bluuebunny/crossref_metadata_2025 huggingface dataset:
A Breath of Atheism in Religious Vietnam
Authors: Trần Văn Toàn
Published: September 2010

Atheism is not a fundamental notion. This negative concept is relative to the object of its negation, which pre-exists: the gods, God, or rather our ideas of him. In monotheistic regimes, such as in the West, atheism is radical and often aggressive. Since its first contacts with the West, Vietnam has experienced both extremes of this situation, through Christianity and communism. In a polytheistic regime, as in traditional Vietnam, atheism is less exclusive, more tolerant and more nuanced. Appealing to certain gods implies ignorance of, indifference to or the rejection of others; it often betrays a desire to use gods as a means to serve man, who thus believes himself to be the last link in the chain. As monotheism rejects the power of the divinity of nature and of humans, its negation can inversely result in subjecting man to nature and society to the State.
Le Vietnam au défi de la diversité protestante
Authors: Willaime Jean-Paul
Published: September 2010

La République socialiste du Vietnam doit faire face à deux importants défis: d’une part, une pluralisation religieuse accrue de sa population, marquée, notamment, par un développement diversifié du protestantisme; d’autre part, une nouvelle politique religieuse dépassant la traditionnelle disqualification marxiste des religions au profit d’une reconnaissance contrôlée de celles-ci dans le cadre du patriotisme national. L’auteur cherche à montrer en quoi la diversité protestante représente un défi pour le Vietnam à l’heure de la mondialisation religieuse.
Ethnic and Transnational Dimensions of Recent Protestant Conversion among the Hmong in Northern Vietnam
Authors: Ngô Thị Thanh Tâm
Published: September 2010

The author argues that ethnic and transnational dimensions are crucial to an understanding of the conversion of the Hmong to Protestantism in Northern Vietnam. Although a number of scholars have proposed that the study of religion be incorporated into the study of transnationalism, the “transnationalization” of religion is still rather understudied, and there have been few scholarly efforts to analyze the transnational aspects of the conversions to world religions of marginalized ethnic minority groups in countries with high levels of emigration. The author examines the transnationalization of religion via the case of the Hmong conversion to show that the impact of missionization is twofold, as not only does the habitus of the Hmong in Vietnam change through massive conversion but so also does the subjectivity of the Hmong missionaries. She proposes to conceptualize the evangelical mission of the Hmong diasporas in Vietnam in particular and in Asia in general as a form of “remittance of faith and modernity”.
Les relations entre l’Église catholique et l’État au Vietnam depuis le Đổi Mới. Perspectives
Authors: TRÄN Thi Liën Claire
Published: September 2010

La situation des relations entre l’Église et l’État au Vietnam se distingue de celle de son voisin chinois par l’existence d’une Église restée fidèle à Rome. Religion minoritaire regroupant 7 pour cent de la population, l’Église catholique a adopté, après la réunification du pays en 1975, une politique de dialogue avec l’État communiste. Après une première période difficile, l’Église connaît un renouveau incontestable. La mise en place de la politique de réforme (đ i m i) depuis 1986 et l’ouverture du pays qui en a résulté, après plus de 40 ans de guerre, ont contribué à l’amélioration des relations entre Église et État. Engagé dans une politique d’intégration internationale, sous la pression conjointe des puissances occidentales, des organismes internationaux et de contestations populaires grandissantes, l’État vietnamien poursuit sa politique d’ouverture aux religions, ce qui suscite encore, dans le parti, des réticences et tensions au niveau local. Le processus vers l’établissement de relations diplomatiques avec le Saint-Siège ne semble pourtant pas compromis.
Divination and Politics in Southern Vietnam: Roots of Caodaism
Authors: Jammes Jérémy
Published: September 2010

Caodaism is a Vietnamese religious movement that appeared in colonial Cochinchina in the 1920s. What are the sociological roots of Caodaism? The author attempts to answer this question through an analysis of the Caodaist networks that developed in the early 20th century in Cochinchina. Setting out some ethnographic materials concerning the Chinese Minh religions, the author focuses on only one of the five Minh religions in Vietnam, called Minh Lý (“Enlightened Reason”). He sheds new light on the esoteric roots of Caodaism, on the political regulation of the religious sphere and, finally, on the religious and political map of Southern Vietnam.
Réflexions sur l’institutionnalisation du bouddhisme Hòa Háo. Remise en perspective historique de la reconnaissance de 1999
Authors: Bourdeaux Pascal
Published: September 2010

Le bouddhisme Hòa Háo a commémoré l’anniversaire des 60 ans de sa fondation en 1999. À cette occasion, plus d’un million d’adeptes ont foulé la terre sainte (thánh đ a) du village natal de son fondateur Hu nh Phú S . Cet événement, l’un des plus importants pèlerinages que le Vietnam ait connu ces dernières décennies, a démontré la vitalité de cette pratique religieuse, qui a été contrainte de s’exprimer dans un cadre strictement privé pendant près d’un quart de siècle. Il scelle aussi la reconnaissance sous conditions de ce nouveau mouvement religieux territorialisé (Ouest du delta du Mékong) et désormais transnational (communautés vietnamiennes de l’outre-mer) comme l’une des six religions instituées du pays. Le retour historique et historiographique vise à rappeler les enjeux de mémoire et à éclairer les termes d’une régulation religieuse qui redéfinit depuis 1999 l’institutionnalisation du bouddhisme Hòa Háo et l’engagement dans le monde de ses adeptes.
FRP-confined circular concrete columns subjected to concentric loading
Authors: Csuka Bernát , Kollár László P
Published: September 2010

