bluuebunny/crossref_metadata_2025_split huggingface dataset:
Renal vasodilation induced by hypernatraemia: Role of α‐adrenoceptors in the median preoptic nucleus
Authors: Pedrino Gustavo R , Monaco Luciana R , Cravo Sergio L 
Published: August 2009

Summary1. The renal vasodilation induced by infusion of hypertonic saline (HS) in anaesthetized rats has been shown to depend on the integrity of the median preoptic nucleus (MnPO), as well as noradrenergic afferents to this nucleus. In the present study, we sought to determine the role of α1 and α2‐adrenoceptors in the MnPO in cardiovascular responses induced by intravenous HS infusion (3 mol/L NaCl; 1.8 mL/kg, i.v., over 1 min).2. Male Wistar rats (320–360 g) were anaesthetized with urethane (1.2 g/kg, i.v.) and instrumented for recording of mean arterial pressure (MAP), renal blood flow (RBF) and vascular conductance (RVC). In one experimental group, rats were injected with yohimbine, prazosin or saline (control) 20 min before HS infusion. In another experimental group, rats were injected with yohimbine or prazosin 20 min after HS infusion.3. In control rats (n = 7), HS infusion 20 min after saline nanoinjection produced a transient hypertension. Ten minutes after HS infusion, RBF and RVC increased to 159 ± 14% and 145 ± 11% of baseline, respectively. Nanoinjection of the α1‐adrenoceptor antagonist prazosin (0.25 mmol/L; n = 6) into the MnPO 20 min before HS infusion increased the HS‐induced pressor response. However, HS‐induced increases in RBF and RVC were significantly reduced (130 ± 11% and 105 ± 6% of baseline, respectively, 10 min after HS). Nanoinjection of the α2‐adrenoceptor antagonist yohimbine (0.23 mmol/L; n = 5) into the MnPO 20 min before HS infusion increased the duration of the pressor response and reduced the increases in RBF and RVC induced by HS (117 ± 10% and 97 ± 11% of baseline, respectively, 10 min after HS).4. We also observed that nanoinjections of the prazosin into the MnPO 60 min after HS infusion resulted in a gradual return of RBF and RVC to baseline values. However nanoinjection of yohimbine 60 min after HS failed to reduce renal vasodilatation induced by hypernatremia.5. The results of the present study demonstrate that the integrity of adrenergic neurotransmission in the MnPO is essential for the renal vasodilation that follows acute increases in blood sodium concentration.
B‐type natriuretic peptide attenuates cardiac hypertrophy via the transforming growth factor‐β1/smad7 pathway in vivo and in vitro
Authors: He Jian‐Gui , Chen Yi‐Li , Chen Bai‐Li , Huang Yi‐Yi , Yao Feng‐Juan , Chen Sheng‐Long , Dong Yu‐Gang 
Published: August 2009

