bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect Of Anti‐Oxidant Treatment And Cholesterol Lowering On Resting Arterial Tone, Metabolic Vasodilation And Endothelial Function In The Human Forearm: A Randomized, Placebo‐Controlled Study
Authors: Duffy Stephen J , O'Brien Richard C , New Gishel , Harper Richard W , Meredith Ian T 
Published: March 2003

SUMMARY1. The aim of the present study was to determine whether anti‐oxidant therapy with vitamin E and/or cholesterol‐lowering therapy with simvastatin would augment resting forearm blood flow (FBF) and metabolic vasodilation in response to exercise and improve endothelial function in young patients with hypercholesterolaemia.2. Endothelium‐dependent and ‐independent, nitric oxide (NO)‐mediated vasodilation have been shown to be impaired in young, otherwise healthy subjects with hypercholesterolaemia. Recent experimental and clinical studies suggest that vascular function may be improved with anti‐oxidant or cholesterol‐ lowering therapy, although these treatments may be synergistic.3. We compared FBF at rest, in response to isotonic exercise, the endothelium‐dependent vasodilator acetylcholine (ACh), the endothelium‐independent vasodilator sodium nitroprusside (SNP) and the NO synthase inhibitor NG‐monomethyl‐L‐arginine (L‐NMMA) in 26 young, otherwise healthy volunteers (mean (±SD) age 29±7 years; 14 female, 12 male) with hypercholesterolaemia, before and after 6 months treatment with vitamin E, simvastatin and/or placebo. Treatment was randomized, double‐blinded in a 2 × 2 factorial design. Forearm blood flow was measured using venous occlusion plethysmography.4. Vitamin E therapy increased plasma α‐tocopherol from 39.5±9.6 to 75.7±33.8 μmol/L (P < 0.001). Simvastatin reduced total cholesterol from 6.9±1.7 to 4.9±0.8 mmol/L and low‐ density lipoprotein (LDL) from 4.8±1.7 to 3.0±0.7 mmol/L (both P < 0.001), although total and LDL–cholesterol also decreased slightly in the placebo group. Vitamin E increased resting FBF from 2.1±0.3 to 2.4±0.3 mL/100 mL per min (P = 0.04) and decreased resting forearm vascular resistance from 42.1±4.2 to 36.1±3.4 units (P = 0.01), but the reduction in resting FBF with L‐NMMA was not affected. Vasodilation in response to isotonic exercise, ACh and SNP was similar before and after treatment in the placebo, vitamin E, simvastatin and in the combined vitamin E–simvastatin groups. NG‐Monomethyl‐L‐arginine infusion reduced resting FBF and functional hyperaemia in response to exercise and these responses were not altered by treatment.5. These data suggest that while vitamin E therapy augments resting FBF and reduces forearm vascular resistance in young hypercholesterolaemic subjects, these effects may not be via NO‐dependent pathways. Metabolic vasodilation and responses to the NO‐mediated vasodilators ACh and SNP were not favourably affected by anti‐oxidant or cholesterol‐lowering therapy, either alone or in combination.
Role Of Angiotensin Type 2 Receptors In Human Forearm Vascular Responses Of Normal Volunteers
Authors: Phoon Stephen , Howes Laurence Guy 
Published: March 2003

SUMMARY1. It has been hypothesized that the expression of angiotensin (Ang) II type 2 (AT2) receptors may become important in vascular disease; however, the functional existence of AT2 receptors in normal adult humans remains to be established.2. Vascular responses to AngII after the administration of the specific AT2 receptor antagonist PD 123319 were determined in the forearm circulation of normal volunteers.3. PD 123319 (8 μg/min) did not alter basal forearm blood flow, or forearm blood flow or forearm vascular resistance responses to AngII.4. These results suggest that AT2 receptors do not play a significant role in the regulation of forearm blood flow or forearm vascular resistance of normal volunteers, but do not preclude a role for AT2 receptors in other vascular beds or in patients with cardiovascular disease.
Involvement Of B‐50 (GAP‐43) Phosphorylation In The Modulation Of Transmitter Release By Protein Kinase C
Authors: Iannazzo L 
Published: March 2003

