypothesis to explain central nervous system-mediated natriuresis, as well as an explanation of how central nervous system lesions or neurochemical perturbations affect the renal response to body fluid imbalance.
Problems and pitfalls in the isolation of an endogenous Na+, K+-ATPase inhibitor.
Authors: Mir M A , Morgan K , Lewis M , Spurlock G , Chappell S , Lewis M , Scanlon M
Published: September 2013

Plasma from volume-expanded and salt-loaded hypertensive animals and from patients with essential hypertension has been reported to inhibit Na+, K+-adenosine triphosphatase (ATPase). Inhibition of the sodium pump in vascular smooth muscle caused by such a circulating factor could increase vascular tone and sensitivity to vasoactive agents, and thereby result in arterial hypertension. Numerous efforts in the past failed to isolate the putative factor from urine and plasma. Recent studies have suggested that the hypothalamus is an important source of an endogenous Na+, K+-ATPase inhibitor, but its isolation from the tissue extracts has been rendered difficult by the presence of other cellular constituents that cause artifactual interference with the assays and purification procedures. Using an alternative approach of isolating the inhibitor from culture medium, we found that dispersed fetal rat hypothalamic neurons in a capillary culture system release a heat-stable, peptidic, low-molecular-weight, active sodium transport inhibitor that causes a reversible increase in vascular tone, sensitizes vascular smooth muscle to the vasoactive effect of norepinephrine, and possesses several characteristics of the putative endogenous digitalislike factor. This inhibitor may be a chemical mediator linking kidney, brain, and cardiovascular system in the genesis of experimental volume-expanded and salt-loaded hypertension and human essential hypertension.
Humoral sodium transport inhibitor in acute volume expansion and low renin hypertension.
Authors: Pamnani M B , Bryant H J , Haddy F J
Published: September 2013

This review summarizes our bioassay methods for determining the level of humoral sodium pump inhibiting factor after acute volume expansion in experimental animals and humans, and in low renin experimental and human essential hypertension. In brief, ouabain-sensitive 86Rb uptake and membrane potential in blood vessels from normal animals are measured after incubation in plasma supernate from experimental subjects and animals and their respective controls. The data show that humoral sodium pump inhibitor is elevated after acute volume expansion in normal animals (dogs and rats) and in normal humans. The level of inhibitor is also elevated in patients with low renin essential hypertension and in experimental animals with low renin, volume-dependent types of hypertension, namely, one-kidney, one wrapped hypertension in dogs, and one-kidney, one clip and reduced renal mass-saline hypertension in rats. Humoral sodium pump inhibiting factor inhibits the Na+-K+ pump in the cardiovascular system. Such inhibition by other means (hypokalemia, cardiac glycosides) activates the system. Therefore, we also discuss the possible role of humoral sodium pump inhibitor in low renin volume-dependent hypertension.
Membrane biochemistry of the ouabain-resistant potassium transport system.
Authors: English L H , White B , Cantley L C
Published: September 2013

A 6.5-kilobase fragment of genomic DNA from mutant mouse cells under ouabain selection pressure conferred ouabain resistance when transfected into ouabain-sensitive CV1 green monkey fibroblasts. Ouabain resistance was induced in the presence of 10 microM ouabain. Amiloride (500 microM) completely blocked ouabain-insensitive 86Rb+ uptake into these cells. Plasma membranes from these cells demonstrated little sodium-dependent adenosine triphosphatase (ATPase) activity but had potassium-dependent and ouabain-resistant p-nitrophenylphosphatase activity. Like Na+,K+-ATPase this activity was vanadate- and sodium-inhibitable. Also, like the Na+,K+-ATPase, sodium inhibition of the p-nitrophenylphosphatase was reversed by 10 microM adenosine 5'-triphosphate.
Constricting and stiffening action of atropine on aortic response to angiotensin in dogs.
Authors: Cabrera E , Levenson J , Armentano R , Barra J , Pichel R , Simon A
Published: September 2013

