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Big Pharma Is Hurt, Singapore Management University 2014 Singapore Management University

Big Pharma Is Hurt, Singapore Management University

Perspectives@SMU

Cutting down R&D inefficiency and restoring the trust of investors and consumers are key to curing the industry’s ills.


Role Of Erk1, 2, And 5 In Dopamine Neuron Survival During Aging, Mayur S. Parmar, Juliann D. Jaumotte, Stephanie L. Wyrostek, Michael J. Zigmond, Jane E. Cavanaugh 2014 Duquesne University

Role Of Erk1, 2, And 5 In Dopamine Neuron Survival During Aging, Mayur S. Parmar, Juliann D. Jaumotte, Stephanie L. Wyrostek, Michael J. Zigmond, Jane E. Cavanaugh

HPD Articles

Extracellular signal-regulated kinases (ERKs) 1, 2, and 5 have been shown to play distinct roles in proliferation, differentiation, and neuronal viability. In this study, we examined ERK1, 2, and 5 expression and activation in the substantia nigra (SN), striatum (STR), and ventral tegmental area (VTA) during aging. An age-related decrease in phosphorylated ERK5 was observed in the SN and STR, whereas an increase in total ERK1 was observed in all 3 regions. In primary cultures of the SN and VTA, inhibition of ERK5 but not ERK1 and 2 decreased dopamine neuronal viability significantly. These data suggest that ERK5 is essential …


Effect Of Dichloromethane Fraction Of Areca Catechu Nut On Monoamines Associated Behaviors And Tyramine Pressor Sensitivity In Rodents, Shagufta Khan, Ghulam Abbas, Fahad Shabbir Ahmed, Attaur Rahman, Ahsana Dar 2014 Aga Khan University

Effect Of Dichloromethane Fraction Of Areca Catechu Nut On Monoamines Associated Behaviors And Tyramine Pressor Sensitivity In Rodents, Shagufta Khan, Ghulam Abbas, Fahad Shabbir Ahmed, Attaur Rahman, Ahsana Dar

Department of Biological & Biomedical Sciences

The current study was aimed at investigating the effect of Areca catechu nut dichloromethane fraction (7 mg/kg) on monoamines (serotonin and dopamine) modulation (5-hydroxytryptophan-induced tremors and phenylethylamine-induced stereotypes) and its interaction with tyramine (cheese effect). The dichloromethane fraction caused pronounced increase in 5-HTP-induced tremors (50%) with negligible PEA-induced stereotypes (20%). Additionally, it did not produce a significant increase in the tyramine pressor effects. These results suggest that the dichloromethane fraction of A. catechu nut primarily elevates serotonin levels (probably via monoamine oxidase A inhibition) and does not induce cheese effect.


Spatiotemporal Expression Of Manf In The Developing Rat Brain, Haiping Wang, Zunji Ke, Alexander Alimov, Mei Xu, Jacqueline A. Frank, Shengyun Fang, Jia Luo 2014 University of Kentucky

Spatiotemporal Expression Of Manf In The Developing Rat Brain, Haiping Wang, Zunji Ke, Alexander Alimov, Mei Xu, Jacqueline A. Frank, Shengyun Fang, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an evolutionarily conserved neurotrophic factor which exhibited neuroprotective properties. Recent studies suggested that MANF may play a role in the neural development of Drosophila and zebra fishes. In this study, we investigated the spatiotemporal expression of MANF in the brain of postnatal and adult rats. MANF expression appeared wide spread and mainly localized in neurons. In the cerebral cortex, neurons in layer IV and VI displayed particularly strong MANF immunoreactivity. In the hippocampus, intensive MANF expression was observed throughout the subfields of Cornu Amonis (CA1, CA2, and CA3) and the granular layer of the …


Aged Rats Are Hypo-Responsive To Acute Restraint: Implications For Psychosocial Stress In Aging, Heather M. Buechel, Jelena Popovic, Kendra Staggs, Katie L. Anderson, Olivier Thibault, Eric M. Blalock 2014 University of Kentucky

Aged Rats Are Hypo-Responsive To Acute Restraint: Implications For Psychosocial Stress In Aging, Heather M. Buechel, Jelena Popovic, Kendra Staggs, Katie L. Anderson, Olivier Thibault, Eric M. Blalock

Pharmacology and Nutritional Sciences Faculty Publications

Cognitive processes associated with prefrontal cortex and hippocampus decline with age and are vulnerable to disruption by stress. The stress/stress hormone/allostatic load hypotheses of brain aging posit that brain aging, at least in part, is the manifestation of life-long stress exposure. In addition, as humans age, there is a profound increase in the incidence of new onset stressors, many of which are psychosocial (e.g., loss of job, death of spouse, social isolation), and aged humans are well-understood to be more vulnerable to the negative consequences of such new-onset chronic psychosocial stress events. However, the mechanistic underpinnings of this age-related shift …


Environews #7, Richard Philp 2014 University of Western Ontario

Environews #7, Richard Philp

Data and Test Instruments

Artificial sweeteners in rivers, arsenic underground, gutting of environmental protection laws are topics discussed.