In this article, a new model for FRP-confined circular concrete columns based on a sophisticated material model is presented. With the aid of this model the effect of the stiffness of the confining material on the strength of the structure was investigated. It was found that: (i) in the case of a wide parameter range (low-stiffness confinement) the stiffness has a minor effect on the concrete strength; (ii) in the case of high-stiffness confinement a significant gain in concrete strength can be reached by taking into account the confinement stiffness; and (iii) in theory the concrete can be overconfined (with a lower strength); however, this case is not realistic for conventional FRP. Based on the new model an analytical expression is derived to determine the (lower limit of) strength of confined concrete, and the limit of insufficient confinement is also derived. The results are verified by experiments available in the literature.
Effects of spiked metals on the MSW anaerobic digestion
Authors: Lo HM , Chiang CF , Tsao HC , Pai TY , Liu MH , Kurniawan TA , Chao KP , Liou CT , Lin KC , Chang CY , Wang SC , Banks CJ , Lin CY , Liu WF , Chen PH , Chen CK , Chiu HY , Wu HY , Chao TW , Chen YR , Liou DW , Lo FC
Published: September 2010

This study aimed to investigate the effects of eight metals on the anaerobic digestion of the organic fraction of municipal solid waste (OFMSW) in bioreactors. Anaerobic bioreactors containing 200 mL MSW mixed completely with 200 mL sludge seeding. Ca and K (0, 1000, 2000 and 6000 mg L−1) and Cr, Ni, Zn, Co, Mo and W (0, 5, 50 and 100 mg L−1) of various dose were added to anaerobic bioreactors to examine their anaerobic digestion performance. Results showed that except K and Zn, Ca (~728 to ~1461 mg L−1), Cr (~0.0022 to ~0.0212 mg L−1), Ni (~0.801 to ~5.362 mg L−1), Co (~0.148 to ~0.580 mg L−1), Mo (~0.044 to ~52.94 mg L−1) and W (~0.658 to ~40.39 mg L−1) had the potential to enhance the biogas production. On the other hand, except Mo and W, inhibitory concentrations IC50 of Ca, K, Cr, Ni, Zn and Co were found to be ~3252, ~2097, ~0.124, ~7.239, ~0.482, ~8.625 mg L−1, respectively. Eight spiked metals showed that they were adsorbed by MSW to a different extent resulting in different liquid metals levels and potential stimulation and inhibition on MSW anaerobic digestion. These results were discussed and compared to results from literature.
Challenges and issues in moving towards sustainable landfilling in a transitory country - Malaysia
Authors: Agamuthu P. , Fauziah SH
Published: September 2010

Malaysia disposes of 28 500 tonnes of municipal solid waste directly into landfills daily. This fact alone necessitates sustainable landfills to avoid adverse impacts on the population and the environment. The aim of the present study was to elucidate the issues and challenges faced by waste managers in moving towards sustainable landfilling in Malaysia. Various factors influence the management of a landfill. Among them is the human factor, which includes attitude and public participation. Although Malaysia’s economy is developing rapidly, public concern and awareness are not evolving in parallel and therefore participation towards sustainable waste management through the ‘reduce, reuse and recycle’ approach (3Rs) is severely lacking. Consequently, landfill space is exhausted earlier than scheduled and this is no longer sustainable in terms of security of disposal. Challenges also arise from the lack of funding and the increase in the price of land. Thus, most waste managers normally aim for ‘just enough’ to comply with the regulations. Investment for the establishment of landfills generally is minimized since landfilling operations are considered uneconomical after closure. Institutional factors also hamper the practice of sustainable landfilling in the country where 3Rs is not mandatory and waste separation is totally absent. Although there are huge obstacles to be dealt with in moving towards sustainable landfilling in Malaysia, recent developments in waste management policy and regulations have indicated that positive changes are possible in the near future. Consequently, with the issues solved and challenges tackled, landfills in Malaysia can then be managed effectively in a more sustainable manner.
Science, governance, and public participation: An analysis of decision making on genetic modification in Aotearoa/New Zealand
Authors: Kurian Priya , Wright Jeanette
Published: September 2010

The acceptance of public participation in science and technology governance in liberal democratic contexts is evident in the institutionalization of a variety of mechanisms for participation in recent decades. Yet questions remain about the extent to which institutions have actually transformed their policy practice to embrace democratic governance of techno-scientific decision making. A critical discourse analysis of the response to public participation by the Environmental Risk Management Authority (ERMA), the key decision-making body on genetic modification in Aotearoa/New Zealand, in a specific case demonstrates that ERMA systematically marginalized concerns raised by the public about risk management, ethics, and ecological, economic, and cultural issues in order to give primacy to a positivist, technological worldview. Such delegitimization of public perspectives pre-empts the possibility of the democratic governance of science.
Safety Assessment of a Wheat Bran Extract Containing Arabinoxylan-Oligosaccharides: Mutagenicity, Clastogenicity, and 90-Day Rat-Feeding Studies
Authors: François Isabelle E. J. A. , Lescroart Olivier , Veraverbeke Wim S. , Kubaszky Raluca , Hargitai Judit , Esdaile David J. , Beres Erzsébet , Soni Madhu G. , Cockburn Andrew , Broekaert Willem F.
Published: September 2010

