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Lee Shaashua, Maytal Shabat-Simon, Rita Haldar, Pini Matzner, Oded Zmora, Moshe Shabtai, Eran Sharon, Tanir Allweis, Iris Barshack, Lucile Hayman, Jesusa M G Arevalo, Jeffrey Ma, Maya Horowitz, Steve W Cole, Shamgar Ben-Eliyahu
<br /> <p>Translational studies suggest that excess perioperative release of catecholamines and prostaglandins may facilitate metastasis and reduce disease-free survival. This trial tested the combined perioperative blockade of these pathways in breast cancer patients.</p> <br />Experimental Design: <br /> <p>In a randomized placebo-controlled biomarker trial, 38 early-stage breast cancer patients received 11 days of perioperative treatment with a beta-adrenergic antagonist (propranolol) and a cyclooxygenase-2 (COX-2) inhibitor (etodolac), beginning five days before surgery...
May 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Kuan-Fu Liao, Kao-Chi Cheng, Cheng-Li Lin, Shih-Wei Lai
OBJECTIVE: The aim of this study was to explore the association between etodolac use and acute in Taiwan. DESIGN: We designed a case-control study using the database of Taiwan's National Health Insurance. SUBJECTS: In all, 7577 subjects aged 20 years or older with newly diagnosed acute pancreatitis were defined as cases, and 27032 sex-matched and age-matched subjects without acute pancreatitis were defined as controls. The period considered for this study was from 1998 to 2011...
March 2017: BioMedicine
Carla Janzen, Suvajit Sen, Margarida Y Y Lei, Marina Gagliardi de Assumpcao, John Challis, Gautam Chaudhuri
Context: Biochemical weakening of the amnion is a major factor preceding preterm premature rupture of membranes (PPROMs), leading to preterm birth. Activation of matrix metalloproteinases (MMPs) is known to play a key role in collagen degradation of the amnion; however, epithelial to mesenchymal transition (EMT) that is also induced by MMP activation has not been investigated as a mechanism for amnion weakening. Objective: To measure amniotic EMT associated with vaginal delivery (VD) compared with unlabored cesarean sections (CSs), and to assess changes in amniotic mechanical strength with pharmacologic inhibitors and inducers of EMT, thus testing the hypothesis that EMT is a key biochemical event that promotes amniotic rupture...
April 1, 2017: Journal of Clinical Endocrinology and Metabolism
Rajesh Thipparaboina, Dinesh Thumuri, Rahul Chavan, V G M Naidu, Nalini R Shastri
Combinational therapy has become increasingly popular in recent times due to various advantages like greater therapeutic effect, reduced number of prescriptions, lower administrative costs, and an increase in patient compliance. Drug-drug multicomponent adducts could help in combination of drugs at supramolecular level. Two drug-drug eutectics of etodolac with paracetamol (EP) and etodolac with propranolol hydrochloride (EPHC) were successfully designed and synthesized for the first time. These eutectics significantly improved dissolution and material properties...
March 31, 2017: European Journal of Pharmaceutical Sciences
Dixon Thomas, Zoya Ali, Seeba Zachariah, Kishore Gnana Sam Sundararaj, Matthew Van Cuyk, Jason C Cooper
Non-steroidal anti-inflammatory drugs (NSAIDs) were differentiated from steroidal anti-inflammatory medicines to help clinicians who needed to use anti-inflammatory agents that were safer than steroids. With market entry of rofecoxib in 1999, NSAIDs were then further classified into traditional NSAIDs and cyclooxygenase (COX)-2 inhibitors (coxibs), the latter posing potentially fewer gastrointestinal risks. In 2005, rofecoxib was withdrawn from the market because of concerns about the risk of heart attack and stroke with long-term use, and clinical practice began focusing more on the cardiovascular versus gastrointestinal safety of coxibs...
March 28, 2017: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
Atul P Sherje, Vaidehi Kulkarni, Manikanta Murahari, Usha Y Nayak, Pritesh Bhat, Vasanti Suvarna, Bhushan Dravyakar
The present investigation was aimed to prepare inclusion complexes of a therapeutically important nonsteroidal anti-inflammatory drug, etodolac (ETD) with hydroxypropyl-beta-cyclodextrin (HP-β-CD) and to study the effect of l-arginine (l-Arg) as an auxiliary agent on the complexation efficiency of HP-β-CD to improve aqueous solubility and the dissolution property of ETD. The binary and ternary complexes were prepared by physical mixing, coevaporation, and spray drying methods. The complexes were characterized using differential scanning colorimetry (DSC), Fourier transform-infrared spectroscopy (FT-IR), and powder X-ray diffraction (PXRD) studies...
