bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of ginsenoside Rg1 on proliferation and differentiation of human dental pulp cells in vitro
Authors: Wang P , Wei X , Zhou Y , Wang Y‐P , Yang K , Zhang F‐J , Jiang R 
Published: April 2012

AbstractBackground: Human dental pulp cells (hDPCs) have the potency to proliferate and differentiate into odontoblasts and play an important role in dentine formation and reparation. The aim of the present study is to evaluate the effects of ginsenoside Rg1 on the proliferation and differentiation of hDPCs.Methods: hDPCs were incubated with different concentrations of ginsenoside Rg1 (0.1, 0.5, 2.5, 5, 10 and 20 μmol/L). The effects of ginsenoside Rg1 on the proliferative ability of hDPCs were evaluated by a fibroblast colony forming test, MTT assay and flow cytometry for cell cycle. The control group, osteogenic induction group, ginsenoside Rg1 (5 μmol/L) group and combination group were designed, and alkaline phosphatase (ALP) activity and FQ‐PCR for gene expressions of dentine sialophosphoprotein (DSPP) and dentine matrix protein 1 (DMP1) were performed to evaluate the differentiation of hDPCs.Results: The proliferative ability of hDPCs in ginsenoside Rg1 was significantly enhanced (p < 0.05), especially in the ginsenoside Rg1 (5 μmol/L) group. ALP activity and gene expressions of DSPP and DMP1 were increased in the induction group, ginsenoside Rg1 group, and their combination group compared with the control group (p < 0.05).Conclusions: The results indicate that ginsenoside Rg1 promotes the proliferation and differentiation of hDPCs.
Improvements in skeletal muscle strength and cardiac function induced by resveratrol during exercise training contribute to enhanced exercise performance in rats
Authors: Dolinsky Vernon W. , Jones Kelvin E. , Sidhu Robinder S. , Haykowsky Mark , Czubryt Michael P. , Gordon Tessa , Dyck Jason R. B. 
Published: April 2012

Key points
Resveratrol, an antioxidant found in red wine, has beneficial effects on cardiac and skeletal muscle function, similar to the effects of endurance exercise training.
Combining resveratrol supplementation with exercise training augments the beneficial effects of exercise alone.
We show that endurance capacity is enhanced in rats whose diet includes resveratrol during a 12 week endurance‐training programme.
Increased endurance was associated with increases in skeletal muscle force, cardiac function, and oxidative metabolism.
Our results establish that resveratrol is an effective ergogenic aid that enhances exercise performance over exercise alone.
Cerebellar modulation of human associative plasticity
Authors: Hamada Masashi , Strigaro Gionata , Murase Nagako , Sadnicka Anna , Galea Joseph M. , Edwards Mark J. , Rothwell John C. 
Published: April 2012

Key point
Increases in the strength of synaptic connections in the motor cortex (long term potentiation) can be induced in humans by repetitively pairing peripheral nerve stimuli and motor cortex transcranial magnetic stimuli given 21–25 ms apart – paired associative stimulation (PAS).
This ‘associative plasticity’ effect has been assumed to relate to synchronicity between sensory input and motor output, with a similar mechanism proposed to underlie effects at all interstimulus intervals.
Here we show that modulation of cerebellar activity using transcranial direct current stimulation can abolish associative plasticity in the motor cortex, but only for sensory/motor stimuli paired at 25 ms, not at 21.5 ms.
The results indicate that human associative plasticity can be affected by cerebellar activity and that at least two different mechanisms are involved in the effects previously reported in studies using PAS at different inter‐stimulus intervals.
Nanoscale imaging of the bone cell network with synchrotron X‐ray tomography: optimization of acquisition setup
Authors: Pacureanu Alexandra , Langer Max , Boller Elodie , Tafforeau Paul , Peyrin Françoise 
Published: April 2012