Wheat bran extract (WBE) is a food-grade preparation that is highly enriched in arabinoxylan-oligosaccharides. As part of the safety evaluation of WBE, its genotoxic potential was assessed in a bacterial reverse mutagenicity assay (Ames test) and a chromosome aberration assay on Chinese hamster lung fibroblast cells. These in vitro genotoxicity assays showed no evidence of mutagenic or clastogenic activity with WBE. The safety of WBE was furthermore evaluated in a subchronic toxicity study on rats that were fed a semisynthetic diet (AIN 93G) containing 0.3%, 1.5%, or 7.5% WBE for 13 weeks, corresponding to an average intake of 0.2, 0.9, and 4.4 g/kg body weight (bw) per day, with control groups receiving the unsupplemented AIN 93G, AIN 93G with 7.5% inulin, or AIN 93G with 7.5% wheat bran. Based on this rat-feeding study, the no-observed-adverse-effect level (NOAEL) for WBE was determined as 4.4 g/kg (bw)/d, the highest dose tested.
A Novel Formulation of Ketorolac Tromethamine for Intranasal Administration
Authors: Boyer Kelley C. , McDonald Paddy , Zoetis Tracey
Published: September 2010

Ketorolac tromethamine is a potent analgesic and moderately effective anti-inflammatory drug approved for treatment of moderately severe acute pain as an intravenous/intramuscular injectable solution and an oral tablet. ROXRO PHARMA, Inc has developed an intranasal formulation, SPRIX, that delivers the drug with a similar pharmacokinetic profile to that obtained with intramuscular administration. Local tolerance and systemic toxicology studies were performed in rats and rabbits and showed that intranasal administration of SPRIX exhibits toxicity similar to that of other routes of administration and does not result in any adverse effects on the nasal passage and upper and lower respiratory system.
Critical Review of Preclinical Approaches to Evaluate the Potential of Immunosuppressive Drugs to Influence Human Neoplasia
Authors: Bugelski Peter J. , Volk Amy , Walker Mindi R. , Krayer John H. , Martin Pauline , Descotes Jacques
Published: September 2010

Many immunosuppressive drugs are associated with an increased risk of B-cell lymphoma, squamous cell carcinoma, and Kaposi sarcoma. Thirteen immunosuppressive drugs have been tested in 2-year carcinogenicity studies (abatacept; azathioprine; busulfan; cyclophosphamide; cyclosporine; dexamethasone; everolimus; leflunomide; methotrexate; mycophenolate mofetil; prednisone; sirolimus; and tacrolimus) and in additional models including neonatal and genetically modified mice; chemical, viral, ultraviolet, and ionizing radiation co-carcinogenesis, and in models with transplanted tumor cells. The purpose of this review is to outline the mechanisms by which immunosuppressive drugs can influence neoplasia, to summarize the available preclinical data on the 13 drugs, and to critically review the performance of the models. A combination of primary tumor and metastasis assays conducted with transplanted cells may provide the highest value for hazard identification and can be applied on a case-by-case basis. However, for both small molecules and therapeutic proteins, determining the relative risk to patients from preclinical data remains problematic. Classifying immunosuppressive drugs based on their mechanism of action and hazard identification from preclinical studies and a prospective pharmacovigilance program to monitor carcinogenic risk may be a feasible way to manage patient safety during the clinical development program and postmarketing.
Developmental Toxicity of Homobrassinolide in Wistar Rats
Authors: Murkunde Yogeshkumar V. , Balakrishna Murthy P.
Published: September 2010

Brassinosteroids (BRs) are close analogues of animal cholesterol. Brassinosteroids have shown their great value as yield promoters of a variety of plants. In view of its steroidal moiety and recent use in agriculture in many countries, the teratogenic potential of homobrassinolide (HBR) was evaluated in Wistar rats. Homobrassinolide was administered by oral gavage at doses 0, 100, and 1000 mg/kg body weight in water during gestation days (GD) 6 to 15 in groups of 20 mated females. Maternal and embryo-fetal toxicity was analyzed by studying the effects such as clinical signs, mortality/morbidity, abortions, body weight, feed consumption, and pregnancy data, gravid uterine weights, implantation losses, litter size, external, visceral, and skeletal malformations. No treatment-related effect was observed on any of the maternal/fetal end points in any dose group. From the results, it can be concluded that HBR is nonteratogenic at doses as high as up to 1000 mg/kg body weight in Wistar rats.
Effect of Astragaloside IV on the General and Peripartum Reproductive Toxicity in Sprague-Dawley Rats
Authors: Xuying Wan , Jiangbo Zhu , Yuping Zhu , Xili Ma , Yiwen Zheng , Tianbao Zhang , Weidong Zhang
Published: September 2010

Fertility and early embryonic developmental toxicity in rats were evaluated by intravenously administering astragaloside IV (AS-IV) daily at 0.25, 0.5, and 1.0 mg/kg for 4 weeks before mating, throughout the mating period, and continuing to day 6 of gestation period in females. Perinatal toxicity in rats was evaluated on gestational days (GD) 15 to 21 and lactational days LD (LD) 1 to 21. Astragaloside IV had no maternal toxicity at 0.25 to 1.0 mg/kg in rats. Although it has an inhibitory effect on female fertility in F0/F1 rats, AS-IV was devoid of early embryonic developmental toxicity in F0/F1 rats and in the survival parameters of F1 postnatal rats. Maternal AS-IV exposure at the dose of 1.0 mg/kg per d resulted in a significant delay in time for fur development, eye opening, and cliff parry reflex of pups compared to control group ( P < .05), whereas it did not affect the memory and learning of F1 pups.
Immunomodulatory Effects of Dietary Exposure to Selected Polycyclic Aromatic Hydrocarbons in the Bluegill (Lepomis macrochirus)
Authors: Connelly Helen , Means Jay C.
Published: September 2010

