bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and characterization of a radioiodinated photoaffinity probe for the alpha 1-adrenergic receptor.
Authors: Seidman C E , Hess H J , Homcy C J , Graham R M
Published: August 2012

A radioiodinated aryl azide analog, 2-[4-(4-azido-3- iodobenzoyl ) piperazin -1-yl]-4-amino-6, 7- dimethoxyquinazoline [(125I] CP65 ,526), of the highly selective alpha 1-adrenergic antagonist prazosin was synthesized and characterized using rat hepatic plasma membranes. Prior to photolysis, this ligand bound with high affinity (Kd 0.3 nM), stereoselectively and in a saturable manner to sites with an alpha 1-adrenergic specificity. When membranes pretreated with [125I] CP65 ,526 were irradiated with ultraviolet light, the ligand incorporated irreversibly into the receptor-binding sites, also with typical alpha 1-adrenergic specificity. Sodium dodecyl sulphate polyacrylamide gel electrophoresis of such labeled membranes followed by radioautography revealed major bands at Mr = 77,000, 68,000, and 59,000 daltons. Labeling of each of these bands was inhibitable by a variety of adrenergic ligands, stereoselectively and with a specificity typical of the alpha 1-adrenergic receptor. Smaller peptides with molecular weights of 42,000 and 31,000 daltons also displayed prazosin-inhibitable [125] CP65 ,526-binding. However, as the labeling of these protein species was not inhibitable by other adrenergic agonists or antagonists, they are unlikely to represent subunits of the receptor. Further evidence that [125I] CP65 ,526 incorporates covalently upon photolysis was the ability to specifically label immunoglobulin heavy and light chains of an antiserum that recognized both this ligand and the parent compound, prazosin. This new, radioiodinated, high-affinity probe should thus be uniquely valuable for the molecular characterization of the alpha 1-adrenergic receptor.
Complementary DNA sequences of renin. State-of-the-art review.
Authors: Murakami K , Hirose S , Miyazaki H , Imai T , Hori H , Hayashi T , Kageyama R , Ohkubo H , Nakanishi S
Published: August 2012

The primary structure of human renin precursor was deduced from its complementary DNA (cDNA) sequence. The predicted sequence consists of 406 amino acids with a pre- and a prosegment carrying 20 and 46 amino acids, respectively. A high degree of sequence homology, especially in the catalytically important region, was found upon comparison of the mouse and human renins. An overall homology, including presequence between the two renins, is 68.7%. Close similarities were also observed in the primary structure of renins and other aspartyl proteinases with defined three-dimensional structures, suggesting a tertiary structure for renin that is similar to the other enzymes. A bilobal model of the tertiary structure of human renin with two approximately equal domains separated by a cleft was constructed using the homology of amino acid sequence of renins and other aspartyl proteinases. These results indicate that human kidney renin is homologous with mouse submandibular renin in primary and tertiary structures, proteolytic processing, and catalytic apparatus with small differences. The major structural difference distinguishing the two renins was the presence of the two possible glycosylation sites in human kidney renin, which was not observed in mouse submandibular gland renin.
Determinants of vascular hemodynamic characteristics.
Authors: Mulvany M J
Published: August 2012

This discussion concerns some of the parameters affecting the hemodynamic characteristics of a blood vessel: impedance, flow resistance, and vascular wall stiffness. The parameters of greatest importance are the vessel internal radius (ri) and the elastic modulus of the vascular wall. When the smooth muscle cells in the vascular wall are inactive, the elastic modulus is determined by the combined elastic modulus of the structural components of the connective tissue, primarily elastin and collagen fibers. This combined elastic modulus is found to be proportional to the wall stress. From the proportionality factor and from knowledge of the vessel dimensions in the unpressurized vessel, one can predict the relation of ri to transmural pressure. When a vessel is activated under isometric conditions, the wall force and elastic modulus are increased by the force and elastic modulus of the smooth muscle cells. Under isobaric conditions, however, the effect of activation is to reduce both the ri and the elastic modulus. Pathologic changes resulting either in a stiffening of the connective tissue components, in an increased wall cross-sectional area, which encroaches on the lumen, or in an increased smooth muscle quantity will all cause increases in vascular characteristic impedance, vascular flow resistance, and vascular wall stiffness.
Regression of structural cardiovascular changes by antihypertensive therapy.
Authors: Motz W , Strauer B E
Published: August 2012

Left ventricular (LV) hypertrophy is the structural adaptation of the heart in response to chronic LV pressure load. Studies in spontaneously hypertensive rats (SHR), which represent a model of genetically determined arterial hypertension, reveal that cardiac hypertrophy can be controlled by long-term blood pressure normalization with the use of various antihypertensive agents, such as arterial vasodilatators (hydralazine), converting enzyme inhibitors (captopril), beta-receptor blockers (metoprolol), antiadrenergic substances (alpha-methyldopa, guanethidine), and calcium antagonists (nifedipine, felodipine). Additional drug-specific effects modulate the mechanical effect of LV systolic unloading on cardiac hypertrophy: after a combined treatment with metoprolol and hydralazine, LV hypertrophy was quantitatively lower than after single hydralazine therapy, although blood pressure had been lowered to the same extent. LV collagen concentration remained unchanged when medical treatment prevented the development of myocardial hypertrophy. However, when therapy was begun after hypertrophy had been completely established, reversal of hypertrophy was associated with an increased LV collagen concentration. In concentric LV hypertrophy with normal systolic wall stress, LV function was not impaired. Consequently, antihypertensive therapy could not improve LV function in this condition. However, in the case of LV dilatation with increased systolic wall stress, LV systolic unloading by antihypertensive therapy could considerably improve LV pumping function. Preventive studies reveal that chronic blood pressure control can prevent cardiac dysfunction in SHR, as frequently is seen in the later phase of untreated arterial hypertension in humans.
Regression of structural cardiovascular changes by antihypertensive therapy.
Authors: Hansson L , Sivertsson R
Published: August 2012