Purpose:The fundamental role of the osteocyte cell network in regulating the bone remodeling has become evident in the last years. This has raised the necessity to explore this complex three‐dimensional interconnected structure, but the existing investigation methods cannot provide an adequate assessment. The authors propose to use parallel beam synchrotron radiation computed tomography at the nanoscale to image in three dimensions the osteocyte lacunocanalicular network. To this aim, the authors study the feasibility of this technique and present an optimized imaging protocol suited for the bone cell network. Moreover, they demonstrate the multifaceted information provided by this method.Methods:The high brilliance of synchrotron radiation combined with state of art detectors permits reaching nanoscale spatial resolution. With a nominal pixel size of 280 nm, the parallel beam computed tomography setup at the ID19 experimental station of the ESRF is capable of imaging the bone lacunocanalicular network, considering that the reported diameter of canaliculi is in the range 300–600 nm. However, the actual resolution is limited by the detector and by the radiation dose causing sample damage during the scan. The authors sought to overcome these limitations by optimizing the imaging setup and the acquisition parameters in order to minimize the necessary radiation dose to create the images and to improve the spatial resolution of the detector.Results:The authors achieved imaging of the osteocyte cell network in human bone. Due to the optimization of the imaging setup and acquisition parameters, they obtained simultaneously a radiation dose reduction and an increase of the signal to noise ratio in the images. This permitted the authors to generate the first three‐dimensional images of the lacunocanalicular network in an area covering several osteons, the fundamental functional units in the bone cortex. The method enables assessment of both architectural parameters of the microporosity and of mineralization degree in the bone matrix. The authors found that the cell network is dense and connected inside osteonal tissue. Conversely, the cell lacunae are sparse, unorganized, and disconnected in interstitial tissue.Conclusions:The authors show that synchrotron radiation computed tomography is a feasible technique to assess the lacunocanalicular network in three dimensions. This is possible due to an optimal imaging setup in which the detector plays an important role. The authors could establish two valid setups, based on two different insertion devices. These results give access to new information on the bone cell network architecture, covering a number of cells two orders of magnitude greater than existing techniques. This enables biomedical studies on series of samples, paving the way to better understanding of bone fragility and to new treatments for bone diseases.
Stability of Extemporaneously Prepared 0.5-Percent Caspofungin Eye Drops: a Potential Cost-Savings Exercise
Authors: Neoh Chin Fen , Jacob Jovan , Leung Lok , Li Jian , Stathopoulos Angela , Stewart Kay , Kong David C. M. 
Published: April 2012

ABSTRACTWhile the successful use of topical caspofungin for patients has been reported, topical caspofungin is not commercially available and its stability is unknown, limiting its usefulness in treating fungal keratitis. Caspofungin (0.5%) eye drops were aseptically prepared, and the concentrations were measured using a validated high-performance liquid chromatography (HPLC) analysis. The preparations remained stable for 28 days under refrigerated condition but not at 25.0°C. Our study supports the cost-saving use of caspofungin eye drops in the clinical setting.
Use of Carbapenems against Clinical, Nontyphoid Salmonella Isolates: Results from
In Vitro
and
In Vivo
Animal Studies
Authors: Tang Hung-Jen , Chen Chi-Chung , Zhang Chun-Cheng , Cheng Kuo Chen , Chiang Shyh-Ren , Chiu Yu-Hsin , Ku Yee Huang , Ko Wen-Chien , Chuang Yin-Ching 
Published: April 2012

ABSTRACT

The emergence of multidrug-resistant
Salmonella
isolates has created the need for new therapeutic agents. We evaluated the intracellular activity of four carbapenem compounds against clinical nontyphoid
Salmonella
(NTS) isolates
in vitro
and
ex vivo
. Subsequently, the efficacy of carbapenem treatment against selected
Salmonella
isolates
in vivo
was assessed using a murine peritonitis model. The MIC
50
and MIC
90
for doripenem, ertapenem, imipenem, and meropenem against 126 NTS isolates were found to be 0.062 and 0.062, 0.015 and 0.015, 0.5 and 1, and 0.031 and 0.031 μg/ml, respectively. The intracellular killing effect of ertapenem was sustained for 24 h and was superior to that of imipenem, meropenem, and doripenem; its effect was comparable to that of ceftriaxone. Ertapenem demonstrated an excellent pharmacokinetic profile with a percent time above the MIC of 75.5% and an area under the concentration-time curve/MIC ratio of 20,733. When peritoneal exudate cells were examined directly
ex vivo
from mice with
Salmonella
-induced peritonitis, cells from mice treated with ertapenem and ceftriaxone had intracellular and extracellular bacterial counts reduced 10
2
- to 10
4
-fold and exhibited killing effects similar to each other. The survival rates of mice inoculated with 1 × 10
5
and 10
6
CFU of a ceftriaxone-susceptible
Salmonella
isolate that were subsequently treated with ertapenem or ceftriaxone were 100% and 90%, respectively. When mice were inoculated with 5 × 10
4
and 10
5
CFU of a ceftriaxone-resistant and ciprofloxacin-resistant
Salmonella
isolate, mice treated with ertapenem had a higher survival rate than mice treated with ceftriaxone (70% versus 0% and 50% versus 0%, respectively;
P
< 0.001). Our results suggest that ertapenem is at least as effective as ceftriaxone in treating murine
Salmonella
infections and show that further clinical investigations on the potential use of ertapenem in treatment of human
Salmonella
infections are warranted.
Pharmacokinetic Comparison of Two Piperaquine-Containing Artemisinin Combination Therapies in Papua New Guinean Children with Uncomplicated Malaria
Authors: Salman Sam , Page-Sharp Madhu , Batty Kevin T. , Kose Kaye , Griffin Susan , Siba Peter M. , Ilett Kenneth F. , Mueller Ivo , Davis Timothy M. E. 
Published: April 2012