Summary1. Previously, we showed that long‐term treatment of rats after myocardial infarction (MI) with B‐type natriuretic peptide (BNP) prevented ventricular remodelling. However, it is unclear whether long‐term BNP treatment affects cardiac hypertrophy and, if so, its mechanism of action. In the present study, we investigated the effects of long‐term BNP treatment on cardiac hypertrophy and the molecular mechanisms involved.2. Cardiac hypertrophy was established in rats by ligation of the left anterior descending coronary artery. After treatment with BNP (5 or 15 μg/kg per day) for 8 weeks, indices of cardiac hypertrophy were determined. In separate in vitro experiments, cardiomyocyte hypertrophy was induced by treatment of cardiomyocytes with 10−6 mol/L angiotensin (Ang) II for 48 h and cell surface area and [3H] incorporation were measured. Transforming growth factor (TGF)‐β1 and smad7 mRNA and protein expression in vivo and in vitro were detected using reverse transcription–polymerase chain reaction and western blotting.3. Long‐term BNP treatment dose‐dependently attenuated cardiac hypertrophy and improved cardiac function in rats after MI. Furthermore, BNP attenuated the upregulation of TGF‐β1 and downregulation of smad7 mRNA and protein expression. The in vitro experiments further proved that BNP inhibited cardiac hypertrophy and changes in the TGF‐β1/smad7 pathway, which were completely blocked by the cyclic GMP‐dependent protein kinase (PKG) inhibitor, KT5823 (cells were treated with 10−6 mol/L KT5823 for 48 h).4. The results of the present study demonstrate that long‐term treatment of rats with BNP dose‐dependently attenuates cardiac hypertrophy and that this is associated with downregulation of TGF‐β1 and upregulation of smad7 via PKG signalling. Long‐term BNP treatment may be a new therapeutic strategy to prevent cardiac hypertrophy and progression to heart failure.
14‐3‐3 inhibits insulin‐like growth factor‐I‐induced proliferation of cardiac fibroblasts via a phosphatidylinositol 3‐kinase‐dependent pathway
Authors: Qi Jian‐Yong , Xu Ming , Lu Zhi‐Zhen , Zhang You‐Yi 
Published: August 2009

Summary1. Insulin‐like growth factor (IGF)‐I plays an important role in the pathogenesis of heart disease and has been shown to strongly induce the proliferation of cardiac fibroblasts (CFs). It remains unknown whether 14‐3‐3 proteins, which are associated the regulation of signal transduction, affect IGF‐I‐induced CF proliferation.2. In the present study, we investigated the effects of 14‐3‐3 proteins on CF proliferation in response to IGF‐I. Proliferation of CFs was determined by cell counting and a bromodeoxyuridine incorporation assay. Phosphorylation of signalling molecules was evaluated by western blottling. Activity of nuclear factor of activated T cells (NFAT) was examined using a dual luciferase reporter gene assay and immunofluorescence.3. It was found that adenovirus‐mediated transfection of YFP‐R18 peptide (AdR18), a known inhibitor of 14‐3‐3, significantly enhanced IGF‐I‐induced CF proliferation. This potentiation arose from an increase in phosphorylation of phosphatidylinositol 3‐kinase (PI3‐K) and AKT (protein kinase B), inactivation of glycogen synthesis kinase (GSK) 3β and increased NFAT activity.4. Collectively, the results of the present study suggest that 14‐3‐3 proteins inhibit IGF‐I‐induced CF proliferation via a PI3‐K‐dependent NFAT signalling pathway. This finding may contribute to our understanding of the function of 14‐3‐3 proteins in the heart.
Cellular calcium regulatory machinery of vasorelaxation elicited by petasin
Authors: Wang Guei‐Jane , Lin Yun‐Lian , Chen Chu‐Huang , Wu Xi‐Chen , Liao Jyh‐Fei , Ren Jun 
Published: August 2009

