bluuebunny/crossref_metadata_2025_split huggingface dataset:
Products of advanced glycation in patients with type 2 diabetes and vascular disease
Authors: Turk Z , S̆esto M , Skodlar J , Ferenc̆ak G , Pokupec R , Turk N , Stavljenicć-Rukavina A 
Published: September 2003

Background: Non-enzymatic glycation leading to advanced glycation endproduct (AGE) formation is thought to contribute to vascular pathology. In the present study, AGEs and anti-AGE antibodies in free and immune complex-bound form were assayed in the serum of diabetic (DMCAD) ( n = 69) and nondiabetic ( n = 78) patients with coronary artery disease (CAD) and in control subjects ( n = 47) free from vascular disease. Methods: A blocking enzyme-linked immunosorbent assay (ELISA) was used to test immunoreactivity against AGE epitope(s) and a competitive ELISA was used to measure total AGE content. Results: Anti-AGE immunoreactivity was significantly higher in diabetic than in control subjects ( P = 0.045). Although a wide range of anti-AGE antibody titres were observed in nondiabetic CAD patients, there was no significant difference from those of control subjects. Both diabetic and nondiabetic CAD patients had a higher concentration of circulating immune complexes containing the AGE moiety as antigen than did control subjects (DMCAD versus control, P = 0.041; CAD versus control, P = 0.047). Study patients showed a positive correlation between serum AGE and AGE-immune complexes (DM, r = 0.29, P = 0.014; CAD, r = 0.26, P = 0.019), whereas no such correlation was recorded in controls ( r = 0.08, P = 0.89). Conclusion: To our knowledge, this is the first study demonstrating increased AGE-immune complexes in patients with CAD, either with or without diabetes, suggesting that AGE-immune complexes might be involved in the atherosclerotic process, either as the result of it or as part of the pathophysiologic process.
Elevated results in a vitamin B12 assay when using serum separator blood collection tubes
Authors: Lowrey I , Smith G 
Published: September 2003

Background: In the light of apparently spurious serum vitamin B12 results in some patients, the effect of serum separator sample tubes on serum vitamin B12 values, assayed by the Bayer Centaur analyser, was examined. Method: Results of parallel assays of serum vitamin B12 in plain (non-gel) serum tubes and serum separator gel tubes were compared. Serum in previously centrifuged gel tubes was mixed in the tube and the effect of that mixing on assay results quantitated. A limited investigation of the effect of tube cap type was also carried out. Results: Serum vitamin B12 concentration was 54% higher in samples taken into serum separator tubes after re-mixing the serum in the original tube. This effect could be abolished by re-centrifugation. Conclusions: Use of serum separator tubes may be associated with spuriously elevated serum vitamin B12 concentrations in the Bayer Centaur assay. Laboratories receiving samples for vitamin B12 assay in serum separator tubes that have already been centrifuged should either re-centrifuge the tubes, or aliquot and re-centrifuge serum from the tubes prior to vitamin B12 assay.
Insulin‐like growth factor‐I increases astrocyte intercellular gap junctional communication and connexin43 expression in vitro
Authors: Åberg N. David , Blomstrand Fredrik , Åberg Maria A.I. , Björklund Ulrika , Carlsson Björn , Carlsson‐Skwirut Christine , Bang Peter , Rönnbäck Lars , Eriksson Peter S. 
Published: September 2003

AbstractConnexin43 (cx43) forms gap junctions in astrocytes, and these gap junctions mediate intercellular communication by providing transport of low‐molecular‐weight metabolites and ions. We have recently shown that systemic growth hormone increases cx43 in the brain. One possibility was that local brain insulin‐like growth factor‐I (IGF‐I) could mediate the effect by acting directly on astrocytes. In the present study, we examined the effects of direct application of recombinant human IGF‐I (rhIGF‐I) on astrocytes in primary culture concerning cx43 protein expression and gap junctional communication (GJC). After 24 hr of stimulation with rhIGF‐I under serum‐free conditions, the GJC and cx43 protein were analyzed. Administration of 30 ng/ml rhIGF‐I increased the GJC and the abundance of cx43 protein. Cell proliferation of the astrocytes was not significantly increased by rhIGF‐I at this concentration. However, a higher concentration of rhIGF‐I (150 ng/ml) had no effect on GJC/cx43 but increased cell proliferation. Because of the important modulatory role of IGF binding proteins (IGFBPs) on IGF‐I action, we analyzed IGFBPs in conditioned media. In cultures with a low abundance of IGFBPs (especially IGFBP‐2), the GJC response to 30 ng/ml rhIGF‐I was 81%, compared with the average of 25%. Finally, as a control, insulin was given in equimolar concentrations. However, GJC was not affected, which suggests that rhIGF‐I acted via IGF‐I receptors. In summary, the data show that rhIGF‐I may increase GJC/cx43, whereas a higher concentration of rhIGF‐I—at which stimulation of proliferation occurred—did not affect GJC/cx43. Furthermore, IGFBP‐2 appeared to modulate the action of rhIGF‐I on GJC in astrocytes by a paracrine mechanism. © 2003 Wiley‐Liss, Inc.
Fluorocitrate‐mediated astroglial dysfunction causes seizures
Authors: Willoughby John O. , Mackenzie Lorraine , Broberg Marita , Thoren Anna E. , Medvedev Andrei , Sims Neil R. , Nilsson Michael 
Published: September 2003