The elasticity of the thoracic aorta was studied in nine dogs instrumented with a pressure microtransducer and two ultrasonic crystals diametrically fixed in the adventitia. Systolic and diastolic changes in pressure and diameter were used to calculate Peterson and incremental elastic moduli. Acute hypertension was induced by infusions of angiotensin performed 1) during the control period, 2) after propranolol (1.5 mg/kg), 3) after atropine (0.2 mg/kg), and 4) after propranolol plus atropine. Absolute and percent variations of mean diameter were correlated to pressure in the control period and after autonomic blockade (p less than 0.01). The slopes of these correlations were not different between propranolol and control groups, but were lower with atropine (p less than 0.01) and with atropine plus propranolol (p less than 0.001) than in the control period. Correlations were also found between Peterson and incremental elastic moduli and mean pressure in the control period and after blockade (p less than 0.001). No differences of slopes existed between propranolol and control groups, but the slope of the correlation relative to the incremental elastic modulus was higher with atropine than in the control period (p less than 0.05), and the slopes of the correlations relative to the Peterson and the incremental elastic moduli were respectively higher with atropine plus propranolol than in the control period (p less than 0.05, p less than 0.05). Thus, atropine decreased the distention and increased the stiffness of the aorta in response to acute angiotensin-mediated hypertension.
Contractile response of spontaneously hypertensive rat caudal artery to phorbol esters.
Authors: Bendhack L M , Sharma R V , Bhalla R C
Published: September 2013

Stimulation of phosphatidylinositol metabolism by neurotransmitters produces diacylglycerol, an activator of protein kinase C, which may be involved in hormone-mediated contractions. We studied the effect of a tumor-promoting phorbol ester, 12-deoxyphorbol 13-isobutyrate 20-acetate (DPBA), on contraction of caudal artery rings of Wistar-Kyoto control (WKY) and spontaneously hypertensive rats (SHR) in order to examine whether protein kinase C-mediated mechanisms are increased in SHR. Although DPBA alone did not produce contractions of either WKY or SHR caudal artery rings, it greatly potentiated the contractions evoked by norepinephrine, norepinephrine, vasopressin, potassium, and calcium ionophore A23187. The potentiation of contractile response to these agents by DPBA was dependent on extracellular calcium. The DPBA potentiation of contractions evoked by norepinephrine, vasopressin, and potassium was significantly greater (p less than 0.05) in SHR than in WKY, while no differences were observed between strains for the contractions evoked by calcium ionophore A23187. These results indicate that the protein kinase C-mediated responses are increased in SHR caudal artery rings, and this effect appears to be due to increased calcium influx through cell membrane calcium channels.
Peptide-containing nerves around blood vessels of stroke-prone spontaneously hypertensive rats.
Authors: Lee R M , Nagahama M , McKenzie R , Daniel E E
Published: September 2013

The distribution and density of nerves containing vasoactive intestinal polypeptide, substance P, and neuropeptide Y around the cerebral and peripheral blood vessels of stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY) were studied using an indirect immunofluorescence technique. Neonatal sympathectomy of SHRSP with anti-nerve growth factor and guanethidine was also carried out to study the effect of sympathectomy on the distribution of these nerves. Vasoactive intestinal polypeptide nerve density was higher in the veins and superior mesenteric artery of SHRSP than of WKY and lower in the cerebral arteries of SHRSP than of WKY, but no difference was found in the muscular mesenteric arteries. Sympathectomy reduced the density of these nerves in all the peripheral vessels but had little effect on the cerebral arteries. Density of substance P nerves was similar between SHRSP and WKY in the peripheral vessels but higher in the cerebral arteries of WKY than of SHRSP. Sympathectomy reduced the density of these nerves in the peripheral vessels but increased the density in some cerebral arteries of SHRSP. Neuropeptide Y nerve density was higher in the peripheral blood vessels of SHRSP than of WKY, and no difference was found in the cerebral arteries. Sympathectomy almost completely removed these nerves in the peripheral vessels but had no effect on the cerebral arteries. We suggest that some of the differences in nerve density between SHRSP and WKY, especially those in the peripheral blood vessels, may be related to the development of hypertension in the SHRSP.
Extent of baroreceptor resetting in response to sodium nitroprusside and verapamil.
Authors: Salgado H C , Krieger E M
Published: September 2013

