bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human internal thoracic arteries from diabetic patients are resistant to endothelial dysfunction
Authors: Grapow Martin T.R. , Reineke David C. , Kern Thomas , Müller‐Schweinitzer Else , Carrel Thierry , Eckstein Friedrich S. 
Published: July 2009

AbstractThe aim of this analysis was to compare vasoreactive properties of internal thoracic arteries (ITA) grafts from diabetic (DM) to those of non‐diabetic (ND) patients. Ring segments of ITA, taken from patients undergoing coronary artery bypass grafting, were suspended in organ bath chambers filled with modified Krebs‐Henseleit solution and contractile responses to potassium chloride (KCl), noradrenaline (NA), endothelin‐1 (ET‐l), and endothelium‐dependent relaxant responses to acetylcholine (ACH) were recorded isometrically. The receptor‐mediated agonists NA and ET‐1 stimulated ITA from both groups within similar concentration ranges while ITA from DM patients proved to be significantly more sensitive to KCl than ITA from ND. Furthermore, maximal contractile responses indicated that KCl (3.79 ± 0.30 g, n = 7 in DM and 2.50 ± 0.23 g, n = 29 in ND, P < 0.05) evoked significantly higher responses in ITA from DM as compared to the ND control group while both NA and ET‐l stimulated ITA from both groups with similar efficacies. Endothelium‐dependent relaxant responses to ACH proved to be similar in both groups when expressed as percentages of the pre‐existing tone. The present data support the contention that in comparison to ND controls arteries from DM patients are more sensitive to depolarization but endothelial dysfunction is less frequent in human ITA than expected from observations in systemic vascular beds.
Exploring mechanism of pioglitazone‐induced memory restorative effect in experimental dementia
Authors: Kaur Baljinder , Singh Nirmal , Jaggi Amteshwar Singh 
Published: July 2009

AbstractThe present study was undertaken to investigate possible mechanism of pioglitazone‐induced beneficial effect in memory deficits associated with experimental dementia. Dementia was induced in Swiss albino mice by administration of streptozotocin (STZ; 3 mg/kg administered intracerebroventricularly on 1st & 3rd day). Morris Water‐Maze test was employed to assess learning and memory of the animals. Brain acetylcholinesterase (AChE) activity was measured by Ell Mann’s method. Brain thiobarbituric acid reactive species (TBARS) levels and reduced glutathione (GSH) levels were measured by Ohokawa’s and Beutler’s method respectively to assess total oxidative stress. Blood glucose level was also measured. Streptozotocin (STZ) produced a significant decrease in water‐maze performance of mice hence reflecting loss of learning and memory. Pioglitazone (20 mg/kg p.o. daily for 14 days) successfully attenuated STZ‐induced memory deficits, without any significant per se effect on blood glucose levels. Higher levels of brain AChE activity, TBARS and lower levels of GSH were observed in STZ treated animals, which were significantly attenuated by pioglitazone. Further, the noted beneficial effect of pioglitazone on STZ‐induced dementia was significantly abolished by pre‐treatment of nitric oxide (NO) synthase inhibitorl‐NAME (3 mg/kg i.p.) manifested in the terms of decrease in water‐maze performance and increase in brain AChE activity as well as oxidative stress. It is concluded that anti‐dementic effect of pioglitazone may involve central cholinergic, oxidative and NO pathways.
Prescribing patterns and utilization of antimicrobial drugs in a tertiary care teaching hospital of a Caribbean developing country
Authors: Hariharan Seetharaman , Pillai Gopalakrishna , McIntosh Denero , Bhanji Zahra , Culmer Lendeisha , Harper‐McIntosh Keista 
Published: July 2009

