bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiotensin II receptor blockade and ventricular remodelling
Authors: Anavekar Nagesh S , Solomon Scott D
Published: May 2007

Cardiac remodelling is the expression of molecular, cellular and interstitial changes in response to cardiac injury, manifesting as adverse alterations in the size, shape and function of the ventricle. Several clinical studies have documented significant elevations in the levels of renin, angiotensin II (Ang II) and aldosterone attending acute myocardial infarction and/or congestive heart failure. Similar to catecholamines, markedly elevated activity of the renin-angiotensin-aldosterone system (RAAS) is associated with poor prognosis. The effects of Ang II upon cardiac tissue are related to two primary receptors, Ang II type 1 (AT1)and Ang II type 2 (AT2). The AT1-receptor appears to mediate many of the deleterious effects of chronic RAAS activity, while the AT2-receptor is increasingly shown to have potential cardioprotective effects. Attenuating the deleterious effects of sustained Ang II stimulation can be achieved by direct inhibition of angiotensin-converting enzyme (ACE) and/or direct antagonism of AT receptors. ACE inhibition reduces left ventricular (LV) volumes, retards the progression of LV dilatation and hypertrophy and increases systolic function in systolic dysfunction. By blocking at the receptor level, Ang II receptor blockers (ARBs) provide an alternative and more direct approach to inhibiting the effects of Ang II; however, data relating to their effects upon ventricular remodelling, whether used in isolation or in combination with ACE inhibitors (ACE-Is), are less convincing. Data arising from several recent clinical trials suggest that simultaneous use of ACE-Is and ARBs maybe of more benefit in attenuating ventricular remodelling than either agent alone.
Collagen Production in Cardiac Fibroblasts During Inhibition of Aminopeptidase B
Authors: Lijnen Paul J , Petrov Victor V , Turner Marisa , Fagard Robert H
Published: May 2007

Objective. To determine whether the aminopeptidase B inhibitor, arphamenine A, could affect collagen production and expression in control and TGF-ß1-treated cardiac fibroblasts.

Design and Methods. Cardiac fibroblasts from passage 2 from normal male adult rats were cultured to confluency and incubated with and without 600 pmol/l TGF-ß1 for 2 days in serum-free Dulbecco's modified Eagle's medium and then incubated with 100 µmol/l arphamenine A for 1 day in this medium added ascorbic acid, ß-aminopropionitrile and titriated proline. Soluble collagen was measured in the conditioned medium and non-soluble collagen in the cell layer. Aminopeptidase activity was estimated by spectrophotometric determination of the liberation of p-nitroaniline from alanine- or arginine-p-nitroanilide. Matrix metalloproteinase (MMP) and lysyl oxidase activity were assayed in the conditioned medium. A semi-quantitative reverse transcriptase- polymerase chain reaction was used to examine the expression of lysyl oxidase and collagen type I and III. Results. Arphamenine A dose-dependently

inhibited basal and TGF-ß 1-stimulated aminopeptidase activity. Arphamenine A reduced soluble and non-soluble collagen production in control and TGF-ß1-treated cardiac fibroblasts, while it decreased collagen type I and III expression only in TGF-ß1-treated fibroblasts. Lysyl oxidase, MMP-1 and MMP-2 activity were inhibited by arphamenine A in the conditioned media of control and TGF-ß1treated cardiac fibroblasts.

Conclusions. Our data show that the specific aminopeptidase B inhibitor, arphamenine A, reduces collagen production in cardiac fibroblasts and that this reduction is accompanied by a pronounced inhibition of lysyl oxidase.
Renin Release in Response to Renin System Blockade: Activation of the Renin System in Type 1 Diabetes Mellitus
Authors: Stevanovic Radomir D , Price Deborah A , Lansang M Cecilia , Fisher Naomi DL , Laffel Lori MB , Hollenberg Norman K
Published: May 2007

Activation of the renin-angiotensin system (RAS) in diabetes is thought to contribute to nephropathy. This is suggested by findings of an enhanced renovascular (RPF) response to RAS blockade with angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARBs). An alternative approach to assess RAS activation is the evaluation of renin release following RAS blockade.

Forty-four consecutively enrolled Type 1 diabetic patients (28.2 ± 1.5 years) and 37 normal subjects (37 ± 2.6 years) in high salt balance were given 25 mg of captopril and 16 mg of candesartan p.o. on consecutive days. All subjects were Caucasian. All, except one diabetic patient, had normal renal function. Plasma renin activity (PRA) and renal plasma flow (RPF) were measured for four hours after both drugs, and at eight, and 24 hours after candesartan.

As anticipated, both drugs increased PRA. Peak responses (90' after captopril) were 5.6 ± 1 ng/mL Ang I/hour in diabetic patients, and 1.7 ± 0.9 ng/mL Ang I/hour in normal subjects (p<0.001). Responses to both drugs were correlated in diabetic patients for PRA (r=0.623; p=0.001) and for RPF (r=0.9; p<0.001). When the PRA response to captopril was below the median, the RPF response was limited (22.1 ± 17.6 ml/minute/1.73 m2). When it was above the median, the RPF response was also larger (62.2 ± 13.9 ml/minute/1.73 m2; p=0.006).

Renin response to ACE-I and ARB confirms activation of the RAS in diabetic patients.
Comparison of Monotherapy with Irbesartan 150 mg or Amlodipine 5 mg for Treatment of Mild-to-Moderate Hypertension
Authors: Neutel Joel M , Germino F Wilford , Smith David
Published: May 2007

Objective. The primary objective of this study was to compare the antihypertensive efficacy of the angiotensin II receptor blocker irbesartan 150 mg and the calcium channel blocker amlodipine 5 mg in the treatment of patients with seated diastolic blood pressure (DBP) 95—110 mmHg.

