bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the Responsiveness of Cutaneous Veins of Dog and Rabbit to Adrenergic and Cholinergic Stimulation
Authors: De Mey J.G. , Vanhoutte P.M.
Published: April 2017

The reactivity to sympathetic nerve activation and the metabolism of 3H-norepinephrine were compared in isolated saphenous veins of dogs and rabbits. The veins of both species were equally sensitive to electrical stimulation, but the magnitude of the contractile responses to such stimulation was larger in the dog. The response to depolarization of the adrenergic nerve endings by high K+ solutions was depressed by phentolamine to a greater extent in the dog than in the rabbit vein. After incubation with 3H-norepinephrine, electrical stimulation caused a greater evoked release of tritiated transmitter in the dog than in the rabbit veins. These experiments suggest that the former are more densely innervated. In resting conditions and during electrical stimulation, the dog veins and the rabbit veins degraded 3H norepinephrine in a different way. In both species, neuronal uptake appeared to be of minor importance in the disposition of 3H-norepinephrine released during continuous electrical stimulation. The reactivity to exogenous catecholamines and acetylcholine were also compared in both veins. The apparent sensitivity to exogenous norepinephrine was greater in rabbit than in dog veins. This difference disappeared after inhibition of neuronal uptake with cocaine, suggesting that it is due to the difference in density of adrenergic innervation. There was no interspecies difference in the sensitivity of the β-adrenoceptors, but the maximal effect of β-adrenergic activation by isoproterenol was larger in the dog than in the rabbit veins. In both species acetylcholine caused inhibition of adrenergic neurotransmission, and direct activation of the venous smooth muscle cells. As regards the latter effect, dog veins were less sensitive to acetylcholine but their response was stronger than that of rabbit veins. These results suggest that the density of adrenergic innervation modulates mainly the apparent sensitivity of the venous smooth muscle to α-adrenergic activation.
Absolute Induction Angiometer
Authors: Kolin Alexander
Published: April 2017

The objective of this method is the continuous recording of vascular diameters and their measurement in absolute terms. This can be accomplished by percutaneously introduced intravascular sensors (IVS) or surgically implanted perivascular sensors (PVS). Both types of sensor are made of bifilar insulated wires forming a bifilar loop. One wire of the bifilar loop acts as a transformer primary inducing an electromotive force (EMF) in the secondary loop wire. The latter EMF is a measure of the vascular diameter. The IVS loop is made of resilient wire and is disposed across a vascular diameter in the central plane of a blood vessel. The sensitivity is such that phasic variations of a few micrometers in the diameter of a major blood vessel (such as the aorta or a coronary artery) can be measured and recorded. The surgically implanted perivascular loop sensor permits observation of vasomotion in a conscious, unrestrained animal. Both IVS and PVS permit observation of coronary vasomotion in the beating heart. Unlike the relative induction angiometer, the present device does not require an extracorporeal magnet.
Methionine, Pyridoxine and Endothelial Lesion in Rats
Authors: Hladovec J.
Published: April 2017

Methionine administered orally to rats produced a prolonged dose-dependent increase in endothelemia. The increase was observed after doses exceeding 100 mg/kg and was inhibited by a simultaneous administration of pyridoxine. The effect of methionine was also inhibited by trihydroxyethylrutoside and acetylsalicylic acid. Endothelemia was increased furthermore by oral administration of cysteine and cystine and this increase was again inhibited by pyridoxine.
Indirect Evidence for the Importance of Steady-State [K]o in Determining the Extent of the Effects of Hyperpolarizing Electrogenesis on Vascular Smooth Muscle Reactivity
Authors: Skaug Nancy , Detar Reed
Published: April 2017

Abruptly increasing [K]o and adding ouabain produce short-term depression and enhancement, respectively, of vascular smooth muscle (VSM) reactivity, presumably as a result of stimulating and inhibiting, respectively hyperpolarizing electrogenesis. Moreover, the presence of a steady-state level of electrogenesis is implicated by the enhancing effect of ouabain. The results of this study indicate that the extent of these short-term changes in electrogenesis and the level of this steady-state electrogenesis are regulated by small changes in steady-state [K]o within a physiological range, 3–6 mM.
Effects of Flunarizine on the Distribution of Calcium in Vascular Smooth Muscle
Authors: Borgers M. , Ghoos E. , Thoné F. , Van Nueten J.M.
Published: April 2017

Exposure of depolarized caudal artery preparations of the rat to various calcium concentrations evoked sustained contractions of the smooth muscle in a dose-dependent way. Flunarizine was shown to suppress this sustained muscle contraction. Experiments were undertaken to determine the subcellular site where flunarizine interferes with the calcium-induced contractile process. The subcellular distribution of calcium was assessed by electron microscopy, using a combined oxalate-pyroantimonate method. In depolarized strips precipitated calcium was mainly distributed over the contractile elements and the microvesicles lining the cell membrane. When flunarizine was added to the preparation, the precipitate was predominantly confined to the extracellular space, whereas only spotty precipitates were seen in mitochondria and sarcoplasmic reticulum. The myofibrils were almost free of deposits. Without previous depolarization, the smooth muscle cells demonstrated a moderate amount of precipitate over the mitochondria, nuclei, sarcoplasmic vesicles, plasmalemmal microvesicles and myofibrils. In these conditions neither the amount nor the intracellular distribution of the precipitate was influenced by the addition of flunarizine. These observations suggest that flunarizine interferes with the entry of calcium at the plasma membrane level, but only in conditions where the influx of the ion is stimulated.
Characteristics of Arterial Plasma Membrane in Renovascular Hypertension in Rats
Authors: Kwan C.Y. , Belbeck L. , Daniel E.E.
Published: April 2017

