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Drug Development Research

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https://www.readbyqxmd.com/read/28639316/synergism-between-naproxen-and-rutin-in-a-mouse-model-of-visceral-pain
#1
Angel Josabad Alonso-Castro, Joceline Estefanía Rangel-Velázquez, Mario A Isiordia-Espinoza, Luis Enrique Villanueva-Solís, Othoniel H Aragon-Martinez, Juan Ramón Zapata-Morales
Preclinical Research The aim of the present study was to evaluate the antinociceptive interaction between naproxen and the glycoside flavonoid, rutin in the acetic acid-induced writhing test in mice. Naproxen (5, 20, 50, and 100 mg/kg p.o.) or rutin (10, 25, 50, and 100mg/kg p.o.) were administered 60 min before the intraperitoneal administration with acetic acid. The dose-response curve of each individual compound and the experimental effective dose 50 (ED50 ) value were obtained to determinate different proportions of the combinations between the two compounds (naproxen-rutin 1:1, 3:1, and 3:1) in the writhing test...
June 22, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28639277/serum-derived-transfer-factor-stimulates-the-innate-immune-system-to-improve-survival-traits-in-high-risk-pathogen-scenarios
#2
Bridget V Willeford, Trudy Shapiro-Dunlap, Kenneth O Willeford
Preclinical Research Transfer Factors (TFs) are low molecular weight (<5,000 daltons) biological response mediators. In the present study, a serum derived TF improved the ability of the recipient animal to survive high-risk infectious challenges (salmonellosis and canine parvoviral enteritis (CPV)) by altering the host's cytokine response profile. Mice mortally challenged with 5,000 colony-forming units of Salmonella experienced a group mortality of 73% while mice treated with a single 5 mg dose of the TF demonstrated a significant decrease in morbidity (7%, p ≤ 0...
June 22, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28593649/the-effect-of-gabapentin-and-tramadol-in-cancer-pain-induced-by-glioma-cell-in-rat-femur
#3
Janette Nallely Corona-Ramos, Myrna Déciga-Campos, Mario Romero-Piña, Luis A Medina, Issac Martínez-Racine, Osmar A Jaramillo-Morales, Patricia García-López, Francisco Javier López-Muñoz
Preclinical Research The presence of pain as part of the cancer process is variable. Glioblastoma multiform (GBM) can produce bone metastasis, a condition that involves other pathological phenotypes including neuropathic and inflammatory pain. Tramadol and gabapentin are drugs used in the treatment of neuropathic pain. However, there are no studies evaluating their analgesic effects in bone metastasis. We produced a pain model induced by the inoculation of glioma cells (10(5) ) into the rat femur, by perforating the intercodiloid fossa...
June 7, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28524398/anti-inflammatory-and-analgesic-activities-of-terminalia-muelleri-benth-combretaceae
#4
Nouran M Fahmy, Eman Al-Sayed, Mohamed M Abdel-Daim, Abdel Nasser Singab
Preclinical Research The anti-inflammatory and analgesic activities of a polyphenol-rich fraction (TMEF) obtained from Terminalia muelleri Benth. were measured. The analgesic activity of TMEF was tested using acetic acid-induced writhing and hot plate models in mice. The anti-inflammatory activity was assessed using carrageenan-induced paw edema model by measuring PGE2 , TNF-α, IL-1β, and IL-6 plasma levels as well as the paw thickness. TMEF was tested at doses of 100, 200, and 400 mg/kg p.o. and diclofenac sodium was used as a standard (100 mg/kg) in all experiments...
May 19, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28524372/herbal-formula-baogan-yihao-bgyh-prevented-dimethylnitrosamine-dmn-induced-liver-injury-in-rats
#5
Xiujie Liu, Jing Su, Yu Shi, Ying Guo, Imran Suheryani, Shicong Zhao, Yulin Deng, Weiwei Meng, Yan Chen, Lili Sun, Rongji Dai
Preclinical Research Baogan Yihao (BGYH) is a traditional Chinese herbal medicine for the treatment of chronic liver diseases. In this study, the effects of BGYH on dimethylnitrosamine (DMN)-induced liver fibrosis were investigated using a rat model. BGYH alleviate liver damage, as indicated by decreased levels of AST, ALT, γ-GT, and AKP. BGYH also prevented collagen deposition and reduced pathological tissue injury in liver tissue. In fibrosis, high levels of α-SMA and TGF-β in liver tissue were markedly attenuated by BGYH...