We investigated the effect of sodium nitroprusside, verapamil, and hemorrhage on the resetting of the aortic baroreceptors of normotensive control rats to hypotension, and the reversal of resetting of baroreceptors of one-kidney, one clip hypertensive rats to normotension. Using whole-nerve recording, the extent (%) of resetting (or reversal of resetting) observed 15 minutes after a maintained fall in mean arterial pressure (MAP) was evaluated by the ratio between changes of systolic threshold pressure for baroreceptor activation and changes of control diastolic pressure exhibited by the rats, multiplied by 100. Three groups of normotensive control rats showed a MAP decrease to hypotensive levels of 33%, 39%, and 41%, respectively, with sodium nitroprusside, verapamil, and hemorrhage. The corresponding extent of resetting was 96 +/- 3%, 39 +/- 2%, and 46 +/- 4%, respectively. Only in the group treated with verapamil did MAP and systolic threshold pressure not revert completely to normotensive levels 15 minutes after the end of drug infusion. Three groups of one-kidney, one clip hypertensive rats showed MAP normalization of 30%, 37%, and 31%, respectively, with sodium nitroprusside, verapamil, and hemorrhage. The corresponding extent of reversal of resetting to normotension was 107 +/- 3%, 40 +/- 2%, and 60 +/- 9%, respectively. Again, only in the group treated with verapamil did MAP and systolic threshold pressure not revert to hypertensive levels 15 minutes after infusion. Besides indicating that different vasodilators can differently modulate the rapid (15-minute) resetting (or reversal of the resetting) due to similarly maintained fall in MAP, these data suggest that verapamil has a nonspecific effect on the baroreceptors, whereas sodium nitroprusside appears to affect baroreceptor transduction.
Bidirectional transport of angiotensin II binding sites in the vagus nerve.
Authors: Diz D I , Ferrario C M
Published: September 2013

We previously showed that specific angiotensin II (Ang II) binding sites are present in the canine nodose ganglion and peripheral vagus nerve, and that unilateral removal of the nodose ganglion results in loss of binding in the ipsilateral nucleus tractus solitarii and the dorsal motor nucleus of the vagus. An association of Ang II binding sites with both afferent and efferent vagal fibers is consistent with actions of the peptide on cardiac vagal tone and the baroreceptor reflex. To investigate possible transport of Ang II binding sites, quantitative in vitro receptor autoradiography was used to visualize binding after double ligation of the peripheral process of the cervical vagus nerve. One ligature was tied 0.2 to 0.5 cm distal to the nodose ganglion; the second ligature was tied on the same nerve 1.0 to 1.5 cm from the nodose ganglion. Twenty-four hours later, high-affinity Ang II binding sites (Ka = 0.46 +/- 0.08 nM) accumulated at the first ligature (the side nearest the nodose ganglion), indicating anterograde transport. Since accumulations of similar affinity sites were seen distal to the second ligature, retrograde transport of binding sites also occurred. These data reveal the existence of a mechanism for the bidirectional axonal transport of Ang II binding sites in the cervical portion of the vagus nerve.
Diabetes mellitus and hypertension. State of the art lecture.
Authors: Ramos O L
Published: September 2013

In rats with streptozotocin-induced diabetes an increase in arterial blood pressure was observed as early as the first week after the drug was injected. Blood pressure reached maximal values around the fourth week and remained stable for a long period of follow-up. The responsiveness of these rats to the three major vasopressor hormones, angiotensin II, norepinephrine, and vasopressin, was decreased in the early phase of diabetes and returned to normal in the late phase. Acute treatment at the third, sixth, and twelfth weeks with blockers of these vasopressor hormones resulted in a significant fall in blood pressure at the third week with captopril and at the twelfth week with propranolol plus phentolamine. No significant fall was observed when a specific vasopressin inhibitor was administered. Good control of the blood pressure was obtained when these rats were treated chronically with captopril or prazosin, and partial control was achieved when they were fed a low salt diet. An attenuation in arterial blood pressure levels was observed in rats with two-kidney, one clip hypertension when diabetes was induced by streptozotocin. Plasma creatine levels in diabetic rats were significantly higher than those in control rats only in the sixth and twelfth weeks. Electron microscopy revealed some minor glomerular lesions only at the twelfth week.
Captopril and the response to stress in the spontaneously hypertensive rat.
Authors: Berecek K H , Coshatt G , Narkates A J , Oparil S , Wilson K M , Robertson J
Published: September 2013

