bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gastroprotective effects of the insulin sensitizers rosiglitazone and metformin against indomethacin‐induced gastric ulcers in Type 2 diabetic rats
Authors: Morsy Mohamed A , Ashour Osama M , Fouad Amr A , Abdel‐Gaber Seham A 
Published: June 2009

Summary1. Gastric ulcers are common in Type 2 diabetic patients. Of all drugs used in the treatment of Type 2 diabetes, the insulin sensitizers thiazolidinediones (e.g. rosiglitazone) and metformin exhibit additional effects in ameliorating oxidative stress and inflammation, rendering them attractive candidates for the prevention of gastric ulcer in Type 2 diabetes. Thus, the aim of the present study was to evaluate the gastroprotective effects of rosiglitazone and metformin against indomethacin‐induced gastric ulcer in Type 2 diabetic and non‐diabetic rats.2. Diabetes was induced by a single injection of streptozotocin (60 mg/kg, i.p., dissolved in 0.1 mol/L cold citrate buffer, pH 4.5), 15 min after administration of 120 mg/kg, i.p., nicotinamide. Three weeks after the successful induction of diabetes, rats were subjected to pyloric ligation and then injected immediately with 30 mg/kg, i.p., indomethacin. Three hours after indomethacin administration, rats were killed and gastric injury was evaluated. Ranitidine (50 mg/kg) was used as a reference drug and was administered in a single oral dose 1 h before indomethacin injection, as were rosiglitazone (3 mg/kg) and metformin (500 mg/kg).3. Both rosiglitazone and metformin exhibited gastroprotective effects, as evidenced by significant decreases in the ulcer index, free and total acid output in gastric juice and gastric mucosal malondialdehyde concentrations, with concomitant increases in gastric juice pH (only with rosiglitazone), mucin concentrations, gastric mucosal concentrations of nitric oxide and catalase activity compared with untreated diabetic rats. Conversely, rosiglitazone and metformin had no effect on peptic activity and gastric mucosal prostaglandin E2 content, particularly in the diabetic group, compared with the untreated groups.4. In conclusion, rosiglitazone and metformin protect Type 2 diabetic rats against indomethacin‐induced gastric ulceration, most possibly via antisecretory actions, enhanced mucosal protection and anti‐oxidant activity. Rosiglitazone seems to be provide superior gastroprotection to metformin.
Strategies of treating cancer by cytokine regulation of chromosome end remodelling
Authors: Liu Jun‐Ping , Nicholls Craig , Chen Shi‐Ming , Li He , Tao Ze‐Zhang 
Published: June 2009

Summary1. Telomeres (ends of chromosomes) undergo constant remodelling during cell development, proliferation and differentiation, as well as in neoplastic cell immortalization and transformation. How the cellular microenvironment influences telomere remodelling (lengthening or shortening) remains largely unknown.2. Recently, studies from our laboratories and others have indicated that growth factors and cytokines have significant roles in regulating telomere remodelling and thus influence cell functions and properties. Cancer cells must maintain their already short telomeres either by the enzyme telomerase or, more rarely, through alternative lengthening of telomeres, which functions independently of cellular regulation.3. However, application of transforming growth factor‐β family cytokines induces transcriptional inhibition of telomerase in cancer cells, leading to telomere shortening, cell senescence (ageing) and apoptosis (death) by mechanisms dependent on telomerase inhibition. Furthermore, selective gene silencing of vascular endothelial growth factor and/or the telomerase catalytic subunit (i.e. telomerase reverse transcriptase) potently inhibits the growth of cervical cancer and laryngeal squamous cancer in mice.4. The present paper summarizes our current understanding of the negative regulation by cytokines of telomere maintenance and thus cancer cell proliferation in cultured cells and mouse models.
Sympathetic nerves and the progression of chronic kidney disease during 5/6 nephrectomy: Studies in sympathectomized rats
Authors: Augustyniak Robert A , Picken Maria M , Leonard David , Zhou Xin J , Zhang Weiguo , Victor Ronald G 
Published: June 2009