Polycyclic aromatic hydrocarbons (PAH) have been demonstrated to affect immune system modulation. The freshwater species of fish, Lepomis macrochirus (bluegill), was employed to investigate the effects of a 14-day dietary exposure to PAH including 2-aminoanthracene (2-AA), 2-methylnaphthalene (2-MN), and 9,10-dimethylanthracene (9,10-DMA) and a mixture of these 3 compounds at a total dose of 3.1 ± 0.01 mg on lymphocyte proliferation stimulated with 3 mitogens (concanavalin A [Con A], phorbol ester, and calcium ionophore). 2-Aminoanthracene was mitogenic itself and with added mitogens. 2-Methylnaphthalene induced some stimulatory and some inhibitory effects upon cell proliferation by Con A. 9,10-DMA and the mixture each suppressed cell proliferation. The mixture was highly suppressive to lymphocytes. Intracellular baseline calcium levels were reduced, possibly as a step prior to cell death. All PAH compounds tested were immunomodulatory to bluegill lymphocytes. Bluegill were demonstrated to have utility as a biomarker species for investigation of immunotoxicity.
Characterisation of angiotensin II receptors in isolated human subcutaneous resistance arteries
Authors: Ytterberg Hoa , Edvinsson Lars
Published: September 2010

Subcutaneous arteries have been used as a model for resistance arteries, which are potentially involved in enhanced blood pressure (BP) regulation in man. Angiotensin II (Ang II) is an important regulator of tone, acting via type 1 (AT1-) and type 2 (AT2-) receptor subtypes. The aim of this study was to characterise the Ang II receptors in isolated human subcutaneous arteries, using pharmacological and molecular methods.

Subcutaneous arteries were obtained from patients undergoing elective gut surgery and were carefully dissected from the abdominal wall. Cylindrical segments were mounted on two L-shaped metal prongs, one of which was connected to a force-displacement transducer for continuous recording of isometric tension. Concentration-response curves to Ang II were constructed in the presence and absence of various selective AT1-receptor antagonists, candesartan, EXP3174, irbesartan and losartan, and the AT2-receptor antagonist, PD 123319. Responses to Ang II were measured as increases in force (mN) and expressed as a percentage of the response to 60 mM of KCl. Ang II caused a concentration-dependent contraction (pEC50=9.45±0.48, Emax=120±13%). Candesartan and EXP3174 caused concentration-dependent depression of the Emax of Ang II without any major shift of pEC50. Losartan and irbesartan caused a significant, dose-dependent rightward shift of the Ang II contraction-response curve in human subcutaneous arteries. The results show that contractile responses of human subcutaneous arteries are mediated via the AT1-receptor. The AT1-receptor antagonists, candesartan and EXP3174, acted in an insurmountable manner, while losartan and irbesartan were surmountable AT1-receptor antagonists. The AT2-receptor antagonist, PD 123319, (10, 100 nM) had no effect on Ang II-induced contraction. This is supported by the positive identification of mRNA for the human AT 1-receptor by RT-PCR.
Evidence for a cyclic AMP-dependent pathway in angiotensin AT1-receptor activation of human omental arteries
Authors: Ytterberg Hoa , Edvinsson Lars
Published: September 2010

Enhanced responses to vasoconstriction induced by neuropeptide Y and α2-adrenoceptor agonists have been seen following pharmacological activation of the adenylyl cyclase (AC) system. Since preliminary studies revealed only minor responses to angiotensin II (Ang II) in human omental arteries, we have investigated whether enhanced activity of AC may unravel further functional Ang II receptors. Human omental arteries were obtained in conjunction with elective gut surgery. After dissection of the vessel, the endothelium was removed by 10 sec of Triton X-100 treatment. Ring segments (1—2 mm long) were mounted on a myograph and studied. Ang II produced small contractions, 27±5% relative to the response elicited by 60 mM K+. However, enhanced Ang II (105±10%, p<0.001) responses were seen during AC activation by forskolin (0.1—1 µM). This enhanced contractile response to Ang II was not inhibited by the angiotensin II type 2 (AT2-receptor antagonist PD 123319 (0.1 µM), but was blocked in an insurmountable way by the angiotensin II type 1 (AT1)-receptor antagonist candesartan (1 nM) and in a surmountable manner by losartan (0.1 µM) and irbesartan (0.1 µM). Pertussis toxin (a Gi-protein blocker) and the protein kinase C inhibitor, RO31—8220 (0.01, 0.1 and 1 µM), markedly reduced this response, while the protein kinase A inhibitor, H89 (1, 10 µM), had no effect. RT-PCR provided evidence for the presence of mRNA for both AT1- and AT2-receptors. The results suggest that both a cAMP-dependent and a cAMP-independent mechanism are involved in the contractile responses to Ang II in human omental arteries and that both responses are mediated via the AT1-receptor.
Does protein binding modulate the effect of angiotensin II receptor antagonists?
Authors: Maillard Marc P , Centeno Catherine , Frostell-Karlsson Åsa , Brunner Hans R , Burnier Michel
Published: September 2010

Introduction

Angiotensin II AT 1-receptor antagonists are highly bound to plasma proteins (≥ 99%). With some antagonists, such as DuP-532, the protein binding was such that no efficacy of the drug could be demonstrated clinically. Whether protein binding interferes with the efficacy of other antagonists is not known. We have therefore investigated in vitro how plasma proteins may affect the antagonistic effect of different AT1-receptor antagonists.

