bluuebunny/crossref_metadata_2025_split huggingface dataset:
WHICH OF THE CARDIAC NATRIURETIC PEPTIDES IS MOST EFFECTIVE FOR THE TREATMENT OF CONGESTIVE HEART FAILURE, RENAL FAILURE AND CANCER?
Authors: Vesely David L 
Published: February 2006

SUMMARY

Cardiac natriuretic peptides consist of a family of six peptide hormones that are synthesised by three separate genes and then stored as three separate prohormones (i.e. 126 amino acid atrial natriuretic peptide (ANP), 108 amino acid B‐type natriuretic peptide (BNP) and 103 amino acid C‐type natriuretic peptide (CNP) prohormones). The ANP prohormone contains four peptide hormones: long‐acting natriuretic peptide (LANP), vessel dilator, kaliuretic peptide and ANP.
Currently, the only natriuretic peptide available commercially to treat congestive heart failure (CHF) is BNP (Nesiritide/Natrecor; SCIOS, Sunnyvale, CA, USA), which causes a small increase in the urine volume of 90 38 mL/h compared with 67 27 mL/h and no significant natriuresis, but has beneficial haemodynamic effects in acute CHF individuals. These haemodynamic effects probably contribute to the side‐effects of BNP in patients with acute CHF with a 27% incidence of hypotension and possibly to 22% worsening of renal function, defined as an increase in serum creatinine of 0.5 mg/dL, associated with a worse prognosis. A review of clinical trials suggests a twofold increased risk of death at 30 days post‐nesiritide treatment, a finding that needs further investigation.
The best of the natriuretic peptides for treating chronic CHF is the vessel dilator, which increases urinary flow up to 13‐fold and sodium excretion up to fourfold, without the previously mentioned side‐effects. The natriuretic and diuretic effects of vessel dilators last 6 h, which would allow them to be used on a four times per day basis in treating chronic CHF.
Atrial natriuretic peptide does not cause significant improvement in acute renal failure (ARF) in humans. The only natriuretic peptide that significantly improves ARF is the vessel dilator. Even when ARF has been established for 2 days before treatment in an ischaemic ARF animal model, vessel dilator decreases serum creatinine from 8.2 0.5 to 0.98 0.12 mg/dL in 6 days. At day 6 of ARF, mortality decreases to 14% (from 88%) without the vessel dilator. After 6 days of treatment with the vessel dilator, the proximal and distal tubules regenerate.
In cancer, vessel dilator, LANP, kaliuretic peptide and ANP at 1 mmol/L, decrease up to 97% of human breast, pancreatic and prostate adenocarcinoma cells, as well as small cell and squamous cell lung cancer cells within 24 h. In vivo, vessel dilator, LANP and kaliuretic peptide completely stop the growth of human pancreatic adenocarcinomas in athymic mice and decrease their tumour volume by 49, 28 and 11%, respectively in 1 week.
IMPACT OF CORTISOL ON α‐ACTIN CONTENT IN VASCULAR SMOOTH MUSCLE CELLS OF FETAL SHEEP
Authors: Matuszek Maria A , Gibson Karen J , Lumbers Eugenie R , Simonetta Giuseppe 
Published: February 2006