Protein content, enzymatic activites and Ca2+ accumulation capacities were studied in plasma membrane fractions isolated from mesenteric arteries of rats made hypertensive by renal artery stenosis with and without contralateral nephrectomy, i.e., one-kidney, one clip (1-KHR) and two-kidney, one clip (2-KHR) hypertension, respectively. Both types of renovascular hypertension showed similar vascular plasma membrane abnormalities which included increased total protein contents, enhanced alkaline phosphatase activities and reduced ATP-dependent Ca2+ accumulation compared to control values. The altered alkaline phosphatase activity and ATP-dependent Ca2+ accumulation appeared to be associated with blood pressure elevation in both types of hypertension and may be related to the elevation of blood pressure insensitive to captopril (SQ 14,225) in 1-KHR and 2-KHR. These results are consistent with the current concept of biochemical abnormalities of arterial smooth muscle in the development of renovascular hypertension in rats in addition to the involvement of the renin-angiotensin system.
Effect of Moderate Cooling on Adrenergic Neuroeffector Interaction in Canine Cutaneous Veins
Authors: Janssens W.J. , Verbeuren T.J. , Vanhoutte P.M.
Published: April 2017

Experiments were performed to investigate the effect of moderate cooling on adrenergic neuroeffector interaction in canine cutaneous veins. Helical strips of dog’s saphenous vein, untreated or first incubated with 3H-norepinephrine were mounted for superfusion and isometric tension recording; the overflow of endogenous catecholamines or 3H-norepi-nephrine and its metabolites, respectively, were measured in the superfusate. In other experiments the monoamine oxidase activity or the catechol-O-methyltransferase (COMT) activity of the saphenous vein wall was determined. Moderate cooling (from 37 to 24 °C) decreased the evoked release of endogenous norepinephrine during electrical stimulation of the adrenergic nerve endings in the blood vessel wall. Moderate cooling depressed the overflow of 3H-norepinephrine and its metabolites in unstimulated preparations, during electrical stimulation during superfusion with high K+ solution and during exposure to tyramine. Moderate cooling reduced the activity of monoamine oxidase significantly more than that of COMT. The relative alterations in overflow of norepinephrine and its metabolites caused by a same degree of cooling in basal conditions and during the different forms of increased overflow of adrenergic transmitter suggest that lowering the temperature inhibits the exocytotic process, but at the same time slows down the diffusion of norepinephrine from the junctional cleft to the extracellular space to the extent that during sympathetic nerve stimulation at 24 °C the effective junctional concentration of the transmitter may be comparable to that obtained at 37 °C. The inhibitory effect of moderate cooling on the extraneuronal metabolism of norepinephrine appears to affect little the effective junctional concentration of the adrenergic transmitter.
The Nature of Cerebral Vasospasm
Authors: Mchedlishvili George
Published: April 2017

The article comprises mainly the personal views of the author on the following aspects of cerebral vasospasm: the definition of vasospasm; historical physiological concepts of cerebral bloodflow regulation; relation of spasm development in cerebral arteries to their functional behavior during regulation of cerebral blood flow; the essence of vasospasm from the standpoint of smooth muscle physiology; physiological stimuli involved in its development; the disturbances in plasmatic membrane function and intracellular processes of smooth muscles inducing vasospasm; systems approach to development which may assist in systematization of data and in efficiency and direction of further research.
Characteristics of Plasmalemma Alkaline Phosphatase of Rat Mesenteric Artery
Authors: Kwan C.Y.
Published: April 2017

General characteristics of alkaline phosphatase activity of the plasma membrane-enriched fraction isolated from rat mesenteric arteries were investigated. The vascular smooth muscle plasmalemma alkaline phosphatase is a metalloenzyme which is strongly inhibited by chelating agents and this inhibition can be completely overcome by addition of Mg2+ or Ca2+. Zn2+ only partially reactivates the enzyme in the presence of low concentrations of EDTA. The enzymatic hydrolysis of p-nitrophenyl phosphate, β-glycerophosphate, α-glycerophosphate, or 3’-adenosine monophosphate showed an optimal activity in the alkaline region between pH 9 and 11. The alkaline phosphatase activity is distinctly different from the plasmalemma ATPase and 5’-nucleotidase activities with respect to their pH dependence, influence by added divalent metal ions and stability against heat inactivation. Vanadate ion, being structurally similar to the transition state analog of the phosphoryl group, potently inhibits alkaline phosphatase with an apparent Ki of 1.5 µM. The altered alkaline phosphatase activity of vascular smooth muscle in relation to its possible physiological function and pathophysiological manifestation associated with hypertensive disease are discussed.
Altered Membrane Electrical Properties of Smooth Muscle Cells from Small Cerebral Arteries of Hypertensive Rats
Authors: Harder David R. , Brann Linda , Halpern William
Published: April 2017

Certain electrophysiological properties of smooth muscle cells within middle cerebral arteries of spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto (WKY) controls were recorded with glass microelectrodes. Under control conditions the smooth muscle cells of arteries from SHR rats exhibited fast and slow oscillations of the resting membrane potential (Em). In marked contrast the smooth muscle cells of WKY cerebral arteries were electrically quiescent. The Em vs. log [K]o relationship was similar for arteries from both SHR and WKY rats and extrapolated to similar [K]i values of 150–155 mM when determined under control conditions. When Em vs. log [K]o curves were obtained in the presence of ouabain to block electrogenic Na-K transport, the smooth muscle cells of SHR cerebral arteries exhibited a lower mean slope per decade change in [K]o (i.e., depolarized more at various concentrations of [Ko in the presence of ouabain) when compared to WKY. Arterial smooth muscle cells from SHR also depolarized to a greater extent when exposed to zero K+ solutions. The results of this study indicate that smooth muscle cells of cerebral arteries from SHR rats have a greater electrogenic Em component as well as altered ionic conductances for K+ and possibly Na+ both of which may contribute to their spontaneous electrical activity.
Effects of pH and Anion Substitution on Magnesium Accumulation in Rabbit Aortic Smooth Muscle
Authors: Shetty Suraj S. , Weiss George B.
Published: April 2017

