bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Inhibitory Effect of Ciprofloxacin on the β‐Glucuronidase‐mediated Deconjugation of the Irinotecan Metabolite SN‐38‐G
Authors: Kodawara Takaaki , Higashi Takashi , Negoro Yutaka , Kamitani Yukio , Igarashi Toshiaki , Watanabe Kyohei , Tsukamoto Hitoshi , Yano Ryoichi , Masada Mikio , Iwasaki Hiromichi , Nakamura Toshiaki 
Published: October 2015

AbstractThe enterohepatic recycling of a drug consists of its biliary excretion and intestinal reabsorption, which is sometimes accompanied by hepatic conjugation and intestinal deconjugation reactions. β‐Glucuronidase, an intestinal bacteria‐produced enzyme, can break the bond between a biliary excreted drug and glucuronic acid. Antibiotics such as ciprofloxacin can reduce the enterohepatic recycling of glucuronide‐conjugated drugs. In this study, we established an in vitro system to evaluate the β‐glucuronidase‐mediated deconjugation of the irinotecan metabolite SN‐38‐G to its active SN‐38 form and the effect of ciprofloxacin thereon. SN‐38 formation increased in a time‐dependent manner from 5 to 30 min. in the presence of β‐glucuronidase. Ciprofloxacin and phenolphthalein‐β‐d‐glucuronide (PhePG), a typical β‐glucuronidase substrate, significantly decreased SN‐38‐G deconjugation and, hence SN‐38 formation. Similarly, the antibiotics enoxacin and gatifloxacin significantly inhibited the conversion of SN‐38‐G to SN‐38, which was not observed for levofloxacin, streptomycin, ampicillin and amoxicillin/clavulanate. Ciprofloxacin showed a dose‐dependent inhibitory effect on the β‐glucuronidase‐mediated conversion of SN‐38‐G to SN‐38 with a half‐maximal inhibitory concentration (IC50) value of 83.8 μM. PhePG and ciprofloxacin afforded the inhibition in a competitive and non‐competitive manner, respectively. These findings suggest that the reduction in the serum SN‐38 concentration following co‐administration of ciprofloxacin during irinotecan treatment is due, at least partly, to the decreased enterohepatic circulation of SN‐38 through the non‐competitive inhibition of intestinal β‐glucuronidase‐mediated SN‐38‐G deconjugation.
An open randomized controlled clinical trial to evaluate ridge preservation and repair using SocketKAP™ and SocketKAGE™: part 2 – three‐dimensional alveolar bone volumetric analysis of CBCT imaging
Authors: Abdelhamid Alaa , Omran Mostafa , Bakhshalian Neema , Tarnow Dennis , Zadeh Homayoun H. 
Published: October 2015

AbstractObjectivesThe aims of this study were (i) to evaluate the efficacy of ridge preservation and repair procedures involving the application of SocketKAP™ and SocketKAGE™ devices following tooth removal and (ii) to evaluate alveolar bone volumetric changes at 6 months post‐extraction in intact sockets or those with facial wall dehiscence defects using 3‐dimensional pre‐ and postoperative CBCT data.Materials and MethodsThirty‐six patients required 61 teeth extracted. Five cohorts were established: Group A: Intact Socket Negative Control Group B: Intact Socket + SocketKAP™ Group C: Intact Socket Filled with Anorganic Bovine Bone Mineral (ABBM) + SocketKAP™ Group D: Facial Dehiscence Socket Negative Control Group E: Facial Dehiscence Socket Filled with ABBM + SocketKAP™ + SocketKAGE™. Preoperative CBCT scans were obtained followed by digital subtraction of the test teeth. At 6 months post‐extraction, another CBCT scan was obtained. The pre‐ and postoperative scans were then superimposed, allowing highly accurate quantitative determination of the 3D volumetric alveolar bone volume changes from baseline through 6 months.ResultsSignificant volumetric bone loss occurred in all sockets, localized mainly in the 0–3 mm zone apical to the ridge crest. For intact sockets, SocketKAP™ + ABBM treatment led to a statistically significant greater percentage of remaining mineralized tissue volume when compared to negative control group. A significant difference favoring SocketKAP™ + SocketKAGE™ + ABBM treatment was observed for sockets with facial dehiscence defects compared to the negative control group.ConclusionsSocketKAP™, with ABBM, appears effective in limiting post‐extraction volumetric bone loss in intact sockets, while SocketKAP™ + SocketKAGE + ABBM appears effective in limiting post‐extraction bone loss in sockets with dehiscence defects.
Blood flow‐restricted walking in older women: does the acute hormonal response associate with muscle hypertrophy?
Authors: Ozaki Hayao , Loenneke Jeremy P. , Abe Takashi 
Published: October 2015