Design. Multicentre, randomised, double-blind, comparative pilot study.

Methods. Subjects were 18—65 years of age, with DBP 95—110 mmHg, and of non-African American origin. Following a three-week, single-blind, placebo lead-in period, 181 subjects were randomised in a 1:1 ratio to receive once-daily irbesartan 150 mg (n=89) or amlodipine 5 mg (n=92) for four weeks. Trough (24±3 hours post-dosing) BP measurements were obtained at baseline and at Weeks 2 and 4 under standardised, controlled conditions. Response was defined as DBP <90 mmHg or a reductionfrom baseline of ≥10 mmHg.

Results. After four weeks of treatment, the mean (±SE) decrease from baseline in DBP was 9.4±0.6 mmHg in the irbesartan group vs. 9.6±0.6 mmHg in the amlodipine group (p=0.806). The mean decrease from baseline in seated systolic BP was 12.2±1.0 mmHg in the irbesartan group vs. 12.0±1.0 mmHg in the amlodipine group (p=0.885). Overall, 62% of subjects in the irbesartan group and 63% in the amlodipine group had a response (p=0.609), and 54% and 56% of patients (p=0.596), respectively, had their DBP normalised (<90 mmHg). Adverse events were reported by 21.3% of patients receiving irbesartan and 20.7% receiving amlodipine.

Conclusions. Irbesartan 150 mg demonstrated comparable efficacy to amlodipine 5 mg, thereby confirming its value as an antihypertensive treatment option in non-African American patients with DBP 95—110 mmHg.
Review: Angiotensin Peptides and their Pleiotropic Actions
Authors: Haulica Ion , Bild Walther , Serban Dragomir N
Published: May 2007

The concept of tissue renin-angiotensin systems (RAS) is now well established and it is now usual to think in terms of renal and tissue systems. At the same time it has emerged that angiotensin II (Ang II) is not the only biologically active peptide generated by the RAS. At least three others have been identified: the heptapeptide Ang III, the hexapeptide Ang IV and Ang 1-7. Specific receptors exits for the last two peptides. In addition, the range of possible physiological and pathophysiological properties for Ang II„ has been expanding. The current perception of the RAS is therefore that of a much more complex system than previously believed, with autocrine, paracrine and endocrine properties extending beyond the cardiovascular system. This mini-review focuses on the synthetic pathways of the Ang peptides and describes some of their pleiotropic actions.
High Angiotensin II Responsiveness is Associated with Decreased Endothelium-Dependent Relaxation in Human Arteries
Authors: Voors Adriaan A , van Geel Peter Paul , Buikema Hendrik , Oosterga Margreeth , van Veldhuisen Dirk J , van Gilst Wiek H
Published: May 2007

Introduction. Animal studies demonstrated an interaction between angiotensin II (Ang II) responsiveness and endothelium-dependent relaxation (EDR). However, this relation has not been well described in humans. Therefore, we investigated the relation between Ang II responsiveness and EDR in isolated human arteries.

Materials and Methods. Segments of the internal mammary artery (IMA) were harvested from 89 patients undergoing coronary bypass surgery. Rings of these segments were exposed in organ bath experiments to metacholine (ME; 10 nmol/L -0.1 mmol/L) after precontraction with phenylephrine (PE; 10 µmol/L), and secondly to increasing concentrations of Ang II (0.1 nmol/L —1 µmol/L).

Results. Patients with the highest contraction to Ang II showed the lowest ME relaxation (r=0.312; p=0.003). Angiotensin-converting enzyme (ACE)-inhibition significantly increased Ang II sensitivity (p=0.03). This increase was accompanied by a tendency toward decreased EDR (p=0.07). The inverse relation between Ang responsiveness and endotheliumdependent relaxation could not be explained by an increased tissue or serum ACE-inhibition in patients with a higher endothelium-dependent relaxation.

Conclusions. High Ang II responsiveness inversely correlates to EDR in IMA's of patients with established coronary artery disease. Short-term treatment with an ACE-inhibitor increased the response to Ang II, but had an adverse effect on EDR.
Prevention and Reversal by Enalapril of Target Organ Damage in Angiotensin II Hypertension
Authors: Rugale Caroline , Cordaillat Magali , Mimran Albert , Jover Bernard
Published: May 2007

Angiotensin-converting enzyme inhibitors (ACE-Is) prevent target organ damage in several models of hypertension. The aim of this study was to assess the influence of the ACE-I enalapril (10 mg/kg-1 per day, gavage) on the cardiovascular alterations and production of free radicals induced by chronic infusion of angiotensin II (Ang II, 200 ng/kg-1 per minute, SC) in Sprague-Dawley rats. Enalapril was given concomitantly for the 10 days of Ang II infusion (prevention) or from day 10 to 17 of Ang II infusion (intervention). The influence of the NADPH oxidase inhibitor apocynin (600 mg/L-1 in drinking water) was evaluated. mg/L-l in drinking water) was evaluated. Enalapril and apocynin had no effect on hypertension in the prevention and intervention studies. Enalapril prevented the increase in heart weight index (HWI), carotid cross-sectional area (CSA) and albuminuria induced by Ang II. Enalapril reduced HWI and albuminuria whereas CSA I was not affected in the intervention study. Apocynin had effects comparable to enalapril. Both enalapril and apocynin reduced the overproduction of superoxide anion by the left ventricle and rise in advanced oxidation protein products induced by C Ang II. Therefore, the antioxidant but not the antihypertensive effect of enalapril may participate in the prevention and treatment of the Ang II-induced cardiovascular and renal alterations.
Role of Angiotensin II in Cardiovascular Disease — Therapeutic Implications of More Than a Century of Research
Authors: Ferrario Carlos M
Published: May 2007