Structural vascular changes, consisting mainly of smooth muscle cell hypertrophy of the arterioles, have been found in various hypertensive animal models as well as in hypertensive patients. Although such changes may be to some extent a primary phenomenon in primary or essential hypertension, there is ample proof that an elevation in arterial pressure over a period of time will cause hyperplasia of the media in the resistance vessels; thus, this change is secondary to the rise in pressure. Studies in various animal models have shown that such structural arteriolar changes are reversible if a long-term reduction in arterial pressure can be obtained. In hypertensive patients reversibility of such changes has been demonstrated in some vascular beds as a result of chronic antihypertensive therapy. However, no complete "normalization" has ever been shown, probably because of inadequate reduction of arterial pressure and perhaps also because long-standing hypertension induces fibrosis of the arteriolar media, which is less likely to be positively affected by a lowering of blood pressure. In humans, some vascular beds, for example, the muscle vessel bed of the calves, appear to be less suitable for the demonstration of regression of structural changes. This could be due to erect posture, which increases the transmural pressure in these vessels, since the effect of gravity is added to the intravascular pressure. Finally, it is conceivable that effects other than the reduction in arterial pressure could play a role. Thus, antihypertensive drugs with a vasodilating action appear to be more effective in reducing structural vascular changes than drugs that do not have a vasodilating effect, even if an identical degree of blood pressure reduction is obtained.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of various drug regimens.
Authors: Littler W A
Published: August 2012

Before the introduction of effective hypotensive drugs in the early 1950s, survival from untreated hypertension was closely related to blood pressure level. Cardiac failure, stroke, and uremia were the commonest causes of death. Reduction of blood pressure by antihypertensive drugs in malignant hypertension quickly showed that life could be prolonged and vascular damage arrested. The efficacy of antihypertensive drugs in nonmalignant hypertension has been demonstrated in several randomized controlled trials, but the benefit seems to decline the lower the initial blood pressure. Antihypertensive drug treatment has reduced the incidence of cardiac failure, stroke, and uremia, but it has not clearly been shown to reduce the frequency of myocardial infarctions. At present, the choice of an antihypertensive agent is based on its ability to lower pressure in relation to the possible adverse side effects that it produces. The reduction of blood pressure seems to be the basis for the therapeutic effect, rather than any other special property of the drug.
Hypertension as a vascular response to injury.
Authors: Schwartz S M
Published: August 2012

Both atherosclerosis and hypertension are characterized by smooth muscle proliferation. The atherosclerotic lesion is characterized by proliferation of smooth muscle in the arterial intima of large arteries. Complication of this proliferation by lipid accumulation and thrombosis leads to death. Smooth muscle proliferation in hypertensive vascular disease is characteristic of small arteries. Again, the result is increased wall mass with a narrowed lumen. The small vessel change is thought to be a cause of the increased peripheral resistance of high blood pressure. The common features in atherosclerosis and hypertension suggest that control of cell proliferation may be critical in treating both diseases.
Different types of smooth muscle hypertrophy.
Authors: Johansson B
Published: August 2012

Smooth muscles respond to changes in their working situation by rapid and pronounced adjustments of functional and structural properties. We have examined the effects of experimental portal hypertension on the smooth muscle of the rat portal vein in a series of studies that are summarized in this review. Within one week following partial ligation of the hepatic branches of the vein, the cross-sectional area of its muscle coat increased about twofold owing to increase in the size of the individual muscle cells. The hypertrophy was associated with membrane hyperpolarization, inhibition of spontaneous electrical and mechanical activity, and reduced sensitivity to exogenous norepinephrine. Active force per unit of cross-sectional area decreased, but metabolic studies indicated improved tension economy compared with normal portal veins. The literature on different types of hypertrophy in intestinal smooth muscle, urinary bladder, and uterus is briefly reviewed. The importance of mechanical distention and chemical trophic factors as stimuli for the growth processes is discussed.
Structural cardiovascular adaptation and the consequences for baroreflexes.
Authors: Zanchetti A , Mancia G
Published: August 2012

Changes in arterial baroreflex control of the circulation occur in experimental and in human hypertension. Hypertension can affect the afferent, the central, and the efferent portions of the baroreflex. Structural cardiovascular adaptation due to stiffening of the vascular wall is usually thought to influence the afferent component of the baroreflex, but it can also influence the effector component. Resetting of central mechanisms of the baroreflex also occurs. Cardiopulmonary baroreflexes appear to be enhanced in young spontaneously hypertensive rats (SHR) and in borderline hypertensive patients, probably because of reduced venous compliance that shifts blood to the cardiovascular compartments (atrium, ventricle) where the receptors are located. Progression of cardiac hypertrophy is likely to reverse this enhanced reflex activity. In hypertension the carotid sinus reflex appears to be readjusted in such a way as to protect against a further rise in blood pressure, rather than providing protection, as in normotension, against a fall in blood pressure. Thus the homeostatic functions of the reflex are maintained and readjusted to the needs of the hypertensive circulation. It is interesting to speculate that increased afferent inhibition from "volume" receptors in the cardiopulmonary area may represent a homeostatic attempt to buffer an early increase in sympathetic activity to the kidney.
True versus immunoreactive angiotensin II in human plasma.
Authors: Nussberger J , Brunner D B , Waeber B , Brunner H R
Published: August 2012

