bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of Ang (1-7) in mediating the chronic hypotensive effects of losartan in normal rats
Authors: Collister John P , Hendel Michael D
Published: May 2007

Hypothesis

The following studies were designed to test the hypothesis that Ang (1-7) contributes to the chronic hypotensive effects of the angiotensin II AT1-receptor antagonist, losartan, in normal rats.

Introduction

We have previously shown a chronic, hypotensive response to the AT1-receptor antagonist, losartan, in normotensive rats. The mechanism of this response is not completely understood. Previous studies by others have demonstrated a role for Ang (1-7) in the beneficial antihypertensive effects of angiotensin-converting enzyme (ACE) inhibition. This is thought to be due to vasodilatory effects of increased levels of Ang (1-7) during ACE inhibition. Since it has now been shown that Ang (1-7) levels are also increased during AT1 antagonism, we designed experiments to test the hypothesis above.

Materials and methods

Sprague-Dawley rats were instrumented with venous catheters and radiotelemetric pressure transducers and commenced on a normal (0.4%) NaCl diet. Arterial pressure responses were measured in rats treated with losartan (10 mg/kg/day) (LOS rats, n=8) and compared with those treated with losartan and the Ang (1-7) antagonist, A779 (24 µg/kg/hour) (A779/LOS rats, n=11) for 10 days.

Results

By day 7 of treatment, mean arterial pressure had dropped by 27±1 mmHg in LOS rats, in contrast with a decrease of only 21±2 mmHg in A779/LOS rats. This attenuated response in rats treated with A779 became more prominent and continued through day 10 of losartan treatment.

Conclusion

These results support the hypothesis that the chronic hypotensive effects of losartan in normal rats are mediated in part through the actions of Ang (1-7).
Neutral endopeptidase expression in mesangial cells
Authors: Ebihara Fabiana , Seno Di Marco Giovana , Aparecida Juliano Maria , Casarini Dulce Elena
Published: May 2007

In the kidney, neutral endopeptidase (NEP) is implicated in the metabolism of several peptides involved in blood pressure and sodium homeostasis control, such as the atrial natriuretic peptide, bradykinin and angiotensin I. Due to its physiological importance in the modulation of pressor responses, the presence of NEP in mouse mesangial cells has been investigated, since these cells control glomerular function and are able to synthesise components of the renin-angiotensin system. A NEP-like activity (NEP-like) that cleaves the fluorogenic substrates Abz-BKQ-EDDnp and Abz-DRRL-EDDnp was purified from mesangial cell lysate by ion-exchange, followed by gel filtration chromatography. The enzyme was able to hydrolyse bradykinin at the G4-F5 peptide bond and was inhibited by thiorphan. A pH study established that enzyme activity was maximal at pH 7.5 and the determined Km was 4.86 µM using Abz-DRRL-EDDnp as substrate. NEP-like was recognised by monoclonal anti-NEP and had a molecular mass of 95 kDa. The purified enzyme was sequenced and showed similarity with human, rat, mouse and rabbit NEPs. We isolated, for the first time, NEP-like from mesangial cells. This enzyme could have an important role in the renal physiology by its action upon different peptides that are able to alter renal haemodynamics.
Haemodynamic and pulse wave responses to intravenous infusions of angiotensin II during chronic telmisartan therapy in normal volunteers
Authors: Vingerhoedt Noreen M , Gilles Rozemarie , Howes Jan B , Griffin Matthew , Howes Laurence Guy
Published: May 2007

Introduction

This study investigated the central haemodynamic, blood pressure (BP) and pulse wave responses to progressively increasing infusion rates of intravenous angiotensin II (Ang II) in normal volunteers during chronic therapy with telmisartan or placebo.

Materials and methods

Ten normal volunteers, aged 21—33 years, completed a ramdomised, double-blind crossover study. Ang II was infused intravenously at increasing infusion rates (0—512 ng/minute) at the end of one week of telmisartan therapy (40—80 mg/day) and one week of placebo therapy. BP, central haemodynamics and pulse wave parameters were monitored continuous using a CardioDynamics Recorder, a Pulse Tracer Recorder and a Finipress Recorder.

Results

Baseline diastolic BP (5712 v G s. 67±13 mmHg) and pulse wave reflection ndex (RI) (38.4±18.6 vs. 60.6±12.5%) were significantly lower U on telmisartan than on placebo therapy. Cardiac index (CI), systolic BP, systemic vascular resistance index (SVRI), RI and pulse wave stiffness index (SI) were all significantly increased in a dose-dependent manner by Ang II on placebo therapy. Telmisartan significantly (p<0.05) attenuated all of these responses to Ang II. Increases in BP during Ang II infusion were associated with increases in SVRI and CI.

Conclusions

Telmisartan effectively blocked the effects of intravenous Ang II on CI, BP, RI and SI in healthy volunteers. Changes in CI make a major contribution to increase in BP response to intravenous Ang II in normal volunteers.
Angiotensin inhibition in heart failure
Authors: Mcmurray John JV
Published: May 2007

Survival in patients with heart failure remains very poor, and is worse than that for most common cancers, including bowel cancer in men and breast cancer in women. The renin-angiotensin-aldosterone system (RAAS) is not completely blocked by angiotensin-converting enzyme (ACE) inhibition. Blockade of the RAAS at the AT1-receptor has the theoretical benefit of more effective blockade of the actions of angiotensin II. ACE inhibitors (ACE-Is) prevent the breakdown of bradykinin: this has been blamed for some of the unwanted effects of ACE-Is although bradykinin may have advantageous effects in heart failure. Consequently, ACE-Is and ARBs might be complementary or even additive treatments; recent trials have tested these hypotheses.

The Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) programme compared the angiotensin receptor blocker (ARB) candesartan (target dose 32 mg once daily) to placebo in three distinct but complementary populations of patients with symptomatic heart failure. These were: patients with reduced left ventricular ejection fraction (LVEF) who were ACE-I-intolerant (CHARM-Alternative); patients with reduced LVEF who were being treated with ACE-Is (CHARM-Added); and patients with preserved left ventricular systolic function (CHARM-Preserved).

There were substantial and statistically significant reductions in the primary composite end point (risk of cardiovascular death or hospital admission for heart failure) in CHARM-Alternative. This was also the case in CHARM-Added, supporting and extending the findings of Val-HeFT. In CHARM-Preserved, the effect of candesartan on the primary end point did not reach conventional statistical significance though hospital admission for heart failure was reduced significantly with candesartan. In the CHARM-Overall programme there was a statistically borderline reduction in all-cause mortality with a clear reduction in cardiovascular mortality. All-cause mortality was reduced by 12% in the two CHARM trials in patients with low LVEF.

CHARM succeeded in answering a number of questions about the safety and efficacy of ARB use in heart failure. It showed evidence for a clinical benefit of candesartan both additive to and independent of ACE-I use. The benefits in terms of clinical outcomes were seen irrespective of β-blocker usage. Benefits in patients with preserved LVEF were shown in the proportion of patients hospitalised with worsening heart failure and in overall number of admissions for heart failure. Candesartan had expected effects on blood pressure and renal function, emphasising the need for careful patient monitoring.
Effects of Genetic Polymorphisms of the Renin-Angiotensin System in Children with Nephrotic Syndrome
Authors: Tabel Ytlmaz , Berdeli Afig , Mir Sevgi , Serdaroğlu Erkin , Ytlmaz Ebru
Published: May 2007

Background. The renin-angiotensin system (RAS) has been considered to be responsible for the pathogenesis or progression of many diseases which may or may not be related to kidney. Genetic polymorphisms of the various components of the RAS have been associated with differences in the clinical course of several disease states in adults and children.

Objectives. The purpose of our study was to investigate RAS gene polymorphisms in patients with steroid resistant primary focal segmental glomerulosclerosis (FSGS) and nephrotic syndrome responding to steroid therapy. Furthermore, we aimed to investigate whether there was an association between polymorphic alleles and responses to steroid therapy, the degree of renal dysfunction, and prevalence of end-stage renal disease (ESRD).

Material and methods. One hundred and fifty-eight children with the diagnosis of nephrotic syndrome were recruited from the Nephrology unit in the Department of Paediatrics of Ege University. Forty-nine of them were classified as renal biopsy-proven FSGS and 102 patients were considered to have response to steroid treatment. Renal functional impairment was detected in 19 subjects with FSGS and end-stage renal insufficiency in 13 patients. The control group consisted of 287 healthy adult subjects. Angiotensin-converting enzyme (ACE), angiotensin II type 1 receptor (AT1R) and angiotensinogen (AGT) gene polymorphisms were determined by the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique. Statistical significance was regarded as p<0.05.

Results. There were no statistically significant differences for the C allele of AT1R or the T allele of AGT genes between the children with nephrotic syndrome and control group, but on the other hand statistically significant differences were detected for D allele of ACE gene. There was no significant relationship detected between the D allele of ACE, the C allele of AT1R or the T allele of AGT genes and response to steroid therapy, extent of renal dysfunction and the progression to ESRD. However, there was a significant relationship between T allele of AGT gene and resistance to steroid treatment (OR; 4,837, 95% CI; 1,723—13,577, p=0.01), renal dysfunction (OR; 3,189, 95% CI; 0,999—10,182, p=0.041) and progression to ESRD (OR; 3,852, 95% CI; 1,057—14,040, p=0.03).

Conclusion. In this study, the angiotensino gene -235T allele was found to be related with steroid resistance, renal dysfunction and progression of ESRD in nephrotic syndrome.
New Hypertension Guidelines from the National Institute for Health and Clinical Excellence and the British Hypertension Society
Authors: Sever Peter
Published: May 2007

A joint initiative between the National Institute for Health and Clinical Excellence (NICE) and the British Hypertension Society (BHS) has led to the publication of new guidelines for the management of hypertension in the community. Recent trial evidence highlighting the increased incidence of new-onset diabetes in those exposed to beta-blocker-based treatment regimens, with or without diuretics, compared with those based on calcium channel blockers (CCBs) or angiotensin-converting enzyme (ACE-Is) inhibitors has led to a recommendation that in the uncomplicated patient, beta-blockers are no longer considered suitable options for first-line therapy. Together with mounting A evidence that age and ethnicity dictate blood pressure (BP) responsiveness to different classes of antihypertensive drugs, the ACD algorithm is now proposed (formerly ABCD), with ACE inhibitors (ACE-Is) (or angiotensin receptor blockers [ARBs] when ACE-Is are poorly tolerated) preferred in younger patients and or patients and CCBs or diuretics preferred for older patientsand in black patients of any age. Pathophysiological considerations have influenced proposals for combination therapies with CCBs or diuretics added to older patients. Health economic analyses have ACE-Is in younger patients and vice versa in clearly indicated the cost effectiveness of CCBs which are now elevated to equal standing with diuretics in older patients.
Genetic Clamping of Renin Gene Expression Induces Hypertension and Elevation of Intrarenal Ang II Levels of Graded Severity in Cyp1a1-Ren2 Transgenic Rats
Authors: Mitchell Kenneth D , Bagatell Stuart J , Miller Chad S , Mouton Cynthia R , Seth Dale M , Mullins John J
Published: May 2007