Summary1. The present study examined the cytosolic Ca2+regulatory machinery involved in the vasorelaxation produced by petasin, a sesquiterpene isolated fromPetasites formosanus.2. Aortic rings isolated from Sprague‐Dawley rats were exposed to petasin (0.01–100 μmol/L) to elucidate its vascular effects on isometric contraction elicited by vasoconstrictors, as well as the contribution of the endothelium and Ca2+to the responses observed. In addition, L‐type voltage‐dependent Ca2+channel (VDCC) activity and [Ca2+]iwere determined in cultured vascular smooth muscle cells (VSMCs) from Sprague‐Dawley rats in the presence of 1–100 μmol/L petasin using whole‐cell patch‐clamp recording and the fluorescent probe fura‐2/AM. The effects of petasin on vascular responses were compared between aortic rings from spontaneously hypertensive rats (SHR) and normotensive Wistar‐Kyoto (WKY) rats.3. Petasin reduced isometric contraction elicited by KCl or the L‐type Ca2+channel opener BayK 8644 (IC503.0 ± 0.4 and 4.1 ± 1.1 μmol/L, respectively) in aortic rings isolated from Sprague‐Dawley rats, independent of the endothelium. In addition, petasin triggered a rightward shift in the concentration–response curve to KCl while reducing the maximal response by 82%. In Ca2+‐depleted and high K+‐depolarized aortic rings, 1–100 μmol/L petasin pretreatment attenuated the Ca2+‐induced contraction in a concentration‐dependent manner.4. In cultured VSMCs, whole‐cell patch‐clamp recording revealed that petasin inhibited VDCC activity. Measurement of [Ca2+]iusing fura‐2/AM fluorescence indicated that petasin suppressed the KCl‐induced increase in [Ca2+]i. However, receptor binding assays failed to identify any significant interaction between petasin and the dihydropyridine binding sites of the L‐type VDCC.5. In aortic rings from SHR and WKY rats, petasin inhibited Ca2+‐induced contractions in Ca2+‐depleted and high K+‐depolarized solution with a more pronounced effect in rings from SHR.6. Together, the results suggest that direct Ca2+antagonism of L‐type VDCC in vascular smooth muscle may account, at least in part, for petasin‐induced vasorelaxation. The more pronounced effect of the sesquiterpene in blood vessels from SHR suggests its possible therapeutic potential in the mangement of hypertension.
Could hypertension possibly be adaptive?‡
Authors: Prakash ES , Fink GD 
Published: August 2009

Summary1. We believe that the ultimate goal of cardiovascular regulatory mechanisms is not the regulation of arterial blood pressure (BP), but the maintenance of tissue blood flows commensurate with metabolic requirements. Thus, elevated BP can potentially contribute to optimizing tissue blood flows under select circumstances; for example, when there are primary defects in autoregulation of tissue blood flows.2. The hypothesis that a primary defect in autoregulation of tissue blood flows may be responsible for the development of hypertension is presented. It is argued that, in this context, at least part of the rise in BP may be reflexly driven by a ‘metaboreflex’, a homeostatic mechanism acting to regulate tissue blood flows.3. We argue that in the context of primary defects in autoregulation of tissue blood flows, the ability to generate and sustain a hypertensive phenotype increases the lifespan of species (i.e. if it were not for this adaptive hypertensive phenotype, death due to circulatory failure would occur much earlier).4. Experimental and clinical evidence that indirectly supports the hypothesis is reviewed briefly and a means for testing this hypothesis is suggested.
Pharmacokinetics and pharmacodynamics of low doses of midazolam administered intravenously and orally to healthy volunteers
Authors: Misaka Shingen , Uchida Shinya , Imai Hiromitsu , Inui Naoki , Nishio Shinichiro , Ohashi Kyoichi , Watanabe Hiroshi , Yamada Shizuo 
Published: August 2009

Summary1. Midazolam, a short‐acting benzodiazepine, has been considered a probe for estimating hepatic and intestinal cytochrome P450 (CYP) 3A activity in humans. The aim of the present study was to evaluate the pharmacokinetics and pharmacodynamics of midazolam administered intravenously (i.v.) and orally (p.o.) at relatively low doses to healthy volunteers.2. The present study was an open‐label, single‐sequence trial in three phases distinguished by differing doses of midazolam. Plasma concentrations of midazolam and its metabolites, as well as pharmacodynamic parameters, were measured simultaneously after administration of 5, 15 and 30 μg/kg, i.v., midazolam and 15, 50 and 100 μg/kg, p.o., midazolam.3. The area under the concentration–time curve (AUC) of midazolam was significantly correlated with dose after both i.v. and oral administration (bothP < 0.001). The AUC0–6of midazolam after oral administration was also well correlated with the area under the effect curve for peak saccadic velocity (PSV;P < 0.018), postural sway area (PSA;P < 0.069) and mental sedation as measured on a visual analogue scale (VAS;P < 0.054), but not for critical flicker fusion.4. The present study has shown that the pharmacokinetics of midazolam at relatively low doses are linear for both intravenous and oral dosing regimens. In addition, PSV, PSA and VAS may be useful for the simultaneous evaluation of the pharmacokinetics and pharmacodynamics of midazolam at subtherapeutic doses.
Ginsenoside Rd prevents glutamate‐induced apoptosis in rat cortical neurons
Authors: Li Xiao‐Yan , Liang Jian , Tang Yong‐Bo , Zhou Jia‐Guo , Guan Yong‐Yuan 
Published: August 2009