Methods

A radio-receptor binding assay was used to analyse the interaction between proteins and the ability of various angiotensin II (Ang II) antagonists to block AT1-receptors. In addition, the Biacore technology, a new technique which enables the real-time monitoring of binding events between two molecules, was used to evaluate the dissociation rate constants of five AT1-receptor antagonists from human serum albumin.

Results

The in vitro AT 1-antagonistic effects of different Ang II receptor antagonists were differentially affected by the presence of human plasma, with rightward shifts of the IC50 ranging from one to several orders of magnitude. The importance of the shift correlates with the dissociation rate constants of these drugs from albumin. Our experiments also show that the way that AT1-receptor antagonists bind to proteins differs from one compound to another. These results suggest that the interaction with plasma proteins appears to modulate the efficacy of some Ang II antagonists.

Conclusion

Although the high binding level of Ang II receptor antagonist to plasma proteins appears to be a feature common to this class of compounds, the kinetics and characteristics of this binding is of great importance. With some antagonists, protein binding interferes markedly with their efficacy to block AT1-receptors.
Reversal of cardiovascular remodelling with candesartan
Authors: Brown Lindsay , Fenning Andrew , Shek Annie , Burstow Darryl
Published: September 2010

Cardiovascular remodelling, defined as ventricular and vascular hypertrophy together with fibrosis, characterises hypertension following inhibition of the production of the endogenous vasodilator, nitric oxide (NO). This study has determined whether the cardiovascular remodelling following chronic NO synthase inhibition can be reversed by administration of the selective angiotensin II AT1-receptor antagonist, candesartan. Male Wistar rats were treated with L-nitroarginine methyl ester (L-NAME, 400 mg/l in drinking water) for eight weeks and with candesartan cilexetil (2 mg/kg/day by oral gavage) for the last four weeks. L-NAME-treated rats became hypertensive with systolic blood pressure increasing from 110±4 mmHg (control) to 170±10 mmHg. Rats developed left ventricular hypertrophy (control 1.70±0.06; L-NAME 2.10±0.04 mg/kg body wt) with markedly increased deposition of perivascular and interstitial collagen. Candesartan returned blood pressure, left ventricular weights and collagen deposition to control values. Echocardiographic assessment showed concentric hypertrophy with an increased fractional shortening; this was reversed by candesartan treatment. Heart failure was not evident. In the isolated Langendorff heart, diastolic stiffness increased in L-NAME-treated rats while the rate of increase in pressure (+dP/dt) increased after eight weeks only; candesartan reduced collagen deposition and normalised +dP/dt. In isolated left ventricular papillary muscles, the potency (negative log EC50) of noradrenaline as a positive inotropic compound was unchanged, (control 6.56±0.14); maximal increase in force before ectopic beats was reduced from 5.0±0.4 mN to 2.0±0.2 mN. Noradrenaline potency as a vasoconstrictor in thoracic aortic rings was unchanged, but maximal contraction was markedly reduced from 25.2±2.0 mN to 3.0±0.3 mN; this was partially reversed by candesartan treatment. Thus, chronic inhibition of NO production with L-NAME induces hypertension, hypertrophy and fibrosis with increased toxicity and significant decreases in vascular responses to noradrenaline. These changes were at least partially reversible by treatment with candesartan, implying a significant role of AT1-receptors in L-NAME-induced cardiovascular changes.
Regression of cardiac hypertrophy in the SHR by combined renin-angiotensin system blockade and dietary sodium restriction
Authors: Abro Emad , Griffiths Cory D , Morgan Trefor O , Delbridge Lea MD
Published: September 2010

Altered operation of the renin-angiotensin-aldosterone system (RAAS) and dietary sodium intake have been identified as independent risk factors for cardiac hypertrophy. The way in which sodium intake and the operation of the renin-angiotensin-aldosterone system interact in the pathogenesis of cardiac hypertrophy is poorly understood. The aims of this study were to investigate the cardiac effects of the renin-angiotensin system (RAS) blockade in the spontaneously hypertensive rat (SHR), using co-treatment with an angiotensin II receptor blocker (ARB) and an angiotensin-converting enzyme (ACE) inhibitor with different sodium intakes. Our experiments with SHR show that, at high levels of sodium intake (4.0%), aggressive RAS blockade treatment with candesartan (3 mg/kg) and perindopril (6 mg/kg) does not result in regression of cardiac hypertrophy. In contrast, RAS blockade coupled with reduced sodium diet (0.2%) significantly regresses cardiac hypertrophy, impairs animal growth and is associated with elevated plasma renin and dramatically suppressed plasma angiotensinogen levels. Histological analyses indicate that the differential effect of reduced sodium on heart growth during RAS blockade is not associated with any change in myocardial interstitial collagen, but reflects modification of cellular geometry. Dimensional measurements of enzymatically-isolated ventricular myocytes show that, in the RAS blocked, reduced sodium group, myocyte length and width were decreased by about 16—19% compared with myocytes from the high sodium treatment group. Our findings highlight the importance of `titrating' sodium intake with combined RAS blockade in the clinical setting to optimise therapeutic benefit.
Candesartan abrogates G protein-coupled receptors agonist-induced MAPK activation and cardiac myocyte hypertrophy
Authors: Lebeche Djamel , Zhao Bin Kang  , Hajjar Roger
Published: September 2010