Introduction. Transgenic rats with inducible angiotensin II (Ang II)-dependent hypertension (strain name: TGR[Cyp1a1-Ren2]) were generated by inserting the mouse Ren2 renin gene, fused to the cytochrome P450 1a1 (Cyp1a1) promoter, into the genome of the rat. The present study was performed to characterise the changes in plasma and kidney tissue Ang II levels and in renal haemodynamic function in Cyp1a1-Ren2 rats following induction of either slowly developing or malignant hypertension in these transgenic rats.

Materials and Methods. Arterial blood pressure (BP) and renal haemodynamics and excretory function were measured in pentobarbital sodium-anaesthetised Cyp1a1Ren2 rats fed a normal diet containing either a low dose (0.15%, w/w for 14—15 days) or high dose (0.3%, w/w for 11—12 days) of the aryl hydrocarbon indole-3-carbinol (I3C) to induce slowly developing and malignant hypertension, respectively. In parallel experiments, arterial blood samples and kidneys were harvested for measurement of Ang II levels by radioimmunoassay.

Results. Dietary I3C increased plasma renin activity (PRA), plasma Ang II levels, and arterial BP in a dose-dependent manner. Induction of different fixed levels of renin gene expression and PRA produced hypertensive phenotypes of varying severity with rats developing either mild or malignant forms of hypertensive disease. Administration of I3C, at a dose of 0.15% (w/w), induced a slowly developing form of hypertension whereas administration of a higher dose (0.3%) induced a more rapidly developing hypertension and the clinical manifestations of malignant hypertension including severe weight loss. Both hypertensive phenotypes were characterised by reduced renal plasma flow, increased filtration fraction, elevated PRA, and increased plasma and intrarenal Ang II levels. These I3C-induced changes in renal haemodynamics, PRA and kidney Ang II levels were more pronounced in Cyp1a1-Ren2 rats with malignant hypertension. Chronic administration of the AT1-receptor antagonist, candesartan, prevented the development of hypertension, the associated changes in renal haemodynamics, and the augmentation of intrarenal Ang II levels.

Conclusions. Activation of AT1-receptors by Ang II generated as a consequence of induction of the Cyp1a1-Ren2 transgene mediates the increased arterial pressure and the associated reduction of renal haemodynamics and enhancement of intrarenal Ang II levels in hypertensive Cyp1a1-Ren2 B transgenic rats.
Review: Autosomal Dominant Polycystic Kidney Disease: Role of the Renin-Angiotensin System in Raised Blood Pressure in Progression of Renal and Cardiovascular Disease
Authors: Lawson Catherine R , Doulton Timothy W , MacGregor Graham A
Published: May 2007

Raised blood pressure (BP) is extremely common in individuals with autosomal dominant polycystic kidney disease (ADPKD) and is almost invariably raised once they develop renal failure. The underlying mechanisms for the rise in BP in individuals with ADPKD are unclear. The progressive number and enlargement of renal cysts, causing structural damage to the kidneys and, thereby, affecting tubular function as well as causing distortion of the glomeruli and renal ischaemia, is likely to be of primary importance.There is some evidence from animal models that there may be over-activity of the intra-renal renin-angiotensin system (RAS) that could account for the rise in BP. Studies in man have shown conflicting results, but a recent more carefully controlled study using both measurements of activity and pharmacological blockade of the RAS clearly demonstrated no evidence of over-activity of the circulating RAS in ADPKD compared to matched individuals with essential hypertension. A more likely explanation for the rise in BP that occurs in ADPKD is retention of sodium and water due to tubular damage. Disappointingly, in spite of good evidence that RAS blocking drugs slow the progression of other renal, particularly glomerular, diseases, there is little evidence to suggest this is true for patients with ADPKD. Nevertheless, there is no doubt that lowering BP in ADPKD is just as important, if not more important, as in essential hypertension to prevent cardiovascular disease and strokes, with a recommended BP target of < 120/80 mmHg.
Aliskiren: A clinical profile
Authors: Schmieder Roland E
Published: May 2007

Aliskiren is a novel oral antihypertensive agent, and the first in the new class of direct renin inhibitors. Here we review the key criteria that a new antihypertensive drug should possess, notably effective blood pressure lowering as monotherapy and combination therapy, 24-hour blood pressure control, safety and tolerability end-organ protective effects, minimal drug interaction and efficacy during long-term use.