SUMMARY

The effects of gestation on a‐actin levels in vascular smooth muscle aortae were studied in 31 fetal sheep, aged 66–144 days (term = 150 days). Aortae were collected post‐mortem.
Aortae, carotid and femoral arteries from two groups of chronically catheterized fetal sheep (110–114 days) were also examined. One group was infused with cortisol (n = 6; hydrocortisone sodium succinate, total dose 16.8 mg in 48 h) and the control group received saline (0.15 mol/L, 0.33 mL/h, n = 7).
Vascular homogenate protein was separated by sodium dodecyl sulphate–polyacrylamide gel electrophoresis and western transfer. a‐Actin was identified using a monoclonal mouse anti‐a actin antibody and standardized against tissue protein and DNA content.
Between 60 and 144 days gestation, there was an exponential increase in the a‐actin content of vascular smooth muscle cells from fetal sheep aorta (P < 0.0001). a‐Actin concentration (densitometry units (U) relative to DNA 260 nm absorbance (Abs)) was significantly (P < 0.05) higher in the aortae of cortisol‐infused (12 601 2499 U/Abs) fetal sheep compared with those that were saline‐infused (4514 670 U/Abs). a‐Actin (relative to DNA absorbance) of carotid and femoral vessels in cortisol‐infused animals (20 659 4812 U/Abs) compared with those that were saline‐infused (14 461 2645 U/Abs) was increased, but the difference was not significant.
Therefore, the a‐actin concentration of the vascular smooth muscle of the aorta increases throughout gestation. Cortisol treatment is associated with further increases in a‐actin concentration in the fetal aorta, indicating that the development of large conduit vessels can be altered by this glucocorticoid.
HIGH GLUCOSE‐INDUCED INHIBITION OF 2‐DEOXYGLUCOSE UPTAKE IS MEDIATED BY cAMP, PROTEIN KINASE C, OXIDATIVE STRESS AND MITOGEN‐ACTIVATED PROTEIN KINASES IN MOUSE EMBRYONIC STEM CELLS
Authors: Han Ho Jae , Heo Jung Sun , Lee Yun Jung , Min Jung Jun , Park Kwang Sung 
Published: February 2006

SUMMARY

Abnormally high glucose levels may play an important role in early embryo development and function. In the present study, we investigated the effect of high glucose on 2‐deoxyglucose (2‐DG) uptake and its related signalling pathway in mouse embryonic stem (ES) cells.
2‐Deoxyglucose uptake was maximally inhibited by 25 mmol/L glucose after 24 h treatment. However, 25 mmol/L mannitol and dextran did not affect 2‐DG uptake. Indeed, 25 mmol/L glucose decreased GLUT‐1 mRNA and protein levels. The glucose (25 mmol/L)‐induced inhibition of 2‐DG uptake was blocked by pertussis toxin (a Gi‐protein inhibitor; 2 ng/mL), SQ 22536 (an adenylate cyclase inhibitor; 10‐6 mol/L) and the protein kinase (PK) A inhibitor myristoylated PKI amide‐(14–22) (10‐6 mol/L). Indeed, 25 mmol/L glucose increased intracellular cAMP content.
Furthermore, 25 mmol/L glucose‐induced inhibition of 2‐DG uptake was prevented by 10‐4 mol/L neomycin or 10‐6 mol/L U 73122 (phospholipase C (PLC) inhibitors) and staurosporine or bisindolylmaleimide I (protein kinase (PK) C inhibitors). At 25 mmol/L, glucose increased translocation of PKC from the cytoplasmic fraction to the membrane fraction. The 25 mmol/L glucose‐induced inhibition of 2‐DG uptake and GLUT‐1 protein levels was blocked by SQ 22536, bisindolylmaleimide I or combined treatment. In addition, 25 mmol/L glucose increased cellular reactive oxygen species and the glucose‐induced inhibition of 2‐DG uptake were blocked by the anti‐oxidants N‐acetylcysteine (NAC; 10‐5 mol/L) or taurine (2 ¥ 10‐3 mol/L).
Glucose (25 mmol/L) activated p38 mitogen‐activated protein kinase (MAPK) and p44/42 MAPK. Staurosporine (10‐6 mol/L), NAC (10‐5 mol/L) and PD 98059 (10‐7 mol/L) attenuated the phosphorylation of p44/42 MAPK. Both SB 203580 (a p38 MAPK inhibitor; 10‐7 mol/L) and PD 98059 (a p44/42 MAPK inhibitor; 10‐7 mol/L) blocked 25 mmol/L glucose‐induced inhibition of 2‐DG uptake.
In conclusion, high glucose inhibits 2‐DG uptake through cAMP, PLC/PKC, oxidative stress or MAPK in mouse ES cells.
THE CATECHOLAMINE–β‐ADRENORECEPTOR–cAMP SYSTEM AND PREDICTION OF CARDIOVASCULAR EVENTS IN HYPERTENSION
Authors: Peng Ying‐Xin , Shan Jiang , Qi Xiao‐Yong , Zhang Su‐Jun , Ma Shu‐Ping , Wang Na , Li Jun‐Ping , Xue Hao , Wu Min 
Published: February 2006