ABSTRACT

Pharmacokinetic differences between piperaquine (PQ) base and PQ tetraphosphate were investigated in 34 Papua New Guinean children aged 5 to 10 years treated for uncomplicated malaria with artemisinin-PQ (ART-PQ) base or dihydroartemisinin-PQ (DHA-PQ) tetraphosphate. Twelve children received ART-PQ base (two daily doses of 3 mg of ART and 18 mg of PQ base as granules/kg of body weight) as recommended by the manufacturer, with regular clinical assessment and blood sampling over 56 days. PQ concentrations in plasma samples collected from 22 children of similar ages with malaria in a previously published pharmacokinetic study of DHA-PQ tetraphosphate (three daily doses of 2.5 mg of ART and 20 mg of PQ tetraphosphate as tablets/kg of body weight) were available for comparison. The disposition of ART was also assessed in the 12 children who received ART-PQ base. Plasma PQ was assayed by high-performance liquid chromatography with UV detection, and ART was assayed using liquid chromatography-mass spectrometry. Multicompartment pharmacokinetic models for PQ and ART were developed using a population-based approach. ART-PQ base was well tolerated, and initial fever abatement and parasite clearance were prompt. There were no differences between the two treatments in the values for the PQ area under the concentration-time curve from time zero to infinity (AUC
0–∞
), with medians of 49,451 (
n
= 12) and 44,556 (
n
= 22) μg · h/liter for ART-PQ base and DHA-PQ tetraphosphate, respectively. Recurrent parasitemia was associated with lower PQ exposure. Using a two-compartment ART model, the median AUC
0–∞
was 1,652 μg · h/liter. There was evidence of autoinduction of ART metabolism (relative bioavailability for the second dose, 0.27). These and previously published data suggest that a 3-day ART-PQ base regimen should be further evaluated, in line with World Health Organization recommendations for all artemisinin combination therapies.
Effect of Coadministration of Moxifloxacin and Rifampin on Mycobacterium tuberculosis in a Murine Aerosol Infection Model
Authors: Balasubramanian V. , Solapure S. , Gaonkar S. , Mahesh Kumar K. N. , Shandil R. K. , Deshpande Abhijeet , Kumar Naveen , Vishwas K. G. , Panduga Vijender , Reddy Jitendar , Ganguly Samit , Louie A. , Drusano G. L. 
Published: April 2012

ABSTRACT

Coadministration of moxifloxacin and rifampin was evaluated in a murine model of
Mycobacterium tuberculosis
pulmonary infection to determine whether the finding of antagonism documented in a hollow-fiber infection model could be recapitulated
in vivo
. Colony counts were followed in a no-treatment control group, groups administered moxifloxacin or rifampin monotherapy, and a group administered a combination of the two agents. Following 18 days of once-daily oral administration to mice infected with
M. tuberculosis
, there was a reduction in the plasma exposure to rifampin that decreased further when rifampin was coadministered with moxifloxacin. Pharmacodynamic analysis demonstrated a mild antagonistic interaction between moxifloxacin and rifampin with respect to cell kill in the mouse model for tuberculosis (TB). No emergence of resistance was noted over 28 days of therapy, even with monotherapy. This was true even though one of the agents in the combination (moxifloxacin) induces error-prone replication. The previously noted antagonism with respect to cell kill shown in the hollow-fiber infection model was recapitulated in the murine TB lung model, although to a lesser extent.
Effect of Mutation and Genetic Background on Drug Resistance in Mycobacterium tuberculosis
Authors: Fenner Lukas , Egger Matthias , Bodmer Thomas , Altpeter Ekkehardt , Zwahlen Marcel , Jaton Katia , Pfyffer Gaby E. , Borrell Sonia , Dubuis Olivier , Bruderer Thomas , Siegrist Hans H. , Furrer Hansjakob , Calmy Alexandra , Fehr Jan , Stalder Jesica Mazza , Ninet Béatrice , Böttger Erik C. , Gagneux Sebastien ,   for the Swiss HIV Cohort Study and the Swiss Molecular Epidemiology of Tuberculosis Study Group
Published: April 2012