Aliskiren fulfils key criteria for a new antihypertensive agent. The drug demonstrates effective blood lowering in a number of studies as monotherapy and in combination with a thiazide diuretic (hydrochlorothiazide), an angiotensin-converting enzyme inhibitor (ramipril) and a calcium channel blocker (amlodipine). Other studies applying ambulatory blood pressure monitoring show that aliskiren maintains blood pressure control for more than 24 hours. Aliskiren, 150 mg and 300 mg have demonstrated a placebo-like safety and tolerability profile with no interactions with a wide range of commonly used drugs. Three studies (AVOID, ALOFT and ALLAY) are ongoing with aliskiren to assess end-organ protective properties.
Review: Potential protective effects of telmisartan on renal function deterioration
Authors: Remuzzi Andrea , Remuzzi Giuseppe
Published: May 2007

Experimental and clinical evidence is now available that antagonism of angiotensin II (Ang II) with both angiotensin-converting enzyme inhibitors and Ang II receptor antagonists (AIIAs) is effective in slowing the rate of renal functional loss in patients affected by proteinuric kidney diseases.Among AIIAs, telmisartan has been shown to be characterised by a potent and long lasting antihypertensive effect that may be associated with another specific effect of this molecule, the partial agonism of the peroxisome-activated receptor-gamma.Although this action has also been observed with other AIIAs, telmisartan seems to exert a more effective and specific action as in such a way to influence beneficially adipocyte metabolism, diabetes onset and insulin resistance. Recently, we have demonstrated, at the experimental and clinical level, that sustained blockade of Ang II biological activity with this class of compounds can potentially reduce the progression of renal dysfunction and in some circumstances induce the regression of renal functional and structural changes. In this review we analyse available experimental and clinical data that suggest that blocking Ang II with telmisartan may effectively ameliorate renal dysfunction in patients affected by the now frequently observed condition termed metabolic syndrome.
Role of connective tissue growth factor in vascular and renal damage associated with hypertension in rats. Interactions with angiotensin II
Authors: de las Heras Natalia , Ruiz-Ortega Marta , Rupérez Mónica , Sanz-Rosa David , Miana María , Aragoncillo Paloma , Mezzano Sergio , Lahera Vicente , Egido Jesús , Cachofeiro Victoria
Published: May 2007

We have evaluated the role of connective tissue growth factor (CTGF) in vascular and renal damage associated with hypertension and possible interactions with angiotensin II (Ang II). Spontaneously hypertensive rats (SHR) were treated with either the Ang II receptor antagonist candesartan (C;2 mg/Kg-1/day-1) or antihypertensive triple therapy (TT; in mg/Kg-1/day-1 ;20 hydralazine +7 hydrochlorothiazide +0.15 reserpine) for 10 weeks. Wistar Kyoto rats were used as a normotensive control group. Hypertension was associated with an increase in aortic media area, media-to-lumen ratio and collagen density. Kidneys from SHR showed minimum renal alterations. Aorta and renal gene expression and immunostaining of CTGF were higher in SHR. Candesartan decreased arterial pressure, aortic media area, media-to-lumen ratio and collagen density. However, although arterial pressure decrease was comparable for both treatments,TT partially reduced these parameters. Candesartantreated rats showed lower levels of vascular CTGF expression, aortic media area, media-to-lumen ratio and collagen density than TT-treated animals. Treatments improve renal damage and reduce renal gene exp Pression and CTGF immunostaining in SHR in a similar manner.The results show that vascular and renal damage is associated with stimulation of CTGF gene and protein content.These results also might suggest that CTGF could be one downstream mediator of Ang II in hypertension-associated organ damage in SHR.
Review: Angiotensin-converting enzyme inhibitors and coronary heart disease prevention
Authors: Donnelly Richard , Manning Gillian
Published: May 2007

A number of large randomised controlled trials have shown that angiotensin-converting enzyme (ACE) inhibitors, compared with placebo or other blood pressure-lowering drugs, improve coronary heart disease outcomes (fatal and non-fatal myocardial infarction, and coronary revascularisation) in diverse patient groups, e.g. in primary and secondary prevention, those with and without left ventricular dysfunction, and among hypertensive and non-hypertensive subjects. An updated meta-regression analysis which included five major trials in patients with established coronary artery disease (CAD) (EUROPA, INVEST, ACTION, PEACE and CAMELOT) concluded that ACE inhibitor (ACE-I) therapy has clear benefits in secondary prevention, but there are important and unexplained differences between trials in clinical outcome, baseline cardiovascular risk, blood pressure changes and trial design which deserve further discussion of the underlying mechanisms and clinical interpretation. For example, in placebo-controlled trials the biggest (20—22%) reductions in primary end points (including mortality) have been observed with perindopril and ramipril, whereas trials using trandolapril and quinapril had no effect on survival or recurrent CAD events. This review summarises and compares the major findings of these recent trials, and provides further analysis of the underlying mechanisms and clinical significance of secondary CAD prevention with ACE-I therapy.
Association of ACE genotype and predominantly diastolic hypertension: a preliminary study
Authors: Jiménez Pablo Martin , Conde Cecilia , Casanegra Ana , Romero Cesar , Hugo Tabares Aldo , Orías Marcelo
Published: May 2007

Background. The insertion/deletion (I/D) angiotensin-converting enzyme (ACE) polymorphism has been established as a cardiovascular risk factor in some populations, but the association with essential hypertension is controversial. Predominantly diastolic hypertension (PDH), or narrow pulse pressure hypertension, has been shown to have increased peripheral resistance. Because a DD genotype has been associated with higher plasma ACE levels and angiotensin II activity, we genotyped PDH patients for ACE I/D polymorphism.

Methods. Ninety-three patients with systolic blood pressure (BP) < 140 mmHg systolic and diastolic BP > 90 mmHg, or BP > 140/90 mmHg with a pulse pressure < 45 mmHg, were defined as PDH. The II, ID and DD genotype variants of ACE were characterised by the triple primer nested-PCR method. Results were compared to 75 normotensive control individuals. Statistical significance was assessed by the Chi square test.