The renin-angiotensin-aldosterone system (RAAS) has been identified as a major contributor to the development of cardiac hypertrophy and the subsequent transition to heart failure. G protein-coupled receptors agonists such as angiotensin II (Ang II), endothelin-1 (ET-1) and phenylephrine (PE) have been implicated in hypertrophic responses in ventricular myocytes through the activation of several families of MAP kinases. In this study we examined the effect of candesartan, an Ang II type 1-(AT1)-receptor antagonist, on cardiac hypertrophy by using cultured neonatal rat cardiomyocytes. Stimulation with Ang II (100 nM), ET-1 (100 nM) or PE (1 µM) induced marked increases in [3H]Leucine incorporation (≥ 50%), compatible with enhanced protein synthesis. The addition of candesartan abrogated the increase in [3H]Leucine incorporation in response not only to Ang II but also to ET-1 and PE. To elucidate the mechanisms involved in this antihypertrophic effect of candesartan, we studied the activation of p38-MAPK, extracellular signal-regulated kinases (ERK1/2) and stress-activated protein kinases (SAPKs). Ang II, ET-1 and PE increased the phosphorylation levels of ERK1/2, p54 SAPK and p46SAPK and p38 in a time-dependent manner. This activation was completely blocked in the case of Ang II by pretreatment with candesartan. ET-1-induced activation of ERKs, SAPKs and p38 was also partially, but significantly, reduced by candesartan. PE-induced activation of SAPKs, but not ERKs and p38, was also reduced by candesartan. These results suggest that the hypertrophic response to ET-1 and PE, along with Ang II, is dependent upon a functioning AT1-receptor and may be mediated by AT 1 activation of the MAP kinases.
The role of angiotensin II and TGF-beta on the progression of chronic allograft nephropathy
Authors: Weir Matthew R , Chiming Wei
Published: September 2010

Chronic allograft nephropathy is the most prevalent cause of graft dysfunction and failure. Its pathogenesis and treatment remains poorly defined. The calcineurin inhibitors, cyclosporine and tacrolimus, may play a role in the progressive loss of renal function in patients with chronic allograft nephropathy. This effect may be either related to the direct stimulation of profibrogenic cytokines such as transforming growth factor (TGF-β) or indirect mechanisms, through increases in blood pressure or alterations in either carbohydrate or lipid metabolism. Experimental studies have demonstrated that angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARBs) can attenuate cyclosporine-mediated increases in TGF-β production in renal tissue.

Clinical studies have demonstrated that either cyclosporine or tacrolimus dose reduction may help reduce the rate of loss of renal function in patients with chronic allograft nephropathy. Moreover, other studies have demonstrated that a chronic reduction in the dose of cyclosporine in transplant patients can reduce serum TGF-β levels. Treatment with an ARB can normalise the plasma levels of TGF-β in renal transplant patients receiving cyclosporine. All these observations suggest that there may be a role of cyclosporine, and possibly tacrolimus, in worsening chronic allograft nephropathy through their effects on the renin-angiotensin-aldosterone system (RAAS) and TGF-β production.
Relative antihypertensive and glomeruloprotective efficacies of enalapril and candesartan cilexetil in the remnant kidney model
Authors: Griffin Karen A , Picken Maria M , Bakris George , Bidani Anil K
Published: September 2010

The present studies were performed to investigate whether the differences described between the two modalities for interruption of the renin-angiotensin-aldosterone system (RAAS), angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin AT 1receptor antagonists (AIIA) result in differences in renoprotective efficacy in the rat remnant kidney model. Male Sprague-Dawley rats with an initial body weight of 225—300 g, underwent 5/6 renal ablation and had radiotransmitters installed for radiotelemetric blood pressure (BP) measurements, owing to the known limitations of periodic tail-cuff BP measurements to adequately reflect ambient BP profiles. After renal ablation surgery, the rats received no treatment (n=10); enalapril (n=11) or candesartan (n=9) after the first week, both administered initially at a dose of 50 mg/l of drinking water (~10 mg/kg). However, the dose of candesartan had to be reduced to 10—25 mg/l in 4/9 rats to avoid excessive hypotension. Both enalapril and candesartan produced significant reductions in average systolic BP during the subsequent approximately six weeks of observations as compared with untreated rats (187±4 mmHg, p<0.001), but candesartan was significantly more effective at these relative doses (121±3 vs. 133±4 mmHg, p<0.05). At approximately seven weeks, serum creatinine and proteinuria were measured before sacrifice for morphologic assessment of percentage glomerulosclerosis (GS). Despite the described differences between ACE-I and AIIA after acute administration, the percentage GS was reduced similarly by enalapril (down to 6.8±2.8%) and candesartan (down to 2.9±1.5%) as compared with untreated rats (37.2±4.3%). Moreover, GS in individual animals paralleled the BP reductions achieved. Proteinuria was reduced in parallel to the decrease in % GS. These data indicate that, at least in the 5/6 renal ablation model, RAAS blockade by either ACE-I or AIIA provides protection by BPdependent rather than BP-independent mechanisms. This may reflect the primarily hypertensive pathogenesis of GS in this model, and the fact that hypertension is also very angiotensin II-dependent in this model. Thus, these data suggest that models other than the 5/6 ablation model may be more appropriate to demonstrate the BP-independent protective effects of RAAS blockade.
Angiotensin II blockade causes acute renal failure in eNOS-deficient mice
Authors: Schnermann Jürgen , Huang Yuning G , Briggs Josie P
Published: September 2010

