Chemicals and Drugs Commons^™

Lipopolysaccharide Induced Map Kinase Activation In Raw 264.7 Cells Attenuated By Cerium Oxide Nanoparticles, Vellaisamy Selvaraj, Niraj Nepa, Steven Rogers, Nandini D.P.K. Manne, Ravi K. Arvapalli, Kevin M. Rice, Shinichi Asano, Erin Fankenhanel, J. Y. Ma, Tolou Shokuhfar, Mani Maheshwari, Eric R. Blough

Mani Maheshwari

High mortality rates are associated with the life threatening disease of sepsis. Improvements in septic patient survivability have failed to materialize with currently available treatments. This article represents data regarding a study published in biomaterials (Vellaisamy et al., Biomaterials, 2015, in press). with the purpose of evaluating whether severe sepsis mortality and associated hepatic dysfunction induced by lipopolysaccharide (LPS) can be prevented by cerium oxide nanoparticles (CeO2NPs) treatment in male Sprague Dawley rats. Here we provide the information about the method and processing of raw data related to our study publish in Biomaterials and Data in Brief (Vellaisamy et al., …

Dengue Virus Ns2b/Ns3 Protease Inhibitors Exploiting The Prime Side, Kuan-Hung Lin, Akbar Ali, Linah Rusere, Djade I. Soumana, Nese Kurt Yilmaz, Celia A. Schiffer

Celia A. Schiffer

The mosquito-transmitted dengue virus (DENV) infects millions of people in tropical and subtropical regions. Maturation of DENV particles requires proper cleavage of the viral polyprotein, including processing of 8 of the 13 substrate cleavage sites by dengue virus NS2B/NS3 protease. With no available direct-acting antiviral targeting DENV, NS2/NS3 protease is a promising target for inhibitor design. Current design efforts focus on the nonprime side of the DENV protease active site, resulting in highly hydrophilic and nonspecific scaffolds. However, the prime side also significantly modulates DENV protease binding affinity, as revealed by engineering the binding loop of aprotinin, a small protein …

Interdependence Of Inhibitor Recognition In Hiv-1 Protease, Janet L. Paulsen, Florian Leidner, Debra A. Ragland, Nese Kurt Yilmaz, Celia A. Schiffer

Celia A. Schiffer

Molecular recognition is a highly interdependent process. Subsite couplings within the active site of proteases are most often revealed through conditional amino acid preferences in substrate recognition. However, the potential effect of these couplings on inhibition and thus inhibitor design is largely unexplored. The present study examines the interdependency of subsites in HIV-1 protease using a focused library of protease inhibitors, to aid in future inhibitor design. Previously a series of darunavir (DRV) analogs was designed to systematically probe the S1' and S2' subsites. Co-crystal structures of these analogs with HIV-1 protease provide the ideal opportunity to probe subsite interdependency. …

The Changing Landscape Of Biosimilars In Rheumatology, Thomas Dorner, Vibeke Strand, Paul Cornes, Joao Goncalves, Laszlo Gulacsi, Jonathan Kay, Tore K. Kvien, Josef S. Smolen, Yoshiya Tanaka, Gerd R. Burmester

Jonathan Kay

Biosimilars remain a hot topic in rheumatology, and some physicians are cautious about their application in the real world. With many products coming to market and a wealth of guidelines and recommendations concerning their use, there is a need to understand the changing landscape and the real clinical and health-economic potential offered by these agents. Notably, rheumatologists will be at the forefront of the use of biosimilar monoclonal antibodies/soluble receptors. Biosimilars offer cost savings and health gains for our patients and will play an important role in treating rheumatic diseases. We hope that these lower costs will compensate for inequities …

Which Drugs Cause Cancer?, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jarrod Bailey, PhD

Animal tests yield misleading results.