SummaryLow‐load exercise can increase serum hormones such as growth hormone (GH) concentration in young adults when combined with blood flow restriction (BFR), but it is unclear whether walking with BFR (BFR‐walk) can elevate them for older adults. Furthermore, it remained untested whether changes in these purported anabolic hormones contribute to BFR‐walk‐induced muscle hypertrophy. To examine the relationship between the acute and chronic effects of BFR‐walk, seven women (age: 64 ± 2 years) performed treadmill walking with (BFR‐walk) and without BFR (CON‐walk) at 45% of heart rate reserve for 20 min in a randomized crossover design. During BFR‐walk, subjects wore 5‐cm cuffs on the proximal part of the upper legs. Blood samples were taken before (PRE), immediately after (POST‐1) and 15 min post (POST‐2) exercise. There was a main effect of time for GH (P<0·01) with levels increasing following exercise. In addition, there was a condition and time main effect for insulin; with insulin increasing to a greater degree with BFR at POST‐2. Noradrenaline increased across time for both BFR‐walk (P = 0·012) and CON‐walk (P<0·001); but BFR‐walk induced greater elevations at POST‐1 and POST‐2. The change in GH, insulin and noradrenaline was not significantly correlated with BFR‐walk‐induced muscle hypertrophy. These preliminary results suggest that the BFR‐walk‐induced elevation in the purported anabolic hormones may not have a large impact on muscle growth.
High cut‐off dialysis in chronic haemodialysis patients
Authors: Girndt Matthias , Fiedler Roman , Martus Peter , Pawlak Michael , Storr Markus , Bohler Torsten , Glomb Marcus A. , Liehr Kristin , Henning Christian , Templin Markus , Trojanowicz Bogusz , Ulrich Christof , Werner Kristin , Zickler Daniel , Schindler Ralf 
Published: October 2015

AbstractBackgroundHaemodialysis patients suffer from chronic systemic inflammation and high incidence of cardiovascular disease. One cause for this may be the failure of diseased kidneys to eliminate immune mediators. Current haemodialysis treatment achieves insufficient elimination of proteins in the molecular weight range 15–45 kD. Thus, high cut‐off dialysis might improve the inflammatory state.DesignIn this randomized crossover trial, 43 haemodialysis patients were treated for 3 weeks with high cut‐off or high‐flux dialysis. Inflammatory plasma mediators, monocyte subpopulation distribution and leucocyte gene expression were quantified.ResultsHigh cut‐off dialysis supplemented by a low‐flux filter did not influence the primary end‐point, expression density of CD162 on monocytes. Nevertheless, treatment reduced multiple immune mediators in plasma. Such reduction proved – at least for some markers – to be a sustained effect over the interdialytic interval. Thus, for example, soluble TNF‐receptor 1 concentration predialysis was reduced from median 13·3 (IQR 8·9–17·2) to 9·7 (IQR 7·5–13·2) ng/mL with high cut‐off while remaining constant with high‐flux treatment. The expression profile of multiple proinflammatory genes in leucocytes was significantly dampened. Treatment was well tolerated although albumin losses in high cut‐off dialysis would be prohibitive against long‐term use.ConclusionsThe study shows for the first time that a dampening effect of high cut‐off dialysis on systemic inflammation is achievable. Earlier studies had failed due to short study duration or insufficient dialysis efficacy. Removal of soluble mediators from the circulation influences cellular activation levels in leucocytes. Continued development of less albumin leaky membranes with similar cytokine elimination is justified.
Chronic myeloid leukemia in the Netherlands: a population‐based study on incidence, treatment, and survival in 3585 patients from 1989 to 2012
Authors: Thielen Noortje , Visser Otto , Ossenkoppele Gert , Janssen Jeroen 
Published: October 2015