AbstractThis study aimed to evaluate the prescribing practices and utilization of antimicrobials in a tertiary care teaching hospital of a Caribbean developing country. A prospective observational cohort study was undertaken for a period of 12 weeks in the general wards and the intensive care unit (ICU) of the hospital. Demographic data, diagnoses on admission, antimicrobials prescribed, dosage and duration, route of administration, leukocyte count and microbiological culture and sensitivity reports were recorded. Hospital length of stay and final outcome were recorded. The usage was determined in terms of prescribed daily dose and the total costs of antimicrobials were calculated. Of 889 patients admitted, 335 (37.7%) received 22 different antimicrobial drugs. Overall, 67% of the prescriptions adhered to the hospital protocol. Median length of stay in the hospital was 7 days. Skin and soft tissue infections were the most common diagnoses for which antimicrobials were prescribed. Amoxicillin‐clavulanate was the most common (32%) antimicrobial used. Eighty‐nine percent of the antimicrobials were given through the intravenous route. Sixty percent of the patients received two antimicrobials, 26% received three, and 14% of patients were prescribed four or more antimicrobials during their stay at the hospital. There was significantly higher inappropriate choice of antimicrobials in ICU when compared with general wards (Mantel‐Haenszel Odds Ratio 3.3; 95% Confidence Intervals 1.4, 7.7). Prescribing patterns did not strictly adhere to the hospital antimicrobial protocol. There is a need for monitoring and control of antimicrobial prescription.
Hepatoprotective activity of picroliv, curcumin and ellagic acid compared to silymarin on paracetamol induced liver toxicity in mice
Authors: Girish C. , Koner Bidhan Chandra , Jayanthi S. , Ramachandra Rao K. , Rajesh B , Pradhan Suresh Chandra 
Published: July 2009

AbstractOxidative stress is implicated as a common pathologic mechanism contributing to the initiation and progression of hepatic damage in a variety of liver disorders. Present study attempts to evaluate the hepatoprotective activity of picroliv, curcumin and ellagic acid in comparison to silymarin using paracetamol (PCM) induced acute liver damage. Hepatotoxicity was induced by administering a single oral dose of PCM (500 mg/kg) and was assessed by quantifying the serum enzyme activities, phenobarbitone induced sleeping time and histopathological analysis of liver tissues. The antioxidant parameters, malondialdehyde (MDA), reduced glutathione (GSH) and catalase of the liver tissue were also assessed. The herbal drugs were administered for 7 days by oral route at 50 and 100 mg/kg. PCM induced hepatic damage was manifested by a significant increase in the activities of marker enzymes (alanine transaminase, aspartate transaminase and alkaline phosphatase) in serum and MDA level in liver. There was also a significant decrease in activity of GSH and catalase levels. The histopathological examination on toxic models revealed centrizonal necrosis and fatty changes. Pretreatment of mice with picroliv, curcumin and ellagic acid reversed these altered parameters towards normal values, which were compared with silymarin. The normalization of phenobarbitone induced sleeping time suggests the restoration of liver cytochrome P450 enzymes. This study supports the use of these active phytochemicals against toxic liver injury, which may act by preventing the lipid peroxidation and augmenting the antioxidant defense system or regeneration of hepatocytes. These active phytochemicals may be developed as drugs for the treatment of liver diseases.
P‐glycoprotein is not involved in the differential oral potency of naloxone and naltrexone
Authors: Kanaan Mouna , Daali Youssef , Dayer Pierre , Desmeules Jules 
Published: July 2009

AbstractThe poor oral bioavailability of the opioid receptor antagonist naloxone (NA) when compared with naltrexone (NX) may be related to a greater interaction of naloxone with the efflux drug transporter P‐glycoprotein (P‐gp). We studied the involvement of P‐gp in the transepithelial transport of the two opioid receptor antagonists, using a validated human in vitro Caco‐2 cell monolayer model. The bidirectional transport of NA and NX (1, 50 and 100 μm) across the monolayers was investigated in the presence and absence of the specific P‐gp inhibitor GF120918 (4 μm). NA and NX showed equal transport rates between the apical‐to‐basolateral (A–B) and the basolateral‐to‐apical (B–A) directions and neither the influx nor the efflux transport was affected by the P‐gp inhibitor (P > 0.05). In conclusion, NA and NX are not P‐gp substrates. The differential oral bioavailability of the two opioid antagonists is P‐gp independent.
Citral inhibits cell proliferation and induces apoptosis and cell cycle arrest in MCF‐7 cells
Authors: Chaouki Wahid , Leger David Y. , Liagre Bertrand , Beneytout Jean‐Louis , Hmamouchi Mohamed 
Published: July 2009

