bluuebunny/crossref_metadata_2025_split huggingface dataset:
Poly[N-(2-aminoethyl)ethyleneimine] as a New Non-Viral Gene Delivery Carrier: The Effect of Two Protonatable Nitrogens in the Monomer Unit on Gene Delivery Efficiency
Authors: Khazaie Yahya , Dorkoosh Farid Abedin , Novo Luis , Gaal Ethlinn Van , Fassihi Afshin , Mirahmadi-Zareh Seyedeh Zohreh , Esfahani Mohammad Hossein Nasr , Van Nostrum Cornelus F. , Hennink Wim E. 
Published: March 2016

Purpose. The aim of this study was to investigate the in vitro gene delivery efficiency of poly[N-(2-aminoethyl)ethylene-imine](PAEEI), a polymer with a linear Polyethyleneimine (LPEI) backbone and with aminoethyl side groups that has two protonatable nitrogen atoms per monomer unit instead of one as in LPEI (an established gene delivery polymer). Method. PAEEI (Mn=4.5 kDa, Mw= 10 kDa) was synthesized by ring-opening polymerization of N-(2-(1’-aziridino)ethyl)formamide followed by hydrolysis of the amide groups. The buffering capacity of the resulting polymer was determined by acid-base titration and consequently the percentage of the protonated nitrogen atoms was calculated. Polyplexes were prepared separately in buffers with different ionic strength including Hepes buffered saline (150 mM NaCl) and Hepes buffered glucose (5% glucose) and their zeta-potential, hydrodynamic diameter and colloidal stability were measured. Transfection activity (and toxicity in Hela cells) of the polyplexes were done in HeLa, CHO and HEK293T cells. Cell incubations with polyplexes were done both in the presence and absence (HeLa cells) of serum. Results. PAEEEI showed two times more buffering capacity than LPEI. PAEEI-based Polyplexes had about the same size and zeta-potential as those of LPEI, with a higher colloidal stability in saline buffer in continuous particle size measurement. Their transfection activity was slightly higher than 22-kDa LPEI polyplexes whereas their toxicity profiles were similar in cell lines studied. The PAEEI polyplexes showed gene expression activity both in the presence and absence of serum. Conclusion. Paying attention to the fact that LPEI molecules with smaller sizes than 22 kDa show less transfection efficiency than LPEI 22, the effect of smaller size of PAEEI (10 kDa) on the gene delivery efficiency was compensated by its higher buffering capacity due to carrying more protonatable nitrogen per monomeric unit comparing with LPEI (22 kDa). Having slightly higher transfection efficiency and better colloidal stability than PEI-based systems, PAEEI is an attractive candidate for future in vivo gene delivery studies.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.
The Impact of Implementation of the Canadian Regulatory Requirements on the Quality of Natural Health Products: The Glucosamine Case
Authors: Aghazadeh-Habashi Ali , Duke John , Jamali Fakhreddin 
Published: March 2016

ABSTRACT – Purpose. We investigated whether the recent implementation of the regulatory requirements for the entry to the Canadian market of natural products has resulted in improved quality of the available glucosamine products. Methods. Eleven available products, of which 8 had been tested in 2002 (7 had contained substantially lower than the label claim of the active ingredient), and a European pharmaceutical grade tablet were assayed for their glucosamine content. The potassium and sodium contents of the products were also tested. Results. Nine of the 11 Canadian products and the European tablet had more than 91% of the label claim of the active ingredient, hence, met the criterion. Two products contained 71 and 78% label claim. The electrolyte contents were very variable but constituted only a small fraction of the daily requirements. Conclusion. Most tested glucosamine products passed the Health Canada requirements. This improvement is likely due to the publicity regarding the low quality of the products in the past and also a result, at least in part, of the introduction of the new regulatory requirements. The sub-standard quality of a few tested products is still of concern.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.
A Rapid and Sensitive HPLC Method for Quantitation of Paclitaxel in Biological Samples using Liquid-Liquid Extraction and UV Detection: Application to Pharmacokinetics and Tissues Distribution Study of Paclitaxel Loaded Targeted Polymeric Micelles in.....
Authors: Rezazadeh Mahboubeh , Emami Jaber , Mostafavi Abolfazl , Rostami Mahboubeh , Hassanzadeh Farshid , Sadeghi Hojjat , Minaiyan Mohsen , Lavasanifar Afsaneh 
Published: March 2016