AbstractA role for astroglia in epileptogenesis has been hypothesised but is not established. Low doses of fluorocitrate specifically and reversibly disrupt astroglial metabolism by blocking aconitase, an enzyme integral to the tricarboxylic acid cycle. We used cerebral cortex injections of fluorocitrate, at a dose that we demonstrated to inhibit astroglial metabolism selectively, to determine whether astroglial disturbances lead to seizures. Rats were halothane‐anesthetized, and 0.8 nmol of sodium fluorocitrate was injected into the cerebral cortex. Extradural electroencephalogram (EEG) electrodes were implanted, after which the anesthesia was ceased and the animals were observed. In all experiments, 14 of 15 fluorocitrate‐treated animals exhibited epileptiform EEG discharges, with some animals exhibiting convulsive seizures. Discharges commenced as early as 30 min postfluorocitrate injection. Intraperitoneal octanol, but not halothane by inhalation, given to test the possible participation of gap junctions in EEG discharge generation, blocked or delayed the occurrence of discharges after fluorocitrate. These results indicate that focal cerebrocortical astroglial dysfunction leads to focal epileptiform discharges and sometimes to convulsive seizures and that the process possibly depends on effects mediated by gap junctions. © 2003 Wiley‐Liss, Inc.
Intrapartum chlorhexidine vaginal irrigation and chorioamnion and placental microbial colonization
Authors: Rouse D.J. , Lincoln T. , Cliver S. , Lyon M.D. , Andrews W.W. , Hauth J.C. 
Published: September 2003

AbstractObjectives: To determine whether intrapartum chlorhexidine vaginal irrigation reduces microbial colonization of the chorioamnion or placenta. Methods: Secondary analysis was made of a randomized trial. Cultures for aerobic and anaerobic bacteria, Mycoplasma species and Ureaplasma urealyticum were performed using standard isolation techniques. Results: The placentas of 83 trial participants allocated to chlorhexidine and 93 allocated to placebo underwent evaluation. These two groups were statistically balanced for risk factors for infection. Aerobic bacteria were isolated from 47% of the chlorhexidine placentas vs. 51% of the placebo placentas (relative risk 0.9, 95% confidence interval 0.7–1.3), anaerobic bacteria from 30% and 35%, respectively (0.8, 0.5–1.3), group B streptococcus from 12% and 15% (0.8, 0.4–1.7), U. urealyticum from 18% and 29% (0.6, 0.4–1.1), Mycoplasma species from 6% and 11% (0.6, 0.2–1.6), and any organism from 57% and 67%, respectively (0.8, 0.7–1.1). Conclusions: Intrapartum chlorhexidine vaginal irrigation was associated with non‐significant reductions in the rates of placental microbial isolation.
Use of Patient Satisfaction Data in a Continuous Quality Improvement Program for Endoscopic Sinus Surgery
Authors: Tai Chih‐Jaan , Chu Chia‐Chen , Liang Shu‐Cheng , Lin Ting‐Fu , Huang Zu‐Jin , Tsai Yao‐Han , Wang Pa‐Chun 
Published: September 2003