More than a century of research on the renin-angiotensin system (RAS) has uncovered the widespread involvement of angiotensin II (Ang II) in the pathophysiology of cardiovascular diseases. A number of outcomes-based mega trials utilising hard clinical endpoints have revealed beneficial effects of angiotensin receptor antagonists (AIIAs/ARBs) in patients with hypertension, heart failure, diabetic nephropathy, and post-myocardial infarction (MI). The results of these studies not only emphasise the importance of Ang II in the pathophysiology of these diseases but have provided the basis for an evidence-based approach for the use of AIIAs in clinical practice. It is hoped that the next 100 years of research into the RAS will uncover hitherto unimaginable therapeutic opportunities.
Beneficial Effect of Eplerenone on Cardiac Remodelling and Electrical Properties of the Failing Heart
Authors: De Mello Walmor C
Published: May 2007

Introduction. The effect of chronic administration of eplerenone on cardiac remodelling and electrical properties was investigated in the failing heart of cardiomyopathic hamsters (TO-2) at five months of age.

Materials and Methods. Two-month-old hamsters were treated with eplerenone (200 mg/kg/day) administered into the chow for a period of three months. Measurements of membrane potential were performed with intracellular microelectrodes connected to a high impedance DC amplifier. The thickness of the ventricular wall as well as the area of fibrosis were measured. To investigate the influence of eplerenone on the electrogenic sodium pump myocytes were isolated from the ventricle and the pump current density was whole cell clamp configuration. measured in voltage clamped cells using the whole cell clamp configuration

Results. The results indicated that: 1) the width of the left and right ventricular wall was significantly reduced; 2) the heart weight/body weight ratio was decreased by 38±2.4% (n=24 P ) (p<0.05); 3) the fibrotic area in the left ventricle (LV) was reduced by 12.6±2% (n=25) (p<0.05); 4) the incidence of cardiac arrhythmias was decreased from 58±3.8% (n=20) in the control to 40±4.1% (n=20) (p<0.05) in animals treated with eplerenone. Moreover, a significant reduction in the dispersion of the QT interval was found with the drug; 5) eplerenone increased the resting potential of ventricular fibres from 64.3±1.5 mV to 73.4±1.4 mV (n=30) (p<0.05), an effect related to the activation of an electrogenic sodium pump. The conduction velocity, in longitudinal direction, was enhanced from 50±2.2 cm/s (n=10) in the controls to 59±2.4 cm/s (n=13) (p<0.05) in animals treated with eplerenone.

Conclusions. Eplerenone reduces cardiac remodelling, the incidence of cardiac arrhythmias and improves impulse propagation, an effect in part related to the antifibrotic effect of the drug but also to the activation of the electrogenic sodium pump.
CNP, but not ANP or BNP, Relax Human Isolated Subcutaneous Resistance Arteries by an Action Involving Cyclic GMP and BKCa Channels
Authors: Garcha Robinder S , Hughes Alun D
Published: May 2007

Natriuretic peptides play an important role in sodium regulation and blood pressure (BP) control. We examined the effects of atrial natriuetic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) on human isolated resistance arteries and the mechanisms involved in vasorelaxation. Human subcutaneous resistance arteries were mounted in an isometric myograph and contracted with phenylephrine. CNP, but not ANP or BNP, relaxed arteries in a concentration dependent manner. The action of CNP was unaffected by removal of the endothelium, inhibition of nitric oxide synthase by NG-monomethyl-Larginine or inhibition of soluble guanylate cyclase by 1H-[1,2,4] oxadiazolo [4,3-alpha] quinoxalin-1-one. Blockade of cyclic GMP-dependent kinase by 8- bromoguanosine-3', 5'- cyclic monophosphorothioate, Rp-isomer (Rp-8-Br-cGMPS) inhibited CNP relaxation. CNP relaxation was also inhibited by high potassium or iberiotoxin, indicating that it was due to opening of BKCa channels. Omapatrilat, a vasopeptidase inhibitor of neutral endopeptidase and angiotensin-converting enzyme, enhanced the effect of CNP and inhibited responses to Ang I. In summary, CNP, but not ANP or BNP, relaxes human resistance arteries by activating cyclic GMP-dependent kinase and BKCa. The effects of CNP are enhanced by vasopeptidase inhibition and this may contribute to the vasodilator effects of these agents in vivo. Since CNP is widely present in endothelium it may play a role in the regulation of peripheral resistance in man in physiological and pathological circumstances.
Targeting Hypertension with Valsartan: Lessons Learned from the Valsartan/HCTZ Versus Amlodipine in Stage II Hypertensive Patients (VAST) Trial
Authors: Ruilope Luis M , Zanchetti Alberto
Published: May 2007

Many patients with hypertension, especially those at increased risk because of additional cardiovascular risk factors, require treatment with more than one antihypertensive agent to achieve target blood pressure (BP) goals. Many different classes of antihypertensive agents are available: a renin-angiotensin-aldosterone system (RAAS) blocker and a diuretic are widely used in combination.

Here we report the results of the recently completed Valsartan/HCTZ versus Amlodipine in STage II hypertensive patients (VAST) trial. In this 24-week study, patients with moderate hypertension and at least one other cardiovascular risk factor were treated with a combination of valsartan 160 mg and hydrochlorothiazide (HCTZ) 12.5 or 25 mg once daily (o.d.), or with amlodipine monotherapy (10 mg o.d.). Overall, valsartan plus HCTZ 25 mg reduced systolic BP significantly more than amlodipine monotherapy, and with fewer adverse events. In addition, combination therapy resulted in a trend towards more favourable outcomes with respect to pro-thrombotic and pro-inflammatory markers than amlodipine alone.
Effects of the PPAR-γ Agonist Rosiglitazone on Renal Haemodynamics and the Renin-Angiotensin System in Diabetes
Authors: Lansang M Cecilia , Coletti Caroline , Ahmed Sofia , Gordon Michael S , Hollenberg Norman K
Published: May 2007

Background. Thiazolidinediones (TZD) have been reported to improve early stages of diabetic nephropathy independent of glycaemic control. Since blockade of the renin-angiotensin system (RAS) is known to reduce the risk of nephropathy, we hypothesised that the renal effect of TZDs might be related to a favourable effect on the intrarenal RAS. We aimed to determine if the TZD rosiglitazone could reduce RAS activation.