The Characterization Of Pb2+ Toxicity In Rat Neural Development: An Assessment Of Pb2+ Effects On The Gaba Shift In Neural Networks And Implications For Learning And Memory Disruption, Lorenz Simon Neuwirth 2014 CUNY Graduate Center

The Characterization Of Pb2+ Toxicity In Rat Neural Development: An Assessment Of Pb2+ Effects On The Gaba Shift In Neural Networks And Implications For Learning And Memory Disruption, Lorenz Simon Neuwirth

Dissertations, Theses, and Capstone Projects

The toxic effects of Pb2+ on the developing rat nervous system has been investigated to assess early developmental GABAergic disruption and its implications with altering inhibitory learning and memory. This goal was achieved using a multi-systems approach: blood lead levels (clinical physiology), qRT-PCR (molecular genetics), brain and primary neuronal culture immunology (immunohistochemical and cellular approaches), physiological cellular components (synaptosomes and protein expression) and finally through learning and memory assessment with GABA mimetic drug manipulations in the intact animal (behavioral pharmacology). The influence of a 956ppm Pb2+ gestational diet (i.e. from birth to sacrifice) resulted in pup mean blood lead levels …


Characterization Of Particle Emissions And Fate Of Nanomaterials During Incineration, Eric P. Vejerano, Elena C. Leon, Amara L. Holder, Linsey C. Marr 2014 University of South Carolina

Characterization Of Particle Emissions And Fate Of Nanomaterials During Incineration, Eric P. Vejerano, Elena C. Leon, Amara L. Holder, Linsey C. Marr

Faculty Publications

As the use of nanotechnology in consumer products continues to grow, it is inevitable that some nanomaterials will end up in the waste stream and will be incinerated. Through laboratory-scale incineration of paper and plastic wastes containing nanomaterials, we assessed their effect on emissions of particulate matter (PM) and the effect of incineration on the nanomaterials themselves. The presence of nanomaterials did not significantly influence the particle number emission factor. The PM size distribution was not affected except at very high mass loadings (10 wt%) of the nanomaterial, in which case the PM shifted toward smaller sizes; such loadings are …


The Rak/Frk Tyrosine Kinase Associates With And Internalizes The Epidermal Growth Factor Receptor, Ling Jin, Rolf J. Craven 2014 University of Kentucky

The Rak/Frk Tyrosine Kinase Associates With And Internalizes The Epidermal Growth Factor Receptor, Ling Jin, Rolf J. Craven

Pharmacology and Nutritional Sciences Faculty Publications

Src is the founding member of a diverse family of intracellular tyrosine kinases, and Src has a key role in promoting cancer growth, in part, through its association with receptor tyrosine kinases. However, some Src-related proteins have widely divergent physiological roles, and these proteins include the Rak/Frk tyrosine kinase (Frk stands for Fyn-related kinase), which inhibits cancer cell growth and suppresses tumorigenesis. Rak/Frk phosphorylates and stabilizes the Pten tumor suppressor, protecting it from degradation, and Rak/Frk associates with the retinoblastoma (Rb) tumor suppressor. However, the role of Rak/Frk in receptor-mediated signaling is largely unknown. Here, we demonstrate that Rak/Frk associates …


Changing Microspatial Patterns Of Sulfate-Reducing Microorganisms (Srm) During Cycling Of Marine Stromatolite Mats, Alexandru I. Petrisor, Sandra Szyjka, Tomohiro Kawaguchi, Pieter T. Visscher, Robert Sean Norman, Alan W. Decho 2014 University of South Carolina - Columbia

Changing Microspatial Patterns Of Sulfate-Reducing Microorganisms (Srm) During Cycling Of Marine Stromatolite Mats, Alexandru I. Petrisor, Sandra Szyjka, Tomohiro Kawaguchi, Pieter T. Visscher, Robert Sean Norman, Alan W. Decho

Faculty Publications

Microspatial arrangements of sulfate-reducing microorganisms (SRM) in surface microbial mats (~1.5 mm) forming open marine stromatolites were investigated. Previous research revealed three different mat types associated with these stromatolites, each with a unique petrographic signature. Here we focused on comparing “non-lithifying” (Type-1) and “lithifying” (Type-2) mats. Our results revealed three major trends: (1) Molecular typing using the dsrA probe revealed a shift in the SRM community composition between Type-1 and Type-2 mats. Fluorescence in-situ hybridization (FISH) coupled to confocal scanning-laser microscopy (CSLM)-based image analyses, and 35SO42−-silver foil patterns showed that SRM were present in surfaces of …


An Introduction To Drugs And The Neuroscience Of Behavior, Adam J. Prus 2014 Northern Michigan University

An Introduction To Drugs And The Neuroscience Of Behavior, Adam J. Prus

Books

This up-to-date text provides an introductory overview of the nervous system actions and behavioral effects of the major classes of psychoactive drugs, using pedagogy unique among pharmacology texts to make the topic approachable.


