bluuebunny/crossref_metadata_2025 huggingface dataset:
Robots Learn Writing
Authors: Tan Huan , Du Qian , Wu Na
Published: August 2012

This paper proposes a general method for robots to learn motions and corresponding semantic knowledge simultaneously. A modified ISOMAP algorithm is used to convert the sampled 6D vectors of joint angles into 2D trajectories, and the required movements for writing numbers are learned from this modified ISOMAP-based model. Using this algorithm, the knowledge models are established. Learned motion and knowledge models are stored in a 2D latent space. Gaussian Process (GP) method is used to model and represent these models. Practical experiments are carried out on a humanoid robot, named ISAC, to learn the semantic representations of numbers and the movements of writing numbers through imitation and to verify the effectiveness of this framework. This framework is applied into training a humanoid robot, named ISAC. At the learning stage, ISAC not only learns the dynamics of the movement required to write the numbers, but also learns the semantic meaning of the numbers which are related to the writing movements from the same data set. Given speech commands, ISAC recognizes the words and generated corresponding motion trajectories to write the numbers. This imitation learning method is implemented on a cognitive architecture to provide robust cognitive information processing.
Scaling of the Transient Hydroelastic Response and Failure Mechanisms of Self-Adaptive Composite Marine Propellers
Authors: Motley Michael R. , Young Yin L.
Published: August 2012

The load dependent deformation responses and complex failure mechanisms of self-adaptive composite propeller blades make the design, analysis, and scaling of these structures nontrivial. The objective of this work is to investigate and verify the dynamic similarity relationships for the hydroelastic response and potential failure mechanisms of self-adaptive composite marine propellers. A fully coupled, three-dimensional boundary element method-finite element method is used to compare the model and full-scale responses of a self-adaptive composite propeller. The effects of spatially varying inflow, transient sheet cavitation, and load-dependent blade deformation are considered. Three types of scaling are discussed: Reynolds scale, Froude scale, and Mach scale. The results show that Mach scaling, which requires the model inflow speed to be the same as the full scale, will lead to discrepancies in the spatial load distributions at low speeds due to differences in Froude number, but the differences between model and full-scale results become negligible at high speeds. Thus, Mach scaling is recommended for a composite marine propeller because it allows the same material and layering scheme to be used between the model and the full scale, leading to similar 3D stress distributions, and hence similar failure mechanisms, between the model and the full scale.
A Short Walk along the Gravimeters Path
Authors: Marson Iginio
Published: August 2012

The history of gravity measurements begun in 1604 with Galileo Galilei experiments on the acceleration due to the gravity force of the earth,g, along inclined planes. In his memory, the most used unit to measuregis the gal (10−2 m/s2). The paper takes the interested reader through a walk along some of the most important achievements in gravity measurements and gives some perspectives for future developments in terrestrial gravity.
Feasibility of Functional Electrical Stimulation-Assisted Neurorehabilitation following Stroke in India: A Case Series
Authors: Khattar Bhawna , Banerjee Alakananda , Reddi Rajsekhar , Dutta Anirban
Published: August 2012

Functional Electrical Stimulation (FES) facilitates ambulatory function after paralysis by electrically activating the muscles of the lower extremities. The Odstock Dropped Foot Stimulator (ODFS, Odstock, UK) called ODFS Pace, was used for heel-switch triggered FES-assisted walking. The ODFS is recommended as an intervention for neurologically impaired gait in the Royal College of Physicians (UK) Clinical Guidelines on Stroke. Based on the guidelines by the National Institute of Clinical Excellence (NICE, UK), we started first clinical study in India on ODFS Pace as an orthotic intervention for daily use. In this preliminary study, we also investigated improvement in volitional walking following 6 sessions (3 times per week, for 2 weeks) of 30 minutes of FES-assisted treadmill walking on 7 chronic (>6 months after stroke) stroke survivors. We found that short-duration, moderately intensive FES-assisted gait therapy improved volitional gait in 3 out of 7 stroke survivors suffering from foot drop. Even in absence of improvement in volitional walking, there were no adverse effects and the subjects found heel-switch triggered FES-assisted walking mostly “easy” (6 out of 7). Therefore FES is promising as an orthotic intervention for daily use; however, tailoring the intensity and/or frequency based on patient's ability may make it viable as a therapeutic intervention.
Theoretical Studies of Dynamic Interactions in Excited States of Hydrogen-Bonded Systems
Authors: Wójcik Marek J. , Boczar Marek , Boda Łukasz
Published: August 2012

Theoretical model for vibrational interactions in the hydrogen-bonded benzoic acid dimer is presented. The model takes into account anharmonic-type couplings between the high-frequency O–H and the low-frequency O⋯O stretching vibrations in two hydrogen bonds, resonance interactions between two hydrogen bonds in the dimer, and Fermi resonance between the O–H stretching fundamental and the first overtone of the O–H in-plane bending vibrations. The model is used for theoretical simulation of the O–H stretching IR absorption bands of benzoic acid dimers in the gas phase in the first excited singlet state. Ab initio CIS and CIS(D)/CIS/6-311++G(d,p) calculations have been carried out in the Ã state of tropolone. The grids of potential energy surfaces along the coordinates of the tunneling vibration and the low-frequency coupled vibration have been calculated. Two-dimensional model potentials have been fitted to the calculated potential energy surfaces. The tunneling splittings for vibrationally excited states have been calculated and compared with the available experimental data. The model potential energy surfaces give good estimation of the tunneling splittings in the vibrationally ground and excited states of tropolone, and explain monotonic decrease in tunneling splittings with the excitation of low-frequency out-of-plane modes and increase of the tunneling splittings with the excitation of low-frequency planar modes.
Neogenesis of Lymphoid Structures and Antibody Responses Occur in Human Melanoma Metastases
Authors: Cipponi Arcadi , Mercier Marjorie , Seremet Teofila , Baurain Jean-François , Théate Ivan , van den Oord Joost , Stas Marguerite , Boon Thierry , Coulie Pierre G. , van Baren Nicolas
Published: August 2012

