bluuebunny/crossref_metadata_2025_split huggingface dataset:
Karanjin interferes with ABCB1, ABCC1, and ABCG2
Authors: Michaelis Martin , Rothweiler Florian , Nerreter Thomas , Sharifi Mohsen , Ghafourian Taravat , Cinatl Jindrich 
Published: March 2016

PURPOSE: The prominent ATP-binding cassette (ABC) transporters ABCB1, ABCC1, and ABCG2 are involved in substance transport across physiological barriers and therefore in drug absorption, distribution, and elimination. They also mediate multi-drug resistance in cancer cells. Different flavonoids are known to interfere with different ABC transporters. Here, the effect of the furanoflavonol karanjin, a potential drug with antiglycaemic, gastroprotective, antifungal, and antibacterial effects, was investigated on ABCB1, ABCC1, and ABCG2-mediated drug transport in comparison to the flavonoids apigenin, genistein, and naringenin. METHODS: Cells expressing the relevant transporters (ABCB1: UKF-NB-3ABCB1, UKF-NB-3rVCR10; ABCC1: G62, PC-3rVCR20; ABCG2: UKF-NB-3ABCG2) were used in combination with specific fluorescent and cytotoxic ABC transporter substrates and ABC transporter inhibitors to study ABC transporter function. Moreover, the effects of the investigated flavonoids were determined on the ABC transporter ATPase activities. RESULTS: Karanjin interfered with drug efflux mediated by ABCB1, ABCC1, and ABCG2 and enhanced the ATPase activity of all three transporters. Moreover, karanjin exerted more pronounced effects than the control flavonoids apigenin, genistein, and naringenin on all three transporters. Most notably, karanjin interfered with ABCB1 at low concentrations being about 1µM. CONCLUSIONS: Taken together, these findings should be taken into account during further consideration of karanjin as a potential drug for different therapeutic indications. The effects on ABCB1, ABCC1, and ABCG2 may affect the pharmacokinetics of co-administered drugs. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.METHODS: Cells expressing the relevant transporters (ABCB1: UKF-NB-3ABCB1, UKF-NB-3rVCR10; ABCC1: G62, PC-3rVCR20; ABCG2: UKF-NB-3ABCG2) were used in combination with specific fluorescent and cytotoxic ABC transporter substrates and ABC transporter inhibitors to study ABC transporter function. Moreover, the effects of the investigated flavonoids were determined on the ABC transporter ATPase activities.RESULTS: Karanjin interfered with drug efflux mediated by ABCB1, ABCC1, and ABCG2 and enhanced the ATPase activity of all three transporters. Moreover, karanjin exerted more pronounced effects than the control flavonoids apigenin, genistein, and naringenin on all three transporters. Most notably, karanjin interfered with ABCB1 at low concentrations being about 1µM.CONCLUSIONS: Taken together, these findings should be taken into account during further consideration of karanjin as a potential drug for different therapeutic indications. The effects on ABCB1, ABCC1, and ABCG2 may affect the pharmacokinetics of co-administered drugs.
A Systematic Review and Meta-Analysis of the Risk of Microbial Contamination of Aseptically Prepared Doses in Different Environments
Authors: Austin Peter David , Elia Marinos 
Published: March 2016

ABSTRACT

Purpose
To review microbial contamination rates and examine guidelines about preparation of individual and batch doses using aseptic techniques within pharmaceutical (controlled) and clinical (ward and theatre) environments.

Methods
Systematic review and meta-analysis.

Results
A total of 18 studies (7293 doses) were identified for analysis. A lower rate of contamination was found in a pharmaceutical compared to clinical environments when preparing either individual (6.8% v 3.3%; p=0.051; 10 studies (8 clinical 2 pharmaceutical)) or batch doses (8% v 0.05%; p
Can Pentoxifylline be used as Adjunct Therapy to ACE Inhibitors and ARBs in Preserving Kidney Function?
Authors: Carson Cody , Al-Makki Akram , Shepler Brian 
Published: March 2016