To measure specifically angiotensin-(1-8)octapeptide, peptides were extracted from 2 ml of plasma by reversible adsorption to bonded-phase silica. The angiotensin-(1-8)octapeptide was then isolated by isocratic reversed-phase high-performance liquid chromatography and quantified by radioimmunoassay. The extraction recovery of 125I-angiotensin II added to 2 ml of plasma was 99 +/- 2% (mean +/- SD). The overall recovery of 5, 10, and 20 fmol unlabeled angiotensin II added to 1 ml of plasma was 80 +/- 10%. The coefficient of variation for within-assay precision was 0.06 and for between-assay precision 0.13. The detection limit was 0.4 fmol/ml. Buffer and plasma blanks were below the detection limit. Normal subjects on a free diet in supine position averaged 4.2 +/- 1.7 fmol/ml angiotensin-(1-8)octapeptide. Furosemide (40 mg p.o.) and standing increased these values to 22 +/- 7.6 fmol/ml. In four volunteers, immunoreactive "angiotensin II" (more or less angiotensin-like material) was measured serially before and after converting-enzyme inhibition (Hoe 498) with conventional Dowex extraction. At peak inhibition, plasma immunoreactive "angiotensin II" levels decreased by only 44%. In contrast, angiotensin-(1-8)-octapeptide isolated by high-performance liquid chromatography completely disappeared. In hypertensive patients receiving long-term treatment with enalapril, plasma levels of angiotensin-(1-8)octapeptide fell from 2.7 +/- 0.9 to 0.9 +/- 0.3 fmol/ml (mean +/- SEM) 2 hours after the morning dose, whereas levels of immunoreactive "angiotensin II" were not significantly changed. We found that this sensitive method specifically measured angiotensin-(1-8)octapeptide and demonstrated that true angiotensin II virtually disappears during converting-enzyme inhibition.
Angiotensin increases cytosolic free calcium in cultured vascular smooth muscle cells.
Authors: Brock T A , Alexander R W , Ekstein L S , Atkinson W J , Gimbrone M A
Published: August 2012

We used the calcium-sensitive fluorescent indicator quin 2 to monitor changes in cytosolic free calcium concentration ([Ca2+]i) associated with angiotensin II receptor activation in cultured vascular smooth muscle cells isolated from rat aorta. Resting [Ca2+]i in unstimulated vascular smooth muscle cells was 198 +/- 7 nM. Angiotensin II induced concentration-dependent rapid increases in [Ca2+]i (threshold congruent to 10(-11) M; effective concentration, 50% congruent to 5 X 10(-10) M; maximum congruent to 10(-8) M); the rate of increase in [Ca2+]i also appeared to be concentration dependent. The angiotensin II-induced changes were completely blocked by the angiotensin II receptor antagonist [Sar1, Ile8]-angiotensin II. In the presence of extracellular calcium, 10(-8) M angiotensin II induced an increase in [Ca2+]i that reached peak values of five to six times the resting levels within 15 seconds, followed by a gradual decline to a plateau at two to three times the resting level. When EGTA was added to chelate external calcium, the angiotensin II-induced increases in peak [Ca2+]i were attenuated and the plateau phase was abolished. These data show that (1) quin 2 can be used in cultured vascular smooth muscle cells to study changes in calcium homeostasis induced by angiotensin II, and (2) angiotensin II acts on cultured vascular smooth muscle cells to cause a rapid increase in [Ca2+]i that appears to depend on both the mobilization of intracellular calcium and the influx of extracellular calcium.
Unconjugated and conjugated urinary 19-nor-deoxycorticosterone glucosiduronate. Elevated levels in essential hypertension.
Authors: Griffing G T , Wilson T E , Melby J C
Published: August 2012

The mineralocorticoid 19-nor-deoxycorticosterone (19-nor-DOC) is present in the urine of rats and humans in unconjugated and conjugated forms. This study sought to compare levels of unconjugated and conjugated 19-nor-DOC glucosiduronate in essential hypertensive subjects. The essential hypertensive and normal subjects were admitted to a metabolic unit, and plasma and urine were collected at fixed intervals on a fixed-electrolyte intake (Na+, 128 mEq/day, K+, 80 mEq/day). The 19-nor-DOC was purified by chromatography and measured by radioimmunoassay. Unconjugated urinary 19-nor-DOC was elevated in essential hypertensive subjects (195 +/- 21 [SE] ng/day; n = 21) compared with levels in normal subjects (118 +/- 30 [SE] ng/day; n = 13, p less than 0.05). Two essential hypertensive subjects had very high levels (673, 729 ng/day), while levels in seven essential hypertensive subjects were below 118 ng/day. Conjugated 19-nor-DOC glucosiduronate also was elevated in essential hypertensive subjects (950 +/- 88 [SE] ng/day; n = 8) compared with levels in normal subjects (680 +/- 90 [SE] ng/day; n = 5). Seven of eight essential hypertensive subjects had levels greater than 680 ng/day. The unconjugated and conjugated urinary 19-nor-DOC glucosiduronate levels were positively correlated in both of these groups (rho = 0.82, p less than 0.01). Other test results including plasma renin activity, plasma aldosterone levels, aldosterone secretion rates, and plasma and urine electrolyte levels were not different between groups. These results indicate that essential hypertensive subjects have increased 19-nor-DOC excretion, which is reflected by increases in both unconjugated and conjugated glucosiduronate forms.(ABSTRACT TRUNCATED AT 250 WORDS)
Sodium channel blockers are vasodilator as well as natriuretic and diuretic agents.
Authors: Haddy F J , Pamnani M B , Swindall B T , Johnston J , Cragoe E J
Published: August 2012