Lymphoid neogenesis, or the development of lymphoid structures in nonlymphoid organs, is frequently observed in chronically inflamed tissues, during the course of autoimmune, infectious, and chronic graft rejection diseases, in which a sustained lymphocyte activation occurs in the presence of persistent antigenic stimuli. The presence of such ectopic lymphoid structures has also been reported in primary lung, breast, and germline cancers, but not yet in melanoma. In this study, we observed ectopic lymphoid structures, defined as lymphoid follicles comprising clusters of B lymphocytes and follicular dendritic cells (DC), associated with high endothelial venules (HEV) and clusters of T cells and mature DCs, in 7 of 29 cutaneous metastases from melanoma patients. Some follicles contained germinal centers. In contrast to metastatic lesions, primary melanomas did not host follicles, but many contained HEVs, suggesting an incomplete lymphoid neogenesis. Analysis of the repertoire of rearranged immunoglobulin genes in the B cells of microdissected follicles revealed clonal amplification, somatic mutation and isotype switching, indicating a local antigen-driven B-cell response. Surprisingly, IgA responses were observed despite the nonmucosal location of the follicles. Taken together, our findings show the existence of lymphoid neogenesis in melanoma and suggest that the presence of functional ectopic lymphoid structures in direct contact with the tumor makes the local development of antimelanoma B- and T-cell responses possible. Cancer Res; 72(16); 3997–4007. ©2012 AACR.
Plasmacytoid Dendritic Cells Promote Immunosuppression in Ovarian Cancer via ICOS Costimulation of Foxp3+ T-Regulatory Cells
Authors: Conrad Curdin , Gregorio Josh , Wang Yi-Hong , Ito Tomoki , Meller Stephan , Hanabuchi Shino , Anderson Sonya , Atkinson Neely , Ramirez Pedro T. , Liu Yong-Jun , Freedman Ralph , Gilliet Michel
Published: August 2012

Epithelial ovarian cancer (EOC) is the fifth most common cause of cancer death among women. Despite its immunogenicity, effective antitumor responses are limited, due, in part, to the presence of forkhead box protein 3–positive (Foxp3+) T regulatory (Treg) cells in the tumor microenvironment. However, the mechanisms that regulate the accumulation and the suppressive function of these Foxp3+ Treg cells are poorly understood. Here, we found that the majority of Foxp3+ Treg cells accumulating in the tumor microenvironment of EOCs belong to the subset of Foxp3+ Treg cells expressing inducible costimulator (ICOS). The expansion and the suppressive function of these cells were strictly dependent on ICOS-L costimulation provided by tumor plasmacytoid dendritic cells (pDC). Accordingly, ICOS+ Foxp3+ Treg cells were found to localize in close vicinity of tumor pDCs, and their number directly correlated with the numbers of pDCs in the tumors. Furthermore, pDCs and ICOS+ Foxp3+ Treg cells were found to be strong predictors for disease progression in patients with ovarian cancer, with ICOS+ Treg cell subset being a stronger predictor than total Foxp3+ Treg cells. These findings suggest an essential role for pDCs and ICOS-L in immunosuppression mediated by ICOS+ Foxp3+ Treg cells, leading to tumor progression in ovarian cancer. Cancer Res; 72(20); 5240–9. ©2012 AACR.
The Rectal Cancer microRNAome – microRNA Expression in Rectal Cancer and Matched Normal Mucosa
Authors: Gaedcke Jochen , Grade Marian , Camps Jordi , Søkilde Rolf , Kaczkowski Bogumil , Schetter Aaron J. , Difilippantonio Michael J. , Harris Curtis C. , Ghadimi B. Michael , Møller Søren , Beissbarth Tim , Ried Thomas , Litman Thomas
Published: August 2012

Purpose: miRNAs play a prominent role in a variety of physiologic and pathologic biologic processes, including cancer. For rectal cancers, only limited data are available on miRNA expression profiles, whereas the underlying genomic and transcriptomic aberrations have been firmly established. We therefore, aimed to comprehensively map the miRNA expression patterns of this disease.

Experimental Design: Tumor biopsies and corresponding matched mucosa samples were prospectively collected from 57 patients with locally advanced rectal cancers. Total RNA was extracted, and tumor and mucosa miRNA expression profiles were subsequently established for all patients. The expression of selected miRNAs was validated using semi-quantitative real-time PCR.

