bluuebunny/crossref_metadata_2025 huggingface dataset:
Arterial Wall Thermography
Authors: DIAMANTOPOULOS LEONIDAS
Published: May 2003

An atherosclerotic plaque is considered vulnerable when it is at higher risk of inducing acute cardiac events. The early detection and follow‐up of the vulnerable plaque are crucial to prevent these events from happening. To date there are no proven techniques to detect such a plaque. Arterial wall thermography, tracing the heat signature of the activated macrophages, is a new and promising method in this direction. However, the difficulties of applying such a method in vivo should not be neglected. Current science proposes several potential thermographic methods. They can be generally categorized as noninvasive and invasive. Magnetic resonance thermometry (MRT) is the most important noninvasive method. It is novel, accurate, and reproducible, but is unfortunately hampered by resolution limitations due to the size and motion of the target vessels. The “infrared” and the “contact‐sensor” are the most important invasive thermographic methods. Mainly due to the difficulties of infrared radiation in penetrating the flowing blood, the contact thermographic methods seem to be the most feasible at present. The superiority of thermal mapping of the arterial wall versus the localized temperature measurements is clear. The use of multiple thermal sensors arranged around the vessel's circumference and the application of motorized catheter pullback, not only ensure a large area of coverage, but also enable us to build thermal maps and vascular thermoanatomical reconstructions by using modern computer technology. It is expected that arterial thermography will undoubtedly initiate debate, mainly concerning the most appropriate therapy for the vulnerable plaque. Data collection and correct interpretation are expected to lead us into making wise decisions. (J Interven Cardiol 2003;16:261–266)
Pathology of the Thin‐Cap Fibroatheroma:
Authors: VIRMANI RENU , BURKE ALLEN P. , KOLODGIE FRANK D. , FARB ANDREW
Published: May 2003

Thin cap atheroma is the precursor of plaque rupture, which accounts for a majority of coronary thrombi. The morphologic features of thin cap atheromas that predict rupture are unknown, but we know from studies of ruptured plaques that large necrotic cores, fibrous cap <65 microns and numerous macrophages within the cap likely indicate instability. There is some evidence that a speckled pattern of calcification is associated with vulnerability to rupture. There are usually multiple thin cap atheroma in the hearts of patients dying with acute plaque rupture, as well as multiple fibroatheromas with intraplaque hemorrhage. Targeted therapy for the purpose of stabilizing coronary lesions that are prone to rupture is a major future goal of the interventionist. (J Interven Cardiol 2003;16:267–272)
Vulnerable Plaque:
Authors: STEFANADIS CHRISTODOULOS , VAVURANAKIS MANOLIS , TOUTOUZAS PAVLOS
Published: May 2003

In order to understand, treat, and prevent acute coronary syndromes we need to improve our ability to identify the rupture‐prone, vulnerable atherosclerotic coronary plaque. The diagnostic modalities that are currently available to clinical practice have not fulfilled this expectation, and newer diagnostic techniques based on the recently identified features of the vulnerable plaque are quite promising. Coronary angiography, intravascular ultrasound, and angioscopy have been used in the clinical arena of interventional cardiology with several limitations regarding the identification of the vulnerable plaque. Thermography, optical coherence tomography, elastography, Raman spectroscopy, and infrared spectroscopy are used in clinical trials and the results are encouraging. Ultrafast computed tomography and magnetic resonance imaging have the advantage of being noninvasive. With our progress in the identification of the rupture‐prone vulnerable coronary plaque, we will be able to identify patients that are at high risk and will benefit from a more aggressive therapeutic approach. (J Interven Cardiol 2003;16:273–280)
A Randomized Comparison of a Percutaneous Suture Device versus Manual Compression for Femoral Artery Hemostasis after PTCA
Authors: TRON CHRISTOPHE , KONING RENÉ , ELTCHANINOFF HÉLÈNE , DOUILLET RÉMY , CHASSAING STÉPHAN , SANCHEZ‐GIRON CARLOS , CRIBIER ALAIN
Published: May 2003

Background:
The prolonged bed rest following femoral sheath removal after PTCA is a source of discomfort for the patient. We designed a randomized study to evaluate the efficacy and safety of an arterial suture device developed to percutaneously close the vascular access site after PTCA, allowing immediate sheath removal and early ambulation, compared to manual compression.

Methods:
After successful PTCA, patients were randomized to manual compression or immediate femoral percutaneous closure. Exclusion criteria were arteritis, age >80 years and >3 previous femoral punctures on the same side. The two‐needle device was used for the 6F sheath removal and the four‐needle device for the 8F sheath. Ambulation was allowed 4 hours after the arterial suture.

Results:
One hundred and sixty‐seven patients (

59 ± 10 years

, 81% males) were randomized to suture device

(n = 91)

or to manual compression

(n = 76)
. The two groups were similar in terms of age, sex, size of sheath, number of patients with stent implantation (62 vs 61%), procedural anticoagulation. Procedural duration was8 ± 6 minuteswith percutaneous suture versus25 ± 11 minuteswith manual compression(P < 0.0001). Procedural success with percutaneous suture was 93% whereas six technical failures were treated with prolonged manual compression. Nonsurgical hematoma occurred in five patients (5%) with the suture device and in two (3%) with manual compression with no need for blood transfusion(P = NS). Uneventful blood oozing occurred in 11 patients (12%) with percutaneous suture and in only 2 (3%) with manual compression(P < 0.06). The tolerance of the hemostasis procedure and the length of post‐procedure hospital stay(40 ± 32 hours)were similar in the two groups.Conclusion:Percutaneous suture of the femoral artery, allows immediate closure of femoral puncture sites after PTCA, without increasing the incidence of vascular complications. The use of this device should allow earlier discharge and subsequent cost savings. (J Interven Cardiol 2003;16:217–221)
Safety, Efficacy, and Cost Advantages of Combined Coronary Angiography and Angioplasty
Authors: LE FEUVRE CLAUDE , HELFT GÉRARD , BEYGUI FARZIN , ZERAH THIERRY , FONSECA EDOUARD , CATULI DIDIER , BATISSE JEAN PAUL , METZGER JEAN PHILIPPE
Published: May 2003