SUMMARY

Although the importance of elevated circulating plasma catecholamines on cardiac structural and functional remodelling of hypertension is well documented, it is unclear whether the catecholamine–b‐adrenoreceptor (bAR)–cAMP system can predict different cardiovascular events.
A total of 601 identified hypertensive patients with baseline and follow‐up plasma levels of noradrenaline (NA) and adrenaline (Adr), lymphocyte bAR density (Bmax) and intralymphocyte cAMP levels in peripheral blood (last examination 60 ± 26 months apart) were followed up for an additional 24 ± 12 months.
After the last follow up, a composite end‐point of cardiovascular death, non‐fatal myocardial infarction (MI) and stroke occurred in 139 patients (23.1%). In Cox analyses, adjusting for other standard factors as well as treatment effect, NA (hazard ratio 1.22; 95% confidence interval (CI) 1.17–1.28; P = 0.0008), Adr (hazard ratio 1.53; 95% CI 1.18–2.00; P = 0.002), bAR (hazard ratio 1.12; 95% CI 1.06–1.17; P = 0.007) and cAMP (hazard ratio 1.15; 95% CI 1.09–1.21; P = 0.005) separately predicted cardiovascular mortality. Noradrenaline, Adr, bAR and intralymphocyte cAMP separately predicted fatal/non‐fatal MI; NA and Adr predicted fatal/non‐fatal stroke, whereas Bmax and intralymphocyte cAMP levels were not a significant predictor of fatal/non‐fatal stroke. When stratifying the study population by NA or Adr (median 4 nmol/L), Bmax (median 600 fmol/107 cells) and cAMP (median 5.0 pmol/mg protein) above and below the median values in both parameters categories, patients above the median had composite cardiovascular end‐point (all P < 0.001) and high cardiovascular death (all P < 0.01, log‐rank test).
These results suggest that plasma NA and Adr are significant predictors of cardiovascular mortality, MI and stroke. The Bmax and intralymphocyte cAMP levels are significant predictors of cardiovascular mortality and MI, but not stroke.
HYPERTENSION, OBESITY AND GNB3 GENE VARIANTS
Authors: Danoviz María E , Pereira Alexandre C , Mill José G , Krieger José E 
Published: February 2006

SUMMARY

The polymorphism C825T of the gene encoding the G‐protein b3‐subunit (GNB3) was found to be associated with an increased prevalence of hypertension in a number of studies. The aim of the present study was to investigate the association between this polymorphism and blood pressure phenotypes in an urban, large and ethnically mixed population of Brazil.
Individuals (n = 1 568) were randomly selected from the general population of the Vitória City metropolitan area. The GNB3 C825T polymorphism was genotyped in each individual. Baseline cardiovascular risk factors were collected for all participants. Cardiovascular risk variables and genotypes were compared using anova and the Chi‐squared test for univariate comparisons and logistic regression for multiple comparisons.
A statistically significant interaction between the 825T allele and obesity was observed for systolic blood pressure (SBP; P = 0.02). In fact, the C825T genotype was predictive of SBP only in individuals with increased body mass index (P = 0.02). In addition, in a multiple logistic regression model conducted in the obese population and adjusted for age, sex, ethnicity, diabetes, triglycerides and total cholesterol, the presence of the T allele was significantly associated with a 1.5‐fold (95% confidence interval 1.04–2.26) increased risk of hypertension. Lack of statistical power does not explain the absence of other positive gene–environment interactions.
The present results suggest that an important gene ¥ environment interaction may take place between bodyweight regulation and the GNB3 gene. This finding provides further evidence for a role of the 825T allele in hypertension susceptibility and may be used for better disease stratification.
CONTRIBUTION OF PROSTANOID TP RECEPTORS TO THE PRESSOR AND INTRARENAL HAEMODYNAMIC RESPONSE TO ENDOTHELIN
Authors: Williams Jan Michael , Pollock David M 
Published: February 2006