The effects of anion substitution, pH and extracellular Mg2+ concentration on 28Mg accumulation were examined in rabbit aortic smooth muscle. Accumulation of 28Mg (expressed as a 28Mg/Mg2+ ratio) was not changed when the concentration of added, nonradioactive MgCb was increased from 1.5 to 15.0 mM. The 28Mg efflux rate was increased by added MgCh (0.15, 0.5 or 1.5 mM) in a dose-related manner after a similar delay of 5–10 min. Addition of 1.5 mM MgCl2, MgSO4 or magnesium aspartate hydrochloride enhanced 28Mg efflux and inhibited accumulation of 28Mg to the same extent. An increase or decrease in extracellular pH correspondingly increased or decreased 28Mg accumulation. However, the 28Mg efflux rate was not altered when extracellular pH was decreased. Efflux of 28Mg was increased by added 1.5 mM MgCl2 at pH 7.4 but not at pH 5.8. Thus, the net uptake of Mg2+ appears to be proportional to the concentration of extracellular Mg2+ in rabbit aorta. Low external pH decreases 28Mg retention in rabbit aorta by inhibiting the uptake of 28Mg rather than by increasing 28Mg efflux. Effects of added Mg2+ on transmembrane movements of 28Mg are not altered by changes in the associated anion. Extracellular Mg2+ appears to enter the cell and exchange with an intracellularly located pool of 28Mg in the same manner, regardless of whether the accompanying anion is sulfate, chloride or monoaspartate hydrochloride.
Substance P Activates Leukocytes and Platelets in Rabbit Microvessels
Authors: Öhlén Anders , Thureson-Klein Åsa , Lindbom Lennart , Persson Magnus G. , Hedqvist Per
Published: April 2017

The effect of substance P on leukocytes and platelets in rabbit skeletal muscle microvasculature was studied by intravital microscopy and electron microscopy. Local application of substance P caused vasodilatation and formation of aggregates of platelets and leukocytes in postcapillary venules with subsequent migration of leukocytes through the vessel wall. Many neutrophils were partially degranulated. Aggregate formation induced by substance P could not be prevented by autacoid antagonists. However, superfusion with calcitonin gene-related peptide prior to challenge with substance P greatly inhibited aggregate formation and leukocyte extravasation.
Cryopreservation of Innervation, Endothelial and Vascular Smooth Muscle Function of a Rabbit Muscular and Resistance Artery
Authors: Thompson Loren , Duckworth John , Bevan John
Published: April 2017

The extent of preservation of endothelial, neurogenic and vascular function following frozen storage was studied using the rabbit central ear artery and a resistance artery branch. Fresh and frozen-stored artery segments were placed in tissue baths containing a physiological buffer solution and attached to a wire myograph apparatus for measurement of isometric force. Responses to cumulative additions of norepinephrine, histamine, acetylcholine and sodium nitroprusside were compared between fresh arteries and adjacent segments that had been stored frozen for 2–8 days at –70 °C. Responses to transmural nerve stimulation were measured in central ear artery segments that were fresh or stored frozen for 13–26 days. Large and small artery segments were frozen in ampules containing newborn calf serum and 1.8 Mdimethylsulfoxide used as a cryoprotective agent. Following frozen storage, the vascular sensitivity of large and resistance arteries to norepinephrine and histamine were unaltered although maximal contractile responses were significantly reduced. Agonist affinity (KA values) to norepinephrine was also unchanged following frozen storage of large artery segments. Constrictor responses to varied frequencies of transmural nerve stimulation were similar between fresh and frozen-stored large arteries, suggesting that adrenergic nerve function is well preserved. In resistance arteries, vascular sensitivity and maximal relaxation to acetylcholine and sodium nitroprusside were unchanged. Similarly, relaxation of large arteries to sodium nitroprusside was well preserved. Although vascular sensitivity to acetylcholine was reduced in large arteries following frozen storage, much of the endothelial function was still preserved as indicated by only a 10% decrease in maximal relaxation. These results indicate that frozen storage of large and small artery segments preserves endothelial and vascular smooth muscle function as well as adrenergic neurotransmission.
Release of Vasoactive Peptides from Autonomic and Sensory Nerves
Authors: Lundberg J.M. , Franco-Cereceda A. , Lacroix J.S. , Pernow J.
Published: April 2017

Release of specific vasoactive peptides occurs upon activation of perivascular parasympathetic (vasoactive intestinal polypeptide and peptide histidine isoleucine), sympathetic (neuropeptide Y) and sensory (calcitonin gene-related peptide and tachykinins) nerves. These peptides may serve as cotransmitters with acetylcholine and noradrenaline with interactions both at the pre- and postjunctional levels. Some long-lasting nonadrenergic, noncholinergic vascular effects upon nerve activation may thus be peptide-mediated. Strong activation seems to be necessary for peptidergic transmission in the parasympathetic and sympathetic system while local sensory mechanisms may occur even at single impulses.
Hypernoradrenergic Innervation and Vascular Smooth Muscle Hyperplastic Change
Authors: Head Richard J.
Published: April 2017

