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30 records – page 1 of 3.

Advancement into the Arctic region for bioactive sponge secondary metabolites.

https://arctichealth.org/en/permalink/ahliterature294048
Source
Marine Drugs. 2011;9(11):2423-37. doi: 10.3390/md9112423. Epub 2011 Nov 21.
Publication Type
Article
Date
2011
Author
Abbas S
Kelly M
Bowling J
Sims J
Waters A
Hamann M
Source
Marine Drugs. 2011;9(11):2423-37. doi: 10.3390/md9112423. Epub 2011 Nov 21.
Date
2011
Language
English
Publication Type
Article
Keywords
Animals
Arctic Regions
Biological Products
Isolation & purification
Pharmacology
Drug Design
Drug Discovery
Methods
Humans
Porifera
Classification
Metabolism
Abstract
Porifera have long been a reservoir for the discovery of bioactive compounds and drug discovery. Most research in the area has focused on sponges from tropical and temperate waters, but more recently the focus has shifted to the less accessible colder waters of the Antarctic and, to a lesser extent, the Arctic. The Antarctic region in particular has been a more popular location for natural products discovery and has provided promising candidates for drug development. This article reviews groups of bioactive compounds that have been isolated and reported from the southern reaches of the Arctic Circle, surveys the known sponge diversity present in the Arctic waters, and details a recent sponge collection by our group in the Aleutian Islands, Alaska. The collection has yielded previously undescribed sponge species along with primary activity against opportunistic infectious diseases, malaria, and HCV. The discovery of new sponge species and bioactive crude extracts gives optimism for the isolation of new bioactive compounds from a relatively unexplored source.
PubMed ID
22163194 View in PubMed
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Application of ALOGPS 2.1 to predict log D distribution coefficient for Pfizer proprietary compounds.

https://arctichealth.org/en/permalink/ahliterature9356
Source
J Med Chem. 2004 Nov 4;47(23):5601-4
Publication Type
Article
Date
Nov-4-2004
Author
Igor V Tetko
Gennadiy I Poda
Author Affiliation
Biomedical Department, Institute of Bioorganic and Petroleum Chemistry, Ukrainian Academy of Sciences, Murmanskaya 1, Kyiv, 02094, Ukraine. itetko@vcclab.org
Source
J Med Chem. 2004 Nov 4;47(23):5601-4
Date
Nov-4-2004
Language
English
Publication Type
Article
Keywords
1-Octanol
Administration, Oral
Biological Availability
Chemistry, Pharmaceutical
Databases, Factual
Drug Design
Drug Industry
Hydrogen-Ion Concentration
Neural Networks (Computer)
Pharmaceutical Preparations - chemistry - metabolism
Private Sector
Quantitative Structure-Activity Relationship
Research Support, Non-U.S. Gov't
Software
Solubility
Water
Abstract
Evaluation of the ALOGPS, ACD Labs LogD, and PALLAS PrologD suites to calculate the log D distribution coefficient resulted in high root-mean-squared error (RMSE) of 1.0-1.5 log for two in-house Pfizer's log D data sets of 17,861 and 640 compounds. Inaccuracy in log P prediction was the limiting factor for the overall log D estimation by these algorithms. The self-learning feature of the ALOGPS (LIBRARY mode) remarkably improved the accuracy in log D prediction, and an rmse of 0.64-0.65 was calculated for both data sets.
PubMed ID
15509156 View in PubMed
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Application of biomarkers in the clinical development of new drugs for chondroprotection in destructive joint diseases: a review.