Results. The genotype distribution among PDH patients was II=20 (21.5%), ID=34 (36.5%), DD=39 (42%), while the distribution among normotensive controls was II= O 16 (21.4%), ID=42 (56%), DD=17 (22.6%).The difference in genotype distribution between PDH patients and controls was significant (p<0.02). ACE allele frequencies in PDH patients and controls were D=0.60, I=0.40 and D=0.51, and controls were D=0.60, 1=0.40 and D=0.51, I=0.49, respectively, statistically non-significant (ns).

Conclusion. These results suggest an association between ACE genotype DD and predominantly diastolic hypertension.
Changes of gene expression profiles in macrophages stimulated by angiotensin II — Angiotensin II induces MCP-2 through AT1-receptor
Authors: Tone Atsuhito , Shikata Kenichi , Ogawa Daisuke , Sasaki Sakiko , Nagase Ryo , Sasaki Motofumi , Yozai Kosuke , Kataoka Usui Hitomi , Okada Shinichi , Wada Jun , Shikata Yasushi , Makino Hirofumi
Published: May 2007

Introduction. Macrophages play critical roles in the development of atherosclerosis and diabetic nephropathy as well as many inflammatory diseases. Angiotensin II type 1 receptor antagonists (AIIA) are beneficial for the prevention of atherosclerosis and diabetic nephropathy suggesting that angiotensin II (Ang II) promotes the development of these diseases. It has recently been reported that Ang II exerts proinflammatory actions in vivo and in vitro. This study was aimed to clarify the direct effects of Ang II on monocytes/macrophages.

Materials and methods. PMA-treated THP-1 cells, a human monocytic leukaemia cell line, were treated with Ang II (10-6 mol/L) for 24 hours with or without AIIA (CV11974). We evaluated gene expression profiles of these cells using DNA microarray system and quantified them by real-time RT-PCR.

Results. DNA microarray revealed that in total 19 genes, including monocyte chemoattractant protein (MCP)-2, were up-regulated by Ang II and down-regulated by AIIA. Real-tim D e RT-PCR showed that up-regulation of MCP-2 with Ang II is blocked by the AIIA (CV11974) but not by an AT2-receptor antagonist.

Conclusions. These results suggest that Ang II directly stimulates MCP-2 expression through AT1-receptors in activated macrophages.Ang II may contribute to the persistence or amplification of microinflammation in vessel walls, heart and kidney.Vasculoprotective or renoprotective effects of AIIA might partly depend on direct antiinflammatory effects on macrophages.
A chronometric study of mental addition in profoundly deaf children
Authors: Mulhern Gerry , Budge Ally
Published: May 2007

In attempting to account for inferior mathematical attainment among deaf children of all ages, some researchers have proposed that observed deficits may be partly the result of an absence of vocalization and subvocalization in the acquisition and execution of arithmetic by the deaf. When performing mental arithmetic, hearing children, it is claimed, rely on covert counting mechanisms based on internalized speech, while their deaf counterparts, due to a lack of articulatory prowess, are unable to utilize such mechanisms and instead are forced to adopt other less effective methods based on associative retrieval of arithmetical facts from long‐term memory. The present study sought to throw light on these assertions. Ten prelingually profoundly deaf 12‐13‐year‐olds, and 10 hearing controls were required to solve the 100 simple addition combinations. Analysis of response times revealed strong similarities between the two groups, with all children appearing to employ mechanisms based on covert counting. Implications of the present results are discussed in the light of previous findings.
The effect of actual event duration and event memory on the reconstruction of duration information
Authors: Burt Christopher D. B.
Published: May 2007

Two experiments investigated the effect of actual event duration and event memory on the retrospective estimation of public event duration. Experiment 1 provided a typicality score for each of 20 public events. The typicality score represents the degree to which the event's actual duration deviates from the typical duration of its category. Subjects in Experiment 2 estimated the duration of the events used in Experiment 1 and indicated whether they remembered the events. Typicality scores were found to be highly correlated with estimation accuracy, and to predict whether event duration was under‐ or over‐estimated. Remembering an event slightly increased estimation accuracy. The results are discussed in terms of their implications for the assessment of eyewitness retrospective duration estimation abilities, and the reconstructive model of retrospective duration estimation proposed by Burt and Kemp (1991).
Prediction of psychosis onset in Alzheimer disease: The role of depression symptom severity and the HTR2A T102C polymorphism
Authors: Wilkosz Patricia A. , Kodavali Chowdari , Weamer Elise A. , Miyahara Sachiko , Lopez Oscar L. , Nimgaonkar Vishwajit L. , DeKosky Steven T. , Sweet Robert A.
Published: May 2007

Psychotic symptoms in Alzheimer disease (AD + P) identify a heritable phenotype associated with a more severe course. We recently found an association of AD + P with depression symptom severity. Reports have shown an association of a serotonin‐2A receptor (HTR2A) gene T102C polymorphism with AD + P and with depression during AD. We examined the interaction of this common genetic polymorphism with depression and increased psychosis risk. Subjects with possible or probable AD or mild cognitive impairment (MCI) without psychosis at study entry were genotyped for the HTR2A T102C polymorphism and reassessed every 6 months until psychosis onset. Psychotic and depressive symptoms were rated using the CERAD behavioral rating scale (CBRS). Cox proportional hazard models with time‐dependent covariates were used to examine associations with psychosis onset. A total of 324 Caucasian subjects completed at least one follow‐up exam. Depressive symptom severity was a strong predictor of psychosis onset. Neither psychosis onset nor depression severity was associated with the HTR2A genotype. Genotype interacted with depression severity to moderate the risk of AD + P onset. This did not result from an interaction of HTR2A genotype with antidepressant use. Psychosis onset in AD is strongly associated with severity of depressive symptoms, an association that may be modified by HTR2A genotype. © 2007 Wiley‐Liss, Inc.
Analysis of DRD4 and DAT polymorphisms and behavioral inhibition in healthy adults: Implications for impulsivity
Authors: Congdon Eliza , Lesch Klaus Peter , Canli Turhan
Published: May 2007