Two distinguishing features of the vasculature of the spontaneously hypertensive rat (SHR) are an increased sympathetic innervation and vascular smooth muscle hyperplasia. Evidence supporting the existence of hypernoradrenergic innervation and vascular smooth muscle cell hyperplasia is presented with emphasis upon the possible interrelationships between the two events. The results of experiments designed to explore this relationship are presented and include the determination of the role of endogenous nerve growth factor (NGF) and the influence of exogenous NGF on the development of sympathetic innervation of blood vessels and blood pressure change. Attention is focused upon elevated levels of 3-methylhistidine (a biochemical marker for contractile proteins) in the mesenteric vasculature of the SHR. The potential relationships between hypernoradrenergic innervation and increased concentrations of 3-methylhistidine are explored.
Two Indices of Functional Damage of the Artery Wall Parallel the Time Course of Irreversible Narrowing in Experimental Vasospasm in the Rabbit
Authors: Vorkapic Peter , Bevan John A. , Bevan Rosemary D.
Published: April 2017

Autologous blood placed around the basilar artery caused angiographic narrowing with a biphasic time course. The first immediate phase was reversed by intraarterial papaverine; the second exhibited an increasing component of narrowing which was papaverine-resistant. In vitro studies showed that vessels became increasingly suffer, less capable to develop active tone, and less responsive to vasoconstrictors and vasodilators. The papaverine-resistant component of angiographic narrowing (in vivo) could be directly correlated with loss of contractility and increased artery wall stiffness (in vitro).
Development of Collaterals in the Cerebral Circulation
Authors: Coyle Peter , Heistad Donald D.
Published: April 2017

Sudden occlusion of the middle cerebral artery (MCA) in normotensive rats increases blood flow through anastomosing branches into the territory of the occluded artery. Three weeks after MCA occlusion, anastomoses to anterior cerebral branches are increased by more than 50% in luminal diameter. One month after MCA occlusion, blood flow and blood flow reserve to the territory of the occluded MCA are returned to normal levels. In stroke-prone spontaneously hypertensive rats (SHRSP), the anastomoses are significantly narrower and blood flow through the anastomoses is less than in normotensive rats. Tissue infarction invariably develops in the territory of the occluded MCA in SHRSP. We propose that the luminal width of the anastomosis is a major determinant of blood flow into the territory of the occluded artery and of the amount of tissue protected from infarction by collateral circulation.
Vascular Production and Regulation of Angiotensin
Authors: Hilgers Karl F. , Mann Johannes F.E. , Hilgenfeldt Ulrich , Ganten Detlev
Published: April 2017

To test the hypothesis that angiotensin (Ang) I and II are produced by blood vessels, we investigated the formation of both Ang I and Ang II in isolated, perfused rat hindquarters. To characterize the nature of this production further, we modulated plasma renin by total or subtotal nephrectomy and tested the effects of exogenous renin and renin substrate on vascular Ang formation. Assays of the perfusate by high-performance liquid chromatography and radioimmunoassay demonstrated the spontaneous release of Ang I and Ang II from the hindlimb vasculature. Conversion of Ang I to Ang II in hindquarter vasculature was approximately 75% and was totally suppressed by captopril. The spontaneous formation of Ang peptides was abolished by bilateral nephrectomy but was not affected by subtotal 5/6 nephrectomy. The addition of purified rat angiotensinogen to the preparation increased Ang II levels. The infusion of renin into the hindlimb vasculature led to substantial increases in local Ang formation and also raised the perfusion pressure. Both effects were sensitive to captopril and to the renin inhibitor H-142. The data indicate that Ang I and Ang II are produced locally within blood vessels. However, the origin of vascular renin remains controversial. Our results suggest that part of the enzyme is taken up from plasma.
Role of Vascular Wall Renin: Intracellular and Extracellular Mechanism
Authors: Inagami Tadashi , Murakami Tetsuo , Higuchi Kazumi , Nakajo Shigeo
Published: April 2017

Inhibitors of angiotensin-converting enzyme, renin and angiotensin II receptor lower the blood pressure of spontaneously hypertensive rats (SHRs) used as a model of essential hypertension. Since their plasma renin levels were normal or subnormal, renin in the vascular tissue was considered to play a key role in the maintenance of the hypertension. To clarify the source and localization of vascular renin in SHRs, the effects on blood pressure of antirenin antibodies, the converting enzyme inhibitors delapril and enalapril, and the angiotensin II receptor antagonist DuP 753 were examined in intact and bilaterally nephrectomized SHRs and their normotensive controls. The efficient hypotensive action of the renin antibody indicated that renin of the renal origin is a dominant factor. The gradual but complete disappearance of the antihypertensive action of these inhibitors of the renin-angiotensin system upon bilateral nephrectomy indicated the importance of membrane-associated renin of the renal origin and angiotensin-converting enzyme in the maintenance of the spontaneous hypertension.
Spatial and Temporal Resolution of Serotonin-Induced Changes in Intracellular Calcium in a Cultured Arterial Smooth Muscle Cell Line
Authors: Goldman William F.
Published: April 2017