May 19, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28449192/anti-inflammatory-effects-of-pegylated-human-adrenomedullin-in-a-mouse-dss-induced-colitis-model
#6
Sayaka Nagata, Motoo Yamasaki, Kazuo Kitamura
Preclinical Research Human adrenomedullin (hAM), a hypotensive peptide, also has anti-inflammatory effects. hAM can reduce the severity of the dextran sulphate sodium (DSS)- and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in animal models. Furthermore, in a clinical study, hAM treatment reduced the Disease Activity Index in ulcerative colitis. However, these therapeutic effects required continuous administration of hAM as the half-life of native hAM is quite short in blood. To resolve this problem, hAM N-terminal was conjugated with two kinds of polyethylene glycol (PEG); 5 kDa PEG or 60 kDa PEG (5 kDa PEG-hAM and 60 kDa PEG-hAM respectively)...
April 27, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28370133/isobolographic-analyses-of-proglumide-celecoxib-interaction-in-rats-with-painful-diabetic-neuropathy
#7
Samuel Suarez-Mendez, Carlos A Tovilla-Zarate, Luis F Ortega-Varela, Deysi Y Bermudez-Ocaña, Jorge L Blé-Castillo, Thelma B González-Castro, Alma M Zetina-Esquivel, Juan C Diaz-Zagoya, Isela Esther Juárez-Rojop
Preclinical Research The aim of the present study was to analyze the antihyperalgesic and antiallodynic interaction between the non-selective cholecystokinin (CCK) antagonist receptor, proglumide, and the selective cyclooxygenase-2 inhibitor, celecoxib in streptozotocin (STZ)-induced diabetic rats. Hyperalgesia was evaluated in the formalin test and tactile allodynia using von Frey filaments. Isobolographic analyses were employed to define the nature of the compound interactions, using a fixed dose ratio (0...
April 3, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28608491/toxicity-and-protective-effect-of-phenolic-enriched-ethylacetate-fraction-of-ocimum-gratissimum-linn-leaf-against-acute-inflammation-and-oxidative-stress-in-rats
#8
Abayomi M Ajayi, Solomon Umukoro, Benneth Ben-Azu, Bulus Adzu, Olusegun G Ademowo
Preclinical Research Ocimum gratissimum L. leaves have attracted considerable attention from researchers because of their medicinal value that include anti-inflammatory, analgesic, antimicrobial, and antioxidant activities. In the present study, the toxicity and the protective effect of phenolic extract of O. gratissimum leaf (EAFOg) against acute inflammation and oxidative stress in rats was assessed. EAFOg, enriched in phenols had no cytotoxic effect against CHO-k1 cells, and no lethality against brine shrimp eggs or mice at a dose of 2000 mg/kg...
June 2017: Drug Development Research
https://www.readbyqxmd.com/read/28608490/antiestrogenic-activity-of-triptolide-in-human-breast-cancer-cells-mcf-7-and-immature-female-mouse
#9
Yi Tang, Jun Wang, Jinghua Cheng, Lijun Wang
Preclinical Research To investigate the antiestrogenic activity of triptolide in human breast cancer cell line MCF-7 and immature female C57BL/6 mouse. The effects of triptolide on cell proliferation, cell cycle, and the expression of estrogen receptor alpha (ERα) and progesterone receptor (PR) were examined in MCF-7 cells. In vivo antiestrogenic effects of triptolide were observed after cotreatment of mice with E2 and triptolide for 4 days. Triptolide dose- and time-dependently inhibited cell growth in untreated or E2 -treated MCF-7 cells, which was associated with increased S phase arrest...
June 2017: Drug Development Research
https://www.readbyqxmd.com/read/28345130/antiallodynic-activity-of-ceftriaxone-and-clavulanic-acid-in-acute-administration-is-associated-with-serum-tnf-%C3%AE-modulation-and-activation-of-dopaminergic-and-opioidergic-systems
#10
A Ochoa-Aguilar, M A Sotomayor-Sobrino, R Jaimez, R Rodríguez, R Plancarte-Sánchez, R Ventura-Martinez
Preclinical Research The aim of this study was to determine the antiallodynic effect of acute administration of the β-lactam antimicrobials, ceftriaxone (CFX) and clavulanic acid (CLAV), for the control of established pain on a model of neuropathic pain (NP). We also investigated the involvement of dopaminergic and opioidergic pathways as well as alterations in serum concentrations of TNF-α in the antiallodynic actions of these drugs. CFX, CLAV, or gabapentin (GAP), a reference drug, were administered i.p...