Tolerability Of Induction Chemotherapy Dosing Practices In Acute Myeloid Leukemia Patients, Kaylene M. Peric, David J. Reeves

David Reeves

For patients with high body surface areas (BSA), differing chemotherapy dosing strategies have been utilized in attempts to reduce toxicity. In a retrospective evaluation, we compared the effects of chemotherapy dosing in acute myeloid leukemia patients with high BSA (>2 m2) who received capped doses (n = 12) to those who received uncapped doses (n = 24), and to patients with BSA ≤ 2 m2 (n = 42). There were no statistically significant differences among groups (BSA ≤ 2 m2, BSA > 2 m2 capped, and BSA > 2 m2 uncapped) in the incidences of febrile neutropenia (85.7, 66.7, and 75.0%, …

Successful Desensitization To Docetaxel After Severe Hypersensitivity Reactions In Two Patients, David J. Reeves, Michael J. Callahan, Gregory P. Sutton

David Reeves

Purpose Two cases of successful desensitization to docetaxel after severe hypersensitivity reactions are reported. Summary Two patients with gynecological malignancies (uterine leiomyosarcoma and ovarian adenocarcinoma) experienced severe hypersensitivity reactions with docetaxel, including flushing, numbness, sharp radiating pain, severe nausea and vomiting, apnea, and unresponsiveness. Both patients received ondansetron before docetaxel. One patient received dexamethasone, diphenhydramine, and famotidine premedication before docetaxel, as she had previously reacted to paclitaxel. Docetaxel infusions were stopped, and the reactions were treated with diphenhydramine and dexamethasone (one patient also received famotidine). After resolution of symptoms, the docetaxel was not reinitiated due to the nature of the …

Drug-Drug Interaction Between Methotrexate And Levetiracetam Resulting In Delayed Methotrexate Elimination, Emily Bain, Ruemu E. Birhiray, David J. Reeves

David Reeves

Objective: To report a case of delayed methotrexate (MTX) elimination while receiving concomitant levetiracetam. Case Report: A 46-year-old man with relapsed osteosarcoma of the base of the skull receiving high-dose MTX tolerated his first cycle of MTX with elimination to nontoxic MTX levels (≤0.1 µmol/L) within 90 hours. After hospital discharge, the patient experienced seizures secondary to brain metastasis and started on levetiracetam, which was continued as maintenance therapy. The patient experienced delayed MTX elimination during cycles 2, 3, and 4 while receiving levetiracetam. On average, elimination to nontoxic MTX levels took 130 hours (106-144 hours). Before the fifth cycle …

Bone Health Management In Prostate Cancer Patients Receiving Androgen Deprivation Therapy, Vishnuprabha Dhanapal, David J. Reeves

David Reeves

Purpose. Patients receiving androgen deprivation therapy undergo a rapid decline in bone mineral density during the first 6 to 12 months of initiating therapy. The World Health Organization has developed and implemented the Fracture Risk Assessment Tool (FRAX) to predict the ten year risk of a major fracture & hip fracture. Additionally, the National Comprehensive Cancer Network and the National Osteoporosis Foundation have developed osteoporosis guidelines. This study aims to characterize the fracture risk (based on the FRAX tool) and the current management of bone health based on national guidelines compliance. Methods. A retrospective chart review of patients receiving a …

Ascorbic Acid For The Treatment Of Rasburicase Induced Methemoglobinemia In The Setting Of Acute Renal Failure, David J. Reeves, Lindsay Saum, Ruemu Birhiray

David Reeves

Purpose A case of apparent rasburicase-induced methemoglobinemia and acute kidney injury treated with i.v. ascorbic acid because of suspected glucose-6-phosphate dehydrogenase (G6PD) deficiency is reported. Summary A 46-year-old African-American man with a recent diagnosis of multiple myeloma and renal insufficiency was admitted to the hospital with a cough, hemoptysis, and fatigue. His medical history included hypertrophic cardiomyopathy, ventricular tachycardia, attention deficit/hyperactivity disorder, and pleural effusion. No treatments for multiple myeloma were started before hospital admission. Levofloxacin 750 mg orally daily for possible pneumonia, lenalidomide 10 mg orally daily, and dexamethasone 20 mg orally weekly were administered. Plasmapheresis was also initiated. …

Biosimilars In Rheumatology: What The Clinician Should Know, Gilberto Castaneda-Hernandez, Rodrigo Gonzalez-Ramirez, Jonathan Kay, Morton A. Scheinberg

Jonathan Kay

Biosimilars are now a reality in rheumatology. Although analytical and non-clinical procedures to establish similarity have evolved significantly, clinical trials demonstrating equivalent efficacy and safety are absolutely required for all biosimilars. The design of such trials, including equivalence and non-inferiority statistical approaches, are discussed. Clinical evidence on biosimilars that have been approved recently or are presently being developed for use in rheumatology is also reviewed and contrasted with that available for biomimics (or intended copies), which are non-innovator biologics that are marketed in several countries but have not undergone review according to a regulatory pathway for biosimilars.

