bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Use of Sonophoresis in the Administration of Drugs Throughout the Skin
Authors: Escobar-Chavez Jose Juan , Bonilla-Martínez Dalia , Villegas-González Martha Angélica , Rodríguez-Cruz Isabel Marlen , Domínguez-Delgado Clara Luisa 
Published: March 2016

Abstract

Transdermal drug delivery offers an attractive alternative to the conventional drug delivery methods of oral administration and injection. However, the stratum corneum acts as a barrier that limits the penetration of substances through the skin. Application of ultrasound to the skin increases its permeability (sonophoresis) and enables the delivery of various substances into and through the skin.
Ultrasound has been used extensively for medical diagnostics and to a certain extent in medical therapy (physiotherapy, ultrasonic surgery, hyperthermia). Nevertheless, it has only recently become popular as a technique to enhance drug release from drug delivery systems. A number of studies suggest the use of ultrasound as an external mean of delivering drugs at increased rates and at desired times.
This review presents the main findings in the field of sonophoresis, namely transdermal drug delivery and transdermal monitoring. Particular attention is paid to proposed enhancement mechanisms and trends in the field of topical and transdermal delivery.
Conference 2015: Drug Discovery and Development in the Post Genomic Era. An international symposium held jointly by CSPS and CC-CRS, May 26-28, 2015, Toronto, ON, Canada
Authors: Berekoff Beverley 
Published: March 2016

Plenaries and Special Presentations:Shana Kelley, University of Toronto: "New Technologies for Ultrasensitive Analysis of Clinically-relevant Biomolecules"Richard Hargreaves, BIOGEN IDEC: "Imaging in CNS Drug Discovery and Development"Roger Williams: CSPS Lifetime Achievement Award - "0.5 X 102: Looking Back and Forward"Neal Davies, University of Manitoba: CSPS Award of Leadership in Canadian Pharmaceutical Sciences - "30 Years of Coffee, Beer and Serendipity in Pharmacy Research"Conference Sessions:Special CSPS Session: The Future of Pharmaceutical Sciences1. The Evolving Business of Pharmaceuticals2. Analysis of Peptide and Protein Drug Targets by LC/MS/MS3. Mucosal Drug Delivery4. New Methodologies of Genome Wide Target Validation5. Regulatory Updates and Developments6. Antibody-based Therapeutics7. Imaging in Drug Delivery8. Nuclear Receptors in Drug Discovery9. IV-IVC Modeling and Simulation as a Tool to Facilitate Drug Development and Marketing10. Pharmacogenomics in Drug Development11. Bioavailability of Novel Dosage Forms
HPLC Analysis of Mesembrine-Type Alkaloids in Sceletium Plant Material Used as An African Traditional Medicine
Authors: Patnala Srinivas , Kanfer Isadore 
Published: March 2016

Abstract
PURPOSE: Sceletium plant species have been reported to contain psychoactive alkaloids, specifically belonging to mesembrine-type alkaloids. Sceletium is presently marketed through health shops and on the internet as dried plant powder and as pharmaceutical dosage forms and purported to be useful in the treatment of psychological disorders. However, there are no validated analytical methods and reference standards of the relevant alkaloids are not commercially available for use in the analysis and quality control of Sceletium products and dosage forms. Hence, the objective of this research was to isolate and characterize appropriate analytical markers for use in the assay and as well as markers for fingerprinting by high performance liquid chromatography (HPLC). METHODS: The separation of the relevant alkaloids was carried out on a C18 column and detected at a UV wavelength of 228nm. The method was validated and used to assay the mesembrine-type alkaloids namely Δ7mesembrenone, mesembranol, mesembrenone, mesembrine and epimesembranol. RESULTS: The calibration curves were found to be linear over the entire concentration range of 400-60,000 ng/ml with correlation coefficients >0.99. The accuracies of the relevant alkaloids were found to be between 94.8 and 103.6% with an inter-day relative standard deviation (RSD) of less than 2.8%. The precision studies showed inter-day RSD’s of less than 3%. The recoveries were all within the range of 95 and 105% (RSD
Lipid-lowering Activity of Natural and Semi-Synthetic Sterols and Stanols
Authors: Taha Dhiaa A , Wasan Ellen K , Wasan Kishor M , Gershkovich Pavel 
Published: March 2016