Methods. We studied adult type 2 diabetic patients and placed them on rosiglitazone for three months. We have previously used the renal haemodynamic response to angiotensin-converting enzyme (ACE) inhibition to demonstrate the state of RAS activation, and thus measured renal plasma flow (RPF) and glomerular filtration rate (GFR) before and after administration of captopril at 0 month and at three months. Plasma renin activity (PRA), active renin, aldosterone and natriuretic peptides were analysed.

Results. The RPF response to ACE inhibition was not altered.There was no change in GFR, PRA, active renin and aldosterone levels. Two patients developed oedema — one had an elevated baseline active renin and another had an elevated baseline aldosterone level.

Conclusion. The favourable effects of TZDs on diabetic nephropathy is likely not related to an influence on the RAS.
Lack of change in serum angiotensin-converting enzyme activity during the menstrual cycle
Authors: Sanders Julie , Harris Joanna , Cooper Jackie , Gohlke Peter , Humphries Steve E , Montgomery Hugh , Woods David R
Published: May 2007

Introduction. The Deletion (D) rather than Insertion (I) variant of the angiotensin-converting enzyme (ACE) gene is associated with higher circulating ACE activity. Meanwhile, coronary risk rises with the menstrual nadir in oestrogen levels, exogenous oestrogen reduces serum ACE activity (with a greater reduction the higher the baseline ACE activity), and pharmacological reduction in ACE activity is cardioprotective. Alterations in coronary risk associated with the menstrual cycle may thus be mediated through (genotype-dependent) changes in ACE activity. We have examined this hypothesis.

Materials and methods. Twenty-three healthy female subjects (12 II, 11 DD genotype) were studied. None were taking oral contraceptive agents. Blood was assayed for oestrogen, follicle stimulating hormone (FSH), luteinising hormone (LH), progesterone and ACE activity every three days throughout their menstrual cycle. Results ACE activity was unrelated to oestrogen, FSH or LH during the menstrual cycle, irrespective of ACE genotype.

Conclusions. The increase in myocardial ischaemia during low oestrogen phases of the menstrual cycle does not appear mediated through a fall in serum ACE activity.
Association of somatic and N-domain angiotensin-converting enzymes from Wistar rat tissue with renal dysfunction in diabetes mellitus
Authors: Ronchi Fernanda A , Irigoyen Maria-Claudia , Casarini Dulce E
Published: May 2007

Diabetes mellitus (DM) is characterised by alterations in the intrarenal renin-angiotensin system (RAS). Insulin treatment may reverse these changes by an unknown mechanism. We aimed to verify the association between somatic ACE with 136 kDa (sACE) and N-domain ACE with 69 kDa (nACE) from Wistar (W) rat tissue with DM.Three groups were studied: control (CT), insulin treated diabetic (DT) and untreated (D). ACE activity was determined using Hippuryl-His-Leu and Z-Phe-His-Leu as substrates. In D group, urine ACE activity increased for both substrates when compared with CT and DT, despite the decreased activity of renal tissues. Immunostaining of renal tissue demonstrated that ACE is more strongly expressed in the proximaltubule of D than in the same nephron portion in the other groups. Angiotensin (Ang) 1-7 and Ang II are less expressed in DT group when compared with CT and D. Ang II levels decreased in the D and DT groups showed when compared to the control. Ang 1-7 was detected in all studied groups with low levels in DT.The modulation of angiotensin peptides suggests that sACE, nACE, ACE 2 and NEP could have important functions in renal RAS regulation through a counter-regulatory mechanism to protect the kidney in diabetes mellitus.
Variable structure control with sliding sector based on hybrid switching law
Authors: Pan Yaodong , Furuta Katsuhisa
Published: May 2007

In general, a variable structure (VS) control system should be designed such that a sliding mode (or a boundary layer, or a high‐order sliding mode, or a sliding sector), where the reduced‐order system is stable, is reached in finite time, i.e. a reaching movement is necessary for VS control systems. This paper proposes a VS controller without the requirement of reaching movement. With the proposed controller, a system is stabilized by switching the system control input among a set of feedback control laws no matter whether a sliding mode happens or not. Each feedback control law is easy to be designed, because it uses only one of state variables with a fixed plus or minus feedback gain. For ann‐order system, 2nfeedback control laws are needed to realize the proposed VS control. The concept of the sliding sector is used in the paper to show that there exists an area for each feedback control law, inside which a Lyapunov function decreases with the control law although the system may not be stabilized by it alone. A common Lyapunov function for all control laws exists if the system is controllable. Based on the extremum seeking control algorithm, a switching function is defined as the variation between the Lyapunov function and a pre‐determined decrease function. Then a VS control rule is designed such that a series of sliding modes happen with the switching function being a constant and the Lyapunov function decreases in every period after switching once through all control laws. The proposed VS control system is quadratically stable. Simulation results are given to show the convergence of the proposed VS control algorithm. Copyright © 2007 John Wiley & Sons, Ltd.
MOP‐Type Binaphthyl Phosphite and Diamidophosphite Ligands and Their Application in Catalytic Asymmetric Transformations
Authors: Gavrilov Konstantin N. , Lyubimov Sergey E. , Zheglov Sergey V. , Benetsky Eduard B. , Petrovskii Pavel V. , Rastorguev Eugenie A. , Grishina Tatiana B. , Davankov Vadim A.
Published: May 2007