AbstractMany natural components of plants extract are studied for their beneficial effects on health and particularly on carcinogenesis chemoprevention. In this study, we investigated the effect of citral (3,7‐dimethyl‐2,6‐octadienal), a key component of essential oils extracted from several herbal plants, on the proliferation rate, cell cycle distribution, and apoptosis of the human breast cancer cell line MCF‐7. The effects of this compound were also tested on cyclo‐oxygenase activity. Citral treatment caused inhibition of MCF‐7 cell growth (IC50‐48 h: 18 × 10−5 m), with a cycle arrest in G2/M phase and apoptosis induction. Moreover, we observed a decrease in prostaglandin E2 synthesis 48 h after citral treatment. These findings suggest that citral has a potential chemopreventive effect.
Early activation of the coagulation system during lower body negative pressure
Authors: Zaar M. , Johansson P. I. , Nielsen L. B. , Crandall C. G. , Shibasaki M. , Hilsted L. , Secher N. H. 
Published: July 2009

SummaryWe considered that a moderate reduction of the central blood volume (CBV) may activate the coagulation system. Lower body negative pressure (LBNP) is a non‐invasive means of reducing CBV and, thereby, simulates haemorrhage. We tested the hypothesis that coagulation markers would increase following moderate hypovolemia by exposing 10 healthy male volunteers to 10 min of 30 mmHg LBNP. Thoracic electrical impedance increased during LBNP (by 2·6 ± 0·7 Ω, mean ± SD; P < 0·001), signifying a reduced CBV. Heart rate was unchanged during LBNP, while mean arterial pressure decreased (84 ± 5 to 80 ± 6 mmHg; P < 0·001) along with stroke volume (114 ± 22 to 96 ± 19 ml min−1; P < 0·001) and cardiac output (6·4 ± 2·0 to 5·5 ± 1·7 l min−1; P < 0·01). Plasma thrombin–antithrombin III complexes increased (TAT, 5 ± 6 to 19 ± 20 μg l−1; P < 0·05), indicating that LBNP activated the thrombin generating part of the coagulation system, while plasma D‐dimer was unchanged, signifying that the increased thrombin generation did not cause further intravascular clot formation. The plasma pancreatic polypeptide level decreased (13 ± 11 to 6 ± 8 pmol l−1; P < 0·05), reflecting reduced vagal activity. In conclusion, thrombin generation was activated by a modest decrease in CBV by LBNP in healthy humans independent of the vagal activity.
Securitization, Insurance, and Reinsurance
Authors: Cummins J. David , Trainar Philippe 
Published: July 2009

AbstractThis article considers strengths and weaknesses of reinsurance and securitization in managing insurable risks. Traditional reinsurance operates efficiently in managing relatively small, uncorrelated risks and in facilitating efficient information sharing between cedants and reinsurers. However, when the magnitude of potential losses and the correlation of risks increase, the efficiency of the reinsurance model breaks down, and the cost of capital may become uneconomical. At this juncture, securitization has a role to play by passing the risks along to broader capital markets. Securitization also serves as a complement for reinsurance in other ways such as facilitating regulatory arbitrage and collateralizing low‐frequency risks.
Incremental Pacing for the Diagnosis of Complete Cavotricuspid Isthmus Block During Radiofrequency Ablation of Atrial Flutter
Authors: BAZAN VICTOR , MARTÍ‐ALMOR JULIO , PEREZ‐RODON JORDI , BRUGUERA JORDI , GERSTENFELD EDWARD P. , CALLANS DAVID J. , MARCHLINSKI FRANCIS E. 
Published: July 2009