Cycloastragenol, A Triterpene Aglycone Derived From Radix Astragali, Suppresses The Accumulation Of Cytoplasmic Lipid Droplet In 3t3-L1 Adipocytes (Abstract), Shifeng Wang, Chenxi Zhai, Qing Liu, Xing Wang, Zhenzhen Ren, Yuxin Zhang, Yanling Zhang, Qinghua Wu, Shengnan Sun, Shiyou Li, Yanjiang Qiao 2014 Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China

Cycloastragenol, A Triterpene Aglycone Derived From Radix Astragali, Suppresses The Accumulation Of Cytoplasmic Lipid Droplet In 3t3-L1 Adipocytes (Abstract), Shifeng Wang, Chenxi Zhai, Qing Liu, Xing Wang, Zhenzhen Ren, Yuxin Zhang, Yanling Zhang, Qinghua Wu, Shengnan Sun, Shiyou Li, Yanjiang Qiao

NCPC Publications and Patents

No abstract provided.


Identification Of Natural Compound Carnosol As A Novel Trpa1 Receptor Agonist, Chenxi Zhai, Qing Liu, Yuxin Zhang, Shifeng Wang, Yanling Zhang, Shiyou Li, Yanjiang Qiao 2014 Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China

Identification Of Natural Compound Carnosol As A Novel Trpa1 Receptor Agonist, Chenxi Zhai, Qing Liu, Yuxin Zhang, Shifeng Wang, Yanling Zhang, Shiyou Li, Yanjiang Qiao

NCPC Publications and Patents

The transient receptor potential ankyrin 1 (TRPA1) cation channel is one of the well-known targets for pain therapy. Herbal medicine is a rich source for new drugs and potentially useful therapeutic agents. To discover novel natural TRPA1 agonists, compounds isolated from Chinese herbs were screened using a cell-based calcium mobilization assay. Out of the 158 natural compounds derived from traditional Chinese herbal medicines, carnosol was identified as a novel agonist of TRPA1 with an EC50 value of 12.46 µM. And the agonistic effect of carnosol on TRPA1 could be blocked by A-967079, a selective TRPA1 antagonist. Furthermore, the specificity of …


Chemical Constituents From Pterocarpus Soyauxii, Zushang Su, Ping Wang, Wei Yuan, Shiyou Li 2014 National Center for Pharmaceutical Crops, Arthur Temple College of Forestry and Agriculture, Stephen F. Austin State University

Chemical Constituents From Pterocarpus Soyauxii, Zushang Su, Ping Wang, Wei Yuan, Shiyou Li

NCPC Publications and Patents

Three new benzofurans (1-3) and one new isoflavan (4), pteroyanin G, H, I and J, together with 21 known compounds, were isolated from the heartwood of Pterocarpus soyauxii. Their structures were determined by the NMR and MS spectral data in comparison with literature data. Compounds (1-25) did not show cytotoxicity against three human cancer cell lines, A549, Panc-28, and HCT-116 (Gl50 > 50 μM)


Ethnobotany Of Camptotheca Decaisne: New Discoveries Of Old Medicinal Uses, Shiyou Li, Wanli Zhang 2014 Stephen F Austin State University, Arthur Temple College of Forestry and Agriculture

Ethnobotany Of Camptotheca Decaisne: New Discoveries Of Old Medicinal Uses, Shiyou Li, Wanli Zhang

NCPC Publications and Patents

Camptotheca trees had been used as fuelwood and an ornamental species in its native China. There were no reports on medicinal uses of Camptotheca in China and thus it was believed the trees had no medicinal before its antitumor activity discovered in 1957. We conducted national surveys of Camptotheca in China from 1994 to 1999. We found that Camptotheca acuminate is commonly known as happytree (xi shu) because the trees can be used as folk medicine to cure stubborn phlegm as well as other diseases, thus making patients “happy”. There are three local names to refer the uses of C. …


Trichome Management To Enhance Camptothecins In Camptotheca Decaisne, Shiyou Li, Zhizhen Zhang, Ping Wang, Wei Yuan 2014 Stephen F Austin State University, Arthur Temple College of Forestry and Agriculture