Results: Forty-nine miRNAs were significantly differentially expressed (log2-fold difference >0.5 and P < 0.001) between rectal cancer and normal rectal mucosa. The predicted targets for these miRNAs were enriched for the following pathways: Wnt, TGF-beta, mTOR, insulin, mitogen-activated protein kinase, and ErbB signaling. Thirteen of these 49 miRNAs seem to be rectal cancer-specific, and have not been previously reported for colon cancers: miR-492, miR-542-5p, miR-584, miR-483-5p, miR-144, miR-2110, miR-652, miR-375, miR-147b, miR-148a, miR-190, miR-26a/b, and miR-338-3p. Of clinical impact, miR-135b expression correlated significantly with disease-free and cancer-specific survival in an independent multicenter cohort of 116 patients.

Conclusion: This comprehensive analysis of the rectal cancer miRNAome uncovered novel miRNAs and pathways associated with rectal cancer. This information contributes to a detailed view of this disease. Moreover, the identification and validation of miR-135b may help to identify novel molecular targets and pathways for therapeutic exploitation. Clin Cancer Res; 18(18); 4919–30. ©2012 AACR.
A Long-term Prospective Population Pharmacokinetic Study on Imatinib Plasma Concentrations in GIST Patients
Authors: Eechoute Karel , Fransson Martin N. , Reyners An K. , de Jong Floris A. , Sparreboom Alex , van der Graaf Winette T.A. , Friberg Lena E. , Schiavon Gaia , Wiemer Erik A.C. , Verweij Jaap , Loos Walter J. , Mathijssen Ron H.J. , De Giorgi Ugo
Published: August 2012

Purpose: Imatinib minimal (trough) plasma concentrations after one month of treatment have shown a significant association with clinical benefit in patients with gastrointestinal stromal tumors (GIST). Considering that a retrospective pharmacokinetic analysis has also suggested that imatinib clearance increases over time in patients with soft tissue sarcoma and GIST, the primary aim of this study was to assess systemic exposure to imatinib at multiple time points in a long-term prospective population pharmacokinetic study. As imatinib is mainly metabolized in the liver, our secondary aim was to elucidate the potential effects of the volume of liver metastases on exposure to imatinib.

Experimental Design: Full pharmacokinetic blood sampling was conducted in 50 patients with GIST on the first day of imatinib treatment, and after one, six, and 12 months. In addition, on day 14, and monthly during imatinib treatment, trough samples were taken. Pharmacokinetic analysis was conducted using a compartmental model. Volume of liver metastases was assessed by computed tomographic (CT) imaging.

Results: After 90 days of treatment, a significant decrease in imatinib systemic exposure of 29.3% compared with baseline was observed (P < 0.01). For every 100 cm3 increase of metastatic volume, a predicted decrease of 3.8% in imatinib clearance was observed.

Conclusions: This is the first prospective pharmacokinetic study in patients with GIST, showing a significant decrease of approximately 30% in imatinib exposure after long-term treatment. This means that future "trough level – clinical benefit" analyses should be time point specific. GIST liver involvement, however, has a marginal effect on imatinib clearance. Clin Cancer Res; 18(20); 5780–7. ©2012 AACR.
Antihypertensive drug use. Trends in the United States from 1973 to 1985.
Authors: Gross T P , Wise R P , Knapp D E
Published: August 2012

Hypertension, a major public health problem, often requires drug therapy. We examined trends in outpatient antihypertensive drug use in the United States from 1973 to 1985. The numbers of prescriptions and the diagnostic and drug treatment information were obtained from the National Prescription Audit (Ambler, Pa, IMS America, 1985) the National Disease and Therapeutic Index (Ambler, Pa, IMS America, 1985), ongoing surveys of pharmacies, and office-based physicians. We adjusted drug-use data for the fact that several antihypertensive drugs also have other uses. During the study period, the annual numbers of prescriptions for treatment of hypertension progressively increased from 128.1 to 208.6 million, an average change of 5% per year. In 1973, the three leading classes of antihypertensive drugs were thiazide diuretic agents, peripheral neuronal inhibitors, and central alpha-adrenergic receptor stimulators. By 1985, the thiazide drugs were still the leader, followed by beta-adrenergic receptor blockers and potassium-sparing diuretic drugs. The use trends presented are consistent with surveys indicating increased drug therapy of hypertension from 1960 to the present.
Controlled clinical trials of drug treatment for hypertension. A review.
Authors: Cutler J A , MacMahon S W , Furberg C D
Published: August 2012

We reviewed the designs and major results of 17 large-scale, controlled, clinical trials that reported the effects of drug treatment for hypertension on morbidity or mortality. Seven trials conducted in study populations with more-severe hypertension (diastolic blood pressures 100-120 mm Hg or higher), including the more-severe stratum of the Veterans Administration Trial, showed large reductions in stroke, other "hypertensive" events, and, in one trial, total mortality. Of 11 trials in populations with less-severe hypertension (diastolic blood pressures predominantly below 105 mm Hg), including the less-severe stratum of the Veterans Administration Trial, nine met the criteria for pooling of results. Among the aggregate 43,000 patients in the nine trials who were followed up for an average of 5.6 years, mean diastolic blood pressure reduction was 5.8 mm Hg, and a significant 11% reduction in total mortality was observed. This benefit was largely attributable to a 38% reduction in fatal strokes; nonfatal strokes were similarly reduced. Coronary heart disease mortality was 8% lower in drug treatment than in control groups, but this difference was not significant. A similar result was observed for combined coronary mortality and nonfatal myocardial infarction. A possible explanation for the inconclusive result regarding coronary end points was an adverse trend, observed in several trials, in a subgroup with baseline resting electrocardiographic abnormalities. Because all the trials except the propranolol arm of the Medical Research Council trial used drug regimens based on thiazide-like diuretic agents, and because there are now several new drug classes proposed as initial therapy, additional large-scale clinical trials may need to be considered.
Prognostic value of serum creatinine and effect of treatment of hypertension on renal function. Results from the hypertension detection and follow-up program. The Hypertension Detection and Follow-up Program Cooperative Group.
Authors: Shulman N B , Ford C E , Hall W D , Blaufox M D , Simon D , Langford H G , Schneider K A
Published: August 2012