AbstractObjectiveTo assess the impact and results of treatment of CML in the general population, we conducted a population‐based, nationwide study on 3585 CML patients diagnosed between 1989 and 2012 in the Netherlands.MethodsPatient demographics were obtained from the Netherlands Cancer Registry. Information on age, gender, year of diagnosis, first treatment, and date of death were recorded. Overall survival (OS) was adjusted for death rates in the normal population.ResultsIncidence in males decreased slightly from 1.2 per 100.000 person years (PY) in 1989–2000 to 0.9 in 2001–2012. For females, incidence remained stable with 0.7 per 100.000 PY in both periods. Incidence was age dependent and highest in males in the last decades of life. Treatment before 2000 mainly consisted of chemotherapy, while after 2007 TKI use was 88%. Five‐year relative survival was only 36% before the introduction of TKIs but significantly increased to 79% after the introduction of TKI.ConclusionsThis study gives insight into CML incidence, treatment, and survival in routine care in the Netherlands. Although OS improved since the introduction of TKIs, there is still room for further improvement.
Magnetic resonance correlation of iron content with neuromelanin in the substantia nigra of early‐stage Parkinson's disease
Authors: Reimão S. , Ferreira S. , Nunes R. G , Pita Lobo P. , Neutel D. , Abreu D. , Gonçalves N. , Campos J. , Ferreira J. J. 
Published: October 2015

Background and purposeMagnetic resonance (MR) studies have demonstrated a significant reduction of neuromelanin in the substantia nigra (SN) of Parkinson's disease (PD) patients with high accuracy for differential diagnosis compared to non‐PD controls and essential tremor. However, studies state that not knowing how paramagnetic effects of iron influence neuromelanin signal is a limitation. In this study a neuromelanin‐sensitive MR sequence was combined with T2* relaxometry iron quantification analysis to study the SN of early‐stage PD patients to investigate the correlation between these parameters.MethodsThe inclusion criteria were untreated de novo PD patients and a 2–5 year disease duration (early PD); in addition, age‐matched controls were enrolled. These were studied at 3.0 T with a high‐resolution T1‐weighted MR sequence to visualize neuromelanin and a relaxometry sequence for iron quantification. The primary outcome was the correlation of the width of the neuromelanin high signal region and the T2* values in the lateral, central and medial segments of the SN.ResultsVery weak correlations of T2* values with neuromelanin width, positive for global and negative for the medial and lateral SN segments, were found in both PD groups and control subjects. The SN neuromelanin width was markedly reduced in the de novo and early PD groups compared with controls in all SN segments, but no significant difference in T2* values was found between the groups.ConclusionsThe SN neuromelanin signal does not have a significant correlation with iron content in PD patients or controls. The neuromelanin MR signal reduction in PD does not seem to be significantly influenced by paramagnetic iron effects.
Vitamin D in clinically isolated syndrome: evidence for possible neuroprotection
Authors: Mowry E. M. , Pelletier D. , Gao Z. , Howell M. D. , Zamvil S. S. , Waubant E. 
Published: October 2015

AbstractBackground and purposeVitamin D status has been associated with inflammatory activity in multiple sclerosis (MS), but it is not known if it is associated with gray matter volume, the loss of which predicts long‐term disability in MS. The association of vitamin D levels with brain volume measures and inflammatory activity in patients with clinically isolated syndrome (CIS) was investigated.MethodsIn the phase 2 CIS trial of atorvastatin, 25‐hydroxyvitamin D levels were evaluated for their age‐adjusted associations with normalized gray matter and brain parenchymal volumes on brain magnetic resonance imaging (MRI). The relationships between 25‐hydroxyvitamin D levels and clinical and MRI measures of inflammatory activity were also assessed.ResultsIn 65 patients in this substudy, each 25 nmol/l higher 25‐hydroxyvitamin D level was associated with 7.8 ml higher gray matter volume (95% confidence interval 1.0, 14.6, P = 0.025). There was a tendency for an inverse association of average 25‐hydroxyvitamin D levels and the composite end‐point of ≥3 new brain T2 lesions or ≥1 relapse within a year (odds ratio per 25 nmol/l higher 25‐hydroxyvitamin D level 0.66, 95% confidence interval 0.41, 1.08, P = 0.096).ConclusionsVitamin D status may impact neurodegeneration after CIS, although these results should be replicated in a second study. If confirmed in clinical trials, vitamin D supplementation may reduce long‐term disability.
Differential spectral quantitative electroencephalography patterns between control and Parkinson's disease cohorts
Authors: Caviness J. N. , Utianski R. L. , Hentz J. G. , Beach T. G. , Dugger B. N. , Shill H. A. , Driver‐Dunckley E. D. , Sabbagh M. N. , Mehta S. , Adler C. H. 
Published: October 2015

