bluuebunny/crossref_metadata_2025_split huggingface dataset:
COMPUTER SIMULATIONS OF TRANSPORT THROUGH MEMBRANES: PASSIVE DIFFUSION, PORES, CHANNELS AND TRANSPORTERS
Authors: Tieleman D Peter 
Published: September 2006

SUMMARY

A key function of biological membranes is to provide mechanisms for the controlled transport of ions, nutrients, metabolites, peptides and proteins between a cell and its environment.
We are using computer simulations to study several processes involved in transport.
In model membranes, the distribution of small molecules can be accurately calculated; we are making progress towards understanding the factors that determine the partitioning behaviour in the inhomogeneous lipid environment, with implications for drug distribution, membrane protein folding and the energetics of voltage gating.
Lipid bilayers can be simulated at a scale that is sufficiently large to study significant defects, such as those caused by electroporation.
Computer simulations of complex membrane proteins, such as potassium channels and ATP‐binding cassette (ABC) transporters, can give detailed information about the atomistic dynamics that form the basis of ion transport, selectivity, conformational change and the molecular mechanism of ATP‐driven transport.
This is illustrated in the present review with recent simulation studies of the voltage‐gated potassium channel KvAP and the ABC transporter BtuCD.
PARADOXICALLY ENHANCED HEART TOLERANCE TO ISCHAEMIA IN TYPE 1 DIABETES AND ROLE OF INCREASED OSMOLARITY
Authors: Chen Hong , Shen Wei‐Li , Wang Xu‐Hui , Chen Hong‐Zhuan , Gu Jian‐Zhong , Fu Jie , Ni Ya‐Feng , Gao Ping‐Jin , Zhu Ding‐Liang , Higashino Hideaki 
Published: September 2006

SUMMARY

There is considerable controversy regarding the tolerance of diabetic hearts to ischaemia and the underlying mechanisms responsible for the increased heart tolerance to ischamia remain uncertain. In the present study, we observed, in vitro, type 1 diabetic heart responses to ischaemia and reperfusion at different degrees of hyperglycaemia. In addition, the possible role of increased osmolarity in cardioprotection due to hyperglycaemia was evaluated.
Hearts from 3 week streptozocin‐induced diabetic rats were isolated and perfused in a Langendorff apparatus and subjected to 30 min ischaemia and 30 min reperfusion. Cardiac function and the electrocardiogram were recorded. Myocardial content of osmolarity associated heat shock protein (hsp) 90, heme oxygenase (HO)‐1 and anti‐oxidant enzymes were determined in diabetic or hyperosmotic solution‐perfused hearts using western blot. The hsp90 inhibitor 17‐allylamino‐17‐demethoxygeldanamycin (17‐AAG; 2 × 10−7 mol/L) or the nitric oxide synthase (NOS) inhibitor Nω‐nitro‐l‐arginine methyl ester (1 × 10−5 mol/L) was added to the perfusate to observe the effects of hsp90 inhibition and hsp90‐associated endothelial NOS on ischaemic responses of diabetic hearts.
Compared with normal control rats, diabetic hearts with severe hyperglycaemia (blood glucose > 20 mmol/L) showed markedly improved postischaemic heart function with fewer reperfusion arrhythmias. Mild hyperglycaemia (< 12 mmol/L) exhibited no significant cardioprotection.
Elevated expression of hsp90 accompanied the enhanced resistance to ischaemia in diabetic hearts, which was abrogated by 17‐AAG. In the presence of the NOS inhibitor, heart function was preserved, whereas reperfusion arrhythmias were increased in diabetes. Diabetic hearts also had markedly elevated HO‐1 and catalase, with no significant change in superoxide dismutase. Hyperosmotic perfusion with glucose or mannitol also increased myocardial hsp90 and catalase.
The present findings reveal that heart resistance to ischaemia is increased in short‐term type 1 diabetes with severe hyperglycaemia. Elevated osmolarity caused by significant hyperglycaemia may contribute to the enhanced myocardial activity against oxidative injury during ischaemia and reperfusion.
HEPATOPROTECTIVE AND HYPOLIPIDAEMIC EFFECTS OF GLYCOPROTEIN ISOLATED FROM GARDENIA JASMINOIDES ELLIS IN MICE
Authors: Lee Sei‐Jung , Oh Phil‐Sun , Lim Kye‐Taek 
Published: September 2006