ABSTRACT

Bacterial factors may contribute to the global emergence and spread of drug-resistant tuberculosis (TB). Only a few studies have reported on the interactions between different bacterial factors. We studied drug-resistant
Mycobacterium tuberculosis
isolates from a nationwide study conducted from 2000 to 2008 in Switzerland. We determined quantitative drug resistance levels of first-line drugs by using Bactec MGIT-960 and drug resistance genotypes by sequencing the hot-spot regions of the relevant genes. We determined recent transmission by molecular methods and collected clinical data. Overall, we analyzed 158 isolates that were resistant to isoniazid, rifampin, or ethambutol, 48 (30.4%) of which were multidrug resistant. Among 154 isoniazid-resistant strains,
katG
mutations were associated with high-level and
inhA
promoter mutations with low-level drug resistance. Only
katG
(
S315T
) (65.6% of all isoniazid-resistant strains) and
inhA
promoter −15C/T (22.7%) were found in molecular clusters.
M. tuberculosis
lineage 2 (includes Beijing genotype) was associated with any drug resistance (adjusted odds ratio [OR], 3.0; 95% confidence interval [CI], 1.7 to 5.6;
P
< 0.0001). Lineage 1 was associated with
inhA
promoter −15C/T mutations (OR, 6.4; 95% CI, 2.0 to 20.7;
P
= 0.002). We found that the genetic strain background influences the level of isoniazid resistance conveyed by particular mutations (interaction tests of drug resistance mutations across all lineages;
P
< 0.0001). In conclusion,
M. tuberculosis
drug resistance mutations were associated with various levels of drug resistance and transmission, and
M. tuberculosis
lineages were associated with particular drug resistance-conferring mutations and phenotypic drug resistance. Our study also supports a role for epistatic interactions between different drug resistance mutations and strain genetic backgrounds in
M. tuberculosis
drug resistance.
Whole Exome Sequencing to Identify a Novel Gene (Caveolin-1) Associated With Human Pulmonary Arterial Hypertension
Authors: Austin Eric D. , Ma Lijiang , LeDuc Charles , Berman Rosenzweig Erika , Borczuk Alain , Phillips John A. , Palomero Teresa , Sumazin Pavel , Kim Hyunjae R. , Talati Megha H. , West James , Loyd James E. , Chung Wendy K. 
Published: April 2012

Background—
Heritable and idiopathic pulmonary arterial hypertension (PAH) are phenotypically identical and associated with mutations in several genes related to transforming growth factor (TGF) beta signaling, including bone morphogenetic protein receptor type 2, activin receptor-like kinase 1, endoglin, and mothers against decapentaplegic 9. Approximately 25% of heritable cases lack identifiable mutations in any of these genes.

Methods and Results—

We used whole exome sequencing to study a 3-generation family with multiple affected family members with PAH, but no identifiable TGF beta mutation. We identified a frameshift mutation in caveolin-1 (
CAV1
), which encodes a membrane protein of caveolae abundant in the endothelium and other cells of the lung. An independent de novo frameshift mutation was identified in a child with idiopathic PAH. Western blot analysis demonstrated a reduction in caveolin-1 protein, while lung tissue immunostaining studies demonstrated a reduction in normal caveolin-1 density within the endothelial cell layer of small arteries.

Conclusions—

Our study represents successful elucidation of a dominant Mendelian disorder using whole exome sequencing. Mutations in
CAV1
are associated in rare cases with PAH. This may have important implications for pulmonary vascular biology, as well as PAH-directed therapeutic development.
Impact of Changes in Resuscitation Practice on Survival and Neurological Outcome After Out-of-Hospital Cardiac Arrest Resulting From Nonshockable Arrhythmias
Authors: Kudenchuk Peter J. , Redshaw Jeffrey D. , Stubbs Benjamin A. , Fahrenbruch Carol E. , Dumas Florence , Phelps Randi , Blackwood Jennifer , Rea Thomas D. , Eisenberg Mickey S. 
Published: April 2012

Background—
Out-of-hospital cardiac arrest (OHCA) claims millions of lives worldwide each year. OHCA survival from shockable arrhythmias (ventricular fibrillation/ tachycardia) improved in several communities after implementation of American Heart Association resuscitation guidelines that eliminated “stacked” shocks and emphasized chest compressions. “Nonshockable” rhythms are now the predominant presentation of OHCA; the benefit of such treatments on nonshockable rhythms is uncertain.