Monodentate phosphite and diamidophosphite ligands have been developed based on O‐methyl‐BINOL. These chiral ligands are easy to prepare from readily accessible phosphorylating reagents – (Sa or Ra)‐2‐chlorodinaphtho[2,1‐d:1′,2′‐f][1,3,2]dioxaphosphepine and (2R,5S)‐2‐chloro‐3‐phenyl‐1,3‐diaza‐2‐phosphabicyclo[3.3.0]octane. The new ligands have demonstrated excellent enantioselectivity in the palladium‐catalysed allylic substitution reactions of (E)‐1,3‐diphenylallyl acetate with sodium p‐toluenesulfinate (up to 99 % ee), pyrrolidine (up to 97 % ee), dipropylamine (up to 95 % ee) and dimethyl malonate (up to 99 % ee). In the palladium‐catalysed deracemization of ethyl (E)‐1,3‐diphenylallyl carbonate, up to 96 % enantioselectivity has been achieved. The diamidophosphite ligands have exhibited very good enantioselectivity in the Rh‐catalysed asymmetric hydrogenation of dimethyl itaconate (up to 90 % ee).
Stereoselective Prostereogenic 3‐Oxo Ester Reduction Mediated by a Novel Yeast Alcohol Dehydrogenase Derived from Kluyveromyces marxianus CBS 6556
Authors: Perrone Maria Grazia , Santandrea Ernesto , Scilimati Antonio , Syldatk Christoph
Published: May 2007

A yeast alcohol dehydrogenase (ADH) has been purified up to a purification factor value of 21,731‐fold from Kluyveromyces marxianus CBS 6556. The purification procedure consisted of two chromatographic steps (DEAE‐anion exchange and affinity chromatography). The optimal pH was 7, its optimal temperature was 40 °C and its co‐factor was NADPH. This novel ADH efficiently mediated the reduction of 3‐oxo esters with a high degree of stereoselectivity, providing chiral alcohols having the (S) absolute configuration at the newly formed stereogenic centre by delivering the hydride from the re‐face of the prochiral carbonyl compounds.
Gallium Trichloride‐Catalyzed Exhaustive α‐Ethynylation Reaction of 1‐Silylacetylenes
Authors: Amemiya Ryo , Yamaguchi Masahiko
Published: May 2007

Gallium trichloride (GaCl3) catalyzes the ethynylation reaction of a 1,4‐enyne with chlorosilylacetylene at the propargyl position giving a triethynylvinylmethane. This catalytic method can be applied to the exhaustive α‐ethynylation of 1‐silylacetylenes possessing less acidic propargyl protons, and mono‐, di‐, and triethynylated products are obtained depending on the structure of the starting materials.
Transesterification of Vegetable Oil to Biodiesel using a Heteropolyacid Solid Catalyst
Authors: Chai Fang , Cao Fenghua , Zhai Fengying , Chen Yang , Wang Xiaohong , Su Zhongmin
Published: May 2007

A clean, facile, and ecologically friendly method for the production of biodiesel has been developed. A solid acid, namely the heteropolyacid (HPA) Cs2.5H0.5PW12O40, has been used as a heterogeneous catalyst for the production of biodiesel from Eruca sativa Gars. oils (ESG oil) with methanol at a certain temperature. A study for optimizing the reaction conditions such as the reaction time, temperature, the oil to methanol ratio, the amount of catalyst, and the usage times of the catalyst, has been performed. The Cs2.5H0.5PW12O40 heterogeneous acid catalyst shows almost the same activity under the optimized reaction conditions as compared to a conventional homogeneous catalyst such as sodium hydroxide or sulfuric acid, and can easily be separated from the products and can be used for several more runs. The most important features of this catalyst are that the catalytic activity is not effected by the content of free fatty acids and content of water in the vegetable oil and that the esterification can occur at a lower temperature (room temperature) and be finished within a shorter time. The results illustrate that the Cs2.5H0.5PW12O40 is an excellent, water‐tolerant and environmentally benign solid acid catalyst for the production of biodiesel. The fuel properties of ESG biodiesel were found to be in agreement with the ASTM standard.
Quinine‐Catalyzed Enantioselective Michael Addition of Diphenyl Phosphite to Nitroolefins: Synthesis of Chiral Precursors of α‐Substituted β‐Aminophosphonates
Authors: Wang Jian , Heikkinen Lora D. , Li Hao , Zu Liansuo , Jiang Wei , Xie Hexin , Wang Wei
Published: May 2007

A quinine‐promoted, enantioselective Michael addition reaction of diphenyl phosphite with nitroalkenes has been developed. This methodology affords a facile access to enantiomerically enriched β‐nitrophosphates, precursors for the preparation of synthetically and biologically useful β‐aminophosphonates.
Amine‐Catalyzed Asymmetric Epoxidation of α,β‐Unsaturated Aldehydes
Authors: Zhao Gui‐Ling , Ibrahem Ismail , Sundén Henrik , Córdova Armando
Published: May 2007