Aim: The safety and efficacy of ad hoc PTCA has been previously reported and this approach is performed in many angioplasty centers as a routine procedure. The aim of this study is to examine whether this approach reduces the length, and cost of hospital stay. Methods and results: To determine the hospital costs we studied 2,440 PTCAs over 11 years in our institution (1990–2000). Urgent PTCA for acute coronary syndromes refractory to medical treatment were excluded. In 1809 patients (74%) angioplasty was performed immediately after coronary angiography, while separate procedures were performed in 631 patients. Indication for PTCA was unstable angina in 1342 patients (55%). In the ad hoc PTCA group, 92% of the culprit lesions were successfully treated; complications included myocardial infarction (2%), urgent bypass surgery (0.6%) and death (0.9%). The rate of combined procedure progressively increased from 54% in 1990 to 88% in 2000, with a significant decrease in the rate of complications. After adjusting for clinical and angiographic differences between combined and separate procedures, angiographic success and complication rates were not statistically different in the two groups. Mean length of hospital stay decreased all along the years, and was 45% less in the ad hoc PTCA group (

11.4 ± 6.9

vs

18.2 ± 7.7

in 1990,

5.4 ± 4.3

vs

10.8 ± 5.7

in 2000,

P < 0.0001

). The cost was 40% lower in the ad hoc PTCA group. For patients with stable angina, the savings were 49%, and for those with unstable angina, they were 29%. Conclusion: In the era of coronary stenting, ad hoc PTCA can be performed in most of the patients as safely and successfully as a separate procedure. It reduces the length, and the cost of hospital stay in patients with stable or unstable angina. (J Interven Cardiol 2003;16:195–199)
Simple Technique to Ensure Coaxial Guidewire Positioning for Placement of Iliac Limb of Modular Aortic Endograft
Authors: DAWSON DAVID L. , TERRAMANI THOMAS T. , LOBERMAN ZEEV , LUMSDEN ALAN B. , LIN PETER H.
Published: May 2003

Endovascular abdominal aortic aneurysm repair using a modular bifurcated stent‐graft requires the initial placement of the main component in the infrarenal aorta, followed by insertion of additional iliac stent‐graft(s) to exclude aneurysm and to securely affix the device. Placement of the contralateral iliac component within the main bifurcated device is critical in this endovascular procedure, as malpositioning of the contralateral iliac limb can require conversion to open aneurysm repair. A simple adjunctive technique utilizing a rotational maneuver of a pigtail catheter is described. This maneuver reliably confirms the proper placement of the contralateral iliac stent‐graft within the main bifurcated device. (J Interven Cardiol 2003;16:223–226)
Acute Myocardial Infarction Complicated by Early Onset of Heart Failure:
Authors: BEDNÁŘ FRANTIŠEK , WIDIMSKÝ PETR , GROCH LADISLAV , ASCHERMANN MICHAEL , ŽELÍZKO MICHAEL , KRUPIČKA JIŘÍ ,   PRAGUE‐1 Study Group Investigators
Published: May 2003

Objective: The objective of this study is to assess the feasibility and safety of interhospital transfer (within up to 60 minutes) for primary/rescue coronary angioplasty of patients with myocardial infarction (AMI) complicated by an early onset of acute heart failure (AHF) admitted to a community hospital without PCI facilities. Design and patients: From the multicenter randomized PRAGUE‐1 study, a subgroup of 66 patients with AMI complicated by AHF on the first presentation to the community hospital were retrospectively analyzed. Group A patients

(n = 21)

were treated on site in community hospitals using thrombolysis (streptokinase), group B patients

(n = 20)

were transported with thrombolytic infusion to a PCI center for coronary angioplasty, and group C patients

(n = 25)

were immediately transported to a PCI center for primary angioplasty without thrombolysis. Results: No patient died during transportation. One group B patient developed ventricular fibrillation during transfer. The time delay from the onset of chest pain to reperfusion was >142 minutes, and 253 and 251 minutes in groups A, B, and C, respectively. Hospital stay (16 vs 11 vs 10 days,

P = NS

) was shorter in the angioplasty groups. Transported patients (groups B, C) displayed a significant decrease in heart failure progression within the first 24 hours after treatment (48% vs 15% vs 8%,

P < 0.05

). The combined end point, i.e., mortality + nonfatal reinfarction (43% vs 25% vs 8%,

P < 0.05

), was significantly less frequent in the coronary angioplasty group. Conclusions: Interhospital transfer for coronary angioplasty of patients with AMI complicated by an early onset of AHF is feasible and safe. Transport for angioplasty may even reduce the risk of heart failure progression and improve clinical outcome compared to immediate thrombolysis in the nearest community hospital. (J Interven Cardiol 2003;16:201–208)
The Long‐Term Clinical Outcomes after Rescue Percutaneous Coronary Intervention in Patients with Acute Myocardial Infarction
Authors: HONG YOUNG JOON , JEONG MYUNG HO , LEE SEUNG HYUN , PARK OK YOUNG , JEONG WOO KON , LEE SANG ROK , KIM WEON , RHEW JAY YOUNG , LEE SANG HYUN , AHN YOUNG KEUN , CHO JEONG GWAN , AHN BYOUNG HEE , PARK JONG CHUN , KIM SANG HYUNG , KANG JUNG CHAEE
Published: May 2003

Rescue percutaneous coronary intervention (PCI) has been used to treat patients after failed thrombolysis in acute myocardial infarction. However, the short‐ and long‐term benefits of rescue PCI have not been known exactly. The goal of this study was to examine the clinical and angiographic outcomes, the success rate of the procedure, and the long‐term survival rate after rescue PCI. The clinical and angiographic outcomes of 31 patients (Group I;