Summary1. Chronically increased sympathetic nerve activity is present during chronic kidney disease (CKD); however, its role in contributing to hypertension or the progression of CKD remains poorly understood. The aim of the present study was to determine whether neonatal sympathectomy attenuates hypertension in 5/6 nephrectomized rats and affects renal structure and function in a blood pressure‐independent manner.2. We performed 5/6 nephrectomy (referred to as CKD) in both sympathetically intact and sympathectomized (injected neonatally with guanethidine; referred to as CKD + Sympath) male Sprague‐Dawley rats. Sham‐operated sympathetically intact and sympathectomized rats (Sham and Sham + Sympath, respectively) were used as controls. Radiotelemetry was used to monitor blood pressure throughout the 6 week duration of the study, after which renal function and histology were assessed.3. Overall average systolic arterial pressure and final urinary protein excretion were significantly lower in CKD + Sympath compared with CKD rats (168 ± 7 mmHg and 33 ± 5 mg/24 h vs. 184 ± 6 mmHg and 66 ± 7 mg/24 h, respectively). However, the level of proteinuria in the CKD + Sympath group was reduced to a greater extent than what would be expected solely on the basis of lower blood pressure. All other indices of renal function and histology were comparable between both CKD groups. All measurements were comparable between Sham and Sham + Sympath groups.4. In conclusion, sympathectomy attenuated hypertension by approximately one‐third in 5/6 nephrectomized rats. Furthermore, sympathetic nerves to the kidney during 5/6 nephrectomy may contribute to proteinuria in a blood pressure‐independent manner.
Rhythm of digestion: keeping time in the gastrointestinal tract
Authors: Bron Romke , Furness John B 
Published: June 2009

Summary1. The best characterized mammalian circadian rhythms follow a light‐entrained central master pacemaker in the suprachiasmatic nucleus and are associated with fluctuations in the activities of clock genes, including Clock, Bmal1, Per and Cry, the products of which bind to sequences in the promoters of effector genes. This is the central clock.2. In the present review, we discuss evidence for an independent, but interacting, gut‐associated circadian clock, the peripheral clock, which is entrained by food.3. Disruption of circadian rhythms is associated with a wide range of pathologies, most prominently metabolism linked, but the effects of disruption of circadian rhythms on the digestive system are less well studied, although also likely to lead to functional consequences. There are clues suggestive of links between gastrointestinal disorders related to inflammation, cancer and motility and disruption of peripheral rhythms. Research aimed at understanding these links is still in its infancy.4. We also discuss practical aspects of the presence of circadian rhythms in gastrointestinal tissues for researchers related to experimental design, data interpretation and the choice of animal models.5. There is currently sufficient evidence to suggest that circadian rhythms are important to gut function, metabolism and mucosal defence and that further investigation will uncover connections between disordered rhythms and gastrointestinal malfunction.
Effect of 17β‐oestradiol replacement on vascular responsiveness in ovariectomized diabetic rats
Authors: Ceylan‐Isik Asli F , Erdogan‐Tulmac Ozlem B , Ari Nuray , Ozansoy Gulgun , Ren Jun 
Published: June 2009

Summary1. Women with functional ovaries exhibit a gender advantage in terms of the prevalence of cardiovascular diseases. However, whether this gender bias pertains in diabetes is unknown.2. The aim of the present study was to examine the effects of 17β‐oestradiol (E2) on vascular responsiveness in normal and diabetic ovariectomized (OVX) rats. Aged‐matched female rats were divided into four groups as follows: (i) OVX; (ii) OVX + E2 treated; (iii) diabetic OVX; and (iv) diabetic OVX + E2 treated. Bilateral ovariectomy was performed and streptozotocin was used to induce experimental diabetes. Rats were treated with 1 mg/kg per day, p.o., E2 for 8 weeks.3. Although E2 treatment had no effect on blood glucose levels in normal and diabetic OVX rats, it significantly reduced systolic blood pressure and prevented diabetes‐induced loss of bodyweight gain.4. In segments of the thoracic aorta, concentration‐dependent vasoconstrictor responses to KCl and phenylephrine were significantly attenuated following E2 treatment in both the normal and diabetic groups. The sarcoplasmic/endoplasmic reticulum calcium ATPase inhibitor thapsigargin (10−6 mol/L) and the Ca2+ channel blocker nifedipine (10−6 mol/L) inhibited the transient vasoconstriction to PE in all groups. The constrictor effect of PE was increased by the nitric oxide synthase inhibitor NG‐nitro‐l‐arginine methyl ester (l‐NAME; 10−6 mol/L), but was reduced by superoxide dismutase (SOD; 100 U/mL) and the cyclo‐oxygenase inhibitor indomethacin (10−6 mol/L) in all groups. Responses to acetylcholine (ACh; 10−6 mol/L) demonstrated reduced endothelium‐dependent relaxation in non‐E2‐treated groups. Relaxation responses to ACh were increased by 100 U/mL SOD and 10−6 mol/L indomethacin, but were reduced by 10−6 mol/L l‐NAME in all groups. There were no differences among the four groups in terms of relaxation responses to sodium nitroprusside (10−11 to 10−6 mol/L).5. In conclusion, the results of the present study suggest that oestrogen treatment has beneficial effects on vascular function in both diabetic and non‐diabetic OVX rats due to Ca2+ regulation and anti‐oxidation.
Purinergic regulation of the epithelial Na+channel
Authors: O’Mullane Lauren M , Cook David I , Dinudom Anuwat 
Published: June 2009