Purpose. To determine if there is sufficient evidence to recommend the addition of pentoxifylline to standard ACE inhibitor and ARB therapy in chronic kidney disease patients to reduce proteinuria and preserve kidney function. Methods: A search of the literature was conducted using the PubMed.gov and ClinicalTrials.gov search engines and the search terms “pentoxifylline renoprotection”, “pentoxifylline CKD”, and “pentoxifylline nephropathy”. Results were limited to studies in human subjects and published in the English language. No date range was specified. Studies focused on the effects of pentoxifylline on drug induced nephropathy were excluded. Results: Nine relevant articles were retrieved and evaluated. The two main populations studied were patients with chronic kidney disease (CKD) and patients with CKD and comorbid type 2 diabetes. Six of the nine studies reported a significant reduction in proteinuria in pentoxifylline treated patients. Four studies reported a significant change in estimated glomerular filtration rate (eGFR). Conclusion: Addition of pentoxifylline to ACE inhibitor and ARB therapy may improve proteinuria in CKD patients. There is conflicting evidence as to whether pentoxifylline will improve kidney function as measured by eGFR.Key words: pentoxifylline renoprotection, pentoxifylline CKD , pentoxifylline nephropathy.This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
Effectiveness of Academic Detailing to Optimize Medication Prescribing Behaviour of Family Physicians
Authors: Chhina Harpreet K , Bhole Vidula M , Goldsmith Charles , Hall Wendy , Kaczorowski Janusz , Lacaille Diane 
Published: March 2016

PURPOSE. To synthesize current knowledge about the effectiveness and the magnitude of the effect, of Academic Detailing (AD), as a stand-alone intervention, at modifying drug prescription behavior of Family Physicians (FPs) in primary care settings. METHODS. A search of MEDLINE, EMBASE, CENTRAL, and Web of Science databases of all English language articles between January 1983 and July 2010 was conducted. We hand-searched the bibliographies of articles retrieved from the electronic search to identify additional studies. Inclusion criteria were: full-length articles describing original research; randomized controlled trial (RCT), or observational study design with a control group; studies of AD delivered to FPs; AD as a stand-alone intervention; drug prescription as the target behavior. Data extraction was done independently by two reviewers. Outcomes evaluated were: the difference in relative change in prescription rate between the intervention and control groups; the difference in absolute change in prescription rate between the intervention and control groups; and effect size, calculated as the standardized mean difference. RESULTS. 11 RCTs and 4 observational studies were included. Five RCTS described results showing effectiveness, while 2 RCTs reported a positive effect on some of the target drugs. Two observational studies found AD to be effective, while 2 did not. The median difference in relative change among the studies reviewed was 21% (interquartile range 43.75%) for RCTs, and 9% (interquartile range 8.5%) for observational studies. The median effect size among the studies reviewed was - 0.09 (interquartile range 2.73). Conclusion. This systematic review demonstrates that AD can be effective at optimizing prescription of medications by FPs. Although variable, the magnitude of the effect is moderate in the majority of studies. This systematic review also provides evidence supportive of the use of AD as a strategy to promote evidence based prescription of medications or incorporation of clinical guidelines into clinical practice. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
Pravastatin Modulate Niemann-Pick C1-Like 1 and ATP-Binding Cassette G5 and G8 to Influence Intestinal Cholesterol Absorption
Authors: Kawase Atsushi , Hata Seiji , Takagi Mai , Iwaki Masahiro 
Published: March 2016

Purpose. Niemann-Pick C1-like 1 (NPC1L1), ATP-binding cassette (ABC)G5, and ABCG8 mediate intestinal cholesterol absorption. It is unclear whether pravastatin (PR) or ezetimibe (EZ) affect expression of these transporters. We examined the effects of PR and EZ on NPC1L1, ABCG5, and ABCG8 expression in human hepatoma HepG2 cells and the murine small intestine. We also assessed expression of the transcription factors liver X receptor (LXR)a, LXRb and sterol regulatory element-binding protein. Methods. Transporter mRNA levels were determined in murine small intestines 6 and 24 h after oral PR and EZ administration by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). In PR- and EZ-treated HepG2 cells, transporter and transcription factor mRNA and protein levels were examined by RT-PCR and western blot, respectively. Results. Significant decreases in NPC1L1, ABCG5, and ABCG8 mRNA expression were observed in the duodenum, but not jejunum and ileum, of mice 24 h after treatment with PR, but not EZ. In HepG2 cells, PR but not EZ treatment for 24 h also significantly decreased NPC1L1 protein and ABCG5, and ABCG8 mRNA expression, while increasing LXRa mRNA levels. Conclusion. PR but not EZ treatment reduced duodenal cholesterol transporter expression in mice. PR-induced increases in LXRa mRNA levels may be involved in attenuation of NPC1L1 expression, subsequently decreasing intestinal cholesterol absorption. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
Interactions Between Nutraceutical Supplements and Standard Acute Myeloid Leukemia Chemotherapeutics
Authors: Spagnuolo Paul 
Published: March 2016