Ca2+ transients (1–2 µM) evoked by serotonin (5-HT) in cultured A7r5 cells were studied using fura-2 and digital imaging microscopy. Fura-2 was introduced into cells either by incubation with its acetoxymethyl ester analogue fura-2/AM or by transient ATP-induced permeabilization of the sarcolemma such that the free fura-2 entered the cell directly. The distribution of cytoplasmic Ca2+ in unstimulated cells loaded by the former method was heterogeneous, reflecting, in part, separate pools of Ca2+ in the cytosol and sarcoplasmic reticulum (SR). In contrast, the distribution of Ca2+ was uniform in cells loaded with fura-2 by transient permeabilization; this reflected the restriction of fura-2 to the cytosol. Average Ca2+ in these cells was substantially lower than that in fura-2/AM-loaded cells, because SR Ca2+ influences the fura-2 signal from fura-2/AM-loaded cells, but not from cells loaded with free fura-2. The differences in the Ca2+ distribution measured by the two loading methods were also evident during the course of 5-HT-evoked Ca2+ transients. Spatial and temporal resolution of the rising phase of 5-HT-evoked Ca2+ transients in fura-2/AM-loaded cells revealed that the onset of the Ca2+ transients was first manifested as small regions of elevated Ca2+ that subsequently expanded until peak apparent intracellular Ca2+ levels were present in virtually all of the nonnuclear regions of the cells. The rate of rise of Ca2+ varied in different cell regions with the nucleus responding the slowest.
Relaxant Effect of Chemotactic Peptides on Rabbit Vascular Strips: Evidence for Nitric Oxide Release from a Nonendothelial Source
Authors: Petitclerc Eric , Marceau François
Published: April 2017

Two distinct peptides, C5a and f-Met-Leu-Phe (FMLP), that are chemotactic for phagocytic leukocytes affect profoundly the circulation in various in vivo systems. These peptides are known to relax strips of rabbit isolated blood vessels, the portal vein and pulmonary artery. In the present study, the effect of recombinant human C5a (2.5–25 nM) was examined and found to be qualitatively similar to that previously reported for FMLP. Indomethacin completely or partially inhibited the vasorelaxations induced by either peptide in the pulmonary artery and the portal vein, respectively. The relaxation induced by C5a was not abolished by removing the endothelial lining of the model vessels. The C5a or FMLP effects were more tachyphylactic in tissues continuously exposed to cycloheximide; this phenomenon was particularly pronounced for FMLP. A series of experiments were focused on the indomethacin-resistant component of the relaxation induced by either peptide on the portal vein. This component was not inhibited by capsaicin pretreatment or by endothelium removal, but was suppressed by treatment with NG-nitro-L-arginine or reduced by LY-83583. These findings suggest that the chemotactic peptides elicit their mechanical effect on rabbit vascular smooth muscle through the release of secondary mediators not related to the endothelium; the mediators are tentatively identified as prostaglandins and nitric oxide. It is the coordinated combinations of the metabolic pathways that are involved in the final responses, with inherent differences between vessel sources and the agonists used.
Effect of Papaverine on Endothelial Cell Harvest from Canine External Jugular Veins
Authors: Ranvaí Timothy J. , Townsend Laurace E. , Fietsam, Jr. Robert , Bendick Phillip J. , Reitz-Vick Darlene M. , Glover John L.
Published: April 2017

Endothelial cell seeding procedures have been developed to line prosthetic bypass grafts used in peripheral vascular disease; however, because of current inefficient cell harvest techniques a high ratio of vein-to-graft area is necessary. This study was done to determine if the use of papaverine, a smooth muscle cell relaxant, would affect the number or viability of endothelial cells harvested from canine external jugular veins. Using a 0.12 mg/ml solution of papaverine in tissue culture medium to bathe the veins during disscetion and excision, the viable cell yield was 2.20 ± 1.16 (cells × 104/cm2). A control group of veins using standard dissection technique gave a yield of 0.97 ± 0.40 (p = 0.025). A second group of veins dissected while bathed in tissue culture medium alone gave a yield of 1.82 ± 0.75, compared to a yield of 2.73 ± 0.45 for papaverine harvested veins (p = 0.009). Percent cell viability was not significantly different for any of the groups: 73, 70, and 76% for papaverine, control and media only veins, respectively. The papaverine-harvested cells and those harvested with medium alone grew to 95% confluence in tissue culture in 9.8 ± 1.1 and 9.9 ± 0.9 days, respectively. Compared to conventional surgical techniques, use of papaverine more than doubled the endothelial cell yield from excised vein segments without adversely affecting viability or rate of growth in cell culture.
Morphometric Analysis of Monkey Cerebral Arteries Exposed in vivo to Whole Blood, Oxyhemoglobin, Methemoglobin, and Bilirubin
Authors: Macdonaid Loch , Weir Bryce K.A. , Grace Michael G.A. , Martin Thomas P. , Doi Mamoru , Cook David A.
Published: April 2017

Whether vasospasm results from smooth muscle contraction or from arterial wall infiltration by cells and other material is subject to debate. Computer-assisted image analysis was used to measure lumen area, total wall area, and area of tunica media plus tunica intima of cross-sections of monkey right middle cerebral arteries (MCAs), exposed in vivo for 6 days to whole blood (n = 4), oxyhemoglobin (OxyHb, n = 5), methemoglobin (MetHb, n = 5), bilirubin (n = 5), mock cerebrospinal fluid (CSF, n = 6), and supernatant fluid from an incubated mixture of autologous blood and mock CSF (n = 5). Five control (left) MCAs from each group and 4 MCAs contracted in vitro with potassium chloride were measured. Significant angiographic vasospasm occurred in groups receiving whole blood, supernatant fluid, and OxyHb (p < 0.05). There was significant correlation (r = 0.58, p < 0.05) between right MCA diameter on angiography and diameter calculated from lumen area. When compared to effects of mock CSF, OxyHb significantly increased total wall area. When right and left MCAs were compared within groups, total wall area increased in every group with significant increases in groups exposed to mock CSF, OxyHb, and bilirubin (p < 0.05). No changes developed in area of tunica media plus tunica intima, whether comparing right versus left MCAs within groups or right MCAs between groups. Contraction in vitro did not significantly increase total wall area or area of tunica media plus tunica intima. Light
Reduction of Postischemic Reperfusion Injury by the Vasoactive Drug Buflomedil
Authors: Nolte Dirk , Lehr Hans-Anton , Sack Falk-Udo , Messmer Konrad
Published: April 2017