https://arctichealth.org/en/permalink/ahliterature80122
Source
Biomarkers. 2006 Nov-Dec;11(6):485-506
Publication Type
Article
Author
Sumer E U
Schaller S.
Sondergaard B C
Tankó L B
Qvist P.
Author Affiliation
Nordic Bioscience A/S, Herlev, Denmark. eus@nordicbioscience.com
Source
Biomarkers. 2006 Nov-Dec;11(6):485-506
Language
English
Publication Type
Article
Keywords
Arthritis, Rheumatoid - drug therapy - pathology
Biological Markers - analysis
Cartilage - drug effects - metabolism
Drug Design
Humans
Joint Diseases - drug therapy - pathology
Osteoarthritis - drug therapy
Protective Agents - therapeutic use
Abstract
Emerging evidence supports the concept that biochemical markers are clinically useful non-invasive diagnostic tools for the monitoring of changes in cartilage turnover in patients with destructive joint diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA). Epidemiological studies demonstrated that measurements of different degradation products of proteins in the extracellular matrix of hyaline cartilage in urine or serum samples are (1) increased in OA or RA patients compared with healthy individuals, (2) correlate with disease activity, and (3) are predictive for the rate of changes in radiographic measures of cartilage loss. The present review provides an updated list of available biomarkers and summarize the research data arguing for their clinical utility. In addition, it addresses the question whether or not the monitoring of biomarkers during different treatment modalities could be a useful approach to characterize the chondro-protective effects of approved and candidate drugs. Finally, it briefly reviews the in vitro/ex vivo experimental settings - isolated chondrocyte cultures and articular cartilage explants - that can assist in the verification of novel markers, but also studies assessing direct effects of drug candidates on chondrocytes. Collectively, biomarkers may acquire a function as established efficacy parameters in the clinical development of novel chondro-protective agents.
PubMed ID
17056470 View in PubMed
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[A procedure for calculating needs for antituberculous drugs].

https://arctichealth.org/en/permalink/ahliterature157421
Source
Probl Tuberk Bolezn Legk. 2008;(3):3-10
Publication Type
Article
Date
2008
Author
E M Bogorodskaia
N V Antonova
M I Perel'man
K G Puchkov
T N Ivanushkina
Source
Probl Tuberk Bolezn Legk. 2008;(3):3-10
Date
2008
Language
Russian
Publication Type
Article
Keywords
Antitubercular Agents - therapeutic use
Drug Design
Drug Industry
Drug Utilization - statistics & numerical data
Humans
Needs Assessment - organization & administration
Russia
Tuberculosis - drug therapy
Abstract
to develop a procedure for calculating needs for antituberculous drugs (ATD).
A unified E-form (UEF) was developed as an "Excel" file with the underlying invariable formulas and coefficients for the computer-based calculation of ATD needs in any subject of the Russian Federation. The needs were estimated using the average number of tablets (capsules, vials) of each ATD required per man/course, by taking into account the conventional chemotherapy regimens, the duration of chemoprophylaxis, antirecurrent courses, ATD test therapy, a treatment regimen for complications due to BCG vaccination. Information on the inventory of ATDs at the end of the previous year and their estimated deliveries from various sources was additionally considered. Data to be filled in the UEF were obtained from the reporting documents: 1) TB Form No. 2 "Information on patients registered for treatment" approved by Order No. 50 "On Consummation of Recording and Reporting Documents as to Tuberculosis Monitoring" issued by the Ministry of Health of the Russian Federation on February 13, 2002; 2) Form No. 030-4/y "Tuberculosis Patient Follow-Up Schedule"; and 3) Form No. 33 "Information on Patients with Tuberculosis" approved by Regulation No. 80 issued by the Russian Statistics Agency on November 11, 2005. The filled-in UEFs were obtained from 82 subjects of the Russian Federation.
among all the contingents of antituberculosis dispensaries, who were given ATDs, the absolute majority was the persons receiving chemoprophylaxis. Only 18.3% received chemotherapy for active tuberculosis. Of them, 56.8 and 15.3% were treated in accordance with chemotherapy regimens 1 and 3, respectively. The regimes (2B and 4) using second-line agents were given least frequently (7.1 and 7.1%, respectively). Comparing the data from Form No. 33 and those obtained on filling in UEF showed with a fair degree of assurance that the treatment of patients with a chronic tuberculous process had been incompletely registered. Personified registration of patients with multidrug Mycobacterium tuberculosis resistance should be performed in order to have objective information on the scope of required medical aid and the real calculation of needs for second-line ATDs. For unified calculation of needs for ATDs for chemotherapy, it is necessary to introduce a standardized approach to its performance at different dispensaries. By taking into account that ATDs are purchased and dispensed free of change, one should have a responsible attitude to consuming drugs, determining indications for their usage, and filling the UEF. TB Form No. 2 "Information on patients registered for treatment" and Register No, 03-TB/y "Register of patients with tuberculosis" should be improved, by adding data on the number of patients receiving chemoprophylaxis, antirecurrent courses, test therapy, and treatment of complications due to BCG vaccination.
PubMed ID
18453052 View in PubMed
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Assessing abuse liability during drug development: changing standards and expectations.