Background and purposeIt is believed that progressive Lewy‐type synucleinopathy (LTS) is primarily responsible for the worsening of motor and non‐motor Parkinson's disease (PD) signs and symptoms. Characterization of quantitative electroencephalography (QEEG) abnormalities across the spectrum of LTS to PD dementia (PD‐D) may provide insight into the pathophysiology of PD cortical dysfunction. Here our enlarged EEG database was leveraged to characterize spectral QEEG abnormalities in asymptomatic autopsy‐defined groups of control participants and incidental Lewy body disease (ILBD) and three clinically defined groups of participants with PD (cognitively normal PD, mild cognitive impairment PD, and PD‐D).MethodsThe PD cohort was studied as part of the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND). AZSAND utilizes its Brain and Body Donation Program to perform prospective, standardized, regular longitudinal pre‐mortem assessments until death. Resting EEG from subjects was analyzed for spectral domain QEEG measures of background rhythm frequency and global relative power in delta, theta, alpha and beta bands.ResultsThe various spectral QEEG measures showed differential changes specific to the groups compared. Important findings were background rhythm frequency showing the most pairwise differences across the groups, and this also was the only significant difference between control and ILBD. An increase in delta bandpower was characteristic of worsening cognitive deficits.ConclusionsDifferent patterns of change amongst QEEG measures across LTS and PD cognitive states suggest that they correlate with heterogeneous pathophysiologies of cortical dysfunction within the PD clinical spectrum. In addition, the biomarker application of a specific spectral QEEG measure needs to be selectively suited to its study purpose.
Performance of cognitive tests, individually and combined, for the detection of cognitive disorders amongst community‐dwelling elderly people with memory complaints: the EVATEM study
Authors: Vannier‐Nitenberg C. , Dauphinot V. , Bongue B. , Sass C. , Bathsavanis A. , Rouch I. , Deville N. , Beauchet O. , Krolak‐Salmon P. , Fantino B. 
Published: October 2015

Background and purposeDementia is a leading cause of dependence amongst the aged population. Early identification of cognitive impairment could help to delay advanced stages of dependence. This study aimed at assessing the performance of three neuropsychological tests to detect cognitive disorders in elderly subjects with memory complaints.MethodsThe EVATEM study is a prospective multicentre cohort with a 1‐year follow‐up. Subjects with memory complaints were selected during preventive health examinations, and three neuropsychological tests (five‐word, cognitive disorders examination, verbal fluency) were administered. Two groups were identified in memory clinics: (i) cognitively healthy individuals (CHI) and (ii) mild cognitive impairment or demented individuals (MCI‐DI). Cross‐sectional analyses were performed on data at inclusion. The relationship between the diagnosis of MCI‐DI/CHI and the neuropsychological tests was assessed using logistic regressions. The performance of the neuropsychological tests, individually and combined, to detect cognitive disorders was calculated.ResultsOf 585 subjects, 31.11% had cognitive disorders (MCI, 176 subjects; DI, six subjects). Amongst the three tests studied, the odds ratio for MCI‐DI was higher for the five‐word test <10 [odds ratio 3.2 (1.81; 5.63)]. The best performance was observed when the three tests were combined: specificity 90.5% and sensitivity 42.4% compared to respectively 89.2% and 28.3% for the five‐word test.ConclusionsDespite the poor sensitivity of the five‐word test, it seems to be the most adapted for the diagnosis of MCI‐DI in older adults with a memory complaint, in prevention centres, taking into account its high specificity and its rapid administration compared to the other tests.
Factors associated with dust dispersed in the air of indoor riding arenas
Authors: Lühe T. , Mielenz N. , Schulz J. , Dreyer‐Rendelsmann C. , Kemper N. 
Published: October 2015

SummaryReasons for performing studyEnvironmental factors contribute to respiratory diseases in horses and man. During exercise, equine ventilation is increased, potentially increasing exposure of the airways to inhaled particulates. Currently, there is very little information on the quality of air in riding arenas.ObjectivesTo evaluate air quality and dust particle concentrations in indoor riding arenas before and after use for riding.Study designLongitudinal study.MethodsAir quality was assessed in 4 indoor riding arenas in Saxony‐Anhalt, Germany on a monthly basis for 1 year. Concentrations of particles in 6 particle fractions from 0.3 to 5.0 μm were measured in air collected at 4 points in the riding arenas approximately at the height of the horses’ (1.5 m) and riders’ noses (2.5 m), before and after the arenas were used by one horse performing standardised riding session.ResultsThere were significant differences in the numbers of particles between the arenas within months and between months within the arenas. Particle numbers were significantly influenced by the month and activities in the arenas before and after riding. The effect of the month on differences in the dust concentration may relate to surface watering. A significant increase in numbers of particles was observed after the riding session. Significant interactions were found between measuring heights and month within arena (P<0.01) and there was an interaction between measuring height and time points (before and after riding, P = 0.02).ConclusionsThe amount of dust dispersed in the air increases during riding in indoor arenas and this appears to be influenced by footing material, direct connections between the arena and stables and season, possibly reflecting surface watering practices.
Neuronal chromatolysis in the subgemmal plexus of gustatory papillae in horses with grass sickness
Authors: McGorum B. C. , Pirie R. S. , Shaw D. , Macintyre N. , Cox A. 
Published: October 2015