Consumption of plant sterols/ stanols has long been demonstrated to reduce plasma cholesterol levels. The objective of this review is to demonstrate the lipid-lowering activity and anti-atherogenic effects of natural and semi-synthetic plant sterols/ stanols based on evidence from cell-culture studies, animal studies and clinical trials. Additionally, this review highlights certain molecular mechanisms by which plant sterols/ stanols lower plasma cholesterol levels with a special emphasis on factors that affect the cholesterol-lowering activity of plant sterols/stanols. The crystalline nature and the poor oil solubility of these natural products could be important factors that limit their cholesterol-lowering efficiency. Several attempts have been made to improve the cholesterol-lowering activity by enhancing the bioavailability of crystalline sterols and stanols. Approaches involved reduction of the crystal size and/or esterification with fatty acids from vegetable or fish oils. However, the most promising approach in this context is the chemical modification of plant sterols /stanols into water soluble disodium ascorbyl phytostanyl phosphates analogue by esterification with ascorbic acid. This novel semi-synthetic stanol derivative has improved efficacy over natural plant sterols/ stanols and can provide additional benefits by combining the cholesterol-lowering properties of plant stanols with the antioxidant potential of ascorbic acid. 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.
Preparation and Evaluation of a New Nano Pharmaceutical Excipients and drug Delivery System Based in Polyvinylpyrrolidone and Silicates
Authors: Dornelas Camila Braga , Silva Alex Moura , Dantas Cide Brizio , Rodrigues Carlos Rangel , Coutinho Sandra Solange , Sathler Plínio Cunha , Castro Helena Carla , Dias Luiza Rosaria Sousa , Sousa Valeria Pereira , Cabral Lúcio Mendes 
Published: March 2016

PURPOSE: This work describes the preparation of new nanocomposites based on lamellar silicates (AAM-alkyl ammonium montmorillonite) obtained by the intercalation of PVP K30 and glyceril monostearate.
METHODS: By XRD, TGA and DSC analysis the AAM was characterized and its compactation characteristics, functionality and toxicity were also tested. The AAM/PVP K-30 and AAM/GME nanocomposite obtained were evaluated to identify the interlamellar spacing values by XRD diffratograms. Tablets were prepared using methyldopa and theophylline as model drugs and the dissolution tests were carried out in simulated gastric fluid and simulated enteric fluid.
RESULTS: AAM showed a good compactability and compressibility characteristics for tablets preparation. The intercalation yields (approximately 25%) of the nanocomposites were efficient. The AAM/PVP K-30 nanocomposites were successfully tested as dissolution enhancers and sustained release matrixes.
CONCLUSIONS: The results also suggested the promising use of AAM (viscogel B8) and the new nanocomposite prepared by clay/PVP K-30 intercalation as a new matrix for sustained release and the feasibility of using these new nanocomposites as dissolution enhancer.
Osthole Regulates TGF-β1 and MMP-2/9 Expressions via Activation of PPARα/γ in Cultured Mouse Cardiac Fibroblasts Stimulated with Angiotensin II
Authors: Chen Rong , Xue Jie , Xie Meilin 
Published: March 2016

PURPOSE. Our previous studies have demonstrated that osthole, an active constituent isolated from the fruit of Cnidium monnieri (L.) Cusson, can prevent isoprenaline-induced myocardial fibrosis in mice, but the underlying mechanism is still unclear. METHODS. The mouse cardiac fibroblasts (CFs) stimulated with angiotensin II (Ang II) were cultured and treated with different concentrations of osthole. The mRNA expressions of peroxisome proliferator-activated receptor (PPAR) α/γ, transforming growth factor β1 (TGF-β1), and matrix metalloproteinase (MMP)-2/9 were detected by reverse transcription polymerase chain reaction method, and the protein expressions of nuclear factor-κB (NF-κB) and TGF-β1 were detected by Western blot method, respectively. RESULTS. Following treatment of cells with osthole at 2.5, 5, 10 and 20 μg/mL, the NF-κB and TGF-β1 expressions were dose-dependently decreased, while the expressions of PPARα/γ and MMP-2/9 were dose-dependently increased. After the cells were preincubated with PPARα antagonist (MK886) or/and PPARγ antagonist (GW9662), the inhibitions of osthole on the NF-κB and TGF-β1 expressions were decreased or completely halted and the increment of osthole on the MMP-2/9 expressions were also decreased or completely cancelled. CONCLUSION. Osthole could inhibit the NF-κB and TGF-β1 expressions by activation of PPARα/γ, and subsequently enhance the MMP-2/9 expressions in cultured CFs, and these effects of osthole may play the beneficial roles in the prevention and treatment of myocardial fibrosis. 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.
Efficient Peroral Delivery of Insulin via Vitamin B12 Modified Trimethyl Chitosan Nanoparticles
Authors: Ke Zhiyang , Guo Han , Zhu Xi , Jin Yun , Huang Yuan 
Published: March 2016