SUMMARY1. Protein kinase C (PKC) is a family of enzymes that is activated by diacylglycerol (DAG) following phospholipase (PL) C activation. Protein kinase C may also be activated by metabolites and arachidonic acid generated by breakdown of membrane phospholipids by PLD and PLA2, respectively. Subsequent to PKC activation, key protein substrates are phosphorylated, resulting in the facilitation of transmitter release.2. Phorbol esters are compounds that mimic the actions of DAG on PKC and have been shown to facilitate stimulation‐induced (S‐I) transmitter release in rat brain. However, some phorbol esters that have a high affinity for PKC have no effect on transmitter release, whereas others with a lower affinity for PKC markedly elevate S‐I transmitter release.3. The structure and, more importantly, the lipophilicity of the phorbol esters determines their ability to access and activate the intraneuronal pools of PKC that are involved with transmitter release. In studies in which cell membranes were intact, phorbol esters did not display the characteristics expected based on their affinities for PKC in contrast with studies in disrupted synaptosomes. This supports the hypothesis that the membrane plays a critical role in determining the effects of phorbol esters on PKC.4. B‐50, a PKC substrate thought to be involved in transmitter release, also appears to be differentially phosphorylated by various phorbol esters. The effects on B‐50 phosphorylation in intact synaptosomes, but not disrupted synaptosomes, are well correlated with the effects of phorbol esters on S‐I transmitter release.5. B‐50 is colocalized with actin, which has also been suggested to play an important role in facilitating the movement of reserve pools of transmitter vesicles to the readily releasable state. Therefore, it is possible that the phosphorylation status of B‐50 directly influences the organization of actin filaments, thereby allowing transmitter output to be sustained under high levels of stimulation.
Role Of Arterial Smooth Muscle Tone And Geometry In The Regulation Of Peripheral Conduit Artery Mechanics By Shear Stress
Authors: Joannides Robinson , Costentin Agathe , Iacob Michaela , Bakkali El‐Hassan , Richard Marie‐Odile , Thuillez Christian 
Published: March 2003

SUMMARY1. Although arterial blood flow is recognized as an important modulator of vascular tone and geometry, the effect of acute changes in shear‐stress on conduit artery mechanics has not been fully investigated in humans because of technical limitations.2. To assess, respectively, the effects of decreases and increases in flow and shear stress on radial artery tone and mechanics, arterial pressure (photoplethysmography), total blood viscosity, radial artery internal diameter, wall thickness (echotracking) and blood flow (Doppler) were measured in healthy volunteers (mean (±SEM) age 25 ± 1 years) during a distal flow arrest (n = 12) and hand skin heating (n = 18).3. Radial artery flow decreased from 31 ± 4 to 7 ± 1 10–3 L/min during distal flow arrest (P < 0.001) and increased from 10 ± 2 to 22 ± 4 and 69 ± 6 10–3 L/min during heating (P < 0.001). At mean arterial pressure, these changes in flow were respectively associated with a parallel flow‐dependent reduction and increase in diameter and midwall stress. There was no significant modification in mean elastic modulus. Compliance did not change when flow decreased and only increased at the highest level of flow. Finally, the cross‐sectional compliance and incremental modulus were fitted as functions of midwall stress. The decrease in flow was associated with an upward shift of the modulus–midwall stress curve and a downward shift of the compliance–midwall stress curve. The increase in flow was associated with a downward shift of the modulus–midwall stress curve and an upward shift of the compliance–midwall stress curve at each level of wall shear stress.4. By using two different procedures, we obtained similar results concerning the direct effects of increases and decreases in flow on stiffness of the arterial wall and on arterial compliance and demonstrated the presence of a flow‐dependent regulation of arterial smooth muscle tone of peripheral conduit arteries in humans.
Protective Effect Of α‐LIPOIC Acid Against Ischaemic Acute Renal Failure In Rats
Authors: Takaoka Masanori , Ohkita Mamoru , Kobayashi Yutaka , Yuba Mikihiro , Matsumura Yasuo 
Published: March 2003