The effect of buflomedil on postischemic reperfusion injury was studied in the dorsal skin fold chamber preparation of awake hamsters. Microvascular events were investigated in the striated skin muscle by means of intravital fluorescence microscopy prior to 4 h of pressure-induced ischemia and 30 min, 2 and 24 h after reperfusion. In untreated control animals, ischemia and reperfusion provoked marked leukocyte sticking and macromolecular leakage while functional capillary density was reduced. Treatment with buflomedil (3 mg/kg b.w. in 0.3 ml saline, administered as bolus of 0.1 ml 10 min prior to release of ischemia followed by i.v. infusion of 0.2 ml during the first 20 min of reperfusion) significantly reduced leukocyte sticking and macromolecular leakage, while functional capillary density was effectively preserved. No differences in macro- and microhemodynamic parameters were observed between buflomedil-treated and untreated animals. These findings support the concept that activated leukocytes are involved in the microvascular manifestation of reperfusion injury and indicate that leukocyte sticking and its sequelae can be efficiently prevented by treatment with buflomedil.
Evaluation of Flux Motion in Man by the Laser Doppler Technique
Authors: Bollinger A. , Hoffmann U. , Franzeck U.K.
Published: April 2017

Analysis of flux motion by the laser Doppler technique in the forefoot of healthy controls and patients with peripheral arterial occlusive disease was performed by establishing computerized frequency histograms. It was found that the low frequency components (1–10 cycles/min) are caused by local vasomotion. The prevalence of high frequency flux waves (15–25 cycles/min) is significantly increased in peripheral ischemia compared to normal conditions. After successful reopening of large arteries by angioplasty the prevalence decreases (p < 0.001). Preliminary results indicate that these high frequency rhythmic fluctuations might by induced by respiration.
Exercise-Induced Variations in Muscle Tissue Oxygen Pressure in Claudicants: Effects of Buflomedil
Authors: Ehrly Albrecht Michael , Saeger-Lorenz Katrin
Published: April 2017

The amount of oxygen actually supplied to the ischemic muscle tissue of patients with intermittent claudication was quantified before and after a standardized pedal ergometric test. Muscle tissue pO2 was measured with micro-platin needle electrodes directly in the lower limb muscles at rest and 3, 10, 20 and 60 min after a 4-min work load. Time-dependent variations in the behavior of pO2 values as well as changes in the shapes of pooled pO2 histograms make it possible to monitor the effect of therapeutic measures. In claudicants (stage lib) with ascertained occlusions or stenosis of the femoral artery or the pelvis region, it was demonstrated that the delayed increase in tissue pO2 after exercise could be improved by the infusion of 400 mg buflomedil. Comparison between the time-related pooled histograms confirmed improvement of oxygen supply under the influence of this drug.
Executive Dysfunction and Left Frontal White Matter Hyperintensities Are Correlated with Neuropsychiatric Symptoms in Stroke Patients with Confluent White Matter Hyperintensities
Authors: Mok Vincent C.T. , Wong Adrian , Wong Kelvin , Chu Winnie C.W. , Xiong Yunyun , Chan Anne Y.Y. , Kwok Timothy C.Y. , Hu Xintao , Lee W.K. , Tang Wai-kwong , Wong Ka-sing Lawrence , Wong Stephen
Published: April 2017

Background/Aims: This study aimed to determine the clinical and neuroimaging correlates of the presence of neuropsychiatric symptoms in stroke patients with age-related confluent white matter hyperintensities (WMH). Methods: The Neuropsychiatric Inventory was utilized to detect the presence of 12 symptoms. Multivariate logistic regression models were used to identify clinical and neuroimaging correlates of the presence of symptoms. Results: Seventy-seven stroke patients (mean WMH volume: 39.5 cm3) were recruited. Thirty patients (39%) had ≧1 neuropsychiatric symptom. Poor executive function was associated with the presence of any symptoms and symptoms other than depression. More severe left frontal WMH was associated with depression. Conclusion: Executive dysfunction and left frontal WMH are correlated with neuropsychiatric symptoms in these patients.
Does Age at Observation Time Affect the Clinical Presentation of Mild Cognitive Impairment?
Authors: Vicini-Chilovi Barbara , Riva Maddalena , Conti Marta , Zanetti Marina , Caratozzolo Salvatore , Mombelli Gulia , Bertoletti Erik , Rozzini Luca , Padovani Alessandro
Published: April 2017