SummaryReasons for performing studyDiagnosis of equine grass sickness (EGS) can be challenging. We hypothesised that subgemmal plexus neurons are chromatolytic in EGS. If correct, histopathological examination of gustatory papillae biopsies could aid premortem diagnosis of EGS, and EGS could represent a spontaneous model of subgemmal neuronal chromatolysis to facilitate study of the pathology of structures involved in taste.ObjectiveTo compare subgemmal plexi and gustatory papillae in EGS and control horses.Study designObservational study.MethodsConventional histology and immunohistochemistry were used to compare subgemmal plexi and gustatory papillae in post mortem samples from 10 EGS and 13 control horses.ResultsChromatolytic neurons were present in all 57 EGS sections which had identifiable neurons, and in only one of 57 control sections. Blinded examination of all haematoxylin‐eosin stained sections from each horse for chromatolysis facilitated accurate differentiation of EGS and control horses, with a sensitivity of 100% (95% confidence interval 93.7–100) and specificity of 98.2% (90.6–100) for diagnosing EGS; however, the presence of chromatolytic neurons in one control section indicated that multiple sections per horse must be analysed to achieve diagnostic accuracy. Equine grass sickness was not associated with alterations in taste bud density or morphology, proportion of taste buds with neurofilament immunopositive intragemmal axons or proportion of taste buds containing cells undergoing apoptosis, suggesting taste buds had adequate neurotrophic support at the time of sampling. Horses with EGS had no detectable alteration in lingual gland morphology, but had increased proportions of apoptotic lingual serous gland cells.ConclusionsWhile identification of chromatolytic subgemmal neurons in post mortem samples correctly differentiated EGS and control horses, further study is required to evaluate this technique for premortem EGS diagnosis. Equine grass sickness represents a spontaneous model of subgemmal neuronal chromatolysis that facilitates study of the pathology of structures involved in taste.
Cytokine, catabolic enzyme and structural matrix gene expression in synovial fluid following intra‐articular administration of triamcinolone acetonide in exercised horses
Authors: Knych H. K. , Vidal M. A. , Chouicha N. , Mitchell M. , Kass P. H. 
Published: October 2015

SummaryReason for performing studyThe frequent use of intra‐articular triamcinolone acetonide (TA) in performance horses warrants further study of the duration of as well as the beneficial and detrimental effects on gene expression associated with administration.ObjectivesTo assess the effects of intra‐articular administration ofTAon the expression of selected anti‐ and proinflammatory and structural matrix genes following its administration into joints of exercised Thoroughbred horses and to correlate these effects with plasma and synovial fluid drug concentrations.Study designBlock design experiment.MethodsEight exercised horses received a single intra‐articular administration of 9 mg ofTA. Synovial fluid samples were collected from the treated and contralateral joints prior to and up to 49 days following drug administration. Microarray and quantitative reverse transcription polymerase chain reaction analysis were used to assess changes in expression levels of various inflammatory and structural genes post drug administration.ResultsDrug concentrations in plasma and synovial fluid, were no longer quantifiable by 6 and 28 days following drug administration respectively. In total, the expression level of 5490 genes were significantly altered on micro array analysis, following intra‐articularTAadministration. Of the genes selected for further study by quantitative reverse transcription polymerase chain reaction analysis, significant changes in inflammatory genes (annexin type 1, cyclooxygenase‐1 and tumour necrosis factor stimulated gene 6) and structural genes (collagen and aggrecan) were noted.ConclusionsThis study supports the use of synovial fluid as a biological matrix for studying the effects of corticosteroids on gene expression. For the majority of genes studied the effects on expression relative to baseline for both inflammatory and matrix genes were prolonged relative to plasma and synovial fluidTAconcentrations. Downregulation of collagen gene expression warrants the careful use ofTAin horses.