A simple, rapid, and sensitive reversed-phase HPLC method was developed and validated for determination of paclitaxel (PTX) in plasma, various organs and tumor tissues of tumor-bearing mice. Tissue specimens of liver, kidneys, spleen, lungs, heart and tumor were separately homogenized in normal saline. Plasma or tissue homogenate (250 µl) containing PTX and internal standard (diazepam) were extracted by diethyl ether (6 ml). The separation was achieved on a µ-Bondapak C18 HPLC column using sodium acetate buffer solution (0.01 M)/acetonitrile (58/42 v/v) at pH 5 ± 0.1 and flow rate of 1.9 mL/min. The effluent was monitored at 227 nm and column temperature was adjusted at 58ºC. The internal standard and PTX were eluted at 4.2 and 5.2 min, respectively and no interfering peaks were observed. Calibration curves were linear over the concentration range of 0.25-10 µg/ml of PTX in plasma and 0.3-20 µg/ml PTX in tissue homogenates with acceptable precision and accuracy (<15%). The mean recoveries of the drug after plasma extraction was 87.4% ± 3.6 while those of tissue homogenates ranged from 62.1± 4.5 to 75.5± 3.2 depending on the type of tissues studied. PTX was stable in samples with no evidence of degradation during 3 freeze–thaw cycles and 3 months storage at −70 °C. The developed HPLC method was applied to quantify PTX in the mouse plasma and tissues after intravenous administration of 10 mg equivalent PTX/Kg dose of PTX-loaded tocopherol succinate-chitosan-polyethylene glycol-folate (TS-CS-PEG-FA) micelles formulation or Anzatax® (Cremophor® EL- based formulation of PTX) to female Balb/c mice. 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.
Melatonin Interaction Resulting in Severe Sedation
Authors: Foster Brian C , Cvijovic Kosta , Boon Heather S , Tam Teresa W , Liu Rui , Murty Mano , Vu Duc , Jaeger Walter , Tsuyuki Ross T , Barnes Joanne , Vohra Sunita 
Published: March 2016

Purpose. Natural health products (NHPs), including melatonin, are widely used products. Despite the widespread assumption that all NHPs are safe, they contain pharmacologically active substances and can therefore have adverse effects and/or interact with pharmaceuticals. Objective: To investigate the mechanism underlying NHP interactions identified through the Pharmacy SONAR active surveillance study. Methods: Active surveillance was undertaken in community pharmacies to identify adverse events in patients who had recently taken NHPs together with conventional pharmaceuticals. For suspected NHP-pharmaceutical interactions, the possible mechanism of action was explored by in vitro analysis of samples of different products to identify cytochrome P450 enzyme (CYP) inhibition potential. Results: Active surveillance identified a 19-year-old male taking citalopram, nortriptyline and oxycodone concomitantly and who experienced severe sedation when melatonin was added to this regimen. In vitro analysis involving several melatonin products showed product-dependent inhibition of CYP1A2, CYP2C19 and CYP3A7. Conclusion: The adverse event was likely due to a primary pharmacokinetic interaction between melatonin and citalopram; although mechanistically, interactions affecting cytochrome P450-mediated metabolism may have occurred with all of these health products. A pharmacodynamic interaction may also be possible, but beyond the capacity of this study to establish.Key words: Melatonin, citalopram, nortriptyline, oxycodone, drug interaction. 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.
Retrospective and Prospective Human Intravenous and Oral Pharmacokinetic Projection of Dipeptidyl peptidase-IV Inhibitors Using Simple Allometric Principles – Case Studies of ABT-279, ABT-341, Alogliptin, Carmegliptin, Sitagliptin and Vildagliptin
Authors: Gilibili Ravindranath R , Bhamidipati Ravi Kanth , Mullangi Ramesh , Srinivas Nuggehally R 
Published: March 2016