https://arctichealth.org/en/permalink/ahliterature159216
Source
Clin Pharmacol Ther. 2008 Apr;83(4):622-6
Publication Type
Article
Date
Apr-2008
Author
K A Schoedel
E M Sellers
Author Affiliation
Clinical Pharmacology Group, DecisionLine Clinical Research Corporation, Toronto, Ontario, Canada. k.schoedel@dlcrc.com
Source
Clin Pharmacol Ther. 2008 Apr;83(4):622-6
Date
Apr-2008
Language
English
Publication Type
Article
Keywords
Canada
Central Nervous System Depressants - adverse effects
Central Nervous System Stimulants - adverse effects
Dose-Response Relationship, Drug
Drug Design
Drug and Narcotic Control - legislation & jurisprudence
European Union
Humans
Psychotropic Drugs - adverse effects
Substance-Related Disorders - etiology
Time Factors
United States
United States Food and Drug Administration
Abstract
As public health concerns have changed, regulatory expectations for assessing abuse liability of new central nervous system (CNS) drugs have increased. All CNS-active drugs with any properties indicating stimulant, depressant, hallucinogenic, or mood-elevating effects will require an evaluation of abuse liability. Abuse liability assessment involves the collection, analysis, and interpretation of data on chemistry and tampering, animal behavioral pharmacology, clinical trial adverse events (AEs), diversion and overdose, and potentially reinforcing (subjective) effects in recreational drug users.
PubMed ID
18212799 View in PubMed
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[Brief characteristic of comprehensive project "development of technology of differential proteomics and its application to development of new anticancer drugs"].

https://arctichealth.org/en/permalink/ahliterature167692
Source
Mol Gen Mikrobiol Virusol. 2006;(3):3-10
Publication Type
Article
Date
2006

[Development of the anti-influenza H5N1 vaccines worldwide and in Russia]

https://arctichealth.org/en/permalink/ahliterature80634
Source
Zh Mikrobiol Epidemiol Immunobiol. 2006 Jul-Aug;(5):28-38
Publication Type
Article
Author
Kiselev O I
Tsybalova L M
Pokrovskii V I
Source
Zh Mikrobiol Epidemiol Immunobiol. 2006 Jul-Aug;(5):28-38
Language
Russian
Publication Type
Article
Keywords
Animals
Clinical Trials
Drug Design
Genes, Viral - immunology
Genetic Engineering
Humans
Influenza A Virus, H5N1 Subtype - genetics - immunology
Influenza Vaccines - administration & dosage - genetics
Orthomyxoviridae Infections - prevention & control
Plasmids - immunology
Russia - epidemiology
Vaccination
World Health
Abstract
Article is dedicated to analytical investigation of the problem of current technologies in construction and manufacturing of anti-influenza vaccines. Epidemiological events in July-November 2005 in Russia (mainly in Siberia) and later in Ukraine showed that Health Care system was not ready for that turn over of epidemiological situation. It was completely the same situation in other countries. There are two general questions of a readiness in pre-pandemic situation: level of a diagnostic monitoring of epidemiological situation and preparedness to fast production of actual vaccine preparations. First task can be solved by immediate production of diagnostic sets for regional branches of National WHO Centers, and a second one depends on application of a novel approaches in construction of a anti-influenza vaccines. The construction of anti-influenza vaccines is based on genetic engineering (reverse genetics) and manipulation with plasmids carried out basic viral genes. Reassortation technology for preparation of hybrid viruses is going to the past by objective reasons. Advanced technologies are safety in laboratories and in manufacturing facilities. Moreover, genetic engineering in this field allows to planing the construction of vaccines bank, when the prognoses for actual viruses include more then two strains with different antigenic properties.
PubMed ID
16981491 View in PubMed
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Effects of the Arctic (E22-->G) mutation on amyloid beta-protein folding: discrete molecular dynamics study.