Amiloride (100-400 micrograms) injected intra-arterially into the dog forelimb perfused at constant flow produced a prompt but transient dose-dependent decrease in perfusion pressure. Intravenous injection lowered systemic arterial pressure, but effects were small and transient except in doses exceeding 10 mg. We tested 11 analogues of amiloride, 3 other diuretics, and a hypotensive imidazopyrazine for vasodilator activity in the dog forelimb and found one analogue, 6-iodo-amiloride, with twice the activity of amiloride. Intravenous injection of 3 mg of 6-iodo-amiloride promptly decreased systemic arterial pressure and forelimb perfusion pressure 65 and 47 mm Hg respectively. The decreases with 3 mg of amiloride were only 5 and 23 mm Hg respectively. Intravenous infusion of 17 to 77 mg of 6-iodo-amiloride produced diuresis, natriuresis, and antikaliuresis and, with the higher doses, hypotension. The latter occurred promptly on starting the infusion and was sustained for the duration of the infusion. Wistar rats responded to an intravenous infusion of 0.38 mg/100 g in 11 minutes in the same manner. In the spontaneously hypertensive rat, this same dose produced a large, sustained antihypertensive effect with little change in the urinary parameters. These studies indicate that 6-iodo-amiloride is a vasodilator and a vasodepressor as well as natriuretic and diuretic in the normal dog and rat and that it produces a sustained, large fall in blood pressure, independently of urinary effects, in the spontaneously hypertensive rat. These results suggest that 6-iodo-amiloride and other sodium channel blockers might be useful as vasodilatory antihypertensive agents, particularly in those types of hypertension characterized by increased vascular smooth muscle cell permeability to sodium.
The antihypertensive function of the kidney. Its elucidation by captopril plus unclipping.
Authors: Muirhead E E , Pitcock J A , Nasjletti A , Brown P , Brooks B
Published: August 2012

Unclipping the one-kidney, one-clip hypertensive rat during a free flow of urine caused the blood pressure to return to normal levels within about 3 hours. We found that administration of captopril plus unclipping caused the blood pressure to return to normal in minutes (17 +/- 4). Ureterocaval anastomosis plus captopril plus unclipping also caused the blood pressure to return to normal in minutes (8.8 +/- 2). Thus, the potentiation of the drop in blood pressure does not seem to be due to a volume effect. Administration of indomethacin and aprotinin did not prevent a rapid decline of the blood pressure after unclipping, but the decline was less rapid than that occurring after captopril and unclipping, which suggests that prostaglandin may have some effect on this mechanism. Saralasin administration did not potentiate the antihypertensive action of captopril plus unclipping. Chemical papillectomy prevented the drop in blood pressure after unclipping. The bolus dose of captopril to the hypertensive rat often caused a transient depressor effect resembling that due to the antihypertensive neutral renomedullary lipid, which suggests secretion of this lipid into the blood. The renomedullary interstitial cells accumulated large lipid granules after captopril administration. These cells also degranulated after unclipping. These findings are consistent with the hypothesis that the renal papilla secretes an antihypertensive hormone after unclipping. At present, antihypertensive neutral renomedullary lipid is the main putative hormone.
Oscillatory contractions in tail arteries from genetically hypertensive rats.
Authors: Lamb F S , Myers J H , Hamlin M N , Webb R C
Published: August 2012

This study characterizes a cellular mechanism for oscillatory contractions induced by norepinephrine in vascular smooth muscle from spontaneously hypertensive stroke prone rats (SHRSP). Helically cut strips of tail arteries from SHRSP and normotensive Wistar-Kyoto rats (WKY) were mounted in a muscle bath for measurement of isometric force generation. Norepinephrine-induced responses of arteries from SHRSP were characterized by fluctuations in contractile activity, whereas those in arteries from WKY remained constant with time. The magnitude of the oscillatory contractile activity (frequency X mean amplitude) varied directly with norepinephrine concentration (5.9 X 10(-9) to 1.8 X 10(-7) M). The oscillatory contractile activity varied inversely with the potassium concentration (3-20 mM) of the buffer solution and directly with the calcium concentration (0.1-5.0 mM) of the buffer solution. The oscillatory activity was converted to maintained contraction by barium (10(-4) M), quinidine (3 X 10(-6) M), sparteine (10(-3) M), D-600 (10(-7) M), and nifedipine (10(-8) M). Tetraethylammonium and 3,4-diaminopyridine, inhibitors of voltage-dependent potassium channels, did not alter the oscillatory contractile activity induced by norepinephrine. These observations suggest that oscillatory contractile activity in tail arteries from SHRSP is caused by an abnormal variation in potassium efflux during stimulation with norepinephrine. The altered potassium efflux appears to be related to calcium entry, which is sensitive to inhibition by channel blockers. This altered membrane property may contribute to changes in vascular sensitivity in hypertension.
beta-Adrenergic and cholinergic receptors in hypertension-induced hypertrophy.
Authors: Vatner D E , Kirby D A , Homcy C J , Vatner S F
Published: August 2012