The Hypertension Detection and Follow-up Program followed up 10,940 persons for 5 years in a community-based, randomized, controlled trial of treatment for hypertension. Participants were randomized to one of two treatment groups, stepped care and referred care. The primary end point of the study was all-cause mortality, with morbid events involving the heart, brain, and kidney as secondary end points. Loss of renal function, ascertained by a change in serum creatinine, was among these secondary events. Baseline serum creatinine concentration had a significant prognostic value for 8-year mortality. For persons with a serum creatinine concentration greater than or equal to 1.7 mg/dl, 8-year mortality was more than three times that of all other participants. The estimated 5-year incidence of substantial decline in renal function was 21.7/1,000 in the stepped-care group and 24.6/1,000 in the referred-care group. Among persons with a baseline serum creatinine level between 1.5 and 1.7 mg/dl, the 5-year incidence of decline was 113.3/1,000 (stepped care) and 226.6/1,000 (referred care) (p less than 0.01). The incidence of decline in renal function was greater in men, blacks, and older adults, as well as in those with higher entry diastolic blood pressure. Among persons with a baseline serum creatinine level greater than or equal to 1.7 mg/dl, serum creatinine concentration declined by 25% or more in 28.6% of stepped-care and 25.2% of referred-care participants. Although the incidence of clinically significant hypercreatininemia in a hypertensive population is low, an elevated serum creatinine concentration is a very potent independent risk factor for mortality. The slightly lower rate of development of hypercreatininemia and the higher rate of improvement in stepped-care compared with referred-care participants is consistent with the belief that aggressive treatment of hypertension may reduce renal damage and the associated increased risk of death.
The renin-angiotensin system during acute myocardial ischemia in dogs.
Authors: Santos R A , Brum J M , Brosnihan K B , Ferrario C M
Published: August 2012

We used the technique of high-performance liquid chromatography combined with radioimmunoassay to establish the profile of angiotensin peptides in the periphery and across the circulation of the dog's heart. Data were obtained before and after blockade of angiotensin converting enzyme, and after acute myocardial ischemia produced by occlusion of the left anterior descending coronary artery. Baseline values of plasma renin activity and immunoreactive angiotensin II were higher in the aortic root than in the coronary sinus but concentrations of angiotensin I and angiotensin-(1-7) were similar. In untreated animals, coronary occlusion produced significant increases in renin activity and arterial and venous levels of angiotensin I and angiotensin II. Inhibition of converting enzyme with benazeprilat (CGS-14,831) increased baseline circulating levels of angiotensin I, whereas angiotensin II and its carboxyl terminal fragments were reduced markedly. Baseline plasma levels of angiotensin-(1-7) and its fragments did not change. Myocardial ischemia in benazeprilat-treated dogs increased plasma renin activity and circulating levels of angiotensin I. Concentrations of angiotensin II and angiotensin-(1-7) did not change either in peripheral blood or across the coronary circulation. These results indicate that angiotensin peptides can be formed endogenously by enzymatic pathways alternate to converting enzyme. Furthermore, these data provide the basis for a further understanding of the role of the renin-angiotensin system after myocardial ischemia.
A reevaluation of the hemodynamics of pheochromocytoma.
Authors: Bravo E , Fouad-Tarazi F , Rossi G , Imamura M , Lin W W , Madkour M A , Wicker P , Cressman M D , Saragoca M
Published: August 2012

We examined the hemodynamic features of 24 untreated patients with surgically proven pheochromocytoma during steady-state periods and compared them with 24 untreated essential hypertensive patients individually matched for sex, age, body surface area, and arterial blood pressure. We found that, despite having 10-fold higher levels of circulating catecholamines, pheochromocytoma patients have hemodynamic characteristics similar to patients with essential hypertension and that, in individual patients, the ratio of circulating norepinephrine to epinephrine had no relation to the hemodynamic profile. In both groups, increased total peripheral resistance is primarily responsible for maintenance of hypertension. These results suggest that, unlike the acute administration of catecholamines, long-term exposure to high levels of circulating catecholamines does not produce hemodynamic responses characteristic of this group of compounds. This might be due in part to desensitization of the cardiovascular system to catecholamines and might explain the clinical observation that some patients can be completely asymptomatic despite harboring an actively catecholamine-secreting pheochromocytoma.
Hypotensive effect of captopril. Role of bradykinin and prostaglandinlike substances.
Authors: Pontieri V , Lopes O U , Ferreira S H
Published: August 2012