SUMMARY1. In the present study, we investigated whether treatment with α‐lipoic acid (LA), a powerful and universal anti‐oxidant, has renal protective effects in rats with ischaemic acute renal failure (ARF).2. Ischaemic ARF was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Blood urea nitrogen (BUN), plasma concentrations of creatinine (Pcr) and urinary
osmolality (Uosm) were measured for the assessment of renal dysfunction.
Creatinine clearance (Ccr) and fractional excretion of Na+
(FENa) were used as indicators of glomerular and tubular function, respectively.3. Renal function in ARF rats decreased markedly 24 h after reperfusion. Intraperitoneal injection of LA at a dose of 10 mg/kg before the occlusion tended to attenuate the deterioration of renal function. A higher dose of LA (100 mg/kg) significantly (P
< 0.01) attenuated the ischaemia/reperfusion‐induced increases in BUN (19.1 ±
0.7 vs 7.2 ± 0.7 mmol/L before and after treatment, respectively),
Pcr (290 ± 36 vs 78.1 ± 4.2 μmol/L
before and after treatment, respectively) and FENa (1.39 ±
0.3 vs 0.33 ± 0.09% before and after treatment, respectively).
Treatment with 100 mg/kg LA significantly (P < 0.01) increased Ccr
(0.70 ± 0.13 vs 2.98 ± 0.27 mL/min per kg before
and after treatment, respectively) and Uosm (474 ± 39 vs
1096 ± 80 mOsmol/kg before and after treatment, respectively).4. Histopathological examination of the kidney of ARF rats revealed severe lesions. Tubular necrosis (P < 0.01), proteinaceous casts in tubuli (P <
0.01) and medullary congestion (P < 0.05) were significantly suppressed by the higher dose of LA.5. A marked increase in endothelin (ET)‐1 content in the kidney after ischaemia/reperfusion was evident in ARF rats (0.43 ± 0.02 ng/g tissue) compared with findings
in sham‐ operated rats (0.20 ± 0.01 ng/g tissue). Significant attenuation
(P < 0.01) of this increase occurred in ARF rats treated with the higher
dose of LA (0.24 ± 0.03 ng/g tissue).6. These results suggest that administration of LA to rats prior to development of ischaemic ARF prevents renal dysfunction and tissue injury, possibly through the suppression of overproduction of ET‐1 in the postischaemic kidney.
Stress‐Specific Opioid Modulation Of Haemodynamic Counter‐Regulation
Authors: Molina Patricia E 
Published: March 2003