https://arctichealth.org/en/permalink/ahliterature153906
Source
J Am Chem Soc. 2008 Dec 24;130(51):17413-22
Publication Type
Article
Date
Dec-24-2008
Author
A R Lam
D B Teplow
H E Stanley
B. Urbanc
Author Affiliation
Center for Polymer Studies, Physics Department, Boston University, Boston, Massachusetts 02215, USA. arlam@buphy.bu.edu
Source
J Am Chem Soc. 2008 Dec 24;130(51):17413-22
Date
Dec-24-2008
Language
English
Publication Type
Article
Keywords
Amyloid beta-Peptides - chemistry - genetics
Animals
Circular Dichroism
Computer simulation
Drug Design
Humans
Hydrogen Bonding
Models, Statistical
Mutation
Neurons - metabolism
Peptides - chemistry
Protein Conformation
Protein Folding
Protein Structure, Secondary
Protein Structure, Tertiary
Abstract
The 40-42 residue amyloid beta-protein (Abeta) plays a central role in the pathogenesis of Alzheimer's disease (AD). Of the two main alloforms, Abeta40 and Abeta42, the longer Abeta42 is linked particularly strongly to AD. Despite the relatively small two amino acid length difference in primary structure, in vitro studies demonstrate that Abeta40 and Abeta42 oligomerize through distinct pathways. Recently, a discrete molecular dynamics (DMD) approach combined with a four-bead protein model recapitulated the differences in Abeta40 and Abeta42 oligomerization and led to structural predictions amenable to in vitro testing. Here, the same DMD approach is applied to elucidate folding of Abeta40, Abeta42, and two mutants, [G22]Abeta40 and [G22]Abeta42, which cause a familial ("Arctic") form of AD. The implicit solvent in the DMD approach is modeled by amino acid-specific hydropathic and electrostatic interactions. The strengths of these effective interactions are chosen to best fit the temperature dependence of the average beta-strand content in Abeta42 monomer, as determined using circular dichroism (CD) spectroscopy. In agreement with these CD data, we show that at physiological temperatures, the average beta-strand content in both alloforms increases with temperature. Our results predict that the average beta-strand propensity should decrease in both alloforms at temperatures higher than approximately 370 K. At physiological temperatures, both Abeta40 and Abeta42 adopt a collapsed-coil conformation with several short beta-strands and a small (
Notes
Erratum In: J Am Chem Soc. 2011 Mar 2;133(8):2789
PubMed ID
19053400 View in PubMed
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Gastrointestinal effects of nonsteroidal anti-inflammatory drugs.