Captopril (0.15-10 mg/kg) administration in the anesthetized dog causes immediate hypotension concomitant with an increase in tonus of the assay tissue (cat terminal ileum) superfused with circulating blood (Vane's cascade method). The increase in cat terminal ileum tonus was antagonized by a bradykinin receptor antagonist, L-349b. Treatment of the animals with indomethacin blocked or reversed the hypotensive effect of captopril without affecting the increase in tonus of the cat terminal ileum. Captopril potentiated the hypotension induced by bradykinin injected intra-arterially, and indomethacin reduced the hypotensive effect of intra-arterially injected bradykinin. Addition of captopril or enalapril to the superfusing blood maintained at 37 degrees C in an extracorporeal circuit caused a long-lasting increase in the tonus of the cat terminal ileum. The present results support the hypothesis that immediate hypotension induced by captopril involves a prostaglandin-dependent component possibly resulting from increased bradykinin levels generated in the vicinity of captopril action.
Intravenous fenoldopam versus sodium nitroprusside in patients with severe hypertension.
Authors: Reisin E , Huth M M , Nguyen B P , Weed S G , Gonzalez F M
Published: August 2012

In an open-label study, we compared the efficacy and safety of intravenous infusion of fenoldopam mesylate with that of sodium nitroprusside in patients with severe hypertension or in hypertensive crisis. Both antihypertensive medications were infused at a maximal dose increment of 0.2 microgram/kg/min (fenoldopam) and 1 microgram/kg/min (nitroprusside), with a maximal infusion rate of 1.5 micrograms/kg/min fenoldopam mesylate or 8 micrograms/kg/min sodium nitroprusside. Once the desired reduction in diastolic blood pressure was achieved (less than 110 mm Hg if initial diastolic blood pressure was 120-149 mm Hg, or by at least 40 mm Hg if initial diastolic blood pressure was 150-190 mm Hg), the maximal infusion rate used was maintained for at least 1 hour, and then, the infusion was slowed gradually over 2 hours. After the infusion treatment, patients remained in the hospital for 2 days of follow-up. Both antihypertensive agents successfully controlled the blood pressure in all the patients by the end of the maintenance periods. Between the baseline and the end of the maintenance period, analysis of variance showed that the changes in the variables induced by fenoldopam mesylate did not differ significantly from those induced by sodium nitroprusside. The incidence of side effects listed were similar in both groups of patients. The detection of toxic levels of thiocyanate in two patients treated with nitroprusside, however, shows that fenoldopam might be preferable for the control of a hypertensive crisis or severe hypertension in patients with decreased renal function.
Salt sensitivity and resistance of blood pressure. Age and race as factors in physiological responses.
Authors: Luft F C , Miller J Z , Grim C E , Fineberg N S , Christian J C , Daugherty S A , Weinberger M H
Published: August 2012

To identify characteristics that may contribute to salt sensitivity, we conducted studies of normal subjects who are at risk for hypertension, namely blacks, subjects older than 40 years of age, and first-degree relatives of subjects with essential hypertension. We also formulated definitions for salt sensitivity and resistance with a short-term volume expansion and contraction protocol and additionally from data derived from studies of long-term reduced dietary salt intake. We examined the effects of augmented potassium and calcium intake and also those of sodium as the chloride or the bicarbonate salt. Finally, we sought genetic markers that are associated with salt sensitivity. We found that salt sensitivity is a function of age and is more common in blacks than whites. These groups also have relatively delayed acute salt excretion compared with controls. We were unable to identify effects of gender. Haptoglobin phenotypes (HP 1-1) may facilitate identification of salt-sensitive individuals. A high potassium intake may make individuals less salt sensitive. Sodium chloride and sodium bicarbonate differ in their effects on blood pressure. Sodium chloride augments urinary calcium excretion, but sodium bicarbonate does not. Differences between susceptible and nonsusceptible groups, together with improved knowledge of electrolyte interactions, may facilitate our understanding of salt-sensitive hypertension.
Racial and ethnic modifiers of the salt-blood pressure response.
Authors: Flack J M , Ensrud K E , Mascioli S , Launer C A , Svendsen K , Elmer P J , Grimm R H
Published: August 2012

The relation between sodium and blood pressure is a centuries-old question. A substantial body of epidemiological and experimental data has accumulated that strongly implicates NaCl as having a causal role in the genesis of arterial hypertension. Prospective studies that have been performed in diverse populations that have manipulated NaCl exposure by diet or infusion have repeatedly documented an NaCl pressor effect. Further, similar studies in biracial populations have also demonstrated a greater prevalence of "salt sensitivity" in blacks compared with whites. The reasons for this observation are not entirely clear; however, intrinsic or hypertension-induced renal abnormalities that limit natriuretic capacity, reduced Na+,K(+)-ATPase pump activity, other membrane ion transport disturbances, differential exposure to psychological stressors, greater insulin resistance, and dietary factors (reduced Ca+ and K+ intake) have all been suggested as possibly playing a role. Salt sensitivity appears to be a widespread phenomenon. However, it is critically important to determine what factors account for racial differences in salt sensitivity. Moreover, the prevalence of salt sensitivity in the general population is unknown. Current definitions of salt sensitivity are varied and unidirectional. In comparison with bidirectional criteria (blood pressure increase with salt loading and blood pressure decrease with salt restriction), they are probably inadequate to identify salt-sensitive individuals who manifest less extreme blood pressure change after dietary sodium or plasma volume manipulations. More sensitive criteria for diagnosing salt sensitivity will facilitate a better understanding of racial and ethnic differences in the prevalence of salt sensitivity.
Importance of dietary chloride for salt sensitivity of blood pressure.
Authors: Boegehold M A , Kotchen T A
Published: August 2012