The direct organocatalytic enantioselective epoxidation of α,β‐unsaturated aldehydes with different peroxides is presented. Proline, chiral pyrrolidine derivatives, and amino acid‐derived imidazolidinones catalyze the asymmetric epoxidation of α,β‐unsaturated aldehydes. In particular, protected commercially available α,α‐diphenyl‐ and α,α‐di(β‐naphthyl)‐2‐prolinols catalyze the asymmetric epoxidation reactions of α,β‐unsaturated aldehydes with high diastereo‐ and enantioselectivities to furnish the corresponding 2‐epoxy aldehydes in high yield with up to 97:3 dr and 98 % ee. The use of non‐toxic catalysts, water and hydrogen peroxide, urea hydroperoxide or sodium percarbonate as the oxygen sources could make this reaction environmentally benign. In addition, one‐pot direct organocatalytic asymmetric tandem epoxidation‐Wittig reactions are described. The reactions were highly diastereo‐ and enantioselective and provide a rapid access to 2,4‐diepoxy aldehydes. Moreover, a highly stereoselective one‐pot organocatalytic asymmetric cascade epoxidation‐Mannich reaction, which proceeds via the combination of iminium and enamine activation, is presented. The mechanism and stereochemistry of the amino acid‐ and chiral pyrrolidine‐catalyzed direct asymmetric epoxidation of α,β‐unsaturated aldehydes are also discussed.
Tandem Catalysis: Access to Ketones from Aldehydes and Arylboronic Acids via Rhodium‐Catalyzed Addition/Oxidation
Authors: Mora Guilhem , Darses Sylvain , Genet Jean‐Pierre
Published: May 2007

Direct cross‐coupling reactions of aromatic aldehydes with arylboronic acids afforded ketones in high yields and under mild conditions in the presence of a rhodium catalyst, acetone and a base. This new reaction, involving a formal aldehyde CH bond activation, is believed to proceed via a tandem process involving addition of the organometallic species to the aldehyde followed by oxidation by β‐hydride transfer.
Epoxide Hydrolase‐Catalysed Kinetic Resolution of a Spiroepoxide, a Key Building Block of Various 11‐Heterosteroids
Authors: Bottalla Anne‐Lise , Ibrahim‐Ouali Malika , Santelli Maurice , Furstoss Roland , Archelas Alain
Published: May 2007

Two microbial epoxide hydrolases – i.e., Aspergillus niger (AnEH) and Rhodococcus erythropolis (the so‐called “Limonene EH”: LEH) were used to achieve, for the first time, the biocatalysed hydrolytic kinetic resolution (BHKR) of spiroepoxide rac‐1. This compound is a strategic key building block allowing the synthesis of 11‐heterosteroids. Interestingly enough, the two enzymes exhibited opposite and therefore complementary enantioselectivity allowing us to isolate the residual (R,R)‐1 (from AnEH) and the residual (S,S)‐1 (from LEH) in nearly enantiopure forms (>98 %). Their absolute configurations were determined by X‐ray crystallography. An opposite regioselectivity of the oxirane ring opening for both enantiomers of substrate 1, determined using H218O labelling and chiral GC‐MS analysis, was also observed, corresponding to an attack at the less substituted carbon atom using AnEH, and at the most substituted carbon atom using LEH. A chemical process‐improving methodology was also developed. This allowed us to obtain both enantiomers of the substrate in high enantiomeric purity (99 %) and optimised quantity. In the case of the AnEH, the use of a biphasic (water/isooctane) reaction medium allowed us to increase the global substrate concentration up to 200 g/ L. The preparation of both enantiomers of 1 clearly paves the way to the preparative scale synthesis and biochemical evaluation of the corresponding 11‐heterosteroid enantiomers.
Organocatalytic Enantioselective Decarboxylative Addition of Malonic Half Thioesters to Imines
Authors: Ricci Alfredo , Pettersen Daniel , Bernardi Luca , Fini Francesco , Fochi Mariafrancesca , Herrera Raquel Perez , Sgarzani Valentina
Published: May 2007

We describe a biomimetic organocatalytic enantioselective decarboxylative addition of malonic acid half thioesters to imines. This simple protocol makes use of readily available Cinchona‐derived organocatalysts and nucleophiles at the carboxylate oxidation state. The resulting β‐amino thioesters, being attractive precursors for the preparation of optically active β‐amino acids, are formed in good yields and in up to 79 % ee. As suggested by several mechanistic insights the desired products are formed via initial formation of a thioester acetate enolate via decarboxylation of the malonic acid half thioester, followed by addition to the imine.
Synthesis of Pyrrolizidine, Indolizidine, and Quinolizidine Derivatives Using Ruthenium‐Catalyzed Ring‐Opening Metathesis and Ring‐Closing Metathesis of Cycloalkene‐ynes
Authors: Wakamatsu Hideaki , Sato Yoshihiro , Fujita Reiko , Mori Miwako
Published: May 2007

Ring‐opening metathesis and ring‐closing metathesis (ROM‐RCM) of a cyclopentene‐yne having an ester moiety was demonstrated using first‐ and second‐generation Grubbs’ catalysts. When the reaction of cycloalkene‐yne was carried out in the presence of 5 mol % of a ruthenium carbene complex under an ethylene atmosphere at room temperature, ROM‐RCM proceeded smoothly to give a pyrrolidine derivative in good yield, which could be converted to a pyrrolizidine derivative. Furthermore, ROM‐RCM of azabicyclo[2.2.1]heptene‐ynes using the second‐generation Grubbs’ catalyst was investigated. When an azabicycloheptene derivative was exposed to a catalytic amount of a ruthenium carbene complex, pyrrolizidine and indolizidine derivatives were obtained in good yields. The distribution of these products depends on the substituents on the alkyne. When azabicyclo[2.2.1]heptene‐ynes bearing large substituents on the alkyne were treated with ruthenium catalyst 1b, a pyrrolizidine derivative was obtained as the major product. ROM‐RCM of azabicyclo[2.2.2]octene‐ynes with 1b afforded quinolizidine derivative 20, although the yield was moderate.
Bioreactors Based on Monolith‐Supported Ionic Liquid Phase for Enzyme Catalysis in Supercritical Carbon Dioxide
Authors: Lozano Pedro , García‐Verdugo Eduardo , Piamtongkam Rungtiwa , Karbass Naima , De Diego Teresa , Burguete M. Isabel , Luis Santiago V. , Iborra José L.
Published: May 2007