Which Drugs Cause Cancer?, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Andrew Knight, Ph.D.

Animal tests yield misleading results.

A Comparison Of Pharmacist Travel-Health Specialists' Versus Primary Care Providers' Recommendations For Travel-Related Medications, Vaccinations, And Patient Compliance In A College Health Setting, Melissa J. Durham, Jeffery A. Goad, Lawrence S. Neinstein, Mimi Lou

Jeff Goad

Background. Pretravel medication and vaccination recommendations and receipt were compared between primary care providers (PCPs) without special training and clinical pharmacists specializing in pretravel health. Methods. A retrospective chart review of patients seen for pretravel health services in a pharmacist-run travel clinic (PTC) compared to PCPs at a University Student Health Center. Vaccine/medication recommendations were assessed for consistency with national/international guidelines. Medical/pharmacy records were queried to determine the receipt of medications/vaccinations. Results. The PTC recommended antibiotics for travelers' diarrhea were given more often when indicated (96% vs 50%, p < 0.0001), and patients seen in the PTC received their medications more …

Intravenous Artesunate For Severe Malaria, Karl M. Hess, Jeffery A. Goad, Paul M. Arguin

Jeff Goad

OBJECTIVE: To review the pharmacodynamics and pharmacotherapeutic use of intravenous artesunate for the treatment of severe malaria.

DATA SOURCES: Literature was retrieved through PubMed (1999 March 2010), MEDLINE (1996 March 2010), and the Centers for Disease Control and Prevention (CDC), using the search terms artemisinin, artesunate, malaria, and severe malaria. In addition, reference citations from publications identified were reviewed.

STUDY SELECTION AND DATA EXTRACTION: All articles in English that were identified from the data sources were reviewed. Focus was placed on post-marketing trials examining the safety and efficacy of artesunate in comparison with other regimens.

DATA SYNTHESIS …

Cross-Sector Review Of Drivers And Available 3rs Approaches For Acute Systemic Toxicity Testing, Troy Seidle, Sally Robinson, Tom Holmes, Stuart Creton, Pilar Prieto, Julia Scheel, Magda Chlebus

Troy Seidle, PhD

Acute systemic toxicity studies are carried out in many sectors in which synthetic chemicals are manufactured or used and are among the most criticized of all toxicology tests on both scientific and ethical grounds. A review of the drivers for acute toxicity testing within the pharmaceutical industry led to a paradigm shift whereby in vivo acute toxicity data are no longer routinely required in advance of human clinical trials. Based on this experience, the following review was undertaken to identify (1) regulatory and scientific drivers for acute toxicity testing in other industrial sectors, (2) activities aimed at replacing, reducing, or …

Antispasmodic And Ca++ Antagonist Potential Of Marrubiin, A Labdane Type Diterpene From Phlomis Bracteosa, Javid Hussain, Riaz Ullah, Arif-Ullah Khan, Fazal Mabood, Mohammad Raza Shah, Ahmed Al-Harrasi, Anwar Gilani

Anwar Gilani

A tricyclic labdane type diterpene was isolated for the first time from ethyl acetate soluble part of Phlomis bracteosa. Its structure was confirmed by x-ray which was found to be marrubiin. When studied in isolated rabbit jejunum, marrubiin caused concentration-dependent relaxation of spontaneous and high K+ (80 mM)-induced contractions, like that caused by verapamil, indicating that marrubiin exhibits spasmolytic activity, possibly mediated through Ca++ channel blocking action.

Asthma Knowledge, Adherence, And Administration Techniques In Hispanic Caregivers Of Pediatrics, Joshua Arnold, Rachel Culp, Kyle Hultz, Benjamin Robertson, Jon Wilkie, Amy Wuobio, Marty L. Eng, Kelly J. Hiteshew

Kelly J. Wright, R.Ph., Pharm.D.

7.5% of Hispanics in the United States suffer from asthma-related diseases, and Latino children are not as likely to use preventative asthma medications as compared with Caucasians. Educational interventions may reduce the number of visits to emergency-care. The reasons for non-adherence are currently unknown, and discovering these reasons will help to address the problem.