Methods and Results—

We studied 3960 patients with nontraumatic OHCA from nonshockable initial rhythms treated by prehospital providers in King County, Washington, over a 10-year period. Outcomes during a 5-year intervention period after adoption of new resuscitation guidelines were compared with the previous 5-year historical control period. The primary outcome was 1-year survival. Patient demographics and resuscitation characteristics were similar between the control (n=1774) and intervention (n=2186) groups, among whom 471 of 1774 patients (27%) versus 742 of 2186 patients (34%), respectively, achieved return of spontaneous circulation; 82 (4.6%) versus 149 (6.8%) were discharged from hospital, 60 (3.4%) versus 112 (5.1%) with favorable neurological outcome; 73 (4.1%) versus 135 (6.2%) survived 1 month; and 48 (2.7%) versus 106 patients (4.9%) survived 1 year (all
P
≤0.005). After adjustment for potential confounders, the intervention period was associated with an improved odds of 1.50 (95% confidence interval, 1.29–1.74) for return of spontaneous circulation, 1.53 (95% confidence interval, 1.14–2.05) for hospital survival, 1.56 (95% confidence interval, 1.11–2.18) for favorable neurological status, 1.54 (95% confidence interval, 1.14–2.10) for 1-month survival, and 1.85 (95% confidence interval, 1.29–2.66) for 1-year survival.

Conclusion—
Outcomes from OHCA resulting from nonshockable rhythms, although poor by comparison with shockable rhythm presentations, improved significantly after implementation of resuscitation guideline changes, suggesting their potential to benefit all presentations of OHCA.
Dietary habits prone to lifestyle-related disease
Authors: Nagai M , Uyama O , Kaji H 
Published: April 2012

Objective: To evaluate relations among dietary habits, bone mineral density (BMD), visceral fat area (VFA), and arterial stiffness and recommend better dietary habits. Methods: One hundred and six men and 381 women (aged 18–84) received a health checkup and answered questionnaires, with subsequent measurements of BMD (speed of sound), VFA (bioelectrical impedance), and arterial stiffness (acceleration plethysmography). Results: Snacking, intake of meat, fried foods, sweet foods, and instant foods were associated with higher BMD; regular lunch hours, skipping meals, calorie restriction, and eating moderate amounts were associated with lower BMD as indicated using analysis of variance (ANOVA) analysis. Only skipping meals was an independent factor of high BMD. Age was an independent factor of low BMD, large VFA, and high arterial stiffness. Female sex was an independent factor of low BMD and VFA as indicated using multiple regression analysis. Conclusions and implications: BMD was associated with eating behaviours and food contents, among which only skipping meals was an independent contributor.
Analyzing repeated measures semi-continuous data, with application to an alcohol dependence study
Authors: Liu Lei , Strawderman Robert L , Johnson Bankole A , O'Quigley John M 
Published: April 2012

Summary Two-part random effects models (Olsen and Schafer, 1 Tooze et al. 2 ) have been applied to repeated measures of semi-continuous data, characterized by a mixture of a substantial proportion of zero values and a skewed distribution of positive values. In the original formulation of this model, the natural logarithm of the positive values is assumed to follow a normal distribution with a constant variance parameter. In this article, we review and consider three extensions of this model, allowing the positive values to follow (a) a generalized gamma distribution, (b) a log-skew-normal distribution, and (c) a normal distribution after the Box-Cox transformation. We allow for the possibility of heteroscedasticity. Maximum likelihood estimation is shown to be conveniently implemented in SAS Proc NLMIXED. The performance of the methods is compared through applications to daily drinking records in a secondary data analysis from a randomized controlled trial of topiramate for alcohol dependence treatment. We find that all three models provide a significantly better fit than the log-normal model, and there exists strong evidence for heteroscedasticity. We also compare the three models by the likelihood ratio tests for non-nested hypotheses (Vuong 3 ). The results suggest that the generalized gamma distribution provides the best fit, though no statistically significant differences are found in pairwise model comparisons.