Bioreactors with covalently supported ionic liquid phases (SILP) were prepared as polymeric monoliths based on styrene–divinylbenzene or 2‐hydroxyethyl methacrylate–ethylene dimethacrylate, and with imidazolium units loadings ranging from 54.7 to 39.8 % wt IL per gram of polymer. The SILPs were able to absorb Candida antarctica lipase B (CALB), leading to highly efficient and robust heterogeneous biocatalysts. The bioreactors were prepared as macroporous monolithic mini‐flow systems and tested for the continuous flow synthesis of citronellyl propionate in supercritical carbon dioxide (scCO2) by transesterification. The catalytic activity of these mini‐flow‐bioreactors remained practically unchanged for seven operational cycles of 5 h each in different supercritical conditions. The best results were obtained when the most hydrophobic monolith, M‐SILP‐8‐CALB, was assayed at 80 °C and 10 MPa, reaching a total turnover number (TON) of 35.8×104 mol product/mol enzyme. The results substantially exceeded those obtained for packed‐bed reactors with supported silica‐CALB‐Si‐4 catalyst under the same experimental conditions.
An Unprecedented Rhodium‐Catalyzed Asymmetric Intermolecular Hydroacylation Reaction with Salicylaldehydes
Authors: Stemmler René T. , Bolm Carsten
Published: May 2007

An unprecedented enantio‐ and diastereoselective rhodium‐catalyzed intermolecular hydroacylation reaction of salicylaldehydes with norbornenes is reported in which the corresponding aryl ketones are obtained in high diastereomeric and moderate enantiomeric excesses. It was found that monodentate phosphoramidite ligands gave rise to endo products, while bidentate phosphine ligands catalyzed the reaction to form exo products predominantly.
Convenient Preparation of Chiral α,β‐Epoxy Ketones via Claisen–Schmidt Condensation‐Epoxidation Sequence
Authors: Wang Yongcan , Ye Jinxing , Liang Xinmiao
Published: May 2007

A novel Clasisen–Schmidt condensation‐epoxidation sequence of aldehydes and ketones was developed to produce a series of chiral α,β‐epoxy ketones under asymmetric phase‐transfer catalytic conditions. The organocatalytic method reported here can afford chiral α,β‐epoxy ketones under mild conditions with moderate to good yields and up to 96 % ee.
Efficient Heterogeneously Palladium‐Catalysed Heck Arylation of Acrolein Diethyl Acetal. Selective Synthesis of Cinnamaldehydes or 3‐Arylpropionic Esters
Authors: Noël Sébastien , Luo Ciahong , Pinel Catherine , Djakovitch Laurent
Published: May 2007

A heterogeneous tetrakis(ammine)palladium‐NaY zeolite {[Pd(NH3)4]/NaY} catalyst was applied successfully to the Heck arylation of acrolein diethyl acetal using a large variety of aryl and heteroaryl bromides. Depending on the reaction conditions (Heck versus Cacchi) good to high selectivities toward the 3‐arylpropionic esters or to the cinnamaldehydes were achieved, respectively. Under classical Heck conditions, while the catalyst was found to be stable over the two first runs, it showed significant loss of activity from the third cycle. Under Cacchi conditions, the catalyst could not be reused as it led to high dehalogenation rates. All results indicate that the reactions proceed through dissolved palladium species in the bulk solution (leaching). As observed by transmission electronic microscopic (TEM) analyses, while these species can be trapped and stabilised by the zeolite framework under the Heck conditions, they tend to form large palladium(0) aggregates under the Cacchi conditions leading to dehalogenation rather than to the expected Heck coupling.
Cyclopropyl Building Blocks for Organic Synthesis, 139. Ethyl Cyclopropylidenepyruvate as a Novel Multifunctional Cyclopropyl Building Block: Facile Preparation and Basic Reaction Patterns
Authors: Bagutski Viktor , de Meijere Armin
Published: May 2007

1 Tin(II) chloride‐mediated Barbier‐type coupling of ethyl glyoxylate with 2,3‐dibromopropene followed by Simmons–Smith cyclopropanation and subsequent Dess–Martin oxidation, afforded ethyl 3‐(1‐bromocycloprop‐1‐yl)‐2‐oxopropionate (5), a stable precursor of ethyl cyclopropylidenepyruvate (1j), in good overall yield (65 %), even on a multi‐gram scale. The potentially rich chemistry of this novel cyclopropyl building block was illustrated by some basic transformations such as Michael additions of N‐, S‐, O‐ and C‐nucleophiles (10–91 % yields), Diels–Alder reactions with cyclopentadiene (65 %) and 2,3‐dimethylbuta‐1,3‐diene (66 %) as well as [4+2] cycloadditions across the enone moiety of 1j (hetero‐Diels–Alder reactions) with furan and enol ethers (65–79 %), thus opening up a ready access to a wide range of new variously functionalized cyclopropane derivatives.
Palladium‐Catalyzed Cross‐Coupling Reaction Using Arylgermanium Sesquioxide
Authors: Endo Mayuko , Fugami Keigo , Enokido Tatsuki , Sano Hiroshi , Kosugi Masanori
Published: May 2007

Powdery reagents obtained by complete alkaline hydrolysis of arylgermanium trichlorides were found to undergo the palladium‐catalyzed cross‐coupling reaction with aryl bromides and iodides in good yields. The reaction is performed in an aqueous medium taking sodium hydroxide as an activator. Some base‐sensitive functionalities such as acetyl and trifluoromethyl groups survived the reaction.
Dopaminergic candidate genes in Tourette syndrome: Association between tic severity and 3′ UTR polymorphism of the dopamine transporter gene
Authors: Tarnok Zsanett , Ronai Zsolt , Gervai Judit , Kereszturi Eva , Gadoros Julia , Sasvari‐Szekely Maria , Nemoda Zsofia
Published: May 2007