SUMMARY

The present study was performed to investigate the hepatoprotective and hypolipidaemic effects of a 27 kDa glycoprotein isolated from Gardenia jasminoides Ellis (GJE glycoprotein) in glucose/glucose oxidase (G/GO)‐treated BNL CL.2 cells, as well as in CCl4, Triton WR‐1339 and corn oil‐treated mice.
In G/GO‐treated BNL CL.2 cells, the results showed that GJE glycoprotein has an inhibitory effect on G/GO‐induced cytotoxicity and intracellular reactive oxygen species production. In addition, GJE glycoprotein has an anti‐oxidant effect against the lipid peroxidation process in the Fe2+/ascorbic acid system.
In CCl4 (1.0 mL/kg)‐treated mice, pretreatment with GJE glycoprotein (80 mg/kg) blocked lactate dehydrogenase release and the formation of thiobarbituric acid‐reactive substances. In addition, in these mice GJE resulted in increased nitric oxide production and the activation of anti‐oxidant enzymes, accompanied by the inhibition of the cytotoxic‐related signals hepatic cytochrome c, nuclear factor‐κB and activator protein‐1.
In both Triton WR‐1339 (400 mg/kg) and corn oil (1.0 g/kg)‐treated mice, pretreatment with GJE glycoprotein (80 mg/kg) lowered the levels of plasma lipoproteins (triglyceride, total cholesterol and low‐density lipoprotein).
On the basis of these results, we assume that GJE glycoprotein can ameliorate liver function, because it has hepatoprotective and hypolipidaemic activities.
DOCOSAHEXAENOIC ACID‐INDUCED PROTECTIVE EFFECT AGAINST IMPAIRED LEARNING IN AMYLOID β‐INFUSED RATS IS ASSOCIATED WITH INCREASED SYNAPTOSOMAL MEMBRANE FLUIDITY
Authors: Hashimoto Michio , Hossain Shahdat , Shimada Toshio , Shido Osamu 
Published: September 2006

SUMMARYIn the present study, we investigated the relationship between the docosahexaenoic acid (DHA)‐induced protection of learning deficit of amyloid β(1−40)‐infused Alzheimer's disease (AD) model rats and changes in synaptosomal plasma membrane fluidity of the cerebral cortex.Synaptosomal membrane lateral and rotational fluidity were measured using pyrene excimer spectroscopy and fluorescence polarization of 1,6‐diphenyl‐1,3,5‐hexatriene (DPH), respectively.Avoidance learning ability, as assessed by a two‐way active avoidance paradigm, decreased significantly in the AD model rats.Pyrene‐determined annular/non‐annular fluidity ratio and the DPH‐determined bulk fluidity of the synaptosomal plasma membrane decreased in the amyloid β(1−40)‐infused rats. Oral pre‐administration of DHA (300 mg/kg per day for 12 weeks) significantly increased both lateral and rotational fluidity.The synaptosomal membrane DHA content increased and the cholesterol to phospholipid molar ratio and lipid peroxidation decreased.The annular to non‐annular fluidity ratio of the synaptic plasma membrane was positively correlated with total avoidance learning.The present results indicate that DHA‐induced alterations in synaptic plasma membrane fluidity may contribute to the synaptic plasma membrane‐related functions that constitute avoidance learning‐related memory in amyloid β(1−40)‐infused rats.
PROSTAGLANDINS, CAPSAICIN‐SENSITIVE SENSORY NERVES AND NEUTROPHIL INFILTRATION, BUT NOT NITRIC OXIDE, CONTRIBUTE TO COLD RESTRAINT STRESS‐INDUCED GASTRIC ADAPTATION IN RATS
Authors: Tan Ruken , Bülbül Mehmet , Öngüt Gözde , Tosun Özgür , İzgüt‐Uysal V Nimet 
Published: September 2006