Reinforcing Effects Of Compounds Lacking Intrinsic Efficacy At Α1 Subunit-Containing Gabaa Receptor Subtypes In Midazolam- But Not Cocaine-Experienced Rhesus Monkeys, Nina M. Shinday, Eileen K. Sawyer, Bradford D. Fischer Phd, Donna M. Platt, Stephanie C. Licata, John R. Atack, Gerard R. Dawson, David S. Reynolds, James K. Rowlett

Bradford Fischer

A Thousand Tiny Pieces: The Federal Circuit’S Fractured Myriad Ruling, Lessons To Be Learned, And The Way Forward, Jonathan R. K. Stroud

Jonathan R. K. Stroud

No abstract provided.

Reviewing The American University Law Review On Extraterritoriality: A Critical Response To Viki Economides, Note, Tianrui Group Co. V. Itc: The Dubious Status Of Extraterritoriality And The Domestic Industry Requirement Requirement Of Section 337(Link), Jonathan R. K. Stroud

Jonathan R. K. Stroud

Recently, the Federal Circuit upheld the Commission’s decision to exclude goods based on a trade secret violation that largely happened abroad. The American University Law Review critiqued that decision on two grounds: First, that a presumption against extraterritorial application of U.S. law applied; and second, that licensing alone could not establish a domestic industry. The American University Law Review's critique remains incomplete, however, as the Federal Circuit correctly decided the case for at least two reasons. first, the Federal Circuit correctly applied the “extraterritorial presumption” canon of construction; and second, the recent Federal Circuit decision in InterDigital Communications LLC v. …

Erectogenic Effects Of Clerodendron Capitatum: Involvement Of Phosphodiesterase Type-5 Inhibition, Dr Syam Mohan

Syam Mohan

No abstract provided.

Clausena Excavata Burm. F. (Rutaceae): A Review Of Its Traditional Uses, Pharmacological And Phytochemical Properties., Dr Syam Mohan

Syam Mohan

The present review describes the morphological, traditional, phytochemical and pharmacological aspects of Clausena excavata (Burm. f., Rutaceae). The plant grows wild in the tropical and subtropical parts of Asia and represents one of the richest sources of medicinal natural products. It is intensively used currently in traditional medicine for treatment of different illnesses. One part or a mixture of two or more parts of the plant in the form of powder or liquid doze is usually given to the patient. Phytochemically, many pure compounds from several secondary metabolite groups of C. excavata have been isolated from different parts of the …

Chloroform Fraction Of Centratherum Anthelminticum (L.) Seed Inhibits Tumor Necrosis Factor Alpha And Exhibits Pleotropic Bioactivities: Inhibitory Role In Human Tumor Cells, Dr Syam Mohan

Syam Mohan

We investigated the antioxidant potential, cytotoxic effect, and TNF-α inhibition activity with NF-κB activation response in a chloroformfraction of Centratherum anthelminticum seeds (CACF). The antioxidant property of CACF was evaluated with DPPH, ORAC, and FRAP assays, which demonstrated significant antioxidant activity. The cytotoxicity of CACF was tested using theMTT assay; CACF effective inhibitory concentrations (IC50) for A549, PC-3, MCF-7, and WRL-68 cells were 31.42 ± 5.4, 22.61 ± 1.7, 8.1±0.9, and 54.93±8.3 μg/mL, respectively. CACF effectively and dose-dependently inhibited TNF-α release, in vitro and in vivo. CACF inhibited TNF-α secretion in stimulated RAW264.7macrophage supernatants with an IC50 of 0.012 μg/mL, …

In Vitro Anti-Inflammatory, Cytotoxic And Antioxidant Activities Of Boesenbergin A, A Chalcone Isolated From Boesenbergia Rotunda (L.) (Fingerroot), Dr Syam Mohan

Syam Mohan

The current in vitro study was designed to investigate the anti-inflammatory, cytotoxic and antioxidant activities of boesenbergin A (BA), a chalcone derivative of known structure isolated from Boesenbergia rotunda. Human hepatocellular carcinoma (HepG2), colon adenocarcinoma (HT-29), non-small cell lung cancer (A549), prostate adenocarcinoma (PC3), and normal hepatic cells (WRL-68) were used to evaluate the cytotoxicity of BA using the MTT assay. The antioxidant activity of BA was assessed by the ORAC assay and compared to quercetin as a standard reference antioxidant. ORAC results are reported as the equivalent concentration of Trolox that produces the same level of antioxidant activity as …