The purpose of this study was to determine the effect of chronic blockade of the brain renin-angiotensin system on the hormonal response to stress in spontaneously hypertensive rats (SHR). To this end, we measured changes in plasma corticosterone, vasopressin, plasma renin activity, aldosterone, norepinephrine, and epinephrine in SHR treated with a 4-week intracerebroventricular infusion of captopril (osmotic minipump, 1.25 micrograms/hr) or vehicle in response to cold stress (4 degrees C x 4 hours) or ether stress (5 minutes). Within the fourth week of treatment, the average systolic blood pressure of captopril-treated SHR was significantly lower than that of vehicle-treated rats. Basal plasma levels of corticosterone, but not vasopressin, were significantly lower in SHR treated with captopril. In response to cold stress, captopril-treated SHR showed significantly lesser increases in both corticosterone and vasopressin than did vehicle-treated SHR. There were no differences in basal plasma levels of norepinephrine, epinephrine, plasma renin activity, or aldosterone between captopril-treated and vehicle-treated SHR, and both groups showed elevations of a similar magnitude after exposure to cold. In response to ether stress, captopril-treated SHR also showed significantly smaller increases in corticosterone and vasopressin than did vehicle-treated SHR. These results suggest that chronic intracerebroventricular administration of captopril, through blockade of the brain renin-angiotensin system, alters the hormonal response of SHR to stress.
Long-term captopril treatment. Angiotensin II receptors and responses.
Authors: Wilson K M , Magargal W , Berecek K H
Published: September 2013

The purpose of this study was to elucidate the mechanism of the antihypertensive effect of the angiotensin I (Ang I) converting enzyme inhibitor captopril in spontaneously hypertensive rats (SHR). Drinking responses, peripheral vascular reactivity, and angiotensin II (Ang II) receptor binding in both the brain and vascular smooth muscle were examined in control and captopril-treated SHR. Pregnant and nursing dams were treated with oral captopril (100 mg/kg). After weaning, offspring were maintained on captopril (50 mg/kg). The average systolic pressures after 21 weeks of captopril treatment were 122 +/- 3 mm Hg (male) and 118 +/- 4 mm Hg (female) as compared with 169 +/- 4 mm Hg (male) and 162 +/- 2 mm Hg (female) in age-matched controls. Drinking responses to intracerebroventricular (10 ng) and subcutaneous (100 micrograms/kg) administration of Ang I and II were attenuated in captopril-treated SHR in comparison to control SHR. Ang II receptor binding in the hypothalamus, thalamus, and septum of captopril-treated SHR was also significantly reduced. In contrast to a depressed angiotensinergic system in the brain, peripheral vascular reactivity to Ang II, as determined in isolated, artificially perfused kidneys, was elevated. Threshold and ED50 values for Ang II were significantly lower in captopril-treated SHR than in controls. Ang II receptor binding in aortic smooth muscle cells prepared from captopril-treated SHR was also significantly greater than in cells from controls. Thus, lifetime treatment with captopril induced alterations in the renin angiotensin systems in the periphery and brain that were manifested by changes in receptor binding and responsiveness to Ang II.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypotensive spinal serotonergic effect. Are S1 or S2 receptors involved?
Authors: Berger A , Ramirez A J
Published: September 2013