SUMMARY

The aim of the present study was to determine the role of prostaglandins (PG), nitric oxide (NO) and capsaicin‐sensitive sensory nerves in neutrophil infiltration in gastric adaptation to cold restraint stress in rats.
Wistar rats were exposed to single or repeated cold restraint stress for 3.5 h every other day for up to 4 days. Prior to repeated stress, rats were pretreated with NG‐nitro‐l‐arginine methyl ester (l‐NAME; 10 mg/kg, s.c.), indomethacin (10 mg/kg, s.c.) or capsaicin (125 mg/kg, s.c.). The extent of gastric mucosal lesions was evaluated histologically and myeloproxidase (MPO) activity, PGE2, NO and calcitonin gene‐related peptide (CGRP) levels were measured in gastric tissue.
Cold restraint stress produced haemorrhagic lesions and reduced PGE2 and CGRP levels in the stomach, with an increase in MPO activity and NO levels. Repeated stress insults reduced stress‐induced gastric damage, NO production and MPO activity, with an increase in PGE2 and CGRP levels compared with rats exposed to single cold restraint stress. Adaptation to cold restraint stress was prevented by indomethacin and capsaicin pretreatment, but not by l‐NAME.
We conclude that the stomach has the ability to adapt to repeated exposure to cold restraint stress and that the adaptation, via inhibition of neutrophil infiltration, is mediated, at least in part, by endogenous PG and CGRP.
INTRARENAL OXYGEN IN DIABETES AND A POSSIBLE LINK TO DIABETIC NEPHROPATHY
Authors: Palm Fredrik 
Published: September 2006

SUMMARY

Diabetic nephropathy is a major cause of morbidity and mortality. The exact mechanism mediating the negative influence of hyperglycaemia on renal function remains unclear, although several hypotheses have been postulated. The cellular mechanisms include glucose‐induced excessive formation of reactive oxygen species, increased glucose flux through the polyol pathway and formation of advanced glycation end‐products. The renal effects in vivo of each and every one of these mechanisms are even less clear. However, there is growing evidence that hyperglycaemia results in altered renal oxygen metabolism and decreased renal oxygen tension and that these changes are linked to altered kidney function.
Clinical data regarding renal oxygen metabolism and oxygen tension are currently rudimentary and our present understanding regarding renal oxygenation during diabetes is predominantly derived from data obtained from animal models of experimental diabetic nephropathy.
This review will present recent findings regarding the link between hyperglycaemia and diabetes‐induced alterations in renal oxygen metabolism and renal oxygen availability.
A possible link between reduced renal oxygen tension and the development of diabetic nephropathy includes increased polyol pathway activity and oxidative stress, which result in decreased renal oxygenation and subsequent activation of hypoxia‐inducible factors. This initiates increased gene expression of numerous genes known to be involved in development of diabetic nephropathy.
HYPOXIA‐INDUCED ERYTHROPOIETIN PRODUCTION: A PARADIGM FOR OXYGEN‐REGULATED GENE EXPRESSION
Authors: Stockmann Christian , Fandrey Joachim 
Published: September 2006

SUMMARY

The mechanisms controlling the expression of the gene encoding for the hormone erythropoietin (EPO) are exemplary for oxygen‐regulated gene expression. In humans and other mammals, hypoxia modulates EPO levels by increasing expression of the EPO gene. An association between polycythaemia and people living at high altitudes was first reported more than 100 years ago.
Since the identification of EPO as the humoral regulator of red blood cell production and the cloning of the EPO gene, considerable progress has been made in understanding the regulation of EPO gene expression. This has finally led to the identification of a widespread cellular oxygen‐sensing mechanism. Central to this mechanism is the transcription factor complex hypoxia‐inducible factor (HIF)‐1.
The abundance and activity of HIF‐1, a heterodimer of an α‐ and β‐subunit, is predominantly regulated by oxygen‐dependent post‐translational hydroxylation of the α‐subunit. Non‐heme ferrous iron containing hydroxylases use dioxygen and 2‐oxoglutarate to specifically target proline and an asparagine residue in HIF‐1α. As such, the three prolyl hydroxylases (prolyl hydroxylase domain‐containing protein (PHD) 1, PHD2 and PHD3) and the asparagyl hydroxylase (factor inhibiting HIF (FIH)‐1) act as cellular oxygen sensors. In addition to erythropoiesis, HIF‐1 regulates a broad range of physiologically relevant genes involved in angiogenesis, apoptosis, vasomotor control and energy metabolism. Therefore, the HIF system is implicated in the pathophysiology of many human diseases.
In addition to the tight regulation by oxygen tension, temporal and tissue‐specific signals limit expression of the EPO gene primarily to the fetal liver and the adult kidney.
INTRARENAL OXYGENATION IN CHRONIC RENAL FAILURE
Authors: Norman Jill T , Fine Leon G 
Published: September 2006