Background: To date, there are no published data investigating the role of age in the clinical and neuropsychological presentation of mild cognitive impairment (MCI). The aim of the study was to evaluate whether age at the time of evaluation modulates clinical, functional or cognitive profiles in MCI subjects. Methods: A total of 167 outpatients with a clinical diagnosis of MCI were consecutively enrolled and entered in the study. Clinical and demographic characteristics were carefully recorded. Each patient underwent a wide neuropsychological standardized assessment. Results: MCI subjects were divided into 3 groups according to their age at observation time: 58 MCI patients were classified as young (≤69 years), 89 as old (70–79 years) and 20 as very old (≧80 years). The 3 groups did not differ in demographic characteristics, general cognitive functions and memory impairment. Very old MCI subjects showed a significantly greater impairment than younger MCI patients in cognitive domains involving executive functions. In particular, very old MCI patients were more frequently classified as having multiple-domain amnestic MCI. Conclusion: Present data highlight that the clinical presentation of MCI is affected by age: at presentation, very old MCI subjects show a worse performance than younger MCI subjects on multiple abilities, particularly on executive functions.
Distinctive Phenotypic Abnormalities Associated with Submicroscopic 21q22 Deletion Including DYRK1A
Authors: Oegema R. , de Klein A. , Verkerk A.J. , Schot R. , Dumee B. , Douben H. , Eussen B. , Dubbel L. , Poddighe P.J. , van der Laar I. , Dobyns W.B. , van der Spek P.J. , Lequin M.H. , de Coo I.F.M. , de Wit M.-C.Y. , Wessels M.W. , Mancini G.M.S.
Published: April 2017

Partial monosomy 21 has been reported, but the phenotypes described are variable with location and size of the deletion. We present 2 patients with a partially overlapping microdeletion of 21q22 and a striking phenotypic resemblance. They both presented with severe psychomotor delay, behavioral problems, no speech, microcephaly, feeding problems with frequent regurgitation, idiopathic thrombocytopenia, obesity, deep set eyes, down turned corners of the mouth, dysplastic ears, and small chin. Brain MRI showed cerebral atrophy mostly evident in frontal and temporal lobes, widened ventricles and thin corpus callosum in both cases, and in one patient evidence of a migration disorder. The first patient also presented with epilepsy and a ventricular septum defect. The second patient had a unilateral Peters anomaly. Microarray analysis showed a partially overlapping microdeletion spanning about 2.5 Mb in the 21q22.1–q22.2 region including the DYRK1A gene and excluding RUNX1. These patients present with a recognizable phenotype specific for this 21q22.1–q22.2 locus. We searched the literature for patients with overlapping deletions including the DYRK1A gene, in order to define other genes responsible for this presentation.
APOE ε2 Allele Is Associated with Larger Regional Cortical Thicknesses and Volumes
Authors: Liu Yawu , Paajanen Teemu , Westman Eric , Zhang Yi , Wahlund Lars-Olof , Simmons Andrew , Tunnard Catherine , Sobow Tomasz , Proitsi Petroula , Powell John , Mecocci Patrizia , Tsolaki Magda , Vellas Bruno , Muehlboeck Sebastian , Evans Alan , Spenger Christian , Lovestone Simon , Soininen Hilkka ,   for the AddNeuroMed Consortium
Published: April 2017

Background: The protective effect of the apolipoprotein E (APOE) Ε2 allele against Alzheimer’s disease (AD) is controversial. Objective: Our purpose was to clarify if the Ε2 allele affects regional cortical thicknesses and volumes. Methods: Regional cortical thicknesses and volumes were measured with an automated pipeline in 109 subjects with mild cognitive impairment, 114 AD patients and 105 age-matched healthy controls. Results: In the mild cognitive impairment group, the Ε2 carriers had thicker regional cortices at the transverse temporal cortex and parahippocampal gyrus than the subjects with Ε3/Ε3, and a larger cerebral gray matter and smaller lateral ventricles than the Ε3/Ε3 and Ε4 carriers. In the AD group, the Ε2 carriers had significantly thicker entorhinal and transverse temporal cortices, a larger whole cerebral gray matter, and smaller lateral ventricles than the subjects with the Ε3/Ε3 genotype, and a significantly thicker entorhinal cortex and larger cerebral gray matter than Ε4 carriers. No APOE2 effect was found in the control group. Conclusion: The APOE Ε2 allele is associated with larger regional cortical thicknesses and volumes in mild cognitive impairment and AD.
Cerebrospinal Fluid Tau Protein Levels and 18F-Fluorodeoxyglucose Positron Emission Tomography in the Differential Diagnosis of Alzheimer’s Disease
Authors: Yakushev Igor , Bartenstein Peter , Siessmeier Thomas , Hiemke Christoph , Scheurich Armin , Lotz Johannes , Fellgiebel Andreas , Müller Matthias J.
Published: April 2017

Aims: In this study, we aimed to compare cerebrospinal fluid (CSF) levels of total tau (t-tau), phosphorylated tau (p-tau181) and positron emission tomography with 18F-fluorodeoxyglucose (FDG-PET) in the differential diagnosis of Alzheimer’s disease (AD) under clinical conditions. Method: In a cross-sectional, blinded, single-center study, we examined a sample of 75 unselected memory clinic patients with clinical diagnoses of dementia of Alzheimer type (DAT; n = 24), amnestic mild cognitive impairment (MCI; n = 16), other dementias (n = 13) and nondemented controls (n = 22). Discriminative accuracy, sensitivity and specificity were calculated and compared using ROC analyses. Results: p-tau181 and FDG-PET were comparable in separating DAT from controls (sensitivity: 67 vs. 79%; specificity: 91% for both) and patients with other dementias (sensitivity: 71 vs. 79%; specificity: 100% for both). The sensitivity of p-tau181 in differentiating MCI patients from controls was significantly (p < 0.05) superior to that of FDG-PET (75 vs. 44%) at a comparably high specificity (82 vs. 91%); t-tau measures were less accurate in all analyses. Conclusions: FDG-PET and CSF p-tau181 levels are able to discriminate DAT in heterogeneous and unselected samples with a high accuracy. CSF p-tau181 might be somewhat superior for a sensitive detection of patients with MCI.
Prevalence of Dementia in Elderly Living in Two Cities of Central Africa: The EDAC Survey
Authors: Guerchet Maëlenn , M’belesso Pascal , Mouanga Alain M. , Bandzouzi Bébène , Tabo André , Houinato Dismand S. , Paraïso Moussiliou N. , Cowppli-Bony Pascale , Nubukpo Philippe , Aboyans Victor , Clément Jean-Pierre , Dartigues Jean-François , Preux Pierre-Marie
Published: April 2017

