315 research outputs found
Capsaicin and Its analogues impede nocifensive response of caenorhabditis elegans to noxious heat
Capsaicin is the most abundant pungent molecule identifed in red chili peppers, and it is widely used for food favoring,
in pepper spray for self-defense devices and recently in ointments for the relief of neuropathic pain. Capsaicin and several
other related vanilloid compounds are secondary plant metabolites. Capsaicin is a selective agonist of the transient receptor
potential channel, vanilloid subfamily member 1 (TRPV1). After exposition to vanilloid solution, Caenorhabditis elegans
wild type (N2) and mutants were placed on petri dishes divided in quadrants for heat stimulation. Thermal avoidance index
was used to phenotype each tested C. elegans experimental groups. The data revealed for the frst-time that capsaicin can
impede nocifensive response of C. elegans to noxious heat (32–35 °C) following a sustained exposition. The efect was
reversed 6 h post capsaicin exposition. Additionally, we identifed the capsaicin target, the C. elegans transient receptor
potential channel OCR-2 and not OSM-9. Further experiments also undoubtedly revealed anti-nociceptive efect for capsaicin
analogues, including olvanil, gingerol, shogaol and curcumin
Eugenol and other vanilloids hamper caenorhabditis elegans response to noxious heat
Eugenol, a known vanilloid, was frequently used in dentistry as a local analgesic in addition, antibacterial and neuroprotective effects were also reported. Eugenol, capsaicin and many vanilloids are interacting with the transient receptor potential vanilloid 1 (TRPV1) in mammals and the TRPV1 is activated by noxious heat. The pharmacological manipulation of the TRPV1 has been shown to have therapeutic value. Caenorhabditis elegans (C. elegans) express TRPV orthologs (e.g. OCR-2, OSM-9) and it is a commonly used animal model system to study nociception as it displays a well-defined and reproducible nocifensive behavior. After exposure to vanilloid solutions, C. elegans wild type (N2) and mutants were placed on petri dishes divided in quadrants for heat stimulation. Thermal avoidance index was used to phenotype each tested C. elegans experimental groups. The results showed that eugenol, vanillin and zingerone can hamper nocifensive response of C. elegans to noxious heat (32-35 °C) following a sustained exposition. Also, the effect was reversed 6 h post exposition. Furthermore, eugenol and vanillin did not target specifically the OCR-2 or OSM-9 but zingerone did specifically target the OCR-2 similarly to capsaicin. Further structural and physicochemical analyses were performed. Key parameters for quantitative structure-property relationships (QSPR), quantitative structure-activity relationships (QSAR) and frontier orbital analyses suggest similarities and dissimilarities amongst the tested vanilloids and capsaicin in accordance with the relative anti-nociceptive effects observed
Student Acceptance of Using Augmented Reality Applications for Learning in Pharmacy: A Pilot Study
Creating engaging learning experiences that are easy to use and support the different learning requirements of university students is challenging. However, improvements in simulation technologies, such as augmented reality (AR) and virtual reality (VR), are making such changes possible. The aim of this study is to use a mobile-based AR technology to develop an interactive learning module about contraceptive devices and medicines and to measure its acceptability and usability by undergraduate pharmacy students. The learning module comprising AR images of contraceptive medicines, case studies relating to their use and a series of directed questions was completed by 33 pharmacy students. Students answered a survey to collect information about the usability and acceptability of AR for learning. The results show that the majority of students reported that AR is a useful resource for learning about medicines compared to more traditional methods, such as didactic lectures and tutorials. Students indicated that the AR application was easy to use and improved their knowledge of medicines. These findings suggest that AR technology is a useful tool to create engaging and easy to use learning experiences for university students
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Covalent Inhibitors of Protein-Protein Interactions Targeting Lysine, Tyrosine, or Histidine Residues.