SUMMARYPrevious studies have shown that endothelin (ET)‐1 stimulates thromboxane (Tx)A2production and so we hypothesized that inhibiting prostanoid TP receptors would prevent the pressor and intrarenal haemodynamic response to an acute infusion of ET‐1.Male Sprague‐Dawley rats were anaesthetized with Inactin (Sigma Chemical, St Louis, MO, USA; 50 mg/kg) and catheters were inserted into the femoral artery and vein for recording mean arterial pressure (MAP) and infusion of ET‐1 and receptor antagonists, respectively. A jugular vein catheter was used for the infusion of bovine serum albumin (6.2% in saline) during surgery (1.25% bodyweight). The pressor response to a 1 h infusion of ET‐1 (6 pmol/kg per min) was determined in rats that had been pretreated with vehicle (0.9% NaCl) or the TP receptor antagonist SQ29548 (2 mg/kg per h). Laser Doppler single‐optic fibres were implanted in the left kidney for the measurement of medullary blood flow (MBF) and cortical blood flow (CBF).Prostanoid TP receptor blockade completely inhibited the acute pressor response to ET‐1; the change in MAP was 14 2% versus ‐3 4% in vehicle and SQ29548 groups, respectively (P < 0.05). Endothelin‐1 reduced CBF (‐15.2 3.3%), a response that was not significantly changed by SQ29548 (‐6.2 7.6%). Similarly, the ET‐1‐mediated response in MBF was not altered by the TP receptor antagonist (7.7 4.9vs6.5 5.2%).To determine the influence of the ETBreceptor in modulating the response to ET‐1 during TP receptor blockade, additional groups were pretreated with A‐192621, an ETBreceptor‐selective antagonist (10 mg/kg, i.v.). A‐192621 potentiated the increase in MAP produced by ET‐1 (32 5%;P < 0.05vsET‐1 alone). SQ29548 significantly inhibited, but did not completely block, the increase in MAP produced by ET‐1 during ETBantagonist treatment (18 4%;P < 0.05). Endothelin‐1‐induced decreases in CBF were significantly enhanced in rats that were pretreated with A‐192621, whereas ET‐1 also significantly decreased MBF following A‐192621 treatment. During ETBreceptor blockade, TP receptor inhibition had no effect on the ET‐1‐mediated response of CBF and MBF.These results suggest that TP receptor activation is not involved in the renal haemodynamic responses to ET‐1. However, TP receptor activation contributes to the acute pressor response to ET‐1, but does not account for the potentiated increase in MAP during ETBreceptor blockade.
HEAT SHOCK‐INDUCED AUGMENTATION OF VASCULAR CONTRACTILITY IS INDEPENDENT OF RHO‐KINASE
Authors: Seok YoungMi , Kim Jee In , Ito Masaaki , Kureishi Yasuko , Nakano Takeshi , Kim Si‐Oh , Lim Dong Gun , Park Wee Hyun , Kim InKyeom 
Published: February 2006