Summary1. The role of voltage‐independent Ca2+ entry in cell apoptosis has recently received considerable attention. It has been found that ginsenoside Rd significantly inhibits voltage‐independent Ca2+ entry. The aim of the present study was to investigate the protective effects of ginsenoside Rd against glutamate‐induced apoptosis of rat cortical neurons.2. Ginsenoside Rd significantly reduced glutamate‐induced apoptotic morphological changes and DNA laddering. In comparison, nimodipine only had a weak effect.3. Ginsenoside Rd (1, 3 and 10 μmol/L) concentration‐dependently inhibited caspase 3 activation and expression of the p20 subunit of active caspase 3 (by 30 ± 10%, 41 ± 9% and 62 ± 19%, respectively, compared with glutamate alone; P < 0.05), whereas 1 μmol/L nimodipine had no effect.4. Glutamate decreased cell viability to 37.4 ± 4.7 (n = 8) and evoked cell apoptosis. Ginsenoside Rd (1, 3, 10 and 30 μmol/L) concentration‐dependently inhibited glutamate‐induced cell death, increased cell viability and reduced apoptotic percentage (from 47.5 ± 4.9% to 37.4 ± 6.9%, 28.3 ± 5.2% and 22.5 ± 5.6%, respectively; P < 0.05). At 1 μmol/L, nimodipine had no effect on cell viability. Furthermore, although 1, 3, 10, 30 and 60 μmol/L ginsenoside Rd concentration‐dependently inhibited glutamate‐induced Ca2+ entry by 8 ± 2%, 24 ± 4%, 40 ± 7%, 49 ± 8% and 50 ± 8% (P < 0.05), respectively, nimodipine had no effect.5. In conclusion, the results indicate that ginsenoside Rd prevents glutamate‐induced apoptosis in rat cortical neurons and provide further evidence of the potential of voltage‐independent Ca2+ channel blockers as new neuroprotective drugs for the prevention of neuronal apoptosis and death induced by cerebral ischaemia.
Digoxin increases peripheral chemosensitivity and the ventilatory response to exercise in normal subjects
Authors: Janssen C , Lheureux O , Beloka S , Deboeck G , Adamopoulos D , Naeije R , Van De Borne P 
Published: August 2009

Summary1. The contribution of peripheral chemoreceptors to the regulation of ventilation during exercise remains incompletely understood. Digoxin has been reported to increase chemoreflex sensitivity in humans. In the present randomized, cross‐over, double‐blind study, we tested the hypothesis that this increases the ventilatory response to exercise in normal subjects, as assessed by changes in minute ventilation (VE) in response to the rate of CO2production (Vco2).2. Minute ventilation, end‐tidalPco2, pulse oximetric O2saturation (Spo2), heart rate and blood pressure (BP) were measured in 11 healthy young male untrained subjects after intravenous infusion of digoxin (0.01 mg/kg) or placebo during normoxia, isocapnic hypoxia and hyperoxic hypercapnoea. All participants underwent a maximum cardiopulmonary exercise test.3. During normoxia, digoxin increased systolic BP only. During hypoxia, digoxin increasedVEcompared with placebo (P = 0.009) for the same fall inSpo2(P = NS). Moreover, no significant effects on ventilation and haemodynamic responses were recorded during hypercapnoea. Digoxin increased theVE /Vco2slope above the anaerobic threshold from 30.4 ± 2.9 to 32.8 ± 3.7 (P < 0.05), but did not affectVo2max.4. In conclusion, enhanced peripheral chemosensitivity with digoxin increases the ventilatory response to CO2production above the anaerobic threshold, but does not affect exercise capacity in healthy humans.
Confidence in Altman–Bland plots: A critical review of the method of differences
Authors: Ludbrook John 
Published: August 2009