SUMMARY

In chronic renal failure (CRF), renal impairment correlates with tubulointerstitial fibrosis characterized by inflammation, interstitial expansion with accumulation of extracellular matrix (ECM), tubular atrophy and vascular obliteration. Tubulointerstitial injury subsequent to glomerular sclerosis may be induced by proteinuria, leakage of glomerular filtrate or injury to the post‐glomerular peritubular capillaries (hypoxia).
In vivo data in animal models suggest that CRF is associated with hypoxia, with the decline in renal Po2 preceding ECM accumulation.
Chronic renal failure is characterized by loss of microvascular profiles but, in the absence of microvascular obliteration, hypoxia can occur by a variety of complementary mechanisms, including anaemia, decreased capillary flow, increased vasoconstriction, increased metabolic demand and increased diffusion distances due to ECM deposition.
Hypoxia regulates a wide array of genes, including many fibrogenic factors. Hypoxia‐inducible factors (HIF) are the major, but not the sole, transcriptional regulators in the hypoxic response.
In CRF, hypoxia may play a role in the sustained inflammatory response.
In vitro studies in tubulointerstitial cells suggest that hypoxia can induce profibrogenic changes in proximal tubular epithelial cells and interstitial fibroblasts consistent with changes observed in CRF in vivo. The effect of hypoxia on renal microvascular cells warrants investigation.
Hypoxia may play a role in the recruitment, retention and differentiation of circulating progenitor cells to the kidney contributing to the disease process and may also affect intrinsic stem cell populations.
Chronic hypoxia in CRF fails to induce a sustained angiogenic response.
Therapeutic manipulation of the hypoxic response may be of benefit in slowing progression of CRF. Potential therapies include correction of anaemia, inhibition of the renin–angiotensin system, administration of exogenous pro‐angiogenic factors to protect the microvasculature, activation of HIF and hypoxia‐mediated targeting of engineered progenitor cells.
INTRARENAL OXYGEN AND HYPERTENSION
Authors: Welch William J 
Published: September 2006

SUMMARY

The kidney has a unique environment that results in relatively low tissue oxygen tension (Po2). However, recent studies have shown that renal hypoxia is more severe during hypertension and may reflect changes in the way O2 is used. The present review summarizes studies that explore the relationship between renal oxygen tension (Po2), oxygen consumption and hypertension.
More recent studies suggest that oxidative stress accompanying hypertension, rather than the elevated blood pressure per se reduces Po2. The Po2 in various sections of the kidney often reflects the level of oxygen consumption, which varies depending on the sites of Na+ reabsorption, a process that consumes nearly 90% of total renal oxygen.
The efficient use of oxygen for the transport of Na+ in the kidney is reduced during hypertension, which may contribute to the resulting hypoxia. Conversely, the defect in renal oxygen usage due to oxidative stress may exacerbate hypertension in animal models. The goal of many of these studies is to determine the impact of renal hypoxia in the generation of hypertension.
Shifting discourses of professionalism: a case study of general practitioners in the United Kingdom
Authors: Jones Lorelei , Green Judith 
Published: September 2006

AbstractThis paper addresses shifting constructions of professional identity in the context of debates about reflexive modernisation and the changing role of professionals in the provision of primary healthcare. Data are drawn from interviews with 20 early‐career general practitioners (GPs), who accounted for their orientations towards work in rather different ways from those typically reported in much primary care research. In particular, they reported high job satisfaction and success in achieving what they called ‘nice work’. We argue that these GPs typify a shift in discourses of professionalism, characterised by respondents as the ‘new general practice’, which explicitly rejects many values attributed to ‘traditional’ general practice. Within the ‘new general practice’, professionalism has been de‐coupled from some of the paradigmatic traits of traditional rhetorical accounts (such as vocation), and has significantly reframed others. Despite policy concerns that a retreat from ‘vocational’ professionalism will lead to reductions in service quality, we argue that this is not inevitable. The ‘new general practice’ resonates with the social values of reflexive modernisation, and has the potential to enable new, less paternalistic, forms of relationships with clients, although it remains to be seen whether this potential is realised in healthcare delivery.
BALTHASAR AND GNOSTIC GENEALOGY
Authors: O'REGAN CYRIL 
Published: September 2006