Compared with wild-type mice, adult endothelial nitric oxide synthase (eNOS) knockout mice (eight months of age) have increased blood pressure (BP) (126±9 mmHg vs. 100±4 mmHg), and an increased renal vascular resistance (155±16 vs. 65±4 mmHg.min/ml). Renal vascular resistance responses to i.v. administration of noradrenaline were markedly enhanced in eNOS knockout mice. Glomerular filtration rate (GFR) of anaesthetised eNOS -/- mice was 324±57 µl/min gKW, significantly lower than the GFR of 761±126 µl/min.gKW in wild-type mice. AT1-receptor blockade with i.v. candesartan (1—1.5 mg/kg) reduced arterial blood pressure and renal vascular resistance, and increased renal blood flow (RBF) to about the same extent in wild-type and eNOS -/- mice. Candesartan did not alter GFR in wild-type mice (761±126 vs. 720±95 µl/min.gKW), but caused a marked decrease in GFR in eNOS -/- mice (324.5±75.2 vs. 77±18 µl/min.gKW). A similar reduction in GFR of eNOS deficient mice was also caused by angiotensin-converting enzyme (ACE) inhibition. Afferent arteriolar granularity, a measure of renal renin expression, was found to be reduced in eNOS -/- compared with wild-type mice. In chronically eNOS-deficient mice, angiotensin II (Ang II) is critical for maintaining glomerular filtration pressure and GFR, presumably through its effect on efferent arteriolar tone.
Comparison of the AT1-receptor blockers candesartan, irbesartan and losartan for inhibiting renal microvascular constriction
Authors: van Rodijnen William F , van Lambalgen Ton A , van Teijlingen Marco E , Tangelder Geert-Jan , ter Wee Piet M
Published: September 2010

Angiotensin II (Ang II) type 1 (AT1) receptor blockers differ in their affinity for the AT1-receptor, suggesting a dissimilar potency for inhibiting Ang II-induced vascular constriction. In the present study, we compared the effects of candesartan, irbesartan and losartan on the renal microvascular constriction to locally-formed Ang II, using isolated, perfused hydronephrotic rat kidneys. Addition of 1 nmol/L angiotensin I (Ang I, the precursor of Ang II) significantly reduced the diameters of interlobular arteries (ILAs; -47.6±2.6%), afferent arterioles (AAs; -43.6±2.3%) and efferent arterioles (EAs; -31.6±2.4%). Candesartan and irbesartan were more potent in antagonising the constriction to Ang I than losartan. By contrast, candesartan and irbesartan differed only slightly in potency. After a washing period of 60 minutes with drug-free medium, a second application of Ang I failed to induce vasoconstriction only in candesartan-treated kidneys. Pretreatment of hydronephrotic kidneys with candesartan, to further explore its antagonistic properties, shifted the dose-response curves of Ang II approximately 2 log units to the right without reducing the maximal Ang II-induced constriction of ILAs, AAs or EAs. Additionally, dose-response curves of Ang II were similar after short (10 minutes) and prolonged (60 minutes) preincubation with candesartan. Our findings indicate that candesartan and irbesartan are more potent inhibitors of renal microvascular constriction to locally-formed Ang II than losartan. The inhibitory effect of candesartan is more prolonged, suggesting a slow dissociation from the AT1-receptor. Additionally, candesartan was found to block the Ang II-induced constriction of renal microvessels in a surmountable manner.
Improvements of renal lesions and function by angiotensin and endothelin receptor antagonism in nitric oxide-deficient rats
Authors: Boffa Jean-Jacques , Ying Lu  , Dussaule Jean-Claude , Chatziantoniou Christos
Published: September 2010

In previous studies, we have observed that antagonism of angiotensin or endothelin receptors prevented the development of nephroangio- and glomerulo-sclerosis during hypertension by inhibiting collagen I gene synthesis, through a mechanism independent of systemic haemodynamics. The present study investigated whether treatment with angiotensin or endothelin receptor antagonists, given at doses that did not reduce blood pressure, could produce regression of renal sclerotic lesions and improve renal function during hypertension. Hypertension and renal vascular fibrosis were induced in rats by chronic inhibition of NO synthesis using NGnitro-L-arginine methyl ester (L-NAME). Systolic blood pressure gradually increased following L-NAME administration, reaching a plateau of 170 mmHg after four weeks of treatment. At the same time, urinary protein excretion and plasma creatinine concentration were increased ten- and three-fold compared with controls, respectively (p<0.001). This increase was accompanied by the appearance of sclerotic lesions within renal vessels and glomeruli, as evidenced by Masson's trichromic staining (sclerotic index 2.34±0.29 vs. 0.10±0.01 in L-NAME four weeks and control, respectively, p<0.001). Thereafter, the L-NAME treatment was combined with either losartan (an AT1receptor antagonist), bosentan (an ETA/B antagonist), co-treatment with both agents, or vehicle for an additional period of four weeks. Blockade of AT1and/or ETA/B-receptors significantly reduced urinary protein excretion and plasma creatinine levels (p<0.01) and substantially improved renal vascular histology (sclerotic index 1.78±0.13, 1.57±0.22 and 1.85±0.15 respectively, p<0.01, vs. L-NAME eight week) without altering the L-NAME-induced increase of systolic pressure. These data indicate that angiotensin II and endothelin-1 participate in the mechanism(s) of renal vascular fibrosis by increasing extracellular matrix formation. Treatment with their respective receptor antagonists leads to the regression of renal vascular fibrosis and to the improvement of renal function by a common antifibrogenic mechanism that is independent of systemic haemodynamics.
Policy and politics
Authors: Cronin Eugenia
Published: September 2010