Multiple evidence suggests an involvement of the dopamine neurotransmitter system in Tourette syndrome (TS). Therefore, dopaminergic candidate genes are in the center of genetic association analyses of TS. In this study, 103 TS patients and their parents have been characterized for different dopamine‐related polymorphisms including the 48 bp variable number of tandem repeats (VNTR) of the dopamine D4 receptor (DRD4) gene, the 40 bp VNTR of the dopamine transporter (DAT1, SLC6A3) gene and the Val158Met polymorphism of the catechol‐O‐methyltransferase (COMT) gene. In addition, the 120 bp duplication and three single nucleotide polymorphisms (SNPs) were assessed in the promoter region of the DRD4 gene. The −616G allele and the 2‐G‐A‐C haplotype (i.e., the 2‐repeat form of the 120 bp sequence ∼ −616G ∼ −615A ∼ −521C combination) were preferentially transmitted, however, these results did not remain significant after correction for multiple testing. Case‐control analyses have also been carried out, resulting in negative findings. On the other hand, using a dimensional approach, the DAT1 40 bp VNTR showed an association with the peak tic‐severity as measured by the Yale Global Tic Severity Scale. Patients with at least one copy of the 9‐repeat allele had significantly more severe symptoms than individuals with the homozygous 10/10 genotype (P = 0.002). In summary, allele frequencies did not differ between cases and controls, but DAT1 genotype accounted for variations of tic severity within the TS group. © 2007 Wiley‐Liss, Inc.
A review of association and linkage studies for genetical analyses of learning disorders
Authors: Caylak Emrah
Published: May 2007

Learning disorders (LD) commonly comprise of a heterogeneous group of disorders manifested by unexpected problems in some children's experiences in the academic performance arena. These problems especially comprise of a variety of disorders which may be subclassified to attention‐deficit hyperactivity disorder (ADHD), reading disability (RD), specific language impairment (SLI), speech‐sound disorder (SSD), and dyspraxia. The aim of this review is to summarize the current molecular studies and some of the most exciting recent developments in molecular genetic research on LD. The findings for the association and linkage of LD with candidate genes will help to set the research agendas for future studies to follow. © 2007 Wiley‐Liss, Inc.
Catechol‐O‐methyltransferase polymorphism (COMT) in suicide attempters: A possible gender effect on anger traits
Authors: Baud Patrick , Courtet Philippe , Perroud Nader , Jollant Fabrice , Buresi Catherine , Malafosse Alain
Published: May 2007

Anger‐related personality traits are considered contributory risk factors for suicidal behavior. According to twin studies, they are partially under genetic control and their various clinical expressions have been associated with serotonergic and catecholaminergic activities. A functional polymorphism on the human catechol‐O‐methyltransferase (COMT) gene, which codes for the catecholamines inactivating enzymeCOMT, has been shown to influence aggressive and anger‐related traits in various clinical populations. The aim of the present study was to investigate the association between anger traits (as characterized by the State‐Trait Anger Expression Inventory, STAXI) andCOMTVal158Met polymorphism in suicide attempters (n = 427) and control subjects (n = 185). Results showed that the high activity genotype (Val/Val) was more frequent in suicide attempters than in normal controls. Moreover, the Val/Val genotype markedly affected the scores on two STAXI subscales—Trait Anger and Anger Control—in female suicide attempters, thus suggesting a possible gender effect of theCOMTgenotype on a stable personality trait. These results are discussed in the light of recently published data on the effect ofCOMTVal158Met polymorphism on different cognitive and behavioral traits. © 2007 Wiley‐Liss, Inc.
The influence of urban/rural residency on depressive symptoms is moderated by the serotonin receptor 2A gene
Authors: Jokela Markus , Lehtimäki Terho , Keltikangas‐Järvinen Liisa
Published: May 2007

Gene–environment interactions are thought to be involved in the development of depression. Here we examined the interaction effect between urban/rural residency and the serotonin receptor 2A (HTR2A) gene on subclinical depressive symptoms. The participants were 1,224 Finnish men and women being followed in the on‐going population‐based study of “Cardiovascular Risk in Young Finns”. Urban/rural residency was determined on the basis of a (1) subjective report and (2) the population density of the residential area. Depressive symptoms were measured in two test settings four years apart. There was a significant gene–environment interaction, such that the urban residency was associated with low depressive symptoms in individuals carrying the T/T or T/C genotype of the T102C polymorphism, but not in those carrying the C/C genotype. The T allele was associated with high depressive symptoms in remote rural areas, but with low depressive symptoms in urban or suburban areas. The gene–environment interaction was not accounted by level of education, social support, unemployment, or partnership status. The HTR2A gene may be involved in the development of depression by influencing how individuals respond to environmental conditions. © 2007 Wiley‐Liss, Inc.
Effects of proximity and behavioral context on acoustic variation in the coo calls of Japanese macaques
Authors: Sugiura Hideki
Published: May 2007

Acoustic features of coo calls in Japanese macaques (Macaca fuscata) show large and graded variation. To explore the relevance of acoustic variation in coo calls, I examined whether acoustic features differed by the caller's activity and proximity to group members. The subjects were five adult females from a wild, habituated group of Japanese macaques consisting of 23 individuals. Coo calls from the five females were recorded with their activity and proximity to group members. Acoustic features of 280 calls were measured with a sound spectrograph. Some of the acoustic variables differed by proximity but not by activity. The callers produced coo calls with larger frequency modulation and longer duration when they were far from group members compared to when they were near another member. The results suggest that Japanese macaques produce calls with more detectable and locatable features depending on the proximity to group members. Am. J. Primatol. 69:1412–1424, 2007. © 2007 Wiley‐Liss, Inc.