Purpose: The purpose of this exercise was to explore the utility of allometric scaling approach for the prediction of intravenous and oral pharmacokinetics of six dipeptidy peptidase-IV (DPP-IV) inhibitors viz. ABT-279, ABT-341, alogliptin, carmegliptin, sitagliptin and vildagliptin. Methods: The availability of intravenous and oral pharmacokinetic data in animals enabled the allometry scaling of 6 DPP-IV inhibitors. The relationship between the main pharmacokinetic parameters [viz. volume of distribution (Vd) and clearance (CL)] and body weight was studied across three or four mammalian species, using double logarithmic plots to predict the human pharmacokinetic parameters of CL and Vd using simple allometry. Results: A simply allometry relationship: Y = aWb was found to be adequate for the prediction of intravenous and oral human clearance/volume of distribution for DPP-IV inhibitors. The allometric equations for alogliptin, carmegliptin, sitagliptin, vildagliptin, ABT-279 and ABT-341 were 1.867W0.780, 1.170W0.756, 2.020W0.529, 1.959 W0.847, 0.672 W1.016, 1.077W 0.649, respectively, to predict intravenous clearance (CL) and the corresponding equations to predict intravenous volume of distribution (Vd) were: 3.313W0.987, 6.096W0.992, 7.140W0.805, 2.742W0.941, 1.299W0.695 and 5.370W0.803. With the exception of a few discordant values the exponent rule appeared to hold for CL (0.75) and Vd (1.0) for the predictions of various DPP-IV inhibitors. Regardless of the routes, the predicted values were within 2-3 fold of observed values and intravenous allometry was better than oral allometry. Conclusion: Simple allometry retrospectively predicted with reasonable accuracy the human reported values of gliptins and could be used as a prospective tool for this class of 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.
Smart Polymeric Nanofibers for Topical Delivery of Levothyroxine
Authors: Fathi Azarbayjani Anahita , Venugopal Jayarama Reddy , Ramakrishna Seeram , Lim Fung Chye , Chan Yew Weng , Chan Sui Yung 
Published: March 2016

Topical administration of levothyroxine (T4) helps to reduces deposits of adipose tissue on skin. The question is whether topical application of T4 could lead to systemic effects.
In the present study a series of nanofibrous membranes were electrospun into blends of poly vinyl alcohol (PVA) and poly-N-isopropylacrylamide (PNIPAM) to develop a sustained topical delivery of T4. The polymeric nanofiber mats were characterized by field emission scanning electron microscopy (FESEM) and fourier transform infrared (FTIR) spectroscopy. In vitro permeation of the drug from the polymeric nanofibers was studied using excised human skin and the permeation mechanism investigated using confocal microscopy.
It was observed that polymeric nanofibers were able to sustain the penetration of T4 to the skin and help maintain the effective drug concentration in the skin layers for longer period of time. These formulations may have potential uses in topical skin products and can help to increase the accumulation of the active compound on the skin surface thus minimize the adverse side effects which may be caused by systemic absorption. This may result in great improvement in consumer compliance, avoid frequent dosing and enhance the therapeutic effectiveness.
Quercetin Ameliorates Experimental Autoimmune Myocarditis in Rats
Authors: Milenković Marina , Arsenović-Ranin Nevena , Stojić-Vukanić Zorica , Bufan Biljana , Vučićević Dragana , Jančić Ivan 
Published: March 2016