59.7 ± 11.4

years, 80.6% male), who underwent rescue PCI were compared with those of 177 patients (Group II;

59.7 ± 9.7

years, 79.7% male), who underwent primary PCI at Chonnam National University Hospital between January 1997 and December 1999. There were no significant differences in the risk factors for coronary artery diseases except for smoking (Group I;

24/31, 77.4%

vs. Group II;

76/177, 42.9%, P = 0.011

). The incidence of cardiogenic shock was higher in Group I than in Group II (Group I;

7/31, 22.6%

vs. Group II;

11/177, 6.2%, P = 0.021

). The coronary angiographic findings were not different between two groups, except for Thrombolysis in Myocardial Infarction (TIMI) flow of Group I was lower than in Group II (Group I;

1.14 ± 0.93

vs. Group II;

1.61 ± 1.14, P = 0.001

). The primary success rate was

93.6% (29/31)

in Group I and

94.9% (168/177)

in Group II

(P = 0.578)
. The baseline ejection fraction was lower in Group I than in Group II (Group I;44.2 ± 8.9%vs. Group II;50.8 ± 11.7, P = 0.023), which improved in both groups (Group I;51.7 ± 7.9%vs. Group II;60.7 ± 13.4%, P = 0.001respectively) at 6 months after the procedures. The survival rates of Group I were 93.5%, 93.5%, and 90.3% and those of Group II were 94.5%, 93.7%, and 91% at 1, 6, and 12 months, respectively. Rescue PCI is associated with the risk factor of smoking. The indication for rescue PCI was more common in patents with cardiogenic shock. The success rate of rescue PCI was comparable to that of primary PCI, and left ventricular function is improved after rescue PCI on long‐term clinical follow‐up with relatively high survival rate. (J Interven Cardiol 2003;16:209–216)
Intravascular Elastography:
Authors: DE KORTE CHRIS L. , SCHAAR JOHANNES A. , MASTIK FRITS , SERRUYS PATRICK W. , VAN DER DER STEEN ANTON F.W.
Published: May 2003

An unstable lesion may rupture and cause an acute thrombotic reaction. These lesions contain a large lipid pool covered by a thin fibrous cap. The stress in the cap increased with decreasing thickness and increasing macrophage infiltration. Intravascular ultrasound (IVUS) elastography might be an ideal technique to assess the presence of lipid pools and identify high stress regions. Elastography assesses the local mechanical properties of tissue using its deformation caused by the intraluminal pressure. The technique was validated in vitro using diseased human coronary and femoral arteries. These experiments demonstrated that the strain in the three plaque types is different

(P < 0.001)
. Especially between fibrous and fatty tissue, a highly significant difference(P = 0.0012)was found. Additionally, the predictive value for identifying the vulnerable plaque was investigated. A high strain region at the lumen vessel wall boundary has 88% sensitivity and 89% specificity for identifying these plaques. In vivo, the technique is validated in an atherosclerotic Yucatan mini‐pig animal model. This study also revealed higher strain values in fatty than fibrous plaques(P < 0.001). The presence of a high strain region at the lumen plaque interface has a high predictive value for identifying macrophages. Patient studies revealed high strain values (1–2%) in soft plaques. Calcified material shows low strain values (0–0.2%). With the development of three‐dimensional elastography, identification of weak spots over the full length of a coronary artery becomes possible. In conclusion, intravascular elastography is a unique tool to assess lesion composition and vulnerability. The development of three‐dimensional elastography provides a technique that may develop into a clinical available tool for identifying the rupture‐prone plaque. (J Interven Cardiol 2003;16:253–259)
Stenting for Restenotic Lesions with the BARD XT Stent
Authors: RAHEL BRAIM M. , SUTTORP MAARTEN J. , TE RIELE HANS A.M. , BAL EGBERT T. , ERNST SJEF M. P. G. , MAST E. GIJS , TEN BERG JURRIËN M. , KELDER JOHANNES C. , THIJS PLOKKER H.W.
Published: May 2003

Background: Conventional PTCA for the treatment of restenotic lesions is associated with a high rate of recurrence (30–50%). Primary stenting decreases the restenosis rate at long‐term follow‐up. Methods: One‐hundred consecutive patients with restenosis received a Bard XT stent. Follow‐up angiography was performed after 6 months. Angiograms were compared by means of computed quantitative analysis. Results: The mean pretreatment reference diameter was

2.88 ± 0.51 mm
. The mean minimal luminal diameter (MLD) increased from1.09 ± 0.57 mmto2.70 ± 0.44 mm. The percent diameter stenosis decreased from66 ± 13%to15 ± 10%. The procedural success rate was 99%. At 6 month follow‐up repeat angiography was performed in 86 patients. The mean MLD was1.74 ± 0.67 mmwith a mean diameter stenosis of 41 ± 20%. Residual anginal complaints were reported in 29% of patients. In‐stent restenosis (defined as diameter stenosis of more than 50%) occurred in 18% of the patients. Conclusion: Placement of the Bard XT stent in restenotic lesions is feasible, has an excellent short term outcome and yields a favorable result at 6 month follow‐up angiography. (J Interven Cardiol 2003;16:227–230)
Percutaneous Intervention of Unprotected Left Main Coronary Artery
Authors: SADEGHI H. MEHRDAD , O'NEILL WILLIAM W. , GRINES CINDY L.
Published: May 2003

Successful percutaneous intervention of unprotected left main coronary artery (LMCA) in lieu of surgical revascularization represents the next wave of challenges that the field of interventional cardiology will try to overcome. Significant LMCA stenosis, commonly secondary to atherosclerosis, is seen in about 4–10% of cases presenting to the cardiac catheterization laboratory. Currently, the vast majority of these patients undergo surgical revascularization unless there are prohibitive reasons for surgical revascularization. Several challenges of percutaneous revascularization have been overcome with stents, intravascular brachytherapy, and other technical improvements. Yet, several remaining limitations of percutaneous intervention, such as in‐stent restenosis, have to be improved further before randomized clinical trials of surgical and percutaneous revascularization of unprotected LMCA disease can be contemplated to establish a new standard of care. (J Interven Cardiol 2003;16:281–288)
Effect of a kinin B2 receptor antagonist on LPS‐ and cytokine‐induced neutrophil migration in rats
Authors: Santos Danielle R , Calixto João B , Souza Glória E P
Published: May 2003

This study examines the involvement of kinins in neutrophil migration into rat subcutaneous air pouches triggered by lipopolysaccharide (LPS), as well as the putative roles played by kinin B1 and B2 receptors, tumour necrosis factor alpha (TNF‐α), interleukin‐1 beta (IL‐1β) and selectins in this response.