Background: Data on dementia from low- and middle-income countries are still necessary to quantify the burden of this condition. This multicenter cross-sectional study aimed at estimating the prevalence of dementia in 2 large cities of Central Africa. Methods: General population door-to-door surveys were conducted in the districts of Bangui (Republic of Central Africa) and Brazzaville (Congo) in elderly aged ≧65 years. The subjects were screened with the Community Screening Interview for Dementia and the Five-Words Test. Diagnosis of dementia was made according to the DSM-IV criteria and to the clinical criteria proposed by the NINCDS-ADRDA for Alzheimer’s disease. Results: We enrolled 496 subjects in Bangui and 520 in Brazzaville. The prevalence of dementia was estimated at 8.1% (95% CI = 5.8–10.8) in Bangui and 6.7% (95% CI = 4.7–9.2) in Brazzaville. Conclusion: The prevalence of dementia in urban areas of Central Africa is close to those observed in high-income countries.
Psychometric Evaluation of the Characteristics of Delusions Rating Scale as an Expert Rating Scale
Authors: Gentner Nana Christina , Büche Liesa , von Bock Anique , Rückl Sarah , Marx Jens , Kaiser Stephan , Barthel Andreas , Vedder Helmut , Mundt Christoph , Kronmüller Klaus-Thomas
Published: April 2017

Background: Research suggests delusions may be better viewed as multidimensional rather than dichotomous phenomena. The aim of this study was to assess the reliability and validity of a German version of the Characteristics of Delusions Rating Scale (CDRS) as an expert rating scale. Method: 200 inpatients with schizophrenic spectrum and affective disorders with delusions were assessed with the CDRS and other delusion rating scales. Factorial validity was analysed, and differences between diagnostic groups on the CDRS subscales as well as on the total score were examined. Results: The CDRS was found to have good inter-rater reliability and internal consistency as an expert rating. Factor analysis yielded an interpretable structure with 3 factors – cognition, emotion and bizarreness – accounting for 70% of the variance. The convergent and differential validity of the scales was supported. Compared to other scales, the CDRS measures all dimensions of delusional experience that have been suggested to date with the exception of behavioural aspects. Conclusions: The results support the view of delusions as multidimensional phenomena. The CDRS as an expert rating is a reliable and valid assessment tool for dimensions of delusional experience and an economical instrument for research and clinical practice. Further research is needed to examine the dimensional structure underlying delusional phenomena and the relationship of the dimensions to neurobiological and psychotherapeutic processes.
Validation of the Combined Emotional and Affective Temperament Scale in a Large Sample with High Prevalence of Psychiatric Disorders
Authors: Ottoni Gustavo L. , Lorenzi Taise M. , Reppold Caroline , Lara Diogo R.
Published: April 2017

Background: Based on a model where temperament works as a system with activation, inhibition and control, which produce the affective tone, we developed and validated the Combined Emotional and Affective Temperament Scale (CEATS). This paper aims to validate the CEATS in a large population with high prevalence of psychiatric disorders. Methods: 4,381 subjects (25.5% males) completed an internet version of the scale on a psychoeducational website on bipolar disorders. The CEATS has both emotional and affective sections and an evaluation of problems and benefits related to temperament. Data were analyzed with standard psychometric batteries. Results: In the emotional section, four factors with an eigenvalue >1 explained 47.3% of the variation. They were interpreted as anger, control, fear and drive. They had a normal distribution and satisfactory Chronbach’s alphas. Anger was particularly associated with problems, and drive with benefits. In the Affective section, all 10 categorical affective temperaments were selected, cyclothymic being the most prevalent (32%), and 97.6% of the sample was able to ascribe to at least one affective temperament. Only the euthymic and hyperthymic temperaments were associated with a favorable problem/benefit profile. Each affective temperament had a particular emotional configuration. Conclusion: The CEATS is adequate to assess emotional and affective temperament in subjects with high prevalence of psychiatric disorders.
Apolipoprotein Alleles and the Response to Interferon-β-1b in Multiple Sclerosis
Authors: Carmona Olga , Masuet Cristina , Alía Pedro , Moral Ester , Alonso-Magdalena Lucía , Casado Virginia , Martín-Ozaeta Gisela , Arbizu Txomin
Published: April 2017

Background: Results for the e4/e2 alleles of the ApoE gene as markers of susceptibility, clinical and radiological progression, and cognitive deterioration in patients with multiple sclerosis (MS) are contradictory. Aim: The usefulness of these markers in predicting the response to interferon-β-1b (IFNβ-1b) was evaluated. Material and Methods: 95 patients with relapsing-remitting MS treated with IFNβ-1b (mean follow-up 7.44 years) were studied. We correlated the e4 and e2 alleles with the time to the first relapse or to a 1-point worsening on the Expanded Disability Status Scale, time to moderate disability, progression index, and treatment discontinuation due to inefficacy. Results: We found no association between the e4 allele and any of the variables. The e2 allele was associated with increased time to moderate disability. Conclusion: The e4 allele of ApoE has no prognostic value for the response to IFNβ-1b. The e2 allele delayed the progression of disability in our MS patient cohort.