Purpose: Experimental autoimmune myocarditis (EAM) in rats is an animal model of human giant cell myocarditis and post-myocarditis dilated cardiomyopathy. The pathogenesis of EAM has not been elucidated, but there is accumulating evidence that cytokines secreted from monocytes/macrophages and T cells play a crucial role in the induction and progression of disease. Flavonoids are a large group of polyphenolic compounds abundantly present in the human diet, which scavenge oxygen radicals and have anti-inflammatory activities. Having in mind in vivo beneficial effects of flavonoid quercetin in different animal models of immunoinflammatory diseases such as experimental autoimmune encephalomyelitis and adjuvant arthritis, on the one side, and its in vitro suppressive effect on production of tumor necrosis factor–alpha (TNF-alpha on the other side, we investigated the effects of quercetin on EAM in rats.
Methods: Myocarditis was induced in Dark Agouti (DA) rats by injection of porcine cardiac myosin and quercetin at doses of 10 or 20 mg/kg was orally administered from days 0 to 21 after induction of disease. The severity of myocarditis was evaluated by determination of heart weight / body weight ratio (Hw/Bw) and histopathological examination of hearts. The levels of cytokines (TNF-alpha, IL-12, IL-17 and IL-10) in serum and lymph node cells (LNC) culture supernatants were measured by ELISA.
Results: The rats treated with 20 mg/kg of quercetin had significantly decreased incidence of EAM, Hw/Bw, macroscopic and microscopic scores of hearts. Further, in EAM rats treated with quercetin levels of TNF-alpha and IL-17 were significantly lower, while the level of IL-10 was significantly higher both in serum and culture supernatants of LNC stimulated with concanavalin A compared with vehicle-treated animals.
Conclusions: The present study suggests that quercetin ameliorates EAM, at least in part, by interfering production of proinflammatory (TNF-alpha and IL-17) and/or anti-inflammatory (IL-10) cytokines.
Predictors of Pharmacy Students’ Intentions to Monitor Diabetes
Authors: Guirguis Lisa M , Chewning Betty A , Kieser Mara A 
Published: March 2016

PURPOSE: This research explores predictors of pharmacy students’ adoption of one specific behavior, monitoring diabetes ABCs (A1c, blood pressure, and cholesterol) in the community pharmacy. Specifically, this research assessed which student situation and attitudinal factors are predictors of students’ intentions and behavior in asking patients about the diabetes targets and goals as per a conceptual model.
METHODS: Data was drawn from a randomized controlled trial to assess the impact of the diabetes check in pharmacy students during their community pharmacy clerkships. A survey measured students’ self-efficacy, outcome expectancies, role beliefs, mattering as well as students’ experiences with the Diabetes Check and intentions to routinely monitor diabetes. Stepwise hierarchical multiple linear regression reflected the conceptual model and was used to assess the research questions.
RESULTS: Survey response rate was 94% and analysis was performed on a sample of 118 students. In summary, pharmacy students’ intentions and monitoring behaviors were predicted by the students’ situation and attitudes. Specifically, students’ intentions to ask patients about the diabetes ABCs were predicted by pharmacy site counseling, monitoring role beliefs, self-efficacy, and positive outcome expectancies (F(7, 109)=21.39, p
Effects of Ginkgo biloba Extract EGb 761, Donepezil and their Combination on Central Cholinergic Function in Aged Rats
Authors: Stein Christoph , Hopfeld Julia , Lau Helene , Klein Jochen 
Published: March 2016

Purpose. Ginkgo extract EGb 761 and cholinesterase inhibitors have been shown to be effective in the treatment of dementia patients. In addition to neuroprotective effects, Ginkgo extract EGb 761 has been reported to elevate brain levels of certain neurotransmitters such as dopamine, noradrenaline, and acetylcholine. In the present study, we investigated the impact of EGb 761, donepezil and the combination of both drugs on the central cholinergic system in aged rats. Methods. 24 month old rats received EGb 761 (100 mg/kg/day), donepezil (1.5 mg/kg/day), the combination of both drugs or vehicle control by oral gavage for 14 days. We used microdialysis in rat hippocampus to monitor extracellular concentrations of acetylcholine (ACh), choline, glucose and lactate. Brain homogenates were prepared to measure activities of acetylcholinesterase (AChE), choline acetyltransferase (ChAT) and high affinity choline uptake (HACU). Results. While EGb 761 alone had no effect, donepezil and the combination of donepezil and EGb 761 increased basal ACh levels by 2- to 3-fold. Concomitantly, significant reductions of AChE and HACU were measured in both groups. No differences were seen between donepezil and the combination in these parameters. Treatment with EGb 761 decreased extracellular choline release and showed a tendency to moderately elevate ChAT activity. Conclusions. We found that donepezil and EGb 761 do not display a pharmacological interaction when given together. Adding EGb 761 did not modify the effects of donepezil on the hippocampal cholinergic system. Reduced choline levels indicate neuroprotective properties of EGb 761. Therefore, the combination of EGb 761 and donepezil may be beneficial in the treatment of Alzheimer’s disease (AD). 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.
Quantitative Structure – Pharmacokinetics Relationships Analysis of Basic Drugs: Volume of Distribution
Authors: Zhivkova Zvetanka Dobreva , Mandova Tsvetelina , Doytchinova Irini 
Published: March 2016