OBJECTIVEContinuous quality improvement (CQI) is an effort by health care providers to improve the quality of service by continuously exceeding patients' expectations. Patient satisfaction is one of the measures of the quality of care. The aims of this study were to report the patients' evaluation of endoscopic sinus surgery (ESS) and to explore the feasibility in using patient satisfaction data in the CQI program for ESS.METHODSEighty‐three patients completed a validated patient satisfaction survey (PSS) 1 month after undergoing ESS. Logistic regression models were applied to determine the confounders of patient satisfaction.RESULTSIn general, 72% of patients were very satisfied with the services. Education level and milder disease correlated with higher overall satisfaction levels (P ≤ 0.01). Anesthesia, the addition of nasal septal surgery, intranasal packing, and postoperative sinuscopy had significant impacts on patient satisfaction (P < 0.05).CONCLUSIONESS is a good technique to evaluate for implementing efforts in quality improvement. Confounding factors need to be adjusted before patient satisfaction data can be used in a CQI program.
Dispositional anxiety and the experience of pain: gender‐specific effects
Authors: Jones Allan , Zachariae Robert , Arendt‐Nielsen Lars 
Published: September 2003

AbstractAim of Investigation: Increased anxiety is believed to correlate with increased pain sensitivity in men and women. However, one laboratory‐based study and one clinical‐based study have offered evidence to suggest that the effect of anxiety in modulating pain sensitivity is specific to men only. The aim of the present study was to examine further whether anxiety differentially effects men and women's report of experimentally induced pain.Methods: One hundred forty‐four healthy university students (75 women, 69 men) were exposed to a contact heat pain procedure (ascending method of limits procedure, baseline temperature 30 °C, ±0.2 °C, rate of change 2.0 °C/s, cut‐off limit 52 °C) and a cold pressor pain procedure (constant temperature +1 °C; ±1 °C, cut‐off limit 240 s).Results: The results agreed with the previous two studies indicating a sex‐specific effect of anxiety on pain report. Male participants scoring above the median on the Trait Anxiety Inventory reported significantly greater pain intensity, unpleasantness and showed lower pain tolerance compared to males scoring below the median on the cold pressor pain procedure, while no such differences in cold pressor pain report were found between high and low anxious women. No effect of anxiety was found on measures taken from the contact heat pain procedure, indicating that the sex‐specific effect of anxiety on laboratory induced pain is dependent upon the method of stimulation used.Conclusion: Anxiety is an important factor when considering gender differences in pain perception and warrants further investigation.
Personalized pain words and Stroop interference in chronic pain patients
Authors: Andersson Gerhard , Haldrup Deborah 
Published: September 2003

AbstractAttentional bias in patients with chronic pain was investigated using the emotional Stroop task with personalized pain words. A group of 20 chronic pain patients with 20 matched controls participated in the experiment. Before administration of the emotional Stroop patients were asked to select the five best descriptors of their pain from a list of 19 sensory pain descriptors. These words were later used in the computerized Stroop test. Also included in the Stroop task were threat words and color words with corresponding control conditions. Apart from the emotional Stroop, measures of pain related distress, anxiety, and depression symptoms were included. Results showed a weak Stroop interference effect with slower reaction times to pain words in the patient group, but they did not differ significantly from the controls. Both groups were slower on the threat words and displayed the classical Stroop interference effect for color words. The overall pattern of results are in line with previous Stroop studies on pain patients showing weak support for the attentional bias hypothesis.
Effect of rifampicin on the pharmacokinetics and pharmacodynamics of nateglinide in healthy subjects
Authors: Niemi Mikko , Backman Janne T. , Neuvonen Mikko , Neuvonen Pertti J. 
Published: September 2003

Aims  Our aim was to investigate the effects of rifampicin on the pharmacokinetics and pharmacodynamics of nateglinide, a novel short‐acting antidiabetic drug.Methods  In a randomized crossover study with two phases, 10 healthy volunteers took 600 mg rifampicin or placebo orally once daily for 5 days. On day 6 of both phases, they ingested a single 60 mg dose of nateglinide. Plasma nateglinide and blood glucose concentrations were measured for up to 7 h postdose.Results   Rifampicin decreased the mean AUC(0,7 h) of nateglinide by 24% (range 5–53%; P = 0.0009) and shortened its half‐life (t1/2) from 1.6 to 1.3 h (P = 0.001). However, the peak plasma nateglinide concentration (Cmax) remained unchanged. The AUC(0,7 h) of the M7 metabolite of nateglinide was decreased by 19% (P = 0.002) and its t1/2 was shortened from 2.1 to 1.6 h by rifampicin (P = 0.008). Rifampicin had no significant effect on the blood glucose‐lowering effect of nateglinide.Conclusions   Rifampicin modestly decreased the plasma concentrations of nateglinide probably by inducing its oxidative biotransformation. In some patients, rifampicin may reduce the blood glucose‐lowering effect of nateglinide.
Population pharmacokinetics of liposomal daunorubicin in children
Authors: Hempel Georg , Reinhardt Dirk , Creutzig Ursula , Boos Joachim 
Published: September 2003