LPS (5 ng to 10 μg cavity−1) injected into the 6‐day‐old pouch induced a dose‐ and time‐dependent neutrophil migration which peaked between 4 and 6 h, and was maximal following the dose of 100 ng cavity−1 (saline: 0.46±0.1; LPS: 43±3.70 × 106 cells cavity−1 at 6 h).

Bradykinin (BK) (600 nmol) injected into the pouch of saline‐treated rats induced only modest neutrophil migration (0.73±0.16 × 106 cells cavity−1). A more robust response to BK (3.2±0.25 × 106 cells cavity−1) was seen in animals pretreated with captopril, but this was still smaller than the responses to IL‐1β or TNF‐α (15 pmol: 23±2.2 × 106 and 75 pmol: 29.5±2 × 106 cells cavity−1, respectively). Nevertheless, the B1 agonist des‐Arg9‐BK (600 nmol) failed to induce neutrophil migration.

HOE‐140 (1 and 2 mg kg−1), a B2 receptor antagonist, reduced LPS‐induced neutrophil migration. HOE‐140 also reduced the neutrophil migration induced by BK, but had no effect on the migration promoted by IL‐1β or TNF‐α. des‐Arg9‐[Leu8]‐BK, B1 receptor antagonist was ineffective in changing neutrophil migration caused by any of these stimuli.

Neutrophil migration induced by LPS or BK was reduced by interleukin‐1 receptor antagonist (IL‐1ra) (1 mg kg−1), sheep anti‐rat TNF serum (anti‐TNF serum) (0.3 ml cavity−1), and the nonspecific selectin inhibitor fucoidin (10 mg kg−1).

TNF‐α levels in the pouch fluid were increased by LPS or BK injection, peaking at 0.5–1 h and gradually declining thereafter up to 6 h. IL‐1β levels increased steadily throughout the 6 h period. HOE‐140 markedly inhibited the rise in IL‐1β and TNF‐α levels in pouch fluid triggered by both stimuli.

These results indicate that BK participates importantly in selectin‐dependent neutrophil migration into the air pouch triggered by LPS in the rat, by stimulating B2 receptors coupled to synthesis/release of TNF‐α and IL‐1β.

British Journal of Pharmacology (2003) 139, 271–278. doi:10.1038/sj.bjp.0705236
Signaling mechanisms of enhanced neutrophil phagocytosis and chemotaxis by the polysaccharide purified from Ganoderma lucidum
Authors: Hsu Ming‐Jen , Lee Shiuh‐Sheng , Lee Sho Tone , Lin Wan‐Wan
Published: May 2003

The polysaccharide from Ganoderma lucidum (PS‐G) has been reported to enhance immune responses and to elicit antitumor effects. In our previous study, we found that PS‐G efficiently inhibited spontaneously and Fas‐enhanced neutrophil apoptosis when cultured in vitro. Since phagocytosis and chemotaxis play essential roles in host defense mediated by neutrophils, it is of great interest to know the effect of PS‐G on these two cell functions, and the molecular events leading to these actions.

Using latex beads and heat‐inactive Escherichia coli serving as particles for neutrophil engulfment, we found that PS‐G is able to enhance phagocytic activity of human primary neutrophils and neutrophilic‐phenotype cells differentiated from all trans retinoic acid‐treated HL‐60 cells.

Chemotactic assay using Boyden chamber also revealed the ability of PS‐G to increase neutrophil migration.

Exposure of neutrophils to PS‐G time dependently caused increases in protein kinase C (PKC), p38 mitogen‐activated protein kinase (MAPK), Hck, and Lyn activities.

Results with specific kinase inhibitors indicate that phagocytic action of PS‐G was reduced by the presence of wortmannin (Phosphatidylinositol 3‐kinase, PI3K inhibitor), pyrazolpyrimidine 2 (Src‐family tyrosine kinase inhibitor), Ro318220 (PKC inhibitor), and SB203580 (p38 MAPK inhibitor), but not by PD98059 (mitogen‐activated protein/ERK kinase inhibitor). Moreover, chemotactic action of PS‐G requires the activities of PI3K, p38 MAPK, Src tyrosine kinases and PKC.

All these results demonstrate the abilities of PS‐G to enhance neutrophil function in phagocytosis and chemotaxis, and further provide evidence to strengthen the beneficial remedy of G. lucidum in human to enhance defense system.

British Journal of Pharmacology (2003) 139, 289–298. doi:10.1038/sj.bjp.0705243
Effects of methyl p‐hydroxybenzoate (methyl paraben) on Ca2+ concentration and histamine release in rat peritoneal mast cells
Authors: Fukugasako Sanae , Ito Shinichi , Ikemoto Yoshimi
Published: May 2003

Mechanisms of methyl p‐hydroxybenzoate (methyl paraben) action in allergic reactions were investigated by measuring the intracellular Ca2+ concentration ([Ca2+]i) and histamine release in rat peritoneal mast cells (RPMCs).