Purpose. The early prediction of pharmacokinetic behavior is of paramount importance for saving time and resources and for increasing the success of new drug candidates. The steady-state volume of distribution (VDss) is one of the key pharmacokinetic parameters required for the design of a suitable dosage regimen. The aim of the study is to propose a quantitative structure – pharmacokinetics relationships (QSPkR) for VDss of basic drugs. Methods: The data set consists of 216 basic drugs, divided to a modeling (n = 180) and external validation set (n = 36). 179 structural and physicochemical descriptors are calculated using validated commercial software. Genetic algorithm, stepwise regression and multiple linear regression are applied for variable selection and model development. The models are validated by internal and external test sets. Results: A number of significant QSPkRs are developed. The most frequently emerged descriptors are used to derive the final consensus model for VDss with good explanatory (r2 0.663) and predictive ability (q2LOO-CV 0.606 and r2pred 0.593). The model reveals clear structural features determining VDss of basic drugs which are summarized in a short list of criteria for rapid discrimination between drugs with a large and small VDss. Conclusions: Descriptors like lipophilicity, fraction ionized as a base at pH 7.4, number of cycles and fused aromatic rings, presence of Cl and F atoms contribute positively to VDss, while polarity and presence of strong electrophiles have a negative effect. 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.
Losartan Protects the Heart Against Ischemia Reperfusion Injury: Sirtuin3 Involvement
Authors: Klishadi Mohsen Sharifi , Zarei Farideh , Hejazian Seyyed Hassan , Moradi Ali , Hemati Mahdieh , Safari Fatemeh 
Published: March 2016

PURPOSE: Sirtuin-3 (SIRT3) deacetylase protects the heart against oxidative stress via survival factors upregulation. Clinical and experimental studies have demonstrated that activation of systemic and local renin-angiotensin system (RAS) is implicated in ischemia-induced cardiac injury. However, the relation between RAS and SIRT3 in pathophysiology of myocardial ischemia reperfusion is unknown. In this study, the cardiac transcription and expression of SIRT3 levels was examined in response to ischemia reperfusion in untreated and losartan treated rats. METHODS: Rats were divided into control group, losartan group (L), and ischemia reperfusion (IR) groups with (L+IR) or without losatran pretreatment. Some rats were included as sham-operated and saline groups. IR was induced by left anterior descending artery occlusion. SIRT3 protein levels were determined by Western blot technique. The genes expression was specified by real-time RT-PCR. Arrhythmias were assessed according to the Lambeth conventions. RESULTS: In L+IR group a significant reduction was noted in the number of ventricular ectopic beats (VEBs) and episodes of ventricular tachycardia (VT) (VEBs: P<0.001; VT: P<0.01 vs. IR). In IR group, SIRT3 protein level was decreased in the ischemic tissue by 26.7±5.9% (P<0.01 vs. Control). However, in the non-ischemic tissue the changes of SIRT3 protein content were not significant. In L+IR group SIRT3 protein levels in the ischemic part of Left ventricle were significantly different from IR group (P<0.001). SIRT3 mRNA level did not change significantly among the experimental groups. Thioredoxin-1 and catalase transcription level was increased in L+IR group compared to IR group (P<0.01). CONCLUSION: A decreased SIRT3 protein levels subsequent to IR might be a novel signaling mechanism involved in IR injury. Losartan at non–hypotensive dose exerts anti-ischemic effects in part by normalizing the SIRT3 protein level and upregulating the survival factors encoding genes transcription in ischemic tissue of the heart. 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.