Impulsivity, a highly prevalent symptom in multiple psychiatric disorders, is a partially heritable trait influenced by specific biological mechanisms. In particular, dopamine is proposed to play a role in impulsive behaviors and recent studies have implicated functional polymorphisms of dopamine‐related genes in impulsive behaviors across different clinical and behavioral classifications. However, most have not isolated the impulsivity construct per se as a biologically based and measurable endophenotype. The present study was therefore undertaken in a sample of healthy adults to investigate the influence of two candidate dopaminergic gene polymorphisms (DRD4 and DAT) on the endophenotype of impulsivity, which we operationalized as behavioral inhibition during the Stop‐signal task. We recruited an ethnically diverse sample of 119 healthy adults to complete a self‐report questionnaire of impulsivity and to perform a Stop‐signal task. We report significant differences in inhibitory control between individuals with at least one 7‐repeat allele of the DRD4 polymorphism, as well as an interaction between DRD4 and DAT genotypes, on inhibitory control. Results of the present study support the influence of dopaminergic variation on impulsive‐related measures, as well as the advantage of using measures which are likely more sensitive to the effects of such genetic variation. © 2007 Wiley‐Liss, Inc.
Evidence that the COMTVal158Met polymorphism moderates sensitivity to stress in psychosis: An experience‐sampling study
Authors: van Winkel Ruud , Henquet Cécile , Rosa Araceli , Papiol Sergi , Faňanás Lourdes , De Hert Marc , Peuskens Jozef , van Os Jim , Myin‐Germeys Inez
Published: May 2007

Gene–environment interactions involving the catechol‐O‐methyltransferase Val158Met polymorphism (COMTVal158Met) have been implicated in the causation of psychosis. Evidence from general population studies suggests that Met/Met subjects are sensitive to stress, a trait associated with psychosis. We hypothesized that the Met allele would moderate the effects of stress on negative affect (NA) in controls, and on NA and psychosis in patients with a psychotic disorder. Thirty‐one patients with a psychotic disorder and comorbid cannabis misuse and 25 healthy cannabis users were studied with the experience sampling method (ESM), a structured diary technique assessing current context and emotional and psychotic experiences in daily life. A significant interaction between COMTVal158Met genotype and ESM stress in the model of NA was found for patients (interaction χ2 = 7.4, P = 0.02), but not for controls (interaction χ2 = 3.8, P = 0.15). In the model of ESM psychosis, a significant interaction between COMTVal158Met genotype and ESM stress was also apparent (interaction χ2 = 11.6, P < 0.01), with Met/Met patients showing the largest increase in psychotic experiences as well as NA in reaction to ESM stress. The findings suggest that the COMTVal158Met polymorphism moderates affective and psychotic responses to stress in patients with psychosis, providing evidence for gene–environment interaction mechanisms in the formation of psychotic symptoms. © 2007 Wiley‐Liss, Inc.
Synthesis of Monodisperse Spherical Nanocrystals
Authors: Park Jongnam , Joo Jin , Kwon Soon Gu , Jang Youngjin , Hyeon Taeghwan
Published: May 2007

Much progress has been made over the past ten years on the synthesis of monodisperse spherical nanocrystals. Mechanistic studies have shown that monodisperse nanocrystals are produced when the burst of nucleation that enables separation of the nucleation and growth processes is combined with the subsequent diffusion‐controlled growth process through which the crystal size is determined. Several chemical methods have been used to synthesize uniform nanocrystals of metals, metal oxides, and metal chalcogenides. Monodisperse nanocrystals of CdSe, Co, and other materials have been generated in surfactant solution by nucleation induced at high temperature, and subsequent aging and size selection. Monodisperse nanocrystals of many metals and metal oxides, including magnetic ferrites, have been synthesized directly by thermal decomposition of metal–surfactant complexes prepared from the metal precursors and surfactants. Nonhydrolytic sol–gel reactions have been used to synthesize various transition‐metal‐oxide nanocrystals. Monodisperse gold nanocrystals have been obtained from polydisperse samples by digestive‐ripening processes. Uniform‐sized nanocrystals of gold, silver, platinum, and palladium have been synthesized by polyol processes in which metal salts are reduced by alcohols in the presence of appropriate surfactants.
Photodegradation of cellulose acetate film in the presence of benzophenone as a photosensitizer
Authors: Hosono Kiyoshi , Kanazawa Akihiko , Mori Hideharu , Endo Takeshi
Published: May 2007