Recent evidence indicates that the anion accompanying sodium plays an important role in determining the magnitude of the blood pressure increase in response to a high dietary intake of NaCl. The purpose of this review is to describe studies of blood pressure responses to selective dietary sodium loading (without chloride) and to selective dietary chloride loading (without sodium) in several experimental models of salt-sensitive hypertension and in hypertensive humans. The full expression of salt sensitivity depends on high dietary intakes of both sodium and chloride. This observation has implications for understanding mechanisms contributing to NaCl-induced hypertension.
High salt intake. Sensory and behavioral factors.
Authors: Beauchamp G K , Engelman K
Published: August 2012

Salt (NaCl) is a ubiquitous component of diets in developed countries. A major reason for this is that people judge many salted foods as more palatable than the same foods without salt. Because recent evidence indicates that an acceptable salt substitute is unlikely, an understanding of the behavioral and sensory factors involved in maintaining high salt preference is a prerequisite to successful programs aimed at reducing intake. Although little evidence exists for a genetic determination of individual differences in consumption and preferred level of salt, more research in this area is necessary. Considerable data support the view that the optimal level of salt in the diet is determined in part by the level an individual is currently consuming; increasing or decreasing customary salt intake, as long as the salt is tasted, increases or decreases the preferred level of salt in food. Although these data are consistent with a hypothesis that optimal salt preferences are learned, other data, from both animal models and human developmental studies, suggest that salt preference has an innate component. Furthermore, early experience with low or high salt diets may have a long-term impact on preferred salt levels. Liking for salt, similar to liking for sweets, has an innate basis that can be modified by individual experience.
Sympathetic drive and vascular damage in hypertension and atherosclerosis.
Authors: Pauletto P , Scannapieco G , Pessina A C
Published: August 2012

Current knowledge of the links between the sympathetic nervous system and vascular damage in hypertension and atherosclerosis is summarized. The main mechanisms leading to the structural changes of the arterial wall as a consequence of enhanced adrenergic drive are reported. Hemodynamic mechanisms, including increase in pressure leading to changes in the arterioles and alteration of flow pattern with impact mainly in the large arteries, respectively, account for the typical target organ damage observed in hypertension and is involved in the development of atherosclerotic lesions. Regarding the direct effect of catecholamines, the atherogenic effects of epinephrine and norepinephrine in the absence of changes in blood pressure and cholesterol levels have been demonstrated in vivo in monkeys and rabbits. In rats, catecholamine administration induces polyploidization of aortic smooth muscle cells in vivo and in vitro. Regarding the effects of lipid metabolism, adrenergic stimulation may induce free fatty acid transformation into triglycerides with secondary increase in very low density lipoprotein plasma levels and decrease of very low density lipoprotein transformation into high density lipoprotein through circulating lipoprotein lipase inhibition. Catecholamines may also increase cholesterol levels of the arterial wall, probably by triggering the acyl-cholesterol-acyl-transferase activity. Finally, indirect evidence of the pathogenetic role played by the sympathetic system in the development of vascular disease derives from the results of experiments showing that sympatholytic agents are capable of reducing both medial hypertrophy and atherogenesis. beta-Blockers, alpha- and beta-blockers, and centrally acting sympatholytic agents not only ameliorate hemodynamics but also appear to inhibit the direct effects of catecholamines on the arterial wall.
Nutrition and hypertension prevention.
Authors: Kotchen T A , Kotchen J M , Boegehold M A
Published: August 2012

Hypertension has been related to both obesity and a high salt intake. Evidence for the associations of blood pressure with body weight and dietary salt intake is summarized. In both adolescents and adults correlations between blood pressure and weight are highly significant, and in longitudinal studies change in blood pressure over time is correlated with change in weight. Correlations between salt intake and blood pressure are less striking, and the results of trials of modest salt restriction demonstrate a small but significant effect on blood pressure. Individuals vary in their susceptibility to salt, and hypertensive individuals are more responsive than normotensive individuals. Dietary deficiencies of potassium and calcium may amplify the effect of a high salt intake on blood pressure. Animal models provide compelling evidence for a genetic component to salt sensitivity of blood pressure. In two hypertension prevention trials, change in blood pressure was more convincingly related to change in weight than to change in dietary salt. Avoidance of obesity, or weight reduction in overweight individuals, should be key strategies for hypertension prevention. Avoidance of salt excess is also appropriate, although currently available trial data do not justify a recommendation of rigorous salt restriction for the entire population.
Is reversal of left ventricular hypertrophy in hypertension beneficial?
Authors: Frohlich E D
Published: August 2012