We have recently reported a series of Lys-covalent agents targeting the BIR3 domain of the X-linked inhibitor of apoptosis protein (XIAP) using a benzamide-sulfonyl fluoride warhead. Using XIAP as a model system, we further investigated a variety of additional warheads that can be easily incorporated into binding peptides and analyzed their ability to form covalent adducts with lysine and other amino acids, including tyrosine, histidine, serine, and threonine, using biochemical and biophysical assays. Moreover, we tested aqueous, plasma stability, cell permeability, and cellular efficacy of the most effective agents. These studies identified aryl-fluoro sulfates as likely the most suitable electrophiles to effectively form covalent adducts with Lys, Tyr, and His residues, given that these agents were cell permeable and stable in aqueous buffer and in plasma. Our studies contain a number of general findings that open new possible avenues for the design of potent covalent protein-protein interaction antagonists
Patient Assessment Skills Pertinent to Practicing Pharmacists
Objectives: To describe pharmacists’ opinions regarding which patient assessment skills are necessary to understand and/or perform to provide optimal patient care in pharmacy practice.
Methods: An online questionnaire was distributed to pharmacists licensed in North Carolina (n=14,167), as identified by the Board of Pharmacy. The 80 patient assessment items in the questionnaire were derived from a course text book and faculty experience. Participants indicated whether they “need to understand and be able to perform”, “need to understand only”, or “not need to understand or be able to perform” each item in their current practice setting. Descriptive statistics were used to describe background demographics and perceived need for each item. Post-hoc chi-square analyses were performed to determine differences in need based on practice setting and Pharm.D. degree completion.
Results: Of 1036 responses received, 770 were used in data analysis; incomplete questionnaires and non-practicing pharmacist responses were excluded. Fifty-nine percent of respondents held a Pharm.D. degree. Participants identified their practice site(s) as inpatient (29%), outpatient (16%), community/retail (50%), long term care (5%), and other (8%). The top five patient assessment items respondents identified as important to understand and perform included automatic blood pressure measurement (63%), point of care testing (57%), manual blood pressure measurement (53%), heart rate measurement (52%), and peak flow meter use (47%). Post-hoc analyses showed a significant difference among those with a Pharm.D. versus those without for the response “need to understand and be able to perform” for 20 patient assessment items; a significant difference was also noted among practice settings for 29 items.
Conclusions: The top items pharmacists identified they need to both understand and perform could be applied in various practice settings. The study results may guide which patient assessment items should be included in pharmacy education and training.
Type: Original Researc
Cytotoxic dendritic cells generated from cancer patients.
International audienceKnown for years as professional APCs, dendritic cells (DCs) are also endowed with tumoricidal activity. This dual role of DC as killers and messengers may have important implications for tumor immunotherapy. However, the tumoricidal activity of DCs has mainly been investigated in animal models. Cancer cells inhibit antitumor immune responses using numerous mechanisms, including the induction of immunosuppressive/ tolerogenic DCs that have lost their ability to present Ags in an immunogenic manner. In this study, we evaluated the possibility of generating tumor killer DCs from patients with advanced-stage cancers. We demonstrate that human monocyte-derived DCs are endowed with significant cytotoxic activity against tumor cells following activation with LPS. The mechanism of DC-mediated tumor cell killing primarily involves peroxynitrites. This observed cytotoxic activity is restricted to immature DCs. Additionally, after killing, these cytotoxic DCs are able to activate tumor Ag-specific T cells. These observations may open important new perspectives for the use of autologous cytotoxic DCs in cancer immunotherapy strategies
Synthesis and Antiviral Activity of Fatty Acyl Conjugates of Remdesivir Against Severe Acute Respiratory Syndrome Coronavirus 2 and Ebola Virus