AbstractAgainst the backdrop of Balthasar's recurrence to genealogical labeling of modern discourses that many believe lacks Christian credibility, this essay examines Balthasar's understanding and use of the category of “Gnosticism” to designate modern speculative discourses and the history of their effects. While it is conceded that Balthasar uses “apocalyptic” and “Neoplatonism” to designate the same phenomenon, it is argued that “Gnosticism” is accorded priority. The essay traces the use of both multiple genealogical categories and the relative privileging of “Gnosticism” back to F. C. Baur. At the same time, it also traces back to Baur the essentially narrative criterion for use: Gnosticism is defined by a developmental narrative which has at its center divine pathos. Balthasar, however, inflects this differently than Baur by appeal to Irenaeus's view that the Gnostic metanarrative is a parasitic discourse that disfigures and refigures the biblical narrative. I illustrate how Balthasar is particularly concerned with what he regards as a “Gnostic return” in modern trinitarian thought of a Hegelian vintage. I conclude with some reflections as to how Balthasar's genealogy of Gnosticism could be further developed and conceptually refined.
MORALITY AND POLITICS IN THE WORK OF MICHAEL WYSCHOGROD
Authors: WALZER MICHAEL 
Published: September 2006

AbstractMichael Wyschogrod claims that his arguments proceed from his biblical faith. But many of the (commendable) things that he has to say about politics and morality seem to derive from an autonomous ethics. I give five examples of arguments that cannot, in my reading of them, be drawn out of the relevant (but not definitive) biblical texts. Either the texts don't support the arguments at all, or they require interpretation, or some texts must be chosen above others if the arguments are to stand. Faith in the texts cannot by itself sustain the arguments that Wyschogrod wants to make.
THE INTENSIFICATION OF TIME: MICHAEL WYSCHOGROD AND THE TASK OF CHRISTIAN THEOLOGY
Authors: LOWE WALTER 
Published: September 2006

AbstractIn conversation with Karl Barth, Michael Wyschogrod observes that with God's promises, unlike humans', “if we have [God's] promise, we have its fulfillment”. The essay considers Wyschogrod's implicit intensification of time, which displaces common linear views of time. Wyschogrod charges that Christian understandings of fulfillment imply a completed line of history which is all too luminous. Edwyn Hoskyns's study of John's Gospel suggests an alternative; namely, a Christian intensification of time which finds in Jesus both life and judgment, love and condemnation. Such realized apocalyptic, as it were, confronts readers with a density or relative darkness more consonant with Hebrew scriptural revelation.
Contributing Factors to the Spread of Sexually Transmitted Diseases
Authors: Ressler Rand W. , Waters Melissa S. , Watson John Keith 
Published: September 2006

Abstract.  Economists have long studied the determinants and effects of income transfers. This article examines an indirect effect of welfare payments on participating individuals: an increase in the incidence of sexually transmitted disease (STD) rates.Several studies have found a significant and positive link between the size of welfare benefits and out‐of‐wedlock fertility rates. Higher welfare payments reduce the cost of bearing and raising a child, and thus reduce the full cost of engaging in unprotected sex. An unintended consequence of unprotected sex is exposure to contagious diseases. This implies that states with higher welfare payments per child will experience higher rates of STDs.We test this hypothesis using statewide data on the incidence of three types of bacterial STDs, chlamydia, gonorrhea, and syphilis, for the years 1994 through 1998. The empirical specification is based on the standard microeconomic model of utility‐maximizing behavior. The included explanatory variables are demographic proxies reflecting differences in state population characteristics. These characteristics capture unobservable or intrinsically unmeasureable differences in the perceived costs and benefits of engaging in unprotected sex.The explanatory variable of primary interest is the size of the real welfare payment per recipient. Our empirical results indicate that states with higher real welfare payments are associated with greater rates of STDs.
Anterior cingulate activation in antipsychotic‐naïve first‐episode schizophrenia
Authors: Yücel M. , Brewer W. J. , Harrison B. J. , Fornito A. , O'Keefe G. J. , Olver J. , Scott A. M. , Egan G. F. , Velakoulis D. , McGorry P. D. , Pantelis C. 
Published: September 2006

Objective:  Anterior cingulate (ACC) hypo‐activity is commonly observed in chronically ill schizophrenia patients. However, it is unclear whether this is secondary to persistent illness and/or medication.Method:  We examined eight antipsychotic‐naïve first‐episode patients and matched healthy controls undergoing PET scanning while performing the Stroop task.Results:  Group‐averaged and single‐subject analyses showed ACC activation in both controls and patients, albeit in different sub‐regions (paracingulate and cingulate respectively). A direct comparison revealed relative under‐activity of the left paracingulate cortex in patients.Conclusion:  These findings suggest that the more pervasive hypo‐activation observed in chronic patients may be secondary to persistent illness and/or medication.