Since previous data obtained in anesthetized rats supported the idea that the activation of spinal serotonergic receptors induced a hypotensive effect, it was decided to characterize more closely the serotonergic spinal involvement and to elucidate the serotonergic receptor type involved in this effect. After female Wistar rats were anesthetized, the femoral artery (for blood pressure measurement) and vein (for parenteral injection of drugs) were cannulated. An intrathecal catheter was positioned with the tip at the T6-L3 intervertebral space. The results showed that the dose-dependent decrease in mean blood pressure induced by serotonin administered at the T6-L3 level was prevented by giving the serotonergic S2 antagonist ritanserin intravenously. The intravenous administration of 5-methoxy-N,N-dimethyltryptamine, a direct serotonergic agonist, induced a dose-dependent hypotension previously shown to originate at spinal cord level. This effect was prevented by intrathecal administration of ketanserin, an S2-receptor antagonist. The selective agonist of the S1-type receptors, 8-hydroxy-dipropylaminotetralin, given at the same level of the spinal cord, failed to induce any effect on mean blood pressure. The results suggest that the hypotensive effect obtained after the spinal serotonergic activation involves serotonin receptors of the S2 type.
Effect of central serotonin depletion on blood pressure and the renin system in rats.
Authors: Mikulic L E , Kurnjek M L , Russo R , Trolliet M R , Basso N
Published: September 2013

In the present study we examined the effect of depletion of central nervous system serotonin by 5,7-dihydroxytryptamine on blood pressure in male Wistar rats. We also analyzed the relationship between the serotonergic and renin-angiotensin systems. Blood pressure was determined before and after intracisternal administration of 5,7-dihydroxytryptamine, 200 micrograms in saline with 1 mg/ml ascorbic acid (n = 9). Control rats (n = 8) received intracisternal vehicle. Before sacrifice, blood and cerebrospinal fluid samples were obtained. The brain was dissected in several areas. Serotonin, norepinephrine, angiotensinogen, and reninlike concentrations were determined in the brain parenchyma; angiotensinogen concentration was evaluated in cerebrospinal fluid and plasma samples; plasma renin activity was also measured. Treatment produced a significant decrease in blood pressure (-10 mm Hg; p less than 0.025) and, simultaneously, a high depletion of serotonin stores in the studied central areas (p less than 0.001), except in the cerebral cortex. Reninlike concentration was increased in the medulla oblongata (p less than 0.005) and the brainstem (p less than 0.02) after 5,7-dihydroxytryptamine treatment. Angiotensinogen concentration was decreased in the hypothalamus and elevated in the spinal cord. Angiotensinogen concentration in cerebrospinal fluid, plasma angiotensinogen concentration, and plasma renin activity did not change with treatment. Serotonin concentration in the cerebrospinal fluid remained unchanged, while the 5-hydroxyindoleacetic acid level was diminished (-47%; p less than 0.001). Intracisternal administration of 5,7-dihydroxytryptamine produced a hypotensive effect in normal rats and several modifications of the renin-angiotensin complex, suggesting a relationship between the monoaminergic and peptidergic systems.
Labetalol blunts morning pressor surge in systolic hypertension.
Authors: DeQuattro V , Lee D D , Allen J , Sirgo M , Plachetka J
Published: September 2013

Twenty-four-hour ambulatory blood pressure, including the acceleration phase, and left ventricular mass were evaluated in 16 patients with isolated systolic hypertension (standing blood pressure greater than or equal to 160 mm Hg systolic and less than or equal to 95 mm Hg diastolic). After a 4-week, single-blind, placebo period, each patient underwent 24-hour ambulatory blood pressure monitoring and echocardiography. Labetalol therapy was then initiated at 100 mg twice a day in a single-blind manner and increased weekly by 100 mg twice a day until blood pressure control was obtained or a maximum dosage of 400 mg twice a day was reached. Blood pressure control was achieved at a mean daily dose of 363 +/- 46 mg of labetalol. Measurements were repeated at the end of an 8-week maintenance phase. Labetalol therapy significantly reduced the mean 24-hour systolic ambulatory blood pressure from 154 +/- 8 (mean +/- SEM) mm Hg at baseline to 142 +/- 6 mm Hg (p greater than 0.01) and controlled the early morning surge in systolic ambulatory blood pressure. Minor reductions in diastolic blood pressure and heart rate were statistically but not clinically significant. Left ventricular mass was not changed. Labetalol monotherapy provides effective 24-hour control of systolic blood pressure, including the acceleration phase, in patients with isolated systolic hypertension.