Summary1. Altman and Bland argue that the virtue of plotting differences against averages in method‐comparison studies is that 95% confidence limits for the differences can be constructed. These allow authors and readers to judge whether one method of measurement could be substituted for another.2. The technique is often misused. So I have set out, by statistical argument and worked examples, to advise pharmacologists and physiologists how best to construct these limits.3. First, construct a scattergram of differences on averages, then calculate the line of best fit for the linear regression of differences on averages. If the slope of the regression is shown to differ from zero, there is proportional bias.4. If there is no proportional bias and if the scatter of differences is uniform (homoscedasticity), construct ‘classical’ 95% confidence limits.5. If there is proportional bias yet homoscedasticity, construct hyperbolic 95% confidence limits (prediction interval) around the line of best fit.6. If there is proportional bias and the scatter of values for differences increases progressively as the average values increase (heteroscedasticity), log‐transform the raw values from the two methods and replot differences against averages. If this eliminates proportional bias and heteroscedasticity, construct ‘classical’ 95% confidence limits. Otherwise, construct horizontal V‐shaped 95% confidence limits around the line of best fit of differences on averages or around the weighted least products line of best fit to the original data.7. In designing a method‐comparison study, consult a qualified biostatistician, obey the rules of randomization and make replicate observations.
Location, Automotive Policy, and Multinational Strategy: The Position of South Africa in the Global Industry since 1995
Authors: BLACK ANTHONY 
Published: September 2009

ABSTRACTThe South African automotive sector has become much more integrated into the global industry since 1995. Rapid export expansion has shifted its orientation fundamentally away from its focus on the small domestic market and the industry is widely regarded as a success story of South Africa's democratic transition. However, important vulnerabilities remain, and it is by no means clear that the mode of integration has been particularly favorable to the long‐term development of the industry. The relatively small size of South Africa's domestic market and its regional location pose clear disadvantages in terms of attracting international investment. Integration into the global industry has therefore been partial and continues to reflect a degree of hesitancy by multinational firms to make really major commitments to the South African industry. The warning signs include recent import expansion and low local content in domestically assembled vehicles. Automotive policy has also produced distortions, encouraged uneconomic investments, and led to unforeseen side effects. These impacts limit the gains that have been made and are likely to cause complications in the future.
Involvement of ABC transporters in melanogenesis and the development of multidrug resistance of melanoma
Authors: Chen Kevin G. , Valencia Julio C. , Gillet Jean‐Pierre , Hearing Vincent J. , Gottesman Michael M. 
Published: August 2009

SummaryBecause melanomas are intrinsically resistant to conventional radiotherapy and chemotherapy, many alternative treatment approaches have been developed such as biochemotherapy and immunotherapy. The most common cause of multidrug resistance (MDR) in human cancers is the expression and function of one or more ATP‐binding cassette (ABC) transporters that efflux anticancer drugs from cells. Melanoma cells express a group of ABC transporters (such as ABCA9, ABCB1, ABCB5, ABCB8, ABCC1, ABCC2, and ABCD1) that may be associated with the resistance of melanoma cells to a broad range of anticancer drugs and/or of melanocytes to toxic melanin intermediates and metabolites. In this review, we propose a model (termed the ABC‐M model) in which the intrinsic MDR of melanoma cells is at least in part because of the transporter systems that may also play a critical role in reducing the cytotoxicity of the melanogenic pathway in melanocytes. The ABC‐M model suggests molecular strategies to reverse MDR function in the context of the melanogenic pathway, which could open therapeutic avenues towards the ultimate goal of circumventing clinical MDR in patients with melanoma.
Rhodobacter capsulatus
Catalyzes Light-Dependent Fe(II) Oxidation under Anaerobic Conditions as a Potential Detoxification Mechanism
Authors: Poulain Alexandre J. , Newman Dianne K. 
Published: August 2009