PURPOSE: We investigated the effect of vitamin B12 (VB12) modification on the insulin absorption from trimethyl chitosan(TMC) nanoparticles (NPs) under the inﬂuence of mucus. METHODS: TMC and TMC-VB12 were synthesized and insulin loaded TMC/TMC-VB12 nanoparticles were prepared and characterized. Modified and unmodified nanoparticles were studied with Caco-2/HT29-MTX cell model and ligated rat ileum loop. RESULTS: Compared with unmodified NPs, VB12 modified NPs showed signiﬁcantly higher drug internalization in Caco-2/HT29-MTX cell model. The internalization mechanism via VB12 mediation included caveolae and clathrin-mediated endocytosis pathway. Meanwhile, an increased transportation of drugs was observed for VB12 modified NPs, possibly due to the ligand-receptor interaction via an intrinsic factor-dependent fashion. Although the uptake and transport of VB12 modiﬁed NPs could be partially inﬂuenced by mucus, they still showed higher drug permeation through Caco-2/HT29-MTX co-cultured cells than unmodified NPs in the presence or absence of mucus. Moreover, in situ study in ligated rat ileum loop demonstrated that VB12 modiﬁed nanoparticles could reduce the residual insulin in intestinal lumen (0.59 times) and increase their absorption in epithelial tissue (4.8 times) compared with the unmodified ones. CONCLUSION: VB12 modiﬁed trimethyl chitosan nanoparticle is a promising carrier for peroral delivery of insulin. 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.
Alteration of Pharmacokinetics of Grepafloxacin in Type 2 Diabetic Rats
Authors: Watanabe Meguho , Kobayashi Masaki , Ogura Jiro , Takahashi Natsuko , Yamaguchi Hiroaki , Iseki Ken 
Published: March 2016

Purpose. Patients with type 2 diabetes are generally treated with various pharmacological compounds and are exposed to a high risk of drug-drug interactions. However, alterations of pharmacokinetics in a type 2 diabetes model have been obscure. The present study was undertaken to investigate the effects of type 2 diabetes on the pharmacokinetics of the fluoroquinolone grepafloxacin (GPFX) and the expression level of P-glycoprotein (P-gp), one of the drug efflux transporters. Methods. We used Goto-Kakizaki (GK) rats, a lean model of type 2 diabetes. Plasma concentration and intestinal, renal, and biliary clearance of GPFX were measured after intravenous and intraintestinal administration in Wistar and GK rats. Real-time PCR and Western blotting were used to assess mRNA and protein expression levels. Results. We found a significant increase in the plasma concentrations of GPFX at 90, 120 and 240 minutes after intraintestinal administration in GK rats compared with the concentrations in Wistar rats but not after intravenous administration. The increase in plasma GPFX concentration was associated with reduction in jejunal clearance of GPFX caused by a decrease in secretory transport of GPFX. However, there was no correlation between the decrease in secretory transport of GPFX and P-gp expression level. Conclusion. Type 2 diabetic conditions alter P-gp function as well as expression level and correlate poorly with each other. 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.
Characterization Of Selective TRPM8 Ligands And Their Structure Activity Response (S.A.R) Relationship
Authors: Sherkheli Muhammad Azhar , Vogt-Eisele Angela K. , Bura Daniel , Beltrán Márques Leopoldo R. , Gisselmann Günter , Hatt Hanns 
Published: March 2016