Incremental Pacing for the Diagnosis of Cavotricuspid Isthmus Block. Background: Complete conduction block of the cavotricuspid isthmus (CTI) reduces atrial flutter recurrences after ablation. Incremental rapid pacing may distinguish slow conduction from complete CTI conduction block. Methods and Results: Fifty‐two patients (67 ± 9 years) undergoing 55 CTI ablation procedures were included. With ablation, double potentials (DPs) separated by an isoelectric line of ≥30 ms were obtained. Incremental atrial pacing (600–250 ms) was performed from coronary sinus (CS) and low lateral right atrium (LLRA). A <20 ms increase in the DPs distance during incremental pacing was indexed as complete CTI block. In 8 patients, an initial <20 ms DPs distance increase was noted; direct complete isthmus block was suggested and no additional ablation performed. In the remaining, the CTI line was remapped for conduction gaps and additional radiofrequency energy pulses applied. Complete block, as indexed by incremental pacing, occurred in 46 of 55 procedures, with one flutter recurrence (follow‐up 8 ± 2 months): DPs interval variation of 116 ± 20 to 123 ± 20 ms (CS), P = 0.21; and 122 ± 25 to 135 ± 35 ms (LLRA), P = 0.17. The remaining 9 patients (persistent rate‐dependent DPs increase) presented 3 flutter recurrences, P = 0.01: DP distance from 127 ± 15 to 161 ± 18 ms (CS), P < 0.001; and 114 ± 24 to 142 ± 10 ms (LLRA), P = 0.007. Conclusion: Incremental pacing distinguishes complete CTI block from persistent conduction. Such identification, accompanied by additional ablation to achieve block, should minimize flutter recurrences after ablative therapy. (J Cardiovasc Electrophysiol, Vol. 21, pp. 33–39, January 2010)
Early Detection of Pulmonary Vein Reconnection After Isolation in Patients With Paroxysmal Atrial Fibrillation: A Comparison of ATP‐Induction and Reassessment at 30 Minutes Postisolation
Authors: JIANG CHEN‐YANG , JIANG RU‐HONG , MATSUO SEIICHIRO , LIU QIANG , FAN YOU‐QI , ZHANG ZHU‐WEN , FU GUO‐SHENG 
Published: July 2009

Introduction: Catheter ablation for paroxysmal AF (PAF) is limited by an unacceptable recurrence rate, mainly due to pulmonary vein (PV) reconnection. Strategies to minimize reconnection include adenosine infusion and also a waiting period of 30 minutes after PV isolation. The aim of the present study was to assess whether these two strategies revealed the same conduction gap. Methods and Results: In total, 88 consecutive patients (54 males, mean age of 60 years) with drug refractory PAF underwent circumferential PV isolation (CPVI). After isolation of ipsilateral PVs, with entry and exit block checked using a circular mapping catheter, 20 mg ATP was injected during isoproterenol infusion to reveal dormant conduction gap(s). Unless the reconnection revealed by ATP persisted, PVs were further remapped with the circular mapping catheter at 30 minutes postisolation. Totally, PV reconnection was observed in 56 (64%) patients. 24.3% veins (80/329) were found reconnected. Reassessment at 30 minutes postablation was more efficient as compared to ATP induction (19.8% vs 14.6% for ATP). The agreement between these 2 methods is moderate (kappa value = 0.50). In veins that transiently reconnected after ATP administration and later observed at 30 minutes postablation, 94% (17 of 19) of them were found being reconnected with the same gap. Conclusion: Acute PV reconnection is common, occurring in 64% of patients, as detected by adenosine infusion and waiting time. Each shows a unique quality as compared to one another. The combined use of these 2 methods may reduce the AF recurrence rate after CPVI.
Subgroup Hypotheses: Clinician’s Friend or Researcher’s Fiction?
Authors: Wyer Peter C. 
Published: July 2009

AbstractResearchers and clinicians may be tempted to consider apparent differences in effects of interventions in subgroups of study populations for the purposes of individualizing care or directing subsequent focused research efforts. Such “subgroup hypotheses” have a high propensity of being artifacts of chance and are rarely supported when stringent criteria are applied. Subgroup hypotheses emerging from single trials should rarely if ever be considered for application. This article describes published criteria for evaluating the believability of a subgroup hypothesis and presents a conceptual framework for understanding the principles underlying those criteria. Examples of both failed and validated subgroup hypotheses drawn from emergency medicine research are given.
Climate Change and Emergency Medicine: Impacts and Opportunities
Authors: Hess Jeremy J. , Heilpern Katherine L. , Davis Timothy E. , Frumkin Howard 
Published: July 2009