March 26, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28294366/antihyperalgesic-effects-of-indomethacin-ketorolac-and-metamizole-in-rats-effects-of-metformin
#11
Crystell Guadalupe Guzmán-Priego, Roberto Méndez-Mena, Manuel Alfonso Baños-González, Claudia Ivonne Araiza-Saldaña, Gabriela Castañeda-Corral, Jorge Elías Torres-López
Preclinical Research Metformin-dependent mechanisms have been implicated in the antinociceptive effect of some non-steroidal anti-inflammatory drugs (NSAIDs). In this study, the effect of local peripheral or systemic administration of metformin on the local peripheral or systemic antinociception induced by indomethacin, ketorolac and metamizole was assessed in the rat carrageenan-induced thermal hyperalgesia model. Rats were injected with carrageenan (1%, 50 µl) into the right hindpaw which reduced paw withdrawal latency, a measure of thermal hyperalgesia...
March 2017: Drug Development Research
https://www.readbyqxmd.com/read/28195646/ns1209-spd-502-a-novel-selective-ampa-antagonist-for-stroke-neuropathic-pain-or-epilepsy-drug-development-lessons-learned
#12
Jan M Keppel Hesselink
Preclinical Research The selective AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor antagonist, NS1209 (also known as SPD 502) has been explored in several research and development campaigns since its selection as a lead drug candidate in the early 1990s by the Danish biotechnology company, NeuroSearch. The compound was successively tested in animal models of stroke, neuropathic pain and epilepsy. The preclinical data to support development for the treatment of stroke were incomplete, as the compound was administered after the stroke episode, and did not protect subcortical areas of the brain...
February 13, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28176369/morin-inhibits-proliferation-migration-and-invasion-of-bladder-cancer-ej-cells-via-modulation-of-signaling-pathways-cell-cycle-regulators-and-transcription-factor-mediated-mmp-9-expression
#13
Seung-Shick Shin, Se Yeon Won, Dae-Hwa Noh, Byungdoo Hwang, Wun-Jae Kim, Sung-Kwon Moon
Preclinical Research Previous studies have shown that morin exerts diverse pharmacological activities. In this study, we investigated the inhibitory activity of morin on bladder cancer EJ cells. Morin significantly inhibited EJ cell proliferation, which was related to the G1-phase cell cycle arrest together with the reduced expression of cyclin D1, cyclin E, CDK2, and CDK4 via increased expression of p21WAF1. Morin also increased ERK1/2 phosphorylation and decreased JNK and AKT phosphorylation without altering the p38MAPK phosphorylation levels...
February 8, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28176363/antinociceptive-and-antihyperalgesic-activity-of-a-traditional-maya-herbal-preparation-composed-of-pouteria-campechiana-chrysophyllum-cainito-citrus-limonum-and-annona-muricata
#14
Myrna Déciga-Campos, Rolffy Ortiz-Andrade, Amanda Sanchez-Recillas, José Salvador Flores-Guido, Mario A Ramírez Camacho
Preclinical Research The purpose of this work was to assess the antinociceptive and antihyperalgesic properties of an herbal preparation, composed of four vegetal species: Pouteria campechiana (P. campechiana), Chrysophyllum cainito (C. cainito), Citrus limonum (C. limonum), and Annona muricata (A. muricata), that is commonly used in combination (PCCA) in traditional Mayan medicine for the treatment of diabetes and pain. An ethanolic extract of PCCA was prepared at a ratio of 1:1:1:1 for each plant. The systemic antinociceptive effect of PCCA extract (50-600 mg/kg, p...
February 8, 2017: Drug Development Research
https://www.readbyqxmd.com/read/27859446/synthesis-of-five-and-six-membered-n-phenylacetamido-substituted-heterocycles-as-formyl-peptide-receptor-agonists
#15
Claudia Vergelli, Igor A Schepetkin, Giovanna Ciciani, Agostino Cilibrizzi, Letizia Crocetti, Maria Paola Giovannoni, Gabriella Guerrini, Antonella Iacovone, Liliya N Kirpotina, Richard D Ye, Mark T Quinn
Preclinical Research Formyl peptide receptors (FPRs) are G-protein-coupled receptors that play an important role in the regulation of inflammatory process and cellular dysfunction. In humans, three different isoforms are expressed (FPR1, FPR2, and FPR3). FPR2 appears to be directly involved in the resolution of inflammation, an active process carried out by specific pro-resolving mediators that modulate specific receptors. Previously, we identified 2-arylacetamido pyridazin-3(2H)-ones as FPR1- or FPR2-selective agonists, as well as a large number of mixed-agonists for the three isoforms...