Summary1. The epithelial Na+channel (ENaC) is a major conductive pathway that transports Na+across the apical membrane of the distal nephron, the respiratory tract, the distal colon and the ducts of exocrine glands. The ENaC is regulated by hormonal and humoral factors, including extracellular nucleotides that are available from the epithelial cells themselves.2. Extracellular nucleotides, via the P2Y2 receptors (P2Y2Rs) at the basolateral and apical membrane of the epithelia, trigger signalling systems that inhibit the activity of the ENaC and activate Ca2+‐dependent Cl−secretion.3. Recent data from our laboratory suggest that stimulation of the P2Y2Rs at the basolateral membrane inhibits ENaC activity by a signalling mechanism that involves Gβγ subunits freed from a pertussis toxin (PTX)‐sensitive G‐protein and phospholipase C (PLC) β4. A similar signalling mechanism is also partially responsible for inhibition of the ENaC during activation of apical P2Y2Rs.4. Stimulation of apical P2Y2Rs also activates an additional signalling mechanism that inhibits the ENaC and involves the activated Gα subunit of a PTX‐insensitive G‐protein and activation of an unidentified PLC. The effect of this PTX‐insensitive system requires the activity of the basolateral Na+/K+/2Cl−cotransporter.
Evidence for the adaptive significance of circadian rhythms
Authors: Yerushalmi Shai , Green Rachel M. 
Published: June 2009

AbstractCircadian (∼24 h) clock regulated biological rhythms have been identified in a wide range of organisms from prokaryotic unicellular cyanobacteria to higher mammals. These rhythms regulate an enormous variety of processes including gene expression, metabolic processes, activity and reproduction. Given the widespread occurrence of circadian systems it is not surprising that extensive efforts have been directed at understanding the adaptive significance of circadian rhythms. In this review we discuss the approaches and findings that have resulted. In studies on organisms in their natural environments, some species show adaptations in their circadian systems that correlate with living at different latitudes, such as clines in circadian clock properties. Additionally, some species show plasticity in their circadian systems suggested to match the demands of their physical and social environment. A number of experiments, both in the field and in the laboratory, have examined the effects of having a circadian system that does not resonate with the organism’s environment. We conclude that the results of these studies suggest that having a circadian system that matches the oscillating environment is adaptive.
The role of landmarks and boundaries in the development of spatial memory
Authors: Bullens Jessie , Nardini Marko , Doeller Christian F. , Braddick Oliver , Postma Albert , Burgess Neil 
Published: June 2009

AbstractIt has been suggested that learning an object’s location relative to (1) intramaze landmarks and (2) local boundaries is supported by parallel striatal and hippocampal systems, both of which rely upon input from a third system for orientation. However, little is known about the developmental trajectories of these systems’ contributions to spatial learning. The present study tested 5‐ and 7‐year‐old children and adults on a water maze‐like task in which all three types of cue were available. Participants had to remember the location of an object hidden in a circular bounded environment containing a moveable intramaze landmark and surrounded by distal cues. Children performed less accurately than adults, and showed a different pattern of error. While adults relied most on the stable cue provided by the boundary, children relied on both landmark and boundary cues similarly, suggesting a developmental increase in the weighting given to boundary cues. Further, adults were most accurate in coding angular information (dependent on distal cues), whereas children were most accurate in coding distance, suggesting a developing ability to use distal cues to orient. These results indicate that children as young as 5 years use boundary, intramaze landmark, and distal visual cues in parallel, but that the basic accuracy and relative weighting of these cues changes during subsequent development.
Evidence for intact memory‐guided attention in school‐aged children
Authors: Dixon Matthew L. , Zelazo Philip David , De Rosa Eve 
Published: June 2009