Perinephritic hypertension was produced in dogs by wrapping one kidney with silk and removing the contralateral kidney 1 week later. Mean arterial pressure rose from 104 +/- 3 to 156 +/- 11 mm Hg, while left ventricular free wall weight, normalized for body weight, was increased by 49%. Muscarinic, cholinergic receptor density measured with [3H]-quinuclidinyl benzilate, fell in hypertensive left ventricles (181 +/- 19 fmol/mg, n = 6; p less than 0.01) as compared with that found in normal left ventricles (272 +/- 16 fmol/mg, n = 8), while receptor affinity was not changed. The beta-adrenergic receptor density, measured by binding studies with [3H]-dihydroalprenolol, rose in the hypertensive left ventricles (108 +/- 10 fmol/mg, n = 7; p less than 0.01) as compared with that found in normal left ventricles (68.6 +/- 5.2 fmol/mg, n = 15), while beta-adrenergic receptor affinity decreased in the hypertensive left ventricles (10.4 +/- 1.2 nM) compared with that found in the normal left ventricles (5.0 +/- 0.7 nM). Plasma norepinephrine levels were similar in the two groups, but myocardial norepinephrine levels were depressed (p less than 0.05) in dogs with hypertension. Moderate left ventricular hypertrophy induced by long-term aortic banding in dogs resulted in elevations in beta-adrenergic receptor density (115 +/- 14 fmol/mg) and decreases in affinity (10.4 +/- 2.2 nM) similar to those observed in the dogs with left ventricular hypertrophy induced by hypertension. Thus, our results suggest that perinephritic hypertension in the dog induces divergent effects on cholinergic and beta-adrenergic receptor density. The increased beta-adrenergic receptor density and decreased affinity may be a characteristic of left ventricular hypertrophy rather than hypertension.
Increased plasma renin during renin inhibition. Studies with a novel immunoassay.
Authors: Hofbauer K G , Wood J M , Gulati N , Heusser C , Ménard J
Published: August 2012

The response of renin release to the administration of renin inhibitors cannot be studied with conventional enzymatic methods used to measure plasma renin. In the present experiments, a novel multirange enzyme-linked immunosorbent assay for human and primate renin was used to investigate the changes in plasma immunoreactive renin after renin inhibition. A potent and long-acting statine-containing renin inhibitor, CGP 29 287, was injected in conscious marmosets after mild or severe sodium depletion. In mildly sodium-depleted marmosets, CGP 29 287 (0.1 mg/kg i.v.) reduced mean arterial blood pressure and completely inhibited plasma renin activity for up to 30 minutes. This response was associated with a transient increase in plasma immunoreactive renin concentration. After a dose of 1.0 mg/kg i.v., the reduction of mean arterial pressure and the complete inhibition of plasma renin activity persisted for up to 120 minutes. These effects were accompanied by a sustained increase in plasma immunoreactive renin concentration. In severely sodium-depleted marmosets, CGP 29 287 (1.0 mg/kg i.v.) induced a marked fall in systolic blood pressure and complete inhibition of plasma renin activity within 30 minutes of injection. Plasma immunoreactive renin levels increased to 257% of pretreatment values. The converting-enzyme inhibitor enalaprilat (2 mg/kg i.v.) induced a fall in systolic blood pressure of similar magnitude, which was accompanied by an increase in plasma renin activity. Levels of plasma immunoreactive renin increased to 210% of pretreatment values. Hydralazine (0.2 mg/kg i.v.) did not increase plasma renin activity or plasma immunoreactive renin levels despite a comparable hypotensive effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Specificity of substrate analogue inhibitors of human urinary kallikrein.
Authors: Okunishi H , Burton J , Spragg J
Published: August 2012

A series of acetyl-peptidyl-amides containing the amino acid sequence around the Arg-Ser kallikrein cleavage site of bovine kininogen were synthesized and tested for their ability to inhibit both the kinin-releasing activity and the amidase activity of purified human urinary kallikrein. The substrate analogues were competitive inhibitors for human urinary kallikrein and the heptapeptides (P4-P3'), hexapeptides (P3-P3'), and pentapeptides (P2-P3') gave Ki values of 140, 64, and 18 microM respectively, while the tetrapeptides (P1-P3'), tripeptides (P1'-P3') and dipeptides (P2'-P3') had little or no inhibitory activity. The effective analogues had neither kinin-like nor kinin-blocking activity on the rat uterus either before or after exposure to human urinary kallikrein. The effective human urinary kallikrein inhibitors were further examined for their effect on other serine proteases, including human plasma kallikrein, plasmin, complement components (C1s, C1r), bovine coagulation factors (IIa, IXa, and Xa), elastase, and trypsin. These peptides showed little inhibition of the circulating serine proteases but yielded a Ki for the nonspecific protease trypsin in the microM range. These results should provide the basis for the development of highly specific tissue kallikrein inhibitors to aid in elucidating the in vivo role(s) of tissue kallikreins.
The anteroventral third ventricle region. Participation in the regulation of blood pressure in conscious dogs.
Authors: Marson O , Chernicky C L , Barnes K L , Diz D I , Slugg R M , Ferrario C M
Published: August 2012