In the presence or absence of extracellular Ca2+, methyl paraben (0.1–10 mM) increased [Ca2+]i, in a concentration‐dependent manner. Under both the conditions, methyl paraben alone did not evoke histamine release.

In RPMCs pretreated with a protein kinase C (PKC) activator (phorbol 12‐myristate 13‐acetate (PMA) 3 and 10 nM), methyl paraben (0.3–3 mM) induced histamine release. However, a high concentration (10 mM) of the agent did not increase the histamine release.

U73122 (0.1 and 0.5 μM), an inhibitor of phospholipase C (PLC), significantly inhibited the methyl paraben‐induced histamine release in PMA‐pretreated RPMCs. U73343 (0.5 μM), an inactive analogue of U73122, did not inhibit the histamine release caused by methyl paraben.

In Ca2+‐free solution, PLC inhibitors (U73122 0.1 and 0.5 μM, D609 1–10 μM) inhibited the methyl paraben‐induced increase in [Ca2+]i, whereas U73343 (0.5 μM) did not.

Xestospongin C (2–20 μM) and 2 aminoethoxydiphenyl borate (30 and 100 μM), blockers of the inositol 1,4,5‐trisphosphate (IP3) receptor, inhibited the methyl paraben‐induced increase in [Ca2+]i in Ca2+‐free solution.

In conclusion, methyl paraben causes an increase in [Ca2+]i, which may be due to release of Ca2+ from storage sites by IP3 via activation of PLC in RPMCs. In addition, methyl paraben possibly has some inhibitory effects on histamine release via unknown mechanisms.

British Journal of Pharmacology (2003) 139, 381–387. doi:10.1038/sj.bjp.0705248
Brain renin–angiotensin system dysfunction in hypertension: recent advances and perspectives
Authors: Veerasingham Shereeni J , Raizada Mohan K
Published: May 2003

This review focuses on the dysfunction of the intrinsic brain renin–angiotensin system (RAS) in the pathogenesis of hypertension. Hyperactivity of the brain RAS plays a critical role in mediating hypertension in both humans and animal models of hypertension, including the spontaneously hypertensive rat (SHR). The specific mechanisms by which increased brain RAS activity results in hypertension are not well understood but include increases in sympathetic vasomotor tone and impaired arterial baroreflex function. We discuss the contribution of endogenous angiotensin (Ang) II actions on presympathetic vasomotor rostral ventrolateral medulla neurons to enhance sympathetic activity and maintain hypertension. In addition, we discuss Ang II‐induced attenuation of afferent baroreceptor feedback within the nucleus tractus solitarius and its relevance to the development of hypertension. We also outline the cellular and molecular mechanisms of Ang II signal transduction that may be critical for the initiation and establishment of hypertension. In particular, we present evidence for a phosphoinositide‐3‐kinase‐dependent signaling pathway that appears to contribute to hypertension in the SHR, possibly via augmented Ang II‐induced increases in neuronal firing rate and enhanced transcriptional noradrenaline neuromodulation. Finally, we outline future directions in utilizing our understanding of the brain RAS dysfunction in hypertension for the development of improved therapeutic intervention in hypertension.

British Journal of Pharmacology (2003) 139, 191–202. doi:10.1038/sj.bjp.0705262
Loperamide mobilizes intracellular Ca2+ stores in insulin‐secreting HIT‐T15 cells
Authors: He Li‐Ping , Mears David , Atwater Illani , Rojas Eduardo , Cleemann Lars
Published: May 2003

We have investigated the effects of loperamide on intracellular Ca2+ stores and membrane K+ channels in insulin‐secreting hamster insulinoma (HIT‐T15) cells.

In cell‐attached patch‐clamp mode, loperamide (3–250 μM) activated large single‐channel currents. The loperamide‐activated currents were tentatively identified as Ca2+‐activated K+ channel (KCa) currents based on their single‐channel conductance (145 pS), apparent reversal potential, and insensitivity to tolbutamide. Smaller single‐channel currents with a conductance (32 pS) indicative of adenosine triphosphate‐sensitive K+ channels (KATP channels) were also recorded, but were insensitive to loperamide.

Surprisingly, the loperamide‐activated currents persisted in the absence of extracellular Ca2+. Yet under these conditions, we still measured loperamide‐induced Ca2+ increases. These effects are dose dependent. Loperamide had no effects in the inside‐out patch configuration, suggesting that loperamide does not directly activate the channels with large conductance, but does so secondarily to release of Ca2+ from intracellular stores.

Carbachol (100 μM), an agonist of muscarinic receptors, which mediates IP3‐dependent intracellular Ca2+ release, enhanced the effects of loperamide on KCa channels.

Both the putative KCa currents and Ca2+ signals induced by loperamide (with ‘0’ [Ca2+]o) were abolished when the intracellular Ca2+ stores had been emptied by pretreating the cells with either carbachol or thapsigargin, an endoplasmic reticulum Ca2+‐ATPase inhibitor that blocks reuptake of calcium.

These data indicate that loperamide in insulin‐secreting β‐cells evokes intracellular Ca2+ release from IP3‐gated stores and activates membrane currents that appear to be carried by KCa, rather than KATP channels.

British Journal of Pharmacology (2003) 139, 351–361. doi:10.1038/sj.bjp.0705263
5‐HT decreases contractile and electrical activities in lymphatic vessels of the guinea‐pig mesentery: role of 5‐HT7‐receptors
Authors: Chan Alice K , von Der Weid Pierre‐Yves
Published: May 2003

Constriction measurements and intracellular microelectrode recordings were performed in vitro on lymphatic vessels isolated from the guinea‐pig mesentery to investigate whether 5‐hydroxytryptamine (5‐HT) affected lymphatic pumping and smooth muscle membrane potential.

5‐HT decreased in a concentration‐dependent manner the frequency of constrictions induced by intraluminal vessel perfusion. In nonperfused vessels, 5‐HT hyperpolarized the lymphatic smooth muscle membrane potential and decreased the frequency and amplitude of spontaneous transient depolarizations (STDs).