Aims  To investigate the population pharmacokinetics of daunorubicin in children after administration of liposomal daunorubicin (Daunoxome®).Methods   Plasma samples from 19 children with relapsed acute myeloic leukaemia and five children with other malignancies were collected. Daunoxome® was administered as a 1‐ to 2.5 h infusion with doses ranging from 30 to 60 mg m−2. Overall, 214 samples were analysed for daunorubicin using capillary electrophoresis, and population pharmacokinetic modelling was performed using NONMEM.Results   The data were best described by a one compartment model. Inclusion of interoccasion variability in the model (16.7% for clearance) improved strongly the precision of the estimates. The inclusion of body surface area or height as a covariate decreased interindividual variability. However, the best fit was obtained using the absolute dose, and when weight was included as a covariate for clearance (CL) and volume of distribution (V ). The final parameter estimates were: CL 6.41 ml h−1 kg−1± 0.5 51% and V 65.4 ml kg−1 ± 0.5 27% (population mean ± 0.5 interindividual variability). The area under the curve at a dose of 60 mg m−2 was 231 mg l −1h.Conclusions   In comparison with free daunorubicin, Daunoxome® shows a low volume of distribution, a lower clearance and a lower interindividual variability in these parameters. This might be advantageous in reducing the variability in exposure to the drug.
Twenty‐four‐hour activity and consistency of activity of levocetirizine and desloratadine in the skin
Authors: Purohit Ashok , Melac Michel , Pauli Gabrielle , Frossard Nelly 
Published: September 2003

Aim  Levocetirizine, the active enantiomer of cetirizine, and desloratadine, the active metabolite of loratadine, are two recently introduced anti‐H1 agents. We set out to compare their antihistaminic activity in the skin for 24 h in a double‐blind, randomized cross‐over trial.Methods  The skin reaction to histamine administered by prick tests (100 mg ml−1) was measured by the surface areas of weals and flares for 24 h [before treatment, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 h after a single dose of levocetirizine (5 mg), desloratadine (5 mg) or placebo] in 18 healthy volunteers (34.8 ± 9.4 years; 14 women). The areas under the curves (AUC) of the weal and flare areas as a function of time were compared by anova.Results  A highly significant overall treatment effect (P < 0.0001) was observed and both weals and flares were inhibited. The pairwise comparisons showed that the activity of levocetirizine and desloratadine was significantly superior to that of placebo (P < 0.0001), and the activity of levocetirizine was significantly superior to that of desloratadine (P < 0.0001). ‘Total’ weal inhibition (≥ 95%) occurred only with levocetirizine. Median values of maximal weal inhibition were 44.2% with placebo, 55.0% with desloratadine and 100% with levocetirizine. The time to maximal weal inhibition was 4 h (median value) for all three study drugs, but scattered over a wider range for desloratadine (3–24 h) than levocetirizine (2–4 h). With desloratadine, five of 18 (28%) subjects reached weal inhibition of at least 70% at between 3 and 10 h, whereas with levocetirizine all subjects [18/18 (100%)] reached this level of weal inhibition at between 1 and 3 h. The median duration of 70% weal inhibition was zero with placebo and desloratadine, and was 21.4 h with levocetirizine (P < 0.0001 between the three study drugs, and P < 0.0001 between the two active drugs). No uncommon adverse events were reported, and no subject withdrew from the study due to an adverse event.Conclusion  This study shows that the activity of levocetirizine in suppressing skin reactivity to histamine was clearly superior to that of desloratadine for 24 h after a single dose. In addition, its activity was more consistent and lasted longer.
Determinants of trapping block of N‐methyl‐d‐aspartate receptor channels
Authors: Bolshakov K. V. , Gmiro V. E. , Tikhonov D. B. , Magazanik L. G. 
Published: September 2003