The anteroventral third ventricle (AV3V) region plays an important role in fluid and electrolyte balance and cardiovascular control in the rat; however, experiments in other species have raised questions about the universality of findings in the rat. The effects of discrete lesions placed within the AV3V area on hydromineral balance, the pressor response to angiotensin II given intravenously, and the initiation of a renin-dependent model of hypertension were examined in the dog. A transpharyngeal approach to the optic chiasm enabled us to destroy only the anterior aspects of the AV3V region (aAV3V group) or to include the entire nucleus medianus (NM) as well (aAV3V + NM group). Lesions of the aAV3V caused polydipsia and transient hypernatremia and hyperosmolality. In contrast, adipsia and a sustained increase in plasma sodium levels and osmolality were observed in dogs with lesions of the aAV3V plus the entire NM. Neither lesion altered baseline arterial pressure, heart rate, plasma levels of catecholamines and vasopressin, or total plasma protein levels. Only in aAV3V + NM lesioned dogs was there a tendency for plasma angiotensin II immunoreactivity to be elevated above control values at 2 and 4 days after operation. Neither lesion attenuated the pressor response to intravenous angiotension II or the initiation of renal hypertension induced by aortic coarctation. As observed in other species, structures within the AV3V region participate in hydromineral balance in the dog; however, in the dog portions of the NM dorsal to the AV3V region are essential for the mediation of drinking behavior.(ABSTRACT TRUNCATED AT 250 WORDS)
Paclitaxel-Coated Versus Uncoated Balloon Angioplasty Reduces Target Lesion Revascularization in Patients With Femoropopliteal Arterial Disease
Authors: Cassese Salvatore , Byrne Robert A. , Ott Ilka , Ndrepepa Gjin , Nerad Mateja , Kastrati Adnan , Fusaro Massimiliano
Published: August 2012

Background—

In disease of the femoropopliteal artery, paclitaxel-coated balloon (PCB) therapy improved angiographic outcomes as compared with uncoated balloon (UCB) angioplasty. Nevertheless, it remains uncertain whether PCB may reduce the need for reintervention.

Methods and Results—

We searched Medline, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), scientific session abstracts, and relevant web sites for trials of PCB versus UCB angioplasty. Key words were: “superficial femoral artery,” “popliteal artery,” “angioplasty,” “drug-eluting balloon,” “paclitaxel-eluting balloon,” and “randomized trial.” Inclusion criteria were: (1) randomized design; (2) intention-to-treat analysis; and (3) ≥6-month follow-up. Exclusion criteria were: (1) vessel treated other than femoropopliteal artery; (2) device used other than PCB/UCB; and (3) irretrievable or duplicated data. No restrictions (language, publication date, or status) were applied. The primary end point was target lesion revascularization. Secondary end points were: angiographic binary restenosis and late lumen loss and all-cause mortality. A total of 381 patients enrolled in 4 randomized trials were included (PCB, n=186 versus UCB, n=195). Median follow-up was 10.3 months. Angioplasty with PCB versus UCB reduces target lesion revascularization (12.2% versus 27.7%; OR, 0.22; 95% CI, 0.13–0.38;
P
<0.00001), angiographic restenosis (18.7% versus 45.5%; OR, 0.26; 95% CI, 0.14–0.48;
P
<0.0001), and late lumen loss (range, −0.05 to 0.50 mm versus 0.61–1.7 mm; weighted mean difference, −0.75 mm; 95% CI, −1.06 to −0.45;
P
<0.00001). No mortality difference was observed for PCB versus UCB (2.1% versus 3.2%; OR, 0.99; 95% CI, 0.39–2.49;
P
=0.98).

Conclusions—

In femoropopliteal arterial disease, PCB therapy is associated with superior antirestenotic efficacy as compared with UCB angioplasty with no evidence of a differential safety profile.
Nitroxyl-Mediated Disulfide Bond Formation Between Cardiac Myofilament Cysteines Enhances Contractile Function
Authors: Gao Wei Dong , Murray Christopher I. , Tian Ye , Zhong Xin , DuMond Jenna F. , Shen Xiaoxu , Stanley Brian A. , Foster D. Brian , Wink David A. , King S. Bruce , Van Eyk Jennifer E. , Paolocci Nazareno
Published: August 2012

Rationale:

In the myocardium, redox/cysteine modification of proteins regulating Ca
2+
cycling can affect contraction and may have therapeutic value. Nitroxyl (HNO), the one-electron-reduced form of nitric oxide, enhances cardiac function in a manner that suggests reversible cysteine modifications of the contractile machinery.

Objective:

To determine the effects of HNO modification in cardiac myofilament proteins.

Methods and Results:

The HNO-donor, 1-nitrosocyclohexyl acetate, was found to act directly on the myofilament proteins, increasing maximum force (F
max
) and reducing the concentration of Ca
2+
for 50% activation (Ca
50
) in intact and skinned cardiac muscles. The effects of 1-nitrosocyclohexyl acetate are reversible by reducing agents and distinct from those of another HNO donor, Angeli salt, which was previously reported to increase F
max
without affecting Ca50. Using a new mass spectrometry capture technique based on the biotin switch assay, we identified and characterized the formation by HNO of a disulfide-linked actin–tropomyosin and myosin heavy chain–myosin light chain 1. Comparison of the 1-nitrosocyclohexyl acetate and Angeli salt effects with the modifications induced by each donor indicated the actin–tropomyosin and myosin heavy chain–myosin light chain 1 interactions independently correlated with increased Ca
2+
sensitivity and force generation, respectively.