PURPOSE: Concomitant use of nutraceuticals with chemotherapy is very common. Cancer patients self-medicate to relieve the side effects associated with chemotherapy, improve disease outcome and to regain control of their medical care. However, there is limited empirical evidence on potential drug-nutraceutical interactions and their resulting effect on chemotherapy efficacy. METHOD: To investigate drug-nutraceutical interactions we created and screened a library of commonly used nutraceuticals for their modulatory effects on the activity of cytarabine and daunorubicin, two primary chemotherapeutics used to treat acute myeloid leukemia (AML). Combination screening was performed in 3 AML cell lines (OCI-AML2, KG1a and U937) using the MTS viability assay. Lead compounds were validated using with the Annexin V/ Propidium iodide assay and CalcuSyn drug combination software. RESULTS: We identified zinc as a nutraceutical that enhanced AML chemotherapy efficacy with combination index (CI) values of 0.649, 0.632 and 0.615 at EC 25, 50 and 75, respectively; CI values <0.9, >1.1 or between 0.9-1.1 denote statistical synergy, antagonism or additivity, respectively. In contrast, we show that echinacea hindered AML chemotherapy efficacy by significantly reducing the ability of cytarabine to induce cell death. CONCLUSION: Given the positive and negative effects of nutraceuticals, patients undergoing chemotherapy must consult with their oncologist before consuming over-the-counter supplements. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
Attenuation of Oxidative Stress in HEK 293 Cells by the TCM Constituents Schisanhenol, Baicalein, Resveratrol or Crocetin and Two Defined Mixtures
Authors: Bend John Richard , Xue Yan Xia Xue Yan (Iris) , Chen Daofeng , Awaysheh Abudi , Lo Andrea , Rieder Michael John , Rylett Rebecca Jane 
Published: March 2016

PURPOSE: Our working hypothesis is that single bioactive phytochemicals with antioxidant properties that are important constituents of Traditional Chinese Medicine (TCM) and their defined mixtures have potential as chemoprotective agents for chronic conditions characterized by oxidative and nitrosative stress, including Alzheimer’s. Here we evaluate the ability of baicalein, crocetin, trans-resveratrol or schisanhenol and two defined mixtures of these TCM phytochemicals to attenuate the toxicity resulting from exposure to cell permeant t-butyl hydroperoxide (tBPH) in wild-type and bioengineered (to express choline acetyltransferase) HEK 293 cells. METHODS: Endpoints of tBHP-initiated oxidative and nitrosative stress in both types of HEK 293 cells and its attenuation by TCM constituents and mixtures included cytotoxicity (LDH release); depletion of intracellular glutathione (GSH); formation of S-glutathionylated proteins; oxidative changes to the disulfide proteome; and real-time changes in intracellular redox status. RESULTS: At low µM concentrations, each of the TCM constituents and mixtures effectively attenuated intracellular toxicity due to exposure of HEK 293 cells to 50 or 250 µM tBHP for 30 min to 3 h. Confocal microscopy of HEK 293 cells transfected with mutated green fluorescent protein (roGFP2) showed effective attenuation of tBHP oxidation by baicalein in real time. Three redox-regulated proteins prominent in the disulfide proteome of HEK 293 cells were identified by MALDI-TOF mass spectrometry. CONCLUSIONS: We conclude that single TCM chemicals and their simple mixtures have potential for use in adjunct chemoprotective therapy. Advantages of mixtures compared to single TCM constituents include the ability to combine compounds with varying molecular mechanisms of cytoprotection for enhanced biological activity; and to combine chemicals with complementary pharmacokinetic properties to increase half-life and prolong activity in vivo. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
Enhanced Prokaryotic Expression of Dengue Virus Envelope Protein
Authors: Ganguly Advaita , Malabadi Ravindra B. , Das Dipankar , Suresh Mavanur R. , Sunwoo Hoon H 
Published: March 2016