April 3, 2017: Molecular Pharmaceutics
Sayuko Shiraishi, Tamami Haraguchi, Saki Nakamura, Dahong Li, Honami Kojima, Miyako Yoshida, Takahiro Uchida
The purpose of this study was to evaluate the taste-masking effects of chlorogenic acid (CGA) on bitter drugs using taste sensor measurements and surface plasmon resonance (SPR) analysis of CGA-drug interactions. Six different bitter drugs were used: amlodipine besylate (AMD), diphenhydramine hydrochloride (DPH), donepezil hydrochloride (DNP), rebamipide (RBM), diclofenac sodium (DCF) and etodolac (ETD). Taste sensor outputs were significantly inhibited by the addition of CGA to all drugs. The inhibition ratio of the taste sensor output decreased in the following order DPH>DNP>AMD≈DCF≈RBM≈ETD...
2017: Chemical & Pharmaceutical Bulletin
Il-Dong Song, Je-Seop Kang, Hyun-Jin Kim, Se-Mi Kim, Dong-Xu Zhao, Shin-Hee Kim, Min-Young Chun, Kyuhyun Lee
We developed a simple and validated liquid chromatography tandem mass spectrometry(LC-MS/MS) for quantification of etodolac using pioglitazone as an internal standard (IS) to assess pharmacokinetics and to appraise bioequivalence of two formulations of etodolac (reference and tested) in 27 healthy Korean subjects. Isocratic mobile phase consisted of 10 mM ammonium formate and acetonitrile were used to separate the analytes on a Gemini C18 column. Also, analytes were analyzed by MS/MS in multiple reaction monitoring (MRM) mode using the transitions of (M+H)+ ions, m/z 288...
January 16, 2017: Drug Metabolism Letters
Carla Janzen, Suvajit Sen, Margarida Y Y Lei, Marina Gagliardi de Assumpcao, John Challis, Gautam Chaudhuri
CONTEXT: Biochemical weakening of the amnion is a major factor preceding preterm premature rupture of membranes (PPROM), leading to preterm birth. Activation of matrix metalloproteinases (MMPs) is known to play a key role in collagen degradation of the amnion, yet epithelial to mesenchymal transition (EMT) that is also induced by MMP activation, has not been investigated as a mechanism for amnion weakening. OBJECTIVE: To measure amniotic EMT associated with vaginal delivery (VD) as compared to non-labored cesarean sections (CS), and assess changes in amniotic mechanical strength with pharmacologic inhibitors and inducers of EMT, thus testing the hypothesis that EMT is a key biochemical event that promotes amniotic rupture...
December 19, 2016: Journal of Clinical Endocrinology and Metabolism
Yoshihiko Uehara, Yasuhiko Murata, Soichiro Shiga, Yoshio Hosoi
BACKGROUND: It is well known that radiation exposure to the heart and the use of non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of myocardial infarction (MI). Some NSAIDs are also known to act synergistically with ionizing radiation and have radio-sensitizing effects in radiotherapy. These evidences suggest that NSAIDs may affect the risk of MI after radiation exposure to the heart. In the present study, we investigated effects of NSAIDs on radiation-induced expression of cell adhesion molecules and COX-2, which are associated with inflammation and an increased risk of MI, in human endothelial cells...
October 28, 2016: Biochemical and Biophysical Research Communications
Ahmed M Mohammed, W Faisal, Khaled I Saleh, Shaaban K Osman
Etodolac, a member of non steroidal anti-inflammatory drugs (NSAIDs), has a poor aqueous solubility. Long term administration of etodolac causes severe gastrointestinal disturbances such as peptic ulcer and bleeding. These disturbances could be overcome by alternative routes such as a topical administration. In the present study, pluronic lecithin organogels (PLOs) were prepared by simple mixing of pluronic solution with lecithin solution. Etodolac was loaded into the prepared gels or added during the gel formation...
September 2, 2016: Current Drug Delivery
Martin Růžička, Dušan Koval, Jan Vávra, Paul E Reyes-Gutiérrez, Filip Teplý, Václav Kašička
Noncovalent molecular interactions between helquats, a new class of dicationic helical extended diquats, and several chiral acidic aromatic drugs and catalysts have been investigated using partial-filling affinity capillary electrophoresis (PF-ACE). Helquats dissolved at 1mM concentration in the aqueous background electrolyte (40mM Tris, 20mM acetic acid, pH 8.1) were introduced as ligand zones of variable length (0-130mm) into the hydroxypropylcellulose coated fused silica capillary whereas 0.1mM solutions of negatively charged chiral drugs or catalysts (warfarin, ibuprofen, mandelic acid, etodolac, binaphthyl phosphate and 11 other acidic aromatic compounds) were applied as a short analyte zone at the injection capillary end...
October 7, 2016: Journal of Chromatography. A
Sohil I Chauhan, Sandeep V Nathwani, Moinuddin M Soniwala, Jayant R Chavda
The present investigation was carried out to develop and characterize a multifunctional co-processed excipient for improving the compressibility of poorly compressible drugs. Etodolac was used as a model drug. Microcrystalline cellulose (MCC), lactose monohydrate (lactose), and StarCap 1500 (StarCap) were selected as components of the co-processed excipient. The spray drying method was used for co-processing of excipients. D-optimal mixture design was applied to optimize the proportion of component excipients...