AbstractVisual scenes contain many statistical regularities such as the likely identity and location of objects that are present; with experience, such regularities can be encoded and can ultimately facilitate the deployment of spatial attention to important locations. Memory‐guided attention has been extensively examined in adults with the ‘contextual cueing’ paradigm and has been linked to specific neural substrates – a medial temporal lobe (MTL)‐frontoparietal network. However, it currently remains unknown when this ability comes ‘online’ during development. Thus, we examined the performance of school‐aged children on an age‐appropriate version of the contextual cueing paradigm. Children searched for a target fish among distractor fish in new displays and in ‘old’ displays on a touchscreen computer. Old displays repeated across blocks of trials and thus provided an opportunity for prior experience with the invariant configuration of the stimuli to guide attentional deployment. We found that over time children searched old displays significantly faster than new displays, thus revealing intact memory‐guided attention and presumed function of an MTL‐frontoparietal network in 5‐ to 9‐year‐olds. More generally, our findings suggest that children are remarkably sensitive to the inherent structure of their visual environment and this enables attentional deployment to become more efficient with experience.
Time, space and structure in an e‐learning and e‐mentoring project
Authors: Loureiro‐Koechlin Cecilia , Allan Barbara 
Published: June 2009

AbstractThis study focuses on a project, EMPATHY Net‐Works, which developed a learning community as a means of encouraging women to progress into employment and management positions in the logistics and supply chain industries (LaSCI). Learning activities were organised in the form of a taught module containing face‐to‐face and online elements and e‐mentoring with successful professional women in the LaSCI. In this particular research, we have used structuration theory, a social theory that concentrates on the relationships between human agency (micro‐level) and social structures (macro‐level). We used structuration as an analytical tool to help us understand what happened within the project e‐learning and e‐mentoring processes. Our analysis suggests that there were two factors that influenced the way project participants carried out their learning activities: the first one being the issue of absence and presence in online environments, and the second one the issue of time frame changes for online users.
Project management in instructional design: ADDIE is not enough
Authors: Van Rooij Shahron Williams 
Published: June 2009

AbstractIn the digital age, instructional designers must possess both a sound instructional design knowledge base and solid project management skills that will enable them to complete courseware projects on time, on budget and in conformance with client expectations. Project management skills include the ability to apply repeatable processes, along with interpersonal skills such as communication and leadership skills. However, courses in project management are often absent from the higher education instructional design curriculum, creating a gap between what is learned in instructional design programmes and real‐world practice. In this paper, the author draws on the education and project management fields to examine this gap. The author argues that the gap between instructional design project management models and how instructional design practitioners view project management is a consequence of the divergent perspectives of higher education subcultures and the extent to which those subcultures are likely to embrace cross‐disciplinary subjects such as project management. The author proposes some research and advocacy opportunities for closing the gap between instructional design education and practice.
Botulinum toxin B increases mouth opening in patients with spastic trismus
Authors: Fietzek U. M. , Kossmehl P. , Barthels A. , Ebersbach G. , Zynda B. , Wissel J. 
Published: June 2009

Background:  Severe generalized spastic movement disorders of various aetiologies often involve the jaw muscles and lead to a spastic trismus with masseter muscle hypertonia. We report a placebo‐controlled randomized study on patients with spastic trismus.Methods:  Eleven patients with masseter hypertonia because of stroke, hypoxic encephalopathy or traumatic brain injury were allocated to either botulinum toxin serotype B (BoNT/B) injections into the masseter muscles or placebo treatment. The dental gap, the amount of saliva, salivation scales, and a clinical goal attainment were evaluated.Results:  Three weeks after injection the BoNT/B group showed a significantly increased mouth opening compared with placebo treatment (P < 0.05). In addition to the muscle paralysing effect, a goal attainment scale demonstrated a clinical benefit for the BoNT/B group (P < 0.01).Conclusions:  Botulinum toxin serotype B injections into the masseter muscles effectively reduce hypertonia and provide for better mouth opening, thereby contributing to a positive and desired clinical goal.
Novel non‐sense GCH1 mutation in a South African family diagnosed with dopa‐responsive dystonia
Authors: Bardien S. , Keyser R. , Lombard D. , Du Plessis M. , Human H. , Carr J. 
Published: June 2009