Purpose. To highlight the expression and purification of the recombinant dengue virus type-1 antigen exploiting the codon optimized full length envelope for increased yield in E. coli. Methods. A 6x His tag was inserted at the C terminus to facilitate purification. The purified protein was recognized in Western blot by Monoclonal antibody specific for the tag. The in vitro refolded recombinant protein was used to immunize mice for the development of hybridomas and also analyzed for its biological functionality with heparan sulfate binding assay. Results. The polyclonal anti-sera from the immunized mice were found to recognize the envelope protein thereby establishing the immunogenicity of the protein. Conclusion. The purified envelope protein could potentially be used towards dengue diagnostics and vaccine development efforts. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
Rheological Investigation of Self-emulsification Process: Effect of Co-surfactant
Authors: Biradar Shailesh V , Dhumal Ravindra S , Paradkar Ananat R. 
Published: March 2016

PURPOSE
The aim of study is to investigate role of co-surfactant in self-emulsification through rheological analysis of intermediate liquid crystalline (LC) phase formed during self-emulsification.

METHODS
To mixture of Captex® 200P (C200) and tween 80 (T80) (SES Plain), either medium hydrocarbon chain co-surfactant (Capmul® MCM (CMCM): SES C) or long hydrocarbon chain co-surfactant (Peceol® (P): SES P) was added separately at different concentration levels. Self-emulsification was monitored by visual observations, turbidimetric and droplet size measurement. Mesophases were obtained by 30% v/v aqueous hydration of SES and characterized by polarizing microscopy, differential scanning calorimetry (DSC) and rheological studies.

RESULTS
SES Plain exhibited ‘bad’ emulsification owing to instantaneous gel formation in aqueous media. Almost all SES C have shown ‘good’ emulsification with transparent appearance, very low turbidity value and nano size droplets. All SES P presented ‘moderate’ emulsification with milky appearance, high turbidity value and coarse droplets. Polarizing microscopy revealed formation of lamellar phase in SES Plain and in all SES P while almost all SES C exhibited formation of micellar cubic phase. In DSC studies, higher extent of LC phase formation was observed in SES C as compared to SES P. Rheological study clearly demonstrated presence of elastic and partially recoverable mesophase in SES Plain, which was transformed into a viscous and non-recovering mesophase with addition of CMCM while there was no change in rheological status of SES Plain after addition of P. The weak and viscous LC phase in SES C must have not presented any resistance to strain induced deformation. Therefore, it might have ruptured easily and quickly, releasing jet of nanosize droplets whereas elastic mesophase in SES P might have ruptured with little resistance resulting in coarse droplets.

CONCLUSION
The ability of co-surfactant to promote self-emulsification was attributed to their influence on viscoelastic properties of intermediate LC phase.
Docetaxel Distribution Following Intraperitoneal Administration in Mice
Authors: Zahedi Payam , De Souza Raquel , Piquette-Miller Micheline , Allen Christine 
Published: March 2016

Purpose: Intraperitoneal (IP) chemotherapy with high molecular weight lipophilic antineoplastic agents such as the taxanes has shown promise in clinical trial evaluation for treatment of localized peritoneal cancers. We have previously developed an IP injectable hydrogel formulation (PoLigel) for sustained peritoneal delivery of docetaxel (DTX), and observed significant efficacy in murine models of ovarian cancer when compared to Taxotere®, the FDA approved formulation of DTX. In order to understand the relationship between drug distribution and efficacy, the current study compares the tissue distribution and pharmacokinetics of DTX administered IP in the PoLigel or Taxotere® formulations.
Methods: The PoLigel was prepared by blending a water-soluble chitosan derivative, egg phosphatidylcholine and lauric aldehyde with DTX (drug to material ratio 1:8 w/w). DTX concentrations in plasma, heart, liver, spleen, stomach, intestine, kidney and peritoneal muscle were measured over a five day period following IP administration of the PoLigel and Taxotere® formulations in CD-1 female mice.
Results: Three days after Taxotere® administration, no detectable levels of DTX were seen in plasma, while sustained DTX plasma levels of 0.06 ug/ml ± 0.01 per day were observed with PoLigel. At five days post Taxotere® administration, only intestine, stomach and peritoneal muscle showed detectable DTX concentrations whereas all tissues and plasma showed sustained DTX levels in mice that received PoLigel. DTX concentrations that resulted from PoLigel administration were significantly higher in the peritoneal cavity and 200 fold higher than concentrations found in plasma.
Conclusions: Overall, the PoLigel formulation increases tissue and plasma drug retention and provides sustained DTX levels compared to the clinically used Taxotere® formulation. The sustained DTX levels seen in the peritoneal cavity following IP administration of the PoLigel may be responsible for the improvement in efficacy that has been observed in our previous studies.
Emerging Significance of Flavonoids as P-Glycoprotein Inhibitors in Cancer Chemotherapy
Authors: Bansal Tripta , Jaggi Manu , Khar Roop , Talegaonkar Sushama 
Published: March 2016