The left ventricle increases its mass and wall thickness in hypertension as a result of the progressive increase in hemodynamic overload offered by increasing arterial blood pressure and total peripheral resistance. However, evidence is increasing that nonhemodynamic factors may also be important in the development of left ventricular hypertrophy (LVH). This LVH resulting from hypertensive disease conveys an independent risk of premature cardiovascular morbidity and mortality. The specific mechanisms accounting for this increased risk are not known with assurance, although several mechanisms are under active study; they include more prominently ventricular dysrhythmias and myocardial ischemia. It is possible to diminish the increased left ventricular mass with pharmacological agents, although currently it is not known whether this reversal also diminishes the risk associated with LVH. Therefore, at the present time the best means for preventing the risk of LVH is to prevent its development in the first place, and this seems to be preventable through control of arterial blood pressure at the earliest stages of hypertension. Risk may also be diminished in patients with existing LVH who are receiving digitalis or diuretics or who have chronic fluid- and electrolyte-disturbing diseases. Under these circumstances, the careful use and selection of antihypertensive therapy and control of electrolyte balance no doubt will prevent unnecessary morbidity and mortality.
Effects of antihypertensive treatment on composition of cerebral arterioles.
Authors: Hajdu M A , Heistad D D , Ghoneim S , Baumbach G L
Published: August 2012

Treatment of chronic hypertension with cilazapril, but not hydralazine, attenuates changes in distensibility of cerebral arterioles that occur in stroke-prone spontaneously hypertensive rats (SHRSPs). In this study, effects of antihypertensive treatment on composition of cerebral arterioles was determined in SHRSPs. Cilazapril (45 mg/kg/day), an angiotensin converting enzyme (ACE) inhibitor, or hydralazine (18 mg/kg/day) was begun when rats were 3 months of age. Both cilazapril and hydralazine reduced systolic arterial pressure in SHRSPs (from 199 +/- 6 to 122 +/- 7 mm Hg for cilazapril versus 143 +/- 5 mm Hg for hydralazine [mean +/- SEM]; p less than 0.05). Cerebral arterioles were fixed in vivo, and the cross-sectional area of the vessel wall was measured histologically. In SHRSPs, both cilazapril and hydralazine reduced cross-sectional area of the vessel wall to values obtained in Wistar-Kyoto (WKY) rats. Thus, both cilazapril and hydralazine prevented hypertrophy of cerebral arterioles in SHRSPs. Composition of the arteriolar wall was determined with point counting stereology. Cerebral arterioles in SHRSPs contained significantly more smooth muscle and elastin than in WKY rats (1,294 +/- 157 versus 853 +/- 88 microns2, respectively, for smooth muscle and 148 +/- 13 versus 108 +/- 7 microns2, respectively, for elastin (120 +/- 8 microns2) in cerebral arterioles in SHRSPs was similar to that in WKY rats. Treatment with hydralazine was effective in preventing increases in elastin (128 +/- 14 microns2) and in attenuating increases in smooth muscle (1,008 +/- 18 microns2). The ratio of nondistensible (collagen, basement membrane) to distensible (smooth muscle, elastin, endothelium) components was greater in SHRSPs than in WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiovascular reflexes and hypertension.
Authors: Zanchetti A , Mancia G
Published: August 2012

Both arterial baroreceptor reflexes and cardiopulmonary reflexes are modified in human hypertension. The arterial baroreceptor reflex regulation of heart rate, when tested by both vasoactive drug injection and the neck chamber technique, has been shown to be reset and blunted. Arterial baroreceptor reflex control of blood pressure, studied by the neck chamber technique, has been found to be reset to more effectively buffer increases in blood pressure than blood pressure falls, but without any loss of overall reflex sensitivity. Cardiopulmonary reflexes, tested by passive leg raising and by application of lower body negative pressure, are also blunted, and their dysfunction involves not only control of peripheral vasoconstriction but also that of renin release. These readjustments of arterial and cardiopulmonary reflexes make buffering of blood pressure falls or of blood volume changes less effective in hypertension. These readjustments appear to be a consequence, rather than a cause, of hypertension. In particular, the blunting of cardiopulmonary reflexes is induced more by left ventricular hypertrophy than by hypertension. It is very marked in hypertensive patients with echocardiographic evidence of left ventricular hypertrophy and very significantly improves when left ventricular hypertrophy is made to regress by prolonged antihypertensive therapy; significant blunting of cardiopulmonary reflexes has also been found in young athletes with marked left ventricular hypertrophy but normal blood pressure. Whether structural changes in the carotid and aortic wall and possibly in the heart are equally important in the readjustment of arterial baroreceptor reflexes is incompletely clarified at the moment, although there are indications that functional and structural modifications may both be involved.
Sympathetic reactivity during a yohimbine challenge test in essential hypertension.
Authors: Goldstein D S , Grossman E , Listwak S , Folio C J
Published: August 2012

Systemic administration of yohimbine augments sympathetic outflow and blocks presynaptic alpha 2-adrenergic receptors, releasing the sympathetic neurotransmitter norepinephrine (NE) into the bloodstream. The present study examined sympathoadrenal and hemodynamic responses to yohimbine in 19 patients with essential hypertension and 19 normotensive control subjects. Baseline mean values for arterial NE, epinephrine, dihydroxyphenylglycol (the main intraneuronal metabolite of NE), spillover of NE into arterial plasma, and corticotropin did not differ between the hypertensive and normotensive groups. Yohimbine (0.125 mg/kg i.v. bolus followed by 0.001 mg/kg/min infusion for a total of 15 minutes) increased mean arterial pressure in all but one subject (by 13 +/- 2% [SEM] in the normotensive and 17 +/- 2% in the hypertensive group) and increased arterial NE levels in all subjects (by 253 +/- 50 pg/ml in the normotensive and 312 +/- 51 pg/ml in the hypertensive group). Among hypertensive patients, pressor, cardiac, output, and arterial NE responses were distributed bimodally. Patients with large hemodynamic and NE responses to yohimbine typically reported a history of anxiety, depression, or other psychopathology and of marked pressor or tachycardic episodes during emotional stress. In the hypertensive and normotensive groups, baseline arterial NE concentrations predicted the magnitude of pressor responses to yohimbine (r = 0.59, r = 0.54,p less than 0.01), whereas baseline mean arterial pressure was unrelated to the pressor response. A yohimbine challenge test can identify patients with pressor hyperresponsiveness and can distinguish patients with pressor hyperresponsiveness due to excessive sympathoadrenal reactivity from patients with enhanced postsynaptic responsiveness to endogenous NE.
Twenty-year follow-up of hemodynamics in essential hypertension during rest and exercise.
Authors: Lund-Johansen P
Published: August 2012