ABSTRACT

Diverse bacteria are known to oxidize millimolar concentrations of ferrous iron [Fe(II)] under anaerobic conditions, both phototrophically and chemotrophically. Yet whether they can do this under conditions that are relevant to natural systems is understood less well. In this study, we tested how light, Fe(II) speciation, pH, and salinity affected the rate of Fe(II) oxidation by
Rhodobacter capsulatus
SB1003. Although
R. capsulatus
cannot grow photoautotrophically on Fe(II), it oxidizes Fe(II) at rates comparable to those of bacteria that do grow photoautotrophically on Fe(II) as soon as it is exposed to light, provided it has a functional photosystem. Chelation of Fe(II) by diverse organic ligands promotes Fe(II) oxidation, and as the pH increases, so does the oxidation rate, except in the presence of nitrilotriacetate; nonchelated forms of Fe(II) are also more rapidly oxidized at higher pH. Salt concentrations typical of marine environments inhibit Fe(II) oxidation. When growing photoheterotrophically on humic substances,
R. capsulatus
is highly sensitive to low concentrations of Fe(II); it is inhibited in the presence of concentrations as low as 5 μM. The product of Fe(II) oxidation, ferric iron, does not hamper growth under these conditions. When other parameters, such as pH or the presence of chelators, are adjusted to promote Fe(II) oxidation, the growth inhibition effect of Fe(II) is alleviated. Together, these results suggest that Fe(II) is toxic to
R. capsulatus
growing under strictly anaerobic conditions and that Fe(II) oxidation alleviates this toxicity.
Multiplexed Bead-Based Mesofluidic System for Detection of Food-Borne Pathogenic Bacteria
Authors: Jin Sheng-Quan , Yin Bin-Cheng , Ye Bang-Ce 
Published: August 2009

ABSTRACT

In the present study, a simple and rapid multiplexed bead-based mesofluidic system (BMS) was developed for simultaneous detection of food-borne pathogenic bacteria, including
Staphylococcus aureus
,
Vibrio parahaemolyticus
,
Listeria monocytogenes
,
Salmonella
,
Enterobacter sakazakii
,
Shigella
,
Escherichia coli
O157:H7, and
Campylobacter jejuni
. This system is based on utilization of isothiocyanate-modified microbeads that are 250 μm in diameter, which were immobilized with specific amino-modified oligonucleotide probes and placed in polydimethylsiloxane microchannels. PCR products from the pathogens studied were pumped into microchannels to hybridize with the oligonucleotide-modified beads, and hybridization signals were detected using a conventional microarray scanner. The short sequences of nucleic acids (21 bases) and PCR products characteristic of bacterial pathogens could be detected at concentrations of 1 pM and 10 nM, respectively. The detection procedure could be performed in less than 30 min with high sensitivity and specificity. The assay was simple and fast, and the limits of quantification were in the range from 500 to 6,000 CFU/ml for the bacterial species studied. The feasibility of identification of food-borne bacteria was investigated with samples contaminated with bacteria, including milk, egg, and meat samples. The results demonstrated that the BMS method can be used for effective detection of multiple pathogens in different foodstuffs.
Inhibition of
Listeria monocytogenes
in Cooked Ham by Virulent Bacteriophages and Protective Cultures
Authors: Holck A. , Berg J. 
Published: August 2009

ABSTRACT

Protective cultures can be used successfully as an additional hurdle together with phages to reduce growth of
Listeria monocytogenes
on sliced cooked ham. Addition of phages resulted in a rapid 10-fold reduction of
L. monocytogenes
. After 14 to 28 days of storage, a 100-fold reduction was observed in samples with phages and protective culture compared to results for samples with phages alone.