https://arctichealth.org/en/permalink/ahliterature184973
Source
Fundam Clin Pharmacol. 2003 Jun;17(3):301-13
Publication Type
Article
Date
Jun-2003
Author
Brendan J R Whittle
Author Affiliation
William Harvey Research Institute, St Bartholomew's and The Royal London School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, UK. b.j.whittle@qmul.ac.uk
Source
Fundam Clin Pharmacol. 2003 Jun;17(3):301-13
Date
Jun-2003
Language
English
Publication Type
Article
Keywords
Anti-Inflammatory Agents, Non-Steroidal - adverse effects - therapeutic use
Clinical Trials as Topic
Cyclooxygenase 1
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors - adverse effects - metabolism
Drug Design
Gastric Mucosa - drug effects - pathology
Gastrointestinal Diseases - chemically induced - pathology - prevention & control
Humans
Intestinal Mucosa - drug effects - pathology
Isoenzymes - antagonists & inhibitors - metabolism
Membrane Proteins
Nitric Oxide Donors - adverse effects - pharmacology - therapeutic use
Prostaglandin-Endoperoxide Synthases - metabolism
Prostaglandins - metabolism
Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) causes extensive damage to the gastrointestinal (GI) tract. The underlying mechanisms of gastric injury include topical irritant actions that disrupt the epithelial barrier, as well as the inhibition of cyclo-oxygenase (COX), which is predominantly the COX-1 isoform in the mucosa. This damage can be attenuated by antisecretory agents or by mucosal protective agents such as the synthetic prostanoids or nitric oxide (NO) donors. Compounds designed to attenuate topical irritancy, or have protective agents incorporated, such as NO-containing NSAIDs, the CINODs (cyclo-oxygenase-inhibiting NO-donating drugs) show reduced mucosal injury. NSAIDs also cause injury in the small intestine, which appears to result from initial COX inhibition, with subsequent translocation of indigenous bacteria, induction of NO synthase and production of the cytotoxic moiety, peroxynitrite. The COX-2 selective agents, the coxibs, which inhibit prostanoid biosynthesis at inflammatory sites, but not the endogenous protective prostanoids in the gut formed by COX-1, have proved so far to be a successful therapeutic approach to reducing NSAIDs GI damage. The clinical outcome of the use of the second generation of coxibs, and the newer NO NSAIDs is now awaited.
PubMed ID
12803569 View in PubMed
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Gram-scale synthesis of pinusolide and evaluation of its antileukemic potential.

https://arctichealth.org/en/permalink/ahliterature81828
Source
Bioorg Med Chem Lett. 2006 Aug 15;16(16):4228-32
Publication Type
Article
Date
Aug-15-2006
Author
Shults E E
Velder J.
Schmalz H-G
Chernov S V
Rubalova T V
Gatilov Y V
Henze G.
Tolstikov G A
Prokop A.
Author Affiliation
Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9 Prosp. Akad. Lavrent'eva, Novosibirsk, Russian Federation. schultz@nioch.nsc.ru
Source
Bioorg Med Chem Lett. 2006 Aug 15;16(16):4228-32
Date
Aug-15-2006
Language
English
Publication Type
Article
Keywords
Antineoplastic Agents - chemical synthesis - pharmacology
Carboxylic Acids - chemistry
Cell Line
Cell Line, Tumor
Crystallography, X-Ray
DNA Fragmentation
Diterpenes - chemical synthesis - pharmacology
Dose-Response Relationship, Drug
Drug Design
Humans
Leukemia, Lymphocytic, Acute - drug therapy
Leukemia, Myelocytic, Acute - drug therapy
Mitochondria - metabolism
Models, Chemical
Models, Molecular
Naphthalenes - chemistry
Abstract
Pinusolide (1), a known platelet-activating factor (PAF) receptor binding antagonist, was synthesized from lambertianic acid (2), a labdane-type diterpene readily accessible in multigram quantities from the Siberian pine tree. It was shown that 1 not only decreases the proliferation activity of tumor cells at relatively low concentrations but specifically induces apoptosis at 100 microM via the mitochondrial pathway in the Burkitt lymphoma cell line BJAB. Also, using primary lymphoblasts and leukemic cells from children with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), a significant DNA fragmentation in pinusolide-treated cells could be detected in an ex vivo apoptosis assay.
PubMed ID
16781150 View in PubMed
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30 records – page 1 of 3.