PURPOSE: Transient receptor potential melastatin-8 (TRPM8) is an ion channel expressed extensively in sensory nerves, human prostate and overexpressed in a variety of cancers including prostate, breast, lung, colon and skin melanomas. It is activated by innoxious cooling and chemical stimuli. TRPM8 activation by cooling or chemical agonists is reported to induce profound analgesia in neuropathic pain conditions. Known TRPM8 agonists like menthol and icilin cross-activate other thermo-TRP channels like TRPV3 and TRPA1 and mutually inhibit TRPM8. This limits the usefulness of menthol and icilin as TRPM8 ligands. Consequently, the identification of selective and potent ligands for TRPM8 is of high relevance both in basic research and for therapeutic applications. In the present investigation, a group of menthol derivates was characterized. These ligands are selective and potent agonists of TRPM8. Interestingly they do not activate other thermo-TRPs like TRPA1, TRPV1, TRPV2, TRPV3 and TRPV4. These ion channels are also nociceptors and target of many inflammatory mediators.
METHODS: Investigations were performed in a recombinant system: Xenopus oocytes microinjected with cRNA of gene of interest were superfused with the test substances after initial responses of known standard agonists. Evoked currents were measured by two-electrode voltage clamp technique.
RESULTS: The newly characterized ligands possess an up to six-fold higher potency (EC50 in low µM) and an up to two-fold increase in efficacy compared to the parent compound menthol. In addition, it is found that chemical derivatives of menthol like CPS-368, CPS-369, CPS-125, WS-5 and WS-12 are the most selective ligands for TRPM8. The enhanced activity and selectivity seems to be conferred by hexacyclic ring structure present in all ligands as substances like WS-23 which lack this functional group activate TRPM8 with much lower potency (EC50 in mM) and those with pentacyclcic ring structure (furanone compounds) are totally inactive.
CONCLUSION: The new substances activate TRPM8 with a higher potency, efficacy and specificity than menthol and will thus be of importance for the development of pharmacological agents suitable for treatment and diagnosis of certain cancers and as analgesics.

STATEMENT OF NOVELTY: The new compounds have an unmatched specificity for TRPM8 ion channels with additional display of high potency and efficacy. Thus these substances are better pharmacological tools for TRPM8 characterization then known compounds and it is suggested that these menthol-derivates may serve as model substances for the development of TRPM8 ligands.
The Role of SIRT3 in Mediating Cardioprotective Effects of RAS Inhibition on Cardiac Ischemia-Reperfusion
Authors: Javadov Sabzali , Escobales Nelson 
Published: March 2016

Cardiac ischemia-reperfusion stimulates the renin-angiotensin system (RAS) associated with elevated levels of circulating angiotensin II. Numerous studies demonstrate that the antagonist for the angiotensin II type 1 receptor, losartan improves cardiac function in animal models of ischemia-reperfusion. Molecular mechanisms of the cardioprotective effects of RAS inhibitors on cardiac ischemia-reperfusion remain poorly understood, and are not associated with the anti-hypertensive action of these drugs. This Commentary focuses on the study published in the Journal of Pharmacy and Pharmaceutical Sciences, 2015, 18:112-123, that elucidates the role of SIRT3 in the cardioprotective action of losartan against ischemic-reperfusion injury. We provide comprehensive discussion of the role of mitochondria in the cardioprotective effects of losartan through SIRT3. 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.
Safety Assessment of Potentially Inappropriate Medications Use in Older People and the Factors Associated with Hospital Admission
Authors: Varallo Fabiana Rossi , Capucho Helaine Carneiro , Planeta Cleópatra Silva , Mastroianni Patrícia De Carvalho 
Published: March 2016