Central hemodynamics were studied invasively (blood pressure intra-arterially and cardiac output by dye-dilution method) at rest and during exercise in men with essential hypertension and in age-matched normotensive controls. At the start of the study, resting cardiac index, heart rate, oxygen consumption, and mean arterial pressure were approximately 15% higher in those hypertensive patients aged 17-29 years than in normotensive subjects, whereas total peripheral resistance index was similar in both groups. During exercise, the stroke index was reduced and total peripheral resistance index was increased in the hypertensive group. After 10 and then 20 years, central hemodynamics were restudied in the hypertensive patients. The initially high cardiac index/normal total peripheral resistance index pattern changed to a low cardiac index/high resistance pattern at 10- and 20-year follow-up. In 25 patients initially aged 40-49 years, treatment with diuretics, beta-blockers, or a combination of the two normalized diastolic pressure. In spite of adequate blood pressure control, a marked increase in total peripheral resistance and fall in cardiac index and stroke index were also seen in this age group treated over 20 years. The study has shown a progressively abnormal hemodynamic pattern over two decades in patients of different ages with essential hypertension.
Effects of hypertension and aging on platelet-derived growth factor and platelet-derived growth factor receptor expression in rat aorta and heart.
Authors: Sarzani R , Arnaldi G , Takasaki I , Brecher P , Chobanian A V
Published: August 2012

Previous investigations have demonstrated certain similarities in the cellular changes occurring in the arterial wall in response to hypertension and aging. We undertook the current studies to examine the expression of platelet-derived growth factor (PDGF) receptors and ligands and transforming growth factor-beta 1 (TGF-beta 1) in aorta and heart of spontaneously hypertensive rats (SHRs), Wistar-Kyoto (WKY) controls, and Wistar rats studied at ages ranging from 5 to 40 weeks. A progressive increase with age in aortic steady-state messenger RNA (mRNA) levels of the receptor for the B chain of PDGF (PDGF-r beta) was present in all three strains but was greatest in the SHR. The aortic expression of PDGF A or B ligands as well as of the PDGF-r alpha-receptor was not significantly influenced by age or blood pressure. In contrast, in the heart of the SHR and WKY rat, there was an age-related decrease in expression of both PDGF receptors and of the PDGF B chain. Hypertension and aging were associated with increases in steady-state mRNA for TGF-beta 1 in aorta, but in the heart, reductions again were observed. These studies indicate that both hypertension and aging increase the in vivo expression of PDGF-r beta and TGF-beta 1 in aortic tissue. Such changes might be functionally significant and provide autocrine or paracrine mechanisms for regulation of cellular growth in the arterial wall in response to these conditions. The findings also provide further support for the concept that hypertension accelerates the arterial changes associated with aging.
Kidneys and fluids in pressure regulation. Small volume but large pressure changes.
Authors: Guyton A C
Published: August 2012

The human body has multiple blood pressure control mechanisms, each of which serves a special and usually different role in pressure regulation. The nervous pressure controllers usually react within seconds and prevent major rapid changes in pressure when acute extraneous forces act on the circulatory system. Then, within minutes to hours, several intermediately acting pressure controllers become activated. Among the more important of these are the renin-angiotensin-vasoconstriction system and the shift of fluid volume between the blood and interstitial fluids. Finally, after several hours to days, the kidneys readjust body fluid volumes, especially the extracellular fluid and blood volumes, to bring the pressure to a very precise level. This final adjustment usually requires little change in body fluid volume for two reasons. First, the other pressure controllers often have already made most of the needed pressure adjustments. Second, the increase in fluid volume required to cause a major increase in blood pressure is usually surprisingly small; this is true because the whole body blood flow autoregulation mechanism causes a secondary increase in total peripheral resistance.
Effects of insulin on renal sodium excretion.
Authors: Gupta A K , Clark R V , Kirchner K A
Published: August 2012

The ability of insulin to decrease urinary sodium excretion has been recognized for more than 30 years. While most investigators agree that this occurs predominantly through increased tubular sodium reabsorption, the nephron segments at which insulin exerts this effect in vivo remain controversial. Additionally, little information is available in mammalian systems on the mechanism of the insulin response or its relation to other hormonal systems important in the regulation of tubular sodium transport. Data from amphibian transporting epithelia suggest a potential for interactions between insulin and several other peptide hormones in the regulation of sodium transport. The following discussion attempts to review our knowledge of the effects of insulin on renal sodium reabsorption and describes new data suggesting that insulin's antinatriuretic response is dependent on antidiuretic hormone but independent of the angiotensin and prostaglandin systems.