A short tale of some known knowns, some known unknowns and one major unknown unknown
If you have health you have hope, if you have hope you have everything
Authors: Clapham David
Published: September 2010

David Clapham, Principal Environmental Health Manager at Bradford Council, questions the emphasis on making the developed world’s clean water even cleaner, while ignoring the fact that dirty water is the best many in the world can hope for
The implication of water on public health: The case of China
Authors: Chan Emily , Griffiths Sian
Published: September 2010

In China, water resources are both inadequate and unevenly distributed. Professor Emily Chan and Professor Sian Griffiths from the Chinese University of Hong Kong, discuss the impact of water quantity, quality, cost and development on public health in China
Need for community water fluoridation in areas with suboptimal fluoride levels in India
Authors: Sulugodu Ramachandra Srinivas , Sulgodu Ramachandra Srikrishna , Rao Mala
Published: September 2010

Dr Srinivas Sulugodu Ramachandra, Senior Lecturer at Kanti Devi Dental College, Dr Srikrishna Sulgodu Ramachandra, Assistant Professor at the Public Health Foundation of India, and Dr Mala Rao, Director of the Indian Institute of Public Health, argue that oral health is being neglected in the world’s second most populous country
Development, Implementation, and Effects of Community-Based Diabetes Prevention Program for Obese Latino Youth
Authors: Shaibi Gabriel Q. , Greenwood-Ericksen Margaret B. , Chapman Cecilia R. , Konopken Yolanda , Ertl Janice
Published: September 2010

Objective: Obesity and type 2 diabetes have emerged as critical health issues among Latino youth. Although both conditions manifest early in life, very few diabetes prevention programs have been developed to specifically meet the needs of this population. The authors describe the development, implementation, and metabolic impact of a culturally informed, community-based diabetes prevention program for obese Latino youth. Methods: A lifestyle education program was developed to address the health needs of Latino youth served by a community-based medical clinic. The program consisted of group education sessions delivered to children and their families to address nutrition, physical activity, family roles and responsibilities, and self-esteem. The metabolic impact of the program was evaluated by assessing body mass index (BMI), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, total cholesterol, triglycerides, glucose, and insulin. Results: On entry, the prevalence of risk factors among the 102 youth (mean BMI, 30.4 ± 4.9 kg/m2) was substantial (68.6% with low HDL cholesterol, 32.1% with elevated triglycerides, 9.4% with impaired fasting glucose, 39.4% with elevated total cholesterol, 43.0% with elevated LDL cholesterol, and 60.6% with hyperinsulinemia). The 50 youth who returned after the program for follow-up measurements exhibited significant health improvements, including a 3.8% reduction in BMI; 5.4% and 8.6% decreases in total and LDL cholesterol, respectively; a 9.3% increase in HDL cholesterol; and a 24.0% decrease in fasting insulin (all P values < .05). Conclusions: These promising findings suggest that a community-based diabetes prevention program for obese Latino youth is a feasible strategy for improving health in this high-risk population. Further studies are warranted to examine whether similar programs can be implemented in diverse communities and settings.
Postpartum Depression Screening
Authors: Wichman Christina L. , Angstman Kurt B. , Lynch Brian , Whalen Denise , Jacobson Nathan
Published: September 2010

Postpartum depression (PPD) has emerged as an important issue for pediatricians and family practitioners because of detrimental effects on children. PPD occurs in 10% to 22% of women who have recently given birth, but fewer than half of cases are recognized. Despite the impact of PPD, many primary care clinicians do not have systemic screening approaches implemented. This paper will review the development of a screening protocol for PPD in a multispecialty clinic, with the implementation utilizing depression care managers and the preliminary results of our process. Of the 333 screened examinations during the 4-month study, 38.1% (n = 127) were performed for the 2-month well child examination; 33.6% (n = 112) were for the 4-month examination, with 28.2% (n = 94) being performed for the 6-month well child examination. Only 15 (4.5%) were positive for possible depression with a screening compliance rate of 47.9%. No significant difference was noted in the timing of the well child visit with a positive screening test result, nor was there any difference in family medicine versus pediatric colleagues in the utilization of the screening or diagnosis of PPD. Implementation of PPD screening in a multispecialty clinic can be effective, given utilization of depression care managers.
Intervention to Reduce Parental Bypass of Community Pediatric Primary Health Facilities in Asmara, Eritrea
Authors: Natale JoAnne E. , Hamburger Ellen , Aman Mussie , Asmerom Woldu , Faisal Amal , Gebremichael Fitsum , Haile Solomon , Maekele Meroni , Mohammed Mahmud , Tesfaye Dawit , Ghiorghis Belai , Joseph Jill G.
Published: September 2010

Objective: To reduce direct parental referral of low acuity ill pediatric patients to the outpatient facilities of a nation’s only pediatric referral hospital. Patients and Methods: Longitudinal monitoring of outpatient visits at Orotta Children’s Hospital (OCH) and primary health facilities (PHFs) following implementation of an intervention designed in response to information provided by parents and health-care providers. Parental surveys were undertaken before and after exposure to the intervention to assess effects on knowledge, attitudes, and behavioral intentions. Results: We analyzed 5,639 visits between baseline and follow-up, documenting a decline in parental referral among OCH outpatients from 95% to approximately 80%. Educational intervention increased the proportion of parents intending to use PHF for future outpatient care from 28% to 82%. Staff of the PHFs responded enthusiastically to this intervention program and requested further activities. Conclusions: Self-referral to tertiary care hospital was reduced following a modest program of parental education designed and implemented by residents in training.