The actions of 5‐HT were significantly reversed by the 5‐HT7 receptor antagonist (2R)‐1‐[(3‐hydroxyphenyl)sulfonyl]‐2‐[2‐(4‐methyl‐1‐piperidinyl)ethyl]pyrrolidine (SB269970, 0.5 μM) and by the 5‐HT1/2/5/7 receptor antagonists methysergide (0.5 μM), and were mimicked by the 5‐HT1/7‐receptor agonist, 5‐CT.

The 5‐HT4‐receptor antagonists 1‐methyl‐1H‐indole‐3‐carboxylic acid [1‐2‐[(methyl sulfonyl) amino] ethyl‐4‐piperidinyl] methyl ester (GR113808, 1 μM) and (1‐piperidinyl) ethyl 1H‐indole 3‐carboxylate (SB203186, 1 μM) did not significantly affect the 5‐HT‐induced responses. The 5‐HT4‐receptor agonist 1‐(4‐amino‐5‐chloro‐2‐methoxy‐phenyl)‐3‐[1‐(2‐methylsulfonylamino) ethyl‐4‐piperidinyl]‐1‐propanone hydrochloride (RS67506) decreased the constriction frequency, albeit only at 50 μM and without affecting the smooth muscle membrane potential.

Responses to 5‐HT were attenuated by the nitric oxide synthase inhibitor NG‐nitro L‐arginine (100 μM), whereas indomethacin (10 μM) and tetrodotoxin (1 μM) were without effects.

5‐HT‐induced responses were inhibited by the ATP‐sensitive K+ channel blocker, glibenclamide (10 μM) and the cAMP‐dependent protein kinase inhibitor N‐[2‐(p‐bromociannamylamino)‐ethyl]‐5‐isoquinolinesulfonamide‐dichloride (H89, 10 μM) blocked the hyperpolarization.

These results suggest that 5‐HT modulates the rate of lymphatic vessel pumping by eliciting KATP channel‐mediated smooth muscle hyperpolarization and decrease in STD activity, which appear to be mediated by activation of 5‐HT7 receptors coupled to cAMP production.

British Journal of Pharmacology (2003) 139, 243–254. doi:10.1038/sj.bjp.0705264
Role of leukotrienes in the regulation of human granulocyte behaviour: dissociation between agonist‐induced activation and retardation of apoptosis
Authors: Murray Joanna , Ward Carol , O'Flaherty Joseph T , Dransfield Ian , Haslett Christopher , Chilvers Edwin R , Rossi Adriano G
Published: May 2003

Since most inflammatory mediators that stimulate granulocyte responsiveness also delay apoptosis, it is often assumed that activation and longevity are causally related. Using isolated human peripheral blood neutrophils and eosinophils, we examined this association by exploiting the proinflammatory lipid mediators, the leukotrienes (LTs), and investigated granulocyte function and apoptosis.

LTB4 induced elevation of intracellular free Ca2+ concentration ([Ca2+]i), cell polarisation and retardation of neutrophil apoptosis, although the antiapoptotic effect occurred only at concentrations 300 nM. LTB4‐induced activation was attenuated by CP‐105,696, a BLT1‐specific antagonist suggesting classical LTB4 receptor BLT1 involvement.

Despite demonstrating the presence of the neutrophil intracellular LTB4 receptor peroxisome‐proliferator activator receptor‐α (PPARα) in neutrophils, the selective PPARα agonist WY‐14,643 did not mimic LTB4‐induced prosurvival effects.

LTB4‐induced survival, however, also appeared to be mediated by BLT1 since CP‐105,696 inhibited the LTB4‐mediated antiapoptotic effect. Furthermore, based on studies with CP‐105,696 and 5‐lipoxygenase inhibitors, lipopolysaccharide (LPS)‐, granulocyte–macrophage colony‐stimulating factor (GM‐CSF)‐, dexamethasone‐ and dibutyryl‐cAMP (db‐cAMP)‐induced delay of neutrophil apoptosis did not involve autocrine production of LTB4.

Although LTB4 and LTD4 induced human eosinophil [Ca2+]i elevation and polarization, these LTs did not influence eosinophil apoptosis. Furthermore, LTB4‐ and LTD4‐induced eosinophil activation was attenuated by CP‐105,696 and the Cys‐LT1 receptor antagonist montelukast, respectively, highlighting specific receptor dependency.

Thus, mediator‐triggered granulocyte activation and antiapoptotic pathways are distinct events that can be differentially regulated.

British Journal of Pharmacology (2003) 139, 388–398. doi:10.1038/sj.bjp.0705265
Inhibition of intracellular hepatitis C virus replication by synthetic and vector‐derived small interfering RNAs
Authors: Yokota Takanori , Sakamoto Naoya , Enomoto Nobuyuki , Tanabe Yoko , Miyagishi Makoto , Maekawa Shinya , Yi Li , Kurosaki Masayuki , Taira Kazunari , Watanabe Mamoru , Mizusawa Hidehiro
Published: May 2003

Small interfering RNAs (siRNAs) efficiently inhibit gene expression by RNA interference. Here, we report efficient inhibition, by both synthetic and vector‐derived siRNAs, of hepatitis C virus (HCV) replication, as well as viral protein synthesis, using an HCV replicon system. The siRNAs were designed to target the 5′ untranslated region (5′ UTR) of the HCV genome, which has an internal ribosomal entry site for the translation of the entire viral polyprotein. Moreover, the 5′ UTR is the most conserved region in the HCV genome, making it an ideal target for siRNAs. Importantly, we have identified an effective site in the 5′ UTR at which ∼80% suppression of HCV replication was achieved with concentrations of siRNA as low as 2.5 nM. Furthermore, DNA‐based vectors expressing siRNA against HCV were also effective, which might allow the efficient delivery of RNAi into hepatocytes in vivo using viral vectors. Our results support the feasibility of using siRNA‐based gene therapy to inhibit HCV replication, which may prove to be valuable in the treatment of hepatitis C.
Human arteries engineered in vitro
Authors: McKee J Andrew , Banik Soma SR , Boyer Matthew J , Hamad Nesrin M , Lawson Jeffrey H , Niklason Laura E , Counter Christopher M
Published: May 2003