Trichome Management To Enhance Camptothecins In Camptotheca Decaisne, Shiyou Li, Zhizhen Zhang, Ping Wang, Wei Yuan

NCPC Publications and Patents

Inducible chemical defenses of plants have received much attention in the last three decades, and these defenses often involve trichomes. It is known that some plant secondary metabolites may accumulate in trichomes which can protect plants from damage by herbivores. However, studies on plant trichomes are largely limited to some major vegetable or cash crops and model species with large glandular trichomes (e.g., Nictotiana and Arabidopsis). In fact, the existing studies on the effect of damage (pruning or defoliation) on trichome density or chemical production in plants are partial and even contradictory. Management strategies to maximize chemical induction in …


Subthreshold Toxic Effects Of Atrazine And Three Degradates On Behavior In Procambarus Clarkii, Carol B. Starkey 2014 Marshall University

Subthreshold Toxic Effects Of Atrazine And Three Degradates On Behavior In Procambarus Clarkii, Carol B. Starkey

Theses, Dissertations and Capstones

Atrazine is among the most heavily applied pesticides worldwide, and recent evidence suggests that it may be unsafe at environmental levels. It is a known endocrine disruptor and a suggested neurotoxin. The US EPA Maximum Contaminant Level (MCL) is 3 μg/L for human ingestion and 200 μg/L for limited human exposure. Several environmentally persistent degradates have been identified, including deethylatrazine (DEA), deisopropylatrazine (DIA) and hydroxyatrazine (HA). No MCLs have been established for these degradates, although some are suggested toxins. Thus, there remains concern for the risk associated with the presence of atrazine and its degradates in the environment. Currently little …


Role Of Bumetanide On Insulin Secretion, Mohammed Mashari Almutairi 2014 Wright State University

Role Of Bumetanide On Insulin Secretion, Mohammed Mashari Almutairi

Browse all Theses and Dissertations

Insulin secretion depends on the electrical properties of the ß-cells in pancreatic islets. The consensus mechanism of insulin secretion involves glucose-stimulated metabolic increase in the ATP/ADP ratio. This increase closes ATP-sensitive K+ (KATP) channels resulting in ß-cell plasma membrane depolarization, which in turn activates voltage-dependent Ca2+ channels further resulting in Ca2+ influx and release of insulin stored in granules. In addition to this well-known consensus mechanism, insulin secretion also depends on electrogenic efflux of Cl- ions. The Na+K 2Cl- cotransporters (NKCCs) maintain the intracellular concentration of Cl- ([Cl-]i) at values higher than those predicted at thermodynamic equilibrium. This distribution of …


Nudging The Fda, W. Nicholson Price II, I. Glenn Cohen 2014 University of New Hampshire School of Law

Nudging The Fda, W. Nicholson Price Ii, I. Glenn Cohen

Law Faculty Scholarship

[Excerpt] "The FDA’s regulation of drugs is frequently the subject of policy debate, with arguments falling into two camps. On the one hand, a libertarian view of patients and the health care system holds high the value of consumer choice. Patients should get all the information and the drugs they want; the FDA should do what it can to enforce some basic standards but should otherwise get out of the way. On the other hand, a paternalist view values the FDA’s role as an expert agency standing between patients and a set of potentially dangerous drugs and potentially unscrupulous or …


Re: Pierce Et Al. Diacetyl And 2,3-Pentanedione Exposures Associated With Cigarette Smoking: Implications For Risk Assessment Of Food And Flavoring Workers Crit Rev Toxicol, 2014; 44(5): 420-435, Muge Akpinar-Elci, Omur Cinar Elci 2014 Old Dominion University

Re: Pierce Et Al. Diacetyl And 2,3-Pentanedione Exposures Associated With Cigarette Smoking: Implications For Risk Assessment Of Food And Flavoring Workers Crit Rev Toxicol, 2014; 44(5): 420-435, Muge Akpinar-Elci, Omur Cinar Elci

Center for Global Health Publications

We were greatly dismayed by Pierce et al.’ s report on the associations between exposure to Diacetyl and 2,3-pentanedione and cigarette smoking (Pierce et al. 2014). It stated that “ Diacetyl and 2,3-pentanedione exposures from cigarette smoking far exceed occupational exposures for most food/flavoring workers who smoke. ” Based on this finding, the authors suggested that “ previous claims of a significant exposure – response relationship between diacetyl inhalation and respiratory disease in food/flavoring workers were confounded because none of the investigations considered or quantified the non-occupational diacetyl exposure from cigarette smoke, yet all the cohorts evaluated had considerable smoking …


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