To study the effectiveness of photosensitizers to accelerate the degradation of cellulose acetate (CA) under ambient environment, CA (degree of substitution = 2.45) films containing benzophenone, which is one of the typical photosensitizers, were prepared and their degradative behavior by photoirradiation was examined. Decrease in molecular weight of CA and generation of carbon dioxide, carbon monoxide, and acetic acid from the CA films were observed by the irradiation of xenon arc lamp light, which was passed through a filter for cutting off the wavelength shorter than 275 nm. With increasing the concentration of benzophenone, the molecular weight of CA decreased and the generation of the degradation products from the CA films increased. These results may suggest that radical reactions of CA films proceed by photoirradiation and lead to oxidation and random cleavage of CA, and that benzophenone is an effective additive to accelerate the degradation of CA under ambient environment. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
All‐trans retinoic acid release from polyion‐complex micelles of methoxy poly(ethylene glycol) grafted chitosan
Authors: Kim Dong‐Gon , Jeong Young‐Il , Nah Jae‐Woon
Published: May 2007

We synthesized a methoxy poly(ethylene glycol) grafted chitosan (ChitoPEG) copolymer to prepare a retinoic acid (RA) encapsulated polymeric micelle. The RA‐encapsulated polymeric micelle of the ChitoPEG copolymer had a particle size of 100–500 nm and a spherical shape when observed by transmission electron microscopy. In a1H‐NMR study, the specific peaks of RA and chitosan as a drug‐carrying inner core disappeared in deuterium oxide, and only the specific peak of methoxy poly (ethylene glycol) (MPEG) was observed, whereas specific peaks of MPEG, RA, and chitosan appeared in dimethyl sulfoxide. This indicated that the RA/ChitoPEG ion complexes were composed of a polymeric micelle with a core–shell structure and that free drug did not exist in the polymeric micelle formulations. Other evidence of drug incorporation into the polymeric micelle was witnessed in a differential scanning calorimetry analysis. The melting peaks of RA and chitosan were 182 and 220°C, respectively. The melting peak of the polymeric micelle was 200°C, whereas the melting peaks of the physical mixtures were those of both RA and the ChitoPEG copolymer. The lyophilized polymeric micelle was successfully reconstituted into phosphate‐buffered saline without the aid of cryoprotectants. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
Influences of various surface pretreatments on the mechanical and degradable properties of photografted oil palm fibers
Authors: Rahman M. Mizanur , Mallik Abul K. , Khan Mubarak A.
Published: May 2007

Natural‐fiber‐reinforced polymers can exhibit very different mechanical performances and environmental aging resistance depending on their interphase properties. A lack of good interfacial adhesion and poor resistance to moisture absorption make oil palm fibers less attractive as reinforcing agents. To improve the interfacial properties, oil palm fibers were grafted with different percentages of allyl methacrylate (AMA) in methanol. Darocur 2959 was added as a photoinitiator and initiated photochemical polymerization. The fiber surfaces were pretreated by an alkali, KMnO4, and dewaxed; this was followed by grafting with AMA to determine the effect of various surface treatments on the physicomechanical properties of grafted fibers. The alkali treatment increased the surface roughness with better impregnation of the polymer, which increased the tensile properties by about 20%. A minute amount of an additive (urea) and a coupling agent (silane) were added to the optimum formulations. These increased the physical properties of the grafted oil palm fibers because of increased crosslinking. The treated and untreated fiber samples were also subjected to various weather conditions, such as simulated weather, soil, and water aging, to determine the degradation properties, and lower losses were observed for the treated samples than the untreated fibers. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007
Vulcanization kinetics of low‐protein natural rubber with use of a vulcameter
Authors: Wang Ping‐Yue , Chen Ying , Qian Hong‐Lian
Published: May 2007

Kinetics of vulcanization of low‐protein natural rubber (LPNR) was studied with the use of a vulcameter. In the induction period of vulcanization, the time t0 of LPNR is longer than that of natural rubber (NR), and the temperature dependences of the time tdis and the rate constant
$ k^{1/\alpha}_1 $
of LPNR are greater than that of NR. Both the curing periods of LPNR and NR (except 170°C for LPNR) consist of two stages. The first stage follows first‐order reaction. The rate constant k2 of LPNR in the first stage is substantially the same as that of NR at the same temperature, and so is the activation energy E2. The second stage (end stage of the curing period) does not follow first‐order reaction, and the calculated reaction order n is in the range of 0.67–0.73. Both rate constants of LPNR (except 170°C) and NR at the same temperature are approximately the same, and so is the activation energy E3. The whole process of curing period for LPNR at 170°C follows n = 0.7 order reaction. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
Sound transmission in archaic and modern whales: Anatomical adaptations for underwater hearing
Authors: Nummela Sirpa , Thewissen J.G.M. , Bajpai Sunil , Hussain Taseer , Kumar Kishor
Published: May 2007

The whale ear, initially designed for hearing in air, became adapted for hearing underwater in less than ten million years of evolution. This study describes the evolution of underwater hearing in cetaceans, focusing on changes in sound transmission mechanisms. Measurements were made on 60 fossils of whole or partial skulls, isolated tympanics, middle ear ossicles, and mandibles from all six archaeocete families. Fossil data were compared with data on two families of modern mysticete whales and nine families of modern odontocete cetaceans, as well as five families of noncetacean mammals. Results show that the outer ear pinna and external auditory meatus were functionally replaced by the mandible and the mandibular fat pad, which posteriorly contacts the tympanic plate, the lateral wall of the bulla. Changes in the ear include thickening of the tympanic bulla medially, isolation of the tympanoperiotic complex by means of air sinuses, functional replacement of the tympanic membrane by a bony plate, and changes in ossicle shapes and orientation. Pakicetids, the earliest archaeocetes, had a land mammal ear for hearing in air, and used bone conduction underwater, aided by the heavy tympanic bulla. Remingtonocetids and protocetids were the first to display a genuine underwater ear where sound reached the inner ear through the mandibular fat pad, the tympanic plate, and the middle ear ossicles. Basilosaurids and dorudontids showed further aquatic adaptations of the ossicular chain and the acoustic isolation of the ear complex from the skull. The land mammal ear and the generalized modern whale ear are evolutionarily stable configurations, two ends of a process where the cetacean mandible might have been a keystone character. Anat Rec, 290:716–733, 2007. © 2007 Wiley‐Liss, Inc.
Adaptive features of aquatic mammals' eye
Authors: Mass Alla M. , Supin Alexander YA.
Published: May 2007