There is a pressing need to develop methods to engineer small‐calibre arteries for bypass surgery. We hypothesized that the rate‐limiting step that has thwarted previous attempts to engineer such vessels from non‐neonatal tissues is the limited proliferative capacity of smooth muscle cells (SMCs), which are the main cellular component of these vessels. Ectopic expression of the human telomerase reverse transcriptase subunit (hTERT) has been shown recently to extend the lifespan of certain human cells. We therefore introduced hTERT into human SMCs and found that the resulting cells proliferated far beyond their normal lifespan but retained characteristics of normal control SMCs. Importantly, using these non‐neonatal SMCs, we were able to engineer mechanically robust human vessels, a crucial step towards creating arteries of clinical value for bypass surgery.
Identification of the fertility restoration locus, Rfo, in radish, as a member of the pentatricopeptide‐repeat protein family
Authors: Desloire Sophie , Gherbi Hassen , Laloui Wassila , Marhadour Sylvie , Clouet Vanessa , Cattolico Laurence , Falentin Cyril , Giancola Sandra , Renard Michel , Budar Françoise , Small Ian , Caboche Michel , Delourme Régine , Bendahmane Abdelhafid
Published: May 2003

Ogura cytoplasmic male sterility (CMS) in radish (Raphanus sativus) is caused by an aberrant mitochondrial gene, Orf138, that prevents the production of functional pollen without affecting female fertility. Rfo, a nuclear gene that restores male fertility, alters the expression of Orf138 at the post‐transcriptional level. The Ogura CMS/Rfo two‐component system is a useful model for investigating nuclear–cytoplasmic interactions, as well as the physiological basis of fertility restoration. Using a combination of positional cloning and microsynteny analysis of Arabidopsis thaliana and radish, we genetically and physically delimited the Rfo locus to a 15‐kb DNA segment. Analysis of this segment shows that Rfo is a member of the pentatricopeptide repeat (PPR) family. In Arabidopsis, this family contains more than 450 members of unknown function, although most of them are predicted to be targeted to mitochondria and chloroplasts and are thought to have roles in organellar gene expression.
The role of the death‐domain kinase RIP in tumour‐necrosis‐factor‐induced activation of mitogen‐activated protein kinases
Authors: Devin Anne , Lin Yong , Liu Zheng‐gang
Published: May 2003

The death‐domain kinase RIP (receptor‐interacting protein) is an important effector of tumour necrosis factor (TNF) signalling and is essential for TNF‐induced nuclear factor‐κB activation. However, the function of RIP in the TNF‐induced activation of mitogen‐activated protein kinases (MAPKs) has not been fully investigated. In this report, using Rip null (Rip−/−) mouse fibroblast cells, we investigated whether RIP is required for TNF‐induced activation of the MAPKs extracellular‐signal‐related kinase (ERK), p38 and c‐Jun amino‐terminal kinase (JNK). We found that TNF‐induced activation of ERK, p38 and JNK is decreased in Rip−/− cells. The activation of these kinases by interleukin‐1 is normal in Rip−/− cells. More importantly, we showed that the kinase activity of RIP is needed for ERK activation.
Repeat prenatal corticosteroids: Who still recommends their use and why?
Authors: McLaughlin Kristin J , Crowther Caroline A
Published: May 2003

Background: Repeat prenatal corticosteroids have been in common use worldwide, even though the National Institutes of Health recommends that ‘Until data establish a favourable benefit‐to‐risk ratio, repeat courses of antenatal corticosteroids, including rescue therapy, should be reserved for patients enrolled in clinical trials.’

Objectives: To describe the current use/recommendations for the use of repeat prenatal corticosteroids by obstetricians and neonatologists and to examine the sources of evidence on which their practice is based.

Design: Postal questionnaire.

Population: All Trainees, Members and Fellows of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists and neonatologists in Australia and New Zealand.

Methods: The questionnaire was mailed to obstetricians and neonatologists in August–September 2001.

Main outcome measures: Practitioner use/recommendations for the use of repeat prenatal corticosteroids and the sources of evidence on which their practice was based.

Results: Use of repeat prenatal corticosteroids was recommended by 332 (44%) obstetricians and 19 (21%) neonatologists. Obstetricians were twice as likely to recommend their use compared with neonatologists (relative risk, 2.04; 95% confidence intervals, 1.36–3.06; P < 0.001). Over half of the respondents (483, 57%) reported they had changed their use/recommendations in the previous 3 years. The sources of evidence behind these practices differed between obstetricians and neonatologists and between those practitioners who recommended the use of repeat prenatal corticosteroids and those who did not.

Conclusions: Fewer practitioners recommend repeat prenatal corticosteroids compared with previous surveys. Sources of evidence behind the practice of groups of obstetricians and neonatologists differ.
Effect of inter‐twin delivery time on Apgar scores of the second twin
Authors: Erdemoglu Evrim , Mungan Tamer , Tapisiz Omer L. , Ustunyurt Emin , Çaglar Ebru
Published: May 2003

Objective: The aim of the present study was to analyse the effect of inter‐twin delivery time on the Apgar scores of the second twin.

Material: Women attempting vaginal delivery of second twins were studied in 2000. Deliveries before 25 weeks’ gestation, complicated pregnancies, operative deliveries, and deliveries by regional or general anaesthesia were all excluded.