August 1, 2016: AAPS PharmSciTech
Gyati Shilakari Asthana, Abhay Asthana, Davinder Singh, Parveen Kumar Sharma
The present study aimed to investigate the delivery potential of Etodolac (ETD) containing topical niosomal gel. Niosomal formulations were prepared by thin film hydration method at various ratios of cholesterol and Span 60 and were evaluated with respect to particle size, shape, entrapment efficiency, and in vitro characteristics. Dicetyl phosphate (DCP) was also added in the niosomal formulation. Mean particle size of niosomal formulation was found to be in the range of 2 μm to 4 μm. Niosomal formulation N2 (1 : 1) ratio of cholesterol and surfactant displayed good entrapment efficiency (96...
2016: Journal of Drug Delivery
I-Che Li, Amanda N Moore, Jeffrey D Hartgerink
The clinical administration of many small molecule hydrophobic drugs is challenged by the insolubility of these drugs under physiological conditions. Because of this, the development of biocompatible scaffolds capable of effectively delivering hydrophobic drug molecules is of particular interest. Multidomain peptides (MDPs) provide biocompatible hydrogel scaffolds that are injectable and space-conforming, allowing for in situ delivery of a variety of drugs. Here we demonstrate that through manipulation of peptide primary sequence, a molecular cavity can be incorporated into the hydrophobic core of these peptide nanofibers allowing for encapsulation and delivery of small molecule drugs with poor water solubility...
June 13, 2016: Biomacromolecules
Liat Sorski, Rivka Melamed, Pini Matzner, Hagar Lavon, Lee Shaashua, Ella Rosenne, Shamgar Ben-Eliyahu
Liver metastases are a major cause of colorectal cancer death, and the perioperative period is believed to critically affect the metastatic process. Here we tested whether blocking excess release of catecholamines and prostaglandins during surgical procedures of different extent can reduce experimental liver metastasis of the syngeneic CT26 colon cancer in female and male BALB/c mice. Animals were either treated with the beta-blocker, propranolol, the COX-2 inhibitor, etodolac, both drugs, or vehicle. The role of NK cells in controlling CT26 hepatic metastasis and in mediating the effect of the drugs was assessed by in vivo depletion or stimulation of NK cells, using anti-asialo GM1 or CpG-C, respectively...
November 2016: Brain, Behavior, and Immunity
Júlio César Silva de Oliveira, Gustavo Augusto Grossi de Oliveira, Ana Paula Farnezi Bassi
PURPOSE: To compare the efficacy of ibuprofen (IBU) and etodolac (ETO) for controlling pain, edema, and trismus after extraction of lower third molars. MATERIALS AND METHODS: Twenty adolescents and adults with 2 impacted mandibular-third molars (in similar positions) were selected for the study. Patients were randomly assigned either to the IBU group (600 mg of IBU 3 times a day for 3 days) or to the ETO group (300 mg of ETO 3 times a day for 3 days). Drugs were administered immediately after dental extraction...
August 2016: Journal of Oral and Maxillofacial Surgery
Manisha Singh, Ravi Bhushan
Separation of racemic mixture of (RS)-bupropion, (RS)-baclofen and (RS)-etodolac, commonly marketed racemic drugs, has been achieved by modifying the conventional ligand exchange approach. The Cu(II) complexes were first prepared with a few l-amino acids, namely, l-proline, l-histidine, l-phenylalanine and l-tryptophan, and to these was introduced a mixture of the enantiomer pair of (RS)-bupropion, or (RS)-baclofen or (RS)-etodolac. As a result, formation of a pair of diastereomeric complexes occurred by 'chiral ligand exchange' via the competition between the chelating l-amino acid and each of the two enantiomers from a given pair...
November 2016: Biomedical Chromatography: BMC
Yasushi Miwa, Hidetoshi Hamamoto, Tatsuhiro Ishida
Poor transdermal penetration of active pharmaceutical ingredients (APIs) impairs both bioavailability and therapeutic benefits and is a major challenge in the development of transdermal drug delivery systems. Here, we transformed a poorly water-soluble drug, etodolac, into an ionic liquid in order to improve its hydrophobicity, hydrophilicity and skin permeability. The ionic liquid was prepared by mixing etodolac with lidocaine (1:1, mol/mol). Both the free drug and the transformed ionic liquid were characterized by differential scanning colorimetry (DSC), infrared spectroscopy (IR), and saturation concentration measurements...
May 2016: European Journal of Pharmaceutics and Biopharmaceutics
B Levi, P Matzner, Y Goldfarb, L Sorski, L Shaashua, R Melamed, E Rosenne, G G Page, S Ben-Eliyahu
We recently reported that immune stimulation can be compromised if animals are simultaneously subjected to stressful conditions. To test the generalizability of these findings, and to elucidate neuroendocrine mediating mechanisms, we herein employed CpG-C, a novel TLR-9 immune-stimulating agent. Animals were subjected to ongoing stress (20-h of wet cage exposure) during CpG-C treatment, and antagonists to glucocorticoids, β-adrenoceptor, COX2, or opioids were employed (RU486, nadolol, etodolac, naltrexone)...
August 2016: Brain, Behavior, and Immunity
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