Purpose: Potentially Inappropriate Medications (PIM) use in elderly people may be responsible for the development of Adverse Drug Reaction (ADR) which, when severe, leads to hospital admissions. Objectives: to estimate the prevalence of elderly who had used PIM before being admitted to hospital admission and to identify the risk factors and the hospitalizations related to ADR arising from PIM. Methods: A descriptive and cross-sectional study was performed in the internal medicine ward of a teaching hospital (Brazil), in 2008. With the aid of a validated form, patients aged ≥ 60 years, with length of hospital stay ≥ 24 hours, were interviewed about drugs taken prior to the hospital admission and the complaints/reasons for hospitalization. Results: 19.1% (59/308) of older patients had taken PIM before hospital admission and in 4.9%; there were a causal relation between the PIM taken and the complaint reported. PIM responsible for admissions were: amiodarone, amitriptyline, cimetidine, clonidine, diazepam, digoxin, estrogen, fluoxetine, lorazepam, short-acting nifedipine and propranolol. 47.0% of the clinical manifestations of PIM-related ADR were: dizziness, fatigue, digoxin toxicity and erythema. Only polypharmacy was detected as a risk factor for the occurrence of ADR of PIM (p = 0.02). Conclusion: PIM use in elderly people is not a risk factor for ADR-related hospital admission. Probably, severe ADR, which lead to hospitalizations of older people, can be explained by idiosyncratic response or the predisposition of these patients to develop adverse drug events, whether or not drugs are classed as PIM.
Key-words: potentially inappropriate medication (PIM), older people, adverse drug reaction (ADR), hospital admission, pharmacovigilance
Phytoestrogens Modulate Breast Cancer Resistance Protein Expression and Function at the Blood-Cerebrospinal Fluid Barrier
Authors: Kaur Manjit , Badhan Raj Kumar Singh 
Published: March 2016

PURPOSE: Breast cancer resistance protein (BCRP/ABCG2) is a drug efflux transporter expressed at the blood cerebrospinal fluid barrier (BCSFB), and influences distribution of drugs into the central nervous systems (CNS). Current inhibitors have failed clinically due to neurotoxicity. Novel approaches are needed to identify new modulators to enhance CNS delivery. This study examines 18 compounds (mainly phytoestrogens) as modulators of the expression/function of BCRP in an in vitro rat choroid plexus BCSFB model. METHODS: Modulators were initially subject to cytotoxicity (MTT) assessment to determine optimal non-toxic concentrations. Reverse-transcriptase PCR and confocal microscopy were used to identify the presence of BCRP in Z310 cells. Thereafter modulation of the intracellular accumulation of the fluorescent BCRP probe substrate Hoechst 33342 (H33342), changes in protein expression of BCRP (western blotting) and the functional activity of BCRP (membrane insert model) were assessed under modulator exposure. RESULTS: A 24 hour cytotoxicity assay (0.001 µM-1000 µM) demonstrated the majority of modulators possessed a cellular viability IC50 > 148 µM. Intracellular accumulation of H33342 was significantly increased in the presence of the known BCRP inhibitor Ko143 and, following a 24 hour pre-incubation, all modulators demonstrated statistically significant increases in H33342 accumulation (P < 0.001), when compared to control and Ko143. After a 24 hour pre-incubation with modulators alone, a 0.16-2.5 -fold change in BCRP expression was observed for test compounds. The functional consequences of this were confirmed in a permeable insert model of the BCSFB which demonstrated that 17-β-estradiol, naringin and silymarin (down-regulators) and baicalin (up-regulator) can modulate BCRP-mediated transport function at the BCSFB. CONCLUSION: We have successfully confirmed the gene and protein expression of BCRP in Z310 cells and demonstrated the potential for phytoestrogen modulators to influence the functionality of BCRP at the BCSFB and thereby potentially allowing manipulation of CNS drug disposition. 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.
Antimicrobial and P450 Inhibitory Properties of Common Functional Foods
Authors: Nguyen San , Huang Huang , Foster Brian C , Tam Teresa W , Xing Tim , Smith Myron L , Arnason John T , Akhtar Humayoun 
Published: March 2016

PURPOSE: To study the effect of functional foods on human cytochrome P450 (CYP) and the gut bacterial microflora that may potentially affect drug metabolism and ultimately affect human health and wellness. METHODS: This study examined a variety of food plants from the Apiaceae, Fabaceae, and Lamiaceae families for their inhibitory potential on cytochrome 2D6-, 3A4-, 3A5-, and 3A7-mediated metabolism. The antimicrobial effects of these samples were also investigated with 7 selected bacterial surrogate species to determine potential effects on the gut microflora. RESULTS: The highest CYP inhibitory activities, based upon visual examination, were observed from extracts of celery seed, cumin, fennel seed, basil, oregano, and rosemary belonging to the Apiaceae and Lamiaceae families, respectively. Likewise, the strongest antimicrobial activities were also observed in the Apiaceae and Lamiaceae. No significant antimicrobial and CYP inhibition was observed in the Fabaceae extracts. CONCLUSION: Results demonstrated the possible risk of food-drug interactions from spice and herb plants may affect drug disposition and safety. 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.