SUMMARY1. The haemodynamic and cardiovascular responses to stress, in addition to being under control of the autonomic nervous system, are also under opiate modulation. Our studies have provided evidence for activation of the endogenous opioid system in haemorrhagic shock, sepsis and trauma. Furthermore, we have demonstrated that both central and systemic opiate administration to naïve rats result in marked alterations in haemodynamic responses, which are associated with activation of the sympathetic nervous system.2. Because of the ubiquitous presence of opiate receptors in both the central nervous system and peripheral tissues, as well as their production and release centrally and peripherally, this facilitates an endocrine as well as a paracrine contribution to modulating vascular responses to stress, either directly or indirectly. Results from previous studies suggest that endogenous opioids are not involved in mediating the lipopolysacharide‐induced hypotensive response.3. In more recent studies, we have examined the role of opiate receptor activation in modulating the haemodynamic and neuroendocrine responses to fixed pressure haemorrhagic shock in conscious unrestrained rats. Using systemic opiate blockade (naltrexone, 15 mg/kg, i.p.) prior to haemorrhage, we have observed that blood loss required to achieve mean arterial blood pressure of 40 mmHg was higher in naltrexone‐treated animals than in time‐matched saline controls. Interestingly, the haemodynamic modulation exerted by naltrexone cannot be attributed to differences in circulating catecholamine levels. Haemorrhage produced an immediate and progressive increase in circulating adrenaline and noradrenaline levels, reaching values that were 50‐ and 20‐fold higher than basal, respectively. Naltrexone pretreatment did not alter the time‐course or magnitude of the rise in circulating levels of catecholamines.4. These results indicate that endogenous opioid activation contributes to the haemodynamic dishomeostasis associated with blood loss. Our findings suggest stress‐specific roles for opiate‐sensitive haemodynamic counter‐regulatory responses.
Nitric Oxide In Mesenteric Vascular Reactivity: A Comparison Between Rats With Normotension And Hypertension
Authors: Chang Huai‐Ren , Lee Ru Ping , Wu Chia Yen , Chen Hsing I 
Published: March 2003

SUMMARY1. Nitric oxide (NO) plays an important role in various physiological functions. The continuous formation of endogenous NO from endothelial cells maintains a vasodilator tone and regulates blood flow and pressure. However, the role of NO in hypertension remains controversial.2. In the present study, we used an in situ mesenteric perfusion system. The primary objectives of the study were to examine whether or not mesenteric vasoreactivity is changed by alterations in perfusion pressure and to assess the role of NO in changes of vascular reactivity in hypertension.3. Spontaneously hypertensive rats (SHR; 12–15 weeks of age) and age‐matched normotensive Wistar‐Kyoto (WKY) rats were used as the experimental and control groups, respectively. Endothelium‐dependent and ‐independent vasodilation was detected by acetylcholine (ACh) or NO donors (sodium nitroprusside (SNP) and S‐nitroso‐N‐acetylpenicillamine
(SNAP)). Dose‐dependent reactivity to these agents (10–6 to 10–4
mol/L) was detected by bolus intra‐arterial injections of 10 μL of the
test agents at 5 min intervals. Dose‐dependent responses to vasoconstrictor drugs,
such as noradrenaline (NA) and phenylephrine (PE; 10–6 to 10–4
mol/L) were also observed. The NO synthase inhibitor NG‐nitro‐L‐arginine
methyl ester (L‐NAME; 10 mg/kg) was given to examine the contribution of NO to the vasoreactivity of the mesenteric bed.4. Acetylcholine, SNP and SNAP produced dose‐dependent vasodilation in both WKY rats and SHR. The magnitude of the vasodilation was significantly greater in SHR than in WKY rats. It was also greater at high than low flow rates in SHR. The increase in mesenteric perfusion pressure following L‐NAME was significantly
higher in SHR than in WKY rats. However, there were no differences in responses to
L‐NAME between low and high flow rates in SHR. Endothelium‐independent vasoconstriction (NA and PE) was dose dependent in both SHR and WKY rats. The magnitude of the endothelium‐independent vasoconstriction was greater in SHR than in WKY rats.5. The results suggest that endothelium‐dependent or ‐independent mesenteric vasoconstriction and vasodilation is enhanced in SHR compared with WKY rats, supporting the concept of enhancement of NO function in the hypertensive state. Flow‐induced shear stress is also a key factor in the regulation of peripheral resistance depending on NO formation in hypertension.
Weight Reduction Decreases Soluble Cellular Adhesion Molecules In Obese Women
Authors: Ito Hiroyuki , Ohshima Akiko , Inoue Misako , Ohto Naoko , Nakasuga Kazuta , Kaji Yoshikazu , Maruyama Toru , Nishioka Kazuo 
Published: March 2003