AbstractThere is scientific consensus that the climate is changing, that human activity plays a major role, and that the changes will continue through this century. Expert consensus holds that significant health effects are very likely. Public health and health care systems must understand these impacts to properly pursue preparedness and prevention activities. All of medicine will very likely be affected, and certain medical specialties are likely to be more significantly burdened based on their clinical activity, ease of public access, public health roles, and energy use profiles. These specialties have been called on to consider the likely impacts on their patients and practice and to prepare their practitioners. Emergency medicine (EM), with its focus on urgent and emergent ambulatory care, role as a safety‐net provider, urban concentration, and broad‐based clinical mission, will very likely experience a significant rise in demand for its services over and above current annual increases. Clinically, EM will see amplification of weather‐related disease patterns and shifts in disease distribution. In EM’s prehospital care and disaster response activities, both emergency medical services (EMS) activity and disaster medical assistance team (DMAT) deployment activities will likely increase. EM’s public health roles, including disaster preparedness, emergency department (ED)‐based surveillance, and safety‐net care, are likely to face increasing demands, along with pressures to improve fuel efficiency and reduce greenhouse gas emissions. Finally, EM’s roles in ED and hospital management, particularly related to building and purchasing, are likely to be impacted by efforts to reduce greenhouse gas emissions and enhance energy efficiency. Climate change thus presents multiple clinical and public health challenges to EM, but also creates numerous opportunities for research, education, and leadership on an emerging health issue of global scope.
Crosstalk between the NF‐κB activating IKK‐complex and the CSN signalosome
Authors: Orel Lukas , Neumeier Hannah , Hochrainer Karin , Binder Bernd R. , Schmid Johannes A. 
Published: July 2009

AbstractA great variety of signalling pathways regulating inflammation, cell development and cell survival require NF‐κB transcription factors, which are normally inactive due to binding to inhibitors, such as IκBα. The canonical activation pathway of NF‐κB is initiated by phosphorylation of the inhibitor by an IκB kinase (IKK) complex triggering ubiquitination of IκB molecules by SCF‐type E3‐ligase complexes and rapid degradation by 26S‐proteasomes. The ubiquitination machinery is regulated by the COP9 signalosome (CSN). We show that IκB kinases interact with the CSN‐complex, as well as the SCF‐ubiquitination machinery, providing an explanation for the rapid signalling‐induced ubiquitination and degradation of IκBα. Furthermore, we reveal that IKK’s phosphorylate not only IκBα, but also the CSN‐subunit Csn5/JAB1 (c‐Jun activation domain binding protein‐1) and that IKK2 influences ubiquitination of Csn5/JAB1. Our observations imply that the CSN complex acts as an inhibitor of constitutive NF‐κB activity in non‐activated cells. Knock‐down of Csn5/JAB1 clearly enhanced basal NF‐κB activity and improved cell survival under stress. The inhibitory effect of Csn5/JAB1 requires a functional MPN+ metalloprotease domain, which is responsible for cleaving ubiquitin‐like Nedd8‐modifications. Upon activation of cells with tumour necrosis factor‐α, the CSN complex dissociates from IKK’s allowing full and rapid activation of the NF‐κB pathway by the concerted action of interacting protein complexes.
Differential regulation of oestrogen receptor β isoforms by 5′ untranslated regions in cancer
Authors: Smith Laura , Brannan Rebecca A. , Hanby Andrew M. , Shaaban Abeer M. , Verghese Eldo T. , Peter Mark B. , Pollock Steven , Satheesha Sampoorna , Szynkiewicz Marcin , Speirs Valerie , Hughes Thomas A. 
Published: July 2009

AbstractOestrogen receptors (ERs) are critical regulators of the behaviour of many cancers. Despite this, the roles and regulation of one of the two known ERs – ERβ– are poorly understood. This is partly because analyses have been confused by discrepancies between ERβ expression at mRNA and proteins levels, and because ERβ is expressed as several functionally distinct isoforms. We investigated human ERβ 5′ untranslated regions (UTRs) and their influences on ERβ expression and function. We demonstrate that two alternative ERβ 5′UTRs have potent and differential influences on expression acting at the level of translation. We show that their influences are modulated by cellular context and in carcinogenesis, and demonstrate the contributions of both upstream open reading frames and RNA secondary structure. These regulatory mechanisms offer explanations for the non‐concordance of ERβ mRNA and protein. Importantly, we also demonstrate that 5′UTRs allow the first reported mechanisms for differential regulation of the expression of the ERβ isoforms 1, 2 and 5, and thereby have critical influences on ERβ function.