The eye of aquatic mammals demonstrates several adaptations to both underwater and aerial vision. This study offers a review of eye anatomy in four groups of aquatic animals: cetaceans (toothed and baleen whales), pinnipeds (seals, sea lions, and walruses), sirenians (manatees and dugongs), and sea otters. Eye anatomy and optics, retinal laminar morphology, and topography of ganglion cell distribution are discussed with particular reference to aquatic specializations for underwater versus aerial vision. Aquatic mammals display emmetropia (i.e., refraction of light to focus on the retina) while submerged, and most have mechanisms to achieve emmetropia above water to counter the resulting aerial myopia. As underwater vision necessitates adjusting to wide variations in luminosity, iris muscle contractions create species‐specific pupil shapes that regulate the amount of light entering the pupil and, in pinnipeds, work in conjunction with a reflective optic tapetum. The retina of aquatic mammals is similar to that of nocturnal terrestrial mammals in containing mainly rod photoreceptors and a minor number of cones (however, residual color vision may take place). A characteristic feature of the cetacean and pinniped retina is the large size of ganglion cells separated by wide intercellular spaces. Studies of topographic distribution of ganglion cells in the retina of cetaceans revealed two areas of ganglion cell concentration (the best‐vision areas) located in the temporal and nasal quadrants; pinnipeds, sirenians, and sea otters have only one such area. In general, the visual system of marine mammals demonstrates a high degree of development and several specific features associated with adaptation for vision in both the aquatic and aerial environments. Anat Rec, 290:701–715, 2007. © 2007 Wiley‐Liss, Inc.
Cetacean brains: How aquatic are they?
Authors: Marino Lori
Published: May 2007

The adaptation of cetaceans to a fully aquatic lifestyle represents one of the most dramatic transformations in mammalian evolutionary history. Two of the most salient features of modern cetaceans are their fully aquatic lifestyle and their large brains. This review article will offer an overview of comparative neuroanatomical research on aquatic mammals, including analyses of odontocete cetacean, sirenian, pinniped, and fossil archaeocete brains. In particular, the question of whether a relationship exists between being fully aquatic and having a large brain is addressed. It has been hypothesized that the large, well‐developed cetacean brain is a direct product of adaptation to a fully aquatic lifestyle. The current consensus is that the paleontological evidence on brain size evolution in cetaceans is not consistent with this hypothesis. Cetacean brain enlargement took place millions of years after adaptation to a fully aquatic existence. Neuroanatomical comparisons with sirenians and pinnipeds provide no evidence for the idea that the odontocete's large brain, high encephalization level, and extreme neocortical gyrification is an adaptation to a fully aquatic lifestyle. Although echolocation has been suggested as a reason for the high encephalization level in odontocetes, it should be noted that not all aquatic mammals echolocate and echolocating terrestrial mammals (e.g., bats) are not particularly highly encephalized. Echolocation is not a requirement of a fully aquatic lifestyle and, thus, cannot be considered a sole effect of aquaticism on brain enlargement. These results indicate that the high encephalization level of odontocetes is likely related to their socially complex lifestyle patterns that transcend the influence of an aquatic environment. Anat Rec, 290:694–700, 2007. © 2007 Wiley‐Liss, Inc.
Scale‐up of upstream and downstream operations for the production of glucosamine using microbial fermentation
Authors: Chmielowski Rebecca A. , Wu Ho‐Shing , Wang Shaw S.
Published: May 2007

Glucosamine is used to treat osteoarthritis or as a nutritional supplement. The synthesis, isolation, and purification of glucosamine play a crucial role in its industrial application. This work presents the production of glucosamine from microbial fermentation, and discusses the production problems at both the upstream and downstream operations when the fermentation process is scaled up. The cost evaluation of process design was used to analyze the feasibility of using microbial fermentation for the production of glucosamine. The calculated result shows that the cost of the production of glucosamine should be designed to be approximately between US$200 and 300/kg for the project to be viable.
Safety assessment of genetically modified organisms of plant origin in the Russian Federation
Authors: Tyshko Nadezhda V. , Aksyuk Irina N. , Tutelyan Victor A.
Published: May 2007

The beginning of the 21st century is characterized by growing interest in the problems of biosafety, which are determined, on the one hand, by the wide use of novel biotechnologies and the necessity to develop the adequate precautionary measures, and, on the other hand, by the objective threat of bioterrorism. Therefore, improvement of the estimation system for genetically modified (GM) sources of food and strengthening the control of their circulation are the urgent problems of modern biology and medicine. Russia is one of the countries where the estimation system of food products obtained from the GM sources is rather efficient. The key features of this system are the complex toxicological and epidemiological examinations. One of the main parts of GM food safety assessment is based upon detection of their potentially toxic properties, which could provoke unintended effects of the genetic modification.