SUMMARY

In a previous study, we demonstrated that heat shock augments the contractility of vascular smooth muscle through the stress response.
In the present study, we investigated whether Rho‐kinases play a role in heat shock‐induced augmentation of vascular contractility in rat isolated aorta.
Rat aortic strips were mounted in organ baths, exposed to 42C for 45 min and subjected to contractile or relaxant agents 5 h later.
The level of expression of Rho‐kinases in heat shock‐exposed tissues was no different to that of control tissues, whereas heat shock induced heat shock protein (Hsp) 72 at 3 and 5 h. Heat shock resulted in an increase in vascular contractility in response to phenylephrine 5 h later.
The Rho‐kinase inhibitors Y27632 (30 nmol/L‐10 mmol/L) or HA 1077 (10 nmol/L‐10 mmol/L) relaxed 1.0 mmol/L phenylephrine‐precontracted vascular strips in a concentration‐dependent manner; these effects were attenuated in heat shock‐exposed strips. Pretreatment with Y27632 resulted in greater inhibition of the maximum contraction in control strips compared with those in heat shock‐exposed strips.
The results of the present study suggest that Rho‐kinases are unlikely to be involved in heat shock‐induced augmentation of vascular contractility.
INFLUENCE OF AIR POLLUTION ON RESPIRATORY HEALTH DURING PERINATAL DEVELOPMENT
Authors: Pinkerton Kent E , Joad Jesse P 
Published: February 2006

SUMMARY

The respiratory system is a highly ordered structure composed of over 40 cell types involved in a multitude of functions. Development of the lungs spans from embryogenesis to adult life, passing through several distinct stages of growth.
Oxidant gases, airborne particles and environmental tobacco smoke are common air pollutants that could have a significant impact on the lungs during both pre‐ and postnatal periods of life. Although the specific target cells for exposure to these pollutants are not clearly identified, these cells are likely to affect critical signals or mediators expressed during distinct stages of lung development.
Neonatal susceptibility to environmental pollutants may be caused by either direct or indirect hits on several cell types to influence cell differentiation, proliferation and/or maturation. Air pollutants may also alter the normal developmental pattern for metabolic, immune and neurological functions that are constantly changing during in utero and postnatal growth.
The sensitivity of neonatal cells to environmental insults is likely to be completely different from these same cell types found in the adult. Delivery of an environmental toxicant to the respiratory system is also dramatically different during the fetal compared with the postnatal period. Passage and interaction of environmental factors through other organ systems and the vasculature, as well as maternal influences, must be taken into consideration when evaluating the impact of an environmental toxicant during early life.
To understand the heath outcomes of exposure to a variety of environmental factors in the respiratory system of children requires careful consideration that lung development is a multistep process and cannot be based on studies in adults.
ENVIRONMENTAL FACTORS AND GENE–ENVIRONMENT INTERACTIONS IN THE AETIOLOGY OF ASTHMA
Authors: Marks Guy B 
Published: February 2006

SUMMARY

The importance of early life environmental influences on the aetiology of asthma is implied by the observed geographic and temporal variation in the prevalence of the disease among children.
There is evidence pointing to the role of exposure to allergen, various aspects of diet and hygiene‐related factors in the aetiology of asthma.
There is also evidence that heritable factors influence the impact of hygiene‐related exposures on the risk of having asthma. Polymorphism within genes coding for the toll‐like receptor–lipopolysaccharide (TLR‐LPS) signalling pathway may underlie variations in effects of hygiene‐related exposures, including specifically endotoxin, on the risk of developing allergic sensitization and allergic disease.
At present there is no unifying theory to explain the childhood origins of asthma and, hence, no solid basis for developing preventative interventions. Progress towards this goal requires better understanding of the heterogeneous nature of the disease in early childhood, improved characterization of relevant environmental exposures and long‐term follow up of birth cohorts with reliable and valid measures of allergy and asthma outcomes.
Forcing single‐chain variable fragment production in tobacco seeds by fusion to elastin‐like polypeptides
Authors: Scheller Jürgen , Leps Michael , Conrad Udo 
Published: February 2006