We report here the synthesis, purification, and characterization of mono- and di-fatty acyl conjugates of remdesivir (RDV) and their in vitro antiviral activity against SAR-CoV-2, an Ebola virus transcription- and replication-competent virus-like particle (trVLP) system, and infectious Ebola virus. The most potent monofatty acyl conjugate was 4b, containing a 4-oxatetradecanolyl at the 3′ position. Monofatty acyl conjugates, 3′-O-tetradecanoyl (4a) (IC50(VeroE6) = 2.3 μM; IC50(Calu3) = 0.24 μM), 3′-O-4-oxatetradodecanoyl (4b) (IC50(VeroE6) = 2.0 μM; IC50(Calu3) = 0.18 μM), and 3′-O-(12-ethylthiododecanoyl) (4e) (IC50(VeroE6) = 2.4 μM; IC50(Calu3) = 0.25 μM) derivatives exhibited less activity than RDV (IC50(VeroE6) = 0.85 μM; IC50(Calu3) = 0.06 μM) in both VeroE6 and Calu3 cells. Difatty acylation led to a significant reduction in the antiviral activity of RDV (as shown in conjugates 5a and 5b) against SARS-CoV-2 when compared with monofatty acylation (3a-e and 4a-e). About 77.9% of 4c remained intact after 4 h incubation with human plasma while only 47% of parent RDV was observed at the 2 h time point. The results clearly indicate the effectiveness of fatty acylation to improve the half-life of RDV. The antiviral activities of a number of monofatty acyl conjugates of RDV, such as 3b, 3e, and 4b, were comparable with RDV against the Ebola trVLP system. Meanwhile, the corresponding physical mixtures of RDV and fatty acids 6a and 6b showed 1.6 to 2.2 times less antiviral activity than the corresponding conjugates, 4a and 4c, respectively, against SARS-CoV-2 in VeroE6 cells. A significant reduction in viral RNA synthesis was observed for selected compounds 3a and 4b consistent with the IC50 results. These studies indicate the potential of these compounds as long-acting antiviral agents or prodrugs of RDV
The Vehicle, Spring 1989
Table of Contents
Home MoviesBob Zordanipage 4
Mummy BreathMichael Salempage 5
Pop ArtMonica Grothpage 6
Grey Haze and MoonAllison Stroudpage 7
The State of Being at a Soap & SudsDenise Santorpage 9
Letter HomeJim Reedpage 10
Thursday Afternoon in the StacksRebecca Dickenspage 11
Sizing DownMichael Salempage 12
Intellectual AnatomyMonica Grothpage 13
Grandmother PoemAmy Sparkspage 14
Blues of the BrothermanAlma Watsonpage 15
MigrationPatrick Peterspage 17
RidingBob Zordanipage 18
All Hallow\u27s EveErik Hansonpage 19
Waiting RoomAmy Sparkspage 20
Father, Forgive HerMonica Grothpage 21
Silent ReplyTom Caldwellpage 22
PhotographRobb Montgomerypage 24
WashdayAnn Moutraypage 25
PhotographDiane Atkinspage 26
Uptown FogRobb Montgomerypage 27
Shinbones and SkullsJennifer Berkshirepage 29
Sudden Small PhrasesPatrick Peterspage 31https://thekeep.eiu.edu/vehicle/1053/thumbnail.jp
Tobacco use and asking prices of used cars: prevalence, costs, and new opportunities for changing smoking behavior
Secondhand smoke (SHS) causes premature death and disease in children and adults, and the scientific evidence indicates that there is no risk-free level of exposure to SHS. Smoking tobacco in a car can pollute the microenvironment of the car with residual SHS, leaving telltale signs to potential buyers (e.g., odor, used ash tray). This study examined (a) the proportion of used cars sold in the private party market that may be polluted with tobacco smoke and (b) whether asking prices of smoker and nonsmoker cars differed for cars of otherwise equivalent value. A random sample of 1,642 private party sellers were interviewed by telephone, and content analyses of print advertisements were conducted. Findings indicate that 22% of used cars were advertised by smokers or had been smoked in during the previous year. Among nonsmokers, 94% did not allow smoking in their car during the past year. Only 33% of smokers had the same restrictions. The smoking status of the seller and tobacco use in the car were significantly (p < .01) associated with the asking price independent of a car's Kelley Blue Book value (KBB). Used nonsmoker cars were offered at a considerable premium above their KBB value (>11%) and above comparable smoker cars (7–9%). These findings suggest that community preferences are affecting the value of smoke-free cars. New directions for research, tobacco control policies, and health education are discussed to further reduce smoking behavior, to help consumers make informed purchasing decisions, and to protect nonsmokers from SHS exposure
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