Synthesis Of Chalcones With Anticancer Activities., Dr Syam Mohan

Syam Mohan

Several chalcones were synthesized and their in vitro cytotoxicity against various human cell lines, including human breast adenocarcinoma cell line MCF-7, human lung adenocarcinoma cell line A549, human prostate cancer cell line PC3, human adenocarcinoma cell line HT-29 (colorectal cancer) and human normal liver cell line WRL-68 was evaluated. Most of the compounds being active cytotoxic agents, four of them with minimal IC50 values were chosen and studied in detail with MCF-7 cells. The compounds 1, 5, 23, and 25 were capable in eliciting apoptosis in MCF-7 cells as shown by multiparameter cytotoxicity assay and caspase-3/7, -8, and -9 activities …

Cucurbitacin L 2-O- Glucoside Demonstrates Apoptogenesis In Colon Adenocarcinoma Cells (Ht-29): Involvement Of Reactive Oxygen And Nitrogen Species Regulation, Dr Syam Mohan

Syam Mohan

Emerging evidence suggests that reactive oxygen (ROS) and nitrogen (RNS) species can contribute to diverse signalling pathways of inflammatory and tumour cells. Cucurbitacins are a group of highly oxygenated triterpenes. Many plants used in folk medicine to treat cancer have been found to contain cucurbitacins displaying potentially important anti-inflammatory actions. The current study was designed to investigate the anti-ROS and -RNS effects of cucurbitacin L 2-O-β-glucoside (CLG) and the role of these signaling factors in the apoptogenic effects of CLG on human colon cancer cells (HT-29). This natural cucurbitacin was isolated purely from Citrullus lanatus var. citroides (Cucurbitaceae). The results …

Dentatin Induces Apoptosis In Prostate Cancer Cells Via Bcl-2, Bcl-Xl, Survivin Downregulation, Caspase-9, -3/7 Activation And Nf-Kb Inhibition., Dr Syam Mohan

Syam Mohan

This study was set to investigate antiproliferative potential of dentatin (a natural coumarin isolated from Clausena excavata Burm. F) against prostate cancer and to delineate the underlying mechanism of action. Treatment with dentatin dose-dependently inhibited cell growth of PC-3 and LNCaP prostate cancer cell lines, whereas it showed less cytotoxic effects on normal prostate epithelial cell line (RWPE-1). The inhibitory effect of dentatin on prostate cancer cell growth was due to induction of apoptosis as evidenced by Annexin V staining and cell shrinkage. We found that dentatin-mediated accumulation of reactive oxygen species (ROS) and downregulated expression levels of antiapoptotic molecules …

Parallel Text Immersion, Daniel P. Becker Ph.D.

Daniel P. Becker

A new method of teaching foreign languages to beginning, intermediate, and advancing foreign language students is proposed involving reading out loud passages, chapters, and entire works of literature that are familiar to the student through required pre-reading in the students’ mother tongue. Testing is proposed to evaluate the success of the method.

The Growth Suppressing Effects Of Girinimbine On Hepg2 Involve Induction Of Apoptosis And Cell Cycle Arrest, Syam Mohan

Syam Mohan

Murraya koenigii is an edible herb widely used in folk medicine. Here we report that girinimbine, a carbazole alkaloid isolated from this plant, inhibited the growth and induced apoptosis in human hepatocellular carcinoma, HepG2 cells. The MTT and LDH assay results showed that girinimbine decreased cell viability and increased cytotoxicity in a dose-and time-dependent manner selectively. Girinimbine-treated HepG2 cells showed typical morphological features of apoptosis, as observed from normal inverted microscopy and Hoechst 33342 assay. Furthermore, girinimbine treatment resulted in DNA fragmentation and elevated levels of caspase-3 in HepG2 cells. Girinimbine treatment also displayed a time-dependent accumulation of the Sub-G(0)/G(1) …

Identification Of 2-Aminothiazole-4-Carboxylate Derivatives Active Against Mycobacterium Tuberculosis H37rv And The B-Ketoacyl-Acp Synthase Mtfabh, Philadelphia University

Philadelphia University, Jordan

No abstract provided.