Results: A total of 37 out of 126 twin pregnancies had the criteria to be included in the present study. The major factor identified to influence Apgar scores was gestational age (P < 0.01). There was a linear relationship between delivery interval and the Apgar scores of the second twin, and the addition of delivery interval significantly improved the predictivity of gestational age. There was no influence of presentation and delivery mode of the second twin. Interval was found to be the only significant predictive factor of the Apgar scores in second twins of >1900 g and where the second twin is in a breech presentation. Caesarean section did not improve the outcome of the second twins.

Conclusion: Gestational age is the most important factor influencing the Apgar scores of second twins. The addition of delivery interval improves the predictivity of second twin Apgar score by gestational age. Inter‐twin delivery time of >15 min is particularly important in the second twin which presents by the breech method and in the second twin of more than 1900 g.
Effect of oestrogen replacement therapy on serum lipid profile
Authors: Nanda Smiti , Gupta Neeta , Mehta Harish C. , Sangwan Krishna
Published: May 2003

Background: Oestrogen deficiency in postmenopausal women alters the lipid metabolism unfavourably.

Aim: To evaluate the effects of oral and transdermal oestrogen replacement therapy (ORT) on serum lipid profile.

Methods: Ninety hysterectomised and oophorectomised women were randomised into three equal groups (no hormones; oral conjugated equine oestrogen, 0.625 mg/day; transdermal oestradiol patches, 50 µg/day). Serum concentrations of total cholesterol, high‐density lipoprotein (HDL) cholesterol, low‐density lipoprotein (LDL) cholesterol and triglycerides were determined at the baseline and after 3 and 6 months of therapy. Student's t‐test was used for statistical evaluation.

Results: Most of the hysterectomised women had abnormal serum lipid profile, especially HDL cholesterol levels (less than 40 mg/dL in 87%). A significant decline in the levels of serum cholesterol (total) as well as LDL and a significant increase in HDL cholesterol levels were observed following ORT by both modes, the response being comparatively rapid with oral route. After 3 and 6 months, the number of cases with HDL cholesterol levels above 40 mg/dL increased from initial 13 to 63% and 87% (oral) and 30 and 60% (transdermal), respectively. Serum triglyceride levels declined significantly with transdermal therapy but increased with oral ORT.

Conclusions: Oestrogen replacement therapy either via oral or transdermal route has a beneficial effect on serum lipid profile of menopausal women. Whereas the oral route is more effective in increasing HDL cholesterol levels, the transdermal route is better for reducing the serum triglyceride level; hence, the latter should be the route of choice in women with high serum triglyceride levels.
Calcium channel blockers for inhibiting preterm labour; a systematic review of the evidence and a protocol for administration of nifedipine
Authors: King James F. , Flenady Vicki , Papatsonis Dimitri , Dekker Gustaaf , Carbonne Bruno
Published: May 2003

Objective: To assess the effects on maternal, fetal and neonatal outcomes of nifedipine (and other calcium channel blockers) administered as a tocolytic agent to women in preterm labour.

Methods: Standard methods of the Cochrane Collaboration and its Pregnancy and Childbirth Review Group were used. All published and unpublished randomised trials in which calcium channel blockers were used for tocolysis for women in preterm labour between 20 and 36 weeks’ gestation, were considered.

Main results: The systematic review includes 12 randomised controlled trials with a total of 1029 participating women. No trials were identified in which calcium channel blockers were compared with a placebo or no alternative tocolytic treatment. Calcium channel blockers appear to be more effective than betamimetic agents in prolonging pregnancy for 7 days or longer, are much less likely to cause maternal side‐effects and are associated with reduced neonatal morbidity.

Conclusion: Calcium channel blockers (especially nifedipine) can be considered safer and more effective tocolytic agents than betamimetics.
The Medical Specialist Outreach Assistance Programme in South Australia
Authors: Cord-Udy Nigel
Published: May 2003

Objective: The present paper aims to provide an overview of the Medical Specialist Outreach Assistance Programme (MSOAP) and its implementation in South Australia with particular reference to the expansion of visiting psychiatric services to rural and remote areas. Included is a discussion of a number of the practical issues and challenges experienced by the author in the development of a visiting psychiatric service to the remote community of Coober Pedy in northern South Australia.

Conclusions: There has been much success to date with the expansion of visiting psychiatric services to rural and remote areas within South Australia under MSOAP. MSOAP appears to have considerable merit, particularly for psychiatrists working in private practice. There are several practical issues to be considered in taking on this type of work. The professional rewards are substantial.
Integrative Neuroscience in Psychiatry: The Role of a Standardized Database
Authors: Gordon Evian
Published: May 2003

Objective: Databases bring together diverse information in neuroimaging and psychiatry. They usually aim for both size and diversity of measures. The present article outlines the potential insights from the first entirely standardized and centralized International Brain Database.

Method: The database consists of data from over 1000 normal subjects (age range 6-70 years) and a growing number of age-matched patients with a psychiatric illness, acquired from seven laboratories (New York, Rhode Island, London, Holland, Adelaide, Melbourne and Sydney). It is an ‘integrative’ neuroimaging (electroencephalography (EEG), event-related potentials (ERP), structural and functional magnetic resonance imaging (sMRI, fMRI)), psychometric, demographic and genomic database.

Results: The most notable relationships in normal controls thus far include (i) an association between grey matter volume and EEG alpha frequency in frontal regions; (ii) a systematic reduction with age in cortical arousal (EEG power), speed of processing (ERP components) and most aspects of cognitive function, particularly for >50 years; (iii) a greater cortical arousal in female versus male subjects, but slower speed of processing; and (iv) a dissociation between speed (greater in male subjects) and accuracy/verbal processing (greater in female subjects) for psychological tasks. There is potential to explore the specificity of findings in psychiatric disorders in this international standardized database.

Conclusions: The size of this database has allowed for statistical tests of greater power than normal. The combination of size and diversity of measure has broader significance in providing a normative framework for evidence-based psychiatric research. It enables control for widespread individual differences, enhancing investigations of the sensitivity and specificity of brain findings, and the efficacy of medication in psychiatric disorders.