Background:  Dopa‐responsive dystonia (DRD), a movement disorder characterized by onset in early childhood and a dramatic response to low doses of levodopa, has been shown to be caused by a number of different mutations in the GCH1 gene.Methods:  We identified a South African family which presented with DRD in three family members. Polymerase chain reaction (PCR) primers were designed to span all six exons of GCH1 and the PCR products were screened for pathogenic mutations using direct sequencing.Results:  A novel non‐sense mutation (c.233delT; p.I78fsX79) was identified in the DRD patients, which would produce a markedly truncated protein of only 78 amino acids. This mutation was also present in a number of asymptomatic family members.Conclusions:  A novel non‐sense mutation in the GCH1 gene can be associated with DRD and reduced penetrance in South African patients.
An exploration of anger phenomenology in multiple sclerosis
Authors: Nocentini U. , Tedeschi G. , Migliaccio R. , Dinacci D. , Lavorgna L. , Bonavita S. , Bresciamorra V. , Comanducci G. , Coniglio G. , Livrea P. , Mannu R. , Orefice G. , Paciello M. , Patti F. , Quattrone A. , Salemi G. , Savettieri G. , Simone I.L. , Valentino P. , Zappia M. , Bonavita V. , Musicco M. , Caltagirone C. 
Published: June 2009

Background and purpose:  Multiple sclerosis (MS) patients are often emotionally disturbed. We investigated anger in these patients in relation to demographic, clinical, and mood characteristics.Patients and methods:  About 195 cognitively unimpaired MS patients (150 relapsing–remitting and 45 progressive) were evaluated with the State Trait Anger Expression Inventory, the Chicago Multiscale Depression Inventory, and the State Trait Anxiety Inventory. The patients’ anger score distribution was compared with that of the normal Italian population. Correlation coefficients among scale scores were calculated and mean anger scores were compared across different groups of patients by analysis of variance.Results:  Of the five different aspects of anger, levels of withheld and controlled Anger were respectively higher and lower than what is expected in the normal population. Although anger was correlated with anxiety and depression, it was largely independent from these mood conditions. Mean anger severity scores were not strongly influenced by individual demographic characteristics and were not higher in more severe patients.Conclusions:  The presence of an altered pattern of anger, unrelated to the clinical severity of MS, suggests that anger is not an emotional reaction to disease stress. An alteration of anger mechanisms might be a direct consequence of the demyelination of the connections among the amygdale, the basal ganglia and the medial prefrontal cortex.
Serum VEGF levels in acute ischaemic strokes are correlated with long‐term prognosis
Authors: Lee S.‐C. , Lee K.‐Y. , Kim Y.‐J. , Kim S. H. , Koh S.‐H. , Lee Y. J. 
Published: June 2009

Background and purpose:  We investigated whether serum vascular endothelial growth factor (VEGF) levels in acute‐stage ischaemic stroke patients with small vessel disease (SVD) or large vessel disease (LVD) are correlated with long‐term prognoses, based on the difference in NIH Stroke Scale (NIHSS) scores between acute and chronic stages.Methods:  From March 2007 to May 2008, we evaluated patients who experienced an ischaemic stroke for the first time, defined as SVD (n = 89) or LVD (n = 91) using the TOAST classification. Serum samples were taken immediately after admission (within 24 h of stroke onset) to evaluate VEGF levels. After 3 months, follow‐up NIHSS scores were collected for all patients.Results:  Serum VEGF levels in the acute stage (within 24 h of stroke onset) were higher in the LVD group than in the SVD group and were correlated with infarction volume. The increase in serum VEGF levels in the acute stage was proportional to an improved NIHSS score after 3 months. After adjustment for covariates, serum VEGF levels in the acute stage were still significantly correlated with the long‐term prognosis of ischaemic stroke.Conclusion:  Serum VEGF levels are correlated with long‐term prognoses in acute ischaemic stroke patients.