SummarySingle‐chain variable fragments (scFvs), as well as other recombinant antibodies, have become powerful tools for therapy and analysis in both human and veterinary medicine. Transgenic plants have been developed as an efficient production system for these recombinant proteins, achieving high yields at moderate cost. Seeds are especially useful organs for molecular farming because of their high protein content and their ability to keep proteins functional during extended storage in ambient conditions. Several concepts have been applied to optimize protein accumulation in seeds, such as the use of specific promoters and transcription enhancers. In this paper, we present a new strategy to enhance substantially the expression of scFvs in transgenic tobacco seeds, based on C‐terminal fusions to elastin‐like polypeptides (ELPs). This strategy resulted in a 40‐fold increase in scFv accumulation, with levels approaching 25% of total soluble protein. The fusion proteins show specific activities and affinities comparable with the properties of the corresponding scFvs. This strategy thus opens up new ways to improve greatly the production of recombinant antibodies in plant seeds.
Five Debates on International Development: The US Perspective
Authors: Natsios Andrew S. 
Published: February 2006

Andrew S. Natsios was Administrator of the United States Agency for International Development until January 2006. The US has the largest aid programme in the world but labours under certain constraints, notably a proliferation of Congressionally‐imposed budget earmarks. Mr Natsios has been an articulate advocate as well as an outspoken reformer of the US approach to aid. It was appropriate, then, for the All‐Party Parliamentary Group on Overseas Development of the Westminster parliament, together with ODI, to invite him to speak in Parliament on 12 October 2005.1 The present article, a version of that APGOOD speech revised by Mr Natsios since his November resignation, has been judged by DPR Editors to be an important development policy statement worthy of publication.Adrian Hewitt
QUASI‐NATURALISM AND MORAL REALITY
Authors: Majors Brad 
Published: February 2006

AbstractIn his recent book Moral Reality, Paul Bloomfield has put forward an original set of arguments for moral realism. Central to his treatment is an argument for the reality of moral properties, one which models them on the property of being healthy. The paper is a critical examination of Bloomfield's central line of argument. It is contended that his proposed method of grounding moral realism fails, inasmuch as his Distinction Test criterion for property reality – essentially the claim that a property exists if its existence is required for distinctions that we make and must make – is inadequate. An alternative approach toward properties is suggested, which has the result, inter alia, that Bloomfield's quasi‐naturalistic approach is unnecessary for the defense of moral realism.1
WHY ESSENTIALISM REQUIRES TWO SENSES OF NECESSITY
Authors: McLeod Stephen K. 
Published: February 2006

AbstractI set up a dilemma, concerning metaphysical modality de re, for the essentialist opponent of a ‘two senses’ view of necessity. I focus specifically on Frank Jackson's two‐dimensional account in his From Metaphysics to Ethics (Oxford: Oxford University Press, 1998). I set out the background to Jackson's conception of conceptual analysis and his rejection of a two senses view. I proceed to outline two purportedly objective (as opposed to epistemic) differences between metaphysical and logical necessity. I conclude that since one of these differences must hold and since each requires the adoption of a two senses view of necessity, essentialism is not consistent with the rejection of a two senses view.1
NATURALISM AND THE TRANSCENDENTAL TURN
Authors: Sacks Mark 
Published: February 2006

AbstractThis paper is to a large extent an exercise in philosophical geography. It traces the way in which a resilient naturalist orientation has derived support, specifically in the analytic tradition, from a central structuring tenet of transcendental idealism. It attempts to bring out the philosophical reasons that drive this Kantian alliance. Attention then turns to the identification of two salient problems that confront this alliance in its most acceptable form. To the extent that a resilient naturalism is desirable, these problems need to be addressed.While the philosophical issue is brought into focus by attending specifically to developments in the analytic tradition, this is primarily a convenience. The preference for a resilient naturalism and the avoidance of metaphysical excess is not by any means confined to that tradition.
THE UNIVERSE AMONG OTHER THINGS
Authors: Varzi Achille C. 
Published: February 2006

AbstractPeter Simons has argued that the expression ‘the universe’ is not a genuine singular term: it can name neither a single, completely encompassing individual, nor a collection of individuals. (It is, rather, a semantically plural term standing equally for every existing object.) I offer reasons for resisting Simons's arguments on both scores.