Conclusions:

HNO exerts a direct effect on cardiac myofilament proteins increasing myofilament Ca
2+
responsiveness by promoting disulfide bond formation between critical cysteine residues. These findings indicate a novel, redox-based modulation of the contractile apparatus, which positively impacts myocardial function, providing further mechanistic insight for HNO as a therapeutic agent.
Tracking Chromatid Segregation to Identify Human Cardiac Stem Cells That Regenerate Extensively the Infarcted Myocardium
Authors: Kajstura Jan , Bai Yingnan , Cappetta Donato , Kim Junghyun , Arranto Christian , Sanada Fumihiro , D'Amario Domenico , Matsuda Alex , Bardelli Silvana , Ferreira-Martins João , Hosoda Toru , Leri Annarosa , Rota Marcello , Loscalzo Joseph , Anversa Piero
Published: August 2012

RETRACTION

This article has been retracted:

Circ Res
. 2018;123:e00. DOI: 10.1161/RES.0000000000000253.
Degradation in the Fatigue Resistance of Dentin by Bur and Abrasive Air-jet Preparations
Authors: Majd H. , Viray J. , Porter J.A. , Romberg E. , Arola D.
Published: August 2012

The objective of this investigation was to distinguish whether the instruments commonly used for cutting dentin cause degradation in strength or fatigue behavior. Beams of coronal dentin were obtained from unrestored 3rd molars and subjected to either quasi-static or cyclic flexural loading to failure. The surfaces of selected beams were treated with a conventional straight-sided bur or with an abrasive air jet laden with glass particles. Under monotonic loading, there was no difference in the strength or Weibull parameters obtained for the control or treated beams. However, the fatigue strength of dentin receiving bur and air-jet treatments was significantly lower (p ≤ 0.0001) than that of the control. The bur treatment resulted in the largest overall degree of degradation, with nearly 40% reduction in the endurance limit and even more substantial decrease in the fatigue life. The methods currently used for cavity preparations substantially degrade the durability of dentin.
Tilted Implants in the Immediate Loading Rehabilitation of the Maxilla
Authors: Menini M. , Signori A. , Tealdo T. , Bevilacqua M. , Pera F. , Ravera G. , Pera P.
Published: August 2012

Tilted implants have been proposed as an alternative to traditional protocols in the rehabilitation of edentulous maxillae. The aim of this meta-analysis was to evaluate the outcomes of upright and tilted implants supporting full-arch fixed dentures for the immediate rehabilitation of edentulous maxillae, after at least 1 year of function. An electronic search of databases and a hand search of relevant journals in oral implantology were performed according to PRISMA guidelines through August, 2011. The literature search yielded 1,069 articles. Eleven articles were available for analysis. A total of 1,623 implants (778 tilted, 845 upright) were inserted into the maxillae of 324 patients. Seventeen tilted (2.19%) and 16 upright implants (1.89%) failed during the first year. No significant difference in failure rate was found between tilted and upright implants (p value = 0.52). Marginal bone level results were obtained from 6 studies. A non-significant mean difference between tilted and upright implants was found with regard to bone loss. Tilted implants demonstrated a favorable short-term prognosis in full-arch immediate loading rehabilitations of the maxillae. Randomized long-term trials are needed to better elucidate long-term success of tilted vs. upright-positioned implants.
Access to the Beach
Authors: Dixon Anthony W. , Oh Chi-Ok , Draper Jason
Published: August 2012

In the United States, an objective of coastal states is providing sufficient access to coastal resources. To better utilize public resources for such projects, decision makers would benefit from possessing reliable estimates of economic values coastal residents and tourists place on public beach access. This study’s purpose is to estimate the economic values coastal residents and tourists assign to public beach access, and provide options for financing such projects. Estimates of these values were calculated using the doubled-bounded dichotomous choice contingent valuation technique. Results indicated that coastal residents were willing to pay $2.46 for additional public beach access, while coastal tourists’ mean willingness to pay was $6.33. Findings suggest additional public beach access locations are desirable to both coastal residents and tourists. Supplying coastal resource managers with these values can assist in justifying the use of public resources on beach access projects, as well as in the development of long-term policies.
One’s a Crowd? On Greenwood’s Delimitation of the Social
Authors: Champagne Marc
Published: August 2012

In an effort to carve a distinct place for social facts without lapsing into a holistic ontology, John Greenwood has sought to define social phenomena solely in terms of the attitudes held by the actor(s) in question. I argue that his proposal allows for the possibility of a “lone collectivity” that is (1) unpalatable in its own right and (2) incompatible with the claim that sociology is autonomous from psychology.  As such, I conclude that the relevant beliefs need to be held by more than one person.
The Digital Divide in Internet‐Based Patient Education Materials
Authors: Sun Gordon H.
Published: August 2012

The ubiquity of the Internet has led to the widespread availability of health‐related information to the public, and the subsequent empowerment of patients has fundamentally altered the patient‐physician relationship. Among several concerns of physicians is the possibility that patients may be misinformed by information obtained from the Internet. One opportunity for health care providers to address this problem exists within Internet‐based patient education materials (IPEMs). According to recent research in Otolaryngology–Head and Neck Surgery, IPEMs found within professional otolaryngology websites are written at the 8th‐ to 18th‐grade reading comprehension level, essentially unchanged over the past 3 years. This greatly exceeds the fourth‐ to sixth‐grade reading level recommended by the National Institutes of Health. Benefits, strategies, and challenges to improving the readability of IPEMs are discussed.
A daily diary study
Authors: Young Valerie , Curran Melissa , Totenhagen Casey
Published: August 2012