February 2017: Drug Development Research
https://www.readbyqxmd.com/read/27767221/from-gutenberg-to-open-science-an-unfulfilled-odyssey
#16
Chris R Triggle, David J Triggle
Preclinical Research With the almost global availability of the Internet comes the expectation of universal accessibility to knowledge, including scientific knowledge-particularly that generated by public funding. Currently this is not the case. In this Commentary we discuss access to this knowledge, the politics that govern peer review and publication, and the role of this knowledge as a public good in medicine.  Gutenberg's invention of the printing press in 1440 opened an avenue for the distribution of scholarly information to the entire world...
February 2017: Drug Development Research
https://www.readbyqxmd.com/read/27654302/fucoidan-induces-ros-dependent-apoptosis-in-5637-human-bladder-cancer-cells-by-downregulating-telomerase-activity-via-inactivation-of-the-pi3k-akt-signaling-pathway
#17
Min Ho Han, Dae-Sung Lee, Jin-Woo Jeong, Su-Hyun Hong, Il-Whan Choi, Hee-Jae Cha, Suhkmann Kim, Heui-Soo Kim, Cheol Park, Gi-Young Kim, Sung-Kwon Moon, Wun-Jae Kim, Yung Hyun Choi
Preclinical Research Fucoidan, a sulfated polysaccharide, is a compound found in various species of seaweed that has anti-viral, anti-bacterial, anti-oxidant, anti-inflammatory, and immunomodulatory activities; however, the underlying relationship between apoptosis and anti-telomerase activity has not been investigated. Here, we report that fucoidan-induced apoptosis in 5637 human bladder cancer cells was associated with an increase in the Bax/Bcl-2 ratio, the dissipation of the mitochondrial membrane potential (MMP, Δψm), and cytosolic release of cytochrome c from the mitochondria...
February 2017: Drug Development Research
https://www.readbyqxmd.com/read/27987222/the-antinociceptive-effect-of-a-tapentadol-ketorolac-combination-in-a-mouse-model-of-trigeminal-pain-is-mediated-by-opioid-receptors-and-atp-sensitive-k-channels
#18
Israel Barreras-Espinoza, José Alberto Soto-Zambrano, Nicolás Serafín-Higuera, Ramón Zapata-Morales, Ángel Alonso-Castro, Ronell Bologna-Molina, Vinicio Granados-Soto, Mario A Isiordia-Espinoza
Preclinical Research The aim of the present study was to evaluate the antinoceptive interaction between the opioid analgesic, tapentadol, and the NSAID, ketorolac, in the mouse orofacial formalin test. Tapentadol or ketorolac were administered ip 15 min before orofacial formalin injection. The effect of the individual drugs was used to calculate their ED50 values and different proportions (tapentadol-ketorolac in 1:1, 3:1, and 1:3) were assayed in the orofacial test using isobolographic analysis and interaction index to evaluate the interaction between the drugs...
December 16, 2016: Drug Development Research
https://www.readbyqxmd.com/read/27888525/breaking-sad-unleashing-the-breakthrough-potential-of-ketamine-s-rapid-antidepressant-effects
#19
David Feifel
Preclinical Research The surprising results of a small clinical trial on the effects of low dose ketamine, a 65-year old anesthetic drug that is also used off-label for chronic pain and recreationally as a club drug, in eight depressed subjects unleashed the most significant advance in antidepressant drug development in decades. That study and subsequent ones have demonstrated that low dose, infused ketamine is able to induce a remission of depression in patients who have failed conventional medications, within 24 h...
December 2016: Drug Development Research
https://www.readbyqxmd.com/read/27813127/psychotropic-drug-development-strategies-that-target-neuropsychiatric-etiologies-in-alzheimer-s-and-parkinson-s-diseases
#20
REVIEW
Cornelis J Van der Schyf
Preclinical Research Neuropsychiatric symptoms are currently recognized as a common burden in patients suffering from Alzheimer's disease (AD), Parkinson's disease (PD), and many other neurodegenerative disorders. Earlier theories positing that these symptoms emerge predominantly in patients with late-stage disease have been largely dismissed. It is now generally accepted that many neuropsychiatric symptoms commonly manifest very early in neurodegenerative disease stages, and in many cases are even considered prodromal indicators...
December 2016: Drug Development Research
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