Chemotherapy forms the mainstay of cancer treatment particularly for patients who do not respond to local excision or radiation treatment. However, cancer treatment by drugs is seriously limited by P-glycoprotein (P-gp) associated multi-drug resistance (MDR) in various tumor cells. On the other hand, it is now widely recognized that P-gp also influences drug transport across various biological membranes. P-gp transporter is widely present in the luminal surface of enterocytes, biliary canalicular surface of hepatocytes, apical surface of proximal tubular cells of kidney, endothelial cells of blood brain barrier, etc. thus affecting absorption, distribution, metabolism and excretion of xenobiotics. Clinical significance of above mentioned carrier is appreciated from the fact that more than fifty percent of existing anti-cancer drugs undergo inhibitable and saturable P-gp mediated efflux. Consequently, there is an increasing trend to optimize pharmacokinetics, enhance antitumour activity and reduce systemic toxicity of existing anti-cancer drugs by inhibiting P-gp mediated transport.
Although a wide variety of P-gp inhibitors have been discovered, research efforts are underway to identify the most appropriate one. Flavonoids (polyphenolic herbal constituents) form the third generation, non-pharmaceutical category of P-gp inhibitors. The effects produced by some of these components are found to be comparable to those of well-known P-gp inhibitors verapamil and cyclosporine. Identification of effective P-gp modulator among herbal compounds have an added advantage of being safe, thereby making them ideal candidates for bioavailability enhancement, tissue-penetration (e.g. blood brain barrier (BBB)), decreasing biliary excretion and multi-drug resistance modulating agents. The dual effects, i.e. P-gp modulation and antitumor activity, of these herbal derivatives may synergistically act in cancer chemotherapy. This paper presents an overview of the investigations on the feasibility and application of flavonoids as P-gp modulators for improved efficacy of anti-cancer drugs like taxanes, anthracyclines, epipodophyllotoxins, camptothecins and vinca alkaloids. The review also focuses on flavonoid-drug interactions as well as the reversal activity of flavonoids useful against MDR. In addition, the experimental models which could be used for investigation on P-gp mediated efflux are also discussed.
Pharmacodynamics of Rocuronium in Cholestatic Patients with or without Hepatocellular Injury : Normal Onset Time of Initial Dose and Prolonged Duration Time After Repeated Doses
Authors: Yang Jian-jun , Wang Yong-guang , Zhang Zhuan , Zhang Zhi-jie , Liu Jin , Xu Jian-guo 
Published: March 2016

Purpose. A prospective controlled study was designed to observe the pharmacodynamics of rocuronium in cholestatic patients with or without hepatocellular injury. Methods. Sixty patients undergoing abdominal surgery were allocated into three groups: group I had 20 cholestatic patients with hepatocellular injury; group II had 20 cholestatic patients without hepatocellular injury, and group III (control group) had 20 patients without hepatic disease. Anesthetized with propofol and fentanyl, all patients received rocuronium 0.6 mg/kg for initial dose followed by intermittent repeated administration of rocuronium 0.15 mg/kg. The twitch high of adductor pollicis muscle was monitored by acceleromyography. The onset time of the initial dose, the duration time of the initial and the repeated doses, and the recovery index were observed. Results. The onset and the duration time of the initial dose had no significant difference among the three groups (P>0.05). After administration of the 5th dose, the duration time of the repeated doses was significantly prolonged than that of the 2nd dose in group I
(31±8 versus 22±4 min) and group II (28±5 versus 21±4 min) (P0.05). The recovery index of rocuronium was longer in group I (48±13 min) and group II (46±9 min) than that in group III (24±5 min) (P