SUMMARY1. Obesity is known to increase the risk for atherosclerotic diseases. Serum levels of cellular adhesion molecules are reported to be indices of atherosclerosis. The aim of the present study was to assess the effect of weight reduction on soluble intercellular adhesion molecule‐1 (sICAM‐1) and soluble E‐selectin (sE‐selectin).2. Eighteen non‐diabetic normotensive obese women participated in a 3 month lifestyle‐modification programme (intervention group). The programme consisted of lectures on diet, exercise sessions and behavioural modification by weight charting. Fourteen women who did not enter the programme served as controls. Body fat mass (FM) was measured by dual‐energy X‐ray absorptiometry. Soluble ICAM‐1 and sE‐selectin were measured by ELISA.3. After 3 months, sICAM‐1 and sE‐selectin, as well as body FM, decreased in the intervention group (P < 0.001), while no changes were observed in the control group. The baseline sE‐selectin was positively correlated with total body FM, trunk FM and percentage body fat (r = 0.50–0.57; P < 0.01), but not with leg FM. The change in sE‐selectin was also correlated with changes in total body FM and trunk FM (both r = 0.46; P < 0.01). Baseline sICAM‐1 was not significantly correlated with these variables. The associations between changes in sICAM‐1 and changes in total body FM or trunk FM were of borderline significance (both r = 0.34; P = 0.06). Linear regression analysis indicated that the change in sE‐selectin was explained by the change in trunk FM (R2 = 0.18; P < 0.01).4. Soluble ICAM‐1 and sE‐selectin were positively correlated with obesity, especially with central obesity. Weight reduction resulted in decreases in soluble adhesion molecules, which may suggest a downregulation of endothelial activation.
Mode‐dependent inhibition by quinidine of Na+–Ca2+ exchanger current from guinea‐pig isolated ventricular myocytes
Authors: Zhang YH , Hancox JC 
Published: March 2003

Summary1. The aim of the present study was to determine whether or not the class Ia anti‐arrhythmic agent quinidine modulates ionic current (INaCa) generated by the sarcolemmal Na+–Ca2+ exchanger of adult ventricular cardiac myocytes.2. Selective whole‐cell voltage‐clamp recordings of INaCa were made from guinea‐pig ventricular myocytes, with major interfering currents blocked. The INaCa was measured as the ionic current sensitive to 10 mmol/L external Ni2+ during a descending voltage ramp protocol.3. The effects of quinidine concentrations in the range 10–100 μmol/L were studied. Quinidine produced a concentration‐dependent partial blockade of outward INaCa, generated by reverse‐mode exchange. At +60 mV, 100 μmol/L quinidine blocked INaCa by 33.0 ± 4.1% (mean±SEM; n = 4). This was the maximal concentration that we were able to test, because concentrations of quinidine higher than 100 μmol/L were found to be toxic to cells under our conditions. The drug did not produce any significant inhibition of inward INaCa (generated by forward‐mode exchange).4. The Ni2+‐insensitive residual current was not significantly altered by quinidine at any membrane potential, confirming that the inhibitory effects of quinidine we observed could be attributed to an action on the Na+–Ca2+ exchanger.5. For the purpose of comparison, quinidine was tested against L‐type Ca current (ICa,L). It blocked peak ICa,L at 0 mV, with an IC50 of 14.9 ± 1.5 μmol/L. Thus, quinidine was less potent against the exchanger than against ICa,L.6. Our data suggest that quinidine preferentially inhibits the Naout/Cain mode of exchanger function. We conclude that this drug is a weak inhibitor of ventricular INaCa and that the inhibitory effect is mode dependent.
Human vascular endothelial growth factor B: Characterization of recombinant isoforms and generation of neutralizing monoclonal antibodies
Authors: Scotney PD , MacKenzie A , Maccarone P , Fabri LJ , Scrofani SDB , Gooley PR , Nash AD 
Published: March 2003