We collected daily diary data from 165 couples ( N = 330) in romantic relationships to examine how working to change the relationship and relational uncertainty influence positive relationship quality (i.e., closeness, satisfaction, and commitment). We used concepts from the investment model and literature on relationship maintenance and relational uncertainty. As hypothesized, we found a positive association between working to change the relationship and relationship quality. Further, this association was stronger on days in which individuals reported lower relational uncertainty, but significantly weaker on days in which individuals reported higher relational uncertainty. We discuss what it means for individuals to report more positive relationship quality when they make more relational investments and feel more certain about their relationship.
Government policy and women in the labour market: The importance of public sector employment
Authors: Green Anne E
Published: August 2012

Women have made important quantitative and qualitative gains in the labour market in recent years. A key feature of women’s employment is their disproportionate concentration in the public sector, and this helps to explain the advances they have made in the labour market given the availability of high quality jobs and opportunities for skills development in this sector across many local areas. This article explores how ongoing economic, labour market and welfare policy changes may undo some of the progress that has been made by women in the labour market, especially because of their vulnerability to job cuts in the public sector, the spatially uneven impact of such job losses and the particular dependence of women on local employment opportunities.
Fracture and thermal behaviour of biomass ash polypropylene composites
Authors: Pardo SG , Bernal C , Abad MJ , Cano J , Ares A
Published: August 2012

In this work, the fracture and thermal behaviour of environmentally friendly composites based on polypropylene (PP), an olefin block copolymer (OBC) and ash from biomass combustion was investigated. PP/OBC/ash composites with different ash contents and 10 wt% OBC were prepared by extrusion followed by compression moulding. Ash particles were treated with a silane coupling agent before blending to promote interfacial adhesion between polymer matrix, OBC and ash. An approach to fracture mechanics was investigated and showed that the fracture parameters increased when OBC was used. Fracture surface analysis by scanning electron microscope revealed that the presence of OBC promotes the material ductile failure and that one of the main failure mechanisms was fibrillised debonding of ash particles encapsulated by OBC from the matrix and its subsequent elongation around them. Free OBC inclusions distributed within the PP matrix would have also induced toughening in the composites investigated. The crystalline state of PP analysed by differential scanning calorimetry is clearly modified by the presence of ash particles, increasing the crystallisation rate and the crystallinity degree of the matrix due to the nucleating effect of the filler. However, the presence of the copolymer counteracted these effects and the PP crystalline state remained practically unchanged in the composites with OBC. Finally, environmentally friendly composites with significantly higher toughness than the matrix or binary PP/ash composites were obtained by introducing an OBC copolymer in the formulation.
Preparation and properties of epoxy resin modified with polyurethane based on hexamethylene diisocyanate and different polyols
Authors: Bakar M , Kostrzewa M , Pawelec Z
Published: August 2012

Polyurethanes (PURs) synthesized using hexamethylene diisocyanate (HDI) and polyethylene glycol with molecular weights of 400 g mol−1 and 600 g mol−1 (PUR 400 HDI and PUR 600 HDI) or polyoxypropylene diol (POPD) of molecular weights 1002 g mol−1 and 2002 g mol−1 (PUR 1002 HDI and PUR 2002 HDI) were used as modifiers for diglycidyl ether of bisphenol A. It was found that maximum improvement in impact strength and critical stress intensity factor ( KC) values was obtained for compositions containing 15% PUR 400 and 5% PUR 1002. Such improvement in the resistance to crack propagation due to PUR incorporation might be related with the soft segments of polyethylene glycol and POPD. The critical stress intensity factor ( KC) values increased from 1.7 MPa m1/2 (virgin epoxy) to 2.5 MPa m1/2 with the addition of 10% PUR 400. Fourier transform infrared spectra confirmed the formation of an interpenetrating polymer network structures with polymeric modifier. Scanning electron micrographs of epoxy resins (EPs) modified with PUR with longer chains (PUR 1002 and PUR 2002) exhibited a deformed leaf-like morphology with larger plastic deformation zones with the presence of microcracks. However, EP/PUR based on polyethylene glycol showed less deformed structure.
Media Democratization in Brazil: Achievements and Future Challenges
Authors: Matos Carolina
Published: August 2012

This article focuses on the achievements in the field of media democratization in Brazil, underlining the current challenges that public communication systems face in the light of the persistence of the misuse of these structures by politicians for their own interests. The role that the public media platform can have in the democratic project is examined, including how it can assist policy-makers concerning vital national as well as global issues. The slow democratization of Brazil during recent decades, however, has taken place while not altogether disassociated from the authoritarian legacy that has characterized the formation of Brazilian society. Nonetheless, the acknowledgement that the mainstream media have become more professional, including wider voices in the mediated sphere, is not reason enough to proclaim the end of the struggles for media democratization.
Border encounters: How children navigate space and otherness in an ethnically divided society
Authors: Christou Miranda , Spyrou Spyros
Published: August 2012

The article draws on ethnographic material from an ongoing study which explores 10- to 12-year-old Greek Cypriot children’s experiences of crossing to the north, the occupied part of Cyprus. By focusing on the act of crossing and the actual physical experience of visiting the occupied territories, the study seeks to highlight the mechanisms implicated in the construction of ethnic difference as children move through spaces and places and encounter ‘others’. The article argues that to understand how children navigate ethnic divisions in the context of these visits, we need to attend to the role of place-making in the construction of identity.