AbstractOpen channel blockers of NMDA receptors interact with the channel gate in different ways. Compounds like MK‐801 and phencyclidine exhibit pronounced trapping block, whereas 9‐aminoacridine and tetrapentylammonium cannot be trapped. Some blockers such as memantine and amantadine exhibit intermediate properties, so called ‘partial trapping’. To analyze the determinants of trapping we have synthesized a series of mono‐ and dicationic derivatives of phenylcyclohexyl. The blocking action of these compounds as well as that of amantadine has been studied on native NMDA receptors of hippocampal pyramidal neurons. Use‐dependence and kinetics of the blockade have been analyzed to estimate the degree of trapping. Dimensions of the blocking molecules apparently do not correlate with their trapping. However, the degree of trapping is voltage‐dependent and correlates with the kinetics of unblock. For instance, amantadine behaved as non‐trapping blocker at positive voltages, but demonstrated significant trapping at negative voltages. The data may be explained by the model in which the NMDA receptor channel has two binding sites: the shallow and deep ones. Binding to the deep but not to the shallow site allows trapping of the blockers.
Hydroxyurea transport across the blood–brain and blood–cerebrospinal fluid barriers of the guinea‐pig
Authors: Dogruel M. , Gibbs J. E. , Thomas S. A. 
Published: September 2003

AbstractHydroxyurea is used in the treatment of HIV infection in combination with nucleoside analogues, 2′3′‐didehydro‐3′deoxythymidine (D4T), 2′3′‐dideoxyinosine or abacavir. It is distributed into human CSF and is transported from the CSF to sub‐ependymal brain sites, but its movement into the brain directly from the blood has not been studied. This study addressed this by a brain perfusion technique in anaesthetized guinea‐pigs. The carotid arteries were perfused with an artificial plasma containing [14C]hydroxyurea (1.6 μm) and a vascular marker, [3H]mannitol (4.6 nm). Brain uptake of [14C]hydroxyurea (8.0 ± 0.9%) was greater than [3H]mannitol (2.4 ± 0.2%; 20‐min perfusion, n = 8). CSF uptake of [14C]hydroxyurea (5.6 ± 1.5%) was also greater than [3H]mannitol (0.9 ± 0.3%; n = 4). Brain uptake of [14C]hydroxyurea was increased by 200 μm hydroxyurea, 90 μm D4T, 350 μm probenecid, 25 μm digoxin, but not by 120 μm hydroxyurea, 16.5–50 μm D4T, 90 μm 2′3′‐dideoxyinosine or 90 μm abacavir. [14C]Hydroxyurea distribution to the CSF, choroid plexus and pituitary gland remained unaffected by all these drugs. The metabolic half‐life of hydroxyurea was > 15 h in brain and plasma. Results indicate that intact hydroxyurea can cross the brain barriers, but is removed from the brain by probenecid‐ and digoxin‐sensitive transport mechanisms at the blood–brain barrier, which are also affected by D4T. These sensitivities implicate an organic anion transporter (probably organic anion transporting polypeptide 2) and possibly p‐glycoprotein in the brain distribution of hydroxyurea and D4T.
Attenuated 5‐HT1A receptor signaling in brains of suicide victims: involvement of adenylyl cyclase, phosphatidylinositol 3‐kinase, Akt and mitogen‐activated protein kinase
Authors: Hsiung Shu‐chi , Adlersberg Mella , Arango Victoria , Mann J. John , Tamir Hadassah , Liu Kuo‐peing 
Published: September 2003

AbstractPositron emission tomography studies in major depression show reduced serotonin (5‐HT)1A receptor antagonist‐binding potentials in many brain regions including occipital cortex. The functional meaning of this observation in terms of signal transduction is unknown. We used postmortem brain samples from depressed suicide victims to examine the downstream effectors of 5‐HT1A receptor activation. The diagnosis was established by means of psychological autopsy using Diagnostic and Statistical Manual of Mental Disorders (DSM) III‐R criteria. Measurements of [35S]GTPγS binding to Gαi/o in the occipital cortex of suicide victims and matched controls revealed a blunted response in suicide subjects and a decrease in the coupling of 5‐HT1A receptor to adenylyl cyclase. No significant group differences were detected in the expression levels of Gαi/o, Gαq/11 or Gαs proteins, or in the activity of cAMP‐dependent protein kinase A. Studies of a parallel transduction pathway downstream from 5‐HT1A receptor activation demonstrated a decrease in the activity of phosphatidylinositol 3‐kinase and its downstream effector Akt, as well as an increase in PTEN (phosphatase and tensin homolog deleted on chromosome 10), the phosphatase that hydrolyzes phosphatidylinositol 3,4,5‐triphosphate. Finally, the activation of extracellular signal‐regulated kinases 1 and 2 was attenuated in suicide victims. These data suggest that the alterations in agonist‐stimulated 5‐HT1A receptor activation in depressed suicide victims are also manifest downstream from the associated G protein, affecting the activity of second messengers in two 5‐HT1A receptor transduction pathways that may have implications for cell survival.