Summary1. The vascular endothelial growth factor (VEGF) family is a focus of interest with respect to novel therapies for cardiovascular disease. Members of this family bind differentially to three receptor tyrosine kinases, namely VEGF‐R1, ‐R2 and ‐R3, and to the semaphorin receptors neuropilin 1 and 2. The role of VEGF‐R1 and the factors that interact exclusively with this receptor (VEGF‐B and placenta growth factor) has remained controversial.2. To further elucidate the role of VEGF‐B in blood vessel formation and function, we have expressed, purified and refolded both naturally occurring VEGF‐B isoforms and a truncated amino acid 10–108 form. All refolded proteins have been demonstrated to bind to VEGF‐R1 with appropriate kinetics in biosensor‐based analysis.3. Robust cell assays for VEGF‐R1 ligands, such as VEGF‐B, have been problematic. We have developed an assay based on a chimeric receptor consisting of extracellular domains 1–4 of VEGF‐R1 and the transmembrane and intracellular domains of gp130. The cell line expresses luciferase to high levels 24 h after exposure to VEGF‐A and both refolded VEGF‐B167 and the short 10–108 isoform have been demonstrated to be active in this assay.4. The novel cell‐based assay, in combination with a variety of immunochemical approaches, has been used to identify and characterize monoclonal antibodies that neutralize VEGF‐B activity.
Identification and characterization of a unique Xenopus laevis egg envelope component, ZPD
Authors: Lindsay LeAnn L. , Yang Joy C. , Hedrick Jerry L. 
Published: March 2003

We report the identification of a previously undetected Xenopus laevis egg envelope component discovered through cloning experiments. A cDNA sequence was found that represented a mature protein of 32 kDa. Peptide antibodies were generated to probe for the protein in egg envelope samples and reactivity was found to a glycoprotein of approximately 80 kDa. When deglycosylated egg envelope samples were probed, a 32 kDa protein was labeled, confirming the size of the translated cDNA sequence. A BLAST analysis showed that it is most closely related (34% amino acid identity) to the ZP domains of mammalian tectorin, uromodulin and ZPA. From a dendrogram of known egg envelope glycoproteins, the new glycoprotein was shown to be unique among egg envelope components and was designated ZPD. A similar glycoprotein was identified by immunocrossreactivity in Xenopus tropicalis and Xenopus borealis egg envelopes.
Of mites and bees: A review of mite–bee associations in Australia and a revision of Raymentia Womersley (Acari: Mesostigmata: Laelapidae), with the description of two new species of mites from Lasioglossum (Parasphecodes) spp. (Hymenoptera: Halictidae)
Authors: Walter David Evans , Beard Jennifer J , Walker Ken L , Sparks Kathryn 
Published: March 2003

AbstractSocial bees have a diverse fauna of symbiotic mesostigmatic mites, including highly pathogenic parasites of the honeybee, but there are few reports of Mesostigmata phoretic on or inhabiting the nests of solitary or communal, ground‐nesting bees. In south‐eastern Australia, however, native bees in the family Halictidae carry what appears to be a substantial radiation of host‐specific mesostigmatans in the family Laelapidae. Herein, we redescribe the obscure genus Raymentia, associated with Lasioglossum
(Parasphecodes) spp. bees (Halictidae) and describe two new species, R.
eickwortiana from L. lacthium (Smith) and R. walkeriana from L.
atronitens (Cockerell). The type species, R. anomala Womersley, is associated
with L. altichum (Smith). In addition, we review the mites known to be associated
with Australian bees, provide a key to differentiate them, and describe and illustrate
acarinaria of the Halictinae. We also report on the first occurrences in Australia
of the genera Trochometridium Cross (Heterostigmata: Trochometridiidae), from
L. eremaean Walker (Halictidae), and Cheletophyes Oudemans (Prostigmata:
Cheyletidae) from Xylocopa Latreille (Xylocopinae), and on the previously
unknown association between a Neocypholaelaps Vitzthum (Mesostigmata: Ameroseiidae)
and Lipotriches tomentifera (Friese) (Halictidae).